Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational studyBMJ 2018; 360 doi: https://doi.org/10.1136/bmj.k668 (Published 07 March 2018) Cite this as: BMJ 2018;360:k668
- Jeffrey Wagner, medical student1,
- John Marquart, medical student1,
- Julia Ruby, medical student1,
- Austin Lammers, hematology/oncology fellow2,
- Sham Mailankody, assistant professor3,
- Victoria Kaestner, research assistant2,
- Vinay Prasad, assistant professor of medicine and senior scholar2 4 5
- 1School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA
- 2Divison of Hematology Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
- 3Division of Myeloma, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- 4Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA
- 5Center for Health Care Ethics, Oregon Health & Science University, Portland, OR, USA
- Correspondence to: V Prasad
- Accepted 23 January 2018
Objective To determine the differences between recommendations by the National Comprehensive Cancer Network (NCNN) guidelines and Food and Drug Administration approvals of anticancer drugs, and the evidence cited by the NCCN to justify recommendations where differences exist.
Design Retrospective observational study.
Setting National Comprehensive Cancer Network and FDA.
Participants 47 new molecular entities approved by the FDA between 2011 and 2015.
Main outcome measures Comparison of all FDA approved indications (new and supplemental) with all NCCN recommendations as of 25 March 2016. When the NCCN made recommendations beyond the FDA’s approvals, the recommendation was classified and the cited evidence noted.
Results 47 drugs initially approved by the FDA between 2011 and 2015 for adult hematologic or solid cancers were examined. These 47 drugs were authorized for 69 FDA approved indications, whereas the NCCN recommended these drugs for 113 indications, of which 69 (62%) overlapped with the 69 FDA approved indications and 44 (39%) were additional recommendations. The average number of recommendations beyond the FDA approved indications was 0.92. 23% (n=10) of the additional recommendations were based on evidence from randomized controlled trials, and 16% (n=7) were based on evidence from phase III studies. During 21 months of follow-up, the FDA granted approval to 14% (n=6) of the additional recommendations.
Conclusion The NCCN frequently recommends beyond the FDA approved indications even for newer, branded drugs. The strength of the evidence cited by the NCCN supporting such recommendations is weak. Our findings raise concern that the NCCN justifies the coverage of costly, toxic cancer drugs based on weak evidence.
Contributors: VP designed the study, analyzed data, ensured accuracy of analysis, and drafted the manuscript. The primary authors (JW, JM, JR, and AL), who contributed equally to the study, initiated the collaboration, assisted in developing the research concept, completed guideline review, performed data collection plus analysis, and drafted the manuscript in collaboration with the principal investigator. VK and SM provided comments, revised the research concept, and revised the manuscript. JW, JM, JR, AL, and VP are the guarantors.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. VP is funded by the Laura and John Arnold Foundation for work on medical reversal.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: Data used for analysis are in the supplementary table.
Transparency: The manuscript’s guarantors (JW, JM, JR, AL, and VP) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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