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MJA 2001; 174: 248-253 Abstract - The tools of EBM - Does it improve outcomes? - The future of EBM - Conclusions - Acknowledgements - References - Authors' details Abstract Evidence-based medicine (EBM) integrates clinical experience and patient values with the best available research information. There are four steps in incorporating the best available research evidence in decision making: asking answerable questions; accessing the best information; appraising the information for validity and relevance; and applying the information to patient care. Applying EBM to individual patients requires drawing up a balance sheet of benefits and harms based on research and individual patient data. The most realistic and efficient use of EBM by clinicians at the point of care involves accessing and applying valid and relevant summaries of research evidence (evidence-based guidelines and systematic reviews). The future holds promise for improved primary research, better EBM summaries, greater access to these summaries, and better implementation systems for evidence-based practice. Computer-assisted decision support tools for clinicians facilitate integration of individual patient data with the best available research data. Medical practice is diverse but has some common tasks. One of these is making the best use of available research evidence to diagnose, prevent and treat disease. Imagine yourself in the following situations: As a general practitioner you see a 72-year-old asymptomatic man who wants to know whether he should be screened for colorectal cancer. What do you say? As a nephrologist you see a 50-year-old man with progressive renal failure due to glomerulonephritis. Should you advise treatment with cyclosporin A? As an interventional radiologist or general surgeon should you be using antibiotic- or antiseptic-impregnated central venous lines to prevent line-associated sepsis? Do you know enough of the research evidence to provide sensible answers to these questions? Even if you know today's answers, chances are that they will change as much in the next five years as they have changed in the past five years.1-4 Therein lies the challenge — keeping up with new research information and incorporating it into clinical decision making. This is the task of evidence-based medicine (EBM). In a survey of 625 office-based primary-care physicians and 100 physician opinion leaders in the United States, nearly two-thirds reported that the current volume of scientific information was unmanageable.4 When the researchers asked about the physicians' knowledge of important recent medical advances, they found deficiencies that would adversely affect patient care. Since 1989, when the above study was published, total biomedical knowledge has probably increased by about 50%.5 In addition to identifying a challenge, EBM also provides tools to find, appraise and apply research evidence better.6 These tools are relevant to all users of health information — clinicians, patients and policymakers — but our focus will be on helping clinicians make better use of EBM tools. The tools of evidence-based medicine In a recent survey, Australasian physicians identified insufficient time (74%), limited search skills (41%) and limited access to evidence (43%) as impediments to making better use of research data.7 The survey showed that, to realise the full potential of EBM to improve care, two things are needed: education in EBM, and systems that quickly deliver high-quality evidence at the point of clinical decision making. The EBM process — incorporating the best available research evidence in decision making — has four steps: asking answerable questions; accessing the best information; appraising the information for validity and relevance; and applying the information to patient care. Asking answerable questions Accept that you may not know: While the knowledge explosion continues, making assumptions about the certainty of our knowledge base is risky. Studies of information needs show that one to two questions are generated for each outpatient consultation and five questions for each inpatient consultation.8,9 About a third of these questions are about treatment of a specific condition, and a quarter are about diagnosis.10 EBM tools help answer these "foreground" questions,11 which are specific and relevant to clinical decision making. Other questions concerning basic biological processes, or "background" questions (questions beginning with What is . . . ? and How does . . . ?), are better answered by standard textbooks. For these the EBM framework is not particularly helpful. Framing the question: population, intervention, comparator, outcome: Once the clinical question has been identified, it then needs to be put into a searchable and answerable form. This consists of four parts: a population with a clinical problem; an intervention or exposure; the comparator intervention or exposure; and the outcomes.11 Such questions are specific, and should focus on patient-centred or clinically important outcomes, rather than laboratory-based or surrogate outcomes that do not always correspond with patient benefit.12 For example, the question posed by the 72-year-old man wanting to know about colorectal cancer screening could be rephrased as: "In asymptomatic people at average risk of colorectal cancer (population), does screening by faecal occult blood testing (intervention) reduce mortality from colorectal cancer (outcome) compared with routine care without screening (comparator)?". Aetiology, prognosis, diagnosis or intervention? This four-part question framework can be applied to all types of foreground questions asked by healthcare providers and consumers — Why me? (aetiology), What's wrong with me? (diagnosis), What will to happen to me? (prognosis), and How will intervention change outcome? (intervention). Examples of each type of question are given in Box 1. Because most questions asked by patients and clinicians are about interventions, we will focus on treatment. Accessing the best available information Summarised primary research — evidence-based guidelines and systematic reviews: The ideal information source is valid (contains high quality data), relevant (clinically applicable), comprehensive (has data on all benefits and harms of all possible interventions), and is user-friendly (is quick and easy to access and use). The recent growth of EBM has provided more useful information sources (Box 2), and better access to these information sources (Boxes 2 and 3). Primary research data can now be organised into systematic reviews and evidence-based guidelines. For treatment questions, systematic reviews typically bring together, summarise and synthesise data from randomised controlled trials of a single intervention. Because many interventions are usually possible for the same clinical problem, systematic reviews of these interventions can be further summarised and combined in the form of an evidence-based guideline. To be most useful to clinicians, guidelines should also include diagnostic and prognostic research which provides some guidance for individualising therapy based on disease severity.13 Guidelines and systematic reviews can be stand-alone products, or, more usefully, can be organised into compendia. Primary research — if quality summarised research is not available: When relevant systematic reviews or evidence-based guidelines are unavailable, or if they fail the quick critical appraisal test outlined in the following section, the clinician will need to find primary research studies. Although a randomised controlled trial is the best study type to assess the effects of a healthcare intervention, it is not the best study design to determine the accuracy of a diagnostic test or the prognosis of a condition, and is frequently not feasible for questions of aetiology. Box 1 includes the ideal primary study design for each type of question, along with the appropriate methodological terms that help focus MEDLINE searches on these studies. For users unfamiliar with methodological filters, the free website for MEDLINE, PubMed, has a "clinical queries" option which allows users to select the content area and the type of question (therapy, diagnosis, aetiology or prognosis). The program then automatically incorporates the methodological filters into the search.14 Appraisal of quality and clinical relevance Why quality assessment is needed: Having found the research information, the user then needs to critically appraise the study or studies. Publication does not guarantee quality, and poor-quality studies tend to overestimate the benefits of interventions by about 30%15 — enough to make ineffective interventions appear effective. Likewise, poor-quality studies of diagnostic tests overestimate the accuracy of the test they are evaluating.16 Tools for critical appraisal: Useful tools for critical appraisal developed for the National Health and Medical Research Council (NHMRC)17,18 are summarised in Boxes 3 and 4. They ask three questions: How strong is the evidence? How big is the effect? Does the effect matter to patients? The strength of evidence incorporates the appropriateness of the study design (often called level of evidence), the quality of the study's design and reporting (was bias minimised?) and the statistical precision of the results (could the results be explained by chance?). A few seconds scanning an abstract to see how well it rates on these criteria is often enough to indicate whether the study is worth reading. If the initial scan suggests that the results may be reliable and important, then critical appraisal means focusing on the methods section to see how the study was done (not to see what statistical tests were used, such as whether a χ 2 or t-test was used) and on the results, particularly the figures and tables. Applying the research evidence to decision making Once the best available evidence has been found and appraised, the final step is to apply the research to decision making. To determine whether the results of a trial of a treatment are applicable to a particular patient, it seems reasonable to compare the patient's characteristics with the trial's inclusion criteria. This approach may lead to treating some patients who may experience more harm than benefit.19 An alternative approach helps avoid this problem.20 1. Make a balance sheet of the benefits and harms of the intervention All outcomes (both beneficial and harmful) that are important to the patient and influenced by the intervention need to be considered. For example, for the man with progressive kidney disease in our second scenario, we would need to consider the possible benefits of cyclosporin (reducing the need for dialysis) alongside the possible harms (gum hypertrophy, hypertension and hypertrichosis). 2. From research data, quantify the likelihood of benefits and harms in relative terms How likely is it that the benefits and harms will affect an individual patient? To estimate this we need to know the average effect of the treatment from systematic reviews (or trials, if systematic reviews are not available) and whether the effect varies according to patient and disease factors or whether it is relatively constant and independent of these factors. This type of information comes from subgroup analyses of systematic reviews and large trials. The benefits and harms of interventions are generally best expressed in relative terms (such as relative risks), because the relative effect is often stable across many different patient subgroups. In the trial of cyclosporin for progressive kidney disease, the relative risk of needing dialysis was 0.4 (the risk of dialysis was 0.4 times lower in those treated with cyclosporin than in those not treated with it), but the study was too small to determine whether the effect varied in different subgroups. 3. Convert the relative benefits and harms into absolute terms for your patient using the patient's specific characteristics If the relative beneficial effect of treatment is stable across patients at different levels of risk from their disease, then those at greatest risk will have the most to gain from treatment, and those at least risk from their disease will have the least to gain. The absolute benefit of treatment (how much they have to gain) can be calculated by combining the relative effect of treatment (from randomised trials and systematic reviews) with the risk of the outcome without treatment (from cohort studies of prognosis). This is demonstrated in Box 5 using two groups of patients with kidney disease treated with cyclosporin. While valid data from trials about the average benefit of a treatment are important, we also need valid data (preferably local) about the prognosis of patients without treatment to estimate the absolute benefit for any particular patient. To return to our example, the patient's renal function, blood pressure and degree of proteinuria indicate that he belongs to the low risk group and has a probability of needing dialysis over the next few years of about 10%, which can be reduced to 4% with treatment.20 The same logic can be used to calculate the risk of treatment-related harms. 4. Decide whether the benefits outweigh the harms Having listed all benefits and harms of an intervention and assigned some likelihood for each outcome based on research and individual patient data, the next step is to determine whether, on balance, the treatment is likely to do more good than harm. If the various benefits and harms are roughly equivalent, then this is relatively easy. For example, in weighing up the benefits and harms of thrombolytic therapy for myocardial infarction, it is reasonable to count deaths prevented (from myocardial infarction) as equal to deaths caused (from cerebral haemorrhage) — they are equally undesirable. But not all outcomes are equal. How does a stroke prevented by aspirin compare with a gastrointestinal haemorrhage caused by it? The differential desirability of outcomes can be measured formally, preferably by patients, but more often this integration of probabilities and preferences is informal. Does providing evidence-based care to patients improve outcomes? Observational studies show that treatments proven in randomised trials and systematic reviews seem to work equally well in routine clinical practice.21-23 However, it is still unclear what interventions are most effective in helping clinicians use research data more effectively in decision making.24-26 Guidelines, computer-generated reminders, opinion leaders, and outreach visits (or combinations) have been shown to improve care and patient outcomes, but passive dissemination strategies (eg, conferences and printed educational materials) have not. The future of EBM Better information systems at the point of care Due to time constraints, it is impractical to access and appraise at the bedside all of the primary studies applicable to individual patients. Only access to summarised research information is realistic. This should preferably be in the form of succinct evidence-based guidelines (including benefit-harm balance sheets of all available interventions), formatted to be rapidly and easily integrated with specific patient details. Many examples already exist, such as the evidence-based guidelines for early breast cancer (developed by the National Breast Cancer Centre13), and are widely available in hard copy and on the Internet. Ultimately, given the complexity of the data, widespread use of high-quality evidence requires computer-based information management systems. Such computerised decision support systems for clinicians have already been developed, and are available to help clinicians provide better care.26-28 The clinician's role is to use clinical judgement to integrate the best available research information and the patient's unique circumstances and preferences into a plan of management. Better primary research The evidence base of medicine needs to improve in its scope (both by disease and study type) and quality. Some diseases, like early breast cancer, have a large research base to guide decision making.29 However, for most diseases, many important questions remain unanswered, and for those with available evidence there is often considerable room to improve its quality.16-18 Editors of major medical journals have recently provided guidelines to encourage better design and reporting of randomised controlled trials30 and systematic reviews.31 As well as unequal coverage of diseases, there is also unequal coverage of question types. While there are many randomised controlled trials of treatments, there are too few high quality studies of diagnostic tests, prognoses and interventions to help clinicians use research information more effectively. The research data relevant to the questions in the Introduction are given in Box 7. Conclusions The EBM-oriented clinicians of tomorrow have three tasks: To use evidence summaries in clinical practice; To help develop and update selected systematic reviews or evidence-based guidelines in their area of expertise; and To enrol patients in studies of treatment, diagnosis and prognosis on which medical practice is based. Acknowledgements Thanks to Elisabeth Hodson and John Knight for helpful comments on earlier drafts. References Towler B, Irwig L, Glasziou P, et al. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult. BMJ 1998; 317: 559-565. Cattran DC, Appel GB, Hebert LA, et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999; 56: 2220-2226. Veenstra DL, Saint S, Saha S, et al. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. JAMA 1999; 281: 261-267. Williamson JW, German PS, Weiss R, et al. Health science information management and continuing education of physicians. A survey of U. S. primary care practitioners and their opinion leaders. Ann Intern Med 1989; 110: 151-160. Wyatt J. Uses and sources of medical knowledge. Lancet 1991; 338: 1368-1372. Sackett DL, Straus SE, Richardson WS, et al. Evidence-based medicine: how to practice and teach EBM. 2nd edition. New York: Churchill Livingston, 2000. Scott I, Heyworth R, Fairweather P. The use of evidence-based medicine in the practice of consultant physicians. Results of a questionnaire survey. Aust N Z J Med 2000; 30: 319-326. Covell DG, Uman GC, Manning PR. Information needs in office practice: are they being met? Ann Intern Med 1985; 103: 596-599. Osheroff JA, Forsythe DE, Buchanan BG, et al. Physicians' information needs: analysis of questions posed during clinical teaching. Ann Intern Med 1991; 114: 576-581. Smith R. What clinical information do doctors need? BMJ 1996; 313: 1062-1068. Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical question: a key to evidence-based decisions. ACP J Club 1995; 123: A12-A13. Bucher HC, Guyatt GH, Cook DJ, et al. Users' guides to the medical literature: XIX. Applying clinical trial results. A. How to use an article measuring the effect of an intervention on surrogate end points. Evidence-Based Medicine Working Group. JAMA 1999; 282: 771-778. National Health and Medical Research Council. Clinical practice guidelines for the management of early breast cancer. 2nd edition. Canberra: NHMRC, 2000. <http://www.health.gov.au/nhmrc/advice/pdfcover/eabrscov.htm> Hunt DL, Jaeschke R, McKibbon KA. Users' guides to the medical literature: XXI. Using electronic health information resources in evidence-based practice. JAMA 2000; 283: 1875-1879. Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 1998; 352: 609-613. Lijmer JG, Mol BW, Heisterkamp S, et al. Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 1999; 282: 1061-1066. National Health and Medical Research Council. How to use the evidence: assessment and application of scientific evidence. Canberra: NHMRC, 2000. Liddle J, Williamson M, Irwig L. Method for evaluating research and guideline evidence. Sydney: NSW Health, 1996. Glasziou PP, Irwig LM. An evidence based approach to individualising treatment. BMJ 1995; 311: 1356-1359. Chitalia VC, Wells JE, Robson RA, et al. Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. Kidney Int 1999; 56: 2236-2242. Mitchell JB, Ballard DJ, Whisnant JP, et al. What role do neurologists play in determining the costs and outcomes of stroke patients? Stroke 1996; 27: 1937-1943. Soumerai SB, McLaughlin TJ, Spiegelman D, et al. Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction. JAMA 1997; 277: 115-121. Krumholz HM, Radford MJ, Ellerbeck EF, et al. Aspirin for secondary prevention after acute myocardial infarction in the elderly: prescribed use and outcomes. Ann Intern Med 1996; 124: 292-298. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 1993; 342: 1317-1322. Oxman AD, Thomson MA, Davis DA, Haynes RB. No magic bullets: a systematic review of 102 trials of interventions to improve professional practice. CMAJ 1995; 153: 1423-1431. Walton R, Dovey S, Harvey E, Freemantle N. Computer support for determining drug dose: systematic review and meta-analysis. BMJ 1999; 318: 984-990. Chatellier G, Colombet I, Degoulet P. Computer-adjusted dosage of anticoagulant therapy improves the quality of anticoagulation. Medinfo 1998; 9 Pt 2: 819-823. Montgomery AA, Fahey T. A systematic review of the use of computers in the management of hypertension. J Epidemiol Community Health 1998; 52: 520-525. Early Breast Cancer Triallists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998; 351: 1451-1467. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996; 276: 637-639. Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999; 354: 1896-1900. Authors' details Department of Public Health and Community Medicine, University of Sydney, NSW. Jonathan C Craig, MM(ClinEpi), PhD, FRACP, Senior Lecturer; Paediatric Nephrologist, Centre for Kidney Research, Children's Hospital at Westmead; and Coordinating Editor, Cochrane Renal Group, NSW. Les M Irwig, PhD, FFPHM, Professor of Epidemiology. Martin R Stockler, MSc(ClinEpi), FRACP, Senior Lecturer; also at Department of Medicine, and NHMRC Clinical Trials Centre, University of Sydney; and Consultant Medical Oncologist, Sydney Cancer Centre, Royal Prince Alfred Hospital and Concord Repatriation General Hospital, NSW. Reprints will not be available from the authors. Correspondence: Dr J C Craig, Department of Public Health and Community Medicine, Edward Ford Building A27, University of Sydney, NSW 2006. joncAThealth.usyd.edu.au . 1: How to ask answerable clinical questions, where to look, and how to search at a glance Question type Diagnosis Harm/Aetiology Prognosis Intervention Population In people with suspected colorectal cancer Do newborns What proportion of children with febrile seizures In asymptomatic people In patients with central venous lines Intervention/ exposure how accurate is faecal occult blood testing given parenteral vitamin K have a develop recurrent episodes does testing for faecal occult blood lead to does antiseptic impregnation Outcome for diagnosing colorectal cancer higher incidence of leukaemia fewer colorectal cancer deaths cause fewer line- associated infections Comparator compared with colonoscopy than newborns not given vitamin K than routine care without screening than ordinary catheters Best feasible primary study design Cross-sectional analytic study Cohort study (best), population-based case-control study (next best) Cohort study Randomised controlled trial Randomised controlled trial Best MEDLINE search term for study type Sensitivity.tw Risk.tw Exp cohort studies/ Clinical trial.pt if no hits with Randomised controlled trial.pt tw (text word search ["risk.tw" finds the word "risk" in the title or abstract]); pt (publication type ["clinical trial.pt" finds studies which are classified as clinical trials]) Back to text 2: Types of research evidence and usefulness for decision making Type of evidence Advantages Disadvantages Evidence-based guideline Very comprehensive -summarises all relevant research information about all possible interventions for a common clinical problem -improved power to detect small and important differences Very useful applicability information -explores the trade-off of benefit and harm according to the level of risk in different patient subgroups Can be difficult to use if not formatted with the end-user in mind May quickly become out of date Systematic review Moderately comprehensive -summarises all relevant research information about a common intervention Less random error -improved power to detect small and important differences Useful applicability information -analyse variability of effects among different patient subgroups Generally only one of many possible interventions considered Often insufficient data about potential harms Generally provides little information from cohort studies for estimating disease risk to individual patients Primary study Very specific information available Not comprehensive -only one of (usually) many studies available Insufficient for clinical application Back to text 3: Useful sources of evidence-based guidelines, systematic reviews and general EBM resources Name Form and purpose Web access (accessed February 2001) Clinical Evidence Compendium of research evidence of interventions for common medical conditions <http://www.clinicalevidenceonline.org/> Cochrane Library Compendium of systematic reviews and randomised controlled trials <http://www.update-software.com/cochrane/cochrane-frame.html> <http://www.ausdoctors.net/> (follow link to Library) Guideline websites Provided by medical colleges or specialty groups Canadian Medical Association - <http://www.cma.ca/cpgs/index.asp> National Guideline Clearinghouse (US) - <http://www.guideline.gov/index.asp> NHMRC -<http://www.health.gov.au/nhmrc/publicat/cp-home.htm> MEDLINE Compendium of published research PubMed - <http://www.ncbi.nlm.nih.gov/PubMed/> Filter for guidelines (practice guideline as a publication type) Filter for systematic reviews (meta-analysis as a publication type) McMaster University Health Information Research Unit Evidence-based medicine: how to practice and teach EBM6 General "how to do" book <http://hiru.mcmaster.ca/ebm.htm> NHMRC Guidelines toolkit How to review, use, apply, implement and communicate evidence Hardcopy and pdf version available <http://www.health.gov.au/nhmrc/advice/contents.htm> JAMA user's guides to the medical literature JAMA series about all aspects of medical literature (26 articles so far) <http://medicine.ucsf.edu/resources/guidelines/users.html> ScHARR Internet guide for EBM <http://www.shef.ac.uk/~scharr/ir/netting/> Back to text 4: Checklist of critical appraisal items (dimensions of evidence) Item Definition Strength of evidence Level Was the best feasible study design used? (see Box 1) Quality How good was the study design and reporting? (see Box 4) Statistical precision How small was the P-value? How narrow were the confidence limits? (What is the degree of uncertainty about the true effect?) Size of effect How large was the effect? Relevance of effect Does the outcome matter to patients? Adapted from a National Health and Medical Research Council (NHMRC) publication.18 Back to text 5: Checklist of quality items for different types of studies and questions Systematic review (all questions) Was a comprehensive and explicit search strategy used? Were the included studies assessed for quality? Were the characteristics and results of the studies summarised appropriately? Were sources of heterogeneity explained? Evidence-based guideline Was a comprehensive and explicit search strategy used? Have all relevant interventions and outcomes been considered, covering both benefits and harms? Is the level and quality of evidence for the recommendations given? Do the recommendations explore the trade-off of benefit and harm according to the level of risk in different patient subgroups? Randomised controlled trial for intervention questions Was allocation to treatment groups concealed from those responsible for recruiting the subjects? Were all randomised participants included in the analysis? Was there a blinded assessment of outcomes? Cross-sectional analytic study for diagnosis questions Was the test compared with a valid reference (gold) standard? Were the test and reference standard measured independently? Was the choice of patients assessed by the reference standard independent of the test results? Cohort study for prognosis questions Was there a representative sample of patients at a well defined point in the course of the disease? Was follow-up sufficiently long and complete? Were all potentially important prognostic factors assessed? Adapted from a National Health and Medical Research Council (NHMRC) publication,17 and Liddle et al.18 Back to text 6: Comparisons of effects of using cyclosporin in two patient subgroups with different risks of dialysis over two years (assuming the same relative treatment effect, 60% reduction in risk) Risk of dialysis Patient No. of patients who have dialysis subgroups If untreated If treated averted for every 100 treated Low risk Normal kidney function Mild proteinuria 10% 4% 6 Normal blood pressure High risk Very abnormal kidney function Marked proteinuria 100% 40% 60 Hypertensive Back to text 7: Research data relevant to the questions posed in the beginning of the article Question Information Source Quality of the study Study result Does colorectal cancer screening reduce mortality from colorectal cancer compared with routine care? Cochrane Library Search term: "colorectal neoplasms" 7 hits, #6 relevant1 Level: systematic review of RCTs (highest level) Quality: high Statistical precision: narrow confidence limits Size of effect: 23% reduction in mortality Relevance: high For every 10000 screened biennially over 10 years eight deaths prevented 2800 extra colonoscopies Does cyclosporin A prevent dialysis in focal and segmental glomerulonephritis? MEDLINE Search terms: "cyclosporine" and "glomerulonephritis" and "randomised controlled trial" as a publication type (.pt) 3 hits, #1 relevant2 Level: single RCT Quality: inadequate allocation concealment Statistical precision: wide confidence limits Size of effect: 33% reduction in ESRD Relevance: high For every 100 treated for 4 years 25 fewer develop ESRD uncertainty remains (small, potentially biased result) Does antiseptic impregnation of central venous lines reduce line-associated sepsiscompared with standard lines? MEDLINE Search terms: "local anti-infective agents" and "central venous catheterisation" and "meta-analysis" as a publication type (.pt) 2 hits, #1 relevant3 Level: systematic review of RCTs (highest level) Quality: high Statistical precision: narrow confidence limits Size of effect: 44% reduction in line sepsis Relevance: high For every 100 lines two fewer episodes of line sepsis RCT=randomised controlled trial.

Jonathan C Craig · Les M Irwig · Martin R Stockler

Abstract Objectives: To compare rates of mortality from coronary heart disease (CHD) between populations living within and outside Australian capital city statistical divisions. Design and setting: Descriptive epidemiological study based on data for all residents of Australia aged 30-69 years who died between 1986 and 1996 in all States and Territories of Australia. Main outcome measures: Standardised mortality rates from all causes and coronary heart disease as coded by the Australian Bureau of Statistics, and estimated excess deaths in populations living outside capital city statistical divisions. Results: Between 1986 and 1996, mortality from CHD declined by 46% in men and 51% in women, and accounted for 61% of the decline in mortality from all causes in men and 48% in women. More deaths than expected from acute myocardial infarction resulted in mortality rates from CHD up to 30% higher in men and 21% higher in women living outside the capital city statistical divisions, and accounted for an overall estimated excess of 3835 deaths from CHD in men (32% of excess deaths from all causes), and 1385 deaths from CHD in women (27% of excess deaths from all causes) over the 11-year study period. Conclusions: Although there were impressive declines in coronary mortality in all Australian States and Territories from 1986 to 1996, populations living outside capital cities continue to have higher death rates from CHD. These differences in mortality rates indicate a need for further research into factors which may influence mortality rates for CHD in rural and remote areas, and immediate measures to ensure optimal treatment of coronary risk factors and acute coronary events in such populations. Coronary heart disease (CHD) remains the largest single cause of death in Australia.1 Although there has been a steady decline in the death rate associated with CHD over the past 30 years, rates of decline have not been equal throughout Australia.2,3 A study of coronary mortality in Tasmania showed higher rates of mortality outside the capital city region.4 We examined official data for Australian men and women aged 30-69 years between 1986 and 1996 for evidence of differences in rates of death from CHD between capital city and regional populations. Methods The Australian Bureau of Statistics (ABS) collects and disseminates social, demographic and economic statistics for 66 Statistical Divisions based on an Australian Standard Geographical Classification (ASGC).5 The boundaries of capital city statistical divisions are determined by the anticipated development of the city for a period of at least 20 years, and delimit an area that is stable for general statistical purposes. Statistical divisions outside a capital city are relatively homogeneous regions characterised by identifiable social and economic links between the inhabitants and between the economic units within the region, under the unifying influence of one or more major towns or cities. We obtained ABS estimates of the size of the Australian population aged 30-69 years, and its distribution between capital city and other statistical divisions for the years 1986 and 1996. We also obtained ABS data for mortality from all causes, and from CHD, acute myocardial infarction (AMI) and subacute and chronic myocardial ischaemia for men and women aged 30-69 years living within and outside capital city statistical divisions for each year from 1986 to 1996. We excluded deaths at 70 or more years because certification of the cause of death in older people may be unreliable.6 We defined mortality from CHD as deaths with an underlying cause classified under rubrics 410, 411, 413 and 414 of the International classification of diseases, ninth revision (ICD-9-CM),7 with mortality from AMI classified under ICD-9-CM rubric 410, and mortality from subacute and chronic myocardial ischaemia classified under rubrics 411, 413, 414. Statistical methods Annual age-standardised rates for mortality from all causes, CHD, AMI and subacute and chronic myocardial ischaemia were calculated as follows: The number of deaths in each age group (30-39, 40-49, 50-59 and 60-69 years), coded to each cause of death category, were summed. Age-specific rates were calculated and then standardised with weightings obtained from Segi's "world population" (World Health Organization standard population).8 The normal approximation for the distribution was used to calculate 95% confidence intervals. For each State and the Northern Territory, we calculated expected numbers of deaths in each age group for populations living outside capital city statistical divisions by applying age-specific mortality rates from populations living within the capital city statistical division. Differences between the actual (observed) number of deaths and the expected number of deaths were then summed across 10-year age strata to give total expected numbers of deaths. Excess deaths were calculated as the difference between the sum of the observed and the sum of the expected number of deaths for all States and the Northern Territory. The population of the Australian Capital Territory living outside the Canberra Statistical Division was less than 0.1% of the total population of the ACT and was not included in the calculation. Results Population size and distribution Unpublished regional population data from the ABS estimated that, in 1986, there were 7 174 246 Australians aged 30-69 years, 64.4% of whom lived in capital city statistical divisions. The sex distribution in capital cities was 49.9% men and 50.1% women, compared with 51.0% men and 49.0% women outside capital cities. By 1996, the estimated population of Australians aged 30-69 years had increased to 8 793 107, 63.5% of whom lived in capital city statistical divisions. The sex distribution in capital cities was 49.8% men and 50.2% women, compared with 50.7% men and 49.3% women outside capital cities. Trends in mortality rates among men Between 1986 and 1996, mortality from all causes in all 30-69-year-old Australian men declined by 23%; this decline within capital city statistical divisions was 25%, compared with 21% among men living outside capital city statistical divisions (Box 1). Mortality from all causes in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 12% in 1986 to 18% in 1996. Between 1986 and 1996, mortality from CHD in Australian men aged 30-69 years declined by 46% and accounted for 61% of the decline in all-cause mortality. Mortality among men living within capital city statistical divisions declined by 49%, compared with 41% among men living outside capital city statistical divisions (Box 1). Mortality from CHD in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 13% in 1986 to 30% in 1996. Mortality from AMI among men living within capital city statistical divisions declined by 62%, compared with 50% among men living outside capital city statistical divisions (Box 1). Mortality from AMI in men living outside the capital cities remained higher than in capital city populations, with the difference increasing from 24% in 1986 to 63% in 1996. Excess mortality outside capital city statistical divisions Box 2 shows that, among men, CHD accounts for 32% of the excess deaths from all causes from 1986 to 1996 occurring outside the capital city statistical divisions. Among those deaths coded as CHD, observed deaths from AMI exceeded expected deaths by 5487. The number of excess deaths from CHD is smaller than that from AMI, as there was a higher rate of death from subacute and chronic myocardial ischaemia in capital city populations. Observed deaths from AMI among men aged 30-39 years living outside capital city statistical divisions exceeded expected deaths by 79%; corresponding figures for the remaining age groups were 72% (40-49 years), 51% (50-59 years), and 25% (60-69 years). Trends in mortality rates among women Between 1986 and 1996, mortality from all causes in all 30-69-year-old Australian women declined by 21%; this decline within capital city statistical divisions was 24%, compared with 18% among women living outside capital city statistical divisions (Box 1). Mortality from all causes in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 6% in 1986 to 15% in 1996. Between 1986 and 1996, mortality from CHD in Australian women aged 30-69 years declined by 51% and accounted for 48% of the decline in all-cause mortality. Mortality among women living within capital city statistical divisions declined by 54%, compared with 50% among women living outside capital city statistical divisions (Box 1). Mortality from CHD in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 13% in 1986 to 21% in 1996. Mortality from AMI among women living within capital city statistical divisions declined by 59%, compared with 54% among women living outside capital city statistical divisions (Box 1). Mortality from AMI in women living outside the capital cities remained higher than in capital city populations, with the difference increasing from 24% in 1986 to 38% in 1996. Excess mortality outside capital city statistical divisions Box 2 shows that, among women, CHD accounts for 27% of the excess mortality from all causes occurring outside the capital city statistical divisions. Observed deaths from AMI exceeded expected deaths by 1479. Observed deaths from AMI among women aged 30-39 years living outside capital city statistical divisions exceeded expected deaths by 108%; corresponding figures for the remaining age groups were 75% (40-49 years), 44% (50-59 years), and 20% (60-69 years). Overall mortality Box 3 shows that death rates from CHD outside capital cities are consistently higher than within capital cities in all Australian States and the Northern Territory, the only exception being mortality from CHD among women in the Northern Territory in 1986. Discussion The contribution of reduced CHD mortality to the overall decline in all-cause mortality in Australia from 1986 to 1996 was 61% for men and 48% for women. However, our findings show that CHD mortality rates were higher outside capital cities, and that discrepancies increased from 1986 to 1996 and were largest in younger age groups. It is likely that the differences we found in CHD mortality are real, as they are matched by parallel trends in all-cause mortality rates, and at least two studies have confirmed the validity of deaths coded by the ABS to CHD.9,10 While a study based on 1979 data questioned the validity of subcategories of CHD such as rubric 410 (AMI),11 we found consistently higher death rates from AMI in populations outside capital cities in all Australian States and the Northern Territory (data not shown), despite variations in medical certification requirements between States. The apparent higher rates of mortality in capital city populations from subacute and chronic CHD may be the result of a coding anomaly or of deaths occurring in large population centres after patients were moved there for the management of their subacute or chronic CHD. Our study was limited to documenting the difference in CHD mortality between capital cities and other areas. Clearly, an understanding of the factors associated with higher CHD mortality outside capital cities has implications for prevention and improved treatment of CHD. This would require detailed examination of population characteristics to determine which populations outside capital cities, including subpopulations such as Indigenous people, are most at risk of higher mortality. It is also necessary to consider factors such as differences in socioeconomic status, in risk factors for CHD, and in access to medical care. Previous reports showed that the decline in mortality from CHD in NSW was slower in lower income populations, many of which were in rural or regional areas.12,13 Also, sudden cardiac death in Tasmanian men was found to occur twice as frequently in unemployed men compared with employed men.14 While the association between populations with lower socioeconomic status and higher risk for CHD is recognised, the actual factors that influence this association have not been well delineated. Risk factors for CHD clearly have an influence on mortality. Much of the decline in mortality from CHD in Finland from 1972 to 1992 can be explained by changes in the three main coronary risk factors: serum cholesterol level, blood pressure and smoking.15 In Australia, the National Heart Foundation (NHF) Risk Factor Prevalence Surveys found significant declines between 1980 and 1989 in the prevalence of hypertension and cigarette smoking, but no overall favourable trend in lipid levels.16 However, these surveys are limited to capital cities, and it is not known whether regional areas of Australia have seen the same trends in risk factor prevalence. In 1992, a major risk factor prevalence survey based on the 1989 NHF Risk Factor Prevalence Survey was undertaken in two rural regions of Tasmania. The prevalence of major coronary risk factors was consistent with the high rate of mortality from CHD among men in North-West Tasmania, but did not explain variation in rates of mortality in women across the three regions of Tasmania.17 Differences in mortality from CHD may be the result of differential incidences of CHD or differences in case-fatality rates. A detailed study of sudden cardiac death among previously asymptomatic men found that the higher rate of deaths in the two rural regions of Tasmania occurred mostly among men for whom symptomatic CHD could have been diagnosed, implying a higher case-fatality rate for CHD.14 This finding was supported by higher rates of coronary deaths occurring after hospitalisation in the two rural regions of Tasmania from 1986 to 1989,4 and in Newcastle in 1984.18 A higher case-fatality rate may result from differences in risk of death from factors such as previous infarction, delays in reaching medical care, or differences in medical care.19 While the relative geographic isolation of most populations outside the capital cities may be expected to result in delays in reaching secondary and tertiary medical centres, the findings of the MONICA study did not support changes in time to medical care (including ambulance staff) having a significant effect on deaths before hospitalisation in major population centres.18 A significant decline in case fatality after hospitalisation did, however, make an important contribution to the overall decline in coronary deaths in the MONICA centres of Auckland (New Zealand), Newcastle (Australia) and Perth (Australia) from 1984 to1993. Medical management of acute coronary events has changed substantially over the past 20 years. The use of aspirin, thrombolytic therapy and coronary angioplasty as first-line treatments for AMI has resulted in reductions in mortality of up to 43%.20,21 The use of thrombolytic therapy in the MONICA centres increased from being rare in the early 1980s, to being used in approximately 50% of hospitalised patients with non-fatal definite myocardial infarction or coronary death by the early 1990s.22,23 The benefits of such treatments are dependent on them being given soon after the event,24 and it is not clear whether populations living at any distance from secondary or tertiary medical centres experience delays in access to new treatment methods for symptomatic CHD. In southern Tasmania between 1992 and 1996, 849 doses of streptokinase and tissue plasminogen activator were administered for AMI. No thrombolytic therapy was administered outside the capital city of Hobart (Royal Hobart Hospital Pharmacy Supplies Report), despite 15% of the population of the Southern Region living outside the capital city and having mortality rates approximately 40% higher than the capital city population. In conclusion, although there have been impressive declines in mortality from CHD in all Australian States and Territories over the past 30 years, the 35% of the Australian population living outside the capital cities continue to have higher coronary mortality. Our results indicate the need for increased research into factors which may influence mortality rates for CHD in rural and remote areas. Acknowledgements This study was supported by funding from Roche Products Pty Ltd and the Tasmanian branch of the AMA, and by assistance in-kind from the Hobart City Council and Australian Hospital Care Ltd. We are grateful to Chris Sweeney from the Australian Bureau of Statistics and to the Pharmacy Department of the Royal Hobart Hospital. References Tonkin AM, Bennett S. Cardiovascular disease at the turn of the century. Med J Aust 1999; 170: 408-409. Gibberd RW, Dobson AJ, Florey C du Ve, Leeder SR. Differences and comparative declines in ischaemic heart disease mortality among sub-populations of Australia 1969-1978. Int J Epidemiol 1984; 13: 25-31. Sexton PT, Woodward DR, Gilbert N, Jamrozik K. Interstate differences in trends in coronary mortality and risk factors in Australia. Med J Aust 1990; 152: 531-534. Sexton PT, Jamrozik K, Walsh J, et al. Regional variation in coronary mortality within Tasmania. Med J Aust 1992; 157: 449-451. Australian Bureau of Statistics. Australian Standard Geographical Classification. Canberra: ABS, 1998. Christie D. Mortality from cardiovascular disease. Med J Aust 1974; 1: 390-393. National Coding Centre, Faculty of Health Sciences, University of Sydney. Australian version of the international classification of diseases. 9th revision, clinical modification (ICD-9-CM). 2nd ed. Vol.1: Tabular list of diseases. Sydney: NCC, University of Sydney, July 1996. Doll R. Comparison between registers, age-standardised rates. IARC Sci Publ 1976; 3: 453-459. Martin CA, Hobbs MST, Armstrong BK. Estimation of myocardial infarction mortality from routinely collected data in Western Australia. J Chron Dis 1987; 40: 661-669. Sexton PT, Jamrozik K, Walsh J. Death certification and coding for ischaemic heart disease in Tasmania. Aust N Z J Med 1992; 22: 114-118. Dobson AJ, Gibberd RW, Leeder SR. Death certification and coding for ischaemic heart disease in Australia. Am J Epidemiol 1983; 117: 397-405. Burnley IH. Inequalities in the transition of ischaemic heart disease mortality in New South Wales, Australia. Soc Sci Med 1998; 47: 1209-1222. Taylor R, Chey T, Bauman A, Webster I. Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales. Aust N Z J Public Health 1999; 23: 20-26. Sexton PT, Jamrozik K, Walsh J. Sudden unexpected cardiac death among Tasmanian men. Med J Aust 1993; 159: 467-470. Vartiainen E, Puska P, Pekkanen J, et al. Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. BMJ 1994; 309: 23-27. Bennett SA, Magnus P. Trends in cardiovascular risk factors in Australia. Results from the National Heart Foundation's Risk Factor Prevalence Study, 1980-1989. Med J Aust 1994; 161: 519-527. Thomson A, Rundle S, Singh BB, et al. Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality. Aust N Z J Med 1995; 25: 290-296. Beaglehole R, Stewart AW, Jackson R, et al. Declining rates of coronary heart disease in New Zealand and Australia, 1983-1993. Am J Epidemiol 1997; 145: 707-713. Beaglehole R. Medical management and the decline in mortality from coronary heart disease. BMJ 1986; 292: 33-35. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-402. Second International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. Doggen CJM, van der Palen J, Beaglehole R. Trends in medical management of acute myocardial infarction. N Z Med J 1993; 106: 278-281. Dobson AJ, Jamrozik KD, Hobbs MST, et al. Medical care and case fatality from myocardial infarction and coronary death in Newcastle and Perth. Aust N Z J Med 1993; 23: 12-18. Bett JHN. LATE assessment of thrombolytic efficacy with alteplase (rt-PA) six-24 hours after onset of acute myocardial infarction. Aust N Z J Med 1993; 23: 745-748. (Received 23 Sep 1999, accepted 31 Jan 2000) Authors' details The Hobart Private Hospital, Hobart, TAS. Peter T Sexton, PhD, FAFPHM, Director of Medical Services; Tiina-Liisa H Sexton, BCom, CA, Research Assistant. Reprints: Dr P T Sexton, The Hobart Private Hospital, Cnr Argyle and Collins Streets, Hobart, TAS 7000. 1: Comparison of mortality rates between populations aged 30-69 years living within and outside capital cities in Australia Back to text 2: Estimated excess deaths from all causes, CHD and AMI among men and women living outside capital city statistical divisions from 1986 to 1996 Age group (years) 30-3940-4950-5960-69Total Men Mortality from all causes Observed deaths8599126982622760856108380 Expected deaths736310718216195672596425 Excess deaths123619804608413111955 Mortality from CHD (ICD-9-CM 410, 411, 413, 414) Observed deaths682270372391824128865 Expected deaths493209959021653625030 Excess deaths189604 133717053835 Mortality from AMI (ICD-9-CM 410) Observed deaths470197253341328721063 Expected deaths263114435411062815576 Excess deaths207828 179326595487 Women Mortality from all causes Observed deaths38877021138633146756238 Expected deaths32025998119722991851090 Excess deaths6851023189115495148 Mortality from CHD (ICD-9-CM 410, 411, 413, 414) Observed deaths143537 187869379495 Expected deaths91381 150361358110 Excess deaths52156 3758021385 Mortality from AMI (ICD-9-CM 410) Observed deaths102391 140050736966 Expected deaths49223 97242435487 Excess deaths53168 4288301479 CHD=coronary heart disease. AMI=acute myocardial infarction Back to text 3: Mortality within and outside capital city statistical divisions by Australian States and Territories Men Age-standardised mortality rate per 100000 (95% CI) % changeEstimated excess 1986 1996 per yeardeaths from CHD All causesCHDAll causesCHDfrom CHD1986-1996 New South Wales Capital722 (702-741)223 (212-234)511 (496-527)106 (99-113)-4.8 Balance761 (736-786)232 (218-246)601 (581-622)143 (133-153)-3.51506 Victoria Capital658 (638-678)199 (188-210)487 (470-503)97 (90-105)-4.7 Balance755 (722-789)242 (223-261)583 (556-611)131 (118-144)-4.21015 Queensland Capital691 (657-724)226 (207-245)549 (523-575)122 (109-134)-4.2 Balance754 (723-785)227 (210-245)585 (562-609)136 (125-147)-3.6444 South Australia Capital653 (619-687)213 (194-232)528 (499-557)125 (110-139)-3.8 Balance707 (650-764)234 (201-267)633 (583-683)160 (135-186)-2.9291 Western Australia Capital638 (603-673)183 (164-202)498 (471-525)102 (89-114)-4.0 Balance779 (716-841)249 (214-285)594 (546-642)121 (100-143)-4.7203 Tasmania Capital605 (526-684)141 (103-179)595 (520-669)102 (71-133)-2.5 Balance758 (685-831)276 (232-320)619 (558-680)144 (115-174)-4.3243 Northern Territory Capital640 (463-817)115 (46-185)716 (569-863)97 (36-158)-1.4 Balance1443 (1206-1679)233 (138-329)1030 (862-1199)132 (73-191)-3.9133 Australian Capital Territory 598 (521-675)205 (159-251)428 (372-484) 111 (82-140)-4.2 All of Australia Capital679 (668-690)209 (203-215)510 (501-519)107 (103-111)-4.4 Balance763 (747-778)237 (228-245)602 (590-614)139 (133-145)-3.83835 Women Age-standardised mortality rate per 100000 (95% CI) % changeEstimated excess 1986 1996 per yeardeaths from CHD All causesCHDAll causesCHDfrom CHD1986-1996 New South Wales Capital391 (377-405)82 (76-88)284 (273-296)32 (28-36)-5.5 Balance420 (401-439)89 (80-97)335 (319-350)45 (39-51)-4.5564 Victoria Capital360 (346-375)65 (59-72)274 (262-286)31 (27-35)-4.8 Balance361 (338-384)68 (58-77)307 (287-327)35 (28-41)-4.4277 Queensland Capital371 (347-395)67 (57-78)308 (288-328)39 (32-46)-3.8 Balance378 (355-400)75 (65-85)299 (282-316)36 (30-42)-4.7171 South Australia Capital347 (323-371)69 (58-79)285 (264-306)31 (24-38)-5.0 Balance291 (317-400)83 (64-103)339 (301-377)39 (26-52)-4.8143 Western Australia Capital349 (324-374)59 (49-70)275 (255-295)37 (30-45)-3.4 Balance386 (339-433)78 (296-372)334 (57-99)36 (24-49)-4.9105 Tasmania Capital424 (360-488)68 (42-93)365 (308-422)49 (28-70)22.5 Balance421 (367-475)87 (62-111)385 (336-434)54 (36-72)-3.462 Northern Territory Capital434 (271-597)46 (-10-103)392 (261-523)41 (-3-86)-1.0 Balance911 (702-1120)37 (-6-81)762 (593-932)88 (28-148)+12.563 Australian Capital Territory 380 (319-440)56 (32-80)267 (223-311)41 (23-59)-2.4 All of Australia Capital372 (363-380)71 (68-75)284 (278-291)33 (31-36)-4.9 Balance396 (384-407)80 (75-85)326 (317-335)40 (37-44)24.51385 CHD=coronary heart disease. Capital=within capital city statistical divisions. Balance=outside capital city statistical divisions. Back to Text

Peter T Sexton · Tiina-Liisa H Sexton

Prostate-specific antigen testing for prostate cancer: the case for informed consent Informed consent should be obtained before testing asymptomatic men MJA 1998; 169: 9-10 The prostate-specific antigen (PSA) test is only the first step in screening asymptomatic men for prostate cancer. Its lack of specificity usually necessitates transrectal ultrasound-guided multiple biopsies for confirmation of the diagnosis. These procedures will discover a large number of cancers, many of which, viewed from one perspective, will be potentially curable by surgery1 or radiotherapy. However, epidemiological evidence suggests that most cancers localised to the prostate will not cause clinically significant disease for at least 10 years.2 PSA-based screening presents unique difficulties because at present there is no means to distinguish those cancers which will impair health to a degree that justifies the risk of iatrogenic morbidity of investigation (biopsy-related sepsis) and curative treatment (incontinence, impotence, and radiation damage to adjacent organs). This issue of the Journal includes four pertinent articles: the incidence of prostate cancer and the prevalence of PSA testing are described and compared in Western Australia3 (Threlfall et al) and New South Wales4 (Smith & Armstrong); reasons for PSA tests being ordered by general practitioners (GPs) in central Sydney are reported5 (Ward et al); and the prevalence of PSA testing among South Australian men is given, together with findings concerning men's understanding of the immediate consequences of having a PSA test6 (Pinnock et al). PSA tests were the sixth most frequent pathology item ordered by GPs in the June quarter of 1996,5 but their use has fallen since the peak in 1995.3,4 This may indicate that GPs are adopting a more discerning approach, in line with guidelines that recommend against the use of PSA tests to screen for prostate cancer.7 However, in the period 1992-1996, it is clear that GPs and asymptomatic men adopted the test enthusiastically. Medicare data show that one in every four Australian men (27%) aged at least 50 years had a PSA test in 1995 or 19964 and, in a random survey of households in South Australia carried out in 1996, 28% of men aged 50 years or older without prostate cancer reported having a PSA test in the preceding 12 months.6 A high proportion of PSA tests were ordered by GPs for screening ("routine for age") or in response to patient request.5,6 Men over 70 years old have been tested as frequently as younger men4,6 -- but the older the man when prostate cancer is detected, the less likely it is that a benefit from early intervention is possible.8 In South Australia, there was an association between PSA testing and visiting a doctor for urinary symptoms.6 PSA testing is not recommended for men presenting with uncomplicated lower urinary tract symptoms (because such symptoms are unlikely to be indicative of localised prostate cancer),6,9 but it is understandable that GPs may order the test because the question of prostate disease has been raised during the consultation. It is evident that PSA tests have been carried out without the consequences of an abnormal test result being adequately explained.6 GPs need a clear-cut structured framework within which the paucity of good scientific evidence and the potential harms and benefits can be discussed with patients. Most GPs will have had difficulty reconciling the negative evidence relating to the cost-benefit of PSA testing with their natural inclination to detect and treat cancer at an early stage. However, in asymptomatic people the balance of harm versus benefit must demonstrably be more clearly in favour of benefit than in usual clinical practice. In the United States, where enthusiasm for both case-finding by PSA testing and treatment by radical prostatectomy occurred some years earlier than in Australia, there appears to have been a small fall in mortality from prostate cancer in the period 1990-1995.10 Interpretation of this fall is far from clear, but it may be attributable to the dramatic increase in use of radical prostatectomy11 or other therapeutic advances in the 1980s. Conclusive evidence of reduced mortality from prostate cancer as a result of PSA screening must await the completion of randomised controlled trials. From an intention-to-treat analysis of men aged 50-79 years with clinically localised prostate cancer in the population-based US Surveillance, Epidemiology, and End Results (SEER) Program, no advantage in 10-year disease-specific survival was found for either radical prostatectomy or radiotherapy compared with conservative management for men with tumours with a Gleason score of 2-4 (well differentiated).12 For men with tumours with a Gleason score of 5-7 (moderately differentiated) there was an advantage for radical prostatectomy but not for radiotherapy -- this may reflect the fact that patients selected for surgery excluded those whose general health, and therefore prognosis, was already bad when prostate cancer was diagnosed. The 10-year disease-specific survival was better for men with tumours with a Gleason score of 8-10 (poorly differentiated) treated by either radical prostatectomy or radiotherapy compared with conservative management. Because of the way screening for breast and cervical cancers has been promoted, the general public will perceive that finding a cancer earlier is beneficial because treatment is more likely to be effective. However, using the PSA test for detecting prostate cancer in asymptomatic men is not analogous to mammography for early detection of breast cancer in asymptomatic women. Apart from the unproven benefit, there is a need for universally applied guidelines for the management of men with an abnormal test result, comparable with those built into the mammographic screening program. Such guidelines would include counselling and provision for a multidisciplinary approach when a decision is being made about the best course of management. At present, the cascade of events following an abnormal PSA test result proceeds without the man always making an informed choice before the test. Indeed, when men are given prior information about the PSA test and its characteristics, the consequences of having a raised PSA level, follow-up diagnostic procedures, treatment options and side effects, they are less likely to decide to have the test.13 GPs have a professional responsibility to give appropriate advice based on current evidence and, where there is uncertainty, this should be conveyed. Obtaining informed consent is accepted in the context of an invasive procedure. Given the medical uncertainties, the invasive nature of the confirmatory and therapeutic procedures that will be required if the test is positive, and the possibility of doing more harm than good, informed consent should be obtained from asymptomatic men before ordering a PSA test. Margaret McCredie Professorial Research Fellow, Department of Preventive and Social Medicine University of Otago, Dunedin, New Zealand, and Cancer Epidemiology Research Unit, NSW Cancer Council, Woolloomooloo, NSW Brian Cox Senior Research Fellow, Department of Preventive and Social Medicine University of Otago, Dunedin, New Zealand Kaye KW. Prostate cancer: enthusiasm for screening. Med J Aust 1995; 162: 540-541. Johansson J-E, Adami H-O, Andersson S-O, et al. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA 1992; 267: 2192-2196. Threlfall TJ, English DR, Rouse IL. Prostate cancer in Western Australia: trends in incidence and mortality from 1985 to 1996. Med J Aust 1998; 169: 21-24. Smith DP, Armstrong BK. Prostate-specific antigen testing in Australia and association with prostate cancer incidence in New South Wales. Med J Aust 1998; 169: 17-20. Ward JE, Gupta L, Taylor NJ. Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer? Med J Aust 1998; 169: 29-31. Pinnock CB, Weller DP, Marshall VR. Self-reported prevalence of prostate-specific antigen testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. Fleming C, Wasson JH, Albertsen PC, et al. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. Prostate Patient Outcomes Research Team. JAMA 1993; 269: 2650-2658. National Health and Medical Research Council. Clinical practice guidelines. The management of uncomplicated lower urinary tract symptoms in men. Canberra: AGPS, 1996. Mettlin CJ, Murphy GP. Why is the prostate cancer death rate declining in the United States? Cancer 1998; 82: 249-251. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Lu-Yao GL, Yao S-L. Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet 1997; 349: 906-910. Flood AB, Wennberg JE, Nease RF, et al. The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team. J Gen Intern Med 1996; 11: 342-349. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company 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/>

Margaret McCredie · Brian Cox