دورية أكاديمية
Strength of Statistical Evidence for the Efficacy of Cancer Drugs: A Bayesian Re-Analysis of Randomized Trials Supporting FDA Approval.
| العنوان: | Strength of Statistical Evidence for the Efficacy of Cancer Drugs: A Bayesian Re-Analysis of Randomized Trials Supporting FDA Approval. |
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| المؤلفون: | Pittelkow MM; Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, the Netherlands; QUEST Center for Responsible Research, Berlin Institute of Health at Charité, Berlin, Germany. Electronic address: merle-marie.pittelkow@bih-charite.de., Linde M; Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, the Netherlands; GESIS - Leibniz Institute for the Social Sciences, Cologne, Germany., Anna de Vries Y; Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Hemkens LG; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA; Meta-Research Innovation Center Berlin (METRIC-B), Berlin Institute of Health, Berlin, Germany., Schmitt AM; Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland; Department of Medical Oncology, University Hospital Basel, Basel, Switzerland., Meijer RR; Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, the Netherlands., van Ravenzwaaij D; Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, the Netherlands. |
| المصدر: | Journal of clinical epidemiology [J Clin Epidemiol] 2024 Jul 22, pp. 111479. Date of Electronic Publication: 2024 Jul 22. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 8801383 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5921 (Electronic) Linking ISSN: 08954356 NLM ISO Abbreviation: J Clin Epidemiol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York : Elsevier Original Publication: Oxford ; New York : Pergamon Press, c1988- |
| مستخلص: | Objective: To quantify the strength of statistical evidence of randomised controlled trials (RCTs) for novel cancer drugs approved by the Food and Drug Administration (FDA) in the last two decades. Study Design and Setting: We used data on overall survival (OS), progression-free survival (PFS), and tumour response (TR) for novel cancer drugs approved for the first time by the FDA between January 2000 and December 2020. We assessed strength of statistical evidence by calculating Bayes Factors (BFs) for all available endpoints, and we pooled evidence using Bayesian fixed-effect meta-analysis for indications approved based on two RCTs. Strength of statistical evidence was compared between endpoints, approval pathways, lines of treatment, and types of cancer. Results: We analysed the available data from 82 RCTs corresponding to 68 indications supported by a single RCT and seven indications supported by two RCTs. Median strength of statistical evidence was ambiguous for OS (BF = 1.9; IQR 0.5-14.5), and strong for PFS (BF = 24,767.8; IQR 109.0-7.3*10 6 ) and TR (BF = 113.9; IQR 3.0-547,100). Overall, 44 indications (58.7%) were approved without clear statistical evidence for OS improvements and seven indications (9.3%) were approved without statistical evidence for improvements on any endpoint. Strength of statistical evidence was lower for accelerated approval compared to non-accelerated approval across all three endpoints. No meaningful differences were observed for line of treatment and cancer type. Limitations: This analysis is limited to statistical evidence. We did not consider non-statistical factors (e.g., risk of bias, quality of the evidence). Conclusion: BFs offer novel insights into the strength of statistical evidence underlying cancer drug approvals. Most novel cancer drugs lack strong statistical evidence that they improve OS, and a few lack statistical evidence for efficacy altogether. These cases require a transparent and clear explanation. When evidence is ambiguous, additional post-marketing trials could reduce uncertainty. (Copyright © 2024. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Bayes Factor; cancer drugs; evidence; overall survival; regulatory approval |
| تواريخ الأحداث: | Date Created: 20240724 Latest Revision: 20240724 |
| رمز التحديث: | 20240726 |
| DOI: | 10.1016/j.jclinepi.2024.111479 |
| PMID: | 39047916 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1878-5921 |
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| DOI: | 10.1016/j.jclinepi.2024.111479 |