Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis
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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.71097 |
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| author | Gabrielle Brown Pavlos Msaouel Avital M. Miller Ramez Kouzy Timothy A. Lin Joseph Abi Jaoude Ethan B. Ludmir Alexander D. Sherry |
| author_facet | Gabrielle Brown Pavlos Msaouel Avital M. Miller Ramez Kouzy Timothy A. Lin Joseph Abi Jaoude Ethan B. Ludmir Alexander D. Sherry |
| author_sort | Gabrielle Brown |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9e79fb6da3854032847a62e2157e104e |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-9e79fb6da3854032847a62e2157e104e2025-08-20T03:46:34ZengWileyCancer Medicine2045-76342025-08-011415n/an/a10.1002/cam4.71097Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological AnalysisGabrielle Brown0Pavlos Msaouel1Avital M. Miller2Ramez Kouzy3Timothy A. Lin4Joseph Abi Jaoude5Ethan B. Ludmir6Alexander D. Sherry7Division of Radiation Oncology, Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USADivision of Cancer Medicine, Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USADivision of Radiation Oncology, Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USADivision of Radiation Oncology, Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USADivision of Radiation Oncology, Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Radiation Oncology Stanford University Stanford California USADivision of Radiation Oncology, Department of Gastrointestinal Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USADivision of Radiation Oncology, Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USAABSTRACT 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.https://doi.org/10.1002/cam4.71097biasblinded independent central reviewdouble‐blindoncologyPhase IIIrandomized trials |
| spellingShingle | Gabrielle Brown Pavlos Msaouel Avital M. Miller Ramez Kouzy Timothy A. Lin Joseph Abi Jaoude Ethan B. Ludmir Alexander D. Sherry Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis Cancer Medicine bias blinded independent central review double‐blind oncology Phase III randomized trials |
| title | Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis |
| title_full | Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis |
| title_fullStr | Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis |
| title_full_unstemmed | Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis |
| title_short | Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta‐Epidemiological Analysis |
| title_sort | patient physician and assessor blinding in phase iii randomized trials in oncology a meta epidemiological analysis |
| topic | bias blinded independent central review double‐blind oncology Phase III randomized trials |
| url | https://doi.org/10.1002/cam4.71097 |
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