Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour
| Autor: | Kexin Deng, Jieyu Wu, Difei Chen, Jianxing He, Lindsey Hamblin, Qihua He, Jiaxuan Xu, Jianrong Zhang, Xinyu Wang, Zhiheng Xu, Shuhan Jiang, Hengrui Liang, Yu Huang, Long Jiang, Jiaqing Zhou, Yaoqi Chen, Yiyin Zhang, Jiaxi He, Wenhua Liang, Shiyan Tang, Xuanzuo Chen |
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| Rok vydání: | 2018 |
| Předmět: |
Solid tumour
medicine.medical_specialty business.industry Statistics as Topic General Medicine Disease control Response assessment 03 medical and health sciences 0302 clinical medicine Treatment Outcome Bias Clinical Trials Phase III as Topic 030220 oncology & carcinogenesis Internal medicine Neoplasms Correlation analysis medicine Clinical endpoint Humans Treatment effect Tumor type 030212 general & internal medicine business Objective response Randomized Controlled Trials as Topic |
| Zdroj: | BMJ open. 8(9) |
| ISSN: | 2044-6055 |
| Popis: | ObjectiveUnbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.DesignLiterature review, pooling analysis and correlation analysis.Data sourcesPubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studiesEligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.ResultsOf 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, pConclusionsNo systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments. |
| Databáze: | OpenAIRE |
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