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

Abstract

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.

Measuring what matters to rare disease patients – reflections on the work by the IRDiRC taskforce on patient-centered outcome measures

“…And, at times, the outcomes considered critical by clinicians are not the same as the priorities of patients. In chronic, debilitating diseases such as most rare diseases, disease stabilisation ‘ is ’ improvement and may thus be considered as a meaningful outcome to patients [ 27 , 28 ]. Another hurdle to accurate outcome measurement relates to a phenomenon known as ‘response shift’, which in this case would refer to situations where rare disease patients adapt to their impairment leading to a ‘new normal’; their self-reported health status becomes ‘fine’ [ 29 ].…”

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