Few new drugs deserve expedited regulatory treatment

Darrow, Jonathan J.

doi:10.18553/jmcp.2021.27.5.685

Cited by 8 publications

(14 citation statements)

References 18 publications

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“… 61 Data limitations at the time of regulatory approval may complicate estimation of cost-effectiveness for reimbursement decisions, 62 which may lead to potential waste of scarce public insurance resources. 63 , 64 Because regulatory approval standards represent not only the current thinking of regulators, but also guide the vision of what a “good drug” should be, 65 our findings highlight the need for more attention to the clinical meaningfulness—in terms of type and magnitude of benefit 66 —of newly authorized and investigational cancer therapies in China. 67 , 68 …”

Section: Discussionmentioning

confidence: 99%

Overall Survival Benefits of Cancer Drugs Approved in China From 2005 to 2020

et al. 2022

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Key Points Question What is the overall survival benefit of cancer drugs approved in China between 2005 and 2020? Findings In this mixed-methods study comprising a systematic review and cross-sectional analysis of 78 cancer drugs for 141 indications, 68 new cancer drug indications approved by Chinese authorities between 2005 and 2020 had documented evidence of overall survival benefit, and 34 did not prolong life. Meaning Given regulatory reforms in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in China.

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Section: Discussionmentioning

confidence: 99%

Overall Survival Benefits of Cancer Drugs Approved in China From 2005 to 2020

et al. 2022

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“…Drug regulators have introduced conditional drug approval pathways to accelerate patient access to promising therapies since the 1990s. Though drugs approved under accelerated or conditional pathways must still demonstrate a positive benefit-risk balance, approvals are based on lower evidentiary standards than standard regulatory approval processes that evaluate safety and efficacy (1)(2)(3). Due to the heightened risk to patients associated with approving drugs on earlier evidence, conditional pathways are justified by limiting eligibility, for example, to drugs intended for serious and life-threatening diseases or where there is unmet need (4).…”

Section: Introductionmentioning

confidence: 99%

Conditional Drug Approval as a Path to Market for Oncology Drugs in Canada: Challenges and Recommendations for Assessing Eligibility and Regulatory Responsiveness

2022

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International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied to conditional drug approvals, eligibility criteria and post-market evidence. Our analysis informs recommendations for Canada's proposed regulatory reforms approach to conditional approvals pathways. Our analysis demonstrates that under the current policy, eligibility criteria are insufficiently defined, resulting in their inconsistent application by Health Canada. Regulatory responsiveness to post-market evidence from post-market clinical trial and foreign jurisdiction regulatory decisions is slow and insufficient. In the absence of sufficient regulatory responsiveness, physicians and patients must make clinical decisions without the benefit of the best available evidence. Together, our analysis of the two core tradeoffs in Canada's conditional drug approval provides insight to inform the further development of Canada's proposed agile regulatory approach to drugs and devices that will expand the use of terms and conditions.

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“…Without a reasonable likelihood that these drugs provide substantial clinical benefits, the argument for more rapid entry becomes less compelling. 35 The FDA and consumers may benefit from a reexamination of how the agency balances time to market with ensuring that approved drugs are sufficiently safe and effective.…”

Section: Discussionmentioning

confidence: 99%

“…The pivotal trials of oncology drugs approved in 2020 had more flexible trial designs than approvals overall, including randomization, use of surrogate end points, and use of a historical control. Without a reasonable likelihood that these drugs provide substantial clinical benefits, the argument for more rapid entry becomes less compelling . The FDA and consumers may benefit from a reexamination of how the agency balances time to market with ensuring that approved drugs are sufficiently safe and effective.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Supportive Evidence for US Food and Drug Administration Approvals of Novel Drugs in 2020

et al. 2022

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IMPORTANCEIn recent years, drug approvals have been based on fewer, smaller, and less rigorous pivotal trials. Less robust preapproval testing raises questions about the efficacy and clinical value of these drugs. OBJECTIVE To assess the regulatory context, pivotal design characteristics, and postmarket requirements (PMRs) and postmarket commitments (PMCs) of novel 2020 drug approvals to characterize the state of evidence at the time of approval. DESIGN, SETTING, AND PARTICIPANTS This cohort study identified novel drugs approved by the US Food and Drug Administration's (FDA) Center for Drug Evaluation and Research in 2020. The Drugs@FDA database was used to extract key characteristics of each drug's pivotal trials. Drug approval packages provided regulatory information. The prevalence of key trial design features was compared between oncology and nononcology drugs. EXPOSURES Drug names, date of approval, indication on labeling, and clinical and regulatory details. MAIN OUTCOMES AND MEASURES Number of pivotal trials, pivotal trial design (randomization, masking, groups), trial comparator, trial hypothesis, trial end points, results, number and type of expedited pathway designations, and number and type of PMRs and PMCs. RESULTSThe 49 novel therapeutics approved in 2020 were supported by 75 pivotal trials. More than half of drugs (28 [57.1%]) were supported by a single pivotal trial. Trial sizes ranged from 19 to 2230 participants. More than three-fourths of trials (57 [76.0%]) had a randomization component, and nearly two-thirds (46 [61.3%]) were double-masked. Most used a superiority approach. Roughly half (39 [52.0%]) compared the novel therapeutic with a placebo or vehicle control; 13 (17.3%), an active control; 2 (2.7%), both a placebo and active control; and 21 (28.0%), a historical, external, or other control. Nearly half of pivotal trials (34 [45.3%]) used a surrogate measure as a primary end point. Pivotal trials supporting oncology approvals were much more likely to have historical controls than nononcology approvals (13 of 18 [72.2%] vs 8 of 57 [14.0%]; P < .001) and to use at least 1 surrogate measure as a primary end point (17 [94.4%] vs 17 [29.8%]; P < .001). Forty drugs had at least 1 PMR or PMC, accounting for 178 PMRs and PMCs across the cohort. CONCLUSIONS AND RELEVANCEThese findings suggest that the increased flexibility in the characteristics of acceptable preapproval evidence can be partially explained by the increase in trials of drugs for rare and other serious conditions that require flexible testing strategies as well as the associated regulatory changes that have accumulated over time. The FDA and consumers may (continued) Key Points Question What were the key design characteristics of the pivotal trials supporting novel drugs approved by the US Food and Drug Administration (FDA) in 2020? Findings This cohort study of 49 drugs approved by the FDA in 2020 found that they were supported by 75 pivotal trials, of which nearly two-thirds were double-masked, more than threefourths had a randomiz...

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Few new drugs deserve expedited regulatory treatment

Cited by 8 publications

References 18 publications

Overall Survival Benefits of Cancer Drugs Approved in China From 2005 to 2020

Overall Survival Benefits of Cancer Drugs Approved in China From 2005 to 2020

Conditional Drug Approval as a Path to Market for Oncology Drugs in Canada: Challenges and Recommendations for Assessing Eligibility and Regulatory Responsiveness

Analysis of Supportive Evidence for US Food and Drug Administration Approvals of Novel Drugs in 2020

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