No type of study is as influential on subsequent medical decisions as the randomized clinical trial, which, for obvious reasons, sits atop the hierarchy that forms the basis of evidence-based medicine. The primary objective of the randomized trial is to ensure internal validity by precluding the possibility of various biases that can, and do, compromise the reliability of other study designs. For a variety of reasons, however, randomized trials can be corrupted as well. This is arguably a more serious problem than the corruption of observational studies since (1) randomized trials are so much more influential and (2) so many more researchers are dismissive of the very possibility of biases in randomized trials. Probability and statistics have been employed extensively to elucidate the nature of various biases in the randomized trial setting, but, despite these objective foundations, various interpretations remain regarding the best methods to ensure that randomized trials be valid and free of biases. This has led to various controversies in the clinical trial setting, very few of which have been resolved.
More progress is needed in clarifying (1) how best to randomize so as to ensure comparable comparison groups,
(2) how best to use surrogate endpoints so as to obviate the need to simply assume that they can safely supplant the use of clinical endpoints, (3) how best to handle multiple endpoints, many of which will be related to each other in various ways, (4) how best to handle complex data structures, such as repeated measures and multiple survival endpoints, without depending on the usual parametric assumptions, (5) what role should be played by enrichment designs and runin phases so as to ensure that the trial remains valid, (6) how best to ensure globally powerful analyses that can help to reduce sample sizes, (7) how best to handle missing data, taking into consideration whatever may be known about the reason for the data to be missing, and (8) identifying previously unknown (or inadequately studied) threats to the validity of randomized trials. Ideally, this progress should be guided by appeal to reason, logic, probability, and statistics, and not so much by precedent or industry standard.
We invite authors to present original research as well as review articles that will stimulate further e ff orts in correctly applying existing methodologies and developing new methodologies. Potential topics include, but are not limited to:
• Comparisons of randomization procedures for both single-center studies and multicenter studies, taking into consideration how successful any attempt as masking is likely to be
• Discussions of how best to use surrogate endpoints in conjunction with, rather than in lieu of, conventional clinical endpoints
• Comparisons of competing procedures for handling multiple endpoints
• Developments of novel permutation tests for longitudinal data or survival endpoints
• Discussions of how best to utilize enrichment designs to ensure power and validity
• Improvements in testing methodologies that will result in improved power profiles
• Comparisons of competing procedures for handling missing data
• Novel studies that clarify threats to internal validity and remedial actions
• Discussions of nonparametric covariate adjustment
Before submission authors should carefully read over the journal’s Author Guidelines, which are located at http://www.hindawi.com/journals/jps/guidelines/ . Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at http://mts.hindawi.com/ according to the following timetable:
Manuscript Due December 15, 2011
First Round of Reviews March 15, 2012
Publication Date June 15, 2012
Lead Guest Editor
Vance W. Berger, Biometry Research Group, National
Cancer Institute, USA; vb78c@nih.gov
Guest Editors
Simon Day, Roche Products Limited, Welwyn Garden City
AL7 1TW, UK; simon.day@roche.com
Maria Knoll, Johns Hopkins Bloomberg School of Public
Health, Baltimore, USA; mknoll@jhsph.edu
Hindawi Publishing Corporation http://www.hindawi.com/