Volume 174 Issue 12

MJA 2001; 174: 621-625 For editorial comment, see Barraclough Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Administration and health services Abstract Objectives: To determine if an integrated clinical risk management program that detects adverse patient events in a hospital, analyses their risk and takes action can alter the rate of adverse events. Design: Longitudinal survey of adverse patient events over eight years of progressive implementation of the risk management program. Participants and setting: 49 834 inpatients (July 1991 to September 1999) and 20 050 emergency department patients (October 1997 to September 1999) at a rural base hospital in the Wimmera region of Victoria. Main outcome measures: Rates of adverse events detected by medical record review and clinical incident and general practitioner reporting. Results: The annual rate of inpatient adverse events decreased between the first and eighth years of the study from 1.35% of all patient discharges (69 events) to 0.74% (49 events) (P < 0.001). Absolute risk reduction was 0.61% (95% CI, 0.23%-0.99%), and relative risk reduction was 44.9% (95% CI, 16.9%-72.9%). The quarterly rate of emergency department adverse events decreased between the first and eighth quarters of monitoring from 3.26% of all attendances (84 events) to 0.48% (12 events) (P < 0.001). Absolute risk reduction was 2.78% (95% CI, 2.04%-3.52%), and relative risk reduction was 85.3% (95% CI, 62.7%-100%). Conclusions: Adverse patient events can be detected, and their frequency reduced, using multiple detection methods and clinical improvement strategies as part of an integrated clinical risk management program. Healthcare delivery in hospitals is associated with adverse patient events,1,2 and clinical risk management aims to reduce the probability of these events. One approach involves detecting adverse events, analysing their causes, estimating their likelihood and consequences and taking appropriate action to prevent the event recurring. Adverse events can be detected by medical record review3 and clinical incident reporting.4 However, after their detection, analysing the events and determining and taking appropriate action to reduce their rates are difficult tasks. Rates have been reduced in other complex industries, such as aviation, by analysing the systems of service delivery in which the events occurred and changing these systems to reduce their probability.5 This systems approach contrasts strongly with the blaming of individuals for errors in healthcare. In this study, we report the effect of an integrated clinical risk management program that used diverse methods to detect adverse patient events in a hospital and a systems approach to their analysis and action to reduce their rates. Methods Setting and patients The study was undertaken at Wimmera Base Hospital in Horsham, 300 km northwest of Melbourne, Victoria. The hospital provides services to 43 000 people in the Wimmera region, including 13 500 in Horsham. Eight specialists and 14 general practitioners live in the town. With the assistance of eight hospital medical officers, they treat about 6000 inpatients and 9000 emergency department patients annually. Another 14 specialists visit the town regularly to treat patients at the hospital. The components of the risk management program (Box 1) evolved over time. In 1989, the hospital medical staff chose four doctors to be medical reviewers and to form a surveillance committee. This committee was expanded to include a nurse in 1995 and a clinical risk manager in 1997. Detection of adverse events Inpatient medical record review: The medical records of all patients admitted to the hospital between July 1991 and September 1999 were reviewed shortly after discharge, using a process described previously.3 Briefly, each medical record was screened by medical records staff using eight general patient outcome criteria (Box 2). Records with at least one of these criteria were sent to one of the four nominated doctors to determine if an adverse event was present. This was defined as "an untoward patient event which, under optimal conditions, is not a consequence of the patient's disease or treatment".1 The reviewer independently completed an adverse event analysis form for discussion at bimonthly meetings of the surveillance committee. Recommendations for action relating to patient care were made by the committee and forwarded to medical and nursing staff groups in the hospital. When a clinical risk manager was appointed, the adverse event analysis forms were first forwarded to the manager to determine if immediate action was required. Emergency department medical record review: The medical records of all patients who attended the emergency department between October 1997 and September 1999 were reviewed. An administrative database of all inpatient admissions and emergency department attendances was screened for five general patient outcome criteria (Box 2), using software designed for the study. Attendances that screened positive were reviewed by the hospital's clinical risk manager and, if an adverse event was detected, by the director of medical services. If an event was confirmed, it was further analysed and recommendations to prevent its recurrence were made to relevant hospital staff, using the same committee review process as used for inpatient records. Clinical incident reporting: A clinical incident reporting system was developed in 1997 by the Australian Patient Safety Foundation, an independent organisation in Adelaide that promotes patient safety. Hospital staff in Horsham were educated about the system and encouraged to report clinical incidents and "near-misses". A clinical incident was defined as "any event that has caused harm, or has the potential to harm, a patient, visitor or staff member, or any event which involves malfunction, damage or loss of equipment or property, and any event which might lead to a complaint".5 Incident reporting forms developed by the Foundation were placed in all departments. These forms comprise two parts: the first provides details of actual or potential clinical incidents, while the second allows the incident to be reported anonymously to a national database. Staff members reporting incidents could identify themselves or remain anonymous. Completed forms for incidents reported between October 1997 and September 1999 were sent to the clinical risk manager for local analysis and were also reported to the national database. General practitioner reporting: As adverse events related to inpatient care may occur or be recognised after patient discharge from hospital, an adverse event reporting form was included in the inpatient summary routinely sent to each patient's general practitioner (GP). GPs were asked to attach the form to the patient's medical record for a month and to complete and return the form if they detected an adverse event. External sources: Some adverse events occur rarely in individual hospitals. Details about serious but infrequent adverse events at other hospitals were obtained from coronial and consultative committee reports, insurers, medical indemnity organisations, medical and nursing journals and the media. If the surveillance committee thought the event could occur locally, action was taken to reduce the risk. Patient satisfaction: Patient perspective on adverse events was sought through patient satisfaction surveys, focus groups and patient complaints. Satisfaction surveys were posted to every 10th patient who attended the emergency department or was admitted to the hospital. Event analysis and action When an adverse event was detected, its likelihood and consequences were estimated in accordance with the Australia/ New Zealand Risk Management Standard6 (Box 3). Events were ranked according to their risk severity (risk severity = consequence score x likelihood score) (Box 4). Events with high risk severity were given priority for analysis, and action was taken to reduce the risk, as described previously7 (Box 5). For adverse events with low risk priority, the surveillance committee decided whether to take action or to accept the risk and continue monitoring for that event. All data from the inpatient adverse event analysis forms were entered into a database program developed from the Clipper database compiler software package.8 Data from emergency department and GP reports were entered into access databases,9 and clinical incidents were entered into the Australian Patient Safety Foundation's database.4 Statistical analysis The χ2 test was used for categorical comparisons of data. A P value < 0.05 was considered to indicate statistical significance; all tests were two-tailed. Statistical analyses were performed using the statistical package GraphPad Instat.10 Confidence intervals were calculated using standard methods.11 Results \ Inpatient medical record review A total of 49 834 inpatients were discharged from the hospital between July 1991 and September 1999. The medical records of 4199 (8.43%) screened positive for one or more of eight general patient outcomes, and 386 (0.77%) contained an adverse event. These events were analysed and action was taken to reduce the probability of recurrence. The annual rate of adverse events decreased between the first and eighth years of the study from 1.35% of all patients discharged (69 events) to 0.74% (49 events) (χ2= 31.31; df = 7; P < 0.001). This trend was linear (χ2=11.52; df = 1; P < 0.001) (Box 6). The absolute risk reduction was 0.61% (95% CI, 0.23%-0.99%), and the relative risk reduction was 44.9% (95% CI, 16.9%-72.9%). Emergency department medical record review A total of 20 050 patients attended the emergency department between October 1997 and September 1999. The medical records of 544 screened positive for one or more of five general patient outcomes (2.71% of all patient attendances), and 250 (1.24%) contained an adverse event. Action was taken to reduce the probability of recurrence. The quarterly rate of adverse events decreased between the first and eighth quarters of monitoring from 3.26% of all attendances (84 events) to 0.48% (12 events) (χ2= 120.43; df = 7; P < 0.001). The trend was linear (χ2= 87.64; df = 1; P < 0.001) (Box 6). The absolute risk reduction was 2.78% (95% CI, 2.04%-3.52%), and the relative risk reduction was 85.3% (95% CI, 62.7%-100%). Clinical incident reporting Between October 1997 and September 1999, hospital staff completed 621 clinical incident forms, and 66 adverse events were found. The most common reported incidents were patient falls (280 incidents, 45% of all reported incidents) and medication errors (93; 15%). In response to the number of falls, a falls risk assessment tool was developed. Each patient over 65 years of age underwent a falls risk assessment on admission to hospital. Subsequently, the number of patient falls resulting in fractures while in hospital decreased. The 66 events detected by clinical incident reporting made up 16.3% of the total of 405 adverse events detected between October 1997 and September 1999 by clinical incident reporting and medical record review; 250 events (61.7%) were detected by emergency department medical record review and 89 (22.0%) by inpatient medical record review. Four adverse events were detected by more than one method; these were associated with failure of equipment in the operating room and an inpatient fall. For analysis, these four events were allocated to the first method by which they were detected. General practitioner reporting Between January and September 1999, 21 reports were made by general practitioners (0.25% of patients discharged). An adverse event was identified in 16 (76% of all reports). Events included discharge medication errors, postoperative wound infections and other surgical complications. Three patients required readmission. External sources Information about 12 adverse events at other hospitals in Victoria was obtained from the media and coronial reports. After analysis, preventive administrative and clinical changes were implemented in Horsham. These included the introduction of an organisation-wide policy on equipment service contracts, installation of thermostatic mixing valves in the hot water system to reduce burns, and development of an intercostal catheter insertion policy. Patient satisfaction Of the 69 formal complaints received by the hospital between October 1997 and September 1999, 11 (16%) related to clinical care. On review, four were associated with an adverse event. Complaints were analysed in the same way as adverse events from other sources. Discussion Our study has demonstrated that adverse events in hospitals can be detected using medical record review, clinical incident reporting and other methods. The rate of adverse events can then be reduced using a systems approach to event analysis, followed by appropriate action and continued monitoring for adverse events to evaluate the effectiveness of the action. As we found that few individual events were identified by more than one detection method, the use of multiple detection methods increased the total number of events identified. Scoring the risk associated with each event, using its likelihood and consequences, allowed events found by different methods to be ranked and prioritised for action to reduce risk. This allowed available resources to be directed to events with the greatest patient risk. To our knowledge, this is the first comparative study over time of a clinical risk management program that used diverse methods to detect adverse events and reduce their rate. Other studies have used a single detection method to measure adverse event rate at one point in time. For example, inpatient medical record review was used in the multihospital Harvard Medical Practice Study1 and the Quality in Australian Health Care Study.2 These studies detected adverse event rates of 3.7%1 and 16.6%2 of hospital admissions, respectively. Both used 18 screening criteria, including some that required clinical judgement, and neither measured the rate of adverse events over time after intervention. Our study found a lower rate of inpatient adverse events, but used only eight screening criteria, none requiring clinical judgement. We are not aware of any comparative studies that measured the adverse event rate in hospital emergency departments. The rate of adverse events found using clinical incident reporting depends on the rate of reporting. For example, an increase in reports of medication errors may reflect an increase in errors, the rate of reporting, or both. Reporting rates vary greatly between hospitals, making meaningful comparisons difficult. In a study in the United States comparing adverse events reported by resident medical staff and those found by medical record review, 30.8% of adverse events were found by both methods.12 This is a much greater proportion than the 0.9% of events found by both methods in our study. However, in our study, most events were reported by nursing staff, with medical staff reporting few events. Although we used multiple methods to detect adverse events, we did not find all adverse events that occurred in the hospital. Although we could have found more by using more screening criteria, our use of five to eight screening criteria for medical record review, rather than the 18 used in some other studies,1,2 meant that this would have required more resources. The study did not include a control hospital where adverse events were detected but no analysis was performed nor action taken. Also, adverse event rates were not adjusted for patient severity. Therefore, other factors may explain the reduction in adverse events. In our study, resource limitations meant that medical records identified by screening were reviewed by a single reviewer. In the Harvard Medical Practice Study and the Quality in Australian Health Care Study, each medical record identified by screening was reviewed by two reviewers and, if they disagreed, by a third. The resources for such intensive review of records are unlikely to be available in most hospitals. The strengths of our study included its eight-year duration and prospective nature. By keeping the method constant (eg, number and types of screening criteria and three of the four reviewers), the rate of adverse events could be meaningfully compared over a long period, and the effects of actions assessed. Further research is required to improve methods of detecting adverse events. A greater proportion of events might be detected with more effective and efficient screening criteria. A potentially effective criterion would be a code for external cause of injury13 to be assigned by medical records staff when coding diagnoses. Another potential screening device is clinical pathways that can detect adverse events by analysing deviations from the pathways. The development of electronic records may also assist in detecting adverse events. In addition, national databases of adverse events reported as clinical incidents or from coronial inquests would provide further information to reduce risk. Actions that are effective in changing clinical behaviour have been discussed in detail previously.7 Although some effective strategies are available, changing health delivery systems and clinical behaviour is frequently complex and difficult, and many strategies in use are not effective.14 More research is required to develop additional effective strategies. The components of the risk management program used in our study could be applied in hospitals of varying sizes. Hospitals or individual departments can decide which detection methods are appropriate for their services and available resources. For example, medical record screening does not need to use all outcome criteria, and further program components can be added over time. Finally, we believe that the risk management program has allowed our patients to receive better care with fewer adverse events and has been an effective use of resources. Acknowledgements We wish to thank the staff of the Wimmera Health Care Group for their enthusiastic participation in the program, especially Mrs Cathy Dooling, Manager Health Information Services, and staff, and previous members of the surveillance committee. This program was partly funded by a grant from the Victorian Department of Human Services. References Brennan TA, Leape LL, Laird NM, et al. Incidence of adverse events and negligence in hospitalised patients: results of the Harvard Medical Practice Study 1. N Engl J Med 1991; 324: 370-376. Wilson RM, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995; 163: 458-471. Wolff AM. Limited adverse event screening: using record review to reduce hospital adverse patient events. Med J Aust 1996; 164: 458-461. <eMJA full text> Australian Patient Safety Foundation. What is incident monitoring? The Australian Incident Monitoring Study. Adelaide: The Foundation, 1997. Leape LL. Error in medicine. JAMA 1994; 272: 1851-1857. Standards Australia. Australian/New Zealand Standard 43:60. Sydney: Standards Association of Australia, 1999. Wolff AM, Bourke J. Reducing medical errors: a practical guide. Med J Aust 2000; 173: 247-251. Clipper. Version 5.0. Los Angeles, Calif: Nantucket Corporation, 1990. Microsoft access. Relational database management system for windows. Version 7.0. Seattle, Wash: Microsoft Corporation, 1999. GraphPad Instat. Version 2.0. San Diego, Calif: GraphPad Software, 1992. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology: a basic science for clinical medicine. 2nd ed. Boston: Little Brown and Co, 1991: 218. O'Neil AC, Peterson LA, Cook EF, et al. Physician reporting compared with medical-record review to identify adverse medical events. Ann Intern Med 1993; 119: 370-376. O'Hara DA, Carson NJ. Reporting of adverse events in hospitals in Victoria, 1994-1995. Med J Aust 1997; 166: 460-463. Oxman AD, Thomson MA, Davis DA, Hayes RB. No magic bullets: a systematic review of 102 trials of interventions to improve professional practice. CMAJ 1995; 153: 1423-1431. (Received 23 Oct 2000, accepted 6 Feb 2001) Authors' details Clinical Risk Management Unit, Wimmera Health Care Group, Horsham, VIC. Alan M Wolff, FRACGP, MBA, Director of Medical Services, and Director of Accident and Emergency Department; Jo Bourke, RN, GradDipCM, Clinical Risk Manager; Ian A Campbell, FRACS, Visiting General Surgeon; David W Leembruggen, FRACGP, Visiting General Practitioner, and Director of Postgraduate Education. Reprints: Dr A M Wolff, Medical Administration, Wimmera Health Care Group, Baillie Street, Horsham, VIC 3400. whcgmedATnetconnect.com.au Make a comment Back to text 2: General outcome criteria used for screening medical records Inpatient criteria Death Return to operating theatre within 7 days Transfer from general ward to intensive care Unplanned readmission within 21 days of discharge Cardiac arrest Transfer to another acute care facility Length of stay greater than 21 days Booked for theatre and cancelled Emergency department criteria Death Unplanned re-presentation to department within 48 hours for same condition Length of stay greater than 6 hours Transfer to another acute care facility Presentation to department for same condition within 28 days of hospital inpatient discharge Back to text 3: Qualitative measures used to determine risk severity of adverse events (modified from Australian/New Zealand Standard 43:606) Measures of consequence or impact 1 Insignificant No injuries, low financial loss 2 Minor Minor treatment required, no increase in length of stay or readmission, minor financial loss 3 Moderate Major temporary injury, increased length of stay or readmission, medium financial loss 4 Major Major permanent injury, increased length of stay or readmission, major financial loss 5 Catastrophic Death, huge financial loss or threat to goodwill Measures of likelihood 1 Rare May occur only in exceptional circumstances 2 Unlikely Could occur at some time 3 Possible Might occur at some time 4 Likely Will probably occur in most circumstances 5 Almost certain Is expected to occur in most circumstances Back to text 4: Examples of risk severity scores Adverse event Source Consequence score (C)* Likelihood score (L)* Risk severity score (C x L) Missed diagnosis (abdominal pain, fracture, myocardial infarction) Emergency Department record review 3 3 9 Drug administration errors Clinical incident reporting 2 3 6 Postoperative wound infection Inpatient record review 3 2 6 Failure to admit when indicated Emergency Department record review 3 2 6 * Scores are defined in Box 2. Back to text 5: Actions taken to reduce the frequency of adverse events Changes to clinical and administrative protocols Focused audits to investigate specific adverse events Discussion with staff involved Education (including presentation of adverse events at postgraduate education meetings and clinical risk management presentations) Creation of worksheets containing details of clinical policy, space to write clinical notes and a patient management checklist Developing checklists for complex procedures Increasing the supervision of junior hospital medical officers Introduction of patient risk assessment tools to determine risk of falling, developing a pressure ulcer or thromboembolus and difficulty with discharge home Regular feedback to clinical staff about adverse events and the results of actions taken to reduce risk Back to text Back to text

Alan M Wolff · Jo Bourke · Ian A Campbell · David W Leembruggen

MJA 2001; 174: 637-640 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Infectious diseases and parasitology Abstract Objective: To determine attitudes towards doctors and hospitals as data custodians, and patients' experiences of unauthorised information releases from health services. Design: Analysis of data from a cross-sectional, descriptive household survey (October-November 1999). Setting: South Australian community. Participants: 3013 randomly selected residents over 15 years of age. Main outcome measures: Level of confidence in doctors and hospitals as data custodians, and patient-reported experience of unauthorised information releases by health services. Results: 288 survey participants (9.6%) were not confident that healthcare providers keep and use information responsibly, 108 (3.6%) reported that healthcare providers had released information without their consent (although at least 48 of these disclosures were legally defensible), and 57 (1.9%) reported harm arising from unauthorised disclosures by health services. Projecting these findings to the South Australian population, over 2000 people experienced harm arising from unauthorised information release in 1999. However, in the same period, there were fewer than 20 formal complaints to major agencies (eg, Ombudsman, Medical Board). Conclusions: Healthcare providers have lost the confidence of a minority of patients. For some, this mistrust is based on experience of unauthorised information release. Some disclosures are mandated by legislation. These findings provide baseline performance measures for benchmarking trends in patient confidence and prevalence of unauthorised release of patient information. The promise of confidentiality encourages the candid communication between doctors and patients required for high quality care. In legal actions concerning breaches of confidence it has been argued that "It is important that those who require medical assistance should not be inhibited in any way from seeking or obtaining it".1This view is supported by research showing that without a guarantee of confidentiality some groups of patients will not seek healthcare2 and others would withdraw from activities such as blood donation.3Australians place more trust in doctors and hospitals to keep and use information in a responsible way than they do in other organisations.4 However, many Australians believe there is less privacy now than there was and that computers make it easier for confidential information to fall into the wrong hands.4 The collection and use of health information has also been identified as a cause for public concern in other countries.5,6 Commentators within the profession have warned that electronic patient records may reduce the protection of patient privacy7 and there is consumer concern about the potential for direct marketing of pharmaceuticals.8 The current legal provisions for protecting confidentiality in South Australia are summarised in Box 1. However, it is not known whether these privacy safeguards are adequate. There is little evidence to support the contention that patient confidentiality is being undermined. In the United States, there has been limited quantitative assessment of the effectiveness of the methods currently used to protect confidential patient information,11 the frequency with which unauthorised releases of information occur,12 or the consequences for patients of these events. Using data from a population survey in South Australia, I investigated the level of confidence in health services, the prevalence of unauthorised information release by health services and the likelihood of harm resulting from these events. Methods Participants A representative sample of South Australians was interviewed in October and November 1999 during the annual Omnibus Health Survey for the South Australian Health Commission Epidemiology Branch. Interviewers started from a random point within each of 340 metropolitan and 100 country Collectors Districts (used by the Australian Bureau of Statistics in the 1996 Census) and chose every fourth dwelling until 10 were selected from each district. Of the 4400 dwellings selected, 133 were vacant. Interviews were conducted with one household member aged over 15 years (the one with the most recent birthday) in 3013 of the remaining 4267 households, giving a response rate of 70.6%. The interview questions are shown in Box 2. Statistical analysis Data were analysed using χ2 tests and the Statistical Package for the Social Sciences (SPSS).13For population projections, I used 1999 figures from the Australian Bureau of Statistics (South Australian population by age and sex).14 Ethical approval Approval to use the data collected in the Omnibus Health Survey was granted by the Flinders University Social and Behavioural Sciences Research and Ethics Committee. Results Confidence in healthcare providers as data custodians While most participants expressed confidence in doctors or hospitals to keep and use information responsibly, nearly one in 10 participants did not share this confidence (Box 3). There was no significant difference between men and women in level of confidence, but there were significant differences in confidence with age: participants aged 25-34 years were significantly less confident about doctors and hospitals as data custodians than those in other age groups (P < 0.001). Prevalence and sources of unauthorised information release One hundred and eight of the 3013 participants (3.6%) had become aware that information had been released by a health service without their permission on at least one occasion. There was no significant difference in reported information release between the sexes or between metropolitan and country dwellers. For 33 (1.1%) participants, the information release had occurred in the previous 12 months. The 108 participants identified 123 instances of information release without authorisation. The services reported to have released the information were general practitioners (47), public hospitals (31), private specialists (23), private hospitals (9), mental health services (4) and other health organisations (9). Lawful and unlawful disclosures Of the 108 participants who reported information disclosures: 48 participants (1.6% of the total sample) reported information releases which would be legally defensible. Of these, 24 participants described information being passed from one treating practitioner to another. While these disclosures are accepted practice, they had not been authorised by the patients. For the other 24 participants, information release had been permitted or mandated by legislation or authorised by the patient. For example, some patients had been required to consent to release information in order to become entitled to benefits such as workers compensation or social security. 32 participants (1.1% of the total sample) described disclosures which would be legally indefensible. Among these were two who had received personally addressed advertisements for respiratory medications and who believed that their addresses and diagnoses had been released to a pharmaceutical company. Others had experienced disclosures by a practitioner of pregnancy, contraceptive use or a diagnosis to family members. 28 participants (0.9% of the total sample) gave responses which did not allow analysis of the lawfulness of the disclosures. Harm resulting from disclosures Of the 108 participants who said that information had been released by health services without their permission, 51 (1.7% of the total sample) were unconcerned, some commenting that it seemed appropriate or that the information release had been required by law. Fifty-seven participants (1.9% of the total sample) reported that unauthorised disclosures had caused trouble or problems for them. For 12 of these (0.40% of the total sample), this had occurred in the previous year. Participants reported distress, embarrassment, arguments between family members and loss of trust in medical services as a result of unauthorised release of information. There were also more tangible losses, such as loss of employment, compensation and insurance entitlements or child custody. Projections to the South Australian population Projecting the proportion of participants who became aware of information releases to the adult population of South Australia indicates that as many as 43 170 ± 8130 South Australians (2 x standard error of the proportion) may have become aware of unauthorised releases of information by a health-care provider, with an estimated 13 190 ± 4550 occurrences in the previous year. Projecting the proportion of participants who reported harm from information release to the South Australian population would indicate that between 2022 and 7530 such events (4776 ± 2 x standard error of the proportion) had occurred in South Australia in the 12 months before the interviews were conducted. Healthcare complaints reported in South Australia Complaints related to healthcare issues, including unauthorised releases of health information, in South Australia may be directed to individual healthcare practitioners, the Medical Board of South Australia, the Ombudsman or individual health units. However, not all complaints are recorded. Box 4 shows complaints recorded by major agencies in South Australia in 1999. Events causing harm could be expected to lead to formal complaints or legal action. However, although there were an estimated 2000 or more South Australians who experienced harm after unauthorised information release in 1999, fewer than 20 formal complaints were made to the largest complaint-handling agencies. It follows that only a minority of patients harmed by unauthorised information release actually initiate a formal complaint. Discussion Healthcare providers have lost the confidence of some patients. For some members of the population, there has been personal experience of harm resulting from the unauthorised release of information. Release of information without authorisation by the patient is not a perfect proxy for breach of confidence. Some disclosures do not require the patient's consent. They may be mandated by law and protect the interests of individuals other than the patient (eg, reporting of child abuse). Transfers of information between treating practitioners have not been the subject of legal sanctions and are accepted as routine practice. However, patients may still experience adverse consequences or become mistrustful as a result of these disclosures. For this reason, all unauthorised releases of patient information resulting in harm may be viewed as adverse events, while recognising that some would not be found to be breaches of confidence if tested in a court. The fact that general practitioners and public hospitals were most often identified as the source of unauthorised releases of information need not indicate less stringent data-handling practices in these settings, but reflects the volume of services being provided. In South Australia, in the 12 months before the survey, there were 7 329 500 Medicare rebates for general practitioner services, 337 144 separations reported by public hospitals and 154 613 separations reported by private hospitals. The cumulative experience of perceptible health information "leaks" is nearly 4% in the adult population in South Australia. By comparison, data from the United States indicate that nearly 20% of adults become aware that health services have disclosed their information "improperly", and nearly 40% do not trust doctors and hospitals to keep information private and confidential.12 While these figures suggest that the South Australian healthcare system compares favourably with that in the United States, healthcare practices vary greatly between countries, as do social expectations of health services. Thus, caution must be exercised in making international comparisons of confidentiality in health services. The South Australian data do not include instances of information release without the patient's being aware of it; nor do they show whether the use of electronic medical records is undermining patient privacy. They do suggest that few harmful disclosures of health information result in formal complaints by patients. The findings provide baseline performance measures for benchmarking trends in patient confidence in health services and in the prevalence of unauthorised disclosures by healthcare providers. It would be important for future research to distinguish between lawful and unlawful disclosures. Apart from the harm to individuals resulting from information disclosures, there is a public interest in ensuring that the general population has confidence in the integrity of health services. Acknowledgements Partial funding for this project was provided by the Royal Australian College of General Practitioners. This research was also supported by an Australian Postgraduate Award and stipend granted by Flinders University of South Australia. References R v Dept of Health, ex parte Source Informatics [1999] 4 All ER 185, Latham J at 196.17(269): 1404. Cheng T, Savageau JA, Sattler AL, De Witt TG. Confidentiality in health care: a survey of knowledge, perceptions, and attitudes among high school students. JAMA 1993; 269: 1404-1407. Banks HD, Williams AE, Nass CC, Gimble J. Changes in intention to donate blood under a hypothetical condition of reduced confidentiality. Transfusion 1993; 33: 671-674. Privacy Commissioner. Community attitudes to privacy. Information paper no 3. Sydney: Human Rights and Equal Opportunity Commission,1995. Bennett C. How do public attitudes on privacy vary among nations: comparative analysis of national privacy surveys prepared for the Global Business Privacy Project of the Center for Social and Legal Research. <http://www.privacyexchange.org> (accessed February 2001). Carman D, Britten N. Confidentiality of medical records: the patient's perspective. Br J Gen Pract 1995; 45: 485-488. Regan BG. Computerised information exchange in health care. Med J Aust 1991; 154: 140-144. Carter M. Integrated electronic health records and patient privacy: possible benefits but real dangers. Med J Aust 2000; 172: 28-30. <eMJA full text> Bray and Smith v Workers Rehabilitation (1994) 62 SASR 218, 30 Mar 1994. Organisation for Economic Cooperation and Development. Guidelines governing the protection of privacy and the transborder flows of personal data 1980. Geneva: OECD, 1980. Saffran C, Rind D, Citroen M, et al. Protection of confidentiality in the computer-based patient record. Clin Comput 1995; 12: 187-192. Princeton Survey Research Associates. Medical privacy and confidentiality survey. Sacramento: California Healthcare Foundation, 1999. Statistical Package for the Social Sciences (SPSS). Version10. Chicago: SPSS Incorporated, 2000. Australian Bureau of Statistics. Population by age and sex, South Australia, as at 30th June, 1999. Canberra: ABS, 2000. (Received 17 Jul 2000, accepted 1 Mar 2001) Authors' details Flinders University of South Australia, Adelaide, SA Ea C Mulligan, BM BS, BMedSci(Hons), MHA, PhD candidate, School of Law. Reprints: Dr E C Mulligan, School of Law, Flinders University of South Australia, GPO Box 2100, Adelaide, SA 5001. Correspondence: Dr E C Mulligan, School of Law, Flinders University of South Australia, GPO Box 2100, Adelaide, SA 5001. ea.mulliganATflinders.edu.au Make a comment 1: Legal provisions protecting confidentiality in South Australia There is no general right to privacy in Australian law. Although there has been a gradual expansion of circumstances in which confidentiality may be defended by the courts, civil action is infrequent. The most recently reported South Australian case involving breach of confidence in health records was decided in 1994.9 In parallel with legislation in other Australian States (Health Administration Act 1991 [NSW] s.22, Health Services Act 1988 [Vic] s.18, Health Services Act 1991 [Qld] s.100), the South Australian Health Commission Act 1976 (s.64) prohibits employees from divulging personal information relating to any patient obtained in the course of employment unless authorised or required by law or by their employer. Other State statutes either permit or require medical practitioners to release specific kinds of patient information (eg, mandatory reporting of child abuse, Children's Protection Act 1993 [SA] s.11), providing a defence to action for breach of confidence in specific circumstances. The Commonwealth Privacy Act 1988 (s.14) includes a set of Privacy Principles derived from the internationally recognised "Guidelines governing the protection of privacy and the transborder flows of personal data".10 The Privacy Act applies to Commonwealth agencies and has recently been amended to apply to the private sector, including private medical practices. Back to text 2: Questions in a 1999 survey of South Australians about confidentiality in health records I am going to ask you some questions about organisations which hold medical records about you. There would be health records about you at the hospital where you were born, with any general practitioners or private specialists you have consulted and at any hospital or mental health service or special clinic where you have been treated. How confident are you in doctors and hospitals to keep and use information in a responsible way? As far as you are aware, has information about you ever been released by a doctor or health service to another person without getting your permission? Did this happen in the last twelve months? Was this information released by a public hospital, private hospital, mental health service, general practitioner, private specialist, or other? When information about you was released without your permission, did it cause any trouble or problems for you? Could you briefly explain what happened and how it affected you? Back to text 3: Confidence in doctors and hospitals as data custodians (n = 3013) Confident/very confident Not very/not at all confident Neither/don't know 2549 (84.6%) 288 (9.6%) 176 (5.8%) Back to text 4: Healthcare complaints recorded in South Australia in 1999 All complaints Complaints concerning confidentiality Medical Board 174 5 Ombudsman 319 1 8 metropolitan hospitals 1792 12 Back to text

Ea C Mulligan

Viewpoint Truth in clinical research trials involving pharmaceutical sponsorship Large clinical trials are expensive to mount. Funding comes mainly from pharmaceutical companies seeking information on drug efficacy and adverse events. Patients should be informed of the financial and publication agreements reached between those conducting the trials. This is unlikely to have a significant effect on trial participation and will provide patients with information relevant to informed consent. A small proportion of monies raised from drug trials could be set aside to fund both a trial register site and further studies on adverse drug reactions. Chris A Commens MJA 2001; 174: 648-649 Intellectual property - Publication bias has consequences - Financial disclosure as part of informed consent - Suggested requirements for drug trials - Is trial information reward enough for the public? - References - Authors' details - - More articles on Statistics, epidemiology and research design More articles on Ethics In recent years, economic rationalism has forced public institutions to look for non-governmental sources of income and links with industry.1 Our dermatology department needed equipment for which funds were not available from the hospital budget, but would be available from payment for participating in a drug trial. The trial sponsors wished to compare their product with the current "best" cream and a placebo in a randomised controlled trial. Participation would be voluntary, the risk of harm minimal, privacy would be protected and patients would be "suitably informed". An administrative and financial agreement was arranged between our department and the professional contract research organisation responsible for the study. Details of this trial are shown in the Box. There was some pressure for quick approval, as doctors working from their private rooms had an impressive head start and were already entering patients in the trial. Our institutional ethics committee sought a number of changes to the trial protocol, but it was eventually approved. We had no sooner entered patients into the trial than it was closed: the required number of patients had been supplied by private practitioners. Was this a case of a public institution being too slow in responding to the demands of industry? Perhaps, but there were other, more important issues, particularly those relating to restrictions of intellectual property, the opportunities for publication bias and informed consent of patients in clinical trials. Intellectual property The rights to the information gathered by the drug trial were legally under the control of the contract research organisation. It is likely that many patients enter drug trials believing that the resulting knowledge will be available for the common good. Would the public readily enter similar trials if they knew the intellectual property was controlled by the sponsors and may not be available for the public record? Commercial sensitivity, the complexity of running multicentre trials and timing of publication demand some flexibility, but an insistence on public record of all trial results should be non-negotiable. Publication bias has consequences My concerns about publication bias are shared by others,2,3 and are as follows: If the findings remain the property of the sponsor, then how much evidence is never reported? How truthful is medical evidence that relies on publications selected by an industry which needs to sell new drugs or variations on existing drugs ("me-too" drugs)? "Me-too" drugs require clinical trials showing some advantage, and these trials may be designed with marketing strategies as the driving hypothesis. Trials that show no difference or no effect, or even adverse effects, are less likely to be published, while positive results are likely to be published and promoted. Pharmaceutical companies have to make a profit or they fail.4 There is evidence for selective publication of drug trial information,5 and even manipulation of information6 and opinion.7,8 Publication bias may result in unsafe or more expensive therapies being used. Health resources are limited and inefficient use results in rationing elsewhere. We need all available information to be on the public record to inform us in clinical decision-making. Financial disclosure as part of informed consent Recent judgments in the Australian justice system suggest that informed consent should involve disclosing all issues that might be significant to the patient making the decision.9 Patients may enter drug trials as part of an ongoing doctor-patient relationship, and this may make them feel more secure in the rigours and supervision imposed by trial conditions.10 Patients' trust in doctors is based on the belief that it is their health that remains the central focus. Full disclosure of financial interests might disturb this trust, particularly in trials conducted in private clinics with financial payment made directly to the medical investigator. In public institutions money gained from trials is not usually paid directly to doctors. Generally, most of it is spent on acquiring necessary equipment or to support further research — something likely to be supported by the public. Disclosing trial financial details to patients will create additional difficulties, but truth is more important than false trust. The Royal Australasian College of Physicians' Ethical guidelines in the relationship between physicians and the pharmaceutical industry11 and the National Health and Medical Research Council's National statement on ethical conduct in research involving humans12 state that there should be disclosure to research participants of relevant aspects of the budget. More recently, financial disclosure in clinical trials has come under scrutiny in the media.13,14 If we don't ensure such disclosure, then either the political or judicial system might impose it on us. Suggested requirements for drug trials We have progressed a long way in the ethical review of research. However, ethics committees also have increasing workloads and diminishing budgets. They are not necessarily equipped to obsessively interrogate and supervise all submitted projects.15,16 I propose that trial submission forms to ethics committees have two or three further questions confirming a commitment to publish trial results17 and to disclose financial details. This would flag this requirement to both researchers and the industry. Some ethics committees may already have these requirements. The resulting transparency would increase public trust in clinical trials, which, in turn, might make patients more likely to volunteer, ensuring wide and valid representation of different trial subjects. Is trial information reward enough for the public? In entering drug trials the public are risking more than the pharmaceutical industries and the investigators. We all agree that clinical trials are necessary and that, in the right setting, they provide information on new and effective therapies. However, there are other rewards that could be offered to the public. Ready public availability of information on the risks of pharmaceutical products would be an appropriate reward. It is estimated that 80 000 Australians are admitted yearly to Australian hospitals with adverse reactions to pharmaceutical products.18 A proportion of drug trial monies could be dedicated to the study and education of adverse drug reactions. Another proportion of drug trial monies could be dedicated to funding a trial register site17 to provide abstracts of all clinical trials and their results. Finally, we need to examine how and by whom clinical trials are conducted as they are taken from academic medical centres into other sites.3,19 Public institutions are the most protective environment for the public for pharmaceutical and biotechnology trials, provided they have transparent and available guidelines on their interactions with the pharmaceutical industry.20-23 References Health and Medical Research Strategic Review. The virtuous cycle. Working together for health and medical research. Canberra: Canberra Info 1999. Chalmers I. Underreporting research is scientific misconduct. JAMA 1990; 263: 1405-1408. Bodenheimer T. Uneasy alliance — clinical investigators and the pharmaceutical industry. New Engl J Med 2000; 342: 1539-1544. Angell M. The pharmaceutical industry — to whom is it accountable? New Engl J Med 2000; 342: 1902-1904. Rennie D. Fair conduct and fair reporting of clinical trials. JAMA 1999; 282: 1766-1768. Hailey D. Scientific harassment by pharmaceutical companies: time to stop. CMAJ 2000; 162: 212-213. Weatherall D. Academia and industry: increasingly uneasy bedfellows. Lancet 2000; 355: 1574. Larkin M. Whose article is it anyway? Lancet 1999; 354: 136. Rogers v Whitaker (1992) 175 CLR 479. Chalmers I. What do I want from health research and researchers when I am a patient? BMJ 1995; 310: 1315-1318. Royal Australasian College of Physicians. Ethical guidelines in the relationship between physicians and the pharmaceutical industry. Sydney: The College, 2000. National statement on ethical conduct in research involving humans. Canberra: National Health and Medical Research Council, 1999. Pyle G. The drug-body snatchers; No cure, Mrs James, but thanks for all the money; Playing patients in the fast lane; It's the money they have to have. Sydney Morning Herald 13 Feb 2001: 1,4. Pyle G. Patient drug tests enrich hospitals; Vulnerable used as guinea pigs but who guards the guardians? Sydney Morning Herald 14 Feb 2001: 1,4. Savulescu J, Chalmers I, Blunt J. Are research ethics committees behaving unethically? Some suggestions for improving performance and accountability. BMJ 1996; 313: 1390-1393. Wise P, Drury M. Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committees of the Royal College of General Practice. BMJ 1996; 313: 1245-1248. Scroccaro G, Venturini F, Alberti C, et al. Registering clinical trials. BMJ 2000; 320: 1339. Roughead E, Gilbert A, Primrose J, Sansom LN. Drug related hospital admissions: a review of Australian studies published 1988-1996. Med J Aust 1998; 168: 405-408. Angell M. Is academic medicine for sale? New Engl J Med 2000; 342: 1515-1518. Lemmens T, Singer PA. Bioethics for clinicians: 17. Conflict of interest in research, education and patient care. CMAJ 1998; 159: 960-965. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000; 283: 2701-2711. Boyd EA, Bero LA. Assessing faculty financial relationships with industry. A case study. JAMA 2000: 284: 2209-2214. DeAngelis C. Conflict of interest and the public trust. JAMA 2000; 284: 2237-2238. Authors' details Department of Dermatology, Westmead Hospital, Sydney, NSW. Chris A Commens, MB BS, FACD, Director. Reprints will not be available from the author. Correspondence: Dr C A Commens, 20 Hillcrest Road, Pennant Hills, NSW 2120. ccommensATmail.usyd.edu.au Make a comment Details of the proposed trial Trial: Phase IIb double-blind, placebo-controlled, parallel-group, multicentre study. Aim: Assess the efficacy of topical creams in different bases. Duration: 12 weeks, with five assessment visits. Procedures: Evaluation and count of lesions and assessment of tolerance of treatments. Patient numbers: 300 patients throughout Australia. Payment: $1200 per patient who completed the trial. Patient travel expenses: $20 per visit. Back to text

Chris A Commens

MJA 2001; 174: 650-651 Clinical record A 35-year-old man, previously well with no known allergies, presented to the emergency department 17 days after starting bupropion (Zyban) to assist him in giving up smoking. He had been taking no other medication before his presentation. Five days before presentation, he complained of discomfort in his throat, and two days later he developed an urticarial rash on his trunk and limbs, joint pain and swelling, and sweating. He had seen his general practitioner three times in the three days before presenting to the emergency department, and was treated with promethazine and prednisolone (50 mg Day 1, 25 mg Day 2, 25 mg Day 3) and cessation of bupropion. Despite this treatment, his symptoms progressed. His rash became more extensive and he started vomiting. At presentation to the emergency department, he had a temperature of 37.6ºC, a diffuse urticarial rash on his trunk and limbs, swelling of the metacarpophalangeal joints and interphalangeal joints, and tender wrists, knees and ankles. Testing with a urine dipstick showed red blood cells (RBC) and 5 g/L protein in his urine. Investigation revealed normal serum electrolyte, urea and creatinine levels. He had neutrophilia of 13.3 x 109/L (normal, 2-8 x 109/L), erythrocyte sedimentation rate of 18 mm/h (normal, < 15 mm/h), C-reactive protein level of 218 mg/L (normal, < 8 mg/L), and gamma glutamate transferase level of 72 U/L (normal, < 43 U/L), but results of other liver function tests were normal. Urine microscopy showed > 108 RBC/L (normal, < 107 RBC/L). Tests for antinuclear antibody, antibodies to dsDNA, antibodies to extractable nuclear antigens, antineutrophil cytoplasmic antibodies, immune complexes, and rheumatoid factor were negative. His immunoglobulin and complement levels were normal. An immunoelectrophoretogram showed raised acute phase reactants. A skin biopsy was consistent with urticaria. There was no evidence of vasculitis. The man was admitted to hospital and treated with prednisolone (50 mg/day) and antihistamines. A repeat urine analysis showed resolution of the haematuria and proteinuria. He developed angioedema of his lip which settled over two days. He was discharged two days after admission on a 10-day steroid taper and a non-steroidal anti-inflammatory drug, and he made a slow recovery over the following two weeks. Discussion of bupropion Bupropion hydrochloride (Zyban sustained-release tablets; GlaxoSmith Kline) has captured the imagination of prescribers and patients in Australia. This drug, which enhances the ability of patients to abstain from smoking, became available on private prescription in the Australian market in November 2000, and on the Pharmaceutical Benefits Schedule from 1 February 2001. By the end of March, 213 000 prescriptions had been approved by the Health Insurance Commission for dispensing for smoking cessation. These data suggest that 10% of all Australian smokers tried the drug in the first two months after it became available on the Pharmaceutical Benefits Scheme. Such rapid take-up of a newly registered drug has not been seen before in this country, and surpassed the manufacturer's ability to maintain supply — the drug allocation for use in Australia in the first year was used in two days. Bupropion hydrochloride is a selective inhibitor of neuronal uptake of catecholamines (noradrenaline and dopamine). The mechanism by which bupropion enhances the ability of patients to abstain from smoking is unknown; however, it is presumed that this effect is mediated in part by noradrenergic or dopaminergic mechanisms.1 Pharmacokinetic studies suggest that both bupropion and its major active metabolite, hydroxybupropion, bind to plasma and cell-surface proteins at a significant level (84% and 77%, respectively). The elimination half-life of bupropion and hydroxybupropion is about 20 hours, and steady-state levels for bupropion and its metabolites are reached within eight days (GlaxoSmith Kline, Therapeutic Goods Administration registration submission). A number of clinical trials have shown that bupropion leads to smoking abstinence for a four-week period in more patients than placebo or nicotine transdermal systems, with an optimal dose response at 300 mg/day.1,2 In addition, bupropion helps patients maintain continuous abstinence for six months, and reduces subjective symptoms of cigarette craving and nicotine withdrawal symptoms.1,2 It is also associated with less weight gain.1-4 Adverse reactions associated with bupropion include headaches, agitation, insomnia, dry mouth, and seizures.4 Bupropion should not be administered to patients with one or more conditions predisposing to a lower seizure threshold, such as a history of seizures, head trauma, tumour of the central nervous system, or other medications known to lower the seizure threshold. A less frequent but significant adverse event seen with administration of bupropion is a hypersensitivity reaction. This occurs at a rate of about 3% (GlaxoSmithKline, Therapeutic Goods Administration registration submission) and most commonly manifests as pruritus, urticaria and/or angioedema; however, some patients present with symptoms suggestive of a serum-sickness-like reaction. These patients usually develop symptoms about 10-20 days after starting bupropion. Their initial symptom is usually an urticarial rash. Over the following days they develop malaise, polyarthralgia/polyarthritis, and fever. Seven patients with the serum-sickness illness have been reported.5-9 There was no evidence of nephritis or complement pathway activation reported in these patients. A serum-sickness-like reaction to a drug is believed to be an immune-complex-mediated illness precipitated by the drug acting as a hapten in a protein-hapten complex. As a high proportion of bupropion binds to protein, it is possible that in some individuals the protein-hapten complex will provoke an immune response, with antibody production. The presence of urticaria in 3% of individuals receiving bupropion suggests the antibodies produced can activate anaphylatoxins such as C3a or C5a, which lead to mast cell and basophil degranulation. Alternatively, the drug might directly activate mast cells or induce specific IgE which activates the mast cells; however, skinprick testing with the drug in our patient provided no evidence for these pathways. It is surprising that we and others8 have not been able to find evidence of complement protein activation or immune complexes in these patients. The absence of circulating immune complexes may be due to the immune complexes being predominantly cell-bound. A serum-sickness-like reaction usually resolves after antigen withdrawal, over about 14 days. Some patients may require hospitalisation. The adverse events with bupropion highlight the importance of postmarketing surveillance of new therapeutic agents, especially those that are used in a large number of people in a short period, as is the case with bupropion. Key points for practice Bupropion (Zyban, GlaxoSmith Kline) is a new therapeutic agent for smoking cessation with rapid and significant market penetration in Australia. Relatively rare adverse events are occurring commonly because of the number of patients receiving treatment. Patients need to have the risk of a hypersensitivity reaction discussed with them and be advised to stop bupropion if symptoms develop. Hypersensitivity reactions can cause significant morbidity, and may require hospitalisation and treatment with prednisolone tapered over a few weeks. References Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997; 337: 1195-1202. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999; 340: 685-691. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation (Cochrane Review). Cochrane Database Syst Rev 2000; CD000031. Holm KJ, Spencer CM. Bupropion: a review of its use in the management of smoking cessation. Drugs 2000; 59: 1007-1024. McLean SE, Pirie SD. A 30-year-old woman with a generalised rash. J Emerg Nurs 1999; 25: 575-576. Tripathi A, Greenberger PA. Bupropion hydrochloride induced serum sickness-like reaction. Ann Allergy Asthma Immunol 1999; 83: 165-166. Yolles JC, Armenta WA, Alao AO. Serum sickness induced by bupropion. Ann Pharm 1999; 33: 931-933. McCollom RA, Elbe DHT, Ritchie AH. Bupropion-induced serum sickness-like reaction. Ann Pharm 2000; 34: 471-473. Peloso PM, Baillie C. Serum sickness-like reaction with bupropion. JAMA 1999; 282: 1817. Make a comment ADRAC reports involving bupropion The Australian Adverse Drug Reactions Advisory Committee has received 780 reports in association with bupropion to mid-May 2001. The more commonly reported problems have involved skin reactions (307 reports), psychological disturbances (285) and nervous system disorders (268). Urticaria has been the most common event reported (167 reports). Other reactions commonly reported have included nausea (87 reports), dizziness/ataxia (78), other rashes (86), insomnia (78), headache (68), and tremor (57). There have been nine deaths involving suspected adverse reactions with bupropion, but it has not been possible to establish or exclude a causal link with bupropion. It should be kept in mind that a high proportion of patients taking bupropion are likely to be in age groups where sudden cardiovascular death occurs and that smoking increases that risk. Thirty-three reports describe a syndrome of a skin rash or urticaria with joint pain or swelling consistent with a serum-sickness-like reaction. This was only recognised by the reporter of the adverse reaction in 10 cases. The delayed onset, ranging from 5 to 37 days (median, 17 days) after commencement of bupropion, is also consistent with a serum-sickness-like syndrome. In at least 16 of the cases, steroids were required. I W Boyd, Executive Secretary, ADRAC, personal communication; <http://www.health.gov.au/tga/docs/html/zyban.htm>. Back to text

Elizabeth Benson