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

Abstract

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 published between January 1, 2011, and December 31, 2013, were reviewed to identify eligible studies of solid tumor treatments. Information related to the subgroup analyses included prespecification, number, subgroup factors, interaction test use, and claim of subgroup difference.

Results: A total of 221 publications reporting data on 184,500 patients were analyzed. One hundred eighty-eight (85%) RCTs were reported with subgroup analyses. Of those, 146 (78%) trials were reported with at least six subgroups. For the majority of trials with subgroup analyses (173; 92%), the actual number of subgroup analyses conducted cannot be determined. Only 59 (31%) RCTs were reported with fully prespecified subgroups and only 64 (34%) trials were reported with interaction tests. In addition, 102 (54%) RCTs were reported with claims of subgroup differences. Of those, only 18 claims of RCTs (18%) were based on significant interaction test results.

Conclusion: The reporting of subgroup analyses in contemporary oncology RCTs is neither uniform nor complete; it requires improvement to ensure consistency and to provide critical information for guiding patient care. Major problems include testing of a large number of subgroups, subgroups without prespecifications, and inadequate use of interaction tests.