Perspectives

Cancer immunotherapy during the COVID‐19 pandemic presents management challenges from immune‐related toxicities, requiring careful patient selection The coronavirus disease 2019 (COVID‐19) pandemic has led to fundamental re‐evaluation of the benefits versus risks of treatment in oncology. Immunotherapy has had an expanding presence in oncology, becoming a primary systemic treatment option in diseases such as melanoma, lung, urothelial, renal, and head and neck cancers. Immune checkpoint inhibitor (ICI) therapy, namely anti‐programmed cell death protein 1 (anti‐PD‐1), anti‐programmed cell death ligand 1 (anti‐PD‐L1) and anti‐cytotoxic T‐lymphocyte‐associated protein 4 (anti‐CTLA‐4) antibodies, halt the negative regulatory checks of T lymphocytes, thus activating the immune response against tumours. Patients with cancer receiving these treatments are faced with a unique set of treatment‐related toxicities driven by an autoimmune mechanism. An association between immune‐related adverse events (irAEs) and severe COVID‐19 has been raised during the current outbreak. In particular, an overlap in the physiological insult from immunotherapy‐mediated pneumonitis and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐related interstitial pneumonia is hypothesised.1 Both conditions may present with lung parenchymal changes, and their coexistence may potentially aggravate the underlying interstitial inflammatory infiltrate and diffuse alveolar damage, leading to a common final pathway of respiratory failure. Pre‐existing lung pathology is expected to be a risk factor for COVID‐19 pneumonia, with higher incidence in patients with lung cancer and smokers.2 Whether prior thoracic radiation may have an impact on outcomes from COVID‐19 pneumonia is unknown. Parallels have been drawn between the cytokine storm driving COVID‐19‐associated acute respiratory distress syndrome and cytokine release syndrome as a complication following T cell‐engaging therapies, such as chimeric antigen receptor T cell and CD3‐based bispecific T cell engager therapies. It is known that interleukin (IL)‐6, IL‐10 and interferon (IFN)‐γ are key drivers behind cytokine release syndrome. Elevated circulating IL‐6 levels have been observed in patients with COVID‐19‐associated pneumonia.3 Patients with severe COVID‐19 have significantly higher circulating levels of pro‐inflammatory cytokines, including IL‐1B, IL‐6, IL‐8 and IL‐10, compared with milder cases of COVID‐19;3 and elevated IL‐6 has been shown to be a predictor of mortality risk. Patients with immune‐related toxicity have higher levels of 11 circulating cytokines, such as G‐CSF, GM‐CSF, IFN‐α‐2, IL‐1a, IL‐1B, IL‐2 and IL‐12,4 with some but incomplete overlap with the cytokine milieu seen in severe COVID‐19 cases.3 The outcomes of COVID‐19 in patients with cancer treated with immunotherapy remain under investigation, with some2,5 but not all6 studies suggesting a more severe outcome. In a multicentre study from China involving 105 patients with cancer infected with SARS‐CoV‐2, 6% received anti‐PD‐1 therapy within 40 days of COVID‐19 symptom onset and experienced increased risk of death and critical symptoms.2 Another series of 423 cancer patients with SARS‐CoV‐2 infection from New York City also reported that treatment with ICI therapy within 90 days was a predictor for admission to hospital and for severe respiratory illness, defined as the requirement for high flow oxygen supplementation or mechanical ventilation.5 Of interest, even after exclusion of patients with lung cancer, the ICI group experienced worse outcomes, inferring that the ICI therapy itself conferred inferior COVID‐19 outcomes without the confounding effect of lung cancer, which had been shown as an independent predictor of poor prognosis in COVID‐19. However, an interim analysis of the first 200 patients from the Thoracic Cancers International COVID‐19 Collaboration (TERAVOLT) registry of patients with thoracic malignancies did not observe a worse outcome among the 37% of patients receiving ICI therapy (23% ICI alone and 14% ICI plus chemotherapy), with data collection ongoing.6 Dual checkpoint inhibitor (anti‐CTLA4 with anti‐PD1 antibody) therapy has achieved high response rates in a number of cancer types,7,8 but is associated with greater incidence and severity of treatment‐related toxicity compared with monotherapy.7 This has several implications. Firstly, differentiating between immune‐mediated pneumonitis and COVID‐19‐associated pneumonia can be difficult due to similarities in clinical and radiological features. Earlier in the pandemic, there were concerns that this may cause delays in initiation of corticosteroids, which is the standard management of irAEs. However, emerging evidence for potential benefit of dexamethasone in severe cases of COVID‐199 reduces concerns for its empirical use in cases where immune‐mediated pneumonitis is a differential diagnosis. Secondly, patients with severe irAEs, such as immune‐mediated pneumonitis requiring intensive care support may face a health system already strained by demand from COVID‐19 cases. Finally, severe irAEs require treatment with high dose corticosteroid and, at times, additional immunosuppressive agents, such as infliximab and mycophenolate. To avoid rebound of the irAEs, corticosteroids are weaned over 6–8 weeks, subjecting patients to prolonged immunosuppression that can predispose them to opportunistic and nosocomial infections.10,11 This has the potential to add further burden to the health care system. The impact of cancer immunotherapy on microbial infection in general is not fully understood. A retrospective study of patients with metastatic melanoma receiving immunotherapy (mainly ipilimumab, an anti‐CTLA4 antibody) reported a 7.3% incidence of serious infections due to a variety of bacterial, viral, fungal or parasitic infections requiring hospitalisation or parenteral antimicrobials.10 Nonetheless, the study of this interaction is complex, with the receipt of corticosteroids for irAEs and having diabetes as a comorbidity10,12 associated with an increased risk of infection in patients with cancer receiving ICI therapy. Furthermore, immune checkpoint blockade can reactivate tuberculosis and viral infections. There are case reports of acute tuberculosis developing in patients with cancer receiving immunotherapy, without concurrent corticosteroid therapy.13 At least three of five cases were suspected to represent reactivation of latent tuberculosis, which may be directly mediated through PD‐1 inhibition driving an exaggerated immune response to tuberculosis infection. Another consideration for patients with cancer receiving immunotherapy is influenza vaccination during the COVID‐19 pandemic. While there is currently no vaccine specifically against COVID‐19, many health authorities encourage the uptake of influenza vaccination to reduce the concurrent burden from influenza illnesses, particularly for nations approaching winter facing the seasonal influenza period. Controversy surrounds whether influenza vaccination in patients receiving cancer immunotherapy heightens the risk of irAEs.14 Numerous retrospective series support the safety of inactivated influenza vaccine in recipients of anti‐PD‐1 monotherapy, with no increase in irAEs observed.15 Reassuringly, influenza vaccination had no adverse impact on the anticancer effect of ICI therapy.14,15 However, there may be heightened concerns for influenza vaccination in combination immunotherapy (anti‐PD‐1 with anti‐CTLA‐4) recipients, as they are more prone to irAEs, including rarer, but potentially fatal, complications such as immune‐mediated myocarditis. This potential concern for influenza vaccination in recipients of combination ICI can leave this patient population more vulnerable from influenza infection. For patients taking monotherapy ICI, current evidence supports the safety and efficacy for influenza vaccination. There are guidelines addressing the use of cancer immunotherapy in the COVID‐19 era.16,17 These call for careful considerations on the use of dual checkpoint inhibitor therapy depending on the local prevalence of community transmission and the capacity of the local health service to cope with demand.16 On a practical note, this requires individual patient risk–benefit assessment. Patient factors such as age, smoking and comorbidities (eg, diabetes and chronic obstructive pulmonary disease) may affect their recovery from irAEs and affect the outcomes from concomitant COVID‐19. Tumour factors for consideration include the burden and biology of disease. Combination immunotherapy may be justified, for example, in a young patient with metastatic melanoma with high disease burden and/or intracranial metastases. This is in contrast to a patient with underlying comorbidities who has low volume disease and/or disease characteristics, such as underlying B‐Raf proto‐oncogene (BRAF) V600K mutation or desmoplastic melanoma subtype, associated with higher likelihood of response to single‐agent anti‐PD‐1/anti‐PD‐L1 therapy. Current guidelines recommend ICI monotherapy to be delivered at increased dosing intervals, such as nivolumab four times per week and pembrolizumab six times per week.16 These approved alternate schedules have been shown to maintain therapeutic efficacy, while advantageous in reducing patient attendance at health care facilities, potentially reducing exposure and community transmission of COVID‐19. The timing of immunotherapy cessation in patients is another consideration. A number of trials in metastatic non‐small cell lung cancer had a 2‐year treatment duration for immunotherapy in responding patients.18 Data on metastatic melanoma support that cessation of anti‐PD‐1 after at least 6 months of therapy in patients achieving complete response can be feasible without adversely affecting outcome.19 Selection of patients with cancer suitable to stop immunotherapy may further reduce these patients’ hospital visits and may potentially reduce the chance of acquiring COVID‐19. There are international efforts to collate the clinical experience of COVID‐19 in patients receiving cancer immunotherapy.6 These registries will provide a valuable resource for further areas of research, such as assessing the impact of irAEs on COVID‐19. The data will also improve our understanding of the outcomes in this patient population to aid management decisions and counsel patients. Research on potential biomarkers of disease severity may also assist in patient triage. In this rapidly evolving area, it is helpful for practising clinicians to maintain current knowledge through regularly updated resources (Box). In summary, the increased role of ICI therapy in oncology calls for consideration of the impact of their use during the COVID‐19 pandemic. While these agents are not directly immunosuppressive, as with cytotoxic chemotherapy, ICI‐associated toxicities pose diagnostic and therapeutic challenges for management in the setting of a COVID‐19 outbreak. Overlapping clinical and radiographic features in immune‐mediated pneumonitis and COVID‐19‐associated pneumonia may cause diagnostic difficulties at initial presentation. Severe irAEs requiring corticosteroids and prolonged immunosuppression may predispose patients to opportunistic infections. Furthermore, there is a possibility of worse outcomes in the setting of COVID‐19 with underlying immune‐mediated pneumonitis and damaging inflammatory response from immune checkpoint blockade. Practical measures, namely prolonging treatment interval and careful patient selection for combination ICI therapy, may help minimise harm. Box – Practice points for cancer immunotherapy during the coronavirus disease 2019 (COVID‐19) pandemic Judicious use of combination anti‐CTLA-4 and anti‐PD-1/anti‐PD-L1 immunotherapy in patients requiring high tumour response rate with good organ functional reserve. Combination checkpoint therapy is associated with higher rate for immune‐related toxicities (eg, pneumonitis), which may potentially have an adverse impact on outcomes in patients with COVID‐19 Use of approved dosing schedule with longer duration between treatments (eg, nivolumab every 4 weeks, pembrolizumab every 6 weeks) Individualised assessment for pausing or cessation of immunotherapy in patients with controlled low disease burden Rapid assessment and COVID‐19 testing for patients receiving cancer immunotherapy who have clinical presentations with overlapping features for COVID‐19 and immune‐related adverse events Prevention of co‐infections: seasonal influenza vaccination for patients taking single‐agent immune checkpoint inhibitor (the use in combination checkpoint recipients should be individualised). Pneumocystis jirovecii prophylaxis for patients receiving prolonged corticosteroid therapy for immune‐mediated toxicities Maintain current knowledge through professional journals, dynamic resource links (examples below) and webinars sharing clinical knowledge and experience internationally: ▸ Clinical Oncology Society of Australia (https://www.cosa.org.au/publications/covid‐19-updates/articles/) ▸ American Society of Clinical Oncology (https://www.asco.org/asco-coronavirus‐information) ▸ European Society for Medical Oncology (https://www.esmo.org/covid‐19-and‐cancer/covid‐19-full‐coverage) ▸ Journal of Thoracic Oncology (https://www.jto.org/content/covid19) anti‐CTLA‐4 = anti‐cytotoxic T‐lymphocyte‐associated protein 4; anti‐PD‐1 = anti‐programmed cell death protein 1; anti‐PD‐L1 = anti‐programmed cell death ligand 1.

Yada Kanjanapan · Desmond Yip

Fit testing of respirators is recommended to ensure proper fit for individual health care workers and is required to comply with respirator standards

Adrian Regli · Britta S Ungern‐Sternberg

As we face a second wave of the pandemic, mobility data may assist government public health action

Lucinda Adams · Robert J Adams · Tarun Bastiampillai

The arrival of social media coincides with the point at which the antivaccination movement became globally coordinated

Helen Petousis‐Harris · Lisbeth Alley

Name badges are a simple additional method of communicating doctors’ names to patients and their families, but uptake remains poor Most new relationships begin with an exchange of names and most existing relationships are reinforced using names. Except in health care. Despite campaigns such as #hellomynameis (https://www.hellomynameis.org.uk/), clinicians’ names remain absent from many health care experiences and environments. Patients meet many people during an illness journey, particularly when that takes place in a public hospital. There are nurses rotating through different shifts, the specialist under whom the patient is admitted, a registrar, resident or intern, plus maybe a medical student or two. There are also teams of allied health providers. One study found that 75% of inpatients were unable to name anyone when asked to recall the name of the physician in charge of their care.1 Limited recall of doctors’ names is part of a broader pattern. Only 42% of patients can name their diagnosis at discharge,2 and in a study of older patients, only 18% of patients could recall a single message one hour after the ward round, falling to 9% four hours after the ward round.3 The very basic components of effective health care communication, particularly in hospitals, are lagging. Barriers to effective communication are complex and structural.4 Let's for a moment focus on the most fundamental information transfer in any patient–doctor encounter: names. Patients’ names are documented from the moment of admission, printed on sticky labels, placed on wrist bands, attached to meal trays, printed on patient lists, and displayed and discussed in ward and team meetings. In contrast, doctors’ names usually appear only on faded ID swipe cards attached at the hip, or on crowded lanyards around the neck. This asymmetry in identification is just one symptom of the enormous information gulf separating patients and their doctors. Studies consistently show that the majority of patients believe doctors should wear name badges,5 with a preferred site being the breast pocket.6 In 2019, our hospital introduced voluntary name badges for all interns and residents. Something as simple as a name badge, which nearly every other service‐oriented industry employs without question, required careful navigation in the hospital. What name should appear on the badge? Should surnames be included? Should “Intern” or “Resident” or just “Doctor” appear on the badge? Badges were rolled out to interns and residents at the start of the clinical year with a mixed response. Anecdotally, senior doctors commented favourably on the badges, and nurses and allied health workers found it helpful for learning and remembering the names of doctors rotating through their wards. Mid‐year, we collected data on how many interns and residents were wearing badges. During two compulsory teaching sessions, we quietly counted the number of interns and residents wearing name badges: adherence was a lowly 25%. To determine why three‐quarters of interns and residents were not wearing badges, we circulated a voluntary, anonymous and electronic survey to all 108 interns and residents. Our aim was to identify levers or incentives that we could incorporate into a series of behavioural nudges to improve name badge adherence. Around one‐third (34%) of the cohort took part in the survey, 80% of whom did not wear their name badge. Half of respondents reported that their ID swipe card contained their name and was sufficient. About one‐fifth (22%) did not see a need to wear a name badge and a similar number mentioned that senior doctors not wearing badges discouraged them from wearing one. Not wanting members of the public or patients to know their name was a reason indicated by 16% of respondents. Free text responses mainly centred on forgetting to, or being annoyed by, attaching it each day. In response, we have developed new strategies to increase name badge adherence. For example, a brief lecture will be given on the evidence‐base underpinning good communication, coffee vouchers will be provided to doctors seen wearing their badges, badges will be provided to new interns during orientation, and name badges will soon be rolled out across the hospital for all medical staff. Making name badges available to senior doctors is important as they can influence the cultures within units and teams, and our cohort identified a lack of badges among seniors as a barrier to adherence. An informal poll of intern and resident representatives across New South Wales suggests a similar pattern of poor name badge adherence. Five networks with name badges reported that adoption by junior doctors was low. Four networks did not provide name badges. Only three networks provided name badges and have good adherence among junior doctors. As pressure on hospitals, and our clinical interactions, continues to grow, we must look for ways to support effective communication. Alongside a clear introduction, easy‐to‐read name badges reinforce familiarity and contribute to rapport between patients and our (increasingly) busy workforce.

Benjamin D Bravery · Jovana Stojkov · Jeremy Brown

Australia has relied, for most of its history, on international medical graduates (IMGs) to supplement its workforce. Since 1978, IMGs applying for general registration to practise in Australia have usually needed to pass the examinations of the Australian Medical Examining Council, or since 1986, its successor, the Australian Medical Council (AMC). The AMC provides several pathways to registration by the Australian Health Practitioner Regulation Agency (AHPRA). The route now termed “the standard pathway” consists of a two‐part assessment including a multiple choice question (MCQ) examination followed by a clinical examination. While most IMGs are required to pass both examinations, since 2007, IMGs who qualified in the so‐called competent authority countries (the United Kingdom, Ireland, the United States and Canada) have usually not been required to sit these examinations.1 The examinations have sometimes provoked controversy and political responses in various forms.2,3,4 Partly in reaction to these, but mainly through an internal process of continuous improvement, their formats have been adapted considerably over the 42‐year period. The MCQ examination assesses “basic and applied medical knowledge across a wide range of topics,” and since 2000, its pass mark has been set using item response theory.5,6 The original clinical examination used short cases and viva voces; in 2004, this was replaced by a 16‐station objective structured clinical examination (OSCE). The standard of both examinations is set at that “of newly qualified graduates of Australian medical schools who are about to commence intern training”.6 The last account of the demographic features of candidates attempting the examinations and their performance was provided in 2010.5 Now, a decade later, there have been striking changes in both these parameters, which we document and evaluate in this article. A further aim was to identify some demographic or candidate factors that might influence examination success. Source of data De‐identified information about candidates who took the MCQ and clinical examinations of the Australian Medical Examining Council and AMC, from their inception in 1978 until October 2019, were provided by the Council. It included the country and year of primary medical qualification, gender, year of birth, years of first attempt and success, and number of attempts for each candidate. From this information, we calculated the numbers of candidates, numbers of attempts, the success rate per attempt, and the proportion eventually achieving success each year. To examine the contributions of individual countries, results were aggregated into decades. Countries of training were also consolidated into regions, according to the United Nations geographical regions report, last updated in 1999 (Supporting information, table 1).7 Ethics approval was obtained from the University of Melbourne Human Research Ethics Committee (ID: 1750338.3). Demographic features of candidates Over the 42‐year period, a total of 35 699 candidates from 153 countries sat the MCQ examination, 16 588 (46.7%) of whom were female (Box 1). The median age of all candidates at their first MCQ attempt was 32 years (interquartile range [IQR], 28–37 years; range, 20–73 years). The clinical examination was attempted by 20 494 candidates. Their demographic features were similar to that of the candidates for the MCQ. Box 1 shows the number of candidates for the MCQ and clinical examination for the top ten countries of primary medical qualification at each examination. The data for countries grouped by UN region are provided in the online Supporting information, table 1, and data for candidates from all individual countries (except those with very few candidates) are provided in the online Supporting information, table 2. South Asia was the region contributing most candidates, with just under half the total — predominantly graduates from India, Pakistan and Sri Lanka. Next in order were those from South‐East Asia and North Africa. Candidate performance From a low base until about the year 2000, there was a marked increase in candidates attempting each examination, reaching a peak in 2009 for the MCQ and 4 years later for the clinical examination (Box 2 and Box 3). Although the candidate numbers declined slightly after these peaks, they remained almost fourfold higher than in 2000. The pass rate at each attempt in the MCQ examination fluctuated, with most year‐to‐year variations not reaching statistical significance. However, overall pass rates per attempt increased over time, from a low of 28% in 1987 to a high of 66% in 2018. Some candidates showed great persistence: 86 attempted the examination ten or more times. As with the MCQ examination, the pass rate in the clinical examination increased between the 1980s and the 2000s, reaching a peak of 64% in 2007. However, between 2011 and 2012 it fell by more than 10%, followed by a further decline; and for the past 5 years (excepting 2019 when data were incomplete), it has remained just above 30%. Nevertheless, most candidates who persevered managed to pass after one or two further attempts. As with the MCQ, there were a few who found it much more difficult. Five or more attempts were made by 621 candidates (3.0%), 144 of whom have not yet succeeded. Pass rates by individual country are provided in the Supporting information, table 3. In the MCQ, during the past three decades, women had a higher pass rate per attempt and overall, although the magnitude of the difference (about 3%) was small (Box 4). In the clinical examination since 1990, women had both a higher pass rate and fewer attempts. In the most recent decade, the difference in pass rates was substantial (+12%). Box 5 and Box 6 show the pass rates in the MCQ and clinical examinations, respectively, graphed against candidates’ age and the interval (recency) since their medical graduation. There was a marked decline in success with both increasing age and interval since graduation; this was more marked in the clinical examination. While the number of candidates who were 55 years or older was small (245; 1.2% of total), their pass rate was one‐third that of candidates aged 20–29 years, and only 45% of the older group eventually passed. Commentary Before 2000, the number of IMGs attempting AMC examinations annually was usually less than 300 and never exceeded 600. However, between 2000 and 2018, candidate numbers increased more than threefold to an annual mean of 1003 during a period when the number of all Australians born overseas increased only from 4.5 to 7.3 million.8 Some factors likely to have contributed to the increase in candidates were removal in 1998 of the requirement to be an Australian citizen, and offering the computer‐delivered MCQ examination from 2005 in several centres outside Australia. A further increase in candidates for the MCQ examination resulted from the 2006 decision by the Council of Australian Governments that all IMGs with limited or temporary registration with the individual state medical boards should pass that examination. The peak in attempts at the clinical examination in 2013 followed the establishment of the National Registration and Accreditation Scheme in July 2010 and the requirement that limited registrants (non‐specialists) demonstrate progress towards full registration (including passing the AMC clinical examination where applicable). It is important to note that these data are specific to those sitting the AMC examinations. They give only a partial picture of medical immigration over this period. Firstly, they do not include IMGs who were registered as specialists by the various states, and subsequently by AHPRA on advice from specialist colleges. Secondly, until 1992 the Medical Acts in all Australian states allowed graduates from the UK (and usually Ireland) exemption from the need for further examination. For the next 15 years, generalists from those countries usually had to take the AMC examinations, but from 2007 they were again exempted (along with IMGs from Canada and the US) when the AMC introduced the competent authority pathway. The overall success rate in the MCQ examination increased significantly from the 1980s. The AMC made several changes over that time to increase reliability and fairness. One was altering question types to formats less dependent on English language skill; another was publication of annotated question banks to assist candidates in their preparation.5,6,9 From 2000, the pass mark has been set by criterion‐referenced methodology. A further refinement from 2011 was administering the MCQ examination in computer‐adaptive format, where the difficulty of items is adjusted in real time according to a candidate's performance, considered to increase fairness and precision.10 A factor likely to have contributed to the recent lower pass rate in the clinical examination (Box 3) is the removal of nearly all candidates from the competent authority countries. Up till 2009, UK graduates had the highest pass rate in this examination (Supporting information, table 3), and their removal from the pool would inevitably lower the overall rate. However, the decline since 2010 cannot be fully accounted for by this since competent authority candidates comprised less than 10% of the 2000–2009 total. Thus, other factors affecting the most recent cohorts of candidates (eg, the changing mix of parent countries) are likely to have contributed. Many IMGs must often overcome hurdles less likely to be faced by those from competent authority countries. These include adapting to an unfamiliar health system, developing fluency in English, preparing for the examinations while under time pressure from short‐stay visas, and needing to support themselves with sometimes long hours of work outside the health system.11 It is possible, though, that changes in the format or content of the OSCE have also contributed. The differences between the results for women and men in the MCQ should not be overplayed, since the magnitude was small. Others have found little gender effect in postgraduate written examinations in the UK and the US.12,13 However, the outperformance by women in the clinical examination, particularly in the past decade, is more striking. Those findings have been seen elsewhere. Women perform better than men in Step 2 of the United States Medical Licensing Examination.14 Female overseas‐trained doctors were twice as likely as males to pass the UK Federation of Royal Colleges of Physicians’ Practical Assessment of Clinical Examination Skills (PACES) at their first attempt.15 The PACES examination has many similarities to the AMC OSCE, with communication skills important for both. Female superiority in patient–doctor communication has been documented previously,16 and may partly explain the present findings. That performance in the MCQ deteriorated with both age and time since graduation is not entirely surprising: the examination tests knowledge in all domains of medicine, including some of the basic sciences. The longer since these were studied, the more difficult it might be to pass questions based on them, especially for IMGs who had practised as specialists in their original country. More unexpected was the much lower performance in the clinical examination by older candidates. Clinical experience might have been expected to give them an advantage, but this does not appear to have been generally so. We have been unable to find exactly comparable data from medical licensing examinations in other countries. A UK retrospective analysis observed that international graduates aged more than 37 years actually performed better in a postgraduate paediatric examination.17 However, a US analysis noted a negative correlation between age when first certified by the American Board of Internal Medicine and the American Board of Surgery and subsequent success in maintenance of certification examinations.18 Since 1978, these examinations have played an important role in informing the credentialing of generalist IMGs by state medical boards and now the national board. This article has documented substantial changes over the four decades in the demography of candidates, and some factors that were associated with their success in the examinations. The information will be of interest to health planners, but more particularly to those IMGs who have passed through the process and others who are contemplating it. Many rural health services still struggle to meet their workforce needs and rely heavily on doctors who have migrated to practise medicine here.19 Australia continues to owe a debt to its immigrant doctors. Box 1 – Multiple choice question (MCQ) and clinical examinations: numbers of candidates, top ten countries* Country of training 1978–1989 1990–1999 2000–2009 2010–2019 Total MCQ examination India 351 496 2619 2483 5949 Pakistan 32 113 1007 1838 2990 Sri Lanka 159 246 1005 1394 2804 Egypt 179 356 375 1171 2081 Bangladesh 16 99 777 1107 1999 Iran 32 34 664 1197 1927 Philippines 83 182 646 714 1625 China 4 219 641 745 1609 Myanmar 21 66 485 772 1344 Iraq 8 160 420 602 1190 Total all countries 1864 3859 12 722 17 254 35 699 Clinical examination India 190 392 1059 2074 3715 Sri Lanka 101 194 399 960 1654 Pakistan 13 59 342 1168 1582 Bangladesh 7 53 483 831 1374 Iran 8 27 263 688 986 China 0 109 398 475 982 Egypt 78 296 195 375 944 Myanmar 5 45 175 661 886 Philippines 11 104 198 507 820 Iraq 2 85 303 358 748 Total all countries 897 2588 5806 11 203 20 494 * By total number of candidates. Data are listed by the year each candidate first attempted the examination. Many candidates made multiple attempts. International medical graduates trained in the United Kingdom and Ireland were exempted from the Australian Medical Council examinations by most states until 1992. Since 1997, few candidates from the competent authority countries (UK, Ireland, Canada and the United States) were required to take the examinations. Box 2 – Number of candidates and success rate per attempt in the multiple choice question examinations since 1978, and total number of attempts by candidates each year* * Data for 2019 truncated at October. Box 3 – Number of candidates, success rate per attempt and total attempts in the clinical examinations since 1978, and total number of attempts by candidates each year* * Data for 2019 truncated at October. Box 4 – Influence of gender on examination success* Period Gender N Total attempts Total passes Mean (SD) attempts Pass total (%) Pass/attempt (%) MCQ examination 1978–1989 Female 568 1299 412 2.29 ± 1.84 72.5% 31.7% Male 1142 2431 817 2.13 ± 1.68 71.5% 33.6% 1990–1999 Female 1691 3279 1434 1.95 ± 1.57 84.8% 43.7% Male 2164 4275 1729 1.98 ± 1.71 79.9% 40.4% 2000–2009 Female 5438 8666 4813 1.59 ± 1.14 88.5% 55.5% Male 7287 11846 6192 1.63 ± 1.32 85.0% 52.3% 2010–2019 Female 8891 12238 7378 1.38 ± 0.86 83.0% 60.3% Male 8365 12041 6845 1.35 ± 0.85 81.8% 56.8% Clinical examination 1978–1989 Female 257 503 233 1.96 ± 1.58 90.7% 46.3% Male 543 1085 471 2.00 ± 1.47 86.7% 43.4% 1990–1999 Female 1156 2037 1084 1.76 ± 1.07 93.8% 53.2% Male 1432 2917 1243 2.04 ± 1.35 86.8% 42.6% 2000–2009 Female 2636 3662 2428 1.39 ± 0.82 92.1% 66.3% Male 3170 5036 2772 1.59 ± 1.08 87.4% 55.0% 2010–2019 Female 6150 9802 4535 1.59 ± 1.03 73.7% 46.3% Male 5053 9184 3132 1.82 ± 1.30 62.0% 34.1% * MCQ = multiple choice question; SD = standard deviation. * The Australian Medical Examining Council did not list candidates’ gender in a few instances during the first decade. Box 5 – Australian Medical Council multiple choice question (MCQ) examination, 1978–2019: pass rates versus (A) age and (B) recency (interval since graduation) in the year when candidates first attempted the MCQ (all countries combined)* Spearman rank order correlation: (A) r = −0.964, P < 0.001; (B) r = −0.983, P < 0.001. Box 6 – Australian Medical Council clinical examination, 1978–2019: pass rates versus (A) age and (B) recency in year when the examination was first attempted* * Spearman rank order correlation: (A) r = −0.950, P < 0.001; (B) r = −0.950, P < 0.001.

Neville D Yeomans · Jillian R Sewell · Philip Pigou · Stuart Macintyre

Modelling suggests that elimination could have been achieved if Victoria had gone into stage 4 lockdown immediately from 9 July Victoria is the unlucky state in a lucky country. Australian states and territories, other than New South Wales, have achieved elimination of community transmission of the sudden acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2): 28 days of no locally acquired cases where the source is unknown; twice the maximum incubation period. The situation in NSW is mixed. On one hand, NSW had ongoing case notifications of 10–20 per day in the month to mid‐August 2020, arising largely from imported cases from Victoria. On the other hand, on 16 July there had only been three locally acquired cases of SARS‐CoV‐2 infection with no known source in the preceding 28 days, suggesting NSW was on the cusp of elimination.1 If NSW successfully contains the current outbreak, it may resume its prior trajectory towards the elimination of local transmission, leaving Victoria isolated as the only state with community transmission. As of late August, Queensland is also experiencing community transmission — possibly ending its elimination status (28 days of no locally acquired cases where the source is unknown), subject to investigation of the new cases. It seems unlikely that states and territories that have eliminated local transmission will relinquish their status by freely opening borders and engaging with Victoria (and NSW if community transmission remains). Indeed, on 17 August the Queensland Premier stated: “Let me make it very clear, we will always put Queenslanders first and … we do not have any intentions of opening any borders while there is community transmission active in Victoria and in New South Wales”.2 Australia proceeding with two separate systems (six or seven states and territories having eliminated the virus, one or two not) is a significant concern. There are three general strategic policy responses to the challenge of coronavirus disease 2019 (COVID‐19): elimination, suppression, and mitigation (or herd immunity). No response is free of economic, social and health harms; rather, it is about minimising harm. Society has largely rejected a mitigation response because of concerns about the likely high morbidity and mortality arising from such a response. On 24 July, the Australian Health Protection Principal Committee recommended “that the goal for Australia is to have no community transmission of COVID‐19”,3 and on the same day Prime Minister Scott Morrison accepted and affirmed this recommendation, stating “The goal of that is obviously, and has always been no community transmission”.4 Unfortunately, this first clear statement that Australia's goal is to eliminate community transmission was late in coming, as the Victorian outbreak was already in full swing, with case numbers peaking at a 5‐day average of about 500 per day from 29 July to 5 August, resulting in a stage 4 lockdown in metropolitan Melbourne from 6 pm on 2 August. Elimination strategy We know from New Zealand (population, 5.0 million)5 and Taiwan (23.8 million)6 that elimination of community transmission is achievable in island jurisdictions, with NZ having no community transmission for 102 days until 11 August. The advantage of elimination is that despite international border closures or strict quarantine, citizens can go about life with a near‐normal functioning of their society and economy. Elimination presents challenges. First, there is the extra effort to achieve it, and the fact that aiming to achieve elimination does not guarantee success. Second, having achieved elimination, there is the constant risk of the virus re‐entering due to quarantine breaches (eg, the current outbreak in NZ). How frequently a COVID‐19‐free jurisdiction with tight border controls will retain elimination status is unclear, although we know that NZ lasted 102 days with no community transmission and that Western Australia, Northern Territory, South Australia, Australian Capital Territory, Queensland and Tasmania achieved over 100 days without a locally acquired case with no known source (although the status of Queensland is unclear as of early September). Was elimination achievable with a 6‐week stage 3 lockdown as implemented in Victoria from 9 July, or a more stringent lockdown? Lockdowns are effective for COVID‐19 pandemic control.7,8 Our case for an explicit elimination strategy in Victoria at lockdown commencement in early July was that given Victoria was going into a lockdown for 6 weeks, there was probably only a marginal extra cost of “going hard” with a rigorous public health response that increased the probability of achieving elimination. But was elimination achievable within 6 weeks? We examined four policy scenarios using an agent‐based model, a type of microsimulation of individuals. The model accurately reflects the prior experience of both NZ and Australia ( https://github.com/JTHooker/COVIDModel), and here we adapted it to Victoria (including the case counts up to 14 July; see Supporting Information for details). The four policy approaches, all simulated from 9 July 2020, were: Standard: reflecting the first Australian stage 3 lockdown (calibrated to case numbers as described at https://github.com/JTHooker/COVIDModel), with key parameters including 85% of people observing physical distancing; those observing physical distancing doing so 85% of the time; 30% of adult workers being essential workers; 93% of people asked to isolate doing so; 20% uptake of the COVIDSafe app; but no closure of schools and no mask wearing. Standard with masks at 50%: Standard, plus 50% of people wearing masks in crowded indoor environments. Stringent with masks at 50%: Standard with masks at 50%, plus schools closed and essential workers restricted to 20% of workers. Stringent with masks at 90%: Stringent, with mask use increased to 90% (ie, close to stage 4, which was implemented in Melbourne from 6 pm on 2 August after the 5‐day moving average case numbers increased from 300 to 500 in the first 3 weeks of stage 3). Box 1 shows the percentage likelihood of elimination in Victoria, defined as the date of clearance of infection by the last case, and the date of last acquisition of infection. The model is omniscient about infectious status; in the real world, based on a definition of 28 days of no cases, elimination would occur about 2 weeks after the clearance dates shown in Box 1, A. Under the “standard” policy approach (ie, equivalent to stage 3 without masks), there was no chance that all infected people would have cleared their SARS‐CoV‐2 infection by 19 August (6 weeks after lockdown commenced; Box 1, A). The probabilities for the other three policy approaches achieving elimination 6 weeks after implementation (Box 1, A) were 0% for “standard with masks at 50%”; about 4% for “stringent with masks at 50%”; and 30% for “stringent with masks at 90%”. The probabilities of the last actual infection occurring by 19 August were more encouraging at 0%, 1%, 45% and 90%, respectively (Box 1, B). Of particular note, given that the stage 3 lockdown imposed on 9 July failed because caseloads increased to an average of 500 per day, in our simulations 48% of the 1000 iterations of the “standard” scenario (stage 3, no masks) and 22% of the 1000 iterations for “standard with masks at 50%” had peaks in the first 3 weeks in excess of 400 per day. This is consistent with what eventuated, and further speaks (in hindsight) to the desirability of entering a stage 4 lockdown on 9 July; the “stringent with masks at 90%” scenario had no instances of peak cases greater than 400 per day in the first 3 weeks. Undertaking simulation modelling of SARS‐CoV‐2 policy options is challenging and the uncertainties are still considerable even when using the best estimates available. Nevertheless, our results lend weight to the proposition that elimination was achievable if Victoria had gone into stage 4 lockdown with mandatory wearing of masks immediately from 9 July. A ten‐point plan to maximise the chance of elimination in Victoria Box 2 lists enhancements to the stay‐at‐home orders of the 9 July lockdown. The first and critical point was leadership. As above, we did get a clear statement of an elimination goal from the Chief Health Officers (who comprise the Australian Health Protection Principal Committee membership) and Prime Minister Scott Morrison on 24 July, but with the benefit of hindsight it was perhaps too late. Target‐setting is still not occurring (eg, a target number of cases per day could be set for when we step out of stage 4 under both elimination and suppression strategy options). Moreover, an expert advisory group on elimination was not convened, limiting the capacity for an optimal evidence‐informed policy response. Nevertheless, since the 9 July lockdown, progress with other aspects of the ten‐point plan has been made with the closure of schools, mandatory mask wearing, and commitments to improve contact tracing capacity. Conclusion We argued in the preprint version of this article on 17 July that Melbourne and Victoria should not waste the opportunity that the (then) 6‐week lockdown presented and go hard and early. By learning from the lessons on social and preventive measures to lower SARS‐CoV‐2 transmissibility,7,8,12,14 and specifically the lessons from NZ,3 Taiwan and the six Australian jurisdictions that have achieved elimination, Victoria could have increased its chances of also eliminating community transmission. Our work and that of others who have independently considered the alternatives consistently demonstrates that elimination was possible, and if achieved would have been optimal for health and for the economy in the long term.15,16,17 In this article, we modelled the situation as at mid‐July — we are now updating modelling under the current situation. Authors’ note: This Perspective was submitted to the MJA on 16 July 2020 and published as a preprint on 17 July.9 The revised version, submitted on 23 August, retains the simulation modelling of the original but the uncertainty of inputs was updated to include uncertainty other than stochastic uncertainty. Our aim was rapid modelling to estimate the probability of virus elimination during the planned 6‐week stage 3 lockdown that Victoria had just commenced. The revised version was also published as a preprint on mja.com.au on 4 September, following full peer review and prior to typesetting, pagination and proofreading. Box 1 – Percentage likelihood of elimination of community transmission of SARS‐CoV‐2 infection in Victoria, by date of clearance of last active infection (A) and date of acquisition of last infection (B)* * Across 1000 Monte Carlo simulations in an agent‐based SEIR (susceptible, exposed, infectious, recovered) model. The vertical dashed line is the date 6 weeks after implementation of the lockdown policies. Compared with modelling published in the preprint version of this article,9 the only change here is the inclusion of additional parameter uncertainty in addition to stochastic uncertainty (see Supporting Information), resulting in increased sloping in the curves due to a wider range of potential parameter values (ie, the time distribution to elimination is wider). Box 2 – A ten‐point plan to maximise the chance of successful elimination of community transmission of SARS‐CoV‐2 in Victoria, based on the planned 6‐week lockdown from 9 July 2020 (as published on 17 July 2020)9 Strong and decisive leadership with strategic clarity. An explicit goal of elimination should be articulated, learning from the New Zealand experience (Prime Minister Jacinda Ardern, government ministers and senior officials).10 A clear set of targets for loosening of policies needs to be articulated, so citizens know what is likely to happen and when. Convene an advisory group of experts in the elimination strategy and SARS‐CoV‐2 public health response, reporting weekly to the Victorian Chief Health Officer, with the agenda, papers and minutes made publicly available. Close all schools. Although children do not usually suffer severe illness from SARS‐CoV‐2 infection, the virus still transmits between children and staff in schools.11 Accordingly, schools need to close until such time as the daily rate of SARS‐CoV‐2 infection without a known source falls beneath a target set by the Chief Health Officer. Tighten the definition of essential shops to remain open. Supermarkets and chemists need to remain open. However, department stores and hardware stores should be closed. A staged re‐opening based on set target levels of daily numbers of SARS‐CoV‐2 infection without a known source should then be implemented, so long as mask wearing by both staff and patrons is mandatory, along with hand sanitiser use on entry and exit from stores. Require mask wearing by Melbourne residents in indoor environments where 1.5 m physical distancing cannot be ensured, such as supermarkets and (especially) public transport. While no panacea, the wearing of masks reduces the chance of infected people spreading the virus.12 Tighten the definition of essential workers and work. There is currently a loose definition of who is an essential worker and what is essential work. This needs urgent tightening; for example, as per the NZ definitions used in their level 4 lockdown.13 Require mask wearing by essential workers whenever they are in close contact with people other than those in their immediate household. Ensure financial and other supports to businesses, community and other groups most affected by more stringent stay‐at-home and lockdown requirements, and provide enhancements, targeted where warranted, to programs such as JobKeeper and JobSeeker. Further strengthen contact tracing to ensure the majority of notifications (and their close contacts) are interviewed within 24 hours of the index case notification and placed in isolation if necessary. The use of smart phone and digital adjuncts needs to be improved, be that for initial contact tracing (eg, the COVIDSafe app, or a South Korean‐style use of telecommunications data) or monitoring of adequacy of isolation (eg, text message follow‐up, GPS monitoring, or electronic bracelets). Extend suspension of international arrivals into Victorian quarantine and divert resources. To allow a stronger focus on elimination within Victoria, extend the suspension of international arrivals to Victoria. Quarantine capacity can be redeployed for isolation of Melbourne residents infected with SARS‐CoV‐2 (and potentially high risk close contacts) if they do not have satisfactory home environments for self‐isolation.

Tony Blakely · Jason Thompson · Natalie Carvalho · Laxman Bablani · Nick Wilson · Mark Stevenson

Serological assays for SARS‐CoV‐2 present challenges and opportunities Timely, scalable and accurate diagnostic testing is crucial in the prevention and control of the coronavirus disease 2019 (COVID‐19) pandemic.1 With limited treatment options and no available vaccine, the accurate and timely identification of infectious patients with COVID‐19 is instrumental to the public health outbreak response. Isolation of patients with COVID‐19, contact tracing and quarantine measures, in addition to physical distancing within the community, have proven effective in reducing case numbers.2 Due to the high sensitivity and specificity in symptomatic individuals, detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection by reverse transcriptase polymerase chain reaction (RT‐PCR) is the gold standard method for confirming cases of COVID‐19.3 In contrast, serological assays have lower utility in the initial investigation of suspected cases, but are essential in the development and evaluation of therapeutic agents and to inform modelling and public health policy as this pandemic progresses. As part of initial laboratory responses, Chinese investigators released the viral whole genome sequence in early January 2020, which enabled the rapid development of RT‐PCR workflows for the detection of SARS‐CoV‐2.4 However, the unprecedented scale of RT‐PCR diagnostic testing has placed extraordinary demands on health care and laboratory systems, with both challenges relating to supply chains of reagents and to the workforce resource required to support population‐level testing. Since the start of the pandemic, a range of commercially available diagnostic tests has been released, including RT‐PCR assays, point‐of‐care and laboratory‐based serological tests. These tests vary both in analytical performance and in their particular utility in the overall public health response to COVID‐19. Performance aspects of serological tests Following SARS‐CoV‐2 infection, specific antibodies to different components of this virus are generated. Depending on the antigen target used by the assay, detection of these antibodies (IgM, IgA, IgG or total antibody) may indicate exposure (non‐neutralising antibodies) or potential immunity (neutralising antibodies). To date, a range of serological tests for COVID‐19 have been developed, each with particular test characteristics (Box 1). Broadly, these serological tests can be divided into tests that (i) can be performed at the point‐of‐care; (ii) can be performed in routine diagnostic laboratories, and (iii) can only be performed in specialised reference laboratories (Box 1). The majority of point‐of‐care and laboratory‐based assays have incorporated either the nucleocapsid antigen (N) or part of the spike protein (S), often the S1 region or the receptor binding domain (RBD). The RBD has been shown to correlate well with the production of neutralising antibodies,5 while some studies have shown N to be immunodominant, producing an earlier or stronger immune response.6 Most patients with COVID‐19 seroconvert by day 10–14 (~ 80%) following the onset of symptoms, with almost 100% seroconversion by day 20.7 However, comparisons across published studies are challenging due to the different antigens used in assays, differences in the complexity of patient populations, variations in the RT‐PCR assays used as the gold standard for determining the sensitivity of serological assays, and often limited data on the timing of sample collection post‐COVID‐19 symptom onset. Further, it is not clear whether the type and amount of antibody correlate with severity of disease or, more importantly, with immune protection from re‐infection. As noted by the World Health Organization, the Australian Public Health Laboratory Network (PHLN) and the Royal College of Pathologists of Australasia (RCPA), a negative result using a serological test does not rule out SARS‐CoV‐2 infection, particularly in individuals with strong epidemiological risk factors, and both the PHLN and the RCPA note that there is no role for serological point‐of‐care tests (PoCT) in the acute diagnosis of COVID‐19.8,9 Point‐of‐care testing As some of the first COVID‐19 serological assays available, significant publicity accompanied the release of PoCT. PoCT involve detection of anti‐SARS‐CoV‐2 antibodies through binding to immobilised antigens, generally bound to colloidal gold on a test strip (Box 2). The relatively cheap and simple nature of lateral flow assays means that production is suited to scale‐up for increased testing capacity. Post‐market validation studies have demonstrated variable performance characteristics, often inferior to that reported by manufacturers, with sensitivities for IgG reported in the range of 53–100% for samples collected more than 14 days after symptom onset, and specificities of 91.7–100%.10,11 Careful test selection and consideration of the clinical utility before application are therefore critical. The National Pathology Accreditation Advisory Council has existing guidelines on the use of PoCT in Australia.12 These guidelines cover issues such as clinical supervision for performing PoCT, ensuring test quality, staff training and competency for performing PoCT, and appropriate reporting of test results. More recently, this advice has been extended to serological PoCT for COVID‐19, with an emphasis on a robust quality framework to support the implementation and deployment of such tests. Of note, in Australia, the supply of self‐testing kits (eg, testing at home) for many infectious diseases, including COVID‐19, is prohibited under another Therapeutic Goods Administration regulation, the Therapeutic Goods (Excluded Purposes) Specification 2010.13 Laboratory‐based assays A wide variety of laboratory‐based serological assays are now available, most commonly enzyme immunosorbent assays (ELISA) or chemiluminescent immunoassay (CLIA/CMIA) format. Assays may be semi‐automatic or completely automated, lending themselves to large scale testing and reporting. In general, performance characteristics have been more consistent and closer to that reported by manufacturer's compared with PoCT, with IgG sensitivities in the range of 80–100% for samples collected more than 14 days after symptom onset, and specificity commonly falling between 95% and 100%.10,11,14 Use of serological assays Given the time lag from symptom onset to detectable antibody, serological PoCT have no role in the detection of acute COVID‐19. However, there are some settings where serological assays, including PoCT, may have potential utility, including defining antibody prevalence in key populations such as frontline workers and determining the extent of COVID‐19 transmission within the community. For other applications, such as identifying individuals for further evaluation of therapeutic immunoglobulin donation and vaccine development and evaluation, assays that assess neutralising antibody response are likely to be required. Regardless of the type of serological assay used, in order to appropriately deploy serological testing, it is critical to understand the limitations of test performance in the epidemiological context in which tests are used. This is particularly important in a setting such as Australia, where, based on the number of reported cases of COVID‐19 (24 236 cases as of 20 August 2020), there is an estimated COVID‐19 period prevalence of 0.095% (January to August 2020). As such, even with serological tests that are highly sensitive and specific, the majority of positive tests are likely to represent false positive results. When considering the use of serology to inform policies relating to relaxing of physical distancing interventions, the specificity of the assay becomes critical. If most individuals considered immune actually represent false positive results, then the threshold to maintain immunity (if this indeed correlates with antibody detection) within the community will not be achieved. Consideration should therefore be given for confirmation of initial positive results by either retesting on an assay with an alternative target, or retesting with serological gold standard assays, such as microneutralisation or western blot assays.15 Application of serological assays and future research needs Understanding local transmission dynamics and/or exposure risk through serological surveys can inform local health policy at an institutional, state or national level. For example, a recent large serological survey in Spain, including more than 50 000 residents, used both PoCT and a laboratory‐based CLIA to estimate a seroprevalence across the country of 5.0%, following an initial COVID‐19 outbreak in February to April.16 It was estimated that approximately a third of cases were asymptomatic, while health care workers had a higher seropositivity than the community (10.2% v 5.0%). This is in contrast to health care workers in Belgium, where direct contact with patients with COVID‐19 did not increase the odds of being seropositive.17 The degree and duration of immunity following SARS‐CoV‐2 infection is unknown, but if in keeping with other coronaviruses (approximately 40 weeks), immunity is unlikely to be lifelong and may be shorter lived in milder infections.7 Duration of immunity is a critical area for future research, as it is the key component in models estimating the frequency of SARS‐CoV‐2 infection incidence in the coming years (eg, second or third waves, or annual seasonal COVID‐19 activity similar to influenza), and to determine the utility of policies such as “immunity passports”.18 Conclusion The unprecedented demands on laboratories to rapidly upscale testing for COVID‐19 has necessarily led to fast‐tracking of normally stringent regulatory requirements for test approval, both globally and in Australia. Following the recent publication of peer‐reviewed high quality validation data, serological testing is now available in many Australian laboratories. Serological testing will complement the current clinical utility of RT‐PCR for SARS‐CoV‐2 infection diagnosis, highlight local transmission dynamics, and further our understanding of what the future brings for the COVID‐19 pandemic. Box 1 – Main serological assays used to date for the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Serological assay Detection method Advantages Disadvantages Implications Neutralisation Determines ability of test sera to inhibit live virus replication Gold standard Highly specific Requires PC3 facilities Technically demanding Slow turnaround time Low throughput Only undertaken in specialist laboratories Gold standard for initial validation of other assays and challenging cases Not suited to routine testing Indirect fluorescent antibody (IFA) Whole virus inactivated and fixed to a slide Addition of test sera with fluorescent detection of antibody binding Can be undertaken at PC2 facilities once slides prepared Less technically demanding than neutralisation assays Preparation of slides requires PC3 facilities Less specific than neutralisation Technically demanding Subjective end point Low throughput Not available in routine laboratories Not suited to large‐scale testing Enzyme immunoassay (EIA) Recombinant antigen fixed to solid surface (often 96 well plate), test sera applied and antigen–antibody binding detected by enzyme‐mediated colour change Good sensitivity Less technically demanding than IFA or neutralisation Semi‐automated High throughput Objective end point with machine‐based optical density reading Less specific than neutralisation Initial expertise and time required to determine, test and manufacture suitable recombinant antigen Generally relies on commercial companies to manufacture and distribute test kits Suitable for routine testing Good for screening Lateral flow EIA A particular type of EIA Recombinant antigen present on immunochromatographic paper, test sera applied to test pad, antigen‐antibody binding detected visually by colour change on a membrane Variable sensitivity Least technically demanding Fast turnaround time for individual tests Test on demand May be less sensitive and specific than laboratory‐based assays Limited scalability Subjective end point Data capture less robust Suited to point‐of‐care testing Can be undertaken by non‐laboratory staff Systems for data capture of results need to be implemented PC2 = physical containment level 2; PC3 = physical containment level 3. Box 2 – Schematic of a lateral flow immunoassay for detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgM and IgG antibodies* *The sample is added to the sample pad, and then travels by capillary motion to the conjugation pad. Anti‐SARS‐CoV‐2 IgM and/or IgG antibodies in the patient sample then bind to the specific SARS‐CoV‐2 antigen. This antigen is bound to colloidal gold, which acts as a colorimetric indicator. The bound antigen‐antibody‐gold complex then travels to the nitrocellulose membrane and bind to specific anti‐human IgM or IgG antibodies, with a resultant colorimetric change. To monitor test validity, excess conjugated colloidal gold binds to antibody on the control line, which allows assessment of whether the fluid has successfully migrated across the test strip. Source: Adapted from Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid IgM–IgG combined antibody test for SARS‐CoV‐2 infection diagnosis. J Med Virol 2020; https://doi.org/10.1002/jmv.25727. [Epub ahead of print]

Katherine Bond · Eloise Williams · Benjamin P Howden · Deborah A Williamson

We need to burn, but it is not a cure-all and the side effects can be serious

Fay H Johnston

Guidelines need to reflect the mounting evidence for airborne transmission of SARS-CoV-2

C Raina MacIntyre · Michelle Ananda‐Rajah · Mark Nicholls · Ashley L Quigley

Some form of diagnostic error occurs in up to one in seven clinical encounters, and most are preventable Diagnosis consists of eliciting information from history and examination, formulating a differential diagnosis, and selecting a final diagnosis based on the predictive value of specific clinical features and laboratory investigations. A timely and accurate diagnosis is every patient’s expectation. Prevalence, impacts and causes of diagnostic error Diagnostic error comprising missed, wrong or delayed diagnoses (Box 1) affects between 8% and 15% of all hospital admissions in the United States,1,2 with similar rates among patients with common diseases attending outpatient clinics.1 As many as 1.1% of adult hospital admissions will involve diagnostic error that causes harm to patients.3 Nearly a third of all preventable deaths in acute hospitals in the United Kingdom are attributed to diagnostic error.4 In Australia, an estimated 140 000 cases of diagnostic error occur each year, with 21 000 cases of serious harm and 2000–4000 deaths.5 Almost one in two malpractice claims against general practitioners involves diagnostic error.6 More than 80% of diagnostic errors are deemed preventable.7 Cognitive factors in clinician decision making are primary or contributory causes of more than 75% of diagnostic errors, with system errors (eg, missed communication or follow‐up of a laboratory test result) being less frequent.1 Failure to formulate an adequate differential diagnosis8 and overconfidence in incorrect diagnoses9 are major contributors. Clinical culture discourages disclosure of diagnostic errors and they are largely neglected within professional training curricula10 and organisational quality and safety programs.11 Identifying the cognitive causes of diagnostic error which can inform preventive strategies requires an understanding of clinical reasoning (Box 2).12,13,14,15 Intuitive thinking is the preferred reasoning mode, using heuristics (ie, mental shortcuts or rules of thumb) to accelerate the process by limiting the load on short term working memory to no more than seven ideas at a time. While efficient and accurate in many situations, heuristics can be misapplied due to cognitive bias (Box 3). Emotions, fatigue, distractions, peer opinions, and cultural norms can also further impair cognitive fidelity. Strategies to prevent diagnostic error Various preventive strategies have been proposed, the choice of which may vary according to clinician experience, types of clinical scenarios encountered, and the clinical environment. Optimise the clinical interview Taking a good history, including collateral information from relatives and other health professionals, and performing an adequate physical examination are fundamental. In combination, these will yield the correct diagnosis in more than 80% of cases,16 while failure to enact them contributes to 40% of missed diagnoses.5,17 Target education to specific scenarios commonly associated with diagnostic error Knowledge deficits are infrequent (< 5%) causes of diagnostic error among practising clinicians.18 It is not that clinicians are unfamiliar with a diagnosis, they simply fail to consider it when appropriate. Educational interventions to increase overall knowledge do not necessarily improve diagnostic performance.19 More useful is tuition focused on scenarios involving frequently missed or wrongly diagnosed conditions, including vascular events, infections, cancer, and neurological disorders (eg, multiple sclerosis).20 Targeted training, such as how to recognise subarachnoid haemorrhage,21 has prevented some condition‐specific diagnostic errors. Verify past diagnostic labels Between 11% and 40% of listed diagnoses in older patients with Parkinson disease, dementia, heart failure and chronic obstructive pulmonary disease do not satisfy accepted diagnostic criteria.22 Verification of past diagnoses, especially those based solely on subjective judgements and lacking specific diagnostic tests, is needed when clinical trajectories are atypical or appropriate therapies yield no response. Implement strategies for reducing cognitive errors Recent reviews describe various strategies for reducing cognitive errors23,24,25 with varying levels of evidence of efficacy. Lectures, seminars, group discussions, and interactive videos can all improve knowledge of cognitive biases and debiasing strategies, broaden differential diagnosis, and enhance reasoning processes. However, evidence of improved diagnostic accuracy is lacking, suggesting that, despite such educational interventions, clinicians may still not reliably identify when biases are influencing diagnostic decisions. Diagnostic checklists can take various forms: a generic checklist prompting clinicians to optimise their cognitive approach; a differential diagnosis checklist prompting clinicians to consider the correct diagnosis as a possibility; and Only the differential diagnosis checklists show improvements in the completeness of differential diagnosis in simulated or actual cases.27 In one study, a differential diagnosis checklist led to fewer errors overall;28 another similar tool combined with a debiasing checklist increased diagnostic accuracy compared with intuitive reasoning.29 Cognitive forcing strategies, defined loosely as any form of disciplined thinking, require clinicians to consciously slow their thinking and systematically evaluate all potential alternatives and mimics before finalising a diagnosis.30 In some studies,31 but not others,32 this approach improves diagnostic accuracy compared with first impression diagnoses or reasoning without any specific instruction. In one study, instructing participants to reconsider their diagnosis after removing a distracting detail from the case outline greatly improved diagnostic accuracy.33 Similar to cognitive forcing strategies, analytical reasoning involves instructing participants to use a guided, analytical approach (System 2) rather than rapid intuition (System 1). Diagnostic accuracy improves,34,35 more so when dealing with complex cases,36 and in a randomised trial,35 this approach overcame deliberate attempts within test cases to induce cognitive biases. Deliberate practice actively engages clinicians in solving diagnostic conundrums (real or vignette) and verbalising their reasoning (“thinking out loud”) as the case unfolds.37 By comparing participants’ reasoning with those of an expert who has worked through the same case, cognitive errors and knowledge deficits can be identified. Simply seeing more cases, without any attempt at calibration, does not guarantee diagnostic expertise,12 although whether deliberate practice improves diagnostic accuracy remains uncertain. Metacognition involves clinicians thinking about their thinking and reflecting on past diagnoses and appropriate use of heuristics. In some studies, cued and modelled reflection improves diagnostic accuracy compared with a more generic, free‐floating reflection38 or leaving participants to reflect in whatever way they choose.39 Seeking second opinions on one’s diagnoses from one’s clinical peers can increase diagnostic accuracy by as much as a third.40 Seeking the diagnostic opinion of patients, families and other members of the health care team, even if expressed in general terms, can also help detect and prevent errors.41 Following up patients over time, asking patients and colleagues to report errors, and implementing protocols for identifying errors (eg, trigger tools within electronic medical records for identifying unexpected adverse events or unplanned readmissions, or systematic identification of errors within mortality and morbidity meetings) all provide information on final outcomes, thus checking the accuracy of initial diagnoses. Such strategies, combined with reflection on identified errors (“cognitive autopsies”), improve diagnostic performance.42,43 Such feedback is important as clinicians’ self‐assessment of their diagnostic accuracy is unreliable and their level of diagnostic confidence can be insensitive to both accuracy and case difficulty.9 Feedback also tempers over‐reliance on the results of diagnostic tests that are at odds with the overall clinical picture and likelihood of a specific disease.44 High risk clinical environments, in which diagnostic error is more likely to occur, require clinicians to be more vigilant about their reasoning in such circumstances.45 Rushed clinical handovers, heavy caseloads, distractions and interruptions, caring for critically ill or complex multimorbid patients, interactions with uncooperative or non‐communicative patients, and clinician fatigue or personal stressors are some examples.46 Computer‐assisted diagnosis in various forms can improve diagnostic performance. Computed decision support systems that generate differential diagnoses using inputted clinical data yield small improvements in diagnostic accuracy when clinicians revisit their diagnoses following a differential diagnosis generator consultation.47 A digital image library of skin eruptions increased diagnostic accuracy of dermatology residents by 19% in a randomised trial.48 An interactive computed decision support system achieved up to 75% reduction in diagnostic errors relating to vignettes of neurological disorders.49 A web‐based system that facilitated internet crowdsourcing of multiple opinions improved diagnostic accuracy among junior physicians.50 Acknowledging, explaining and sharing diagnostic uncertainty with patients helps to protect clinicians from rushing to ill‐considered diagnoses. Up to 40% of first‐contact primary care consultations involving a diagnostic question do not yield a definite answer.51 In such situations, clinicians may feel pressured to prematurely commit to a diagnosis in order to activate management plans and demonstrate competence. In contrast, patients welcome an open discussion of possible differential diagnoses and a plan and timeline for ongoing review.52 Injudicious ordering of multiple diagnostic tests to reduce uncertainty does not reduce patient anxiety and may cause harm from false positive results.53 Need for more research into diagnostic reasoning While we have sought to shed light on the causes and prevention of diagnostic error, we concede current research has several limitations: enrolment of predominantly novice rather than experienced clinicians; non‐randomised or before and after designs; relatively small samples; short term follow‐up; variable methodological rigour; missing data; and multiple, often unvalidated, measures of error and reasoning style. Primary outcome measures are restricted to improvements in knowledge or skills in vignette studies, although these are deemed reliable proxy measures of real‐world decision making.54 Strengthening the evidence base for error mitigation is one objective of the recently established Australian and New Zealand Affiliate of the US Society to Improve Diagnosis in Medicine. This group aims to improve clinical diagnosis in this country with planned initiatives in practice improvement, research, education, and patient engagement (Supporting information). Conclusion Despite limitations in current research, the scale and harm of diagnostic error obliges clinicians to consider adopting preventive strategies that have reasonable face validity, are easily implementable in workplaces, and target individual decision making. Box 1 – Typology of diagnostic error Diagnostic errors can be of three types: missed diagnosis — the correct diagnosis was never considered; wrong diagnosis — the provisional or working diagnosis is incorrect; delayed diagnosis — sufficient information was available to enable the correct diagnosis, which was eventually made, to be made at an earlier time. The term “overdiagnosis” refers to a separate concept where a diagnosis is correct (eg, a patient has prostate cancer) but the diagnosed condition is not causing symptoms, is of low grade of malignancy, and will not prematurely kill the patient before they die of other diseases. In this scenario, the very act of diagnosing this disease may actually cause harm by invoking needless clinical intervention. It is different to when a diagnosis is actually incorrect, which is the focus of this article. Box 2 – Theories of diagnostic reasoning Proponents of organised (or structured) knowledge emphasise content specificity whereby reasoning proficiency varies from case to case, depending on levels of knowledge of particular clinical scenarios. Clinicians construct multiple illness scripts as mental representations of diagnostic, therapeutic and prognostic attributes of specific conditions.12 These scripts store and, with increasing experience, elaborate knowledge in a readily accessible format for application to new clinical scenarios. This emerging expertise is further developed by deliberate practice under supervision coupled with regular feedback.13 Proponents of cognitive processing (or dual processing theory) describe a rapid, intuitive form of pattern recognition (fast [System 1]) and a more deliberate, analytical approach (slow [System 2]).14 When considering different or even single cases, clinicians oscillate between the two systems according to their level of experience and store of memorised patterns. Expert clinicians spend more time in System 1, novice clinicians more in System 2. Central to System 2 is the hypothetico‐deductive model whereby the initial problem representation, gained from history and containing key clinical features (or cues), triggers a number of possible diagnostic hypotheses. These are ranked in decreasing likelihood and, based on further information from hypothesis‐driven, focused physical examination and selected laboratory investigations, gradually eliminated in arriving at a provisional diagnosis. The two schools of thought are not mutually exclusive and are in fact interdependent. Clearly, more hypotheses may be generated, or more patterns recognised, if the clinician can draw on a larger store of illness scripts that share cues with the problem at hand. Similarly, knowledge becomes more organised more quickly if clinicians consistently and systematically apply analytical thinking to obscure or atypical cases. Approaches to improving diagnostic reasoning vary in their emphasis on expanding organised knowledge, mitigating cognitive bias, or optimising system of care factors according to how much each, in different circumstances, is considered the prime determinant of diagnostic error.15 Box 3 – Common cognitive biases in diagnostic reasoning Bias Definition Example Premature closure Narrow rapid focus on single or a few clinical features in the clinical presentation to support a diagnostic hypothesis without considering other alternatives Patient with rheumatoid arthritis who is receiving immunosuppressive medication presents with shortness of breath, inspiratory crackles on chest auscultation and diffuse fine infiltrates on chest x‐ray. Congestive heart failure is quickly accepted as the diagnosis but subsequent bronchoscopy reveals Pneumocystis pneumonia Anchoring bias Tendency for clinicians to cling to their initial diagnostic hypotheses even as contradictory evidence accumulates Patient with end‐stage renal disease presents with altered mental status and myoclonus of the left arm, which is attributed to uraemia (the anchor). Failure of this syndrome to improve with dialysis (contradictory evidence) is underweighted until clinicians finally accept the eventual diagnosis of status epilepticus Confirmation bias Tendency to selectively search for features that support the initial or favoured diagnostic hypotheses rather than take deliberate note of features that challenge these hypotheses Patient with past history of coeliac disease presents with symptomatic anaemia and low reticulocyte count, which is diagnosed as iron deficiency anaemia. Iron studies showing borderline low serum ferritin are interpreted as confirmatory evidence, while the finding of a widened mediastinum on chest x‐ray is ignored. The patient is later diagnosed as having a thymoma associated with aplastic anaemia Availability bias Tendency to overestimate the probability of a diagnosis based on how easily it is recalled, which is often skewed by recent and memorable, or emotionally laden cases A clinician who has recently seen a patient with myosarcoma who presented with left calf pain then begins to evaluate all subsequent similar presentations for the possibility of the same diagnosis Representativeness bias/base rate neglect Tendency to greatly overestimate the likelihood of a rare diagnosis on the basis of some prototypical features of that disease Patient presenting with pulsatile headache, palpitations, diaphoresis and elevated blood pressure is diagnosed as having a pheochromocytoma (rare disease) whereas anxiety syndrome complicated by severe migraine (common disease) is later verified Framing bias Tendency for a presentation to be framed in a certain way according to past diagnostic labels (diagnostic momentum) or clinical setting (eg, medical v a surgical ward) Patient with long‐standing anorexia nervosa and post‐traumatic stress disorder presents with weight loss, abdominal pain and diarrhoea. Her past history causes the clinician to frame the problem as one related to her mental health, leading to a diagnosis of irritable colon and laxative misuse associated with restrictive feeding. The presence of intermittent rectal bleeding and an elevated erythrocyte sedimentation rate (ESR) are underemphasised. The patient is eventually diagnosed as having Crohn’s disease

Ian A Scott · Carmel Crock

Telehealth offers an opportunity to address limited access to early medical abortion during COVID‐19 and beyond Access to early medical abortion (EMA), using mifepristone followed by misoprostol to end an early pregnancy, remains a challenge in Australia, especially for women from vulnerable groups and those living in rural and regional areas.1 Low numbers of general practitioner providers, lack of peer networks to support the establishment and ongoing provision of EMA services, and stigma are real barriers as is a broader lack of knowledge regarding medical abortion among health professionals.2,3 Many women are also unaware of the availability of EMA and the current gestational limit of 63 days.4 They also face difficulties navigating the health system to find an EMA provider, particularly when they encounter conscientious objections.4,5 Women can also face other barriers such as needing to travel to access services, take time off work or find childcare, and many need to source financial support to meet the costs.5 The current coronavirus disease 2019 (COVID‐19) pandemic has further highlighted existing barriers to accessing EMA services in Australia. During the pandemic, there has been an increase in the demand for abortion because of a rise in unplanned pregnancies and domestic violence.6 Financial insecurity and delays in accessing abortion services, due to travel restrictions or other pandemic‐related stressors, means that women are often presenting for an abortion at a later gestational age.6 In addition, flight restrictions may have curtailed the ability of clinicians to travel to rural areas to provide surgical abortion services. Delivering EMA through telehealth has been shown to be safe, effective and acceptable to women, both internationally and in Australia.7,8,9 Originally championed by Women on Web (www.womenonweb.org), telehealth delivery of EMA was used to provide abortions clandestinely in countries where they were illegal, such as in Ireland prior to decriminalisation.10 It has now, however, been implemented in many countries worldwide, irrespective of whether restrictive or non‐restrictive abortion laws exist, to provide abortion care to women and improve access to women geographically isolated from EMA services.9 Using telehealth to deliver EMA offers an opportunity to address many of the barriers to EMA provision in Australia. It removes the necessity for proximity between the provider and patient, an issue of particular importance for women living in rural and regional areas where there are fewer abortion providers.5,7 The need to travel to appointments far from home, especially when more than one appointment might be required, can result in women moving past the 9‐week gestational limit and preclude them from being able to undergo an EMA.5,7 Not only does the telehealth delivery of EMA reduce the need for patients to travel but it also increases the capacity of existing providers to deliver services to women from a larger geographical area.5,8 The availability of Medicare Benefits Schedule (MBS) telehealth item numbers, introduced as part of the government's response to the pandemic, has meant that, for the first time, telehealth EMA can be delivered through Medicare to eligible patients.11 With these item numbers in place, all EMA providers are able to use telehealth to deliver this service at a potentially reduced cost to women. Before COVID‐19, telehealth item numbers had very restrictive criteria and could only be billed if the patient lived in a very rural area (Modified Monash Model 6 or 7 location), had an existing clinical relationship with a GP telehealth provider (defined as three face‐to‐face consultations in the previous 12 months) and lived at least 15 km by road from the GP.12 These restrictions unfairly excluded many women in metropolitan or regional areas, particularly young women (who comprise the largest demographic using abortion services), as this demographic does not necessarily attend GPs on a regular basis. It is imperative therefore that MBS‐funded telehealth remains implementable by all GPs so that women are not disadvantaged, and that telehealth abortion can remain accessible via Medicare. Recent restrictions to the temporary MBS item numbers for telehealth GP consultations, which came into effect on 20 July 2020 — namely restricting eligibility to only those who have visited the GP or practice in the previous 12 months or those who have been referred by a specialist except for where there is a current lockdown in place13 — will greatly reduce women's access to EMA. Placing restrictions on the eligibility criteria for MBS‐subsidised telehealth services severely affects women's access to GPs who can provide EMA, and discriminates against women who have not recently engaged with a GP due to various forms of disadvantage, such as family violence and unemployment. Exemptions to the restrictions have already been identified for people who are homeless and for children aged less than 12 months. Therefore, a further exemption should also be issued so that registered prescribers of medical abortion are able to use MBS telehealth item numbers for the benefit of Australian women. In addition, other measures are required to optimise the ability of telehealth to improve access to EMA for all Australian women. Firstly, a national hotline or online platform, similar to the 1800 My Options service (www.1800myoptions.org.au) in Victoria, which directs women to local abortion service providers, is required to assist women to identify an appropriate provider. Secondly, as outlined in a consensus statement on EMA developed by a coalition of key stakeholders (ie, the National Health and Medical Research Council's Centre of Research Excellence in Sexual and Reproductive Health for Women in Primary Care [SPHERE]) and clinician experts,14 changes are required to current Therapeutic Goods Administration (TGA) and Pharmaceutical Benefits Scheme (PBS) provisions restricting the prescription of MS‐2 Step (mifepristone and misoprostol) to up to 63 days’ gestation.15 These criteria are outdated and discordant with current evidence demonstrating that EMA up to 70 days’ gestation is comparable in safety and efficacy to 63 days’ gestation or less.16 Guidance from the United States, Canada and the United Kingdom all concur.17,18,19 Increasing gestational limits for prescribing EMA will not only align Australia with international guidance but will also provide a greater window of opportunity for women to access this service. However, this change requires an application to be made to the TGA, and if TGA approval of the extended indication is successful, a subsequent application to the Pharmaceutical Benefits Advisory Committee for subsidy of the extended indication would be required. This is a costly and time‐consuming exercise. Thirdly, modifications are required to EMA protocols, particularly during the COVID‐19 pandemic. Internationally, “no‐touch/no‐test” protocols have been devised and endorsed to minimise the risk of COVID‐19 transmission between patients and providers and circumvent delays created by closed health services (ie, sonography).19,20 In the Australian context, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists has already advised that a clinician may appropriately decide not to administer anti‐D IgG before 10 weeks for the medical management of abortion, particularly when an additional visit may increase exposure of women and staff.21 The SPHERE coalition has additionally recommended that, during the COVID‐19 pandemic, while ultrasound is highly desirable for all women having a telehealth EMA, in situations where obtaining an ultrasound is a significant barrier or poses a significant risk during the COVID‐19 pandemic, EMA may proceed without the necessity of ultrasound assessment.14 However, the consensus statement emphasises that women should be carefully screened for risk factors for ectopic pregnancy. This requires an assessment as to whether an accurate gestational age can be estimated from the woman's history; a discussion regarding the risks of foregoing a pre‐procedure ultrasound as part of the consent process and supported by written information; and a robust follow‐up pathway.14 If the gestation is unable to be accurately identified, or there are red flags for ectopic pregnancy, then an ultrasound assessment must be arranged.14 Finally, abortion has been decriminalised in every state and territory in Australia except South Australia,1 where mifepristone can only be supplied in a hospital setting. This precludes South Australian women from being able to access EMA through community‐based providers such as GPs or via telehealth. The relevant South Australian legislation therefore requires a change.

Danielle Mazza · Seema Deb · Asvini Subasinghe

The advent of CAR T‐cell therapy has seen significant improvements in survival and is a potential cure for patients with advanced haematological malignancies Cancer immunotherapy is a burgeoning field which, in the last decade, has produced unprecedented improvements in outcomes across a variety of advanced malignancies. The eventual translation of decades of research into clinically available immunotherapies stems from the expanded knowledge of the role that the immune system plays in preventing tumour initiation and progression as well as the mechanisms by which tumours learn to evade this immune surveillance.1 Immunotherapies that have reached the clinic include monoclonal antibodies and, more recently, their augmented counterparts including antibody–drug conjugates and bi‐specific T‐cell engagers. Other treatments are immunomodulatory, meaning that they augment endogenous anti‐tumour immune activity. These include immune checkpoint inhibitors such as pembrolizumab, which are prolonging survival in melanoma and several solid organ malignancies as well as relapsed or refractory Hodgkin lymphoma. Cellular immunotherapies offer the potential to overcome immune tolerance and generate immune memory.1 Allogeneic stem cell transplantation (ASCT), a largely unmanipulated form of cellular immunotherapy, acts by completely replacing the recipient’s entire haematopoeitic and immune systems, leveraging differences between the recipient and donor to produce a graft‐versus‐tumour effect, with the potential negative consequence of immune attack on recipient’s normal tissues, known as graft‐versus‐host disease, as well as other serious toxicities. ASCT has been the only curative option for many patients with haematological malignancies. However, it is generally considered a consolidative therapy; that is, the patient’s malignancy must be in or near complete remission in order to be effective. This is not always possible in refractory cases. For others, ASCT may be contraindicated because of age or comorbidities. With advances in genetic manipulation technology, the notion of combining the specificity of a monoclonal antibody with the cytotoxicity and memory of a T‐cell came to fruition in the chimeric antigen receptor (CAR) T‐cell. “Chimeric” here means that the DNA comes from two or more sources; the antigen‐binding domain of the CAR construct is an antibody fragment, tethered to the intracellular signalling domain of the T‐cell receptor, with an additional co‐stimulatory domain acting to improve their expansion and persistence in vivo. The fundamental steps in generating and delivering CAR T‐cell therapy are summarised in Box 1.2 Specific toxicities are characteristic of CAR T‐cell therapy, the two most important being cytokine release syndrome and neurotoxicity. Cytokine release syndrome is an inflammatory state induced by the rapid proliferation of CAR T‐cells and tumour cell death, releasing an array of inflammatory cytokines. The hallmark is a fever, with the potential for hypotension, hypoxia and organ dysfunction. As one of the key cytokines driving the syndrome is interleukin‐6, its blockade using the interleukin‐6 receptor antagonist tocilizumab is now routinely used for more severe grades of cytokine release syndrome. The pathogenesis of neurotoxicity has not been fully elucidated; however, it most often manifests with speech disturbance or aphasia, dysgraphia and attention deficits, with more severe manifestations including altered level of consciousness, seizures and, rarely, cerebral oedema. Fortunately, even patients with severe neurotoxicity who are adequately supported in intensive care settings most often have complete neurological recovery. By far the most successful antigen target of all CAR T‐cell therapies developed to date is the pan‐B‐cell antigen CD19, as it arguably comes closest to the characteristics of an ideal target. CD19 is widely expressed across the full maturation spectrum of B‐cell malignancies, from B‐cell lymphoblastic leukaemia cells to mature B‐cell lymphomas, giving broad applicability. Second, CD19 is only expressed on B‐cells (normal and malignant) and not other tissues. Third, the toxicity resulting from the on‐target, off‐tumour effects, in this case normal B‐cell aplasia, is manageable by immunoglobulin replacement in patients who experience recurrent or severe infections. The decision for health authorities to fund a personalised, genetically engineered treatment is a complex one, taking into account considerations such as cost, efficacy, safety, the level of evidence and the maturity of outcome data, alternative therapies, equity of access, and resource utilisation. The cost of a single product is measured in hundreds of thousands of dollars and the mechanism by which such therapies will be funded is certainly not self‐evident. In the Australian context, the new therapy is evaluated by the Medical Services Advisory Committee, an independent committee that appraises new medical services proposed for public funding, taking into account all the above‐mentioned considerations, and providing advice to government. Moreover, given the high cost and limited, immature data, regulatory bodies worldwide have come to unprecedented outcomes‐based reimbursement agreements with pharmaceutical companies — such as rebates and staged payments according to defined response criteria — in order to mitigate risk. Two CAR T‐cell products targeting CD19 were approved by the United States Food and Drug Administration in 2017 and 2018: tisagenlecleucel and axicabtagene ciloleucel. The landmark studies which led to their approval, and a summary of their key outcomes, are shown in Box 2.3,4,5,6 In Australia, tisagenlecleucel is approved by the Therapeutic Goods Administration for paediatric and young adult patients up to 25 years of age with B‐cell lymphoblastic leukaemia that is refractory, in relapse after transplant or in second or later relapse, as well as adult patients with relapsed or refractory diffuse large B‐cell lymphoma after two or more lines of systemic therapy. In April 2019, a joint state and federal government funding initiative commenced for tisagenlecleucel for the B‐cell lymphoblastic leukaemia indication, and in January 2020, the government announced its funding for diffuse large B‐cell lymphoma. Soon after, the Therapeutic Goods Administration approved axicabtagene ciloleucel in February 2020 and the Medical Services Advisory Committee made a positive recommendation for its public funding for the lymphoma indication. Further, Novartis announced an agreement with an Australian cell and gene therapy manufacturing company for manufacture of tisagenlecleucel for the region to commence in late 2020 (https://www.celltherapies.com.au/kymriah-to-be-manufactured-at-cell-therapies-pty-ltd-marking-australias-first-on-shore-commercial-production-of-car-t-therapy/). In the case of tisagenlecleucel for relapsed or refractory B‐cell lymphoblastic leukaemia, evaluation began with a comparison with best available therapy. In the ELIANA trial4 outcomes compared very favourably with other chemo‐ or immunotherapeutic salvage options such as clofarabine7 and blinatumumab,8 respectively. For example, blinatumomab, a bispecific T‐cell engager, in the paediatric relapsed or refractory setting produced a complete remission rate of 39% within the first two cycles, with a relapse‐free survival at 6 months of 42%, and this therapy is considered to be a bridging therapy to ASCT. Tisagenlecleucel on the other hand can be used as a stand‐alone therapy; however, it is notable that a substantial proportion of responders do relapse, particularly between 6 and 12 months, which raises the question of whether this treatment should also serve as a bridge to ASCT. The available evidence is currently insufficient to confidently provide an answer, and practice therefore varies among treating centres worldwide. However, a major concern is the financial implications of CAR T‐cell therapy as a bridge to ASCT, which itself is a highly resource‐intensive therapy, with some suggestion that the cost‐effectiveness may be unbalanced if this practice were routine. In the case of high grade B‐cell lymphomas, patient outcomes also appear to be superior to other available treatments in the third line setting. In the ZUMA‐1 trial, the recently updated 3‐year overall survival rate of 47% does likely reflect a significant cure fraction.6 In comparison, the SCHOLAR‐1 retrospective study of the outcomes of patients with refractory diffuse large B‐cell lymphoma showed that this pooled patient population only achieved complete remission rates of 7% with conventional therapies and had a median overall survival of 6.3 months.9 One concern is that the outcomes of the CAR T‐cell trials may not be generalisable to the real‐world population where patient selection may not be as strict as in clinical trials. Interestingly, the real‐world data seems to be conflicted on this, with the US experience from the Center for International Blood and Marrow Transplant Research registry being comparable to trial data for both tisagenlecleucel and axicabtagene ciloleucel, while preliminary United Kingdom experience appears to be considerably worse.10,11,12 The cause of this discrepancy is unclear. In terms of future directions, many clinical trials are assessing CAR T‐cells in earlier lines of therapy. For example, two trials are randomising patients in first relapse of large B‐cell lymphoma to receive either CAR T‐cell therapy or standard salvage plus autologous stem cell transplant: ZUMA‐7 (NCT03391466) and BELINDA (NCT03570892). The results of these trials, if favourable, could greatly alter treatment paradigms. Other trials are assessing CAR T‐cells in other B‐cell lymphomas, such as follicular non‐Hodgkin lymphoma (ELARA [NCT03568461]) and mantle cell lymphoma.13 The response to KTE‐X19, an anti‐CD19 CAR T‐cell therapy with a manufacturing process that removes circulating tumour cells, seen in the ZUMA‐2 trial in relapsed or refractory mantle cell lymphoma (overall response rate of 93%) is the highest reported response rate in patients with mantle cell lymphoma who failed previous BTK inhibitor treatment, with a high proportion of durable responses in this very challenging malignancy.13 Strategies to improve the availability and timeliness of CAR T‐cell therapy include the development of third party allogeneic CAR T‐cells, which could produce off‐the‐shelf treatments for many patients. Other alterations to the CAR construct aim to improve characteristics such as persistence and safety, as well as addressing the problem of antigen escape, where the malignancy loses the targeted antigen, potentially through multi‐antigen targeting. Others are combining CAR T‐cells with immunomodulatory therapies such as immune checkpoint inhibition to improve efficacy. Finally, there is great interest in CAR T‐cell therapies for malignancies such as multiple myeloma, acute myeloid leukaemia and T‐cell lymphomas and leukaemias, many of which are at various phases of clinical trials. The furthest advanced are CAR T‐cell therapies targeting B‐cell maturation antigen in multiple myeloma. JNJ‐4528, an investigational B‐cell maturation antigen CAR T‐cell therapy, has recently demonstrated very high response rates in the phase 1b/2 CARTITUDE‐1 study in relapsed or refractory myeloma.14 In the 29‐patient cohort, the overall response rate was 100%, with 69% complete remission, the median time to complete remission being 1 month, and measurable residual disease negativity in all 17 evaluable patients. These are very promising times in cancer immunotherapy and the task ahead for regulatory authorities will be immense as evidence rapidly accumulates for these high cost therapies. In the meantime, we are pleased to add CD19 CAR T‐cell therapy to our armamentarium and await the results of trials across a wide range of haematological and solid organ malignancies. Box 1 – Overview of the processes for manufacture and delivery of a chimeric antigen receptor (CAR) T‐cell product Procurement of T-cells, usually via leukapheresis (1); transduction of the CAR genes via viral vector or non-viral methods (2); ex vivo expansion of the CAR T-cells (3); preconditioning with lymphodepleting chemotherapy (4); and infusion into a patient (5). ◆ Box 2 – Summary of data from pivotal CD19 chimeric antigen receptor (CAR) T‐cell trials Trial name CAR T‐cell product Disease Complete response rate Other response parameters Safety ELIANA4 Tisagenlecleucel Relapsed or refractory paediatric B‐ALL 81% 12‐month OS, 76%; 12‐month EFS, 50% Grade ≥ 3 CRS, 47% Grade ≥ 3 NT, 13% JULIET5 Tisagenlecleucel Relapsed or refractory DLBCL 38% Median OS, 12 months Grade ≥ 3 CRS, 23% Grade ≥ 3 NT, 11% ZUMA‐13,6 Axicabtagene ciloleucel Relapsed or refractory DLBCL 58% 3‐year OS, 47% Grade ≥ 3 CRS, 13% Grade ≥ 3 NT, 28% B‐ALL = B‐cell acute lymphoblastic leukaemia; CRS = cytokine release syndrome; DLBCL = diffuse large B‐cell lymphoma; EFS = event‐free survival; NT = neurotoxicity; OS = overall survival.

Adrian G Selim · Constantine S Tam

Current regulations address product safety, but they do not adequately ensure accuracy of formula preparation and provision Breastmilk is the optimum source of nutrition for most infants born at full term. When breastmilk is unavailable or unsuitable, the only safe and nutritious substitutes are commercial infant formulas.1 Infant formula — predominantly powdered infant formula — makes a major contribution to infant nutrition in Australia, with the 2010 Australian National Infant Feeding Survey reporting that 34% of infants had been introduced formula in their first month of life, 45% by 2 months and 69% by 6 months of age.2 In Australia, infant formula products are regulated under Standard 2.9.1 — Infant Formula Products in the Australia New Zealand Food Standards Code (Std2.9.1IFPANZC).3 All commercially produced infant formula products available in Australia and New Zealand must comply with the composition and safety requirements outlined in the Code. Std2.9.1IFPANZC specifies the mandatory nutrient content for infant formula and follow‐on formula to ensure that nutrition requirements are met. The standard includes labelling requirements, specifically prohibiting various claims, images and symbols. While these regulations address product safety, they do not adequately ensure accuracy of formula preparation and provision. In particular, potential for error remains around formula powder reconstitution, given multiple differing brands with variable scoop to water ratios, and volume of feed for differing ages and body weights. In this article, we discuss the infant formula range available in Australia, the infant formula powder reconstitution variability and the potential impacts, and the variability of manufacturer feeding guides compared with recognised recommendations and potential implications. Formula brands and types In Australia, there are more than ten brands of infant formula from which to choose. Within each brand there are often minor variations, from standard formulas meeting basic Food Standards Australia New Zealand (FSANZ) formula composition guidelines through to manufacturer‐specified gold formulas and condition‐specific formulas (Supporting information, table 1). FSANZ guidelines describe the purpose of infant formula labelling as providing information to caregivers to make informed choices, as well as information about appropriate preparation and safe use of infant formula products. Under FSANZ guidelines, all infant formulas must meet essential nutrient requirements. Specific nutrient content and health claims are prohibited in Clause 3 of Standard 1.2.7.4 Despite regulation, there are often misleading names or ingredient claims on infant formulas which construe a health claim or benefit and create doubt or sway opinion in consumers. For example, “[trade name] constipation”, as a name of a formula may be assumed by a consumer to be a superior formula for babies with constipation. Similarly, a statement of “fish oil to help support brain and eye development” could potentially be interpreted by a consumer as a health claim. There is currently no unbiased, freely available source of information to help parents choose a formula and this is often the first point of confusion. The authors frequently encounter parents swapping formulas in response to their infant's behaviour, believing that another formula may offer benefit. Typical examples in clinical practice are changing from a standard term formula to a colic, antireflux, or casein‐predominant formula when there is irritability or spilling. Powdered formula reconstitution While infant formulas are made in liquid ready‐to‐feed and in powdered forms, the latter is predominantly used in the home. Under Std2.9.1IFPANZC, the labelling of a powdered formula product must include the powder to water reconstitution ratio to achieve the specified nutritional composition, and the weight of powder in one scoop. However, the Standard does not dictate scoop size and, consequently, the scoop to water reconstitution ratio is determined by the manufacturer, although the powder weight to water ratio is relatively constant between manufacturers. In Australia, there is significant variation in reconstitution ratios across brands. Australian infant formula dilution reconstitution ratios are most commonly either one scoop per 30 mL water, per 50 mL water or per 60 mL water. The choice between a smaller or larger ratio is manufacturer‐specific. Explanations company representatives have provided for choosing a smaller scoop to water ratio include being able to make up smaller quantities of formula, greater accuracy, and a reconstitution method that yields rounded number volumes of 100 mL. In contrast, companies with larger scoop to water ratios propose reduced risk of error in sleep‐deprived parents who might lose count of scoops. However, none of these justifications are evidenced‐based. While there is a general expectation that parents use the formula label instructions or community advice, brand changes enhance potential for parental miscalculation of formula concentration. Under Std2.9.1IFPANZC, all powdered infant formula products must carry a warning stating, “Warning — follow instructions exactly. Prepare bottles and teats as directed. Do not change proportions of powder except on medical advice. Incorrect preparation can make your baby very ill”.3 This warning is often not obvious, and in practice, we have observed parents swapping between formulas and either assuming that the scoop to water reconstitution ratio is the same, confusing the ratios between brands, or using the incorrect scoop with a different manufacturer's powder, resulting in incorrect formula concentration. A systematic review of five studies supports this observation, finding that significant errors may be made when reconstituting formulas.5 Incorrect dilution ratio results in a formula strength that is either too dilute, increasing risks of nutrient deficiencies and faltering growth, or too concentrated, risking hypernatraemic dehydration or excessive weight gain. A review of reconstitution recipes of the major brands of standard infant formulas reveals a formula powder to water ratio of 0.142–0.15 g/mL (Supporting information, table 2) and a narrow caloric strength range of 4.8–5.2 Kcal/g. Clearly, a standardised reconstitution recipe is possible. We propose that standardisation of reconstitution ratio of powdered infant formula to water would minimise error and risk while providing clarity for parents and health professionals. Formula feeding guides Infant feeding guidelines for health workers1 state that as a formula is designed to remain at a constant strength, it is the amount of formula that should increase as the infant grows. The guidelines outline approximate formula requirements for infants (Supporting information, table 3), which correlate appropriately with the estimated energy requirements of infants as outlined in the National Health and Medical Research Council (NHMRC) Nutrient reference values for Australia and New Zealand.6 The infant feeding guidelines also note that feeding guidelines on formula packaging recommending certain amounts for various ages are guides only and do not necessarily suit every infant.1 Manufacturers of commercial infant formulas usually include a feeding guideline on the formula packaging that outlines the number and volume of feeds recommended for the corresponding ages. This is not a requirement under the Food Standards Code. There is substantial inconsistency in the feeding guidelines for volume and frequency of feed by age printed on the containers (Box), both from one manufacturer to another and also compared with the NHMRC‐recommended volumes by age and weight. The lack of weight standardisation means that the caregivers of a small infant may overfeed, while a genetically larger infant might be underfed. Greater consistency or standardisation of manufacturer feeding guides that correlate appropriately with the NHMRC feeding guidelines may help reduce both over‐ and underfeeding as well as alleviate parental confusion and anxiety around feeding volumes. While both under‐ and overfeeding may have negative clinical consequences, there are no published data to support adverse outcomes as a common consequence of parental misunderstanding. The absence of published evidence, however, should be considered in the light of anecdotal experience of health professionals within our health service, who report spilling and irritability from overfeeding and parental anxiety when their baby does not achieve volumes stated on the formula tin. Expert opinion concurs with our own clinical experience, as shown by the 2018 guideline on gastroesophageal reflux issued jointly by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPAGHAN), where the first step in management of an infant presenting with excess vomiting is to ensure that overfeeding is avoided.7 However, there is clearly a need for further study in the area of parental interpretation and use of the feeding guides provided on formula tins to determine the impact of variation in product labelling on health outcomes. Conclusion Infant formula is commonly used with a choice of brands and types of formula. There is limited access to unbiased advice on formula selection for parents, caregivers and health professionals who encounter feeding‐related problems in daily practice. In addition, there is a wide variation in reconstitution ratios of powdered infant formula due to differences in scoop sizes between manufacturers, which may contribute to error in formula concentration. Standardisation of reconstitution ratios is an opportunity to minimise error. Lastly, formula feeding guides provided on formula tins vary between companies and, by not accounting for weight, differ from NHMRC recommendations, which may lead to over‐ or underfeeding. Standardisation of formula feeding guides in line with NHMRC feeding guidelines, with clearer warning statements, may help reduce these risks. The absence of evidence as to the effectiveness and risks of current food and nutrition policy with respect to infant formula feeding is a significant gap in ensuring the safe care of infants both in our community and worldwide. We propose that this area becomes a future focus of public health research and advocacy for child health. Box – Standard infant formulas — manufacturer-suggested feeding volume(mL) and number of feeds per day juxtaposed as mL/kg/day for a 3rd centile female infant, 50th centile female infant and 97th centile male infant (World Health Organization growth data)

Shelley Farrent · Brian Coppin · Scott Morris

The pandemic has highlighted some important challenges in our health care system, but system reform can occur rapidly when needed

Gabriel Elan Blecher · Grant A Blashki · Simon Judkins

Compared with the mitigation and suppression approaches of most Western countries, elimination can minimise direct health effects and offer an early return to social and economic activity

Michael G Baker · Amanda Kvalsvig · Ayesha J Verrall

The challenge now is how to implement artificial intelligence technology safely into clinical practice Artificial intelligence is a branch of computer science that, in broad terms, deals with either decision making or classification. The aim of artificial intelligence is to surpass human cognitive functioning such that automated decisions can be made. Machine learning — an application of artificial intelligence — is commonly used in image recognition. In general, the machine, or algorithm, learns from exposure to a large dataset. Once learning has taken place, the algorithm can be applied to unseen data. The potential advantages of this approach in health care are clear: machines can learn from very large datasets in relatively short time frames and can apply themselves to new data without fatigue or intra‐observer replication error. Machine learning has recently demonstrated remarkable performance in image‐based diagnosis across various medical fields, including ophthalmology, radiology, pathology and dermatology. In dermatology, the primary focus has been on developing machine learning systems that facilitate classification and decision support for skin cancer management. Skin cancer (including melanocytic and keratinocytic malignancy) is the most common cancer in Australia and among Caucasian populations worldwide. Melanoma is responsible for the majority of skin cancer deaths in Australia and has various presentations.1,2 While dermoscopy has improved the accuracy of melanoma diagnosis, significant variability occurs and is largely a function of clinical expertise. Recent studies show that machine learning algorithms have the potential to surpass the diagnostic performance of experts, and the challenge now is how to implement this new technology safely into clinical practice. Although there are a number of machine learning algorithms that could be used in the dermatology setting, convolutional neural networks (CNNs) are the most promising. This is largely because they learn from data without any feature specification, and they are known to exhibit superior performance for image recognition in comparison with other machine learning algorithms.3 The aim of the CNN is to generalise its previously learned knowledge on unseen images beyond the training dataset. There are numerous parameters within a CNN that can be tweaked to maximise algorithm performance. Most of these parameters are adjusted automatically by the algorithm, without user input. Therefore, very little can be known, in principle, about why and how the algorithm reaches any particular decision. Currently, there are efforts underway to reduce the “black box” effect of CNNs. Some commercial software programs coupled to imaging devices will provide the user with comparable lesions to justify the algorithm's output and improve transparency. However, this retrieval system may fail for rare or unseen cases and does not provide a decision‐making process. While the black box phenomenon remains, there are two potentially negative implications for clinical practice: first, clinicians may have difficulty upskilling by following the algorithms’ outputs; and second, there exists the potential for deskilling and underperforming due to an over‐reliance on technology.4,5 The effect of a faulty system has been explored by manipulating a previously trusted algorithm to generate incorrect classifications and found that doctors of all experience levels were susceptible to being misled by the recommendation.5 Algorithm performance is dependent on both the size and quality of the training image dataset and on whether the algorithm is used in situations for which it was intended. Depending on the training set, the device may be limited in its ability to diagnose specific lesions (eg, non‐pigmented), or lesions in certain skin types (eg, darker skin) or sites (eg, scalp or acral). Retrospective image databases used to train algorithms may be associated with bias. In addition, artefacts (eg, hair, dermoscopic gel, air bubbles, rulers, pen markings, reflections) can distract from key features. However, if a CNN is trained on a large enough cohort, it can learn to deal with potential artefacts. Nonetheless, unbiased lesion selection and standardised image capture would invariably improve algorithm performance, and recent advances in three‐dimensional (3D) imaging modalities will enable this.6 Several studies have now shown that CNNs trained on retrospective image data collected at a single time point are capable of classifying skin cancer with sensitivities and specificities equal or superior to that of dermatologists (Box 1),5,7,8,9,11 and clinicians with less experience gain most from AI support under experimental conditions.5 Hypomelanotic and acral melanoma can be more challenging to diagnose clinically,1 and this could potentially present a challenge for automated classification. However, CNNs have achieved greater accuracy for hypopigmented and acral lesions in comparison with human experts, at least in silica.9,11 In addition to clinical images, CNNs have been applied to histopathological images of melanoma and benign naevi with promising results.10 The ground truth for lesion diagnosis The gold standard for melanoma diagnosis is histopathological assessment. However, there exists significant inter‐ and intra‐observer variability in histological diagnostic labels attributed to atypical melanocytic lesions.12 The existence of such variability in diagnoses poses the dilemma of whether the CNN has learnt from the correct set of diagnoses. Consensus diagnoses, if practical, may help overcome this problem. Molecular biomarkers may assist in establishing a diagnosis13 and identifying high risk biology,14 but they require extensive validation before clinical use. Pathologists and clinicians also rely on metadata (age, personal and family history, lesion symptoms, recent change), which may influence diagnostic likelihoods. Importantly, it is possible to incorporate different data types, including metadata, sequential image data coupled with histopathology, to train future CNN algorithms and improve diagnostic discrimination of borderline lesions (Box 2). Use of artificial intelligence for melanoma screening It is well known that the incidence of invasive melanoma in Australia has increased over the past 40 years. In addition, there has been a striking increase in incidence of in situ melanoma over the past decade, from 32 cases per 100 000 population in 2004 to 80 per 100 000 population in 2019, with age‐standardised mortality remaining fairly stable.2 The potential causes for the increase in incidence are complex, and involve a true increase, driven by poor sun exposure practices of individuals born before the SunSmart era, combined with increased awareness, excessive screening, and overdiagnosis. It has recently been estimated that 54% of melanomas (15% of invasive melanomas) are overdiagnosed.15 Artificial intelligence‐assisted targeted screening of high risk individuals is likely to be a more effective strategy to save lives than the current opportunistic approach. With sequential whole‐body image datasets linked to metadata, molecular biomarkers and clinical outcomes, our ability to identify lesions associated with sinister biological potential will improve (Box 2), thereby reducing unnecessary biopsies, minimising overdiagnosis and other potential harms associated with screening. Use of artificial intelligence in clinical practice There are advantages and disadvantages of introducing artificial intelligence at different points in the patient care pathway.16 An artificial intelligence system used as a triaging tool before clinician assessment would enable automated risk stratification of individuals and/or lesions (Box 2). This approach could dramatically improve clinician workload and timely access to specialist care for people requiring urgent attention. Alternatively, artificial intelligence consulted following an examination by the clinician may act as a second opinion to improve diagnostic sensitivity and reduce unnecessary biopsies.5 The latter is more closely aligned with current clinical workflows and therefore likely to be preferred while the field matures. There is potential for over‐reliance on artificial intelligence systems in both scenarios. A secondary support system may provide the clinician with a diagnosis or a management decision. Doctors are more likely to change their minds if they are uncertain of a diagnosis and an algorithm provides a conflicting result.5 It is thus important to consider how an algorithm might convey uncertainty to avoid false guidance. For example, a decision‐support output (eg, excise, monitor or reassure) avoids the diagnostic dilemma of differentiating between melanoma and dysplastic naevi. However, the problem is complex and arguments exist as to why, in many situations, a diagnostic probability output might be more desirable. Safe implementation of new technologies The Therapeutic Goods Administration (TGA) has developed an action plan to improve the processes by which new devices are approved for use in Australia, strengthen monitoring and follow‐up, and provide more information to consumers about the devices they use.17 International collaborations also exist with groups, such as the International Medical Device Regulators Forum, to establish better processes for medical device regulation globally. If software is classified as a medical device (ie, it is intended for diagnosis, prevention, monitoring, treatment or alleviation of disease), it must be registered on the Australian Register of Therapeutic Goods following TGA approval and before distribution within Australia. Consumers and clinicians need to be aware of the intended use of an application or device. There are several smartphone applications available to the general public, with functionality ranging from education to monitoring and tracking to skin lesion classification. Some of these provide skin lesion risk assessment, although they may state that they are not intended to be used as a diagnostic device. There is concern that, if this is not immediately obvious to the consumer, unregistered applications may be used in lieu of seeking medical advice. Unsupervised consumer‐operated diagnostic devices would require careful testing before they can be recommended. Conclusion As clinicians, we need to be aware of the limitations of any diagnostic tool and interpret outputs accordingly. Although the performance of artificial intelligence to date is promising, it remains to be seen how diagnostic devices in dermatology will influence decision making in the clinic and affect patient outcomes. Regardless of the specialty, any new technologies need to be rigorously tested before implementation and monitored after implementation. Ultimately, responsibility for patient care remains with the clinician and, as such, a high level of clinical acumen must be maintained. Nonetheless, artificial intelligence in dermatology is primed to become a powerful tool in skin cancer assessment. Box 1 – Comparison of skin cancer classification tasks by artificial intelligence (AI) systems and dermatologists/pathologists Study AI architecture Images Classification task Training dataset size Test dataset size AI Dermatologists/pathologists Sensitivity Specificity AUC/overall accuracy Sensitivity Specificity AUC/overall accuracy Tschandl5 ResNet34 CNN Clinical (dermoscopic) Benign v malignant v non‐neoplastic skin lesions 10 015 1412 0.81 (0.79–0.83)* 0.92 (0.90–0.93)* 0.73†(0.70–0.76)* 0.80 (0.78–0.83)* 0.80 (0.77‐0.82)* 0.60† (0.57–0.63)*,‡ 0.86 (0.84–0.88§)* 0.88 (0.87–0.90§)* 0.74† (0.71–0.77§)* Esteva7 GoogleNet Inception v3 CNN Clinical (macroscopic, dermoscopic) Benign v malignant v non‐neoplastic skin lesions 129 450 1942 na na 72.1%¶ ± 0.9% na na 66.0%¶ Haenssle8 GoogleNet Inception v4 CNN Clinical (macroscopic, dermoscopic) Benign melanocytic naevi v melanoma > 100 000 100 86.6%** 82.5%** 0.86** 86.6%** 71.3%** 0.79** 88.9%†† 82.5%†† 0.86†† 88.9%†† 75.7%†† 0.82†† Tschandl9 GoogleNet Inception v3 CNN Clinical (macroscopic, dermoscopic) Benign v malignant hypo‐pigmented lesions 13 724 2072 81% 53.5% 0.73 78% 51.3% 0.68 Hekler10 ResNet50 CNN Histopathology Benign naevus v melanoma 595 100 76% 60% na 51.8%‡‡ 66.5%‡‡ na Fujisawa11 GoogleLeNet DCNN Clinical (macroscopic) Benign v malignant skin lesions§§ 4867 1142 96.3% 89.5% 92.4%¶ ± 2.1% na na 85.3%¶ ± 3.7% AUC = area under the curve; na = not applicable. * 95% CI. † Youden statistic. ‡ Clinicians with varied experience and training. § Clinician accuracy with multiclass probabilistic AI support. ¶ Overall accuracy. ** Level I: AI and human readers provided with dermoscopic images only. †† Level II: AI provided with dermoscopic images only, human readers provided with dermoscopic images, macroscopic images and additional clinical information. ‡‡ Pathologist. §§ 52.6% of melanomas in this study were acral. Box 2 – Incorporation of different data types to train future convolutional neural network (CNN) algorithms and improve diagnostic discrimination of borderline lesions AI = artificial intelligence.

Miki Wada · ZongYuan Ge · Stephen J Gilmore · Victoria J Mar

Enhancing clinical trial recruitment through eConsent has potential but needs more evidence of use Consent for medical interventions or clinical research participation currently relies on the use of printed information combined with a conversation with a health care professional, which is largely undocumented. Studies have shown that few participants are truly informed at all using these traditional means, and have demonstrated that recall or comprehension of what was disclosed is poor.1,2,3 Attempts to develop standardised participant information and consent forms (PICFs) that meet ethical requirements have often resulted in longer and more complex documents. While consumers have been engaged to assist with these programs, the purpose of PICFs is still too heavily weighted toward satisfying regulatory requirements rather than patient information needs. Unsurprisingly, data show that, as PICFs get longer, they are less well understood,4,5 and there is evidence that this is one of the reasons why patients do not agree to participate in clinical research.6 eConsent is not simply a conversion of a paper PICF into an electronically delivered version. It also holds the promise of improving participant engagement in clinical trials through a variety of features that include: the use of multimedia tools to enhance comprehension; ready conversion into multiple languages; a means to track consent in a highly portable manner; and the opportunity to provide information in a more convenient way to persons with an inability to attend clinics. The use of eConsent does not replace the opportunity for participants to ask direct questions to their doctor or the investigators. Moreover, in most instances, participants will still be required to make a physical visit to a clinic to receive their treatment, whereupon they can ask questions and confirm their willingness to participate. There are relatively few studies using eConsent. In an early randomised controlled study, there was a preference for eConsent as well as improved comprehension and intention to participate in people assigned to use computer terminals rather than paper to receive information.7 In a more recent study involving people infected with human immunodeficiency virus,8 eConsent was found to be acceptable and had some advantages over paper information sheets. There were a majority of males included in the study (75%), and more than half were African American, with a mix of sexual orientation. Health literacy of participants was the only factor that emerged as having an impact on comprehension; however, the number of participants (n = 20) is too small to draw statistically sound conclusions. A 2013 study tested comprehension and satisfaction when using iPads to deliver information for a neuropathy in chemotherapy study.9 Importantly, the investigators presented the same information in both formats, but the iPad had an initial video outlining the main features of the study. They found that of the 55 patients who took part in the randomised study, there was a statistically significant association with increased comprehension in the group assigned to the iPad. The sample sizes were too small for definitive findings, but of interest was that use of the iPad did not increase likely participation rates (it was slightly lower). All participants advised that the information provided was still too complex regardless of the media used, and that simplified text, diagrams, animations and other ways to enhance comprehension are needed. A recent study reported on the TransCelerate eConsent Initiative, which employed a large survey of 3045 participants and a number of smaller stakeholder consultations.10 While there was general support by potential participants for the use of eConsent, the survey revealed that people living in the European Union had the greatest level of discomfort with it. In this survey, they also found that people were concerned that eConsent might eliminate site/participant discussion regarding participation, even though this is not the case where it has actually been used. In Australia, there has not been widespread use of eConsent to date. To better understand the Australian context, Clinical Trials: Impact and Quality (CT:IQ) — a cooperative funded by MTPConnect, an Australian Government Industry Growth Centres Initiative, using funds from the federal government's Medical Research Future Fund (MRFF) — set out to investigate stakeholder perceptions of eConsent and, therefore, to identify potential actionable insights. Chrysalis Advisory developed a survey that was sent via email to the members of CT:IQ for distribution to the wider clinical trial sector in the first quarter of 2019. A total of 179 participants completed the survey and as we used a snowball methodology, there is no denominator of persons polled. In addition, there were 19 semi‐structured interviews conducted drawn from the CT:IQ membership. The majority of respondents (68%) were women, 75% were aged 40 years or over, and 80% had more than 10 years of working in trials, demonstrating considerable experience in the sector. The full report is available on the website,11 with the questions presented on pages 58–59 of the report. The key findings are summarised in the Box. We specifically surveyed those deploying eConsent at this stage and not the end users because we wished to understand what the sector was already doing and what the perceived barriers and opportunities were. Although only 29.2% of respondents indicated that they had any direct experience with eConsent, our survey revealed that they were overall cautiously positive toward the use of eConsent. An important finding was that there was optimism that use of electronic formats would enable participants to drive the information‐seeking process in a way that best suited their needs. The physical infrastructure, particularly in some public hospitals, was widely held as not being adequate to support eConsent uptake. Wi‐Fi blind spots within hospitals were cited as a major reason for this, as well as difficulties achieving infrastructure updates within the public health system. Respondents recommended that approaches to eConsent should employ technologies that do not rely on expensive infrastructure delivered by health services. In addition, respondents indicated that, ideally, there should be a sector‐wide standard for site information technology infrastructure requirements combined with clear guidance for sponsors to standardise their approaches. A number of interviewees who had worked on trials with eConsent where sponsors had provided devices noted that the devices were clunky and prone to malfunction, which increased overall study time and burdened trial staff. Clinical trial sites often experienced sponsors insisting on their own standards, resulting in unnecessary duplication or incompatibility of instrumentation at sites. Many respondents cited that differences in the use of eConsent platforms and inconsistencies between organisations regarding eConsent compliance (eg, whether participants would be required to sign electronically, or would be able to consent by using technologies such as face recognition, fingerprint identification etc) made it difficult to adjust to the use of eConsent. Greater industry engagement and collaboration may mitigate this barrier by providing stakeholders with frameworks and support to implement eConsent. Furthermore, setting some national guidelines will facilitate the design, regulatory approval and implementation of strategies to adopt eConsent. While some stakeholders identified data security as a risk associated with eConsent, others did not believe security threats were any greater than similar threats to existing digital technologies in use throughout clinical trials and the medical field more broadly. They suggested that when appropriate security systems are in place and data governance risks are managed, stakeholders were not likely to be concerned about data governance risks for eConsent. Using eConsent does not automatically mean that participants will have the ability to provide consent offsite, simply that they have access to the information offsite. This is no different from participants providing wet ink signatures offsite in terms of risk and the fact that a person comes to a clinic and accepts the study treatments is a clear demonstration of consent. Two‐factor authentication processes enabled by eConsent may provide a more robust means to authenticate consent than current paper‐based processes. It was not surprising that eConsent was considered to add a cost burden over and above a paper‐based approach. However, few of the respondents considered the cost savings made through enabling prior reading of relevant documentation and, in particular, the major cost savings for the site and for the participants this could potentially deliver. A respondent from a large cancer centre articulated the potential benefits by outlining how participants from anywhere outside of a 50 km radius of the tertiary centre could avoid additional time needed in the clinic through being able to use eConsent. This centre is piloting a tele‐trial model to deliver trials in non‐tertiary settings and recognises that eConsent is pivotal to enabling this model, which promises to reduce the burden on patients through reducing their need to travel and to ensure that clinical trial participation is more available beyond metropolitan centres. It appears from our survey that Australia is willing but only partially ready to implement eConsent. The pathway forward will require proactive planning, leading and managing organisational change with the creation of practical demonstration cases of the development, delivery and use of eConsent in the clinical trial setting vital to support wider adoption. CT:IQ is now looking at a program to undertake these pilot projects as part of its initiatives to enhance clinical trial capability across Australia and in other jurisdictions. Box – Key findings of the eConsent survey Barrier Finding Problems with using paper‐based information sheets and consent forms 38% of respondents thought paper consent forms were not a problem, 71.5% thought they were too long, and 62% found them too complex 37.4% of respondents thought paper‐based consent impaired participant comprehension 67% of respondents believed eConsent would improve comprehension, although they did not believe that this would necessarily translate into greater recruitment 59.2% of respondents believed there was a significant issue with providing adequate information to people from culturally and linguistically diverse populations and saw eConsent as a solution to this Perception that regulators, HRECs and hospital governance offices will not accept eConsent 40.8% of respondents believed that ethics committees would not approve use of eConsent, 26.8% were unsure 90.5% of respondents found it necessary to have guidelines for use by both researchers and HRECs Patients will not be sufficiently proficient with technology or have access to suitable devices Certain demographics (eg, older people) were considered likely to struggle with eConsent eConsent was likely to be well received by younger generations Health services lack the infrastructure to deliver eConsent 82.7% of respondents identified a lack of IT infrastructure as a critical barrier to overcome 59.2% indicated that the current infrastructure was inadequate, particularly within hospital sites Difficulties with authentication of individuals and data security 46.3% of respondents believed there would be issues with data governance, security and privacy, but 29% of respondents disagreed with this 59.2% of respondents felt that they would lose the ability to ensure that the person signing the eConsent was actually the participant, the remainder were undecided or felt this was not a problem Lack of consistent practice across the sector 67% of respondents identified a lack of standardised guidelines as a significant barrier to success 49.2% of respondents indicated that staff were able to manage eConsent despite the lack of training and standardised guidance eConsent will be more expensive 60.3% of respondents believed that there would be a significant initial cost, which might be a barrier to uptake HRECs = human research ethics committees; IT = information technology.

Nikolajs Zeps · Nicholas Northcott · Leanne Weekes

AI has arrived, with the potential for enormous change in the delivery of health care, but are we ready? Artificial intelligence (AI) is the trigger for the next great transformation of society: the fifth Industrial Revolution. AI has already arrived in health care, but are we ready for the kind of changes that it will introduce? In this article, we map out the current areas where AI has begun to permeate and make predictions about the kind of changes it will make to health care. Definition of AI AI comprises any digital system “that mimics human reasoning capabilities, including pattern recognition, abstract reasoning and planning”.1 It includes the concept of machine learning, where machines are able to learn from experience in ways that mimic human behaviour, but with the ability to assimilate much more data and with potential for greater accuracy and speed. Machine learning is a research field that has seen recent advances due to exponential increases in computing power (a phenomenon known as Moore's law), algorithmic coding that mimics the human cognitive process (deep learning), and access to large, linked sources of big data. The scope of AI can be specific, performing narrowly defined tasks (narrow AI) such as image interpretation, or more general, applying knowledge and skills in different contexts (general AI) such as making a diagnosis and predicting disease outcome. On the other hand, machine learning can also be designated “supervised”, in which a dataset is provided for the algorithm to evaluate its performance, or “unsupervised”, in which the machine is allowed to extract unknown potential features in developing an algorithm. The arrival of AI into current practice AI, machine learning, and deep neural network tools can assist medical decision making and management, and have already permeated into at least three different levels: AI‐assisted image interpretation; AI‐assisted diagnosis; and AI‐assisted prediction and prognostication. From diagnosing retinopathy to cardiac arrhythmias, from screening for skin cancer to breast cancer, from predicting outcome of stroke to self‐management of chronic diseases, AI and machine learning devices can replace many time‐consuming, labour‐intensive, repetitive and mundane tasks of clinicians and give possible suggestions of management plans (Box 1).2,3,4,5,6,7 While the advancement and new capabilities and opportunities are exciting, the responsibility and liability issues of AI‐assisted clinical diagnosis and management need much deliberation. AI‐assisted image interpretation One of the major advances in AI is pattern recognition enhancing image‐based diagnosis in radiology, pathology and endoscopy. AI‐assisted image analysis aids the detection of adenoma and polyps during colonoscopy. It can even provide optical biopsy to determine the nature of lesions with implications of treatment.8 Wireless capsule endoscopy is a groundbreaking advance in medical technology, allowing painless examination of the gut, reaching areas where conventional endoscopes cannot reach. However, reading thousands of images produced by the capsule is extremely time‐consuming. Deep neural network systems trained to read images of capsule endoscopy can scan thousands of pictures within minutes to reduce the burden of time and energy for gastroenterologists and also minimise the chance of missing significant lesions.9 Similarly, systems have been trained to read echocardiographic images to provide physiological measurements within seconds, and to read coronary computed tomography angiography images to determine coronary calcification, coronary stenosis severity, and functional haemodynamic effects of the stenosis. AI‐assisted diagnosis The diagnosis of many conditions (eg, acute or old myocardial infarction) and arrhythmias (eg, atrial fibrillation and ventricular tachycardia) can be made by experts reading electrocardiograms (ECGs) according to well established rules. Application of such rules in algorithms have allowed computers to make these diagnoses automatically in ECG machines for many years, but the diagnoses are subject to verification by physicians using the same rules. AI using machine learning and deep neural network can do the same from raw ECG data, but does not rely on the same rules, and thus can do much more than conventional ECG analysis. In the most basic AI formulation, diagnoses of important cardiac arrhythmias from a single lead rhythm strip or continuous single lead ECG recordings were made by machine learning using deep neural network algorithms with greater accuracy than an individual cardiologist and similar to a consensus panel of cardiologists.10 Where AI excels, however, is in discerning patterns not apparent to the experts, such that current or future paroxysmal atrial fibrillation can be diagnosed from an ECG in sinus rhythm,11 and asymptomatic left ventricular dysfunction can be diagnosed by a 12‐lead ECG.12 AI‐assisted prediction and prognostication AI may predict the occurrence of certain diagnoses and prognosticate clinical outcomes of patients based on clinical datasets, genomic information and medical images. Cardiologists have developed algorithms to assess the risk of cardiovascular disease and claimed that their prediction is superior to existing scoring systems. Gastroenterologists have also developed AI models to predict recurrence of bleeding and requirement of surgery in patients with gastrointestinal bleeding.13 Combining genomic, epigenetic and metagenomic data with biochemical and lifestyle information using machine learning will be a very powerful tool in medicine. However, mechanisms or reasons for reaching the machine decision may not be comprehensible to clinicians. The integration of various datasets in multilayer informatics could take prediction, prognostication and prevention of diseases to new levels that cannot be achieved by conventional statistical models. This capability, if validated in properly designed studies, will offer new dimensions to personalised medicine. Preparing for the future of AI Health disparities, excluded populations and data biases The quality of AI in health care is dependent on the quality of the data on which it is based. Algorithms are being developed and validated on data generated by health care systems where current practices may already be inequitable. A system built on poor quality, biased data will reflect those problems (“garbage in, garbage out”). If a health care system has excluded populations of patients, the structural inequalities of health care will be repeatedly reinforced by the AI. This is a not a new problem and we must do better science and be awake to the limits of data quality and evidence‐based medicine. Data sovereignty and stewardship AI is built on access to big data. Big data in health care is primarily generated by public health systems, funded by the public for the public. Increasingly, claims over the health data generated by these public systems are being contested.14 There was enormous public outcry over the use of British National Health System data by Google‐owned DeepMind, a company creating an AI‐based smartphone application for kidney disease. Many were angry about the private use of public data, when there was little public control over what would happen to the data or what benefit was being provided back to the National Health System.14 Issues of data sovereignty therefore threaten the existence of effective AI. Patient data should not be provided to technology giants without a good governance structure to protect data sovereignty. Changing standards of care An immediate issue for the use of AI is the question of how it will transform standards of care. Common law jurisdictions judge health professions, by and large, by measuring performance against competent professional practice as set by the professions themselves. If AI keeps its promise of benefit and it is integrated more into practice, standards of care must require AI use, and traditional forms of therapeutics will be forced to change. We will see a time when all medicine and allied health work as a team with AI. Those who refuse to partner with AI might be replaced by it. Legal responsibility for AI‐caused injury AI promises to massively reduce the occurrence of iatrogenic harms via increasing the quality of decision making, but the continued existence of AI‐related injury is easy to foresee. As machine algorithms improve themselves without human intervention, making the “black box” more opaque, regulatory agencies such as the Australian Therapeutic Goods Administration and the United States Food and Drug Administration need to refine their regulations. To the extent that AI continues to play a role in assisting clinical management, questions of responsibility for harm should be determined by ordinary rules of product liability. It is likely that courts will determine some of these liability questions by using analogies with vicarious liability — an employer is responsible for the negligence of the staff when the injury occurs in the course of the staff's employment. A doctor using AI should be responsible for AI decisions made in the course of treatment, especially if the doctor retains the power to make the final decision regarding treatment. But as AI takes on more autonomous decision making, it might be argued by some doctors that they should not be responsible for that which they cannot control. Similarly, it seems unfair for doctors to be held responsible for an AI decision when they are unable to deduce how and why that decision was made. Such matters are outside the scope of clinicians’ expertise and best dealt with legally as a product liability claim. A stepwise gradation model of shared responsibility between the human doctor and the machine in diagnosis and clinical management has been proposed15 (Box 2). Conclusions Before AI tools can be put into daily use in medicine, data quality and ownership, transparency in governance, trust‐building in black box medicine, and legal responsibility for mishaps are some of the hurdles that need to be resolved. Much effort is needed to translate algorithms into problem solving tools in clinical settings and demonstrate improvement in clinical outcomes with saving of resources. Box 1 – Examples of artificial intelligence (AI) permeation into clinical practices of different specialties Clinical management AI capability Diabetic retinopathy2 Detection of early changes in fundi of patients with diabetes Reading the retina and blood vessels to identify patients at risk of developing complicated diabetic retinal disease Breast cancer3 Diagnosis of early breast cancer based on mammography Reading mammographic pictures to detect early malignant transformation in breast cancer screening Skin cancer4 Diagnosis of skin cancer by its clinical morphology Identification of skin cancer by pictures and classification of types of skin neoplasia Cerebrovascular disease5 Predicting outcome after a cerebrovascular accident Predicting the outcome (mobility, morbidity and mortality) of stroke 90 days after the event Non‐communicable chronic diseases6 Monitoring of diabetes and heart failure in primary care setting Assisting patients monitoring of blood pressure and blood glucose at home and transmitting information to family medicine clinics Heart failure7 Predicting the clinical outcome of patients with heart failure Predicting in‐hospital mortality among patients with heart disease based on echocardiography Box 2 – Levels of artificial intelligence (AI)‐assisted decision in diagnosis and clinical management and possible share of responsibility between human doctor and machine

Joseph JY Sung · Cameron L Stewart · Ben Freedman

Resource‐limited emergency departments responding to the COVID‐19 pandemic face many challenges — their strength lies in their unique solutions The coronavirus disease 2019 (COVID‐19) pandemic is stretching hospital resources around the world. Emergency departments (EDs) are on the frontline of care and have been impacted significantly by the surge of patients with both suspected and confirmed infection.1,2 Resource‐limited EDs in low and middle income countries are particularly vulnerable. Pre‐existing issues, including a limited workforce supply, have been exacerbated, and new threats, such as a lack of personal protective equipment (PPE) and oxygen, have emerged.1,2 This article explores the impacts of the COVID‐19 pandemic on resource‐limited EDs across the Indo–Pacific. It considers the unique challenges for the region and describes opportunities for building system resilience at a time of unprecedented demand for emergency care. Emergency departments and the COVID‐19 pandemic Emergency care systems are essential for universal health coverage.3 Effective emergency care improves health outcomes, and is critical to achieving the health‐related Sustainable Development Goal targets.4 EDs are the cornerstone of emergency care systems, enabling access to facility‐based care for patients with acute illness and injury. They provide an interface between community and hospital care, and address unmet needs for vulnerable patients. These roles are augmented during communicable disease outbreaks, when EDs fulfil surveillance, triage and clinical care functions.3,4 Since the World Health Organization (WHO) declared COVID‐19 a global pandemic in March 2020, most low and middle income countries across the Indo–Pacific have reported cases. About 20% of patients require hospital admission, and early recognition and resuscitation can help reduce mortality.1 EDs therefore have a key role to play in risk‐stratifying patients, providing initial therapy, establishing goals of care, and identifying patients who may benefit from advanced interventions. Pandemic preparedness The Indo–Pacific encompasses the eastern Indian Ocean and Western Pacific regions, connected through South‐East Asia. The region is characterised by cultural, geographical and economic diversity.5 The Global Health Security Index reflects a country's ability to detect, communicate and respond to a communicable disease outbreak.6 Most low and middle income countries across the Indo–Pacific score below the average preparedness level of 40.2 (on a scale of 0–100) and are among the least prepared countries.6 These findings reflect pre‐existing gaps in health care capacity that are likely to be exacerbated during a public health emergency.7 A historical lack of investment in emergency care systems across Indo–Pacific low and middle income countries means that many EDs have limited resilience in times of increased demand.3,4 Emergency care has not been a focus for international donors,4 and sequential reductions in the Australian Government's development assistance budget for health have further compromised capacity building efforts.8 Although these projections foreshadow a devastating impact on low and middle income countries across the region, the global experience of the COVID‐19 pandemic has illustrated the limitations of preparedness modelling. Several of the most prepared countries are now disease epicentres with overstretched health services, in part reflecting an initial reluctance to follow WHO advice regarding testing and contact tracing.9 Indo–Pacific nations may have strengths that protect against this trend, such as recent epidemic experience.10 Nimble and innovative responses may help build resilience, potentially providing globally relevant lessons that would typically be expected from high income countries. Challenges in public health response A major determinant of the pandemic's impact on EDs will be the success of broader public health interventions. Low and middle income countries, including those in the Indo–Pacific, will face unique challenges in disease containment.2 As demonstrated by several Pacific countries, island states have greater ability to shut their borders and limit inward passage of the virus. However, a freeze on international access will have a significant socio‐economic impact and is unlikely to be sustainable. It may also affect the supply of essential medical equipment, surveillance capacity (given that certain countries rely on foreign pathology services for COVID‐19 testing) and retrieval systems. An important mechanism to disrupt community transmission of COVID‐19 is physical distancing. This is antithetical to many sociocultural practices across the Indo–Pacific, where communal living is common and regular congregation at community meeting places is the norm. Modelling from a Papua New Guinean setting has demonstrated that physical distancing measures in that community were 60–70% less effective compared with Australia.11 Public health responses across the region have already been complicated by extreme weather events and humanitarian crises. Examples include Cyclone Harold, a category 5 cyclone that recently affected the South Pacific, and the climbing infection rate in the worlds’ largest refugee camp at Cox's Bazar in Bangladesh.12 Worsening climate change will further exacerbate the incidence and severity of natural disasters and disease outbreaks. Challenges for emergency departments As community transmission increases, demand for ED care will escalate. The impact may be more pronounced among Indo–Pacific communities as a result of high rates of non‐communicable disease.13 COVID‐19 appears to be more severe in patients with diabetes, hypertension and chronic pulmonary illness, all of which are prevalent across the region.13 Increasing demand is likely to expose pre‐existing deficiencies in ED systems and resources, including scarce critical care capacity.1,2 A survey of emergency care clinicians in the Pacific recently identified minimal integration of surge response with routine emergency care, and a lack of essential processes, such as triage and patient flow.7 Consistent with these data, Box 1 lists key challenges in systems, spaces, supplies and staff that have become evident to Indo–Pacific clinicians during COVID‐19 response planning.2 Emerging data suggest that frontline clinicians are at an increased risk of death from COVID‐19, in part due to suboptimal PPE.14 Limited access to PPE is a major threat and will place ED clinicians at increased risk of infection. Low and middle income countries face challenges in PPE procurement because of supply chain limitations as well as market‐based competition with high income countries.1,2 Illness among health care workers will stretch an already fragile health care workforce. In the event of a surge, EDs will require significant increases in staffing, and the challenge may be exacerbated by high rates of comorbidities, absenteeism and inadequate training.7,13 Additionally, many Indo–Pacific EDs rely on a sole medical leader for clinical and administrative decision making.15 The pandemic may place these clinicians at risk of burnout, illness and death, thereby exacerbating the mismatch between supply and demand for care. Unintended consequences To meet these challenges, EDs will need to make substantial changes to their processes. However, there is a risk that distraction from pre‐existing health priorities will worsen the overall impact. Patients with chronic disease have poor outcomes at times of increased health system stress, as occurred in West Africa during the 2014 Ebola epidemic when resources were diverted away from routine care.16 Lockdown measures will make it difficult for some patients to access emergency care, and fear of acquiring COVID‐19 in hospital may create a further barrier to ED attendance. Additionally, the socio‐economic consequences of public health interventions are likely to contribute to poor health outcomes in the longer term. There is also a risk that donor funding will target resource intensive equipment (such as ventilators) that may be unsuitable in a low and middle income country context. Many resource‐limited ED clinicians are accustomed to a low cost essential care approach.1 Rather than emphasising expensive and high risk interventions, a focus on simple measures such as rigorous infection control and oxygen therapy is likely to be advantageous.1 The pandemic has already had a gendered impact, exacerbating the “triple burden” of productive, reproductive and community work responsibilities imposed on women.17 This has been particularly evident in low and middle income countries, where women make up a larger proportion of frontline workers and are disproportionately expected to fulfil unpaid household duties.17 Addressing immediate needs Addressing these challenges requires urgent action. While high level guidelines such as the WHO Emergency and Disaster Risk Management Framework18 exist, these often neglect the practical challenges faced by EDs. COVID‐19 guidance for Indo–Pacific EDs must complement WHO recommendations, and be culturally appropriate, fiscally responsible and immediately actionable2 (Box 2). Indo–Pacific ED leaders are already implementing COVID‐19 response plans. Examples from across the region are profiled in Box 3. These early success stories highlight the capacity of local clinicians to lead disaster response activities and provide meaningful care in the face of escalating health care demand. The Australian Government has provided some support for this effort by contributing funds to the WHO response plan and deploying specialist advisors to selected Indo–Pacific countries.8 Opportunities An increasingly interconnected world, combined with climate change and mass migration, will result in more frequent communicable disease outbreaks. COVID‐19 provides an opportunity to build resilient EDs that are better prepared for this challenge. The pandemic is also a chance to enhance the sustainability of routine emergency care through system strengthening, facilitated by multisectoral collaboration between clinicians, governments, technical organisations and donors.3 This effort should be informed by existing guidance for the enhancement of human resources, infrastructure, governance and processes to improve regional emergency care capacity.7 Australian agencies, such as the Indo–Pacific Centre for Health Security, have a key role to play in resourcing this activity. The pandemic provides a unique opportunity for the Australian Government to advance its commitment to strengthening health care systems and deliver on the promise of its Pacific Step‐up.5,8 It also offers a chance to leverage Australia's expertise in emergency care for the benefit of the region.3 Conclusion Time will determine the full impact of COVID‐19 on the Indo–Pacific, but global trends suggest that ED capacity may be severely stretched. Responses should target the unique challenges for disease control and emergency care delivery across the region. Although local ED clinicians are already demonstrating leadership and adaptability in their surge planning, the pandemic provides an opportunity to build resilience in emergency care systems and enhance future capacity for both routine care and outbreak response. Australian clinicians, organisations and governments have a key role to play in supporting this effort. Box 1 – Challenges for COVID‐19 preparedness and response in emergency departments (EDs) Variable Challenge (and selected examples) Systems Disaster and surge plans Many EDs and hospitals do not have standard operating procedures for surge events and communicable disease outbreaks: “ED COVID‐19 operations need a focal point of command at hospital executive level so that ED preparatory activities can be prioritised and fast tracked” (Solomon Islands) Triage Some EDs have no formalised triage systems. Implementing a triage system, for the first time, during a pandemic is fraught with difficulty Patient flow Overcrowding, interdepartmental communication barriers and a lack of ward beds can delay care for both COVID and non‐COVID patients Space Isolation and resuscitation areas Many EDs lack the physical space and infrastructure to adequately provide safe and effective routine care. In the context of the pandemic, a lack of dedicated isolation and resuscitation areas will be a major challenge Storage capacity Attempts have been made stockpile essential resources; however, there is a lack of dedicated on‐site storage space at many hospitals Supplies Personal protective equipment (PPE) and cleaning agents PPE supply is a major and ongoing concern: “There is not a standby supply of PPE … in a normal working day. [There is no] process to ensure a consistent supply of PPE in the department” (Fiji) “Our hospital is not a central level hospital, [so] we [were not given] much supplies” (Myanmar) Laboratory testing There is often limited laboratory capacity, and staff have competing priorities beyond EDsMany testing facilities are offsite or overseas, resulting in delayed isolation, identification and treatment of patients with COVID‐19, placing staff and other patients at risk Oxygen There is a lack of portable oxygen cylinders and oxygen concentrators in many facilities. Relatively few facilities have capacity for intubation and ventilation Novel therapies There is uncertainty surrounding the therapeutic benefits of agents such as hydroxychloroquine, azithromycin and remdesivir. In some countries, these medications are difficult to source, and with international demand increasing, supply will become even more scarce. This will impact the availability of these medications for patients who require them for other indications Staff Critical care training There are few formally trained critical care staff in many EDs. Additionally, there are concerns about workforce shortages and the reliance on volunteers Some hospital staff do not appreciate the importance of early recognition and treatment: “[Some staff lack an] initial understanding of the role of ED in the approach to COVID‐19” (Fiji) Staff morale and safety concerns Many staff are concerned about the risk to themselves and their family members if they are required to care for patients with suspected COVID‐19 without adequate protection: “[There are] difficulties in commuting due to strict curfew/modified lock down and restrictions on inter district transport. [There is] COVID phobia created by the media” (Sri Lanka) “I don't want them to infect, I don't want them to exhaust, I don't want them to depress, I want to create safe and less stress environment” (Myanmar) Box 2 – Strategies for optimising emergency department (ED) preparedness and response* Systems Ensure ED processes are consistent with broader public health and hospital management strategies Utilise local case definitions to identify suspected cases Establish a clearly marked screening and triage process at the entrance to the hospital, and stream patients based on the acuity of their presentation. For example, low acuity patients might be redirected to a co‐located surge clinic Maintain infection prevention and control to the highest possible standards. Ensure patients and staff practice physical distancing, cough etiquette and hand hygiene Minimise the volume of patients in the ED and isolate symptomatic patients from others by establishing a respiratory zone Develop clear admission/discharge criteria and establish ceilings of care for the facility Space Establish a clearly marked screening and/or triage station at the entrance to the facility Ensure the ED and surge clinic (if established) have designated waiting areas for patients with respiratory symptoms Allocate separate areas in the ED for the management of symptomatic, medium and high acuity patients Supplies Anticipate equipment needs and stockpile to the extent that is possible, especially disposable items that will be in high demand (oxygen cylinders, antipyretics, personal protective equipment, etc) Follow World Health Organization guidelines on resource stewardship. For example, implement clear thresholds for providing supplemental oxygen, such as SpO2 < 90% on room air for stable patients, SpO2 < 92% on room air for pregnant women, and SpO2 < 94% on room air for patients with respiratory distress Avoid use of therapies that are likely to increase virus transmission (eg, nebulisers) Develop safe processes for cleaning and reusing equipment based on World Health Organization infection prevention and control advice Staff Make sure that all staff feel included, empowered, motivated and supported Update the staff contact list and plan for absenteeism Identify staff who are high risk for infection and reallocate them to other areas Train staff in the systems and processes that have been developed Remind staff that they should not work if they have acute respiratory symptoms Use ancillary staff and other community members for non‐technical tasks Remind others that COVID requires a whole‐of-government, whole‐of-health and whole‐of-hospital response; the ED cannot do it alone Ensure ED staff are involved in the post‐pandemic review process to promote ongoing systems improvement and sustainability * Adapted from Australasian College for Emergency Medicine. Managing COVID‐19 across the Indo‐Pacific: a guide for resource limited EDs. Melbourne: Australia, 2020. https://acem.org.au/getmedia/3930cc60-abb1-4517-b7af-36da918a3f7b/Managing-COVID-19-across-the-Indo-Pacific-(G763) (viewed Aug 2020). Box 3 – Examples of successful COVID‐19 preparedness and response strategies employed across Indo–Pacific emergency departments (EDs) Variable Strategy (and selected examples) Systems Leadership and coordination Many countries have developed national coordinating bodies that include ED clinicians as key stakeholders. This is a recognition of their pivotal role in crisis coordination: “Once there were initial reports of care in China, the Ministry of Health had formed a National Taskforce and … ED was invited to participate in it as stakeholders” (Fiji) Identification of key leaders at each stage of the patient journey has been essential: “The hospital formed its Taskforce and we had devised operating procedures and a flow chart with important contact persons at each stage” (Fiji) Triage, screening and patient flow There has been a rapid development of triage, screening and flow systems based on specific criteria: “For patients with respiratory symptoms and fever … the high acuity patients can be stabilised in the ED respiratory resus and transferred to ICU. Medium acuity patients to be stabilised in the step down area of the respiratory section of the ED. Ambulance will transport patients to the isolation wards and ICU” (Solomon Islands) Space Isolation and resuscitation areas Guided by experience from Africa during the Ebola outbreak, EDs in Solomon Islands, Fiji, Myanmar and Sri Lanka have undergone significant restructuring of limited spaces to facilitate separate areas for screening, isolation, resuscitation and storage Supplies Infection prevention and control, and personal protective equipment (PPE) Drawing on experience during the 2009 H1N1 pandemic, EDs have adapted guidelines for the judicious use of PPE, while emphasising that staff safety is a priority: “Within the storage area in ED of consumables, a cupboard is allocated to store PPE kits and this is tallied and replenished by the Hospital Infection Control team” (Fiji) “Health care worker exposure assessment protocol was designed” (Sri Lanka) “Luckily we have many people who want to donate what we need so we are still ok” (Myanmar) Resource utilisation Early decisions have been made about distribution of limited resources: “No CPR will be done on COVID‐19 high acuity patients who have (deteriorated) despite maximal non aerosol generating treatment” (Solomon Islands) “We decided to do respiratory team with only three people, because … when positive case came to our ED only these three need PPE” (Myanmar) Novel therapies These are not being used until there is proven evidence of benefit. Local guidelines have been developed: “Cautious use of fluids except in shock. Use of metered dose inhalers (rather than nebulisers) for asthma exacerbations” (Solomon Islands) Staff Critical care training Countries have begun re‐training staff in critical care and there has been redeployment and re‐training of staff from non‐essential areas to the ED. Non‐medical staff are also being utilised to assist with operational requirements such as cleaning and transportation Staff morale and safety There is a focus on open communication and staff wellbeing: “We did meeting every night with zoom and discussed the problems faced in their duty time … we asked their working capacity … and redrew duty roster” (Myanmar) “Special quarantine centres with all the facilities were designated for staff members who had problems in home isolation” (Sri Lanka) “Staff are undergoing medical checks. Staff with comorbidities will not be working in the respiratory section of the ED” (Solomon Islands)

Isobelle G Woodruff · Rob D Mitchell · Georgina Phillips · Deepak Sharma · Patrick Toito'ona · Krishantha Jayasekera · Khine Shwe Wah · Megan Cox · Gerard M O'Reilly

Telehealth can be used to deliver clinical trials, improve access to novel therapies and develop clinical networks Australia is a vast country. Nearly 32% of Australians reside outside the major capital cities, while 95% of medical specialists practise in cities.1 People living in rural and regional areas consistently experience poorer health outcomes.2 Cancer is a considerable health issue, with 395 new cancer diagnoses per day.3 The regional mortality gap in cancer remains.4 Between 2000 and 2010, patients in regional and rural Australia had a 7% higher cancer mortality compared with those in metropolitan centres, equating to 9000 additional regional and rural cancer deaths.3,5 Barriers to better regional cancer care include travel requirements to metropolitan centres, limited access to expert diagnostics and therapeutics, and less access to clinical trials.6 As well as geographical issues, recruitment and retention of qualified health professionals in regional areas can be difficult, due to professional isolation and a perceived or actual lack of career opportunities.7 These issues relate not only to regional Australia but to many regional populations worldwide.4,8 In the past decade, there has been considerable investment by federal and state governments in the development of regional cancer centres, enabling increased research opportunities.9 Clinical trials remain a gateway to accessing cutting edge therapies and technology. Currently, less than 5% of regional cancer patients participate in any clinical trial; barriers include travel distance to a metropolitan site, a lack of trials available locally, and costs involved for patients and carers such as travel and accommodation and loss of earnings.10 While there are no set targets for participation rates, there has been a correlation between trial participation rates and improved cancer survival, such that a higher rate is desirable.11 In 2017, there were 432 actively recruiting cancer clinical trials in Victoria, totalling 1605 participants. Of these, 426 participants were living in a regional or rural area (27%); however, most participants were enrolled at a metropolitan site, with just 81 (5% of all trial participants) recruited to local clinical trials (personal communication, Christie Allan, Cancer Trials Management Scheme, Cancer Council Victoria, April 2019). Telehealth strategies Telehealth strategies have gained acceptance across many aspects of health care to enable delivery for patients closer to home, including anti‐cancer therapies.12 A logical extension is integration into clinical trial models. Such an approach has many benefits for patients, their families, regional health care, as well as potential economic savings by reducing the need to travel for care. Although this model is a change from usual care, patient safety and quality of care is maintained. The Victorian Comprehensive Cancer Centre (VCCC) is an alliance of ten leading research, clinical and academic institutions in Victoria. The VCCC established a teletrials program to build relationships between regional/rural Victoria and metropolitan centres, using telehealth to provide patients with the opportunity to access clinical trials closer to home. Teletrial framework development In developing a teletrial implementation framework, it was important to consider patient safety, ethical and regulatory requirements. In addition, so that the model would allow for differences across clinical trial requirements and capabilities at individual trial sites, we scoped potential barriers and enablers, to ensure its success. The Clinical Oncology Society of Australia model10 was used as a foundation template for the structure and relational concepts (Box). Importantly, the model recognises the potential for heterogeneity across trials and sites, rather than taking a one‐size‐fits‐all approach. Different sites may perform different roles in different trials; for example, taking blood samples, delivering chemotherapy or medication, trial documentation, or imaging. The model has been used in several teletrials enrolling across Australia.13 An important element was the development of standard operating procedures. Initially developed by Queensland Health, these were modified not only for use in Victoria but for consideration as the basis for national standard operating procedures for teletrials. In developing the teletrial framework, input and feedback were sought from stakeholders in cancer clinical trials. These included contract research organisations; the biopharmaceutical industry; principal investigators; Victorian regional sites through the Regional Trials Network; Human Research Ethics Committees (HRECs); local government through the Victorian Department of Health and Human Services; funding bodies; and consumers. Teletrial supervision plan The teletrial supervision plan (https://www.viccompcancerctr.org/what-we-do/clinical-trials-expansion/teletrials/resources/) contains detailed documentation regarding specific trial conduct and responsibilities, in particular the specific responsibilities of investigators at each site within the trial cluster, and which elements of the trial, imaging and drug delivery are performed at each site. Some trials may have all elements delivered at the local site, others may have most delivered locally but specialist services (eg, radionuclide therapy) at the central site. The supervision plan is site‐, trial‐ and time‐specific. It also includes standard operating procedures, Good Clinical Practice training, monitoring, HREC submissions and oversight, trial‐specific indemnity and contracts, plans for safety reporting, investigational product storage and delivery logistics, and details on joint consultations using telehealth, payments, data entry and document management. The supervision plan is generated in agreement with the principal investigators at the metropolitan and regional sites before the study, but with regular review and modifications as required to allow refinement as needed. Indemnity and legal coverage Teletrial indemnity and legal coverage for trial activities are frequently raised concerns. This can be documented in detail in the supervision plan but is no different for a teletrial over other models. The VCCC commissioned a draft clinical trial activity agreement for investigator‐initiated studies including a teletrial component (https://www.viccompcancerctr.org/what-we-do/clinical-trials-expansion/teletrials/resources/). Governance and ethics approval As with any clinical trial, ethics approval is required, usually through a human research ethics application. Local research governance office requirements will not vary, with local assessment of trial capability, including managing potential toxicities. The principal investigator remains responsible for ethics submissions and communication with HRECs. Each site will obtain local governance approval and be listed on the clinical trial notification form. The process for reporting on safety events remains as per standard of care. Proof of concept Using the framework described, a teletrial has commenced between a metropolitan site and two regional sites in Victoria. The first teletrial site patient was recruited in November 2018 and at 24 July 2020, 91 patients had been successfully recruited in regional centres, with all their trial activity delivered locally. Metropolitan and teletrial sites have successfully undergone study monitoring and further model evaluation is underway. Model evaluation Although the teletrial model is not an intervention in itself, merely a method of trial delivery, it is important to its widespread adoption at a new standard of care that there are benefits to all stakeholders. An ongoing health economic evaluation will evaluate costs associated with the teletrial (and potential savings), patient time and travel estimates, and qualitative assessment of patient and clinician participation in a teletrial to detail possible benefits. In addition, consumer and clinician perspectives studies are planned. A leading contract research organisation was commissioned to undertake an independent process review of the first teletrial to evaluate the model. No major protocol deviations were found in comparison to a conventional site in this pilot study. Potential benefits of a teletrial Teletrials provide a mechanism to enable disadvantaged patients to participate in clinical trials. They may also provide wider benefits14 beyond those experienced by individual participants, including: improved recruitment: as trials have a wider reach, they may recruit faster, translating new interventions to patients faster in a real‐world setting; improved retention: making trial access easier may improve participant retention, reduce missing data and accelerate trial objectives; increased diversity: teletrials may allow for easier access to the increasingly specific and rare subsets of cancer trial populations; professional development: partnerships developed from the trial network may translate into improved routine clinical care delivery and opportunities; and trial cost‐savings: while teletrial costs will be evaluated, the resources required to open a teletrial may be reduced, as much of the trial data will be retained at the primary site. Potential or perceived risks Some of the possible risks raised with the authors by stakeholders have been addressed above, including indemnity, legal and governance issues. Others may include: Clinical safety of new treatments in a regional setting: while a trial may involve a novel therapy, toxicities are often managed on a patient's return home to their regional site. Involving local clinicians in the trial may actually reduce this risk through better education regarding managing novel therapies. Clinical trial expertise: most regional sites already have extensive experience in clinical trials, and Good Clinical Practice training is standard. Trial monitoring challenges: with rapidly increased use of secure digital platforms, monitoring is increasingly becoming a remote activity, so location is not a barrier. We acknowledge that this model represents a change to usual process and therefore requires assessment, transparency and strong support and advocacy to overcome barriers to clinical trial participation.15 Teletrials do more than just meet trial metrics. They develop synchronous partnering between regional and metropolitan centres, allowing regional equity of access to cutting edge diagnostics and therapeutics while maintaining patients’ care delivery closer to home, thereby avoiding disruption to family, work and social interactions. Box – Teletrial model

Ian M Collins · Kate Burbury · Craig R Underhill

Voluntary assisted dying is not part of palliative care The Voluntary Assisted Dying Act 2017 (Vic)1 came into effect in Victoria on 19 June 2019. We present the case of an inpatient death under the voluntary assisted dying Act in our health service and describe a short case history followed by a discussion examining two relevant topics related to voluntary assisted dying and palliative care: conscientious objection and the complexity of palliative care involvement. Case report The patient was diagnosed with metastatic (axillary nodes) breast cancer in 2016 at the age of 53 years and declined completion staging and all conventional treatment options. She was referred to community palliative care services in 2019 with clinically progressive locoregional disease, manifesting as fungating malignant disease of the chest wall and axilla. She experienced symptoms of pain, nausea, anorexia, and weight loss. Pharmacological treatment options for her symptoms were refused due to her sensitivities to many medications. The patient lived alone but had support from friends and siblings. She had a history of chronic fatigue syndrome and mood disorder. She did not subscribe to a religion, but believed in the soul and an afterlife. She had been caring for her mother, who died from advanced breast cancer. Her mother's suffering at the end of her life was a significant reason for the patient's decision to pursue voluntary assisted dying. She commenced the voluntary assisted dying process in July 2019. Her initial intention was to self‐administer the voluntary assisted dying substances at her home on her birthday (early December). However, she was admitted to the palliative care unit (PCU) in late November for symptom management. During her admission, it became clear to the patient and her carer (who was also her voluntary assisted dying support person) that her deterioration would preclude her from returning home. She made a request to self‐administer the voluntary assisted dying substances in the PCU. The organisational voluntary assisted dying clinical practice guidelines stated that voluntary assisted dying could not occur in the PCU, in line with the Royal Australasian College of Physicians (RACP) statement on voluntary assisted dying, which recommended that “voluntary assisted dying must not be seen as part of palliative care”.2 The patient was informed of the organisational approach and the need to minimise misperceptions about the PCU. Both the patient and her support person understood and accepted our stance, and we commenced the search for another site within the service that could accommodate her wishes. Staff in the first venue of care option conscientiously objected to the admission. Despite her condition continuing to deteriorate and the imminence of her preferred date of administration, she remained understanding. Another venue of care within the service was found and she was transferred there 2 days before her birthday. She self‐administered the voluntary assisted dying substance on her birthday as originally intended. Conscientious objection Although not defined in the Act, conscientious objection has been outlined by the Victorian Department of Health and Human Services (DHHS) as an outcome of a conflict in beliefs or values.3 A similar conflict was recently discussed in relation to a growing concern about moral injury in health care, where moral injury was defined as “perpetrating, failing to prevent, bearing witness to, or learning about acts that transgress deeply held moral beliefs and expectations”.4 Health care professionals are subject to moral injury as a result of “being unable to provide high‐quality care and healing in the context of health care”.5 In this context, conscientious objection becomes integral to the psychological safety of the health care workforce as voluntary assisted dying is introduced into mainstream medicine. The DHHS in Victoria permitted each health service within its jurisdiction to decide on their extent of involvement in voluntary assisted dying.4 This was determined by “whether participation aligns with the values of the health service”.6 The Catholic Health and Aged Care Services, which are responsible for several health services across Victoria, were clear that they would not provide or facilitate voluntary assisted dying.7 Such health services are under no obligation to refer a patient who has requested voluntary assisted dying. However, there is a requirement to inform the patient as soon as practicable that they will not assist them and the services cannot actively inhibit the patient's access to treatment.3 All health services were obliged to nominate their level of participation, irrespective of the actual number of health care professionals in the organisation willing to be involved with voluntary assisted dying.3 These choices were: pathway A — single service (it has the necessary suite of services and staff with sufficient expertise to provide voluntary assisted dying within their existing health service); pathway B — partnership service (these services would require the assistance of other services to provide the full requirement of voluntary assisted dying); and pathway C — information and support service (it includes services electing not to provide voluntary assisted dying). The dilemma of this approach for health care services is the contentious nature of voluntary assisted dying. Organisations consist of people some of whose individual values and beliefs are unlikely to align neatly under the organisational approach when it comes to voluntary assisted dying. The Voluntary Assisted Dying Act (Part 1, Section 7) outlines scenarios where registered health care practitioners may conscientiously object to participation in the voluntary assisted dying process.1 It provides for health care staff to refuse to participate in, or be present for, the administration of the voluntary assisted dying substance. The DHHS has provided clear guidelines for individual health care practitioners with regards to conscientious objection.3 A health practitioner “has the right to refuse to assist or support the patient when the assistance is associated with voluntary assisted dying”. Health practitioners are expected to “provide routine and other care unrelated to a request for voluntary assisted dying”.3 Health practitioners also need to balance their own moral and ethical beliefs while respecting differences and ensuring the rights of the patient are upheld. Therefore, health services face the challenge of navigating between the principle of justice and equity in access to health care and the responsibilities to their employees. Health practitioners cannot conscientiously object to the routine care of a patient who has elected to undertake voluntary assisted dying. Palliative care The specialty of palliative care is in its infancy, having only received recognition in Australasia as a specialty in 1998. It aims to improve the quality of life of patients and caregivers, faced with life‐limiting illness, by addressing physical, psychosocial and spiritual challenges. There is mounting evidence that it is indeed effective in doing so.8 Nevertheless, population‐based studies demonstrate a public misperception associating palliative care with euthanasia.9 The International Association for Hospice and Palliative Care has stated that assisted dying in all its forms corrodes the work done by the specialty and risks patients refusing palliative care for fear that health practitioners may hasten their death.10 There is a continuing need to increase public awareness of palliative care and clarify misperceptions. Therefore, palliative care services need to maintain their differentiation from voluntary assisted dying. The RACP emphasises that voluntary assisted dying “must not be seen as part of palliative care” and that they need to be seen as “distinct practices”.2 Peak palliative care organisations, such as Palliative Care Australia and the Australia and New Zealand Society of Palliative Medicine, similarly emphasise that voluntary assisted dying is not part of palliative care practice.11,12 The International Association for Hospice and Palliative Care has recommended that assisted dying practices not take place in PCUs.10 The risk otherwise is further blurring of the public perception and an erosion of trust. The RACP has recommended that all patients seeking voluntary assisted dying should be made aware of palliative care and that a referral to palliative care is strongly recommended.2 The Victorian DHHS, in its voluntary assisted dying documentation, has also outlined a key role for palliative care. This includes “managing complex communication interactions with patients and families, and responding to complicated, multifaceted psychosocial and/or spiritual distress”.3 Furthermore, they describe the most “valuable [role] palliative care specialists play is supporting other healthcare teams and professionals through consultation, advice and support to provide end‐of‐life care for their patients”.3 The challenges for palliative care services are therefore clearly visible: how to maintain its distinction and separation from voluntary assisted dying and yet provide a necessary and expected service for patients at the end of life who have elected voluntary assisted dying. The RACP and the DHHS guidelines will necessitate palliative care involvement, not only for our patients and their families but also in support of medical practitioners. Palliative care services risk becoming the gatekeepers for voluntary assisted dying because of our expertise in managing complex communication and discussions around death and dying. In addition, there is the risk of further burdening already stretched palliative care services, with education, counselling and support of fellow health service staff, in matters relating to voluntary assisted dying. It is important to note that the voluntary assisted dying legislation does not provide extra resources to services to support their health care staff. Nevertheless, specialist palliative care services can help patients who elect voluntary assisted dying, as they are well placed to provide specialist support within clear boundaries of engagement. This can include optimal symptom management as well as psychosocial and spiritual support. The RACP, the Australia and New Zealand Society of Palliative Medicine and Palliative Care Australia have all emphasised the need for greater access and resourcing for specialist palliative care. Our concern echoes that of the Catholic Health and Aged Care Services that we cannot, at this time, be distracted by the diversion of limited palliative care resources to voluntary assisted dying and lose focus on the need to ensure adequate and timely access to palliative care across Victoria and Australia.7 The perception of specialist palliative care services in cases where voluntary assisted dying has been requested will remain problematic. Collaboration with families and treating teams is essential and should involve the recognition of specialist palliative care involvement separate from voluntary assisted dying. The challenge remains to educate the public and health care professionals about palliative care and how it differs from voluntary assisted dying, amidst a new background of mixed messages. Regardless of the end‐of‐life choice made, holistic care and good communication skills are not solely related to our specialty, these are skills that can be, and need to be, routine for all areas of medicine.

Eswaran Waran · Leeroy William

Engaging First Nations peoples in public health emergencies is critical to reducing health inequities

Kristy Crooks · Dawn Casey · James S Ward

Understanding the multiple identity groups of Aboriginal and Torres Strait Islander LGBTQ+ young people can assist in meeting their health care needs Where does a young, LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and other non‐heteronormative or non‐binary sexual and gender identities, including asexual) Aboriginal and Torres Strait Islander person go for health care in Australia? Do they attend an Aboriginal community controlled health organisation in search of culturally sensitive care? Or do they visit an LGBTQ+‐friendly health service to access staff trained in sexual and gender diversity? Is there a space for them, and other LGBTQ+ Aboriginal and Torres Strait Islander young people, in the Australian health care landscape? These questions are being posed by Indigenous LGBTQ+ health advocates.1 Recent national policy documents outline the need for comprehensive health care for Aboriginal and Torres Strait Islander LGBTQ+ young people.2,3 Despite this identification in policy, limited information is available to health practitioners on working with Aboriginal and Torres Strait Islander LGBTQ+ young people (Box 1). Practitioners are limited by the absence of an integrated framework as well as a dearth of research into these young peoples’ health needs and service preferences. Intersectionality theory highlights that individuals can face multiple structural inequalities within each of the social groups that they occupy, which also affect their access to health, social and economic resources.4 We suggest intersectionality theory as a guiding principle for research and practice with Aboriginal and Torres Strait Islander LGBTQ+ young people. An intersectional approach means recognising that patients belong to multiple identity groups, such as sexual orientation and cultural groups, which are socially constructed and which affect their social positioning and subsequent treatment, such as discrimination, within health care systems.4 The health and wellbeing of Aboriginal and Torres Strait Islander LGBTQ+ young people Aboriginal and Torres Strait Islander LGBTQ+ young people occupy three intersecting identities, which, when considered separately, are each linked to risks for poor health. The risks for poor physical health and social emotional wellbeing among Aboriginal and Torres Strait Islander peoples are well documented.5 Within Australia, LGBTQ+ individuals experience heightened suicidality, serious assault, homelessness and psychological distress6,7 compared with their heterosexual, cisgender peers. These increased health risks do not indicate inherent vulnerability but rather are outcomes of discrimination, marginalisation, racism, transphobia and homophobia.15 Young people not only experience health risks associated with their development phase — for example, heightened risk of psychopathology, physical injury and emotional dysregulation9,10 — but are also often unaware of health services available to them or have fears around confidentiality.11 LGBTQ+ young people, in particular, report feeling isolated from health services.6 Health practitioners may therefore see Aboriginal and Torres Strait Islander LGBTQ+ young people in a variety of settings, including in suicidal crisis, seeking care after a serious assault or injury, or counselling for prolonged psychological distress. Although health care workers may be aware of the health risks associated with being Aboriginal and Torres Strait Islander, LGBTQ+ or young, the health outcomes for someone with these intersecting identities remain largely unknown. Emerging literature has begun to identify the health concerns of people who are both Aboriginal and Torres Strait Islander and LGBTQ+, although this work is thus far limited to adults.12,13,14 Consistent with research into these groups separately, findings suggest that suicidality, substance misuse and homelessness are primary health concerns for Aboriginal and Torres Strait Islander LGBTQ+ people. However, the evidence in adults also points to a set of health‐related concerns which are unique to being Aboriginal and Torres Islander and LGBTQ+. For example, some individuals move off Country in search of more accepting communities or to access gender‐affirming care.13,14 However, moving off Country can lead to feelings of dislocation due to loss of connection to Country, which can then precipitate illness. Arguably, Aboriginal and Torres Strait Islander LGBTQ+ young people find it harder to move off Country because of reduced financial and personal resources. Support and service in remote areas are also scarce.14 An inability to express gender or sexual identity is another health‐related concern for Aboriginal and Torres Strait Islander LGBTQ+ people. Some people report feeling pressure to suppress their sexual or gender identity when they are in Indigenous communities.12 Exclusion of gender diverse individuals from men's or women's business can negatively affect social and emotional wellbeing.13 Contemporary culture‐based wellbeing programs often continue this practice of providing support along binary gender lines. Some of the authors’ own experiences reiterate this unintentional bias; Indigenous health care providers use terms such as “sis”, “brother” or “sistergirl” when answering the phone, which can mean that people are misgendered. Although we acknowledge that these terms carry meaning to the Indigenous community, they can be problematical for trans and non‐gender‐conforming young people. There is therefore scope to develop a culturally sensitive way to bypass the use of these gendered terms until a young person's pronouns have been established. Intersectionality theory as a guiding framework International models8,15 provide a useful footing on which to consider intersectionality in the Australian health context. These models demonstrate how societal oppressions of racism and heterosexism within health care systems influence internal (eg, an individuals’ self‐concept) and external (eg, lack of LGBTQ+‐specific services, stigma toward multiple minority groups) risk factors. Importantly, the impact of these risk factors resulting from societal oppressions is not simply a multiplicative effect. Rather, individuals living within multiple minority groups face health disadvantage because of their unique social positioning. Common across these models is an emphasis on the social context of health outcomes because membership in multiple minority status groups can be associated with increased stresses and barriers impeding an individual's coping efforts. Further, when practitioners do not consider how a patient's gender, social class, ethnicity and sexual orientation influences their care needs, patients who experience multiple oppressions can become invisible by being left out of health research or ignored in policy and health promotion efforts, leading to delays in seeking care. Such invisibility in health care is a reported concern among Aboriginal and Torres Strait Islander LGBTQ+ people.12 Health care at the intersection: implications for health research and practice Adopting an intersectional approach to health care requires practitioners to consider the relationship between multiple structural inequalities faced by Aboriginal and Torres Strait Islander LGBTQ+ young people, and downstream consequences for this group's wellbeing. Doing so will likely require additional training and professional development. As Box 1 outlines, although not health providers per se, services and supports led by Aboriginal and Torres Strait Islander LGBTQ+ people have emerged in response to the multiple barriers presented by existing health services. These services provide a space for Aboriginal and Torres Strait Islander LGBTQ+ people to discuss intersecting identities. For example, the Gar'ban'djee'lum Network offers a space in which to celebrate sexual and cultural identity, and Black Rainbow partners with an online newspaper to publish content by Aboriginal and Torres Strait Islander LGBTQ+ authors, providing a platform for voices from people living at this intersection. Service providers can increase their awareness of the contemporary issues faced by Aboriginal and Torres Strait Islander LGBTQ+ young people by accessing online information from these organisations. Moreover, concrete steps which practitioners can follow can be guided by an awareness of intersecting categories, diversity of knowledges, power and multilevel analysis, reflexivity, time and space, and equity and social justice.8 Actions that practitioners can take which are consistent with these domains are outlined in Box 2. The increased focus on Aboriginal and Torres Strait Islander LGBTQ+ young people, led by and advocated for by Aboriginal and Torres Strait Islander LGBTQ+ community members and researchers, is a welcome step towards ensuring safe and effective health care for all Australians. However, there has been little guidance for practitioners on how best to work with this patient group. Health services wanting to support Aboriginal and Torres Strait Islander LGBTQ+ young people can: include an LGBTQ+ status question on intake forms; services can also use an open‐ended question format for young people to describe their gender, rather than tick‐boxes of “male”, “female” or “other”; provide visual displays of support in waiting rooms, such as displaying a rainbow pride flag and other pride flags alongside Aboriginal and Torres Strait Islander flags; and establish mechanisms for Aboriginal and Torres Strait Islander LGBTQ+ young people to provide service feedback (eg, asking patients from this group how the service can best meet their needs). Further, although there are increasing calls to apply an intersectional approach in health care — none more powerful than those of Aboriginal and Torres Strait Islander LGBTQ+ young people themselves — research has yet to systematically evaluate treatment outcomes for patients when such an approach is applied. Future research should measure treatment outcomes in services where staff apply an intersectional lens. The omission of young people from previous research into the health and wellbeing of Aboriginal Torres Strait Islander and LGBTIQ+ people also remains a pressing concern. Further research with young people is needed if practitioners and services working with young people are to effectively and appropriately work within an intersectional framework. Box 1 – Current services available for Aboriginal and Torres Strait Islander LGBTQ+ people* Organisation name Description Website Black Rainbow Advocacy for Aboriginal and Torres Strait Islander LGBTQ+ suicide prevention Support for homelessness, domestic violence, and people involved in the justice system http://www.blackrainbow.org.au/ Tekwabi Giz Provides support to the National LGBTI Health Alliance for Aboriginal and Torres Strait Islander LGBTQ+ people, specialised knowledge, advocacy https://lgbtihealth.org.au/tekwabigiz/ IndigiLez Women's Leadership and Support Group Special focus on Indigenous lesbians and same sex‐attracted women Advocacy for Aboriginal and Torres Strait Islander LGBTQ+ people, cultural retreats, safe sex workshops, family days, workshops, social activities, self‐defence workshops https://www.facebook.com/IndigiLez/ Sisters and Brothers NT Social change, advocacy, support, consultation, resource creation, and research, and awareness for sistergirls, brotherboys, and Aboriginal and Torres Strait Islander LGBTQ+ people https://www.facebook.com/SistersBrothersNTCelebratingDiversity/ First Nations Rainbow Acceptance, celebration, raising community awareness, improving wellbeing, and reducing stigma and discrimination https://www.firstnationsrainbow.org.au/ Yarns Heal Suicide prevention among Indigenous peoples, including sistergirls, brotherboys and LGBTQ+ individuals https://www.yarnsheal.com.au/ Gar'ban'djee'lum Network Support, advocacy, information on healthy lifestyles, social events, fundraising, and celebration of sexual and cultural identity https://www.afao.org.au/article/us-mob-garbandjeelum-network/ Blaq Aboriginal Corporation Celebration, representation and increased visibility of Aboriginal and Torres Strait Islander LGBTQ+ community members https://www.blaq.org.au/about-about * This list of organisations in not exhaustive but provides a starting point for practitioners wanting to learn more about Aboriginal and Torres Strait Islander LGBTQ+ health. Information in the table is taken from the organisations’ websites. None of the organisations listed are young people‐specific, although some make note of the importance of young people. Box 2 – Next steps in health care provision for Aboriginal and Torres Strait Islander LGBTQ+ young people Domain8 Next steps for research and practice Intersecting categories: health professionals should consider that patients likely occupy multiple social positions, not just the identity which appears most dominant Develop LGBTQ+ health information guides that are culturally sensitive to Aboriginal and Torres Strait Islander patients and easily accessible to young people Display the Aboriginal and Torres Strait Islander flags alongside the pride flags at health services Including LGBTQ+ status options on patient intake forms Because experiences of discrimination based on sexual and gender diversity among Aboriginal and Torres Strait Islander people can occur within the context of pre‐existing trauma,12 consider applying trauma‐informed care models when working with this patient group Specific health promotion efforts and programs targeted at Aboriginal and Torres Strait Islander LGBTQ+ young people Primary research into the social emotional wellbeing of Aboriginal and Torres Strait Islander LGBTQ+ young people Primary research into experiences and preferences of Aboriginal and Torres Strait Islander LGBTQ+ young people in the health system Diversity of knowledges: consider Indigenous and queer ways of knowing and being Seek Aboriginal and Torres Strait Islander LGBTQ+ young peoples’ perspectives on their health issues Assess whether Aboriginal and Torres Strait Islander LGBTQ+ young people have a culturally specific understanding of their health and wellbeing, which may differ from dominant, medicalised explanations Primary research into how Aboriginal and Torres Strait Islander LGBTQ+ young people conceptualise health and wellbeing Power and multilevel analysis: health professionals hold greater power than Aboriginal and Torres Strait Islander LGBTQ+ young people due to their positions in society; health issues for this patient group occur across multiple levels of society Reducing power differentials in the healing relationship by using less medicalised language with patients and asking them how to best cater to their specific needs Ensuring young people understand limits of confidentiality so that they can trust practitioners with disclosing their LGBTQ+ status Practitioners attend professional development opportunities that promote appropriate ways of working with Aboriginal and Torres Strait Islander LGBTQ+ young people (such training is currently provided by some organisations listed in Box 1). Primary research into the impact of various societal oppressions on Aboriginal and Torres Strait Islander LGBTQ+ young peoples’ wellbeing Primary research into enablers of effective service delivery in this patient group Reflexivity: consistent reflection on practice decisions and how they relate to patients’ social positioning Practitioners regularly reflect on assumptions they may hold about Aboriginal and Torres Strait Islander LGBTQ+ young people and the root cause of their health problems Discussions with LGBTQ+, Indigenous and mainstream health care providers around attitudes toward Aboriginal and Torres Strait Islander LGBTQ+ young people Time and space: patient needs and preferences are not static, and vary with social positioning Practitioners remain up to date on social trends which may affect this patient group (eg, recent legalisation of same sex marriage, release of the Uluru Statement from the Heart) Practitioners ask individual patients about their experience of living at this intersection, and not assume a universal experience Primary research into health care needs and preferences across the life course in this patient group Equity and social justice: advocating for increased inclusion of Aboriginal and Torres Strait Islander LGBTQ+ young people Health professionals can use their positions of social power to advocate for the needs of Aboriginal and Torres Strait Islander LGBTQ+ young people within their collegiate relations, workplaces and the broader health sector

Bep Uink · Shakara Liddelow‐Hunt · Kate Daglas · Dharma Ducasse

“Now we say Black Lives Matter but … the fact of the matter is, we just Black matter to them”1

If Black lives matter we need to be prepared to examine and address racial violence within the Australian health system My name is Kevin Yow Yeh and today I march for every Black death in custody but I especially march for my grandfather Kevin Yow Yeh Sr. At the age of 34 this man apparently had a heart attack at a Mackay watch house … This last month we've seen plenty of stats, 430 plus Black deaths in custody … and that's only since the Royal Commission, but what about all those deaths that led to that. My grandfather was one of them. Let's humanise these stories. When this man had a heart attack, he left his wife and he left five young children. My grandmother was still having his children when she had to put this man in the ground. That's why we march! Of course we stand in solidarity with our brothers in America. And, of course we stand in solidarity with our sisters in West Papua … but today we stand for our lives here, on stolen land.2 The statistical story of Indigenous health and death, despite how stark, fails to do justice to the violence of racialised health inequities that Aboriginal and Torres Strait Islander peoples continue to experience. This story has been reported on unremarkably in federal parliament for over a decade, as an annual account‐keeping exercise of policy failure and statistical targets not met.3 This story of failure and failing health has been told countless times in health and medical journal publications, and despite growing more frequent in number, these contributions to new knowledge never seem to translate to improved health outcomes. This story of failure does not do justice to the trauma and loss that Aboriginal and Torres Strait Islander communities experience. This story of failure does not do justice to the pain of never meeting the grandfather that you are named after. Tragically, despite the parlous state of Indigenous health, we have not been met here with the kind of urgency that the global Black Lives Matter movement has spurred elsewhere. What we have been presented with, aside from the Health Minister admonishing Black Lives Matter protestors for putting the health of the public at risk,4 has been the triumphal announcement of “research projects”,5 the release of a “landmark report”,6 and a drafting of “refreshed” and “historic targets”.7 All of these supposedly fresh responses were on track before the Black Lives Matter movement hit our shore. Rather than the “new normal” which the threat of coronavirus disease 2019 (COVID‐19) inspired, the Australian health system's Black Lives Matter moment is best characterised as indifferent; a “business as usual” approach that we know from experience betokens failure. When the threat of COVID‐19 loomed, action was swift and the Aboriginal and Torres Strait Islander leadership within and outside of the health system was even swifter in establishing taskforces, lobbying for additional resources for the community controlled sector, instituting special border control measures for remote Indigenous communities, and the development of emergency response plans to protect their communities.8,9 The effective response to the COVID‐19 pandemic sits in sharp contrast to the ongoing pandemic of racism that Indigenous peoples have been fighting since 1788 and which has taken far more Black lives in Australia. Sweet points out: “To date, there is very little sign that senior health policy makers, from the Chief Medical Officer to Health Minister Greg Hunt, will use their authority to name and address the system racism that contributes to poorer healthcare, as it does to overincarceration”.10 While broad attention is often focused on Black deaths in custody, the premature deaths of Indigenous peoples from supposed natural causes inside and outside of custody tell a consistent story of failure and violence that marks the Australian health system and society more broadly. Against the quietude of the Australian health system on racism are the powerful voices of Aboriginal and Torres Strait Islander peoples, on television screens, on public streets and in our spreadsheets, speaking the truth about how little Black lives seem to matter. Both Indigenous clients and clinicians have stories to tell of the violence of racism in the health system, of being cast in the category of less capable, less compliant, less deserving of care and less worthy of the category of human. This then brings us to the coronial inquiry, the endgame of not caring; of neglect. Here, never let us forget the mothers, the children, the cousins and the spouses weeping outside coroner's courts, bearing photos of their loved ones in their hands and on their clothing, simultaneously appealing for care and for justice.11 Moreover, let us not for a second dismiss the anguish of having to fight for the release of recorded footage of your loved one's final moments, to be replayed over and over, in which they too plead vainly, “I can't breathe”.12 So many grieving Indigenous families continue to appeal to the state for care and for justice via coronial inquiries in the hope that their tragedy will not befall another. But the awful truth is that the recommendations of coronial inquiries are not enforceable because the inquest is meant to discover what happened rather than determine responsibility. So again, regardless of the findings, the resulting outcome is business as usual. The coronial inquiry represents a theatre of power where, in the presence of an avoidable Indigenous death, the state declares its benevolence; duly recording the steps taken and policies and procedures adhered to or those requiring review, and the best efforts of police, medical officers or first responders, to deem the death another “unavoidable” tragedy. Gomeroi scholar Whittaker11 notes how the discourse of “natural causes” in coronial inquiries works to render Indigenous peoples as “fated to die” and beyond care because they were “already dead”. The coronial inquiry represents a moment of confluence of the health and legal systems and the state that seek to erase Indigenous existence and affirm the settler trope of a dying race. It represents the theatre of Indigenous health policy writ large. The story of Indigenous health failure, of persisting and alarming health statistics that are routinely attributed to a complex web of social, cultural and economic factors, sustains the notion of the inevitability of Indigenous ill health, of a race destined to die out, despite the best of efforts and intentions. How do we explain an unwavering commitment to a failed Indigenous health policy framework amid a global movement centred around the importance of Black lives, and a National Aboriginal and Torres Strait Islander Health Plan vision of a health system “free of racism” with no strategy for addressing systemic racism?13 How do we further explain the focus on the individual health behaviours or “choices” of Aboriginal and Torres Strait Islander peoples when we know “incessant racial health inequities across nearly every major health index reveal less about what patients have failed to feel and more about what systems have failed to do”.14 As Boyd and colleagues point out, “The solution to racial health inequities is to address racism and its attendant harms and erect a new health care infrastructure that no longer profits from the persistence of inequitable disease”.14 Earlier this year, the National Registration and Accreditation Scheme demonstrated the type of Black Lives Matter moment that the Closing the Gap refresh missed, by launching the Aboriginal and Torres Strait Islander Health and Cultural Safety Strategy 2020‐2025.15 The strategy sets clear directions for the Australian Health Practitioner Regulation Agency, the national boards and accreditation authorities, which regulate Australia's 740 000 registered health practitioners to ensure that patient safety for Aboriginal and Torres Strait Islander peoples is the norm. The landmark strategy embodies ambition and partnership to address racism and culturally safe care; shifting the blame of failure for good health from Black bodies and instead demanding structural and individual health reform of health practitioners and the systems that regulate them. It is this shift of focus that has been central to the calls from Aboriginal and Torres Strait Islander peoples. Black wounds have been laid bare, to reveal the violence of health and legal systems upon Aboriginal and Torres Strait Islander peoples in a desperate appeal for those same systems to care. At 34 years of age my grandfather died, where's his justice? … what about all the other families, what about all the other fathers, brothers, sisters, nephews and nieces …? What about all the other mob? Where's their justice? My name's Kevin Yow Yeh, f*** the system, if you're not with us you're against us! What is needed is an Australian health system that has a steadfast commitment to Black lives: not as in need of saving, but as deserving of care; one that matches the staunchness of grieving Black families marching the streets of our capital cities in the midst of a pandemic. Such a commitment demands that we abandon the failed Indigenous health policy of Closing the Gap16 in favour of a health justice framework,17 which would include, but not be limited to: A foregrounding of Indigenous sovereignty rendering visible the strength, capability and humanity of Aboriginal and Torres Strait Islander peoples, services and communities in all processes of health policy formation and implementation, not as partners but as architects. State and federal government commitment to the recommendations of the coronial inquiries into the deaths of Aboriginal and Torres Strait Islander peoples who have died of preventable or avoidable conditions in the health system, and the establishment of an Indigenous taskforce to oversee implementation. An explicit financial commitment from the National Health and Medical Research Council and the South Australian Health and Medical Research Institute (via the Indigenous Medical Research Future Fund) and the Australian Research Council for research that attends to the nature and function of race in producing the conditions that allow racialised health inequalities to persist, from birth to death, including the embodied consequences of racism. The establishment of awareness‐raising campaigns that make clear the various ways in which Aboriginal and Torres Strait Islander peoples may seek justice when experiencing discrimination within the health system, and commeasurable resourcing of legal services to support Indigenous peoples to take action. Introduction of publication guidelines for health and medical journals requiring research relating to racialised health disparities to foreground institutional racism in its analysis, rather than socio‐economic disadvantage and other social and cultural factors. Development of an interdisciplinary Indigenous health workforce agenda that centres the care of Indigenous people beyond capacity building to include attending to racial violence within workplaces across the Australian health system. We offer these strategies not as a solution, but as some small steps towards a radical reimagining of the Black body within the Australian health system; one which demonstrates a more genuine commitment to the cries of “Black Lives Matter” from Blackfullas in this place right now.

Chelsea J Bond · Lisa J Whop · David Singh · Helena Kajlich