PASSReviewer 1· 90% conf
The trial design is rigorous: randomized, open-label, with stratification, prespecified endpoints, and a statistical analysis plan for the biomarker analyses.
Evidence
direct quote[Methods, Trial design, participants and treatments]
“Participants were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg intravenously once every 3 weeks for up to 35 cycles (~2 years) plus axitinib 5 mg by mouth twice daily continuously or sunitinib 50 mg by mouth once daily for 4 weeks on and 2 weeks off, continuously. Randomization was stratified according to the IMDC risk group (favorable versus intermediate versus poor risk) and by geographic region (North America versus Western Europe versus rest of the world).”paraphrase[Methods, Inclusion and ethics]
“KEYNOTE-426 ( NCT02853331 ) is a randomized, open-label, phase 3 trial conducted across 129 medical centers globally.”direct quote[Methods, Statistical analysis]
“The biomarker analysis followed a statistical analysis plan written before merging of the clinical data with biomarker assessment, specifying where statistical testing would be used and what biomarker cutoffs defined the subgroups for treatment arm comparisons.”WARNReviewer 2· 85% conf
The study design is a randomized open-label trial, but several methodological details are insufficiently reported, such as the randomization method, blinding rationale, and a priori power analysis, leading to a warning.
Evidence
direct quote[Methods, Trial design, participants and treatments]
“Participants were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg intravenously once every 3 weeks for up to 35 cycles (~2 years) plus axitinib 5 mg by mouth twice daily continuously or sunitinib 50 mg by mouth once daily for 4 weeks on and 2 weeks off, continuously.”paraphrase[Methods, Inclusion and ethics]
“KEYNOTE-426 (NCT02853331) is a randomized, open-label, phase 3 trial conducted across 129 medical centers globally.”paraphrase[Methods, Statistical analysis]
“The paper does not mention a sample size calculation; it states that the present analysis is exploratory and no formal hypothesis testing was performed.”WARNReviewer 3· 80% conf
The study design is reported but lacks details on randomization method, blinding rationale, and power analysis, while inclusion/exclusion criteria and analysis population are adequately defined.
Evidence
direct quote[Methods, 'Trial design, participants and treatments']
“Participants were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg intravenously once every 3 weeks for up to 35 cycles (~2 years) plus axitinib 5 mg by mouth twice daily continuously or sunitinib 50 mg by mouth once daily for 4 weeks on and 2 weeks off, continuously.”paraphrase[Methods, 'Inclusion and ethics']
“KEYNOTE-426 (NCT02853331) is a randomized, open-label, phase 3 trial”direct quote[Methods, 'Trial design, participants and treatments']
“eligible participants were adults with newly diagnosed stage IV or recurrent clear cell RCC who had not previously received systemic therapy for advanced disease. Participants had a Karnofsky Performance Scale score of 70% or higher at baseline, one or more measurable lesions per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by the investigator and a tumor sample available for biomarker assessment.”