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Table 1 PCOMs bring meaning to surrogate outcomes: the example of ruxolitinib for myelofibrosis [78,79,80]

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

Disease context: Myelofibrosisis is a rare disease of the bone marrow that disrupts the body’s normal production of blood cells. Sometimes the spleen or the liver takes over some of the blood production; these organs then enlarge which causes abdominal discomfort and pain. Typical symptoms also include feeling of fullness, night sweats and itching. Some patients with myelofibrosis develop leukaemia.
Research context & question: Phase 3 study assessing efficacy of ruxolitinib for myelofibrosis. Does shrinking a patient’s spleen lead to a patient-meaningful benefit?
Why add a PCOM? Spleen volume, as such, is a surrogate endpoint that ‘may’ predict treatment benefit, but is not in itself a direct measure of treatment benefit. Thus, as ruxolitinib was being developed, its sponsor chose – after sustained interactions with the U.S. FDA – to supplement the Phase 3 study primary endpoint on the reduction in spleen size with a newly-developed disease-specific patient-reported outcome (PRO) questionnaire (MSAF).
Result: Using a direct measure of treatment benefit from treated patients proved to be an effective complement to the primary surrogate endpoint to allow for fast regulatory approval and the avoidance of the requirement for additional post-marketing confirmatory trials. Its impact extended to reimbursement and HTA outcomes, where the improvement in disease-related symptoms were considered to be very important (for example in Germany and Canada), as very aligned with patients’ experience and values. This subsequently allowed patients affected with myelofibrosis to gain access to ruxolitinib as a new treatment option.