The risks of risk aversion in drug regulation

Eichler, Hans‐Georg; Bloechl-Daum, Brigitte; Brasseur, Daniel; Breckenridge, Alasdair; Leufkens, Hubert G. M.; Raine, June; Salmonson, Tomas; Schneider, Christian K.; Rasi, Guido

doi:10.1038/nrd4129

Cited by 92 publications

(66 citation statements)

References 37 publications

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“…Traditionally, regulators have made assumptions, albeit implicit, about what patients actually think and prefer, including their willingness to trade benefits for harms [1, 2]. Notwithstanding that the ultimate raison d’être of any medicine is to benefit patients who have a unique knowledge about their disease and its current therapeutic environment, traditionally patient views and preferences were rarely explicitly sought.…”

Section: Introductionmentioning

confidence: 99%

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers

Morel

Aymé

Cassiman

et al. 2016

Orphanet J Rare Dis

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BackgroundRare disease patients and caregivers face uncommon, serious, debilitating conditions often characterised by poor prognosis and limited treatment options. This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context.MethodsA mixed-methods survey with patients and caregivers was conducted in the United Kingdom across a range of rare diseases. Discrete-choice experiments that compared hypothetical treatment profiles of benefits and risks were used to measure respondent preferences across a set of seven attributes related to health outcomes, safety, and process of care. Bespoke questions on current disease management and the joint use of the 12-item WHODAS 2.0 questionnaire and of two Likert scales capturing self- and proxy-assessed disease-induced threat to life and impairment were implemented to describe disease context. Additionally, qualitative insights on the definitions of value and risk were collected from respondents.ResultsFinal study sample included 721 patients and 152 informal caregivers, across 52 rare diseases. When choosing between hypothetical novel treatments for rare diseases, respondents attributed most importance to drug response, risk of serious side effects, and the ability to conduct usual activities while on treatment. In contrast, attributes related to treatment modalities were the least important. Respondents expressed a willingness to accept risks in hopes of finding some benefit, such as a higher chance of drug response or greater health improvement potential. Increasing disease severity, impairment or disability, and the lack of effective therapeutic options were shown to raise significantly the willingness to gain benefit through increased risk.ConclusionsThis is the first study performing a quantitative discrete choice experiment amongst patients and caregivers across 52 rare conditions. It enables a more detailed understanding of the relationship between disease context, treatment attributes and the degree of risk respondents are willing to take to gain a specific degree of benefit. Researchers of novel therapeutics for rare diseases should be encouraged to invest in preference elicitation studies to generate rigorous patient evidence and specific regulatory guidance should be issued to acknowledge their importance and their use in marketing authorisations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0444-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers

Morel

Aymé

Cassiman

et al. 2016

Orphanet J Rare Dis

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“…However, only recently, regulators-being criticised for drug approvals based on limited evidence-proposed the concept of 'adaptive pathways' to manage risk and uncertainty after early approvals. 30 To evaluate the benefit of oncology drugs, tools are provided by professional organisations (eg, ASCO, ESMO). 12 13 These scales are highly appreciated 31 and can be approached to support the assessment of the patient-relevant clinical benefit of oncology drugs.…”

Section: Discussionmentioning

confidence: 99%

Between January 2009 and April 2016, 134 novel anticancer therapies were approved: what is the level of knowledge concerning the clinical benefit at the time of approval?

Grössmann

Wild

2016

ESMO Open

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ObjectiveIn the last decade an increasing number of high-priced, new cancer treatments received marketing authorisation in Europe. What is actually known about the clinical benefit of those therapies at the time of approval needs to be elucidated in order to inform decisions about the use and reimbursement of these novel treatment options. Thus, the aim of the current analysis was to systematically investigate oncological therapies approved between January 2009 and April 2016 and extract as well as quantify the level of knowledge of the clinical benefit at the time of marketing authorisation.MethodsTo assess the benefit of new interventions as well as expanded indications, we extracted the median gain of the two study end points: progression-free survival (PFS) and overall survival (OS). Information is based on approval documents provided by the European Medicines Agency and assessments from the Austrian Horizon Scanning programme. We included all cancer therapies approved in Europe between 2009 (January 1) and 2016 (April 15).ResultsCancer drugs for 134 new indications approved since 2009 were identified. In the case of 37 indications (27%), no data were available for PFS or for OS. A positive difference in median OS was reached by 76 licensed indications (55.5%); 22 (16%) of them showed a difference of more than 3 months. Regarding the study end point PFS, an improvement was shown in 90 indications (65.2%).ConclusionScarce knowledge regarding the clinical benefit of anticancer therapies is available at the time of approval. In addition, the survival benefit of the approved indications is less than 3 months in the majority of approved therapies.

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“…This is further supported through transparency measures for building public trust. In summary, proactive, effective and transparent pharmacovigilance, leading to confidence and trust, supports product development to fulfil unmet medical needs and helps ensure that any knowledge gaps are addressed in a timely manner and in the best interests of public health 8 .…”

Section: I N K To O R I G I N a L A Rt I C L Ementioning

confidence: 99%

Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee

Arlett¹,

Portier²,

Lisa³

et al. 2014

Nat Rev Drug Discov

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The risks of risk aversion in drug regulation

Cited by 92 publications

References 37 publications

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers

Between January 2009 and April 2016, 134 novel anticancer therapies were approved: what is the level of knowledge concerning the clinical benefit at the time of approval?

Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee

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