Eligibility criteria in randomized phase II and III adjuvant and neoadjuvant breast cancer trials: not a significant barrier to enrollment

Clin Trials. 2012 Oct;9(5):652-9. doi: 10.1177/1740774512456453.

Abstract

Background: Clinical trial recruitment can be impeded by eligibility criteria being too numerous or too restrictive.

Purpose: This study's principal objective was to determine whether a specific category of eligibility criteria could be identified as a major barrier to patient enrollment.

Methods: Nine phase II or III clinical trials, opened between June 2004 and July 2008, were selected. A retrospective cohort of women diagnosed with invasive, nonmetastatic breast cancer and potentially eligible for these clinical trials was used. All eligibility criteria were sorted into the following categories: definition of disease, precision, safety, ethical and legal, or administrative. A total of 985 patient-trials were evaluated, defined as the experimental unit since one patient could be eligible to more than one trial. Proportions of cases with 'not met' eligibility criteria were assessed for each category in each trial.

Results: Two clinical trials had a 'not met' subcategory criterion of over 20%. 'Pathology' and 'consent' subcategory criteria were 'not met' in 24.2% and 92.7% of cases for the NEOCAN and NCIC CTG MA.27 trials, respectively. NCIC CTG MA.27 had the highest proportion of 'not met' subcategory due to an inclusion criterion requiring participation to two companion studies. National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 had a proportion of 18.8% of cases 'not meeting' the receptor status subcategory criterion. All other subcategories of eligibility criteria assessed were 'not met' by less than 15% of patients. Overall, few subcategories had over 10% of ineligible patients.

Limitations: Many eligibility criteria were considered 'nonevaluable' because the information evaluated would have required additional procedures not performed as part of the general practice.

Conclusion: The subjects from the study population are not precluded from entry in a trial because of stringent eligibility criteria. Eligibility criteria should reflect as much as possible the whole population to whom the treatment will be offered, with the exception of drugs targeting a specific receptor or pathway where only a subpopulation is hypothesized to benefit from the therapy. In the breast cancer clinical trials evaluated for the present study, no criterion precluding recruitment was shared by many or all trials and no specific eligibility criterion was consistently the reason for patients' ineligibility.

MeSH terms

  • Age Factors
  • Breast Neoplasms / therapy*
  • Clinical Trials, Phase II as Topic / methods*
  • Clinical Trials, Phase III as Topic / methods*
  • Female
  • Humans
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Patient Selection*
  • Randomized Controlled Trials as Topic / methods*
  • Retrospective Studies