Lessons from Recent Phase III Trial Failures: Don't Design Phase III Trials Based on Retrospective Subgroup Analyses from Phase II Trials

Design of Phase III Clinical Trials

Sequential design of phase II-III cancer trials.

Although traditional phase II cancer trials are usually single arm, with tumor response as endpoint, and phase III trials are randomized and incorporate interim analyses with progression-free survival or other failure time as endpoint, this paper proposes a new approach that seamlessly expands a randomized phase II study of response rate into a randomized phase III study of time to failure. Thi...

Using meta-analysis of Phase II trials to predict Phase III trial results

Methods We consider a meta-analysis of nine randomised Phase II trials comparing the efficacy of two therapies for acute myocardial infarction. Results for four outcomes were collected: intracranial haemorrhage, stroke, reinfarction and total mortality. We apply univariate and multivariate random-effects meta-analysis methods, and use the obtained summary results to derive 95% prediction interv...

Subgroup Analyses in Reporting of Phase III Clinical Trials in Solid Tumors.

PURPOSE Treatment decisions in clinical oncology are guided by results from phase III randomized clinical trials (RCTs). The results of subgroup analyses may be potentially important in individualizing patient care. We investigated the appropriateness of the use and interpretation of subgroup analyses in oncology RCTs on the basis of the CONSORT statement requirements. METHODS Phase III RCTs ...

Novel methodologic approaches to phase I, II, and III trials.