IMPACT (Immune Monitoring and Phenotype Assessment of Clinical Trajectory) for Patients With Inborn Errors of Immunity From the Primary Immune Deficiency Treatment Consortium (PIDTC)

BACKGROUND: Evaluating natural history and outcomes of rare inborn errors of immunity (IEIs) has been challenging due to the diverse disease manifestations and lack of standardized data. OBJECTIVE: To develop a set of standardized, quantitative, generalizable data collection modules to measure organ dysfunction in IEIs, modeled on the previously validated Common Terminology Criteria for Adverse Event system for grading treatment toxicity. METHODS: Disease conditions were organized by organ system. Experts from the Primary Immune Deficiency Treatment Consortium identified essential features of severe combined immunodeficiency, chronic granulomatous disease, Wiskott-Aldrich syndrome, and primary immune regulatory disorders and compared these to Common Terminology Criteria for Adverse Event conditions, adding and refining features as needed. Dates of onset and resolution, disease-specific laboratory values, and therapeutic interventions were also incorporated. Modules were reviewed by protocol teams, key stakeholders, clinical coordinators, and statisticians to improve feasibility and completeness. RESULTS: We developed a tool called IMPACT (Immune Monitoring and Phenotype Assessment of Clinical Trajectory) containing 15 modules assessing 196 disease conditions. A grading system from 1 to 5 (mild, moderate, severe, life-threatening, fatal) permits longitudinal tracking of disease condition severity. Outcomes of interventions can be measured quantitatively by comparing scores before and after treatment. CONCLUSIONS: Standardized, quantitative assessment tools for IEIs can yield uniform data sets to illuminate their natural history and evaluate outcomes of interventions, not only to understand specific diseases but also to compare effects between disease entities. Tools, such as IMPACT, are essential for therapeutic trials for rare, complex multisystem diseases such as IEIs and other disorders with protean manifestations.