Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview

Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

doi:10.1016/j.jclinepi.2017.07.002

Cited by 26 publications

(32 citation statements)

References 86 publications

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“…NICE has an important role as an assessor of both the clinical and cost effectiveness of oncology drugs approved for use by the EMA. However, as outlined by Woolacott et al [ 10 ], there are methodological challenges to assessing effectiveness when the clinical evidence available to the regulators is limited and/or immature. For example, there has been an increase in the number of NICE appraisals where the only clinical effectiveness data available for consideration comes from single-arm, non-comparative studies that often have small numbers of patients and limited follow-up.…”

Section: Current Uncertaintiesmentioning

confidence: 99%

EMA and NICE Appraisal Processes for Cancer Drugs: Current Status and Uncertainties

Dickson

Boland

Duarte

et al. 2018

Appl Health Econ Health Policy

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Section: Current Uncertaintiesmentioning

confidence: 99%

EMA and NICE Appraisal Processes for Cancer Drugs: Current Status and Uncertainties

Dickson

Boland

Duarte

et al. 2018

Appl Health Econ Health Policy

Self Cite

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“…4 However, evidence suggests that these programs introduce flexible approval standards that can lead to products being approved on the basis of fewer or less robust studies, 5 and are associated with greater likelihood that the FDA will take a safety-related action after the agent has been approved for use. 6 Although a recent study provided an overview of common methodological challenges encountered in pivotal clinical trials supporting expedited regulatory approvals, 7 different methodological and regulatory factors influence the validity of studies conducted in the pre-and postapproval periods. In this paper, we first provide an overview of the evidentiary standards required by FDA's expedited development and review programs for therapeutic agents and summarize the findings of the recent academic literature demonstrating some of the limitations of these programs.…”

Section: Introductionmentioning

confidence: 99%

The US Food and Drug Administration’s expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements

Wallach¹,

Ross

Naci

2018

Clinical Trials

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The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs. In this article, we provide an overview of the evidentiary standards required by the Food and Drug Administration's expedited development and review programs, summarize the findings of the recent academic literature demonstrating some of the limitations of these programs, and outline potential opportunities to address these limitations. Recent evidence suggests that therapeutic agents in the Food and Drug Administration's expedited programs are approved on the basis of fewer and smaller studies that may lack comparator groups and random allocation, and rather than focusing on clinical outcomes for study endpoints, rely instead on surrogate markers of disease. Once on the market, agents receiving expedited approvals are often quickly incorporated into clinical practice, and evidence generated in the postmarket period may not necessarily address the evidentiary limitations at the time of market entry. Furthermore, not all pathways require additional postmarket studies. Evidence suggests that drugs in expedited approval programs are associated with a greater likelihood that the Food and Drug Administration will take a safety action following market entry. There are several opportunities to improve the timeliness, information value, and validity of the pre- and postmarket studies of therapeutic agents receiving expedited approvals. When use of nonrandomized and uncontrolled studies cannot be avoided prior to market entry, randomized trials should be mandatory in the postmarket period, unless there are strong justifications for not carrying out such studies. In the premarket period, validity of the surrogate markers can be improved by more rigorously evaluating their correlation with patient-relevant clinical outcomes. Opportunities to reduce the duration, complexity, and cost of postmarket randomized trials should not compromise their validity and instead incorporate pragmatic "real-world" design elements. Despite recent enthusiasm for widely using real-world evidence, adaptive designs, and pragmatic trials in the regulatory setting, caution is warranted until large-scale empirical evaluations demonstrate their validity compared to more traditional trial designs.

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“…There can be uncertainties in the initial HTA of the benefits of a new drug due to limitations in the available evidence, such as a small sample size or a non-randomised study 30. Therefore, there is a need to develop a mechanism to reassess the benefits of some drugs based on evidence generated after initial HTA recommendation.…”

Section: Canrevalue Working Groupsmentioning

confidence: 99%

Developing a framework to incorporate real-world evidence in cancer drug funding decisions: the Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration

et al. 2020

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BackgroundOncology therapy is becoming increasingly more expensive and challenging the affordability and sustainability of drug programmes around the world. When new drugs are evaluated, health technology assessment organisations rely on clinical trials to inform funding decisions. However, clinical trials are not able to assess overall survival and generalises evidence in a real-world setting. As a result, policy makers have little information on whether drug funding decisions based on clinical trials ultimately yield the outcomes and value for money that might be expected.ObjectiveThe Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration, consisting of researchers, recommendation-makers, decision makers, payers, patients and caregivers, are developing and testing a framework for Canadian provinces to generate and use real-world evidence (RWE) for cancer drug funding in a consistent and integrated manner.StrategyThe CanREValue collaboration has established five formal working groups (WGs) to focus on specific processes in the generation and use of RWE for cancer drug funding decisions in Canada. The different RWE WGs are: (1) Planning and Drug Selection; (2) Methods; (3) Data; (4) Reassessment and Uptake; (5) Engagement. These WGs are acting collaboratively to develop a framework for RWE evaluation, validate the framework through the multiprovince RWE projects and help to integrate the final RWE framework into the Canadian healthcare system.OutcomesThe framework will enable the reassessment of cancer drugs, refinement of funding recommendations and use of novel funding mechanisms by decision-makers/payers across Canada to ensure the healthcare system is providing clinical benefits and value for money.

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Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview

Cited by 26 publications

References 86 publications

EMA and NICE Appraisal Processes for Cancer Drugs: Current Status and Uncertainties

EMA and NICE Appraisal Processes for Cancer Drugs: Current Status and Uncertainties

The US Food and Drug Administration’s expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements

Developing a framework to incorporate real-world evidence in cancer drug funding decisions: the Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration

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