A Clinical Trial Readiness Study of Patient Reported Outcome Measures in Thrombotic Thrombocytopenic Purpura (TTP)

PROJECT SUMMARY/ABSTRACT With a prevalence of 10 cases per million, immune thrombotic thrombocytopenic purpura (iTTP) is classified as a rare disease. Yet, it has significant human and economic impacts – untreated mortality rates of 90%; disproportionate effects on women and minorities; and per-patient costs > $1 million. Adding to these

impacts, patients with iTTP report that their most significant health-related quality of life impact is cognitive function. Yet, despite promising therapeutic candidates (anfibatide and TAK-755) in early phase clinical trials, cognitive function impacts cannot be accurately measured because a comprehensive assessment of aspects of

cognitive function influenced by iTTP has not been conducted. Though used in iTTP clinical trials, available cognitive measures lack sufficient validity evidence. Thus, no validity evidence is insufficient for clinical outcome assessments (COAs) of cognitive function for the context of use of iTTP clinical trials. Without validity evidence

for COAs, iTTP clinical trials cannot align with FDA recommendations for patient-focused drug development: They cannot incorporate outcomes that are important to patients. Even worse, patients’ cognitive function response to new therapies cannot be appropriately assessed. Thus, patients cannot be referred for treatments

that improve cognitive function outcomes. Thus, the absence of validity evidence for COAs of cognitive function is a critical barrier to iTTP clinical trial readiness. To facilitate clinical trial readiness in outcomes that are important to patients, there is an urgent need to develop a measurement strategy for iTTP-associated cognitive

impairment. The objective of the study is to develop a consensus-driven measurement strategy of cognitive function for iTTP clinical trials. To this end, the study will both determine iTTP impacts on cognitive function and develop a cognitive function measurement strategy. To this end, the study will use a sequential mixed methods approach.

First, using qualitative interviews of 24 patient-caregiver dyads, the study will develop an iTTP-induced cognitive impairment draft conceptual model. Second, using both a literature review and a multistakeholder advisory panel, a consensus-based approach will be used to select cognitive function COAs that have sufficient evidence for

being fit-for purpose. The study will benefit from robust recruitment at 3 participating sites within the National Patient-Centered Clinical Research Network – PCORNnet®. The study team has expertise in iTTP, neurogenic disorders, and COA measurement strategy. A boon to iTTP clinical trial readiness, successful completion of this study will support the use of cognitive

function COAs that are psychometrically rigorous. Furthermore, because they will be made available in the public domain, the conceptual and measurement models from this study will be used to further iTTP clinical trials: They can be accessed by both industry and regulatory agencies. This research is significant because it addresses

cognitive function – the aspect of iTTP survivorship most important to patients. Because it will develop a consensus-driven measurement strategy of cognitive function, this research is also innovative. Responsive to PAR-23-159, this research meets the National Center for Advancing Translational Sciences (NCATS) priority of

facilitating clinical trial readiness for rare diseases, disorders, and syndromes.