Publishing the findings of clinical research.

Current regulations and practice may not prevent a sponsor of clinical research from delaying or preventing the dissemination of findings that do not support his or her commercial, professional, or managerial interests. Pharmaceutical trials are particularly subject to this concern, but the issue of non-publication has a wider significance. Patients participate in research on the understanding that it will be of public benefit. To be fair to these patients we must confirm that data will be analysed without bias and that findings will be regarded as being in the public domain and hence available to interested reviewers even if the results do not justify publication. Clinical investigators and ethics committees have the power and the duty to enforce this outcome.     

Meta-analysis: synthesizing research findings in ecology and evolution

The growing number of empirical studies performed in ecology and evolution creates a need for quantitative summaries of research domains to generate higher-order conclusions about general trends and patterns. Recent developments In meta-analysis (the area of statistics that is designed for summarizing and analyzing multiple independent studies) have opened up new and exciting possibilities. Unlike more traditional qualitative and narrative reviews, meta-analysis allows powerful quantitative analyses of the magnitude of effects and has a high degree of objectivity because it is based on a standardized set of statistical procedures. The first pioneering applications in ecology and evolution demonstrate that meta-analysis is both tractable and powerful.     

Meta-analysis of clinical trials with competing time-to-event endpoints

Recommendations for the analysis of competing risks in the context of randomized clinical trials are well established. Meta-analysis of individual patient data (IPD) is the gold standard for synthesizing evidence for clinical interpretation based on multiple studies. Surprisingly, no formal guidelines have been yet proposed to conduct an IPD meta-analysis with competing risk endpoints. To fill this gap, this work details (i) how to handle the heterogeneity between trials via a stratified regression model for competing risks and (ii) that the usual metrics of inconsistency to assess heterogeneity can readily be employed. Our proposal is illustrated by the re-analysis of a recently published meta-analysis in nasopharyngeal carcinoma, aiming at quantifying the benefit of the addition of chemotherapy to radiotherapy on each competing endpoint.     

Meta-analysis and its problems.

Including all relevant material--good, bad, and indifferent--in meta-analysis admits the subjective judgments that meta-analysis was designed to avoid. Several problems arise in meta-analysis: regressions are often non-linear; effects are often multivariate rather than univariate; coverage can be restricted; bad studies may be included; the data summarised may not be homogeneous; grouping different causal factors may lead to meaningless estimates of effects; and the theory-directed approach may obscure discrepancies. Meta-analysis may not be the one best method for studying the diversity of fields for which it has been used.     

Gonorrhea and the beginnings of clinical research ethics

Research on ocular inflammation associated with gonorrhea began in conjunction with the entry of trachoma into Europe during the Napoleonic wars. The initial questions involved the cause of the contagiousness of gonorrhea and how the contagion spreads from the genitalia to other sites. Because efforts to infect animals with gonorrheal matter were unsuccessful, all experiments were conducted on human subjects. Once these two causes of blindness were tentatively differentiated, attempts to restore vision in an eye that had been blinded by a trachomatous membrane over the cornea by instilling gonorrheal pus began to be practiced. In 1841, Joseph Piringer described his use of this method to determine infectiousness decades before the discovery of pathogenic bacteria, as well as ethical concerns about the associated endangerment of patients. Beginning in the 1880s, research focused on the identification of the gonococcus and assessment of its pathogenicity.The ethical dilemma of inducing a disease with an unpredictable outcome persisted until the 1940s, when gonorrhea could be reliably cured by penicillin.