In:
BMJ Open, BMJ, Vol. 8, No. 9 ( 2018-09), p. e017240-
Abstract:
Unbiased 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. Design Literature review, pooling analysis and correlation analysis. Data sources PubMed, from 1 January 2010 to 30 June 2017. Eligibility criteria for selecting studies Eligible 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. Results Of 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, I 2 =0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I 2 =0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I 2 =0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I 2 =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, p 〈 0.01; TTP: r=0.90, p=0.29). Conclusions No 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.
Type of Medium:
Online Resource
ISSN:
2044-6055
,
2044-6055
DOI:
10.1136/bmjopen-2017-017240
DOI:
10.1136/bmjopen-2017-017240.supp7
DOI:
10.1136/bmjopen-2017-017240.supp1
DOI:
10.1136/bmjopen-2017-017240.supp2
DOI:
10.1136/bmjopen-2017-017240.supp8
DOI:
10.1136/bmjopen-2017-017240.supp3
DOI:
10.1136/bmjopen-2017-017240.supp4
DOI:
10.1136/bmjopen-2017-017240.supp5
DOI:
10.1136/bmjopen-2017-017240.supp6
Language:
English
Publisher:
BMJ
Publication Date:
2018
detail.hit.zdb_id:
2599832-8
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