13.4 - Phase III Trials

The outline of reports for comparative efficacy trials (Phase III) is similar to that for safety and efficacy trials. There are many additional issues, however, to consider. For example, the reporting of treatment assignment (randomization) and masking procedures is necessary to assure readers about the internal validity of the trial. This is important because readers want to know how this was implemented. This is a mechanism that reviewers will use to assess the validity of the study.

The motivation and assumptions for the target sample size should be included, especially in a situation where the primary results are “negative” findings. The impact of various prognostic variables should be addressed with appropriate statistical analyses to demonstrate that treatment effects are not due entirely to them. Although the intent-to-treat principle should be followed in randomized trials, it is helpful to report on the results of various exploratory analyses as well.

Since the methods have direct implications on the validity of the results, top-line journals require thorough descriptions. They also expect supplemental reports. When the article is available online, there can be links to more detailed descriptions, figures, graphs, and tables.

Conflict of Interest Section

Major medical journals require that manuscript authors report any financial support for the research presented in the article, and complete a form describing their conflicts of interest. The information on the financial support and conflicts usually appears at the end of the article, prior to the references.


In the VALIANT trial (NEJM 2003, in Wk 5 course material) the authors state
  1. “Supported by a grant from Novartis Pharmaceuticals.” and
  2. that some of them also received financial payments from Novartis for serving as consultants, and some of them also have stock equity in Novartis. Anyone who reads the article should attempt to examine the statements about financial support and conflicts, in order to judge whether the article may present a biased viewpoint.
The International Committee of Medical Journal Editors (ICMJE – http://www.icmje.org/) has developed a standardized form for authors to provide information about their financial interests that could influence how their work is viewed. The form is designed to be completed electronically and stored electronically. It contains programming that allows appropriate data display. Each author listed on the manuscript should submit a separate form and is responsible for the accuracy and completeness of the information. The disclosure form is a fillable pdf file (http://www.icmje.org/coi_disclosure.pdf). The complete list of journals that require completion of the ICMJE form appears at http://www.icmje.org/journals.html