Statistics

To the Editor: We read with interest the article by Koff and Lyons1 and agree that there is a need to develop, implement and evaluate health systems around patient needs and wishes. Implementing value‐based health care is an excellent initiative to address sustainability and patient‐centred care.2 Genuine reform requires a transition away from volume‐based service contracting towards a multidisciplinary approach focused on evidence of improved outcomes.1,2 This would reward doctors and the system for keeping patients healthy and independent in their own homes, with community support, for as long as possible.2 The Leading Better Value Care initiative (2016–2020)1 may be misinterpreted as another set of top‐down policies. It may also have unintended consequences such as reinforcing the silo approach to disease states, diverting finite hospital and local health district resources, such as staff and expertise, to these 13 policy‐driven priority projects. In our work in perioperative health care, we have identified some concerns. First, the sustainability of our health systems is tested by patients who are frailer, who have chronic diseases, and who present for high risk surgery.1,3,4 Second, these patients have a higher incidence of post‐operative complications3,4 and are more likely to be discharged to a higher care facility, rather than back to their home.4 Third, performing surgery on these patients is associated with higher costs and hospital readmissions.4 Fourth, our research has found that past policy for surgical patients5 has led to today's “wicked problem”; that is, frontline perioperative clinicians and managers are dealing with lack of time, increased demand for precision, fragmentation of care, lack of coordination across an episode of care, bed block, complexity of care, and unclear patient outcome measures. In this context, work is required to empower patients and staff in shared decision making to understand the true complexity of risks and outcomes associated with high risk surgery. In conclusion, implementing statewide value‐based care is timely and can be transformational. The high risk surgical patient cohort and the staff providing their care are likely to benefit from, and should be included in, this important reform agenda.

Su‐Jen Yap · Roberto Forero · David Greenfield · Kenneth M Hillman

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

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

It has been reported that about 60% of patients commencing chemotherapy in Australia with curative intent and 47% of those receiving radiotherapy also use complementary medicine.1,2 Ingestible products are frequently used, but are often not discussed with the medical team, which increases the risk of interactions and other undesirable effects. Opportunity costs are another problem; while complementary medicine is typically used by people with cancer for supportive care and wellbeing, some use it to help treat cancer.2 Given the frequent use of complementary medicine by people with cancer, we surveyed Australian public and private hospitals with dedicated cancer services (1 May – 15 December 2016),3,4 to assess various aspects of cancer service coverage, particularly complementary medicine services. In this report, we describe hospital policies on complementary medicine and the availability of related information for patients. The study was approved by the human research ethics committees of the University of Western Sydney (reference, H11389), the University of Wollongong and Illawarra Shoalhaven Local Health District (reference, HREC/16/WGONG/178), and Calvary Health Care, Adelaide (reference, 16‐CHREC‐E011). One staff member from the cancer service of each participating hospital (262 of 282 invited hospitals, 93%) completed a 52‐item electronic survey (online Supporting Information). Chemotherapy was provided by 207 of the participating services (79%) and supportive and allied health care by 196 (75%), including 66 (25%) that provided at least one type of complementary medicine service. Palliative care was provided by 168 hospitals (64%), surgery by 143 (55%), and radiotherapy by 143 (34%). Ninety‐three responding hospitals (36%) could not provide responses to one or more of the five policy‐related survey questions. This was despite the option to complete the survey across several log‐in sessions and 223 of the respondents (85%) having administrator or management roles. Only 89 respondents (34%) were aware of the Council of Australian Therapeutic Advisory Groups (CATAG) position statement on complementary medicines,5 and only 31 of these respondents (35%) thought that their hospital policies were aligned with this statement. A substantial proportion of hospitals did not have policies regarding complementary medicine practitioners or patient‐initiated complementary medicine use (Box). Most hospitals (229, 87%) had policies for documenting complementary medicines: 76 (33%) documented all complementary medicines (including patient‐initiated products) on medication charts, 88 (38%) documented only complementary medicines approved by medical staff, and 48 (21%) documented complementary medicine use only in the clinical history. The policy at 17 hospitals (6%) was that complementary medicines were never permitted, despite CATAG advice.5 In an adjusted backward multinominal logistic regression analysis, hospitals with cancer services without complementary medicine services were significantly less likely to have policies on complementary medicine practitioners and documenting complementary medicines (Box). Further, only 123 services (47%) provided complementary medicine information for patients, and 23 respondents (9%) did not know whether such information was available. The differences in the awareness of and the availability of hospital policies and patient information about complementary medicine are concerning. Irrespective of whether a cancer service provides complementary medicine, consistent policies across Australian hospitals, and staff and patient awareness of these policies, are important because of the widespread use of complementary medicine. Stronger leadership is needed from peak bodies, such as the Australian Commission on Safety and Quality in Health Care and CATAG, to encourage Australian cancer services and hospitals to update or review their complementary medicine policies. Box – Hospital policies regarding complementary medicine products and visiting practitioners, based on survey responses from 262 hospitals with cancer services Complementary medicine (CM) cancer services available Hospitals without v with CM service: adjusted odds ratio* (95% CI) Policy type Number Yes No Total number of hospitals 262 66 (25%) 196 (75%) Documenting CM product use Hospital policy 229 (87%) 60 (91%) 169 (86%) — No policy 24 (9%) 1 (2%) 23 (12%) 10.4 (1.3–81) Unknown 9 (3%) 5 (8%) 4 (2%) 0.29 (0.07–12) Documenting patient‐initiated CM products Hospital policy 43 (16%) 15 (23%) 28 (14%) — No policy 133 (51%) 30 (45%) 103 (53%) 1.8 (0.84–4.0) Case‐by‐case 43 (16%) 9 (14%) 34 (17%) 1.2 (0.48–3.3) Unknown 43 (16%) 12 (18%) 31 (16%) 1.8 (0.68–5.0) Referrals to CM practitioners outside the hospital Hospital policy 25 (10%) 14 (21%) 11 (6%) — No policy 145 (55%) 27 (41%) 118 (60%) 5.2 (2.1–13) Case‐by‐case 43 (16%) 15 (23%) 28 (14%) 2.8 (0.99–8.0) Unknown 49 (19%) 10 (15%) 39 (20%) 4.4 (1.5–13) Scope of practice for visiting CM practitioners Hospital policy 54 (21%) 20 (30%) 34 (17%) — No policy 113 (43%) 16 (24%) 97 (49%) 3.3 (1.5–7.3) Case‐by‐case 34 (13%) 17 (26%) 17 (9%) 0.65 (0.26–1.6) Unknown 61 (23%) 13 (20%) 48 (24%) 2.1 (0.95–5.0) Credentialing for visiting CM practitioners Hospital policy 72 (28%) 32 (48%) 40 (20%) — No policy 103 (39%) 11 (17%) 92 (47%) 6.2 (2.8–14) Case‐by‐case 28 (11%) 11 (17%) 17 (9%) 1.4 (0.56–3.5) Unknown 59 (22%) 12 (18%) 47 (24%) 2.9 (1.3–6.6) CI = confidence interval. * Reference category: hospital has policy and its cancer service provides complementary medicine services. Derived by backward multinominal logistic regression, adjusted for survey responder's role (administration/management: 46 [18%], health care professional: 70 [27%], dual role: 146 [56%]); hospital ownership (public: 132 [50%], private for‐profit: 74 [28%], private not‐for‐profit: 56 [21%]; and Australian Bureau of Statistics remoteness classification (major cities: 117 [40%], inner/outer regional: 87 [30%], remote/very remote: 91 [31%]).

Jennifer Hunter · Suzanne Grant · Geoff P Delaney · Caroline A Smith · Kate Templeman · Jane Ussher

Objectives: To develop and validate a frailty index, derived from aged care eligibility assessment data. Design: Retrospective cohort study; analysis of the historical national cohort of the Registry of Senior Australians (ROSA). Participants: 903 996 non‐Indigenous Australians aged 65 years or more, living in the community and assessed for subsidised aged care eligibility during 2003–2013. Main outcome measures: 44‐item frailty index; summary statistics for frailty index score distribution; predictive validity with respect to mortality and entry into permanent residential aged care during the five years after assessment. Results: The mean frailty index score during 2003–2013 was 0.20 (SD, 0.07; range, 0–0.41); the proportion of assessed older people with scores exceeding 0.20 increased from 32.1% in 2003–2005 to 75.0% in 2012–2013. The risks of death and entry into permanent residential aged care at one, three and five years increased with frailty index score level (at one year, high [over 0.35] v low scores [under 0.05]: hazard ratio for death, 5.99; 95% CI, 5.69–6.31; for entry into permanent residential aged care, 8.70; 95% CI, 8.32–9.11). The predictive validity (area under the receiver operating characteristic curve) of Cox proportional hazard models including age, sex, and frailty index score was 0.64 (95% CI, 0.63–0.64) for death and 0.63 (95% CI, 0.62–0.63) for entry into permanent residential aged care within one year of assessment. Conclusions: We used Australian aged care eligibility assessment program data to construct and validate a frailty index. It can be employed in aged care research in Australia, but its application to aged care planning requires further investigation.

Jyoti Khadka · Renuka Visvanathan · Olga Theou · Max Moldovan · Azmeraw T Amare · Catherine Lang · Julie Ratcliffe · Steven L Wesselingh · Maria C Inacio

Since COVID-19 emerged in December 2019, over 1100 clinical studies have been registered globally, including over 500 RCTs

Joshua S Davis · David Ferreira · Justin T Denholm · Steven YC Tong

To the Editor: We read the perspective by Weinstein and colleagues1 with interest and agree that treatment of snake envenoming in Australia is complex, and that clinicians should seek expert advice in cases of severe or unusual envenoming. There is 24‐hour specialist clinical toxicologist support available through the national Poisons Information Centre network (13 11 26), which takes 300 calls annually regarding snakebite. However, we are concerned that the authors argue for just one non‐evidenced‐based solution — higher doses of antivenom — despite the extensive evidence that this historical approach does not lead to better outcomes. They suggest that the reduction in antivenom doses is based on a study of snakebite data in Australia from 2005 to 2015,2 which concluded that as “the usual antivenom dose for all major snake groups has decreased to one vial, with no evidence of adverse consequences, this approach should be retained” (emphasis added).2 However, the evidence supporting the move to lower doses of antivenom was based on a series of around 15 earlier studies.2 Serial measurement of venom concentrations using enzyme immunoassays in patients with snake envenoming demonstrated complete neutralisation after any dose,2 and the time course of recovery was unaltered by antivenom dose. The evidence suggests benefits from earlier antivenom but not from higher doses.3 Weinstein and colleagues cite a study by O'Leary and colleagues4 when they state that using “samples from rodents injected with venom … inaccurately determines a true neutralising dose”. However, the cited study measured venom–antivenom complexes in vitro to determine the antivenom concentration at which every venom molecule is bound to at least one antivenom molecule, as a measure of efficacy.4 It showed that this was similar to the manufacturer's original recommendation of a dose of a single vial of antivenom. Weinstein and colleagues criticise the use of data from the large multicentre prospective cohort, the Australian Snakebite Project, which reports both clinical and laboratory outcomes and measures venom concentrations. They provide no citations to support their contentions, other than single cases and opinion (often citing their own previous views). A coroner's case in which a person died after three vials of antivenom is strangely cited as highlighting concerns that a single vial of antivenom is insufficient. They suggest two vials may be sufficient, or even larger doses, but offer no research or studies to support this, and no guidance as to when larger doses are required. They also do not provide a useful or practical alternative approach to the treatment of snake envenoming. Current national evidence‐based guidelines and Poisons Information Centres recommend that one vial of brown snake antivenom and one vial of tiger snake antivenom be given as soon as possible in most snake envenoming cases in Australia.5 This ensures that the most common snakes are covered, as snake venom detection kits are unreliable.2 It also means an equivalent of two vials of antivenom is administered, because Australian “monovalent” antivenoms are in fact polyvalent.6 Evidence‐based guidelines continuously evolve, and we believe the key to better outcomes is early identification of envenomed patients and prompt access to the latest evidence‐based advice by consulting a clinical toxicologist through the Poisons Information Centre.

Geoffrey K Isbister · Nicholas A Buckley

Coronavirus disease 2019 (COVID‐19) poses extraordinary challenges for health care in Australia. One of the greatest will be the pressure on hospitals to support people with severe disease. Modelling studies can provide valuable insights into the likely course of the epidemic, and can be particularly useful for anticipating resource requirements, including demand for intensive care services at the peak of the epidemic. In this report, we extrapolate the findings of the Imperial College model of the pandemic1 to the New South Wales population. We also developed a simple SEIR (susceptible–exposed/incubating–infected–removed) model to explore the effect of varying the infection reproduction number (R), which can be reduced by effective social distancing measures, on the timing of the peak of the epidemic. The two models are described in the online Supporting Information. Applying the Imperial College model, the peak demand for intensive care in NSW would be at least 6965 beds if mitigation efforts — isolation of people with confirmed COVID‐19, household quarantine of their contacts, social distancing from people over 70 years of age — are implemented, or almost eight times as many as the baseline number; without mitigation, more than three times as many ICU beds (21 283) could be required (Box 1). Applying our SEIR model to a scenario without social distancing measures (R = 2.4), the number of people requiring hospitalisation in NSW would peak at 450 per 100 000 population (35 375 beds), and the number requiring critical care at 150 per 100 000 population (11 792 ICU beds, or 1349% of baseline ICU capacity). In this scenario, viral transmission would peak during late June and ICU bed occupancy in early July. About 16% of people would be potentially infectious at this point, although a smaller proportion was modelled as exhibiting symptoms (Box 2; Supporting Information, table 3). In a scenario of increased social isolation (R = 1.6) and an assumed hospitalisation rate for people with confirmed COVID‐19 of 6.7%, case numbers would peak in early October and ICU occupancy in mid‐November; about 180 people per 100 000 population would require hospitalisation (14 150 beds) and 65 per 100 000 intensive care (5110 ICU beds, or 585% of baseline ICU capacity) (Box 2; Supporting Information, table 3). That is, the peak figures would be about one‐third the size of those in the no mitigation scenario. Sensitivity analyses in which the proportion of hospitalised patients was varied (5–15%) similarly found that increasing social isolation markedly reduced demand (Supporting Information, table 4). We have used two modelling methods to estimate peak demand for critical care services in NSW during the COVID‐19 epidemic. Both approaches identified that COVID‐19 would impose a major burden on the health care system, and the mismatch between the estimated numbers of ICU beds needed and their availability is stark. Our modelling shows the critical importance of effective COVID‐19 containment strategies, as well as the urgent need to invest in resources that support the surge capacity of critical care services in NSW. Box 1 – Estimated number of intensive care unit (ICU) beds required at the peak of the initial wave of COVID‐19 cases, applying the Imperial College model to New South Wales, by Local Health District (LHD) Mitigation strategy Population (2016)2 No mitigation Close schools, universities Case isolation Case isolation, household quarantine Case isolation, household quarantine, social distancing of people over 70 ICU beds needed per 100 000 population1 — 275 240 190 125 90 ICU beds need, by LHD Sydney 656 460 1805 1576 1247 821 591 South Western Sydney 964 342 2652 2314 1832 1205 868 South Eastern Sydney 914 021 514 2194 1737 1143 823 Western Sydney 948 584 2609 2277 1802 1186 854 Northern Sydney 914 233 2514 2194 1737 1143 823 Illawarra Shoalhaven 405 534 1115 973 771 507 365 Central Coast 335 309 922 805 637 419 302 Other LHDs 2 600 791 7152 6242 4942 3251 2341 All NSW (proportion of baseline bed number)* 7 739 274 21 283 (2435%) 18 574 (2125%) 14 705 (1682%) 9674 (1107%) 6965 (797%) * Estimated number of ICU beds prior to COVID‐19 epidemic: 874.3 Box 2 – The estimated number of patients with COVID‐19 admitted to hospital or to intensive care units (ICUs), according to a SEIR model of the epidemic * For main curves, 10% case hospitalisation rate assumed; shaded areas show range for hospitalisation rates between 5% and 15%.

Gregory J Fox · James M Trauer · Emma McBryde

In 2014, we reported in the MJA our findings, based on linked data for cervical screening and human papillomavirus (HPV) vaccination of women in Victoria, that participation of young women in cervical screening during 2010 and 2011 was significantly lower among HPV‐vaccinated than among unvaccinated women.1 In 2018, we had the opportunity to repeat the study at the national level as part of a broader data linkage study of cancer outcomes and screening behaviour across the three national cancer screening programs in Australia.2 In the original study (2014), the Australian Institute of Health and Welfare (AIHW) data linkage unit applied probabilistic name‐based linkage to HPV vaccination and cervical screening data. We acknowledged it was likely that some screened women who were vaccinated would be incorrectly identified as unvaccinated because many young women would have changed their names and addresses between vaccination and cervical screening. In the more recent study (2018), the AIHW again used probabilistic name‐based linkage, but first updated HPV vaccination and cervical screening data by obtaining histories of name and address changes from the Medicare Enrolment File. Medicare registrants’ details are updated when new data are provided to Medicare, the national health care scheme, and are recorded in new records with dates of change. The Australian Department of Human Services agreed to provide these data to the AIHW for data linkage purposes for our 2018 study. Our investigation was approved by the AIHW Ethics Committee (reference, EO 2014‐4‐130) and by state and territory human research ethics committees. After incorporating Medicare data, annual cervical screening rates for Victorian women aged 20–24 years or 25–29 years were higher during 2010 and 2011 for vaccinated than unvaccinated women,2 contrary to our 2014 findings.1 For 20–24‐year‐old Victorian women, the difference in rate changed from 10.1% lower to 14.7% higher for vaccinated women, and for 25–29‐year‐old women from 13.5% lower to 10.0% higher (Box). Our updated findings are consistent with findings from other countries of higher cervical screening participation among women who have been vaccinated against HPV.3,4,5 Incorporating the Medicare Enrolment File into the 2018 linkage was a test of proof of concept. Its successful use in this and similar studies has led to the AIHW data linkage unit granting ethics approval and relevant authorisations for employing the Medicare Enrolment File as a tool for improving the quality of other data linkage studies. The key message of our original study, however, remains unchanged. All women, whether vaccinated against HPV or not, should be encouraged to participate in cervical screening: the HPV vaccine does not protect against all HPV types, and many women in Australia were sexually active before they were vaccinated. While it is as yet unclear whether the association between vaccination and screening will persist for women who were routinely vaccinated at school, it is crucial that we focus on strategies that effectively engage women who do not currently participate in screening. Box – Estimated participation of Victorian women in cervical screening during 2010 and 2011, by HPV vaccination status and age group: 2014 and 2018 data linkage studies HPV = human papillomavirus.

Alison C Budd · Andrew Powierski · Theresa Chau · Marion Saville · Julia ML Brotherton

We need informative citation metrics that will be less prone to misuse and gaming

John PA Ioannidis · Kevin W Boyack

Objectives: To assess progress in Australia toward the 2030 WHO hepatitis C elimination targets two years after the introduction of highly effective direct‐acting antiviral (DAA) treatments. Design: Analysis of quarterly data on government‐subsidised hepatitis C RNA testing and hepatitis C treatment in Australia, January 2013 – June 2018. Changes in testing and treatment levels associated with DAA availability were assessed in an autoregressive integrated moving average (ARIMA) statistical model, and the impact by 2030 of different levels of testing and treatment were estimated using a mathematical model. Major outcome measures: Hepatitis C prevalence among people who inject drugs; annual hepatitis C incidence relative to 2015 levels; projections for the hepatitis C care cascade in 2030. Results: The mean annual number of treatments initiated for people with hepatitis C increased from 6747 during 2013–2015 (before the introduction of DAAs) to 28 022 during 2016–18; the mean annual number of diagnostic RNA tests increased from 17 385 to 23 819. If current trends in testing and treatment continue (ie, 2018 testing numbers are maintained but treatment numbers decline by 50%), it is projected that by 2030 only 72% of infected people would be treated (by 2025 all people diagnosed with hepatitis C would be treated). The incidence of hepatitis C in 2030 would be 59% lower than in 2015, well short of the WHO target of an 80% reduction. The identification and testing of people exposed to hepatitis C must be increased by at least 50% for Australia to reach the WHO elimination targets. Conclusion: Hepatitis C elimination programs in Australia should focus on increasing testing rates and linkage with care to maintain adequate levels of treatment.

Nick Scott · Rachel Sacks‐Davis · Amanda J Wade · Mark Stoove · Alisa Pedrana · Joseph S Doyle · Alexander J Thompson · David P Wilson · Margaret E Hellard

Weather conditions conducive to extreme bushfires are becoming more frequent as a consequence of climate change.1 Such fires have substantial social, ecological, and economic effects, including the effects on public health associated with smoke, such as premature mortality and exacerbation of cardio‐respiratory conditions.2,3 During the final quarter of 2019 and the first of 2020, bushfires burned in many forested regions of Australia, and smoke affected large numbers of people in New South Wales, Queensland, the Australian Capital Territory and Victoria. The scale and duration of these bushfires was unprecedented in Australia. We undertook a preliminary evaluation of the health burden attributable to air pollution generated by bushfires during this period. Using standard methods for assessing the health impact of air pollution,4 we estimated the numbers of excess deaths, hospitalisations for cardiovascular and respiratory problems, and emergency department presentations with asthma in NSW, Queensland, the ACT and Victoria between 1 October 2019 and 10 February 2020 that could be attributed to bushfire smoke exposure. We estimated population exposure to particulate matter less than 2.5 μm in diameter (PM2.5) for the regions of NSW, Queensland, the ACT and Victoria for which publicly available air quality monitoring data were available (for about 90% of the total population of these states). Data were obtained from the NSW Department of Planning, Industry and Environment,5 the Queensland Department of Science,6 ACT Health,7 and the Environmental Protection Agency Victoria.8 We defined bushfire smoke‐affected days as days on which the 24‐hour mean PM2.5 concentration exceeded the 95th percentile of historical daily mean values for individual air quality stations. We estimated daily mean PM2.5 levels by Statistical Area Level 2 (SA2), using station level data whenever at least one monitoring station was within 100 km of the SA2 centroid, and applying inverse distance weighting.9 Published population and health data from the Australian Bureau of Statistics,10,11 the Australian Institute of Health and Welfare,12,13,14,15 and the NSW Ministry of Health were used.16 We quantified health outcomes by combining baseline incidence rates12,13,14,15 for each health outcome with daily exposure data and applying the relevant exposure–response risk coefficients for each outcome.17,18 We also conducted sensitivity analyses with different PM2.5 thresholds for defining bushfire smoke‐affected days. Further methodological details, including underlying assumptions and limitations, are included in the online Supporting Information. Our analysis of publicly available aggregated data did not require ethics approval. During the study period, PM2.5 concentrations exceeding the 95th percentile of historical daily mean values were recorded by at least one monitoring station in the study area on 125 of 133 days (Box 1). We estimated that bushfire smoke was responsible for 417 (95% CI, 153–680) excess deaths, 1124 (95% CI, 211–2047) hospitalisations for cardiovascular problems and 2027 (95% CI, 0–4252) for respiratory problems, and 1305 (95% CI, 705–1908) presentations to emergency departments with asthma (Box 2). Applying lower thresholds for defining bushfire smoke‐affected days (no threshold, 90th percentile of historical values) did not markedly alter our findings; a higher threshold (99th percentile) reduced the estimates by about 20%. The highest population‐weighted PM2.5 exposure level, 98.5 μg/m3 on 14 January 2020 (Box 1), exceeded the national air quality 24‐hour standard (25 μg/m3)19 and was more than fourteen times the historical population‐weighted mean 24‐hour PM2.5 value of 6.8 μg/m3. We have estimated the excess health burden during 19 weeks’ continuous fire activity in the states most severely affected by smoke. Our estimates are based on air quality data from monitoring stations in the four eastern states — that is, we did not include data for smoke from all extreme fires in Australia during the study period — and we did not attempt to estimate health effects for which exposure–response relationships are less well characterised, such as primary health care attendances and ambulance calls. Detailed epidemiological analysis of more comprehensive exposure estimation and empirical health data will provide more complete information about the harms attributable to the severe air pollution associated with these unprecedented fires, but our findings indicate that the smoke‐related health impact was substantial. Smoke is just one of many problems that will intensify with the increasing frequency and severity of major bushfires associated with climate change. Expanded and diversified approaches to bushfire mitigation and adaptation to living in an increasingly hot and fire‐prone country are urgently needed.20 Box 1 – Population‐weighted PM2.5 levels, New South Wales, Queensland, the Australian Capital Territory and Victoria, 1 October 2019 – 10 February 2020* * Data by state are included in the online Supporting Information. Box 2 – Estimated health burden attributable to bushfire smoke, Queensland, New South Wales, the Australian Capital Territory and Victoria, 1 October 2019 – 10 February 2020 Outcome Estimated number of cases (95% confidence intervals) Queensland New South Wales Australian Capital Territory Victoria Total Excess deaths (any cause) 47 (17–77) 219 (81–357) 31 (12–51) 120 (44–195) 417 (153–680) Hospital admissions, cardiovascular 135 (25–246) 577 (108–1050) 82 (15–149) 331 (62–602) 1124 (211–2047) Hospital admissions, respiratory 245 (0–513) 1050 (0–2204) 147 (0–308) 585 (0–1227) 2027 (0–4252) Emergency department attendances, asthma 113 (61–165) 702 (379–1026) 89 (48–131) 401 (217–586) 1305 (705–1908)

Nicolas Borchers Arriagada · Andrew J Palmer · David MJS Bowman · Geoffrey G Morgan · Bin B Jalaludin · Fay H Johnston

Genetic research with Indigenous Australians is achievable with community engagement and appropriate governance mechanisms in place

Steven YC Tong · Heather D'Antoine · Melita McKinnon · Kyle Turner · Maui Hudson · Ngiare Brown · Jonathan R Carapetis · Dawn C Bessarab

What is value in health care and how can the system deliver it at scale?

Elizabeth Koff · Nigel Lyons

The causes of childhood cancers must be understood before interventions to reduce their incidence can be developed

Danny R Youlden · Peter D Baade · Adèle C Green · Patricia C Valery · Andrew S Moore · Joanne F Aitken

Greater investment is needed to support eye health coordinators, community-based liaison officers, and family members and carers

Aryati Yashadhana · Ling Lee · Jessica Massie · Anthea Burnett

To the Editor: Uncontrolled before‐and‐after studies are highly prone to bias. Wabe and colleagues report on the impact of rapid influenza testing on outcomes for emergency department (ED) patients.1 They compared outcomes across four hospitals between the 2016 influenza season, when standard testing was used, and 2017, when rapid testing was used. Rapid testing was associated with shorter test turnaround times, more patients receiving results, and lower admission rates. Before‐and‐after studies use historical controls, in this case the prior influenza season, to evaluate the impact of interventions. This may be adequate for comparing simple indicators, such as test turnaround time, or for generating hypotheses. However, uncontrolled before‐and‐after studies are not useful for assessing more complex outcomes, such as admission rates, which are highly vulnerable to bias from other factors that may impact the observed results. For this reason, they are discouraged by some publishing groups.2 Frequent genetic drift in influenza virus strains causes variations in the burden and severity of illness each year, which influences ED presentations, testing and admission rates. The 2017 influenza season saw unprecedented numbers of influenza cases and ED presentations in NSW,3 which likely influenced admission practices. Teasing out the effect of rapid testing on admission rates is therefore not possible using an uncontrolled comparison between two disparate influenza seasons, in the manner of Wabe and colleagues. The steps taken to attempt to reduce seasonal effects cannot address this. It is also not possible to determine the net direction of biases in this study. Given the higher cost of rapid tests, it is important to have good estimates of their impact to inform economic evaluations. There are stronger methodologies that still allow timely evaluation using routinely collected data. At minimum, a comparison could be made to hospitals that did not implement rapid testing. When data from more seasons are available, an interrupted time series analysis may be appropriate.4 Interventions that mitigate the burden of seasonal influenza on health services are critical. Rapid testing is likely one such intervention, and therefore warrants careful evaluation with robust methodologies to inform its use.

Anthea L Katelaris · Ross M Andrews · Jeremy McAnulty

Cancer overdiagnosis is a substantial problem that urgently requires changes in public health policy

Paul P Glasziou · Mark A Jones · Thanya Pathirana · Alexandra L Barratt · Katy JL Bell

Survivors of childhood cancer remain at increased risk of a second primary cancer well into adulthood

Danny R Youlden · Peter D Baade · Adèle C Green · Patricia C Valery · Andrew S Moore · Joanne F Aitken

Understanding how to interpret diagnostic test accuracy studies is a key skill that health practitioners need to develop in order to undertake evidence- based practice

Katy JL Bell · Petra Macaskill · Clement Loy

Estimates adjusted for competing risks of mortality can be more meaningful, but make some comparisons more difficult

Elizabeth Buckley · David M Roder

Unlocking the potential of health data to improve patient outcomes requires the integration of research, health care and education

Helena J Teede · Alison Johnson · Jim Buttery · Cheryl A Jones · Douglas IR Boyle · Garry LR Jennings · Tim Shaw

Australia needs to develop and implement policies to ensure that data are disaggregated, analysed and presented by sex and gender

The Sex and Gender Sensitive Research Call to Action Group

Australian Genomics is calling for a change in research ethics and governance frameworks

on behalf of Australian Genomics