However, trials frequently fail to assess clinical benefit, and expenditure for these drugs may be substantial. The FDA requires postapproval trials to confirm benefit, after which the accelerated approval is converted to a standard approval or is withdrawn. Importance Accelerated approval by the US Food and Drug Administration (FDA) grants market authorization for drugs based on clinical trials using surrogate end points likely to anticipate a clinical benefit. Ross is an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. Ross currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from Arnold Ventures in addition, Dr. Published online January 23, 2016.ĬONFLICT OF INTEREST: Dr Skydel is a member of the US Food and Drug Administration (FDA) Task Force for Doctors for America, outside the submitted work. BLA supplemental accelerated approval letter for Opdivo (nivolumab). United States Food and Drug Administration (FDA). BLA accelerated approval letter for Opdivo (nivolumab). Wallach JD, Luxkaranayagam AT, Dhruva SS, et. Wallach JD, Egilman AC, Dhruva SS, et al. Public access to information on regulatory decisions is necessary to inform safe and effective use of therapeutics following accelerated approval.ġ. Confirmatory trials are not necessarily initiated prior to approval, are not thoroughly outlined at the time of approval, and limited information is provided on FDA decisions to convert indications, including whether trials for expanded indications or other data sources are considered when approved indications remain unconfirmed. This update highlights the need for better documentation and increased transparency for the postmarketing requirements imposed by FDA for products granted accelerated approval. Among converted therapeutics, median annualized spending remained 5 times greater for those evaluated using surrogate, rather than clinical, endpoints ($175.9 million vs $33.9 million). Less than 1% of spending was attributable to the sole remaining therapeutic without an identified confirmatory trial. Updated CMS spending for the 14 of 38 (37%) therapeutics with original indications evaluated using clinical endpoints was $27.5 billion (of $67.9 billion, 41%), including $22.7 billion (33%) for those converted to standard approval through 2020. Nivolumab accounted for $9.6 billion in CMS spending through 2020. The confirmatory trial showed no difference in its primary clinical endpoint, overall survival, between nivolumab and the investigator’s choice of chemotherapy. The melanoma indication has been subsequently expanded, including in 2016 for patients regardless of BRAF V600 mutation status, and for use as either single-agent therapy or in combination with ipilimumab (5).Īlthough this trial was not identified using our specified method, we have updated our previously reported results to account for it. Nivolumab was granted accelerated approval in 2014 for unresectable or metastatic melanoma progressing after treatment with ipilimumab and, if eligible, a BRAF inhibitor (4). For 2 therapeutics, we found neither a registration nor published results, a known challenge due in part to the brief descriptions of confirmatory trials outlined in FDA approval letters (2, 3).Īs part of a separate ongoing project, we recently became aware of the confirmatory trial fulfilling postmarketing requirements for the original accelerated approval indication for nivolumab, which we had not previously identified. To identify the confirmatory trials outlined by FDA in product approval letters (ie, required by FDA at the time of approval), we used previously described methods (2). On May 27th, 2022, our analysis of United States Centers for Medicare & Medicaid Services (CMS) spending for therapeutics granted United States Food and Drug Administration (FDA) accelerated approval for original indications was published (1). Shared Decision Making and Communication.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.
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