Understanding and Measuring Key Symptoms and Health-Related Quality of Life in Patients with Chronic Immune Thrombocytopenia

Introduction Immune thrombocytopenia (ITP) is a rare autoimmune disorder in which there is an increase in platelet destruction and a decrease in platelet production, resulting in low platelet count, high bleeding risk and impact on quality of life (QoL). A critical appraisal of the literature was conducted to understand the patient experience with ITP and its treatment, and to assess which clinical outcome assessment (COA) instruments can best capture the ITP patient experience and changes due to disease management. Methods A focused PubMed search was performed for qualitative studies describing patient experience with ITP published prior to June 2019. The search paired population terms (ITP) with qualitative study design terms ("qualitative", "focus group/s", "interview/s", "blog"). Grey literature (congresses, patient advocacy group websites) was also consulted. Key patient-reported concepts of interest for measurement in clinical trials were identified. A second review was conducted to identify COA instruments used in ITP to measure the key concepts using PROQOLID (no limits; prior to November 2019), Clinicaltrials.gov (Phase 2 and 3; November 2009-2019), and PubMed (October 2009-2019). COA instruments were critically appraised based on their published psychometric properties and use in regulatory labels and health technology assessment (HTA) appraisal decisions. Results Of the 52 articles screened in the initial search, 2 relevant articles were identified. One reported the development of ITP-patient assessment questionnaire (ITP-PAQ), a disease-specific measure of health-related QoL (HRQoL) in adults with ITP (Mathias et al. Health and Quality of Life Outcomes 2007); the second introduced a conceptual model informed by literature, clinical expertise and qualitative research to describe the impact of ITP and its treatment on patients' HRQoL (Mathias et al. Health and Quality of Life Outcomes 2008). This conceptual model proposed 1 biological variable (low platelet count), 2 main determinants of HRQoL (symptoms of ITP, treatment side-effects) and 5 conceptual domains of HRQoL (emotional health, functional health, social and leisure, reproductive health, work). Fatigue and bleeding/bruising symptoms were considered the main determinants of HRQoL change for patients with ITP. However, the literature supporting this conceptual model was over 15 years old, from one country (US) and conducted in one clinical setting (tertiary care). A third recent publication reporting an interim analysis from the ITP World Impact Survey in 1,400 patients was identified from grey literature (Cooper et al. EHA Library 2018; PF654). Fatigue and bleeding (including petechiae) were the most frequently reported symptoms, at diagnosis and at time of survey completion, and fatigue was reported as one of the most severe symptoms. Twenty-two COA instruments used in ITP were identified for assessments of bleeding/bruising, fatigue/tiredness, anxiety/fear, and/or avoidance of physical activity. From this search, 8 instruments were analysed in depth: ITP-PAQ; Functional Assessment of Cancer Therapy - Thrombocytopenia 6 (FACT-Th6); FACT-Th11/18; Functional Assessment of Chronic Illness - Fatigue (FACIT-F); WHO Bleeding Score; ITP Bleeding Score; ITP-specific bleeding assessment tool (ITP-BAT); Short Form 36 (SF-36). The WHO Bleeding Scale is widely used in ITP and mentioned in at least one product label for ITP treatments (eltrombopag). The FACIT-F is the most widely-used fatigue instrument and was utilized in non-ITP related regulatory labels in the US and EU. It has also been considered by HTA agencies for ITP and its psychometric properties were validated in ITP. The ITP-PAQ was developed and validated in ITP for HRQoL evaluation; it was used for clinical development of romiplostim and was well considered by the National Institute for Health and Care Excellence (NICE). Conclusion The studies identified in these literature searches indicate that fatigue and bleeding are key determinants of HRQoL in patients with ITP. Three COA instruments (WHO Bleeding scale, FACIT-F and ITP-PAQ) were identified using evidence from the existing literature as potential valid tools to measure these concepts of interest in future ITP clinical trials. Disclosures Joly: Sanofi: Current Employment, Current equity holder in publicly-traded company. Reaney:IQVIA: Current Employment; Sanofi: Research Funding. Daak:Sanofi: Current Employment, Current equity holder in publicly-traded company. Venerus:Sanofi: Research Funding; IQVIA: Current Employment. Roborel de Climens:Sanofi: Current Employment, Current equity holder in publicly-traded company.