Evaluation of the representativeness and generalizability of Japanese clinical trials for localized rectal/colon cancer: Comparing participants in the Japan Clinical Oncology Group study with patients in Japanese registries

Abstract Introduction It is unclear if clinical trial results including patients who meet trial eligibility criteria, are applicable to actual patients in daily practice (generalizability). Moreover, the extent to which are trial participants different from patients seen in daily practice (representativeness) is also unclear. The aim of this study was to evaluate the representativeness of the patients registered in randomized clinical trials to patients in daily practice and examine the generalizability of trial results to daily practice. Methods We compared the results of surgical trials conducted by the Japan Clinical Oncology Group with data from two Japanese cancer registries, representing patients seen in daily practice. We compared overall survival (OS) between trial participants and registry patients to evaluate representativeness of trial participants. We then compared the OS of registry patients who received open surgery (OP) and laparoscopic surgery (LAP) to evaluate the generalizability of trial results. Results We analyzed 3,051 patients (701 in JCOG0212, 2,350 registry patients) with rectal cancer and 3,116 patients (1,057 in JCOG0404, 2,059 registry patients) with colon cancer. Trial participants tended to possess lower clinical stages. Multivariable analyses revealed registry patients with significantly worse survival compared with trial participants. The hazard ratio of LAP to OP among registry patients was 0.305 (95% CI; 0.048–2.188), which did not meet the prespecified generalizability criteria of 0.9. Conclusions Our results failed to ensure either the representativeness or generalizability of clinical trial results, compared to daily practice. Careful considerations are required when applying trial results to patients in daily practice.