In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

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Objective To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions. Design Systematic review and meta-regression analysis of randomised controlled trials. Data sources Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field. Study selection In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months. Data extraction and synthesis Using standardised, prepiloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated.

Use of composite end points as the main outcome in randomised trials can hide wide differences in the individual measures. How should you apply the results to clinical practice? Improvements in medical care over the past two decades have decreased the frequency with which patients with common conditions such as myocardial infarction develop subsequent adverse events. Although welcome for patients, low event rates provide challenges for clinical investigators, who consequently require large sample sizes and long follow up to test the incremental benefits of new treatments. Clinical trialists have responded to these challenges by relying increasingly on composite end points, which capture the number of patients experiencing any one of several adverse events-for example, death, myocardial infarction, or hospital admission. 1 Use of composite end points is usually justified by the assumption that the effect on each of the components will be similar and that patients will attach similar importance to each component. 1 But this is not always the case. In this article we provide a strategy to interpret the results of clinical trials when investigators measure the effect of treatment on an aggregate of end points of varying importance. Example caseConsider a 76 year old man who has disabling angina despite taking blockers, nitrates, aspirin, an angiotensin converting enzyme inhibitor, and a statin. His doctor suggests cardiac catheterisation and possible revascularisation. The patient is reluctant to have invasive management, and wonders how much benefit he might expect from surgery.The trial of invasive versus medical therapy in elderly patients (TIME) is relevant. 2 The study randomised 301 patients aged 75 years or older with resistant angina to optimised drug treatment or cardiac catheterisation and possible revascularisation. Although the groups showed no difference in quality of life at 12 months, the frequency of a composite end point (death, non-fatal myocardial infarction, and hospital admission for acute coronary syndrome) was much lower in the revascularisation group (25.5%) than in the medical management arm (64.2%; hazard ratio 0.31, 95% confidence interval 0.21 to 0.45).Although the overall result suggests invasive treatment would be beneficial, marked differences existed in the absolute reduction in risk across components (table 1). In the invasive group, five more patients died but there were six fewer myocardial infarctions and 78 fewer hospital admissions. How should you interpret these results and inform the patient? Evaluating composite end pointsClinicians can use three questions to help decide whether to base a clinical decision on the effect of treatment on a composite end point or on the component end points (box). We will not expand on statistical issues here, but box A on bmj.com gives a brief outline. Importance of individual components to patientsWhen all components of a composite end point are of equal importance to the patient, it will not be misleading to assume that the effect of the int...

Background— The diagnosis of infective endocarditis (IE) in prosthetic valves and intracardiac devices is challenging because both the modified Duke criteria (DC) and echocardiography have limitations in this population. The added value of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18 F-FDG PET/CT angiography (PET/CTA) was evaluated in this complex scenario at a referral center with a multidisciplinary IE unit. Methods and Results— Ninety-two patients admitted to our hospital with suspected prosthetic valve or cardiac device IE between November 2012 and November 2014 were prospectively included. All patients underwent echocardiography and PET/CT, and 76 had cardiac CTA. PET/CT and echocardiography findings were evaluated and compared, with concordant results in 54% of cases (κ=0.23). Initial diagnoses with DC at admission, PET/CT, and DC+PET/CT were compared with the final diagnostic consensus reached by the IE Unit. DC+PET/CT enabled reclassification of 90% of cases initially classified as possible IE with DC and provided a conclusive diagnosis (definite/rejected) in 95% of cases. Sensitivity, specificity, and positive and negative predictive values were 52%, 94.7%, 92.9%, and 59.7% for DC; 87%, 92.1%, 93.6%, and 84.3% for PET/CT; and 90.7%, 89.5%, 92%, and 87.9% for DC+PET/CT. Use of PET/CTA yielded even better diagnostic performance values than PET/nonenhanced CT (91%, 90.6%, 92.8%, and 88.3% versus 86.4%, 87.5%, 90.2%, and 82.9%) and substantially reduced the rate of doubtful cases from 20% to 8% ( P <0.001). DC+PET/CTA reclassified an additional 20% of cases classified as possible IE with DC+PET/nonenhanced CT. In addition, PET/CTA enabled detection of a significantly larger number of anatomic lesions associated with active endocarditis than PET/nonenhanced CT ( P =0.006) or echocardiography ( P <0.001). Conclusions— 18 F-FDG PET/CT improves the diagnostic accuracy of the modified DC in patients with suspected IE and prosthetic valves or cardiac devices. PET/CTA yielded the highest diagnostic performance and provided additional diagnostic benefits.