Summary Correctable weaknesses in the design, conduct, and analysis of biomedical and public health research studies can produce misleading results and waste valuable resources. Small effects can be ...difficult to distinguish from bias introduced by study design and analyses. An absence of detailed written protocols and poor documentation of research is common. Information obtained might not be useful or important, and statistical precision or power is often too low or used in a misleading way. Insufficient consideration might be given to both previous and continuing studies. Arbitrary choice of analyses and an overemphasis on random extremes might affect the reported findings. Several problems relate to the research workforce, including failure to involve experienced statisticians and methodologists, failure to train clinical researchers and laboratory scientists in research methods and design, and the involvement of stakeholders with conflicts of interest. Inadequate emphasis is placed on recording of research decisions and on reproducibility of research. Finally, reward systems incentivise quantity more than quality, and novelty more than reliability. We propose potential solutions for these problems, including improvements in protocols and documentation, consideration of evidence from studies in progress, standardisation of research efforts, optimisation and training of an experienced and non-conflicted scientific workforce, and reconsideration of scientific reward systems.
Summary Background Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are alternative treatments for multivessel coronary disease. Although the procedures have been ...compared in several randomised trials, their long-term effects on mortality in key clinical subgroups are uncertain. We undertook a collaborative analysis of data from randomised trials to assess whether the effects of the procedures on mortality are modified by patient characteristics. Methods We pooled individual patient data from ten randomised trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics. We used stratified, random effects Cox proportional hazards models to test the effect on all-cause mortality of randomised treatment assignment and its interaction with clinical characteristics. All analyses were by intention to treat. Findings Ten participating trials provided data on 7812 patients. PCI was done with balloon angioplasty in six trials and with bare-metal stents in four trials. Over a median follow-up of 5·9 years (IQR 5·0–10·0), 575 (15%) of 3889 patients assigned to CABG died compared with 628 (16%) of 3923 patients assigned to PCI (hazard ratio HR 0·91, 95% CI 0·82–1·02; p=0·12). In patients with diabetes (CABG, n=615; PCI, n=618), mortality was substantially lower in the CABG group than in the PCI group (HR 0·70, 0·56–0·87); however, mortality was similar between groups in patients without diabetes (HR 0·98, 0·86–1·12; p=0·014 for interaction). Patient age modified the effect of treatment on mortality, with hazard ratios of 1·25 (0·94–1·66) in patients younger than 55 years, 0·90 (0·75–1·09) in patients aged 55–64 years, and 0·82 (0·70–0·97) in patients 65 years and older (p=0·002 for interaction). Treatment effect was not modified by the number of diseased vessels or other baseline characteristics. Interpretation Long-term mortality is similar after CABG and PCI in most patient subgroups with multivessel coronary artery disease, so choice of treatment should depend on patient preferences for other outcomes. CABG might be a better option for patients with diabetes and patients aged 65 years or older because we found mortality to be lower in these subgroups. Funding Agency for Healthcare Research and Quality.
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