Cochrane Collaboration

About: Cochrane Collaboration is a nonprofit organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Systematic review & Randomized controlled trial. The organization has 1995 authors who have published 3928 publications receiving 382695 citations.

Are experimental treatments for cancer in children superior to established treatments? Observational study of randomised controlled trials by the Children's Oncology Group.

Abstract: Objectives To assess how often new treatments for childhood cancer assessed in phase III randomised trials are superior or inferior to standard treatments and whether the pattern of successes and failures in new treatments is consistent with uncertainty being the ethical basis for enrolling patients in such trials. Design Observational study. Setting Phase III randomised controlled trials carried out under the aegis of the Children9s Oncology Group between 1955 and 1997, regardless of whether they were published. Main outcome measures Overall survival, event free survival, and treatment related mortality. Results 126 trials were included, involving 152 comparisons and 36 567 patients. The odds ratio for overall survival with experimental treatments was 0.96 (99% confidence interval 0.89 to 1.03), indicating that new treatments are as likely to be inferior as they are to be superior to standard treatments. This result was not affected by publication bias, methodological quality, treatment type, disease, or comparator. Conclusions New treatments in childhood cancer tested in randomised controlled trials are, on average, as likely to be inferior as they are to be superior to standard treatments, confirming that the uncertainty principle has been operating.

Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis

Abstract: To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC0-8) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC0-8 indinavir decreased by 4.4% (90% CI, −27.5% to −26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, −37.3% to +9%, P=0.25) in phase III. Control group mean AUC0-8 decreased by 21.5% (90% CI, −43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, −55.3% to −15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle–indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle–indinavir trials revealed a non-significant pooled mean difference of 1% in AUC0-8 (95% CI, −53% to 55%, P=0.97). Indinavir levels were not reduced significantly in the presence of milk thistle.

The challenges of systematically reviewing public health interventions.

Abstract: Evidence-based public health concerns the development and implementation of effective programmes and policies. For policy makers and practitioners to implement effective programmes they must have considered the information that is available on which interventions have been shown to work, or not to work (or caused harm). One form of high quality evidence-based information available to decision makers is a systematic review of research of effectiveness. A systematic review is defined as ‘a review of a clearly formulated question that uses systematic and explicit methods to identify, select and critically appraise relevant research, and to collect and analyse data from the studies included in the review’. Many of the tools of research synthesis were developed by American social scientists in the 1960s. However, today’s focus on evidence in health has been largely driven by the evidencebased medicine movement. Some authors have argued that there are concerns that in cost-conscious environments only those interventions for which there is sufficient evidence to complete a review would be supported. In public health the infrastructure that supports and enables the conduct of a review lags behind that of evidence-based medicine and extends beyond the employment of randomized controlled trials. This increased complexity has resulted in an unfortunate focus on the appropriateness (or not) of randomized controlled trials as the priority study design rather than what constitutes evidence in public health and how this should be evaluated. However, after diverging views, the focus has now moved towards ensuring that reviews in public health meet the needs of public health practitioners. Conducting systematic reviews of complex public health interventions is methodologically challenging. The following section outlines many of the issues faced when reviewing evidence of public health intervention effectiveness.

Tea Consumption and Health Outcomes: Umbrella Review of Meta-Analyses of Observational Studies in Humans.

Abstract: Scope The aim of this article is to conduct an umbrella review to study the strength and validity of associations between tea consumption and diverse health outcomes. Methods and results Meta-analyses of observational studies examining associations between tea consumption and health outcomes in all human populations and settings are screened. The umbrella review identifies 96 meta-analyses with 40 unique health outcomes. Tea consumption shows greater benefits than harm to health in this review. Dose-response analyses of tea consumption indicates reduced risks of total mortality, cardiac death, coronary artery disease, stroke, and type 2 diabetes mellitus with increment of two to three cups per day. Beneficial associations are also found for several cancers, skeletal, cognitive, and maternal outcomes. Harmful associations are found for esophageal and gastric cancer when the temperature of intake is more than 55-60 °C. Conclusion Tea consumption, except for very hot tea, seems generally safe at usual levels of intake, with summary estimates indicating the largest reduction for diverse health outcomes at two to three cups per day. Generally, tea consumption seems more beneficial than harmful in this umbrella review. Randomized controlled trials are further needed to understand whether the observed associations are causal.