Fulfillment of Postmarket Commitments and Requirements for New Drugs Approved by the FDA, 2013-2016

Brown, Beatrice L; Mitra-Majumdar, Mayookha; Darrow, Jonathan J.; Moneer, Osman; Pham, Catherine; Avorn, Jerry; Kesselheim, Aaron S.

doi:10.1001/jamainternmed.2022.4226

Cited by 8 publications

(8 citation statements)

References 5 publications

(5 reference statements)

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“…While the majority of established PMRs and PMCs are fulfilled, the median time to fulfillment was around 2.3 years (ranging from 81 days to 9 years). This is comparable with the 2.5 years reported for the fulfillment of all PMRs and PMCs assessed over a 4‐year time period 24 . The range is also reflective of the different types of clinical pharmacology–related studies established as PMRs or PMCs: whereas an in vitro drug interactions assessment may take months to complete, a hepatic impairment study can take years.…”

Section: Discussionsupporting

confidence: 75%

“…This is comparable with the 2.5 years reported for the fulfillment of all PMRs and PMCs assessed over a 4-year time period. 24 The range is also reflective of the different types of clinical pharmacology-related studies established as PMRs or PMCs: whereas an in vitro drug interactions assessment may take months to complete, a hepatic impairment study can take years. It is vital for public health that PMRs and PMCs are completed within a reasonable time frame.…”

Section: Discussionmentioning

confidence: 99%

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US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information

Ridge

Guinn

Fletcher

et al. 2023

The Journal of Clinical Pharma

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Many of the conditions for the safe and effective use of new molecular entities (NMEs) are understood at the time of initial drug approval. However, some remaining knowledge gaps can be addressed after drug approval through postmarketing requirements (PMRs) or commitments (PMCs) established by the US Food and Drug Administration (FDA). Our objective was to conduct an assessment of clinical pharmacology-related PMRs and PMCs established at the time of approval and evaluate the impact of fulfilled PMRs and PMCs on prescription information (PI). This analysis included clinical pharmacology-related PMRs and PMCs established for NMEs approved between 2009 and 2020. Of the 1171 PMRs and PMCs, over one-third were clinical pharmacology-related. Of these, 46% were to evaluate drug interactions, 16% were to evaluate drug dosing in patients with hepatic impairment, and 10% were related to dose. The majority (57%) of PMRs and PMCs were fulfilled at the time of analysis, with a median time to fulfillment of approximately 2.3 years. The majority (94%) of the fulfilled PMRs and PMCs, either with or without a PI revision, resulted in new or modified instructions for use or supported existing instructions for use. This is the first time that clinical pharmacologyrelated PMRs and PMCs have been catalogued and analyzed to understand their impact on PI. An understanding of the knowledge gaps that exist at the time of drug approval could inform the most effective and efficient methods for evidence generation prior to and after new drug approval.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information

Ridge

Guinn

Fletcher

et al. 2023

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…That these serious challenges have arisen despite accelerated approval's built-in postmarket protections is cause for even greater concern where those protections are absent. Beyond the efficacy studies that may be required following accelerated approval, the FDA currently recognizes only 3 other types of postmarket requirements (PMRs): (1) certain pediatric studies; (2) safety and efficacy studies in humans for drugs approved on the basis of animal efficacy data; and (3) by far the most common, 27 studies to assess known or potential serious risks (Table 2). 28,29 When none of these conditions apply, one might expect the FDA to calibrate its approval standards to demand greater certainty up front.…”

Section: Other Postmarket Problemsmentioning

confidence: 99%

Extending the US Food and Drug Administration’s Postmarket Authorities

et al. 2023

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ImportanceThe US Food and Drug Administration (FDA) has expansive regulatory flexibility regarding the quality and quantity of evidence it deems sufficient to approve new drugs, which has been increasingly used to grant approval based on less certain evidence of benefit. However, the FDA’s regulatory flexibility with respect to standards for approval has not been matched by sufficient stringency in its exercise of postmarket safeguards, including the FDA’s authority and willingness to require confirmation of benefit through postmarket efficacy studies or to withdraw approval when benefit is not confirmed.ObjectiveTo identify and evaluate opportunities for the FDA to extend its authority to require postmarket efficacy studies and use expedited withdrawal procedures for drugs approved despite substantial residual uncertainty outside the accelerated approval pathway.EvidenceThe FDA’s current approaches to regulatory flexibility with respect to standards for drug approval; examples of shortcomings in the postmarket period; existing statutes and regulations governing the scope of the FDA’s authority to impose and enforce postmarket study requirements; and recent legislative reform and agency action regarding the accelerated approval pathway.FindingsDrawing on the broad language of the federal Food, Drug, and Cosmetic Act, the FDA could independently extend its core accelerated approval authorities—required postmarket efficacy studies and expedited withdrawal procedures—to any drug approved with substantial residual uncertainty regarding benefit, such as those supported by a single pivotal trial. To avoid exacerbating existing problems that have become evident during the past 3 decades of experience using the accelerated approval pathway, however, the FDA must ensure that postmarket studies are well designed and completed quickly, while compelling expedited withdrawal when needed.Conclusions and RelevanceUnder current FDA approaches to drug approval, patients, clinicians, and payers may be left with little confidence about a drug’s benefit not only when it first enters the market but also for an extended period thereafter. If policy makers continue to favor earlier market access over evidentiary certainty, flexible approvals must be matched by more expansive use of postmarket safeguards, an approach possible within the FDA’s existing legal authorities.

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“…This kind of ongoing evaluation is far more useful for clinicians, patients, and policy makers than a simplistic approval decision made at a single, early point in time on the basis of potentially inadequate outcome measures but not informed by further evidence . Experience in the US indicates that manufacturers are often slow or even inert in implementing such postmarketing requirements required by the Food and Drug Administration, but the concept of reexamination does open the door to such a more systematic assessment after a drug has been approved quickly on the basis of less dependable measures.…”

mentioning

confidence: 99%

Surrogate Measures of Drug Efficacy—A Finger Pointing at the Moon

Avorn

2023

JAMA Netw Open

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Fulfillment of Postmarket Commitments and Requirements for New Drugs Approved by the FDA, 2013-2016

Abstract: This cohort study used the Drugs@FDA database to identify new drugs approved by the US Food and Drug Administration (FDA) and assess fulfillment of postmarket commitments and requirements.

Cited by 8 publications

References 5 publications

US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information

US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information

Extending the US Food and Drug Administration’s Postmarket Authorities

Surrogate Measures of Drug Efficacy—A Finger Pointing at the Moon

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