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The quality of reporting of studies of diagnostic accuracy is less than optimal. Complete and accurate reporting is necessary to enable readers to assess the potential for bias in a study and to evaluate the generalisability of the results. A group of scientists and editors has developed the STARD (Standards for Reporting of Diagnostic Accuracy) statement to improve the quality of reporting of studies of diagnostic accuracy. The statement consists of a checklist of 25 items and flow diagram that authors can use to ensure that all relevant information is present. This explanatory document aims to facilitate the use, understanding and dissemination of the checklist. The document contains a clarification of the meaning, rationale and optimal use of each item on the checklist, as well as a short summary of the available evidence on bias and applicability. The STARD statement, checklist, flowchart, and this explanation and elaboration document should be useful resources to improve the reporting of diagnostic accuracy studies. Complete and informative reporting can only lead to better decisions in health care.

Objective: To systematically review randomised controlled trials (RCTs) of computer-generated medication reminders or feedback directed to healthcare providers or patients., Data Sources: Extensive computerised and manual literature searches identified 76 English-language reports of RCTs reported before 1 January 2002. Searches were conducted between June 1998 and April 2002., Study Selection: 26 papers making 29 comparisons (two papers reported on multiple interventions) of computer-supported medication management to a control group., Data Extraction: The quality of the RCTs was systematically assessed and scored independently by two reviewers. Rates of compliance with (potential) reminders for the control and intervention groups were extracted., Data Synthesis: Heterogeneity of studies prevented a meta-analysis. Where possible, rates were calculated using the intention-to-treat principle. The comparisons were grouped into five areas. Reminders to providers in outpatient settings: six of 12 comparisons demonstrated positive effects (relative rates [RRs: intervention rates/control rates], 1.0 to 42.0). Provider feedback in outpatient settings: five of seven comparisons showed improved clinician behaviour (RRs, 1.0 to 2.5). Combined reminders and feedback in outpatient settings: the single comparison found no improvement. Reminders to providers in inpatient settings: three of five comparisons showed improvements (RRs, 1.0 to 2.1). Patient-directed reminders: two of four comparisons showed improvements in patient compliance., Conclusion: Reminders are more effective than feedback in modifying physician behaviour related to medication management. Patient-directed reminders can improve medication adherence.

The objective of the 'Standards for Reporting of Diagnostic Accuracy' (STARD) initiative is to improve the reporting of studies of diagnostic accuracy, so as to allow readers to assess the potential for bias in a study and to evaluate the generalibility of its results. The group searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies. This was used to draw up a list of potential items. During a consensus meeting, a group of researchers, medical journal editors, and members of professional organisations reduced this list to a usable checklist. Wherever possible, evidence from the literature was used to justify the decisions made. The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which a list of 75 potential items was extracted. At the consensus meeting, participants shortened the list to a 25-item checklist. A generic flow diagram was drawn up to provide guidance on the method for including patients, the order in which tests were to be conducted and the number of patients to undergo the test being evaluated, the reference standard, or both. A scientific publication can only be assessed when the reporting is both correct and complete. Use of the checklist and flow diagram will improve the quality of reports produced, to the advantage of clinicians, researchers, reviewers, journal editors and other interested parties.

The quality of reporting of studies of diagnostic accuracy is less than optimal. Complete and accurate reporting is necessary to enable readers to assess the potential for bias in the study and to evaluate the generalizability of the results. A group of scientists and editors has developed the STARD (Standards for Reporting of Diagnostic Accuracy) statement to improve the reporting the quality of reporting of studies of diagnostic accuracy. The statement consists of a checklist of 25 items and flow diagram that authors can use to ensure that all relevant information is present. This explanatory document aims to facilitate the use, understanding, and dissemination of the checklist. The document contains a clarification of the meaning, rationale, and optimal use of each item on the checklist, as well as a short summary of the available evidence on bias and applicability. The STARD statement, checklist, flowchart, and this explanation and elaboration document should be useful resources to improve reporting of diagnostic accuracy studies. Complete and informative reporting can only lead to better decisions in health care.

Background: To comprehend the results of diagnostic accuracy studies, readers must understand the design, conduct, analysis, and results of such studies. That goal can be achieved only through complete transparency from authors., Objective: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy to allow readers to assess the potential for bias in the study and to evaluate its generalisability., Methods: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two-day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy., Results: The search for published guidelines on diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. The consensus meeting shortened the list to 25 items, using evidence on bias whenever available. A prototypical flow diagram provides information about the method of patient recruitment, the order of test execution and the numbers of patients undergoing the test under evaluation, the reference standard or both., Conclusions: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels., Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo., Patients and Setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992., Main Outcome Measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life., Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626-$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%)., Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Objectives: To determine general practitioners' (GPs') attitudes towards and involvement in general practice research., Design: Postal survey and semi-structured interviews conducted from May to September 2001., Participants and Setting: 467 of 631 GPs in four Queensland Divisions of General Practice responded to the survey (74% response rate); 18 selected GPs were interviewed., Main Outcome Measures: Survey - attitudes to research; access to information resources; and involvement in research. Interviews - the need for general practice research; barriers against and factors enabling greater participation in research., Results: 389/463 (84%) GPs, especially younger and more recent graduates, had positive attitudes to research, but only 29% wanted more involvement. 223/462 (48%) were aware they had access to MEDLINE, although presumably all those with Internet access (89%) would have free access via PubMed. Barriers included the general practice environment (especially fee-for-service funding), and the culture of general practice. Enabling factors included academic mentors; opportunities to participate in reputable, established research activities relevant to general practice; and access to information resources., Conclusions: Although Australian general practice has a weak research culture, about a third of GPs would like to increase their involvement in research. However, the research must be perceived as relevant, and structured to minimise the inherent barriers in the environment and culture of general practice.

What causes heterogeneity in systematic reviews of controlled trials? First, it may be an artefact of the summary measures used, of study design features such as duration of follow-up or the reliability of outcome measures. Second, it may be due to real variation in the treatment effect and hence provides the opportunity to identify factors that may modify the impact of treatment. These factors may include features of the population such as: severity of illness, age and gender; intervention factors such as dose, timing or duration of treatment; and comparator factors such as the control group treatment or the co-interventions in both groups. The ideal way to study causes of true variation is within rather than between studies. In most situations however, we will have to make do with a study level investigation and hence need to be careful about adjusting for potential confounding by artefactual factors such as study design features. Such investigation of artefactual and true causes of heterogeneity form essential steps in moving from a combined effect estimate to application to particular populations and individuals., (Copyright 2002 John Wiley & Sons, Ltd.)

Objective: To assess the (i) benefits, (ii) harms and (iii) costs of continuing mammographic screening for women 70 years and over., Data Sources and Synthesis: (i) We conducted a MEDLINE search (1966 - July 2000) for decision-analytic models estimating life-expectancy gains from screening in older women. The five studies meeting the inclusion criteria were critically appraised using standard criteria. We estimated relative benefit from each model's estimate of effectiveness of screening in older women relative to that in women aged 50-69 years using the same model. (ii) With data from BreastScreen Queensland, we constructed balance sheets of the consequences of screening for women in 10-year age groups (40-49 to 80-89 years), and (iii) we used a validated model to estimate the marginal cost-effectiveness of extending screening to women 70 years and over., Results: For women aged 70-79 years, the relative benefit was estimated as 40%-72%, and 18%-62% with adjustment for the impact of screening on quality of life. For women over 80 years the relative benefit was about a third, and with quality-of-life adjustment only 14%, that in women aged 50-69 years. (ii) Of 10,000 Australian women participating in ongoing screening, about 400 are recalled for further testing, and, depending on age, about 70-112 undergo biopsy and about 19-80 cancers are detected. (iii) Cost-effectiveness estimates for extending the upper age limit for mammographic screening from 69 to 79 years range from $8119 to $27 751 per quality-adjusted life-year saved, which compares favourably with extending screening to women aged 40-49 years (estimated at between $24,000 and $65,000 per life-year saved)., Conclusions: Women 70 years and over, in consultation with their healthcare providers, may want to decide for themselves whether to continue mammographic screening. Decision-support materials are needed for women in this age group.

Objective: To test the feasibility of an evidence-based clinical literature search service to help answer general practitioners' (GPs') clinical questions., Design: Two search services supplied GPs who submitted questions with the best available empirical evidence to answer these questions. The GPs provided feedback on the value of the service, and concordance of answers from the two search services was assessed., Setting: Two literature search services (Queensland and Victoria), operating for nine months from February 1999., Main Outcome Measures: Use of the service; time taken to locate answers; availability of evidence; value of the service to GPs; and consistency of answers from the two services., Results: 58 GPs asked 160 questions (29 asked one, 11 asked five or more). The questions concerned treatment (65%), aetiology (17%), prognosis (13%), and diagnosis (5%). Answering a question took a mean of 3 hours 32 minutes of personnel time (95% CI, 2.67-3.97); nine questions took longer than 10 hours each to answer, the longest taking 23 hours 30 minutes. Evidence of suitable quality to provide a sound answer was available for 126 (79%) questions. Feedback data for 84 (53%) questions, provided by 42 GPs, showed that they appreciated the service, and asking the questions changed clinical care. There were many minor differences between the answers from the two centres, and substantial differences in the evidence found for 4/14 questions. However, conclusions reached were largely similar, with no or only minor differences for all questions., Conclusions: It is feasible to provide a literature search service, but further assessment is needed to establish its cost effectiveness.

Objectives: To compare the productivity of Australian general practice in terms of research publications with the productivity of other medical disciplines., Design: A survey of Australian general practice, medicine, surgery and public health publications carried out by manual searching of specific journals and an electronic search of the US National Library of Medicine's "PubMed" database., Main Outcome Measures: The number of original research publications by Australian general practitioners, physicians, surgeons and public health physicians during 1999; the relative publication rate of Australian general practice, medicine, surgery and public health over the period 1990-1999., Results: Of original research articles published in 1999, GPs authored 65% (17/26) in Australian Family Physician and 3% (3/90) in the Medical Journal of Australia; physicians published 4% and 37%, respectively. The electronic search identified 54 research articles relating to Australian general practice published in 1999 in 21 different journals, only two of which were primary care journals. Over the period 1990-1999, there was a publication rate of one general practice [discipline] article per 1000 GPs in practice per year. Corresponding rates for medicine, surgery and public health were 105/1000, 61/1000 and 148/1000, respectively., Conclusions: There is considerable disparity between the level of research output of general practice and that of the disciplines of medicine, surgery and public health. If we are to have effective general practice research, we urgently need to develop research skills, a supportive infrastructure and a culture that nurtures research.

Aims: To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents., Methods: A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices)., Results: This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling)., Conclusions: This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.

Objective: To pilot single patient trials designed to improve decision making about stimulant use for attention deficit hyperactivity disorder (ADHD) in general practice., Method: Patients previously stabilised on dexamphetamine were enrolled from a general practice. Each undertook a six week same patient randomised, double blind, placebo controlled crossover comparison of dexamphetamine with placebo for ADHD. Rating scales were completed weekly by self, parent and teacher., Results: Three of the four patients were clear responders to dexamphetamine (including a noncompleter, as his results still demonstrated a clear response). The results were clinically useful in each case. Management was confirmed for three patients and changed for one (who ceased dexamphetamine)., Discussion: Prescribing stimulant medications only to children with diagnosed ADHD and who are found to respond, limits use of these worrisome drugs to those who will respond, and minimises their use in those who will not benefit.

Objective: To adjust patients' time trade-off (TTO) scores using information on their utility functions for survival time to derive a measure of health state utility equivalent to the standard gamble (SG)., Methods: A sample of 199 cardiovascular patients were asked three TTO and SG questions (to assess their own health state), and three certainty equivalent questions (to assess their utility function for survival time) in an interview., Results: Patient's utility functions for time were increasingly concave, but being unable to model this successfully, a constant function with an averaged level of concavity was used. The raw TTO scores were significantly higher than SG scores, while the adjusted TTO scores were equivalent to the SG., Conclusions: Raw time trade-off scores will give biased estimates of health state utility when patients' utility functions for time are not linear, but these can be adjusted to yield true utilities. The constant proportional risk-posture assumption of the conventional QALY model, on which previous attempts to adjust time trade-offs have been based, was not supported by the data.

Background: In single patient (n of 1) trials, a patient acts as his or her own control in a study comparing the effectiveness of a drug with placebo or another drug. The aim of a single patient trial (SPT) is to identify the best treatment for the individual patient, formalising a 'trial of treatment' by using blinding and multiple crossover periods., Objective: We have successfully piloted SPTs for osteoarthritis and attention deficit hyperactivity disorder, and several others are currently being piloted. Barriers encountered include: obtaining identical placebos, ethical approval for individual SPTs, standardising doses, determining length of treatment periods, patient withdrawals and cost of the SPTs., Discussion: Only prescribing medications if an individual has been shown to be a responder can greatly benefit general practitioners, patients and the healthcare system. We have established the infrastructure necessary to offer a single patient trial service to GPs and patients anywhere in Australia. This has the potential to revolutionise prescribing for certain chronic conditions.

Objective: To pilot a single-patient trials (SPTs) service in general practice, designed to improve decision-making about long-term medications for chronic conditions., Design: 12-week within-patient, randomised, double-blind, placebo-controlled, crossover comparison of ibuprofen with paracetamol for osteoarthritis, involving three pairs of two-week treatment periods for each participating patient., Setting and Patients: Patients attending an academic general practice with a clinical diagnosis of osteoarthritis, with pain of at least a month's duration severe enough to warrant consideration of long-term non-steroidal anti-inflammatory drug (NSAID) use., Main Outcome Measures: Pain and stiffness; measures of overall arthritis compared with previous fortnight; preference for NSAID at the end of each two-week treatment period; use of escape analgesia; side effects; and management changes as a result of the SPTs., Results: Eight of 14 patients completed SPTs. One was a clear responder to NSAIDs, five were non-responders, and two were indefinite. Of the five who were using NSAIDs' before the SPT, two continued and three ceased using them. Clinically useful information assisted decision-making for all eight participants. Medication management changed for six., Conclusions: Single-patient trials can be successfully implemented in general practice and might be a valuable method for GPs to identify patients who respond to medication for chronic stable conditions such as osteoarthritis, in which individual response to medication is variable.

We present a method to estimate the summary receiver operating characteristic (SROC) curve for combining information on a diagnostic test from several different studies. Unlike previous methods that assume the reference standard to be error free, our approach allows for the possibility of errors in the reference standard, through use of a latent class model. The model provides estimates of the sensitivity and specificity of the diagnostic test and the case prevalence in each study; these parameters can then be used in a meta-analysis, for example, using the regression method proposed by Moses et al., of a measure of test discrimination on a measure of the diagnostic threshold, to fit the SROC. The method is illustrated with an example on Pap smears that shows how adjusting for imperfection in the reference standard typically reduces the scatter of data in the SROC plot, and tends to indicate better performance of the test than otherwise.

Objective: To investigate the psychometric properties of a cardiovascular extension of an existing utility-based quality of life questionnaire (Health Measurement Questionnaire). The new instrument has been named the Utility Based Quality of life--Heart questionnaire, or UBQ-H., Design: Explored the test-retest reliability, construct validity, and responsiveness of the UBQ-H., Patients: A sample of 322 patients attending cardiac outpatient clinics were recruited from two large metropolitan teaching hospitals. A second sample of 1112 patients taking part in the LIPID trial was also used to investigate the validity and responsiveness of the UBQ-H., Results: Ninety per cent of all UBQ-H questionnaires were returned, and item completion rates were high (median of less than 1% missing or N/A answers). Cronbach's alpha measure of internal consistency for the scales ranged between 0.79-0.91, and each item was also most strongly correlated with its hypothesised domain than alternative domains. The intra-class test-retest reliability of the UBQ-H scales ranged from 0.65 to 0.81 for patients with stable health. Results supported the construct validity of the UBQ-H. The UBQ-H was significantly correlated with other information on quality of life (for example, General Health Questionnaire) as anticipated. The instrument was able to distinguish between contrasted groups of patients (for example, with versus without symptoms of dyspnoea, prior myocardial infarction versus none, etc), and was responsive to changes in health associated with adverse events requiring hospitalisation., Conclusions: The modifications made to the Health Measurement Questionnaire has resulted in an assessment designed for cardiovascular patients that has proved to be both reliable and valid.

The research literature provides surprisingly little evidence of benefit for initially treating acute otitis media in children with antibiotics. We show how to calculate the amount of benefit and harm from the evidence, and how this might be applied to change management practice.

The Utility-based Quality of Life--Heart Questionnaire (UBQ-H) is a cardiovascular extension of the Health Measurement Questionnaire. It is a multidimensional instrument that can be scored to yield a utility estimate using the Rosser Index and a classification algorithm developed for the Health Measurement Questionnaire. The aim of this study was to employ a statistical modelling approach to devise an improved scoring system. A sample of 201 cardiovascular patients completed the UBQ-H and assessed the utility of their own health state using standard gamble and time trade-off questions in an interview. Two new scoring methods were devised by regressing the UBQ-H data against patients' self-assessed utilities. The new methods gave utility estimates that correlated with angina/dyspnoea grades, life satisfaction scores and General Health Questionnaire (GHQ) scores. In a second sample of 1,112 cardiovascular patients, the UBQ-H utilities were able to distinguish between patients who had/had not experienced an adverse event (e.g. myocardial infarction) and were responsive to changes in health over time. The new scoring methods were not particularly more sensitive to quality of life effects than the original method based on the Rosser Index. However, they produced significantly lower estimates and more accurately reflected patients' self-assessed utilities.

One way of examining trade-offs between quantity and quality of life (QOL) is to combine them into a single measure such as quality-adjusted life year (QALY). If censoring occurs, then estimation presents some difficulties. One approach, known as Q-TWiST, is to define a series of health states, use a 'partitioned' survival analysis to calculate the average time in each state, and then weight each state according to its quality of life to calculate QALYs. Such health-state models, however, are unhelpful when the transitions between health states are unclear or if they do not adequately reflect variations in quality of life. We therefore examine an alternative analysis to be used when repeated measures of quality of life are available from individual patients in a clinical trial. The method proceeds by separating quality of life and survival, that is, dQALY/dt = S(t)Q(t), where S(t) is the survival curve, estimated from the standard Kaplan-Meier method, and Q(t) is the quality of life function, derived from individual repeated measures of quality of life. We derive single health-state (QALY) and multiple health-state (Q-TWiST) models and illustrate the approach by comparing different durations of adjuvant chemotherapy for breast cancer.

The Long-term Intervention with Pravastatin in Ischemic Heart Disease (LIPID) trial is a double-blind, randomized, placebo-controlled trial evaluating the long-term effect of pravastatin on coronary mortality in patients with a previous myocardial infarction or unstable angina-ischemic heart disease (IHD). It is planned to run for at least five years with 9014 patients from 85 centers in Australia and New Zealand. The trial will monitor cause-specific mortality and major clinical events associated with each treatment. Running in parallel with the main study is a prospective economic analysis, the objectives of which are (1) to estimate the effectiveness of pravastatin compared with placebo in terms of survival, quality of life (QOL), and quality-adjusted life-years (QALY); (2) to estimate the resource usage associated with pravastatin compared with placebo-in particular, to study whether it alters resource usage through prevention of disease progression; and (3) to use this information for a cost-utility analysis with cost per quality-adjusted life-year as the unit of analysis. A novel aspect of the design is the use of a preliminary cost-effectiveness analysis, based on "best-guess" values, and a sensitivity analysis over plausible ranges to guide the choice of subsample size. Some data, such a mortality, days spent in hospital, major clinical events, and drug use, are being collected within the main LIPID trial. However, additional subsamples for the cost-effectiveness study will include information on quality of life, time off work, and resources used, such as time in hospital, procedures, and medications taken. The methods and sample sizes for these substudies have been a crucial issue in validity and feasibility.

To which groups of patients can the results of clinical trials be applied? This question is often inappropriately answered by reference to the trial entry criteria. Instead, the benefit and harm (adverse events, discomfort of treatment, etc) of treatment could be assessed separately for individual patients. Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed. To assess net benefit, the relative risks should come from (a meta-analysis of) randomised trials; the risk in individual patients should come from multivariate risk equations derived from cohort studies. However, before making firm conclusions, the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked.

Objective: To carry out a systematic quality review and meta-analysis of all randomised trials of mammographic screening that included women aged under 50 years., Data Sources: Reports of randomised trials of mammographic screening were identified via MEDLINE and checks of the bibliographies of retrieved articles and reviews., Data Synthesis: Identified trials were assessed for: (i) method of randomisation; (ii) documented comparability of baseline data; (iii) standardised criteria for breast cancer death; (iv) blinded review of cause of death; (v) completeness of follow-up; and (vi) use of an "intention-to-treat analysis". Seven randomised trials including almost 160,000 women aged under 50 were studied. The combined estimate of relative risk was 0.95 (95% confidence interval, 0.77-1.18), a statistically non-significant reduction of 5%. Adjustment for the cluster randomisation of two trials, and for degree of compliance, did not substantially change this result., Conclusions: These analyses suggest little, if any, benefit for women under 50 years of age. The results are not explained by the quality of the trials or the radiology. We recommend that women in this age group intending to be screened should be fully informed of these results.

This study examines the feasibility of using Quality-Adjusted Life Years (QALYs) to assess patient outcome and the economic justification of treatment in an Intensive Care Unit (ICU). 248 patients were followed for three years after admission. Survival and quality of life for each patient was evaluated. Outcome for each patient was quantified in discounted Quality-Adjusted Life Years (dQALYs). The economic justification of treatment was evaluated by comparing the total and marginal cost per dQALY for this patient group with the published cost per QALY for other medical interventions. 150 patients were alive after three years. Quality of life for most longterm survivors was good. Patient outcome (QALYs) was greatest for asthma and trauma patients, and least for cardiogenic pulmonary oedema. The tentative estimated cost-effectiveness of treatment varied from AUD $297 per QALY for asthma to AUD $2323 per QALY for patients with pulmonary oedema. This compares favourably with many preventative and non-acute medical treatments. Although the methodology is developmental, the measurement of patient outcome using QALYs appears to be feasible in a general hospital ICU.

This article examines the principles of probability revision and four different ways of obtaining post-test probabilities: the hypothetical cohort method, likelihood ratios and odds, the Nomogram, and precalculation. The authors then show where pre-test probabilities can be obtained, and then how to interpret multiple tests.

I propose a new authority category for the Pharmaceutical Benefits Scheme (PBS)--authority to prescribe only within a controlled trial. This would benefit both the PBS and the pharmaceutical companies, but the main winners would be the Australian population, who would obtain better value for money spent by the PBS. Drugs which show promise, but for which conclusive evidence of advantage over standard therapy is lacking, or drugs for new indications, could be prescribed within a randomised trial. PBS support would fund a substantial portion of the trial costs. This proposal would greatly boost local and international investment in Australian medical research.

Objective: To assess and compare quality of life of patients six months after an acute myocardial infarction treated with one of two thrombolytic agents, streptokinase (SK) or recombinant tissue plasminogen activator (tPA)., Design: A cohort study of consecutive patients randomly allocated to thrombolytic therapy and treated in hospitals participating in the Australian arm of the International tPA/SK Mortality Trial (AUS-TASK)., Patients and Setting: 776 patients with acute myocardial infarction were asked to complete questionnaires at their follow-up clinic visit six months after the infarct., Main Outcome Measures: Two measures were used: (i) the York Health Measurement Questionnaire, which measures activities and distress and provides basic descriptors of quality of life; and (ii) a time trade-off question about the number of years a person would be willing to give up in exchange for returning to full health., Results: The quality of life of the 714 respondents (92%) was generally high, with a mean index of 0.98. The five main areas causing distress were: lack of energy; breathlessness; anxiety; difficulty sleeping; and pain. In the time trade-off question, the mean number of years respondents were willing to forgo, out of 15 years, was 0.87 years; while 76% did not think it worthwhile to forgo any time. The 8% of patients who declined to answer the questionnaire were in significantly poorer health (New York Heart Association classification, P = 0.01; and Karnofsky index, P < 0.001). There were no significant differences in quality of life or time trade-off answers between patients allocated to streptokinase or tPA (P = 0.96 and 0.73, respectively)., Conclusions: Quality of life six months after myocardial infarction is generally high, and most patients are able to return to normal activities. However, it is significantly impaired in a small group of patients, mainly those with a subsequent stroke or re-infarction. There was no significant difference in quality of life between those treated with tPA and those with streptokinase.

Evaluating a screening test often requires estimation of test sensitivity and specificity with appropriately narrow confidence intervals and at least cost. If the major cost is the reference ("gold") standard, savings arise from reducing the large number of test negatives that are verified by the reference standard. On the basis of the formulae of Begg and Greenes (Biometrics 1983;39:207-15), the authors determine the optimal sampling strategy for test positives and test negatives to minimize the total sample size that needs to be verified for a given confidence interval width for sensitivity. Unless sensitivity is very high, verifying more test positives and fewer test negatives than would occur with equal sampling fractions is appropriate. For example, if the sensitivity is 0.7 and the specificity is 0.99, the optimal sampling strategy is for 6.2% of those verified to be test positives, compared with 1.7% in the case of equal sampling fractions. At a disease prevalence of 0.01, the 3.3-fold increase in test positives results in a saving of about 15% in the test negatives and 11% in the total verified sample size. Overall, savings are about 50% for a sensitivity of 0.3, but are negligible when sensitivity is greater than 0.8. Optimal sampling strategies for sensitivity do not materially alter confidence intervals for specificity. Figures are presented from which readers can easily obtain the optimal sampling strategy given an estimate of specificity, approximated by the proportion of screenees who are test negative, and the range of likely sensitivity.

Quality-adjusted life years or QALYs are used to combine, in a single measure, information about the quantity and quality of life produced by a health intervention. They have been used as outcome measures in clinical trials and in cost-effectiveness analyses. This paper describes how QALYs are assessed and how they are used. Methodological and theoretical problems are discussed as are ethical objections to the utilitarian ethos underlying their use. It is concluded that QALYs are part of a technology that is still in development but, because of the lack of alternatives, they will certainly continue to be used. It is important to resolve the outstanding methodological issues and reach an ethical consensus to ensure that QALYs truly reflect community goals.

Objective: To study the effect of vitamin A supplementation on morbidity and mortality from infectious disease., Design: A meta-analysis aimed at identifying and combining mortality and morbidity data from all randomised controlled trials of vitamin A., Results: Of 20 controlled trials identified, 12 trials were randomised trials and provided "intention to treat" data: six community trials in developing countries, three in children admitted to hospital with measles, and three in very low birth weight infants. Combined results for community studies suggest a reduction of 30% (95% confidence interval 21% to 38%; two tailed p < 0.0000001) in all cause mortality. Analysis of cause specific mortality showed a reduction in deaths from diarrhoeal disease (in community studies) by 39% (24% to 50%; two tailed p < 0.00001); from respiratory disease (in measles studies) by 70% (15% to 90%; two tailed p = 0.02); and from other causes of death (in community studies) by 34% (15% to 48%; two tailed p = 0.001). Reductions in morbidity were consistent with the findings for mortality, but fewer data were available., Conclusions: Adequate supply of vitamin A, either through supplementation or adequate diet, has a major role in preventing morbidity and mortality in children in developing countries. In developed countries vitamin A may also have a role in those with life threatening infections such as measles and those who may have a relative deficiency, such as premature infants.

Randomized controlled trials are usually analysed by the group to which the patient was randomized, i.e. by "intention-to-treat", regardless of the degree of compliance. However, the "explanatory" effect, i.e. the effect that would occur if we had 100% compliance, is often of interest. This "explanatory" effect is diluted by poor compliance, and hence meta-analyses should ideally avoid both the heterogeneity of effect due to variation in compliance rates among studies, and the undeserved weight given to trials with poor compliance. Newcombe's deattenuation method, which adjusts estimates for the degree of compliance, is extended and applied to a meta-analysis of the five reported randomized controlled trials of mammographic screening. Compliance with screening varied across studies: from 61 to 93% assigned to screening had one or more mammograms. The adjusted estimate of the reduction in breast cancer mortality at 9 years follow-up is 0.37 (95% confidence interval: 0.21, 0.49).

Meta-analysis is an important part of assessing cost-effectiveness in that it may help determine which treatments are indeed effective and estimate the level of effectiveness of each. Meta-analysis uses the data from all the relevant trials and is a powerful tool for detecting effects too small to be picked up by individual trials. The assessment of quality of studies in a meta-analysis is critical, with priority needing to be given to high quality randomised studies. A written protocol, literature retrieval system, evaluation and selection criteria, choice of endpoints and ways to evaluate bias must all be pre-defined. Nevertheless, problems can arise when meta-analysis is used for cost-effectiveness analysis, due to variation in study medication protocols, duration of follow-up, and difficulties in interpreting patient subgroups and compliance. Despite being subject to the design flaws of both the trials analysed and the methods used in the analysis itself, meta-analysis provides a more objective and thorough means of evaluating effectiveness and hence the cost-effectiveness of treatments. Based on the meta-analysis evidence, we recommend that the current QALY league tables be split into an implementation table for clearly effective therapies, and a research priority table where the evidence of treatment effectiveness is less clear and more research is needed.

Among those decisions that may be made by a patient in response to an illness, the authors single out a certain class: contingent investment decisions. They are characterized by the patient's committing him- or herself, on the basis of prognostic counseling, to a certain action or non-action that he or she may regret in retrospect. Examples show that, when assessing utilities, the decision analyst runs a risk of handling such investment decisions incorrectly, unless they are made explicit and incorporated into the medical decision process. The anomaly is explained as a violation of the structural rules for decision trees and is also interpreted in terms of "the price of prognostic ignorance," a quantity closely related to the expected utility value of perfect information.