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 study Journal Article


Authors: Wagner, J.; Marquart, J.; Ruby, J.; Lammers, A.; Mailankody, S.; Kaestner, V.; Prasad, V.
Article Title: 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 study
Abstract: 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. © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.
Keywords: osteosarcoma; adult; controlled study; retrospective studies; unclassified drug; antineoplastic agents; drug approval; united states; united states food and drug administration; comparative study; antineoplastic agent; clinical practice; evidence based medicine; organization and management; evidence-based medicine; melanoma; multiple myeloma; phase 2 clinical trial; breast cancer; randomized controlled trial; evidence based practice; amyloidosis; waldenstroem macroglobulinemia; food and drug administration; retrospective study; hodgkin disease; patient care; cancer center; hematologic malignancy; vandetanib; oncology service, hospital; soft tissue sarcoma; thyroid cancer; phase 3 clinical trial; phase 1 clinical trial; observational study; thyroid papillary carcinoma; mycosis fungoides; standards; drug indication; classical hodgkin lymphoma; hairy cell leukemia; non profit organization; castration resistant prostate cancer; non small cell lung cancer; metastatic melanoma; sezary syndrome; radium 223; anaplastic large cell lymphoma; procedures; crizotinib; vemurafenib; pomalidomide; dabrafenib; trametinib; cabozantinib; brentuximab vedotin; humans; human; priority journal; article; palbociclib; ceritinib; patient care management; statistics and numerical data; organizations, nonprofit; solid malignant neoplasm
Journal Title: BMJ: British Medical Journal (International Edition)
Volume: 360
ISSN: 0959-8146
Publisher: BMJ Publishing Group Ltd.  
Date Published: 2018-03-07
Start Page: k668
Language: English
DOI: 10.1136/bmj.k668
PUBMED: 29514787
PROVIDER: scopus
PMCID: PMC5838851
DOI/URL:
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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