Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration
| Autor: | Luis P Del Carpio, Joseph C. Del Paggio, Agustí Barnadas, Eitan Amir, Arnoud J. Templeton, Ariadna Tibau, Alberto Ocaña, Christopher M. Booth, Consolación Molto |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Cancer Research medicine.medical_specialty Surrogate endpoint business.industry medicine.medical_treatment media_common.quotation_subject Odds ratio Confidence interval law.invention Food and drug administration 03 medical and health sciences 0302 clinical medicine Oncology Randomized controlled trial law 030220 oncology & carcinogenesis Internal medicine medicine Clinical endpoint 030212 general & internal medicine business Adjuvant health care economics and organizations media_common |
| Zdroj: | JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Universitat Pompeu Fabra |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/djx232 |
| Popis: | Background: It is uncertain whether drugs approved by the US Food and Drug Administration (FDA) have clinically meaningful benefit as determined by validated scales such as the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Methods: We searched the Drugs@FDA website for applications of anticancer drugs from January 2006 to December 2016. Study characteristics, outcomes, and regulatory pathways were collected from drug labels and reports of registration trials. For randomized controlled trials (RCTs), ESMO-MCBS grades were applied. Meaningful benefit was defined as a grade of A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. All statistical tests were two-sided. Results: We identified 63 individual drugs for 118 indications. These were supported by 135 studies, among which were 105 RCTs for which ESMO-MCBS could be applied. Only 46 (43.8%) met the ESMO-MCBS meaningful benefit threshold (100% of (neo)adjuvant trials and 38.8% of palliative trials). In palliative therapy trials, meaningful ESMO-MCBS grades were associated with phase III trials (compared with phase II; odds ratio [OR] = 38.45, 95% confidence interval [CI] = 3.27 to 452.00, P = .004), those with overall survival as their primary end point (compared with intermediate end points; OR = 8.28, 95% CI = 2.49 to 27.50, P = .001) and trials of targeted drugs with companion diagnostics (OR = 11.62, 95% CI = 2.95 to 45.78, P < .001). Over time, there has been an increase in the number of trials meeting the ESMO-MCBS threshold (P-trend = .04). There were insufficient (neo)adjuvant studies to perform statistical analysis. Conclusions: The number of trials meeting the ESMO-MCBS threshold for clinical benefit has improved over time. However, fewer than half of RCTs supporting FDA approval meet the threshold for clinically meaningful benefit. |
| Databáze: | OpenAIRE |
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