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

BMJ. 2018 Mar 7:360:k668. doi: 10.1136/bmj.k668.

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.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Drug Approval / methods*
  • Evidence-Based Medicine / methods
  • Humans
  • Oncology Service, Hospital / organization & administration*
  • Organizations, Nonprofit / statistics & numerical data
  • Patient Care Management / standards*
  • Retrospective Studies
  • United States
  • United States Food and Drug Administration

Substances

  • Antineoplastic Agents