# Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis

## TL;DR

This study examines how often blinding is used in cancer trials to reduce bias, finding that only about half of the trials use blinding methods.

## Contribution

The study provides a meta-epidemiological analysis of blinding practices in Phase III oncology trials with progression-free survival endpoints.

## Key findings

- Double-blind designs were used in 44% of the 237 analyzed Phase III oncology trials.
- Trials using blinded independent central review had higher odds of meeting primary endpoints.
- Only 16% of trials combined double blinding with blinded independent central review.

## Abstract

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.

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.

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).

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.

Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression‐free survival (PFS), although it is unclear how often Phase III oncology trials utilize blinding. After reviewing 237 trials, a double‐blind design was used in 105 trials, and blinded independent central review was used in 111 trials, including in 39 double‐blind trials. Despite the importance of double blinding in combination with BICR for reducing bias, only a few trials blinded physicians, patients, and primary endpoint assessors.