Unhealthy Pharmaceutical Regulation

Davis, Courtney; Abraham, John

doi:10.1057/9781137349477

Cited by 72 publications

(25 citation statements)

References 81 publications

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“…In the European Union, the European Medicines Agency (EMA) serves as the gatekeeper to the pharmaceutical market; clinicians can only prescribe a new drug after it receives the EMA’s approval 1. The EMA bases its decisions on a small number of key clinical studies completed and submitted by pharmaceutical manufacturers 2. Between 2012 and 2016, about half of new drugs approved by the EMA were associated with a single pivotal study 3…”

Section: Introductionmentioning

confidence: 99%

Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis

Naci

Davis

Savović

et al. 2019

BMJ

Self Cite

139

100

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ObjectiveTo examine the design characteristics, risk of bias, and reporting adequacy of pivotal randomised controlled trials of cancer drugs approved by the European Medicines Agency (EMA).DesignCross sectional analysis.SettingEuropean regulatory documents, clinical trial registry records, protocols, journal publications, and supplementary appendices.Eligibility criteriaPivotal randomised controlled trials of new cancer drugs approved by the EMA between 2014 and 2016.Main outcome measuresStudy design characteristics (randomisation, comparators, and endpoints); risk of bias using the revised Cochrane tool (bias arising from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result); and reporting adequacy (completeness and consistency of information in trial protocols, publications, supplementary appendices, clinical trial registry records, and regulatory documents).ResultsBetween 2014 and 2016, the EMA approved 32 new cancer drugs on the basis of 54 pivotal studies. Of these, 41 (76%) were randomised controlled trials and 13 (24%) were either non-randomised studies or single arm studies. 39/41 randomised controlled trials had available publications and were included in our study. Only 10 randomised controlled trials (26%) measured overall survival as either a primary or coprimary endpoint, with the remaining trials evaluating surrogate measures such as progression free survival and response rates. Overall, 19 randomised controlled trials (49%) were judged to be at high risk of bias for their primary outcome. Concerns about missing outcome data (n=10) and measurement of the outcome (n=7) were the most common domains leading to high risk of bias judgments. Fewer randomised controlled trials that evaluated overall survival as the primary endpoint were at high risk of bias than those that evaluated surrogate efficacy endpoints (2/10 (20%) v 16/29 (55%), respectively). When information available in regulatory documents and the scientific literature was considered separately, overall risk of bias judgments differed for eight randomised controlled trials (21%), which reflects reporting inadequacies in both sources of information. Regulators identified additional deficits beyond the domains captured in risk of bias assessments for 10 drugs (31%). These deficits included magnitude of clinical benefit, inappropriate comparators, and non-preferred study endpoints, which were not disclosed as limitations in scientific publications.ConclusionsMost pivotal studies forming the basis of EMA approval of new cancer drugs between 2014 and 2016 were randomised controlled trials. However, almost half of these were judged to be at high risk of bias based on their design, conduct, or analysis, some of which might be unavoidable because of the complexity of cancer trials. Regulatory documents and the scientific literature had gaps in their reporting. Journal publications did not acknowledge the key limitations of the available evidence identified in regulatory documents.

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Section: Introductionmentioning

confidence: 99%

Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis

Naci

Davis

Savović

et al. 2019

BMJ

Self Cite

139

100

View full text Add to dashboard Cite

show abstract

“…The EMA coordinates Member State regulatory agencies responsible for market authorization and post-authorization surveillance through a decentralized process and oversees the scientific assessment of new biotechnology products through a centralized process. As members of the EMA’s Committee for Human Medicinal Products that oversee EU centralized product reviews are seconded from European state regulators, EU level politicians tend to refrain from imposing their agenda [ 81 ]. In the decentralized process, sponsors may choose the regulator with the least onerous standards, with the market authorization accepted in other Member States through mutual recognition.…”

Section: Results: International Approaches To Pharmacogovernancementioning

confidence: 99%

Transnational pharmacogovernance: emergent patterns in the jazz of pharmaceutical policy convergence

2018

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BackgroundAs a transnational policy network, the International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) aligns international regulatory standards to address the pressures of globalization on the pharmaceutical industry and increase access to new medicines. Founding ICH members include regulators and pharmaceutical industry trade associations in the European Union, the United States and Japan. In this paper we explore the manner in which state interdependence fosters the conditions for regulatory harmonization by tracing the underlying parallels between ICH and member state pharmacogovernance to clarify emergent patterns in regulatory policy convergence.ResultsA shift to the life cycle approach to pharmaceutical regulation corresponded with international convergence in pre-market standards as emphasis shifted to post-market standards where convergence remains unresolved. Transnational pharmacogovernance was found to concentrate regulatory authority within a co-regulatory model of bilateral negotiation with pharmaceutical trade associations in defining safety and efficacy standards. Given a context of state interdependence, parallels were found between transnational and ICH member pharmacogovernance modes that guide policy development. Divergent modes of state regulatory governance that re-calibrate perceptions of risk and risk mitigation were found to coincide with post-market policy dissonance.ConclusionAlthough interdependence fostered harmonization in pre-market standards and aligned with increased focus on post-market approaches, the confluence of divergent state governance modes and perceptions of risk may inspire improvisation in post-market standards. As the ICH expands to an ensemble with a greater global reach, further research is needed to clarify the manner in which interdependence shapes transnational pharmacogovernance and the conditions that foster policy convergence in the public interest.Electronic supplementary materialThe online version of this article (10.1186/s12992-018-0402-5) contains supplementary material, which is available to authorized users.

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“…And as noted, accelerated approval systems may not actually result in incentivisation and faster approval times (Boon et al, 2010) or more efficacious products (Davis and Abraham, 2013). This limited scope of exceptions and exemptions to dominant central regimes is defined by narrow criteria of rare disease, 'orphan' designation, critical but selective disease applications such as cancer, non-routine and thus restricted production runs, emergency or unmet need, and individual medical prescription.…”

Section: Resultsmentioning

confidence: 99%

Special Treatment? Flexibilities in the Politics of Regenerative Medicine’s Gatekeeping Regimes in the UK

Faulkner

2017

Science as Culture

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Emerging flexibilities are apparent in gatekeeping regimes applicable to regenerative medicine products, raising issues about the extent to which and forms in which such flexibilities might promote emerging products as a sector warranting special treatment, in the context of recent policy developments in the UK and wider European Union. Concepts of 'gatekeeping', 'gatekeeping regimes' and 'gateways' can point to the ways in which regulatory institutions, health technology assessment organisations, and national planners and purchasers of health services together define and control entry to the medical product marketplace and the adoption of products into the public healthcare system. Flexibilities in existing regimes and new gateways are a way of maintaining 'connection' between gatekeeping regimes and technoscientific innovation in order to steer innovation pathways. The gateways concept has affinity with that of Callon's 'obligatory passage points'. A wide set of recent policy documents show that the measures promoted exhibit a range of alternative gateways that are being constructed around central, legal, restrictive gatekeeping regimes. However, it would be easy to overestimate the significance of these developments as relaxations that would favour innovative producers and their products on a large scale with wide public health impacts. The concepts of gatekeeping regimes and gateways enable understanding of hybrid developments of exceptions and exemptions to dominant regimes which bridge across the arenas of market regulation, health technology assessment and healthcare system planning. These arenas are being drawn closer together as a means of politically managing stakeholders' aims in the UK, EU and other innovating biomedical health systems globally.

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Unhealthy Pharmaceutical Regulation

Cited by 72 publications

References 81 publications

Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis

Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis

Transnational pharmacogovernance: emergent patterns in the jazz of pharmaceutical policy convergence

Special Treatment? Flexibilities in the Politics of Regenerative Medicine’s Gatekeeping Regimes in the UK

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