Background
Health related quality of life (HRQoL) of patients with hematological malignancies (HMs) is greatly affected by the disease and the treatment and this has not been captured in a systematic manner in routine clinical practice. A systematic review of the HRQoL issues and instruments used in HM showed gaps between what is important to patients and what is being measured. The aims of this study were to develop and validate an instrument for measuring the impact of HMs and their treatment on patients' HRQoL and symptoms in daily clinical practice.
Methods
A multicentre Ethics approval was obtained from the National Research Ethics Service (NRES) of South West Bristols, UK. Adult patients with HM as per 2016 Revised WHO classification, capable of reading English and able to give written informed consent, were recruited from inpatient/outpatient clinics of seven secondary care hospitals in England and Wales for all phases of the study (Table 1). The qualitative study employed semi-structured face-to-face interviews. The generated items were then discussed in data definition panel meeting for inclusion in the prototype version of the new instrument. The content validation was followed by item reduction phase where number of items were reduced to more confined set of items. The version of HM-PRO developed after exploratory factory analysis and confirmatory factor analysis was used to perform Rasch modeling. In next step for demonstrating validity of the HM-PRO, construct and convergent/divergent validity was studied. The score banding was developed and MCID was established.
Results
Face-to-face interviews were performed in 129 patients. The content analysis of the transcribed interviews resulted in a comprehensive item pool. The generated items included in the prototype HM-PRO, were 34 items for impact on HRQoL category (Part A) and 23 items representing disease signs and symptoms (Part B). The version after exploratory and confirmatory factor analysis was used to perform Rasch modeling in 182 patients resulting in 24 items in Part A and 18 items in Part B. The reliability testing (n=150) showed strong stability of measurement with Cronbach's alpha estimates of the HM-PRO for both assessment points (t1 and t2) above 0.9 for Part A, and above 0.8 for Part B. The intraclass correlation coefficient (ICC) for four domains of Part A was 0.85 - 0.91 and >0.8 for the overall scores of Part A and Part B, for all ten diagnoses, confirming strong reliability of the HM-PRO. Construct and convergent/divergent validity were studied in 905 cases. The HM-PRO scores correlated with scores of EORTC QLQ-C30 and FACT-G, both at the scale and at individual item levels. The univariate regression analysis confirmed a strong relationship between the HM-PRO and the other two measures. For the majority of regression models, the HM-PRO domains and individual items explained more than 50% of the variance in domain and item scores of EORTC QLQ-C30 and FACT-G, confirming the construct validity. The responsiveness testing (n=299) showed that HM-PRO is responsive to small but clinically important change in patients' HRQoL. The score banding was developed for the HM-PRO for its interpretability in to day-to-day clinical practice. The MCID for Part A based on standard error of mean was 6.2 and for PART B 5.9 points. It therefore was prudent, for practical reasons, to propose MCID of '6' for the HM-PRO.
Conclusion
This study provides evidence of the value of HM-PRO through content validity, reliability, construct validity, responsiveness and interpretability. The current research has developed and validated the English version of the HM-PRO. Further studies are being carried out to validate the instrument in several global languages for cross-cultural adaptation. Furthermore, the Acute Leukaemia Advocates Network (ALAN) is using the HM-PRO in a multi-country survey including five European (French, German, Italian, Portuguese, Spanish) and five non-European countries (Chinese, Hebrew, Korean, Japanese, Russian) to generate data in order to understand the impact of the disease and treatment on patients with different types of leukaemia. The data collected from this survey will be used to further validate the HM-PRO specifically in patients with leukaemia and potentially improve management of patients and their treatment. The HM-PRO has good potential to be widely used in daily clinical practice as well as in hemato-oncology clinical trials.
Kell:Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Fielding:Incyte: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Collins:Gilead: Consultancy, Honoraria. Salek:Pfizer: Honoraria, Speakers Bureau; Agios Pharmaceuticals, Inc.: Consultancy, Honoraria; Merck: Consultancy.
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