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Chapter 9286considered unsuccessful. Negative trial results may lead to companies not being able to continue their drug development program for rare disorders, and obstacles with market authorization or reimbursement of (orphan) drugs.15,32 Given the high expectations, the negative outcomes have been disheartening to affected individuals and families as they may miss out on important therapies.Too many, too messy: how to choose outcome measurement instruments?Deciding upon an appropriate outcome measure can be a daunting task, especially for rare and heterogeneous disorders. Many outcome measures have been applied in previous research and there are plenty of instruments available with each having its own properties. For many RGNDs multiple organ systems are involved and because most existing instruments focus on a single area, researchers have been forced to select a wide variety of tools to measure treatment effects. Additionally, lack of consensus on the most appropriate and relevant outcome measures has resulted in a situation in which several different outcomes have been reported using hundreds of different outcome measurement instruments, which is addressed in Chapter 5. For example, cognitive function was measured 333 times with 141 different outcome measurement instruments in clinical trials in RGNDs and ID from the past ten years. Similarly, health-related quality of life was measured 77 times with 24 different instruments, apart from being a broad, abstract, and multidimensional concept that can cover different concepts, obscuring the construct to be measured. Considerations and recommendations have been provided with regard to selecting outcomes and outcome measurement instruments in clinical trials for individuals with RGNDs (Chapter 5; Figure 2). The lack of consensus has also resulted in researchers and clinicians designing instruments ad-hoc to capture outcomes relevant to their patients. This is understandable as these might contain less redundant items to be completed and increase acceptability among affected individuals, but might be problematic as well. Measurement properties are often not investigated, and interpretation and extrapolation of results will be hampered. Annelieke Muller sHL.indd 286 14-11-2023 09:08