Randomized and non-randomized patients in clinical trials: experiences with comprehensive cohort studies

Stat Med. 1996 Feb 15;15(3):263-71. doi: 10.1002/(SICI)1097-0258(19960215)15:3<263::AID-SIM165>3.0.CO;2-K.

Abstract

In clinical research, randomized trials are widely accepted as the definitive method of evaluating the efficacy of therapies. Random assignment of patients to treatment ensures internal validity of the comparison of new treatments with controls. An assessment of external validity can best be achieved by comparing the randomized study sample to the population of patients who met the eligibility criteria but did not consent to randomization. The Comprehensive Cohort Study (CCS) is designed to recruit all patients fulfilling the clinical eligibility criteria regardless of their consent to randomization. The CCS concept was adopted in the major clinical trials of the German Breast Cancer Study Group (GBSG) conducted between 1983 and 1989. In this period 124 centres recruited 2084 patients in three clinical trials. 734 (35 per cent) of these patients accepted being randomized, while 1350 (65 per cent) chose one of the treatments under study; the randomization rates differed remarkably between trials. In this paper we examine the representativeness of the randomized patients in the three trials. Based on a median follow-up of about 5 years we present results on the external validity of the treatment effects estimated in the randomized patients by means of Cox's proportional hazards model and compare them between trials. We discuss advantages and disadvantages of the CCS design and conclude that its use is only justified under extraordinary circumstances.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cohort Studies
  • Combined Modality Therapy
  • Data Interpretation, Statistical
  • Disease-Free Survival
  • Female
  • Humans
  • Neoplasm Staging
  • Proportional Hazards Models
  • Reproducibility of Results
  • Treatment Outcome