OBJECTIVES: Treatments for rare diseases are assessed by payers based on their ability to provide value-for-money, as the collective impact of these drugs represents a substantial part of the medication budget. Their value is often measured through cost-effectiveness assessments that are based on health utilities measured using generic instruments (e.g. EQ-5D) that may not adequately capture the full burden on patients and their caregivers/families.

METHODS: We carried out a systematic search of English language publications (16 Nov 2021) from 2000, and no geographical restrictions were applied. The searches were conducted in Medline, Embase, and Cochrane via the OVID platform. Targeted selection of abstracts and full texts identified publications that focused on patient and carer-relevant quality of life dimensions that are not typically captured by conventional generic quality of life (QOL) instruments.

RESULTS: 1,103 abstracts were retrieved and 31 full text articles were selected for in-depth review. Many rare diseases are diagnosed in childhood, and the burden of care and social stigma on patients, their carers/parents and their families is substantial. Aspects related to mental and medical support for carers and the future of their children, including schooling is something that affects parents’ quality of life. One study reported that mothers and fathers predict lower QOL compared to their children who rate their quality of life more positively. This can have implications for using parents as a proxy for QOL assessment. Most studies focused on childhood diseases and there was little published evidence on adolescent and adult rare disease patients. Aspects not captured by current utility instruments include parental stress, medication side-effects, hope and risk preferences, social functioning and stigma, cognition, education and expectations for the future.

CONCLUSIONS: Current utility instruments do not capture all patient/caregiver-relevant health aspects and therefore may underrepresent the true value offered by potential new treatments.