Background

Immune Thrombocytopenia (ITP) is an autoimmune disorder caused by immunologic destruction of otherwise normal platelets, most commonly occurring in response to an unknown stimulus. ITP is diagnosed after excluding other possible causes of disease, and symptoms can present across varying severities and treatments. The poor understanding of the symptoms and cause can result in both misdiagnosis and complex treatment patterns, which may significantly affect health related quality of life (HRQoL) in this patient population. There is currently no disease specific prospective tool in routine clinical practice to capture HRQoL in the adult ITP population.

To help assess the impact of this condition on HRQOL, the ITP Life Quality Index (ILQI), a 10-item patient-reported outcome (PRO) measure was developed as a tool for clinical practice to aid discussions between patients and physicians about disease experience so to inform patient-centric treatment decisions. The ILQI was originally developed by clinical experts in the field of ITP and content validity was confirmed by conducting qualitative interviews with 15 adult patients with ITP. The ILQI was then cognitively debriefed patients with ITP and items refined following qualitative analysis and additional clinical input.

The ILQI was included in the ITP World Impact Survey (I-WISh), a global observational study which collected data on the impact of ITP on patients' HRQoL. This large study provided an opportunity to assess the psychometric properties of the ILQI and confirm the scoring cut-offs.

Methods

The I-WISh survey resulted in data from 1,507 patients with ITP across 12 countries worldwide and was used to assess the structure, reliability and validity of the ILQI. The structure of the ILQI, how the items fit into total scores and subscales, was assessed by splitting the data into two datasets. One dataset was used for identifying the structure using exploratory factor analysis and one was used for checking the structure using confirmatory factor analysis. Validity, the ability of the ILQI to measure the correct construct, was assessed through known groups and convergent validity methods. Reliability, the consistency of the ILQI items and their ability to create reproducible scores, was assessed via internal consistency methods. To understand whether each ILQI item measured ITP in a similar way across countries, differential item functioning (DIF) was assessed using Cochran-Mantel-Haenszel test and Logistic regression. Finally, existing score cut-offs (20-"significantly impaired QoL"; 30 - "severely impaired QoL") were assessed using receiver operating characteristic (ROC) curves and a simulation study was conducted to develop rules for missing data.

Results

Results indicated that the ILQI has an essentially unidimensional structure, supporting the creation of a total score including all 10 items. The ILQI items work together to create a reproducible total score, usable for making judgements on an individual patient basis (Omega total and Cronbach's alpha coefficients ≥ 0.90). Known groups methods showed that ILQI monotonically increased with ITP severity (linear trends p's <0.001). Convergent validity methods confirmed hypothesized relationships between ILQI total/item scores and items which measure aspects of HRQOL, suggesting that the ILQI total score and its items measure the same concept of interest (i.e. HRQOL). DIF analyses showed that ILQI item responses were similar between the USA and Western countries. Some uniform DIF was discovered between the USA and other countries, and some non-uniform DIF was found between the USA and China for culturally relevant items as expected. The previous clinical cut-off of 20 for "significantly impaired QoL" was supported, but a cut-off 30 may be too conservative for assessing "severely impaired QoL". Missing data simulation suggests that a total score can be created even when some items are missing.

Conclusion

The ILQI is a valid and reliable, unidimensional measure to assess HRQoL of patients with ITP. Despite some variations in ILQI item responses between USA and China, adoption of the ILQI in routine care will improve consistency of patient-centric decision making and may lead to better outcomes for those patients whose HRQoL has been affected. The revised cut-off scores for the ILQI developed will also aid patient-centric decision making between patients and physician.

Disclosures

Griffiths:Adelphi Values Ltd: Employment; Novartis: Consultancy. Grant:Novartis: Consultancy; Adelphi Values Ltd: Employment. Bonner:Adelphi Values Ltd: Employment; Novartis: Consultancy. D'Alessio:Novartis: Employment, Equity Ownership. Hill:Apellis: Honoraria; Bioverativ, a Sanofi company: Honoraria; Novartis: Speakers Bureau; Alexion: Research Funding. Provan:Rigel ONO: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; UCB: Consultancy; MedImunne: Consultancy; ONO Pharmaceutical: Consultancy. Ghanima:Bayer: Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Pfizer/BMS: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Cooper:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Viana:Novartis: Employment, Equity Ownership.

Author notes

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Asterisk with author names denotes non-ASH members.