Significant discrepancies found in reporting of protocol eligibility criteria changes in oncology clinical trials

There are substantial rates of changes in patient eligibility criteria known as protocol eligibility criteria changes (PEP), according to results of a recent cross-sectional study examining oncology randomized clinical trials (RCTs).

The analysis included complete oncology Phase 3 RCTs registered on ClinicalTrials.gov and assesed PEP changes with tracking changes on ClinicalTrials.gov, self-reported changes in the article, and changes reported within the protocol documents. Logistic regression analyses were conducted to evaluate the association between PEP changes and both US Food and Drug Administration approval and trial positivity.

Out of the 755 trials included in the study, 145 (19.2%) were found to have PEP changes according to at least 1 of the 3 detection methods. Of note, 102 of the 145 trials (70.3%) did not disclose PEP changes within the published manuscripts. The rates of PEP detection varied significantly across the 3 methods employed.

Further analysis revealed that the detection of PEP changes was higher when multiple versions of the protocol were available (31.8%) compared to having only 1 version (16.4%) or no protocol available (16.1%). Multivariable analysis demonstrated a significant association between PEP changes and trial positivity (odds ratio, 1.86; 95% CI, 1.25-2.82; P = 0.003).

“Significant discrepancies in the rate of detected PEP changes call into question the role of increased protocol transparency and completeness in identifying key changes occurring in active trials,” the authors concluded.

Reference
Florez MA, Jaoude JA, Patel RR, et al. Incidence of Primary End Point Changes Among Active Cancer Phase 3 Randomized Clinical Trials. JAMA Netw Open. 2023;6(5):e2313819. doi: 10.1001/jamanetworkopen.2023.13819. PMID: 37195664; PMCID: PMC10193180.