Page 18 - Demo

Chapter 116that do not demonstrate significant benefits based on these primary endpoints are deemed ‘negative’, with implications for registration and reimbursement by regulatory authorities.55 For example, within the Fragile X syndrome community, promising targeted treatments did not show positive effects on the primary behavioral outcome measures, despite improvements on secondary outcome measures or in post hoc analyses of potentially meaningful clinical subgroups, resulting in discontinuation of drug development and clinical trials by pharmaceutical companies.56,57Subsequently, it was questioned whether it was the intervention that was not effective or the chosen outcome measures were not appropriate.55,58These negative outcomes have been disheartening to families, resulting in a call to develop well-designed studies with sensitive outcome measures. Other hurdles have been encountered to choose appropriate outcome measures for clinical trials in ID, such as varying cognitive abilities of study participants, unavailability of outcome measures for self-report or adults with ID, limited sensitivity and lack of consensus on the best measures for this population.55,59 Choosing appropriate specific outcome measures for clinical trials can thus be challenging, considering feasibility, utility, acceptability, and measurement properties including validity and responsiveness to change. Surrogate outcomes are used as a substitute for a direct measure of how an individual feels or functions.60 However, surrogate or clinical outcomes are often narrow in their focus and it might be unclear whether changes are relevant. To get a better understanding of what is relevant to measure, it is important to monitor symptoms and measure the impact of the disease on functioning or quality of life. The ICF provides a framework for choosing outcome measures, capturing all components for better understanding of the disease’s impact on different life domains of an individual (Figure 4).61Patient-reported outcome measuresInformation about functioning can be obtained from patient-reported outcome measures (PROMs).62–64 PROMs are instruments that measure how affected individuals experience their own health and enable quantification and evaluation of severity and the impact of a disease from the patient’s perspective. It can be used for both monitoring and informing care, and as an outcome measure in clinical trials.65Annelieke Muller sHL.indd 16 14-11-2023 09:07