Reply to F. Perrone et al

Abstract

We appreciate the favorable comments of Perrone et al and their interest in our article. We also appreciate the extent of their previous research in related areas. Their comments highlight the need for better evidence of the effectiveness of oncology drugs and a better means for using the best available evidence to inform coverage decisions. That is the intent of our effectiveness guidance document, and we are optimistic that our guidance, along with other guidance and reports, will motivate future trials that address the many evidence gaps that exist in adult oncology. As Perrone et al suggested, our guidance may well serve to improve the design of oncology trials for expanded indications of drugs that are used off label. We briefly comment on this possibility in the Scope and Purpose of Effectiveness Guidance Document section of our article. We note that the context of drug reimbursement differs between the United States and most European countries, including Italy. In the United States, Medicare, which is one of the largest public payers, provides coverage for off-label uses that are supported by Medicare-approved compendia even if these uses have not been reviewed by the US Food and Drug Administration; most other third-party payers have followed suit. One of the authors(A.A.P.)ofourarticlehasdescribedsomeofthechallengesrelated to this policy and the fact that there is a need for both better evidence and processes for assessing the evidence of cancer drugs. Werecognize that therecannotalwaysbeanewtrial toexploreevery off-label use, and our guidance may not be applicable for every clinical application.However,weareconfidentthat, if futuretrialsofoff-labeluses were designed with our effectiveness guidance document in mind, the results would be more informative and meaningful to patients, prescribers, payers, and policy makers. Meanwhile, as the letter of Perrone et al documents, evidence development in cancer cannot only focus on randomized controlled trials. Multiple evidence sources, continuous aggregating data, and disciplined iterative evaluation must be parts of our ethos to allow for more informed decision making. This approach to continuous learning is exactly the premise behind learning health care approaches, and off-label oncology is the exemplar use case.