Volume 170 Issue 3

Research Mortality associated with New South Wales methadone programs in 1994: lives lost and saved John R M Caplehorn and Olaf H Drummer MJA 1999; 170: 104-109 For editorial comment, see Ali & Quigley Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Drugs and alcohol Abstract Objectives: To estimate the effects of methadone programs in New South Wales on mortality. Design and cases: Retrospective, cross-sectional study of all 1994 New South Wales coronial cases in which methadone was detected in postmortem specimens taken from the deceased. Cases were people we identified as patients in NSW methadone maintenance programs or those whose deaths involved methadone syrup diverted from maintenance programs. Outcome measures: Relative risks of fatal, accidental drug toxicity in the first two weeks of treatment and later; the number of lives lost as a result of maintenance treatment; preadmission risks and the number of lives saved by maintenance programs, calculated from data from a previous study. Results: There was very close agreement between this study's classifications and official pathology reports of accidental drug toxicity. The relative risk (RR) of fatal accidental drug toxicity for patients in the first two weeks of methadone maintenance was 6.7 times that of heroin addicts not in treatment (95% CI RR, 3.3-13.9) and 97.8 times that of patients who had been in maintenance more than two weeks (95% CI RR, 36.7-260.5). Despite 10 people dying from iatrogenic methadone toxicity and diverted methadone syrup being involved in 26 fatalities, in 1994 NSW maintenance programs are estimated to have saved 68 lives (adjusted 95% CI, 29-128). Conclusions: In 1994, untoward events associated with NSW methadone programs cost 36 lives in NSW. To reduce this mortality, doctors should carefully assess and closely monitor patients being admitted to methadone maintenance and limit the use of takeaway doses of methadone. Introduction Methadone maintenance greatly reduces heroin addicts' risk of death.1 A 15-year follow-up of patients in New South Wales showed methadone maintenance saved lives by reducing addicts' risk of fatal heroin overdose.1 When combined in a meta-analysis with the results of overseas cohort studies, the relative risk of death in methadone maintenance was a quarter that of addicts not in treatment (95% CI, 0.19-0.33).1 However, methadone maintenance is also a cause of death. Patients are at risk of fatal iatrogenic toxicity and other drug users may die from taking methadone syrup diverted from maintenance programs.2-6Mortality associated with NSW maintenance programs was independently investigated. The first report from this project presented the case histories of the 13 patients who died in the first two weeks of treatment.7 It identified 10 probable cases of fatal iatrogenic methadone toxicity (ie, where prescribed doses of methadone either caused or contributed to fatal accidental drug toxicity).7 This, the second report, presents an estimate of the relative risk of fatal accidental drug toxicity in the first two weeks and later maintenance. It also presents estimates of the effect of admission to methadone maintenance on the risk of fatal accidental drug toxicity and of the number of lives saved by NSW maintenance programs in 1994. Methods This study was approved by the Human Research Ethics Committee of the Western Sydney Area Health Service and the NSW State Coroner. In late 1995 the database at the NSW Health Department's Division of Analytical Laboratories was searched to identify 1994 coronial cases in which methadone was detected in postmortem specimens. These analytical laboratories receive specimens for toxicological analysis in all cases of sudden death referred to the NSW State Coroner. Autopsy, toxicology and police reports and the statements of family and friends, prescribers and other witnesses were collected from coronial files. The methadone treatment histories of the deceased were extracted from data held by the NSW Health Department's Pharmaceutical Services Section. The Department also provided data on the number of people admitted to and treated with methadone maintenance in NSW in 1994. Cases were grouped according to the source of the methadone: methadone syrup given as maintenance treatment; methadone syrup diverted from the maintenance program; and methadone tablets (Physeptone; Glaxo Wellcome, Boronia, Vic.) prescribed for pain relief. As the Sydney black market consists almost entirely of methadone syrup diverted from maintenance programs,8 illicit drug users who obtained methadone from an unknown source were classified as having taken diverted syrup. We used two parallel classifications of cause of death -- that on the official pathologist's report, and our own. In our classification, we initially established cause of death independently of one another, with one of us (O H D) blind to the official cause of death. Cases were first categorised as "accidental drug toxicity" and "other". The "other" category included suicides, deaths from natural causes and trauma, and deaths in which drug toxicity was considered to have contributed to a death from natural causes. The "accidental drug toxicity" cases were further categorised into "methadone" and "other drug or drugs" on the basis of whether or not methadone was considered to have either caused or made a significant contribution to the death. There were no simple criteria for establishing the contribution of methadone to deaths involving other drugs. However, as deaths to which methadone contributed closely resembled cases of fatal methadone toxicity,2,3,7 a relatively confident decision could be made after a thorough examination of the documentary and toxicological evidence and the autopsy report.2,7,9-12 Police statements and photographs of the deceased at the scene of death provided some assistance. A brownish, frothy oedema fluid was often observed coming from the deceased's mouth or nose (see Box 1).7 Witnesses' statements provided a guide to likely tolerance and chronologies of ingestion and of the development of symptoms and signs of toxicity.2,7 These statements were particularly useful in cases involving methadone as death usually occurred some hours after the drug was taken,14 and some time after the development of coma (see Box 1).2,3,7,10,11 Postmortem blood methadone concentration was helpful but not definitive, as fatal concentration varies widely with tolerance11,12 and the blood concentration of methadone increases after death.15 Moreover, the postmortem increase in blood methadone concentration varies unpredictably from one part of a cadaver to another.16 The autopsy findings were remarkably consistent in cases of fatal drug toxicity involving methadone, with the immediate cause of death being pulmonary oedema secondary to hypoventilation.2,7,10,11 As methadone toxicity usually causes a gradually worsening hypoventilation, the hypoxia and resulting pulmonary hypertension are generally prolonged and severe, and significant quantities of water and electrolytes, large proteins and red blood cells leak from the pulmonary capillaries into the air spaces. Consequently, brownish oedema fluid was often observed in the large airways and the lungs were unusually heavy (see Box 1). Microscopic examination of lung specimens often showed areas of patchy bronchopneumonia and other evidence of prolonged hypoventilation and suppression of the cough reflex.2,7,10 Statistical analysis We used published estimates of NSW methadone patients' risks of death after leaving treatment as approximations of 1994 NSW methadone patients' risks before admission to treatment.1Rates were adjusted for age, as the risk of death was significantly higher for those aged 20-29 years compared with those aged 30-39 years.1 Weighted average risks were calculated in the knowledge that, in 1994, 68% of NSW maintenance patients were at least 30 years of age.17 We assumed half of those admitted to maintenance were aged 20-29 years and half 30-40 years. The 95% confidence intervals of mortality rates were calculated by dividing the estimates by significance factors taken from a published table.18 The standard errors of the relative risks were estimated using the binomial approximation of the Poisson distribution.19 Results Methadone was detected in postmortem material from 89 NSW coronial cases in 1994. These cases comprised 41 methadone maintenance patients (38 registered with the NSW Health Department and three with the Queensland Health Department), one neonate being breastfed by a NSW methadone maintenance patient, 29 cases considered to have involved methadone syrup diverted from the NSW methadone program, and 18 cases considered to have involved methadone tablets. In 18 of the 29 cases involving diverted methadone syrup, either a bottle used to dispense methadone syrup (5 cases), a statement from a witness (10 cases), or both (3 cases), indicated that the maintenance program was the source of the methadone. In the remaining 11 cases, it was assumed methadone syrup was obtained from the black market.8 In 16 of the 18 cases involving methadone tablets, either a statement from the prescribing doctor (8 cases), a tablet bottle (4 cases), or both (4 cases), indicated the source of the methadone. The remaining two people had professional access to methadone tablets and committed suicide. We excluded the three Queensland maintenance patients, the neonate and all cases involving methadone tablets, leaving 67 cases in the study. Methadone maintenance patients Box 2 shows that, of the 38 NSW maintenance patients, 13 died in the first two weeks after admission, and 25 died later in treatment. We and the official pathologists concluded that 12 of the 13 fatalities in the first two weeks of maintenance and six of the 25 deaths later in treatment were caused by accidental toxicity. Three of six deaths from accidental drug toxicity among established maintenance patients were caused by heroin, one by dextromoramide, one by the combined effects of heroin and dextroproxyphene, and one involved injected methadone syrup. Diverted methadone syrup Box 2 shows that, for the 29 cases involving diverted methadone, we concluded methadone contributed to 26 of 27 deaths from accidental drug toxicity compared with 24 of 26 on the official pathologists' reports. One death which we classified as accidental drug toxicity was officially attributed to bronchopneumonia with methadone intoxication as a contributing factor. In another case, we concluded injected, diverted methadone contributed to a death which was officially attributed to acute heroin poisoning. Witnesses' statements or autopsy reports indicated that methadone syrup was injected in 16 of the 26 cases we classified as accidental drug toxicity to which diverted methadone contributed. One of the 10 cases involving oral ingestion of diverted methadone was that of an infant who either took or was given some of his mother's syrup. Relative risks of accidental drug toxicity We concurred with official pathologists' conclusions that 12 patients died of accidental drug toxicity during the first two weeks of maintenance treatment in NSW in 1994 (see Box 2). To calculate the rate of fatal accidental drug toxicity, we estimated the total time patients spent in the first two weeks of maintenance treatment. In 1994, 4449 people were admitted to methadone maintenance in NSW. Assuming all new admissions stayed at least two weeks in treatment,20,21 patients spent approximately 170.5 person-years in the first two weeks of maintenance. Using this estimate as the denominator, the rate of fatal accidental drug toxicity in the first two weeks of maintenance was 70.4 deaths per thousand per year (Box 3). We also agreed with official pathologists' conclusions that six NSW methadone patients died from accidental drug toxicity after being in maintenance treatment for at least two weeks (Box 2). An approximation of the total time methadone patients spent in treatment in NSW in 1994 was derived from the average of the number in treatment at the beginning and end of the year (7975 and 9038, respectively).22 The 170.5 person-years spent in the first two weeks' maintenance were subtracted from the average of the totals, 8506.5, to estimate the total time spent in later maintenance -- 8336 person-years. When this was used as the denominator, the rate of fatal accidental drug toxicity in later maintenance was 0.72 deaths per thousand per year (Box 3). When combined with the previous estimate, the risk of fatal accidental drug toxicity in the first two weeks of treatment in NSW in 1994 was estimated to have been 97.8 times the risk later in maintenance (95% CI RR, 36.7-260.5 times). Based on the results of a previous study,1 the rate of fatal accidental drug toxicity for addicts on the street was estimated to be 10.4 per thousand per year. Using this estimate, the risk of fatal accidental drug toxicity in the first two weeks of methadone maintenance in NSW in 1994 was 6.7 times the risk before admission (95% CI RR, 3.3-13.9 times). Lives saved by NSW maintenance programs The age-adjusted approximation of the expected mortality from all causes among heroin addicts was 15.5 deaths per thousand per year (95% CI, 11.0-21.9 deaths).1 Using this estimate, 132 deaths would have been expected to occur in 8506.5 person-years (95% CI, 93-187 deaths). As 64 people either died while receiving maintenance (38) or from the toxic effects of diverted methadone (26), NSW methadone programs are estimated to have saved 68 lives in 1994 (95% CI, 29-123 lives saved). To save one life approximately 125 patients needed to be given methadone maintenance for a year (95% CI, 69-293 patients). To adjust for possible bias, we assumed that up to three of the 11 cases classified as involving diverted methadone syrup may have actually involved methadone tablets. When added to the two cases involving diverted methadone syrup in which there were differences in the official and study classifications of cause of death (Box 2), the number of lives saved may increase by up to five. Consequently, the upper limit of the confidence interval increased to give an adjusted 95% CI of 29 to 128 lives saved. If all 10 cases of fatal iatrogenic methadone toxicity7 and 26 deaths to which diverted syrup contributed had been avoided, NSW maintenance programs would have saved 104 lives in 1994 (adjusted 95% CI, 65-164 lives saved), making them up to 53% more effective at saving lives (adjusted 95% CI, 37%-124%). Discussion We found that, in NSW in 1994, the risk of fatal accidental drug toxicity in the first two weeks of methadone maintenance was nearly seven times the risk before admission to treatment. A previous report suggested that this excess mortality was primarily the result of iatrogenic methadone toxicity.7 However, the risk of fatal accidental drug toxicity later in maintenance was approximately one-hundredth the risk in the first two weeks of treatment and less than one-tenth the risk before admission. As there was complete agreement between our classification and that of official pathologists, our estimate of the relative risk of fatal accidental toxicity in the first two weeks and later maintenance is unlikely to have been significantly affected by misclassification of causes of death. Further, in estimating that NSW methadone programs saved 68 lives in 1994, we allowed for the difference between our opinion and that of the official report on the role of diverted methadone in two cases when calculating the upper limit of the adjusted 95% confidence interval (29-128) for the number of lives saved by NSW maintenance programs. Another consideration in estimating the number of lives saved is that mortality among patients discharged from maintenance is only an approximation of preadmission risk. If the real risk on the streets was higher than our estimate, NSW methadone programs would have saved more lives and admission to maintenance would not have caused such a dramatic increase in the risk of fatal accidental drug toxicity. Conversely, if the real risk was lower, the reverse applies. Our estimates of the number of lives saved and the increase in the risk of fatal accidental drug toxicity associated with admission to maintenance are approximations only. However, as our estimated 71% reduction in mortality is very similar to that observed in the US during the early 1970s, in Sweden during the 1980s, in Germany in the 1990s and Australia during the 1970s and 1980s,1 they are probably reasonably accurate. Previous Australian studies have also identified mortality associated with methadone programs. Eighteen people died from methadone toxicity in Western Australia in the years 1975 to 1980. However, there were virtually no such deaths after WA maintenance patients were required to take their methadone under supervision.23 In South Australia, nine maintenance patients died from drug toxicity in the years 1984 to 1994, while 12 other people died from the toxic effects of diverted methadone syrup.22 The number of deaths per 1000 SA maintenance patients was approximately 75% of that observed in our study. Our finding that diverted methadone syrup contributed to 26 deaths in NSW in 1994 is supported by the results of a previous investigation which suggested that diverted methadone syrup was involved in up to 100 deaths between July 1990 and December 1995.6 The WA experience23 suggests the number of deaths from diverted methadone syrup is related to the number of takeaway doses dispensed to maintenance patients for consumption on subsequent days. In 1994, two-thirds of private sector patients received four takeaway doses a week, with some programs giving five or six a week to newly admitted patients.24 Although the NSW Health Department argued against such practices, there was no policy enforcement.24 To minimise the diversion of methadone syrup from maintenance programs, the NSW Health Department should monitor and ensure compliance with its current policy which strictly limits the number of takeaway doses available to recent admissions while giving stable, long-term patients access to generous takeaway privileges. A serious problem with iatrogenic methadone toxicity was identified in Victoria, where 10 deaths occurred among newly admitted methadone patients in the last six months of 1989.2 As Victorian methadone programs treated fewer than 1200 maintenance patients in this period, the rate of iatrogenic methadone toxicity was many times that observed in our study. It is noteworthy that, during 1989, the number of Victorian maintenance patients and programs increased rapidly and a number of inexperienced and poorly trained prescribers entered the field.2,3 Persons with minimal or no tolerance were prescribed initial, daily methadone doses of 50-70 mg, with fatal results.2 Two recent British studies, from Sheffield and Manchester, have similarly identified significant numbers of deaths from iatrogenic methadone toxicity early in maintenance treatment.4,5 These problems also arose after the relaxation of admission criteria and during a period of rapid increase in the numbers of maintenance patients and the involvement of new, inexperienced prescribers.4,5 While the official criteria for admission to methadone maintenance in NSW have not changed since 1988,25 they were not being implemented in 1994.26 Statements made by its Chairman in 1996 indicate that the NSW Medical Committee had not been applying the official admission criteria for some time.26 This is significant because, under the NSW Poisons Act, the Medical Committee advises the NSW Health Department on applications from doctors to prescribe methadone maintenance to addicts. There were also problems with prescriber training. Since 1993, the NSW Methadone Prescribers' Accreditation Program has used the Methadone prescribers' manual as its course material.27 Contrary to NSW Health Department policy,25 the "Manual" states heroin users need not have a history of physiological dependence on opioids to be eligible for maintenance treatment.26,27 We urge the NSW Health Department to revise its Methadone prescribers' manual,27 review prescriber training and to ensure compliance with its current admission criteria for maintenance treatment.25,26 In 1994, Victorian and Queensland methadone prescribers were required to examine new patients during the first days of maintenance for signs of toxicity.28,29 Unfortunately, the NSW Health Department did not, and still does not, have a similar policy. Indeed, many private practitioners in NSW are only available to see maintenance patients one day a week (see Box 1), and the day-to-day supervision of patients attending public clinics is left to nurses working in busy dispensaries. The first two weeks of methadone maintenance will always be the "danger period" owing to the difficulty in determining a safe and effective starting dose. There is wide variation in opioid-na•ve individuals' response to and ability to metabolise and excrete methadone,30 and applicants' self-reports of recent drug use are an unreliable measure of tolerance.7 Given this uncertainty and variability, it is not possible to define safe, effective starting doses of methadone. We recommend prescribers be made aware of the risks, signs and symptoms of methadone toxicity and be required to examine newly admitted patients every day for the first one to two weeks of maintenance. People seeking methadone maintenance should be required to give written consent after being warned about the dangers of misleading their doctor and of the use of other drugs, particularly benzodiazepines.7,31 We believe that the forthcoming NSW methadone maintenance treatment clinical practice guidelines will address these issues. We strongly recommend the establishment of independent, expert committees to investigate methadone-related deaths in States and Territories with maintenance programs. These committees should be modelled on those used to monitor anaesthesia-related deaths. Acknowledgements For their advice and generous assistance, we thank the NSW State Coroner at Glebe, the Westmead Court, the Division of Analytical Laboratories, and the Pharmaceutical Services Branch of the NSW Health Department, and the Drugs of Dependence Unit, Queensland Health Department. We also thank Professor Geoffrey Berry of the Department of Public Health and Community Medicine, University of Sydney, who assisted with the statistics and presentation of results. References Caplehorn JRM, Dalton MSYN, Haldar F, et al. Methadone maintenance and addicts' risk of fatal heroin overdose. Substance Use Misuse 1996; 31: 177-196. Drummer OH, Opeskin K, Syrjanen SM, Cordner M. Methadone toxicity causing death in ten subjects starting on a methadone maintenance program. Am J Forensic Med Pathology 1992; 13: 346-350. McPherson CJ. Coronial inquiry into methadone related deaths. Melbourne: State Coroner Victoria, 1996. Clark JC, Milroy CM, Forrest ARW. Deaths from methadone use. J Clin Forensic Med 1995; 2: 143-144. Cairns A, Roberts ISD, Benbow EW. Characteristics of fatal methadone overdose in Manchester, 1985-94. BMJ 1996; 313: 264-265. Sunjic S, Zador D. Methadone-related deaths in New South Wales, Australia, 1990-1995. Euro-Methwork Newsletter 1998; issue 13: 11. Caplehorn JRM. Deaths in the first two weeks of maintenance treatment in NSW in 1994: identifying cases of iatrogenic methadone toxicity. Drug Alcohol Rev 1998; 17: 9-17. Darke S, Ross J, Hall W. The injection of methadone syrup in Sydney, Australia. Sydney: National Drug and Alcohol Research Centre, 1995. (Technical Report No. 23). Helpern M, Rho Y-M. Deaths from narcotism in New York City: incidence, circumstances and postmortem findings. NY State J Med 1966; 66: 2391-2408. Siegel H, Helpern M, Ehrenreich T. The diagnosis of death from intravenous narcotism. J Forensic Sci 1966; 11: 1-16. Segal RJ, Catherman RL. Methadone -- a cause of death. J Forensic Sci 1974; 19: 64-74. Worm K, Steentoft A, Kringsholm B. Methadone and drug addicts. Int J Leg Med 1993; 106: 119-123. Transcript of Proceedings, Case 011 0487/95. New South Wales Coroner's Court Westmead. Ruigrok M, Caplehorn J. A case of near-fatal methadone toxicity following repeated injections of methadone [letter]. Drug Alcohol Rev 1997; 16: 433. Pounder DJ, Jones GR. Post-mortem drug redistribution -- a toxicological nightmare. Forensic Sci Int 1990; 45: 253-263. Levine B, Wu SC, Dixon A, Smialek JE. Site dependence of postmortem blood methadone concentrations. Am J Forensic Med Path 1995; 16: 97-100. Drug and Alcohol Directorate. NSW methadone program 1993/94: annual statistical report. Sydney: NSW Health Department, 1995. Bailar JC, Ederer F. Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 1964; 20: 639-643. Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford: Blackwell Scientific, 1994: 131. Caplehorn JRM, McNeil DR, Kleinbaum DG. Clinic policy and retention in methadone maintenance. Int J Addict 1993; 28: 73-89. Caplehorn JRM, Irwig L, Saunders JB. Physicians' attitudes and retention of patients in their methadone maintenance programs. Substance Use Misuse 1996; 31: 663-677. Williamson PA, Foreman KJ, White JM, Anderson G. Methadone-related overdose deaths in South Australia, 1984-1994. Med J Aust 1997; 166: 302-305. Swensen G. Opioid drug deaths in Western Australia: 1974-1984. Aust Drug Alcohol Rev 1988; 7: 181-185. Transcript of Proceedings, Case 010 1924/94. New South Wales Coroner's Court Glebe, Thursday 15th June 1995: 31-37. Directorate of the Drug Offensive. Policies and Procedures for the Methadone Treatment of Opioid Dependence in NSW. Sydney: New South Wales Department of Health, undated: 15, pars 4.3.1 and 4.3.2. Caplehorn JRM. Official and de facto admission criteria for methadone maintenance in New South Wales, Australia [letter]. Drug Alcohol Rev 1998; 17: 121-122. Bell J, O'Connor D. Methadone prescribers' manual. Sydney: NSW Health Department, 1993: 11, 23. Public Health Branch. Victorian methadone program guidelines for providers. Melbourne: Department of Health and Community Services, 1995: 7, par 3.5.2. (No. 93/0388). Bolton M, Reynolds A, Biggs L. Queensland methadone program: policy and procedures and treatment manual. Brisbane: Queensland Health, 1995: 35, par 4.14. Wolff K, Sanderson M, Hay AWM, Ralstrick D. Methadone concentrations in plasma and their relationship to drug dosage. Clin Chem 1991; 37: 205-209. Caplehorn JRM. More on iatrogenic methadone toxicity [letter]. Drug Alcohol Rev 1998; 17: 467-468. (Received 22 Sep 1997, accepted 18 Oct 1998) Authors' details Department of Public Health and Community Medicine, University of Sydney, NSW. John R M Caplehorn, MB BS, MPH, PhD Student. Victorian Institute of Forensic Medicine, Melbourne, VIC. Olaf H Drummer, PhD, Head of Scientific Services, and Associate Professor, Department of Forensic Medicine, Monash University. Reprints: Dr J R M Caplehorn, Department of Public Health and Community Medicine, Building A27, University of Sydney, Sydney, NSW 2006. Email: johnc@dph1.health.usyd.edu.au 1: A case of fatal iatrogenic methadone toxicity This 1995 NSW case highlights the danger of daily doses of 30-40mg methadone in non-tolerant individuals and presents a classic history of fatal iatrogenic toxicity. The deceased had clear, early signs of methadone toxicity: somnolence; unsteady gait; vomiting; and a general feeling of being unwell. The terminal events were also typical: prolonged coma following sleep; very slow, deep, irregular, noisy breathing; brown pulmonary oedema fluid coming from the mouth or nose. Six weeks before his death, the 19-year-old man was admitted to hospital with hypothermia, pneumonia, right brachial plexus neurapraxia, rhabdomyolysis and acute renal failure after a heroin overdose. He reported using amphetamines for six months and heroin for two weeks. Liver function test and echocardiogram findings were normal, and at discharge three days later his serum creatinine level had fallen from 0.18mmol/L to 0.10mmol/L (upper normal limit, 0.12mmol/L). He was referred to a short-stay, residential program and told the admitting officer he had had problems with alcohol for five years, cannabis for seven years and amphetamines for one year, but had only used heroin six times. While he was considered suitable for admission to a drug-free rehabilitation program, this was delayed pending full recovery of his arm. However, he was advised not to wait to enter this program as he was facing trial for a criminal offence. Soon after, the deceased apparently told a general practitioner and a methadone prescriber he had been using heroin daily for a year. He was prescribed 30mg methadone, with the dose to be increased by 5mg every day for six days and then reviewed. The deceased vomited several times after receiving his second dose (35mg). The next morning, he was difficult to rouse, had trouble walking and urinating and kept falling asleep. His father was unable to contact the methadone prescriber, who was on holiday, and the nurses at the private methadone clinic did not seem to have recognised the seriousness of the situation. By late afternoon he felt much better and travelled by public transport to receive his last dose of methadone (35mg) at 1830. That evening he seemed well, was in a very good mood and ate a large dinner. However, he was still having difficulty urinating. He went to bed at 2245. Around 0645 the next morning his father was unable to wake him, he was breathing deeply, noisily and irregularly and had brown fluid coming from his mouth. After about fifteen minutes he stopped breathing and died. At autopsy, the body weighed 72kg. No "track" or recent injection marks could be identified. The lungs weighed 960g (right) and 860g (left) and were described as "very oedematous and congested". The heart and liver were macroscopically and microscopically normal. The postmortem blood methadone concentration was 0.32mg/L. No other drugs were detected in blood, bile or urine samples. The investigating pathologist determined the cause of death was methadone toxicity. The Deputy NSW State Coroner determined the fatal toxicity was caused by the administration of three daily doses of methadone (30mg, 35mg and 35mg).13 At the inquest, the deceased's methadone prescriber said he did not physically examine methadone patients and had not rejected an applicant for maintenance in the past two years. He routinely saw methadone patients only one day a week at a private methadone clinic.13 Back to text 2: Causes of death determined in this study and in official pathologists' reports for 38 patients in New South Wales methadone maintenance programs and 29 people whose deaths involved methadone diverted from maintenance programs Accidental drug toxicityMethadone*Other drug(s)Other causes of deathMethadone maintenance patientsDeath in first two weeksThis study11 1 1 Official report10 2 1 Death after two weeksThis study1 5 19 Official report1 5 19 Diverted methadoneThis study26 1 2 Official report24 2 3 TotalsThis study38 7 22 Official report 35 9 23 *Methadone either caused or contributed to the death. Back to text 3: Rates of fatal accidental drug toxicity and relative risks of fatal accidental drug toxicity and sudden death from all causes for patients in New South Wales methadone maintenance programs in 1994Rate Relative (Deaths/1000/yr) risk 95%CI Deaths from accidental drug toxicityIn first two weeks' maintenance70.4 36.3-122.8 after two weeks' maintenance0.72 0.26-1.57 First two weeks' maintenance v.out of treatment* 6.7 3.3-13.9 First two weeks' maintenance v.after two weeks' maintenance 97.8 36.7-260.5 Out of treatment* v.after two weeks' maintenance 12.2 4.8-30.6 Deaths from all causesOut of treatment* v.all maintenance 3.5 2.2-5.6 Out of treatment* v.after two weeks' maintenance 5.2 3.1-8.7 *Calculated from approximations derived from previously published data. Back to text

Olaf H Drummer · John R M Caplehorn

Research Australian general practitioners' views and use of colorectal cancer screening tests Michael J Sladden and Jeanette E Ward MJA 1999; 170: 110-113 For editorial comment, see Young Abstract - Introduction - Method - Results - Discussion - Acknowledgements - References - Author's details - - More articles on Gastroenterology Abstract Objectives: To determine general practitioners' (GPs) current beliefs, knowledge and self-reported practices of screening for colorectal cancer. Design and setting: Postal survey of national random sample of 1271 GPs in 1996. Outcome measures: GP views on effectiveness of faecal occult blood testing (FOBT) and flexible sigmoidoscopy in reducing premature death from colorectal cancer in "average-risk" patients (asymptomatic with no family history); views on frequency of tests and target group; use of these tests; and independent predictors of views and use. Results: Response rate was 67%. FOBT and flexible sigmoidoscopy were said to be effective as screening tests by 38% and 61% of GPs, respectively, but 30% and 25% were unsure. Independent predictors of belief in screening effectiveness were State of practice (for FOBT), male sex and awareness of Gut Foundation guidelines (for flexible sigmoidoscopy) and increasing age (for both). Most often chosen screening frequencies were every year for FOBT (29%), and five-yearly for flexible sigmoidoscopy (24%), although 19% and 26%, respectively, were unsure of the appropriate screening interval. Most often cited target group was people aged over 40 years with first-degree relatives with colorectal cancer: 63% of GPs would offer FOBT and 74%, flexible sigmoidoscopy. Fewer than 3% of GPs were likely to adopt an opportunistic approach to screening, yet 15% would be highly likely to recommend FOBT during a dedicated health check-up for a 58-year-old male patient, and 9% for a female patient. Conclusion: The absence to date of a coherent national policy on colorectal cancer screening is associated with wide variations in views and practice that are inconsistent with the available evidence. If GPs are to be involved in implementing population screening, national policy must be widely and effectively promulgated. Introduction The past decade has seen a saga of unfinished policy initiatives on screening for colorectal cancer in Australia. As early as 1990, screening by faecal occult blood test (FOBT) was being promoted for people with "average risk" of colorectal cancer, in the absence of convincing evidence or national policy.1 Since then, a range of bodies have produced guidelines with quite different recommendations, particularly for this "average risk" group.2-8 Examples are shown in Box 1. More recent among these was the 1997 report of the Australian Health Technology Advisory Committee (AHTAC) Working Party on Colorectal Cancer Screening. This working party was formed after a 1994 call for a national symposium to develop "recommendations about early detection of colorectal cancer" as part of Australia's national health goals and targets,9 and a 1995 deputation to the Commonwealth from the Australian Cancer Network. The Network recommended pilot projects of screening and, if these were successful, implementation of national screening. AHTAC found that FOBT was effective in reducing mortality from colorectal cancer in the average-risk population (defined as the "well population aged over 50") and recommended studies to determine the effectiveness of different screening strategies, particularly how best to involve general practitioners (GPs). Meanwhile, in 1998, another set of draft guidelines, not yet nationally endorsed, was circulated by the Clinical Oncological Society of Australia and the Australian Cancer Network.8 Despite the unresolved status of national policy, research has continued to involve Australian GPs overtly or covertly in colorectal cancer screening.10-14 Most recently, a survey of Perth GPs reported high uptake of this screening.15 As no national studies have been conducted, we designed a postal survey to assess GPs' perceptions of the effectiveness of screening for colorectal cancer and self-reported levels of screening. Method GP sample and survey administration A covering letter, questionnaire and reply-paid envelope were mailed in May 1996 to a national random sample of 1271 GPs, as described elsewhere.16 Standardised response-aiding strategies were used to follow up non-respondents.16 Questionnaire Questions on colorectal cancer screening were part of a larger questionnaire on current status of cancer screening in general practice. Respondents were asked to tick the response that matched their views on: Effectiveness of FOBT and flexible sigmoidoscopy in reducing premature deaths from colorectal cancer in "average risk" patients (ie, asymptomatic patients with no family history); Frequency of screening; Who should be screened; Likelihood of their initiating a discussion about FOBT or flexible sigmoidoscopy with a well 58-year-old male, and next female, patient during non-urgent consultations for ear syringing as well as during scheduled health check-ups; and Usefulness of three guidelines available at the time of the surveys (first three items in Box 1). The final section of the questionnaire included eight sociodemographic questions. Data analysis Descriptive, cross-tabulation and logistic regression analyses were performed with SPSS for Windows 7.17 Logistic regression analyses were performed to determine independent predictors of knowledge and practice outcomes. Fourteen potential predictors were considered: GP's sex; age; State; full- or part-time practice; practice type (solo or group); membership of a Division of General Practice; Royal Australian College of General Practitioners (RACGP) affiliation; membership of the Australian Medical Association; personal history of cancer; family history of cancer; awareness of RACGP guidelines; Australian Gastroenterology Institute/Australian Cancer Society guidelines; and Gut Foundation of Australia (GFA) guidelines; and practice location (metropolitan or other18). All independent variables were included in the full model. A further variable -- belief that FOBT/flexible sigmoidoscopy is an effective screening test -- was included in the model to predict behaviour. A backwards stepwise modelling strategy was used to identify significant independent variables, whereby all dependent variables were initially included and non-significant terms were progressively eliminated. Significance was assessed using the Wald chi-squared statistic. Results We received 855 usable questionnaires from 1271 eligible GPs (67% response rate). The response rate for women (75%) was significantly higher than that for men (63%) (chi-squared = 15.4, 1 df, P < 0.001), but did not vary with age, vocational registration status, RACGP affiliation, or practice size and location. GP views about screening GP views about the effectiveness of screening for colorectal cancer in preventing premature deaths are shown in Box 2. More GPs believed flexible sigmoidoscopy to be effective (61%) than believed FOBT to be effective (38%), but there was substantial uncertainty about both screening tests, with 25% and 30% of GPs unsure. Independent predictors of believing either test to be effective are summarised in Figure 1. For FOBT, these comprised increasing GP age and State of practice (specifically, South Australia). For flexible sigmoidoscopy, they comprised increasing GP age, male sex, and awareness of the Gut Foundation guidelines (which favour screening). GPs' views on appropriate screening frequencies and target groups are shown in Box 2. Most often chosen frequencies were every year for FOBT (29%), and five-yearly for flexible sigmoidoscopy (24%). However, 19% and 26%, respectively, were unsure of the appropriate screening interval. The most often cited target group was people aged over 40 years with first-degree relatives with colorectal cancer: 63% of GPs would offer FOBT and 74%, flexible sigmoidoscopy. Self-reported practice Likelihood of suggesting colorectal cancer screening is shown in Box 3. Fewer than 3% of GPs were "highly likely" to adopt an opportunistic approach to colorectal cancer screening for a 58-year-old patient (by either test) or to recommend flexible sigmoidoscopy screening during a dedicated health check-up. More would be "highly likely" to recommend FOBT during a dedicated health check -- 15% if the patient was a man and 9% if a woman. This sex difference was significant (McNemar's chi-squared = 43.7, 1 df, P < 0.0001). Independent predictors of being "highly likely" to include FOBT in a health check-up are shown in Figure 2. They comprised increasing GP age, State of practice, and belief in the effectiveness of the tests. Usefulness ratings of guidelines available at the time of the survey are shown in Box 4. While RACGP, AGI/ACS and GFA guidelines were rated as "very" or "somewhat" useful by 33%, 50% and 45% of respondents, respectively, they were unable to be recalled by 52%, 35% and 41%. Discussion Our study suggests considerable confusion about colorectal cancer screening at the "front line" of general practice. About a third of respondents believed that FOBT was an effective screening test in average-risk individuals, while two-thirds believed this of flexible sigmoidoscopy. These beliefs are inconsistent with the evidence available at the time of our study: level II (randomised controlled trial) evidence19 that FOBT reduced colorectal cancer mortality, but only level III (case-control study) evidence20 supporting flexible sigmoidoscopy. A wide range of responses were given about appropriate screening frequency. This is not surprising, as the three guidelines available at the time offered different and contradictory advice, and none met the criteria for being systematically evidence-based. Further confusion is likely if yet more guidelines8 are published that contradict the evidence-based AHTAC guidelines.7Far fewer GPs reported using the screening tests than reported they were effective; most respondents did not use the tests. This discordance was greater for sigmoidoscopy than for FOBT. Again, it is likely that the lack of clarity and the variation between guidelines, as well as availability of conflicting information and educational material, have caused uncertainty among GPs, with concomitant inconsistency in their behaviour. Perhaps FOBT is used more often than sigmoidoscopy because it is easier to arrange. Increasing GP age and physician belief in screening effectiveness independently predicted self-reported provision of screening. South Australian GPs were more likely to advocate screening, perhaps because of research studies and community-based initiatives in that State.10 GPs also favoured screening men rather than women for colorectal cancer. Sex bias not been reported previously in colorectal cancer screening, and may reflect the higher incidence of colorectal cancer among men.21 Alternatively, perhaps GPs place a lower priority on colorectal cancer screening in women, for whom cervical and breast cancer screening are widely performed, but a higher priority in men, for whom there is, as yet, no "male cancer" screening of proven benefit. National levels of self-reported use of screening tests were less than previously reported,15,22,23 although the higher levels in South Australia were consistent with earlier data.10 GPs' wider endorsement of screening for "above-average-risk" individuals with first-degree relatives with colorectal cancer (63%-74%) was similar to the levels found in recent studies (80%-94% GP support),10,15 but considerably higher than in a similar 1982 study (23% GP support).22 Screening of relatives is apparently becoming more acceptable. Usefulness and recall of guidelines was low, similar to other recent findings.15 Our results suggest an urgent need for a national colorectal cancer screening policy. As GPs remain the most respected source of health information,24 it is vital they have access to timely and accurate information. The AHTAC report, released in 1998, was necessary but insufficient. If GPs are to be involved in implementation of colorectal cancer population screening (which, by definition, will target average-risk individuals), strategies are needed to inform them of the importance of screening and to facilitate appropriate changes in behaviour. When there has been a concerted effort to communicate agreed policy to Australian GPs (eg, about mammographic screening), uniformity of GP views has been achieved.25 However, when evidence is lacking (eg, for clinical breast examination),25 or State-based initiatives are patchy,26 it appears that GPs differ considerably in their views of screening effectiveness and self-reported behaviour. Our study concentrated on screening average-risk individuals, for which previous guidelines have been confusing, non-evidence based and at variance with each other. Most guidelines distinguish between screening for average-risk and above-average-risk individuals, generally recommending colonoscopic screening for above-average-risk groups (eg, those with familial adenomatous polyposis and hereditary non-polyposis colorectal cancer). Clearly, strategies for effective evidence-based screening of above-average-risk groups must also be promoted. Thus, our results reveal our failings to date as an organised healthcare system to provide GPs with timely, consistent and evidence-based health policy, as they and their patients deserve. Our study provides a baseline against which the effectiveness of future dissemination of colorectal cancer screening policy may be measured. Acknowledgements A Commonwealth General Practice Evaluation Program seeding grant funded this study. We thank the GPs who participated in our research with no financial incentive, Phoebe Holt for contributing to questionnaire design, and Tracey Bruce for diligent survey administration. The study was approved by the Ethics Committee of the Royal Prince Alfred Hospital, Sydney, NSW. References Woodward A, Weller D. Colorectal cancer: implications of mass screening for public health. Med J Aust 1990; 153: 81-88. Guidelines for screening for colorectal cancer. Sydney: Australian Gastroenterology Institute, 1991. Australian Cancer Society. National cancer prevention policy, 1993. Sydney: Australian Cancer Society, 1993. Bolin T, Collopy B, Cowen A, et al. Colorectal cancer: prevention, diagnosis and treatment. Sydney: The Gut Foundation and Colorectal Surgical Society of Australia, 1993. Goulston K, St John DJ, Bokey L, et al. Guidelines for early detection, screening and surveillance for colorectal cancer. 2nd ed. Sydney: Australian Gastroenterology Institute and Australian Cancer Society, 1994. Guidelines for preventive activities in general practice. 3rd ed. Sydney: Royal Australian College of General Practitioners, 1994. Australian Health Technology Advisory Committee (Standing Committee of the National Health and Medical Research Council). Colorectal cancer screening. Canberra: Commonwealth Department of Health and Family Services, 1997. Clinical Oncological Society of Australia and Australian Cancer Network. Guidelines for the prevention, early detection and management of colorectal cancer. Draft 3. June 1998. Better health outcomes for Australians. Canberra: National Health Goals and Targets Section, Department of Human Services and Health, 1994. Cockburn J, Thomas R, McLaughlin S, et al. Acceptance of screening for colorectal cancer by flexible sigmoidoscopy. J Med Screen 1995; 2: 79-83. Rae L. Community screening for colorectal cancer in north-eastern New South Wales, 1987-1996. Med J Aust 1998; 168: 382-385. King J, Fairbrother G, Thompson C, Morris D. Colorectal cancer screening: optimal compliance with postal faecal occult blood test. Aust N Z J Surg 1992; 62: 714-719. King J, Fairbrother G, Thompson C, Morris D. Influence of socioeconomic status, ethnicity and an educational brochure on compliance with a postal faecal occult blood test. Aust N Z J Public Health 1994; 18: 87-92. Olynyk J, Aquilia S, Fletcher D, Dickinson J. Flexible sigmoidoscopy screening for colorectal cancer in average-risk subjects: a community-based pilot project. Med J Aust 1996; 165: 74-76. Olynyk J, Aquilia S, Platell C, et al. Colorectal cancer screening by general practitioners: comparison with national guidelines. Med J Aust 1998; 168: 331-334. Ward J, Bruce T, Holt P, et al. Labour-saving strategies to increase response rates in general practice surveys. Aust N Z J Public Health 1998; 22: 394-396. Statistical Package for the Social Sciences. SPSS for Windows 7.5.1. Chicago (Ill): SPSS Inc, 1996. Commonwealth Department of Primary Industries and Energy and Commonwealth Department of Human Services and Health. Rural, Remote and Metropolitan Areas Classification: 1991 Census edition. AGPS, Canberra: 1994. Mandel J, Bond J, Church T, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993; 328: 1365-1371. Selby J, Friedman G, Quesenberry C, Weiss N. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326: 653-657. Jelfs P, Coates M, Giles G, et al. 1996 Cancer in Australia 1989-1990 (with projections to 1995). Canberra: Australian Institute of Health and Welfare (Cancer Series No. 5). Macrae FA, Hill DJ, Dent O, et al. Colorectal cancer: knowledge and attitudes of doctors in Victoria. Aust N Z J Med 1982; 12: 278-283. Rolfe I, Pearson S. Screening recommendations in general practice: a survey of graduates from different medical schools. Med J Aust 1996; 165: 14-17. Cumming R, Barton G, Fahey P, et al. Medical practitioners and health promotion: results from a community survey in Sydney's western suburbs. Community Health Stud 1989; 13: 294-301. Young J, Ward J, Holt P. Breast cancer screening in Australian general practice: results of a national survey. Med J Aust 1998; 169: 364-368. Ward J, Donnelly N, Holt P. Impact in general practice of the policies of the organised approach to preventing cancer of the cervix. Aust N Z J Public Health 1998; 22: 336-341. (Received 25 Jun, accepted 28 Oct, 1998) Author's details Division of Community and Rural Health, University of Tasmania, Hobart, TAS. Michael J Sladden,FRACGP, MAppEpid, Honorary Senior Lecturer. Needs Assessment and Health Outcomes Unit, Central Sydney Area Health Service, Sydney, NSW. Jeanette E Ward, PhD, FAFPHM, Director. Reprints will not be available from the authors. Correspondence: Dr M J Sladden, Division of Community and Rural Health, PO Box 252-33, University of Tasmania, Hobart, TAS 7001. Email: M. Sladden@utas.edu.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> Figure 1 : Independent predictors of general practitioners (GPs) reporting that faecal occult blood testing or flexible sigmoidoscopy is effective in reducing premature deaths from colorectal cancer. Back to text Figure 2 : Independent predictors of general practioners (GPs) reporting they would be "highly likely" to discuss faecal occult blood testing during a deicated health check-up with a 58-year-old patient. (Adjusted odds ratios with 95% confidence intervals are available from the authors.)Back to text 1: Recommendations about colorectal cancer screening for average-risk* people Gut Foundation of Australia (1993)4 Screening by annual FOBT; consider 3-5-yearly flexible sigmoidoscopy Australian Gastroenterology Institute/Australian Cancer Society (1994) 5 Routine screening not recommended; can be performed at patient request Royal Australian College of General Practitioners (1994)6 Screening not recommended Australian Health Technology Advisory Committee (1997)7 Screening by FOBT; research required to determine method and frequency Clinical Oncological Society of Australia/Australian Cancer Network (draft 1998)8 Screening by annual FOBT; consider 5-yearly flexible sigmoidoscopy FOBT=faecal occult blood test. *Asymptomatic people aged over 50 years with no family history Back to text Back to text Back to text Back to text

Michael J Sladden · Jeanette E Ward

Objective: To develop national birthweight percentiles by gestational age for male and female singleton infants born in Australia, and to compare the birthweight percentiles of Indigenous and non-Indigenous infants. Design and setting: Cross-sectional study of singleton live births to Australian-born mothers from 1991 to 1994. Main outcome measures: Birthweight percentiles by gestational age. Results: During 1991–1994 Australian-born women gave birth to 769 077 live singleton infants. Of these, 28 230 (3.7%) were reported as births to Aboriginal or Torres Strait Islander women. Birthweight was missing for 581 (0.1%) births and gestational age was missing for 3014 (0.4%). An additional 3283 (0.4%) births were excluded because the recorded birthweights were extreme outliers for their recorded gestational ages. Indigenous women were more likely to be recorded as giving birth preterm (< 37 weeks’ gestation) than non-Indigenous women (11.6% v. 5.4%) and were more likely to give birth to small-for-gestational-age infants at term. After 34 weeks’ gestation, the median birthweights of Indigenous infants were consistently lower than those of non-Indigenous infants. At 40 weeks’ gestation the difference in the median birthweights between these two groups was 160 g for males and 130 g for females. Conclusions: We present recent birthweight percentiles by gestational age based on national data in Australia. These percentiles provide current Australian norms for clinicians and researchers, and can provide a baseline for monitoring Indigenous perinatal outcomes.

Christine L Roberts · Paul A L Lancaster

Viewpoint Heroin addiction: the science and ethics of the new treatment pluralism As approaches to treating heroin addiction grow in number, their ethics and their meaningful contribution to the science in this field need more careful consideration Matt D Gaughwin and Philip Ryan MJA 1999; 170: 129-130 Introduction - Questions of ethics - Questions of science - Ways forward - References - Authors' details - - More articles on Drugs and alcohol Introduction There is a new pluralism of approaches to treating heroin addiction. Many trials are concerned with relatively small populations of heroin users, among whom researchers hope to demonstrate, by various methods, that one drug or treatment is effective and safe, and perhaps better than, another. At the other extreme are clinics which offer treatments -- such as ultrarapid opiate detoxification (UROD), in which heroin addicts are given opiate antagonists while anaesthetised so that they do not consciously experience withdrawal symptoms -- at a price, and not necessarily with a special interest in evaluation and research. Such approaches have their place, but they can never address the question of how much of what treatments we need to help stem the tide of heroin problems in the community. That question has scientific and ethical implications about the design of trials and treatments and the application of the results of trials to communities. Questions of ethics There are two categories of ethical issues associated with the new treatment pluralism. Firstly, ethics as they relate to individuals and, secondly, ethics as they relate to populations. The proponents of trials, and perhaps the ethics committees that consider these trials, are more concerned with ethics in relation to the individual trial participants. The ethical obligations of treating clinicians, whether they are working in franchised clinics or research institutions, are clear. They must adequately inform patients about the treatments, which must be as safe as they can be. Whether a procedure such as anaesthesia should be used at all for a clinical condition that is not life threatening was raised by Hall and Mattick,1 and countered by Seivewright and Greenwood,2 who said that the same argument is not used for childbirth or dental treatment. There is an important ethical discussion yet to be had about the extent to which we should introduce new elective procedures which require anaesthesia. Importantly, the risk -- perhaps increased risk -- of death from heroin overdose (as a consequence of reduced opiate tolerance) that can accompany poor compliance with naltrexone means that there is a great responsibility to inform patients being treated with naltrexone about that specific risk. There is also an urgent ethical responsibility to decide whether that risk is too great for some or all participants, and thus to act to reduce or eliminate the risk even if that means stopping or modifying trials and treatments. Also, there is yet to be a comprehensive ethical discussion about the allocation of resources for these new treatments. We do not deny that there is a place for new treatments. Rather, in the face of inadequate resources for existing proven treatments (such as methadone), the effect of introducing new treatments or trials on the ability of heroin addicts seeking help to actually obtain that help needs to be considered. Addiction to opiates is a multifaceted problem which may require multifaceted solutions. If we accept a humanitarian view of treatment, including treatment within trials, we must accept our ethical obligation to offer a treatment that we know works if a trial participant or a patient in a UROD clinic "drops out" of a new treatment. Some heroin users, desperate for help, hardly have a choice, and will enrol in a trial of an unknown treatment because standard treatments (such as methadone maintenance) are relatively unavailable. The other, often neglected, dimension is that of public health ethics. Trials which are publicly funded have special ethical obligations to ensure, as far as possible, that the questions being asked, and the design and evaluation of trials, are in the public's best interest -- that is, what a public given the chance to deliberate adequately about the issue would choose. Because there are no standards for deliberation about public health issues such as heroin addiction,3 propsals for trials may be approved or denied at the discretion of those who hold the relevant power. Thus, the ACT heroin trial was halted by the Prime Minister and Cabinet, while State governments, such as the South Australian government, announced trials of rapid opiate detoxification4 without comprehensive consultation and deliberation with the public, heroin addicts or the clinicians who treat them. The idiosyncrasy of such approaches must militate against sustainable solutions to the problem of heroin addiction, and raises the ethical question of how rational and reasonable approaches to this problem can be given a "fair go". If there has not been meaningful public deliberation about proposals, we believe their proponents can not claim that they are ethical trials in a public sense. Questions of science This emergence of a pluralism of approaches to heroin problems brings with it scientific difficulties. As more and more treatments are trialled, we increase the difficulty and the cost of designing studies that can determine which collection or combinations of treatments are better than others. This does not negate the value of small trials, but it does raise the question of the relationship between trials and evaluation of treatments as a whole. The diversity of treatments and trials is wide, ranging from uncontrolled small case series through modest-sized randomised trials to modest treatment programs. It is the view of one researcher that ". . . we are likely to get poorly designed, incompatible trials . . . which produce inconclusive results, ie a null effect in a study lacking adequate power".5 Indeed, a pilot study of naltrexone treatment in New South Wales6 concluded that about 450 participants would be needed for a randomised trial of adequate power -- considerably more than the 100-200 participants proposed for the randomised trials in SA and NSW. Many trials are of short duration, whereas the problem of addiction often occurs over many years. Thus, deciding when to measure outcomes becomes an important issue. Trials risk being irrelevant to the real world of addiction if they ask questions or evaluate outcomes relevant to the short term only. As in cancer epidemiology, we should develop standards for evaluating endpoints in heroin addiction trials so that we might, as with cancer, agree that after a certain period someone is "cured" of their addiction. Or, if we consider addiction to be a chronic relapsing condition, we might perhaps model trials for heroin addiction on those for treating diseases such as epilepsy or diabetes. Moreover, we must never forget that there can be a vast gulf between efficacy demonstrated in clinical trials and meaningful control of a public health problem. Ways forward The new pluralism in treatments for heroin addiction is fragmented and uncoordinated, with no particular strategic direction. This is not surprising given the lack of an agreed strategic framework on which to design treatments and trials in the area of drug addiction. However, a strategic framework will be successful only if all those with an interest in the problem -- experts and non-experts alike -- are justly and fairly engaged in ways which consider and account for the diversity of views about heroin. It is encouraging that the National Drug and Alcohol Research Centre has recently been contracted to coordinate the trials of new pharmacological treatments (Associate Professor Richard Mattick, Director of Research, National Drug and Alcohol Research Centre, University of New South Wales, personal communication). Perhaps this Centre might take on the wider role of considering the ethical and scientific questions we have raised here. In summary, the new pluralism in treatments for heroin addiction poses some dilemmas. We should welcome the opportunities they may offer, but approach them cautiously and comprehensively so that we avoid the traps of ill-considered science and ill-considered ethics. References Mattick R, Hall R. Are detoxification programs effective? Lancet 1996; 347: 97-100. Seivewright N, Greenwood J. What is important in drug misuse treatment? Lancet 1996; 347: 373-376. Gaughwin M. Why Australia needs minimum standards of deliberation for public health. Med J Aust 1998; 168: 228-229. Minister for Human Services, South Australia. Rapid heroin withdrawal treatment trial [media release]. Adelaide: Department of Human Services, March 2 1998. Caplehorn J. Reply to Hall et al: on ROD, UROD and ODs. Drug Alcohol Rev 1998; 17: 222-223. Foy A, Sadler C, Taylor A. An open trial of naltrexone for opiate dependence. Drug Alcohol Rev 1998; 17: 167-174. Authors' details Department of Public Health, University of Adelaide, Adelaide, SA. Matt D Gaughwin, PhD, FAFPHM, Senior Clinical Lecturer; Philip Ryan, MB BS, FAFPHM, Lecturer. Reprints will not be available from the authors. Correspondence: Dr M D Gaughwin, Drug and Alcohol Resource Unit, Level 5, Services and Teaching Wing, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000. Email: mgaughwin@medicine.adelaide.edu.au

Matt D Gaughwin · Philip Ryan