Eligibility criteria in clinical trials in breast cancer: a cohort study

Katarzyna Szlezinger; Katarzyna Pogoda; Agnieszka Jagiełło-Gruszfeld; Danuta Kłosowska; Andrzej Górski; Jan Borysowski

doi:10.1186/s12916-023-02947-y

Eligibility criteria in clinical trials in breast cancer: a cohort study

BMC Med. 2023 Jul 3;21(1):240. doi: 10.1186/s12916-023-02947-y.

Authors

Katarzyna Szlezinger¹, Katarzyna Pogoda², Agnieszka Jagiełło-Gruszfeld², Danuta Kłosowska³, Andrzej Górski⁴, Jan Borysowski⁵

Affiliations

¹ Pharmacovigilance Department, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Aleje Jerozolimskie 181C, 02-222, Warsaw, Poland.
² Department of Breast Cancer and Reconstruction Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.
³ Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka 59, 02-006, Warsaw, Poland.
⁴ Bacteriophage Laboratory, Department of Phage Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfe Weigla 12, 53-114, Wrocław, Poland.
⁵ Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka 59, 02-006, Warsaw, Poland. jan.borysowski@wum.edu.pl.

Abstract

Background: Breast cancer (BC) is the most common cancer type in women. The purpose of this study was to assess the eligibility criteria in recent clinical trials in BC, especially those that can limit the enrollment of older patients as well as those with comorbidities and poor performance status.

Methods: Data on clinical trials in BC were extracted from ClinicalTrials.gov. Co-primary outcomes were proportions of trials with different types of the eligibility criteria. Associations between trial characteristics and the presence of certain types of these criteria (binary variable) were determined with univariate and multivariate logistic regression.

Results: Our analysis included 522 trials of systemic anticancer treatments started between 2020 and 2022. Upper age limits, strict exclusion criteria pertaining to comorbidities, and those referring to inadequate performance status of the patient were used in 204 (39%), 404 (77%), and 360 (69%) trials, respectively. Overall, 493 trials (94%) had at least one of these criteria. The odds of the presence of each type of the exclusion criteria were significantly associated with investigational site location and trial phase. We also showed that the odds of the upper age limits and the exclusion criteria involving the performance status were significantly higher in the cohort of recent trials compared with cohort of 309 trials started between 2010 and 2012 (39% vs 19% and 69% vs 46%, respectively; p < 0.001 for univariate and multivariate analysis in both comparisons). The proportion of trials with strict exclusion criteria was comparable between the two cohorts (p > 0.05). Only three of recent trials (1%) enrolled solely patients aged 65 or 70 and older.

Conclusions: Many recent clinical trials in BC exclude large groups of patients, especially older adults, individuals with different comorbidities, and those with poor performance status. Careful modification of some of the eligibility criteria in these trials should be considered to allow investigators to assess the benefits and harms of investigational treatments in participants with characteristics typically encountered in clinical practice.

Keywords: Breast cancer; Clinical trial; Comorbidity; Elderly; Eligibility criteria; Enrollment criteria; Exclusion criteria; Older adult; Performance status.

MeSH terms

Aged
Breast Neoplasms* / epidemiology
Breast Neoplasms* / therapy
Cohort Studies
Comorbidity
Female
Humans