ABSTRACT
Real-world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non-oncology therapeutic areas. Most were for indications in adults only (N = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single-arm trials. External data to support single-arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site-based charts. Endpoints in oncology use cases commonly included overall survival, progression-free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision-making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross-sector efforts are needed to further improve the quality and utility of RWE in regulatory decision-making.
Subject(s)
Drug Approval , Humans , Drug Approval/legislation & jurisprudence , United States , United States Food and Drug Administration/standards , United States Food and Drug Administration/legislation & jurisprudenceABSTRACT
The effectiveness of the regulatory initiatives, strategies, and incentives put forth in the first two authorizations of the Generic Drug User Fees Act (GDUFA) were evaluated using factors including the number of Abbreviated New Drug Application (ANDA) withdrawals and first-cycle approvals. GDUFA was originally authorized in 2012 for FY 2013-2017 (GDUFA I) and reauthorized for FY 2018-2022 (GDUFA II). ANDA approvals were analyzed from the Drugs @ FDA database covering 2013-2022. From the applications, the approval time, dosage form and route of administration (ROA), product indication, market status of the product, first generic status, company and company size filing the ANDA were noted. Despite the COVID pandemic, there was more than a 40% increase in ANDA approvals during GDUFA II relative to GDUFA I. Oral and parenteral drugs were the two leading categories of approved generics during both iterations of GDUFA. There was more than a 120% increase in withdrawn applications during GDUFA II, which reflects the partial refund that is now offered to incentivize companies to withdraw inadequate applications prior to review. This also appears to have contributed to an increase in the number of first-cycle approvals, which increased by 100% between GDUFA I and II. Due to the COVID-19 public health emergency, there was a decrease in activity within the generic drug program and market. Therefore, it is important to consider this impact when observing actual trends from this study.
Subject(s)
Drug Approval , Drugs, Generic , Drugs, Generic/economics , United States , Humans , Drug Approval/legislation & jurisprudence , United States Food and Drug Administration/legislation & jurisprudence , COVID-19/epidemiologyABSTRACT
This JAMA Forum discusses pending legislation in the US House and Senate and the history of the "firm-based approach" the US Food and Drug Administration (FDA) could use when regulating artificial intelligence (AI) medical devices to augment patient care.
Subject(s)
Artificial Intelligence , United States Food and Drug Administration , United States , United States Food and Drug Administration/legislation & jurisprudence , Humans , Artificial Intelligence/legislation & jurisprudence , Government RegulationSubject(s)
Antineoplastic Agents , Drug Approval , Drug Development , United States Food and Drug Administration , United States Food and Drug Administration/legislation & jurisprudence , United States , Humans , Drug Development/legislation & jurisprudence , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Drug Approval/legislation & jurisprudence , Neoplasms/drug therapyABSTRACT
This Viewpoint discusses the recent US Supreme Court ruling allowing mifepristonea drug used in medication abortionto be widely available in the US, summarizes the history of challenges to the availability of mifepristone, and highlights reasons for concerns that remain after the Court's current ruling.
Subject(s)
Abortion, Induced , Health Services Accessibility , Reproductive Health Services , United States Food and Drug Administration , Female , Humans , United States , United States Food and Drug Administration/legislation & jurisprudence , Reproductive Health Services/legislation & jurisprudence , Abortion, Induced/legislation & jurisprudence , Abortion, Induced/methods , Mifepristone/supply & distribution , Abortifacient Agents, Steroidal/supply & distribution , Patient Advocacy/legislation & jurisprudence , Health Services Accessibility/legislation & jurisprudence , PregnancyABSTRACT
This Viewpoint discusses the ongoing lawsuit between plaintiffs who had been affected by atypical femoral fractures while receiving alendronate and the drug manufacturer.
Subject(s)
Alendronate , Bone Density Conservation Agents , Drug Labeling , Fractures, Bone , Hip Fractures , Humans , Fractures, Bone/chemically induced , Fractures, Bone/prevention & control , United States , United States Food and Drug Administration/legislation & jurisprudence , United States Food and Drug Administration/standards , Alendronate/adverse effects , Alendronate/pharmacology , Alendronate/therapeutic use , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use , Hip Fractures/chemically induced , Hip Fractures/physiopathology , Bone Remodeling/drug effects , Fractures, Spontaneous/chemically induced , Fractures, Spontaneous/physiopathology , Drug Approval/legislation & jurisprudence , Drug Labeling/legislation & jurisprudence , Drug Labeling/standardsABSTRACT
This Viewpoint discusses the death of a patient caused by unregulated biological products and efforts to encourage federal government oversight of such products.
Subject(s)
Bone Transplantation , Bone and Bones , Disease Outbreaks , Government Regulation , Tuberculosis , United States Food and Drug Administration , Humans , Cell- and Tissue-Based Therapy/adverse effects , Cell- and Tissue-Based Therapy/standards , Tissue Banks/legislation & jurisprudence , Tissue Banks/standards , United States/epidemiology , United States Food and Drug Administration/legislation & jurisprudence , United States Food and Drug Administration/standards , Bone Transplantation/adverse effects , Bone Transplantation/standards , Bone and Bones/microbiology , Bone and Bones/surgery , Tuberculosis/epidemiology , Tuberculosis/etiology , Tuberculosis/microbiology , Mycobacterium tuberculosis/isolation & purification , Female , Middle AgedABSTRACT
Diagnosing infectious diseases significantly influences patient care, aiding in outbreak identification, response, and public health monitoring. However, the range of FDA-approved molecular tests remains notably limited, especially concerning neglected tropical diseases (NTDs). Drawing upon our experience as one of the largest healthcare networks in the greater New York metropolitan area, this viewpoint manuscript aims to spotlight the existing diagnostic landscape and unmet clinical needs for 4 emerging NTDs increasingly prevalent in the United States, additionally, it delves into the possible adverse effects of the FDA's Proposed Rule on Laboratory-Developed Tests for these clinical conditions and the broader spectrum of NTDs.
Subject(s)
Communicable Diseases, Emerging , Neglected Diseases , United States Food and Drug Administration , United States/epidemiology , Neglected Diseases/epidemiology , Humans , United States Food and Drug Administration/legislation & jurisprudence , Communicable Diseases, Emerging/epidemiology , Tropical MedicineABSTRACT
PURPOSE: The generic drug industry currently faces multiple, serious issues that threaten the US drug supply. So-called "skinny labels" are one of the few tools authorized by Congress to expedite entry into the market by generic competitors when the first patent for a brand's drug compound (only) expires. This article reviews the law on this expedited marketing pathway for generic competitors, as well as limitations on its use. METHODS: We examined the literature on patent protection of brand drugs, including the timelines for production of generic competitors. We also examined the law concerning skinny labels, including a recent decision of the US Federal Circuit Court that clearly articulates the guidelines concerning entry into the generic market, including labeling, marketing, and promotion. FINDINGS: Skinny labels that follow the regulations set forth in the Hatch-Waxman Act, including the necessary carve-out procedure for "methods of use" still protected by 1 or more active patents, do not infringe a brand drug's label. Furthermore, the skinny label does not induce or contribute to infringement merely because its label contains US Food and Drug Administration-required safety profile data-even when the data cross-reference superiority studies on still-patent protected methods of use elsewhere in the label. IMPLICATIONS: Generic drugs have become essential to the broad, general availability of clinical therapeutic agents. The Hatch-Waxman Act was intended to facilitate entry of generic competitors into the marketplace, and the skinny label is an important tool to accomplish that end. As long as the generic manufacturer follows the essential skinny-label rules, specifically including marketing the compound without promoting or advertising those methods of use still protected by ongoing patents, the law will not find induced or contributory infringement.
Subject(s)
Drug Labeling , Drugs, Generic , Economic Competition , Humans , Drug Industry/legislation & jurisprudence , Drug Labeling/legislation & jurisprudence , Patents as Topic/legislation & jurisprudence , United States , United States Food and Drug Administration/legislation & jurisprudenceSubject(s)
Drug Costs , Drug Industry , United States Federal Trade Commission , Humans , Drug Industry/economics , Drug Industry/legislation & jurisprudence , Government Regulation , United States , United States Federal Trade Commission/economics , United States Federal Trade Commission/legislation & jurisprudence , United States Food and Drug Administration/economics , United States Food and Drug Administration/legislation & jurisprudence , Drug Costs/legislation & jurisprudenceSubject(s)
Nicotine , Smoking Cessation , Tobacco Industry , Tobacco Products , Tobacco Use Disorder , Humans , Government Regulation , Nicotine/administration & dosage , Nicotine/analysis , Smoking Cessation/legislation & jurisprudence , Smoking Cessation/methods , Tobacco Industry/legislation & jurisprudence , Tobacco Products/analysis , Tobacco Products/legislation & jurisprudence , Tobacco Products/standards , Tobacco Use Disorder/prevention & control , United States , United States Food and Drug Administration/legislation & jurisprudenceABSTRACT
Importance: The US Food and Drug Administration's (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered "reasonably likely" to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit. Objective: To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval. Design, Setting, and Participants: In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023. Main Outcomes and Measures: Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval. Results: A total of 129 cancer drug-indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy). Conclusions and Relevance: Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.
Subject(s)
Antineoplastic Agents , Drug Approval , Neoplasms , United States Food and Drug Administration , Humans , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Cohort Studies , Drug Approval/legislation & jurisprudence , Drug Approval/methods , Drugs, Investigational/therapeutic use , Neoplasms/drug therapy , Neoplasms/mortality , Quality of Life , Survival Analysis , Time Factors , Treatment Outcome , United States , United States Food and Drug Administration/legislation & jurisprudence , Follow-Up StudiesSubject(s)
Commerce , Drug Industry , Economics, Pharmaceutical , Health Policy , Pharmaceutical Preparations , Humans , Commerce/economics , Commerce/legislation & jurisprudence , Drug Costs/legislation & jurisprudence , Drug Industry/legislation & jurisprudence , Drug Industry/economics , Economics, Pharmaceutical/legislation & jurisprudence , Patents as Topic/legislation & jurisprudence , Pharmaceutical Preparations/economics , United States , United States Food and Drug Administration/economics , United States Food and Drug Administration/legislation & jurisprudence , Health Policy/economics , Health Policy/legislation & jurisprudenceABSTRACT
In this Policy Forum piece, Robin Feldman discusses how current legislation contributes to informational deficits around drug patents for biologic drugs in the United States.
Subject(s)
Biosimilar Pharmaceuticals , Intellectual Property , United States , Humans , Biological Products , Patents as Topic/legislation & jurisprudence , Legislation, Drug , United States Food and Drug Administration/legislation & jurisprudenceABSTRACT
This Viewpoint outlines the potential effects of the Supreme Court case regarding mifepristone restrictions: a decision for the FDA would allow current dispensing, while ruling against the FDA would severely curtail access to reproductive health options.