The FDA Breakthrough-Drug Designation — Four Years of Experience

Darrow, Jonathan J.; Avorn, Jerry; Kesselheim, Aaron S.

doi:10.1056/nejmhpr1713338

Cited by 43 publications

(40 citation statements)

References 26 publications

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“…7 Since its creation in 2012, the breakthrough therapy designation program has grown rapidly, with more than 30 cancer drug approvals receiving designations to date. 8,9 However, the clinical benefit and cost of breakthrough-designated cancer drugs are uncertain.…”

Section: Introductionmentioning

confidence: 99%

Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration

Molto

Hwang

Borrell

et al. 2020

Cancer

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Background The clinical benefit and pricing of breakthrough‐designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough‐designated and non–breakthrough‐designated cancer drug approvals. Methods A cross‐sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO‐VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO‐CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO‐MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores ≥ 45 for the ASCO‐VF, overall survival gains ≥ 2.5 months or progression‐free survival gains ≥ 3 months for all cancer types for the ASCO‐CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO‐MCBS, and scores of 4 and 5 and a combined score ≥ 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus. Results This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO‐VF, ASCO‐CRC, ESMO‐MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO‐VF (odds ratio [OR], 3.69; P = .022) and the NCCN Evidence Blocks (OR, 5.80; P = .003) but not with the ASCO‐CRC (OR, 3.54; P = .11) or version 1.1 (v1.1) of the ESMO‐MCBS (OR, 1.22; P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001). Conclusions In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO‐VF and the NCCN Evidence Blocks but not with the ESMO‐MCBS v1.1 or the ASCO‐CRC scale.

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Section: Introductionmentioning

confidence: 99%

Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration

Molto

Hwang

Borrell

et al. 2020

Cancer

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“…The FDA's more frequent use of special regulatory pathways has been discussed as a potential risk to high safety and efficacy standards. However, studies on this topic tend to emphasize the overall benefits of this approach [10,21,22].…”

Section: Discussionmentioning

confidence: 99%

FDA and EMA Approvals of New Breast Cancer Drugs—A Comparative Regulatory Analysis

Leo¹,

Hentschel²,

Szucs

et al. 2020

Cancers

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Breast cancer is the most common cancer in women worldwide and the solid tumor type for which the highest number of drugs have been approved to date. This study examines new drug approvals for breast cancer by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), based on an analysis of regulatory documents from both agencies for the period from 1995 to 2018. Of the 29 breast cancer drugs approved over this time span, 17 received positive decisions from both the FDA and EMA, including all drugs licensed after 2008. Nineteen of the 25 FDA-approved drugs, but none of the EMA approvals, benefited from special regulatory pathways (such as fast track, breakthrough therapy, or priority review). In the U.S.A., four accelerated approvals were granted (of which one, for bevacizumab, was later revoked), while only two drugs received provisional approvals following EMA review. New breast cancer drugs were approved approximately twelve months earlier in the United States than in Europe. These results suggest that a broader use of special regulatory pathways by EMA could help to accelerate access to novel drugs for European breast cancer patients.

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“…If this designation is granted, the FDA will offer all fast-track designation benefits as well as guidance on how to execute an efficient drug development program and will involve senior FDA commissioners in the organizational process. 38 A systematic review 39 of all approvals of breakthrough therapy drugs from 2012 to 2017 suggested that rapid approval under the breakthrough therapy pathway can sometimes occur at the expense of the strength of the overall evidence supporting the approval when compared with drugs without a breakthrough designation. From the perspective of the FDA, 40 it is not the breakthrough designation that accounts for differing levels of evidence but rather the pragmatism that the FDA must exercise to allow testing to be "as efficient and flexible as practicable, when scientifically appropriate," 8 such as in the approval of drugs targeting rare diseases.…”

Section: Breakthrough Therapymentioning

confidence: 99%

The Role of the Food and Drug Administration in Drug Development: On the Subject of Proarrhythmia Risk

Thind

Kowey

2020

J Innov Cardiac Rhythm Manage

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The Food and Drug Administration (FDA) is responsible for the regulation of the pharmaceutical industry in the interest of protecting public health. The aim of this review was to outline the evolution and current role of the FDA in the development and approval of new drugs. Additionally, we describe current assessments of proarrhythmia risk to illustrate recent FDA initiatives intended to harness information technology to modernize the regulatory process. In order to identify the literature required to produce this review, search tools such as PubMed and Google Scholar were used to locate relevant web pages and articles. The job of the FDA is not only to ensure that high standards for drug efficacy and safety are applied to products available to American consumers and patients but also to balance the lengthy, costly process of maintaining these standards against the pressure to provide access to effective treatments earlier and without surplus expenditures. In order to provide expedited access to the newest effective therapies for critically ill patients in the safest way possible, the FDA has developed several accelerated pathways to fast-track drug approval. Through partnerships with industry and academic institutions, research is being conducted into how information technology can be integrated into the drug development process to improve its cost-effectiveness.

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The FDA Breakthrough-Drug Designation — Four Years of Experience

Cited by 43 publications

References 26 publications

Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration

Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration

FDA and EMA Approvals of New Breast Cancer Drugs—A Comparative Regulatory Analysis

The Role of the Food and Drug Administration in Drug Development: On the Subject of Proarrhythmia Risk

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