Guidelines for analysis and reporting of clinical trials in oncology.

When analyzing and reporting the results of clinical trials, investigators should follow a simple approach. The purpose of a trial is to estimate an effect or treatment difference, which if present would have clinical utility when treating new patients. Procedures or methods that do not facilitate precisely and impartially estimating and reporting the treatment effect are likely to mislead investigators. Most often in clinical trials, investigators are interested in estimates of risk ratios (specifically odds or hazard ratios) between the treatment groups or levels of a prognostic factor. These simple ideas suggest that the most useful results from clinical trials will be estimated risk ratios and their confidence limits. Especially in cancer, where disease progression, recurrence, and death are common events following treatment, estimates of risk difference are very relevant. Hypothesis tests and associated P-values, although often (or exclusively) reported, are of lesser utility because they do not fully summarize the data. These recommendations may be seen by some investigators to be contrary to accepted practice. It is true that they are somewhat contrary to common practice but their general acceptance is evident in many journals and presentations by clinical trial methodologists. Despite some disagreement among statisticians regarding the need for adjustment of analyses for imbalanced prognostic factors, it is helpful to see if treatment effects change after accounting for imbalances. When this occurs, it may be of clinical interest. Although we discourage analyses that exclude any patients who meet the eligibility criteria, some circumstances will require that this be done (e.g., when a patient refuses to participate after randomization). Investigators should report, and emphasize as primary, those analyses that include all eligible patients. It is our hope and belief that analysis and reporting of trial results along the guidelines suggested here will result in impartial and useful information for journal readers.