Faculty, Staff and Student Publications

Publication Date

8-1-2025

Journal

Cancer Medicine

DOI

10.1002/cam4.71097

PMID

40879280

PMCID

PMC12313818

PubMedCentral® Posted Date

7-31-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression-free survival (PFS). Here, we characterize utilization of and factors associated with blinding in Phase III oncology trials with PFS primary endpoints.

Methods: Two-arm, superiority-design trials investigating systemic therapy were identified in May 2024 from ClinicalTrials.gov with no date limitation. Trials were required to have a PFS primary endpoint. The study outcomes were the presence of double-blind designs and blinded independent central review (BICR) for the primary endpoint. Ninety-five percent credible intervals for binary outcomes were estimated from beta distributions, and multivariable logistic regressions explored associations with trial-level features.

Results: After screening, 237 trials were included, enrolling 127,518 patients. A double-blind design was used in 105 trials (44%, 95% CrI 38%-51%). BICR was used in 111 trials (47%, 95% CrI 41%-53%), including 39 double-blind trials (16%, 95% CrI 12%-22%). Trials with BICR had higher odds of meeting the primary endpoint (OR 1.84; 95% CI 1.06-3.18; p = 0.03). The PFS assessor identity (central vs. local) or blinding status was not reported in 50 trials (26%, 95% CrI 16%-27%). Trials that met prespecified significance criteria for PFS were more likely to report whether PFS assessors were blinded/unblinded and central/local (OR, 3.05; 95% Cl: 1.60-5.81; p = 0.0007).

Conclusions: Despite the importance of double blinding in combination with BICR for reducing bias, only a few trials blinded physicians, patients, and primary endpoint assessors. This meta-epidemiological study illuminates the prevalence of potential assessment biases affecting PFS in Phase III oncology and secondarily emphasizes the need for improved methodology reporting.

Keywords

Humans, Clinical Trials, Phase III as Topic, Randomized Controlled Trials as Topic, Double-Blind Method, Neoplasms, Medical Oncology, Progression-Free Survival, Research Design, Physicians, bias, blinded independent central review, double‐blind, oncology, Phase III, randomized trials

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.