Immune thrombocytopenia (ITP) World Impact Survey (I‐WISh): Impact of ITP on health‐related quality of life

Abstract Immune thrombocytopenia (ITP) has a substantial, multifaceted impact on patients' health‐related quality of life (HRQoL). Data describing which aspects of ITP physicians and patients perceive as having the greatest impact are limited. The ITP World Impact Survey (I‐WISh) was a cross‐sectional survey, including 1507 patients and 472 physicians, to establish the impact of ITP on HRQoL and productivity from patient and physician perspectives. Patients reported that ITP reduced their energy levels (85% of patients), capacity to exercise (77%), and limited their ability to perform daily tasks (75%). Eighty percent of physicians reported that ITP symptoms reduced patient HRQoL, with 66% reporting ITP‐related fatigue substantially reduced patient HRQoL. Patients believed ITP had a substantial impact on emotional well‐being (49%) and 63% worried their condition would worsen. Because of ITP, 49% of patients had already reduced, or seriously considered reducing their working hours, and 29% had considered terminating their employment. Thirty‐six percent of patients employed at the time of the survey felt ITP decreased their work productivity, while 51% of patients with high/very high symptom burden reported that ITP affected their productivity. Note, I‐WISh demonstrated substantive impact of ITP on patients' HRQoL both directly for patients and from the viewpoint of their physicians. Patients reported reduced energy levels, expressed fears their condition might worsen, and those who worked experienced reduced productivity. Physicians should be aware not only of platelet counts and bleeding but also the multi‐dimensional impact of ITP on patients' lives as an integral component of disease management.

patient and physician perspectives. Patients reported that ITP reduced their energy levels (85% of patients), capacity to exercise (77%), and limited their ability to perform daily tasks (75%). Eighty percent of physicians reported that ITP symptoms reduced patient HRQoL, with 66% reporting ITP-related fatigue substantially reduced patient HRQoL. Patients believed ITP had a substantial impact on emotional wellbeing (49%) and 63% worried their condition would worsen. Because of ITP, 49% of patients had already reduced, or seriously considered reducing their working hours, and 29% had considered terminating their employment. Thirty-six percent of patients employed at the time of the survey felt ITP decreased their work productivity, while 51% of patients with high/very high symptom burden reported that ITP affected their productivity. Note, I-WISh demonstrated substantive impact of ITP on patients' HRQoL both directly for patients and from the viewpoint of their physicians. Patients reported reduced energy levels, expressed fears their condition might worsen, and those who worked experienced reduced productivity. Physicians should be aware not only of platelet counts and bleeding but also the multi-dimensional impact of ITP on patients' lives as an integral component of disease management.

| INTRODUCTION
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet counts (< 100 × 10 9 /L) and increased bleeding risk in the absence of another cause or disorder associated with thrombocytopenia. 1 In adults, its prevalence ranges from 9.5 to 12.1 cases/100 000 in the United States, rising with increasing age. 2,3 The impact of ITP and its treatments on patient health-related quality of life (HRQoL) may affect the entire spectrum of patients' lives, encompassing daily activities, emotional health, energy level, fatigue, and work productivity. The HRQoL is often reduced in patients with ITP compared with healthy controls. [4][5][6] Compared with age-matched and sex-matched controls, patients with ITP have lower work productivity, more physician visits, and are more likely to take sick leave. 7 These findings of reduced HRQoL in patients with ITP are largely undisputed. However, one patient survey reported only 11% of respondents felt ITP "often or extremely" affected their school or work activities, and only 7% reported non-occupational activities were adversely affected by their disease. 8 Another survey of patients with ITP and hematologists reported a reverse mismatched perception of disease impact on HRQoL; 9 71% of "ITP-experienced" hematologists felt patient HRQoL was moderately to substantially impaired, whereas only 34% of patients reported any impairment. 9 These findings may be consistent with a study of more than 400 patients showing that those with chronic ITP (disease duration ≥ 12 months) reported being less affected by ITP than patients with persistent disease (duration of ITP 3-12 months). This suggests patients become so accustomed to a life with reduced HRQoL that they may think it is their "normal". 1,4 This hypothesis has been validated in patients with ITP who rediscover their energy after treatment. 10 There are limited data describing which aspects of ITP treating physicians and patients perceive as having the greatest impact on HRQoL nor is there a clear, overall description of the full range of effects on patients.
This report presents the results of the international, online, ITP World Impact Survey (I-WISh) completed by 1507 patients and 472 physicians, summarizing the impact of ITP on various aspects or dimensions of patients' HRQoL, and comparing patient and physician perceptions of symptoms and disease management. Survey data reporting on the patient journey and symptoms associated with ITP will be reported in a separate manuscript (Cooper et al., manuscript in preparation  Patients also completed the newly-developed ITP Life Quality Index (ILQI) 12 that included 10 questions on impact of ITP on: work or studies, time taken off work or education, ability to concentrate, social life, sex life, energy levels, ability to undertake daily tasks, ability to provide support, hobbies, and capacity to exercise. The response options were "never", "sometimes", "more than half the time", and "all of the time". Survey materials and the study protocol were reviewed and approved by central Institutional Review Boards (IRB) in both Europe and North America. Patients and physicians were given an overview of the study and the ethical approval details; those who wished to participate had to provide consent via a tick/check box before initiating.

| Statistical analyses
Patient and physician survey data were analyzed separately using descriptive statistics. No formal hypotheses were tested. The objective of this research was to conduct a global study with a sample size of over 1500 patients to understand the burden of living with ITP. As finding a representative, well-matched control group would have been very difficult given the nature of the study, we opted to evaluate as many patients as possible in this exploratory analysis. This also enabled us to meaningfully explore various subgroups.
Subgroups that were explored included sex (males vs females), age (18-49 vs ≥ 50 years), and symptom burden (low, moderate, high, and very high). Symptom burden score for the time of ITP diagnosis was retrospectively estimated by the patient when they completed the survey. The overall symptom burden was calculated by summarizing individual symptom severity scores and then dividing into quartiles where Q1 = lowest symptom burden and Q4 = highest symptom burden (supplementary methods).

| RESULTS
The I-WISh survey was completed by 472 physicians and 1507 patients between December 2017 and August 2018. The largest number of patients and physicians were recruited from the US, China, and the UK (Table S1). Physicians had a mean (SD) ITP patient caseload of 34 (50) and saw a mean (SD) of 18 (36) newly diagnosed patients in the past year (Table S2).
The mean age of patients with ITP was 47 years, 65% were female, and respondents had been diagnosed with ITP a median of 5 years earlier (Table S2). Forty-eight percent of patients reported a high or very high symptom burden at diagnosis (Table S2).

| Impact of ITP on functional aspects of patients' HRQoL
Within the I-WISh survey, the ILQI asked 10 questions that explored the impact of ITP on aspects of patients' daily lives within the last month ( Figure 1A). Sixty percent, or more, of patients answered "sometimes" to "all the time" to all 10 questions. The aspects most affected ("more than half the time" or "all the time") were energy levels (42%; n = 631/1505) and ability to exercise (34%; n = 515/ 1505), with the other eight aspects being most affected between 15% and 25% of the time. Fewer patients recruited by physicians (35%) reported that ITP affected their energy levels compared with patients recruited by PAGs (47%). Seventy percent of patients reported some impact of ITP on their social lives and 60% reported impact on their sex lives. More than one-third of patients had high or very high symptom burden at diagnosis (n = 590, 39%) and 97% (n = 572) of these patients stated that ITP reduced their energy levels at some time.
Similar to the patient response, where 75% of patients felt the ability to undertake daily tasks was impacted by their ITP at least sometimes, two-thirds (63%, n = 297/468) of physicians felt that ITP had a negative effect on the overall level of physical activity in their patients (a score ≥ 5 on a 7-point Likert scale; 7 = a great deal).  There was evidence of concern about physical appearance, however patients did not rate this concern as high as other issues.

| Impact of ITP on patients' psychological and emotional well-being
Thirty-five percent (n = 527/1507) of patients indicated substantial concern about physical appearance (ie, bruising, rashes, and lumps), and 28% (n = 422/1507) of patients reported wearing long-sleeved clothing to hide evidence of bleeding (score ≥ 5 on a Likert scale 1-7; 7 = a great deal) ( Figure 1B). When separated by gender, 31% of males were not concerned about physical appearance (Likert score of 1) compared with 22% of females; however, the proportions of women and men reporting concern about their physical appearance were similar (score ≥ 5 on a Likert scale 1-7; 7 = a great deal).
Thirty-nine percent of younger patients (aged 18-49 years) voiced concerns about their physical appearance compared with 30% of older patients (aged ≥ 50 years).

| Impact of ITP on work and activities
The Organisation for Economic Co-operation and Development (OECD) indicates that, across its 37 member countries, 68.9% of the population of working age (15 to 64 years of age) are employed and that 16.5% of this total are in part-time employment. 13 At survey completion, 60% of respondents reported that they were employed; 44% (n = 661/1507) were in full-time employment and 16% (n = 235/ 1507) in part-time employment (Table 1).
Forty-nine percent of respondents (n = 538/1091) reported that they had reduced or seriously considered reducing their working hours because of their ITP, with 29% (n = 307/1070) reporting that they had considered terminating their employment (Figure 2A). Overall, 11% of patients were forced to stop working because of their ITP, How often has ITP impacted your energy levels? (n = 1505) 26% + 16% = 42%  Forty-three percent of all patients reported that their ITP affected regular activities outside of work (described as work around the house, shopping, childcare, exercise, and studying [score ≥ 5 on a scale of 1-10; 10 = completely prevented productivity]) ( Figure 2C).
Proportions of women and men who reported an impact of ITP on their regular activities were similar. Forty-eight percent of younger patients (18-49 years) reported an impact on regular activities compared with 39% of patients aged ≥ 50 years ( Figure 2D). Fifty-two percent (n = 239/461) of physicians felt that ITP had a negative impact on their patients' ability to undertake daily activities (food preparation, housework, gardening, childcare, and oral hygiene).

| Patient satisfaction and perception of treatment
Patients were asked about their satisfaction with the current pharma-

| Treatment goals and relationship with physician
Outside of sustained remission or a cure for ITP and reducing side effects, the three most important treatment goals identified by patients were "healthy blood counts" (64%; n = 968/1507), The 10-scale ITP-patient assessment questionnaire (PAQ), which was not available at the time of design of this study, suggested that successful treatment of ITP was associated with improvement in HRQoL. 15 The I-WISh survey, which included the 10-question ILQI, is a novel, very extensive QoL questionnaire which identifies the degree of impact that ITP has on patients' HRQoL, emotional health, social, personal, and work life. Concerns about unstable platelet counts, low energy levels, inability to exercise, and reduced participation in hobbies and work had the greatest negative impact. While most patients reported "good health", nonetheless half of patients reported a negative impact on their emotional well-being that worsened with increasing burden of disease and was often substantial. This "overly good" report about health may reflect that they were not bleeding at the time of survey completion, but probably more so that they were acclimated to their reduced state of energy, and did not consider this in their "health" assessment, perhaps not realizing it was at least partially connected with the ITP. People also have the tendency to say that they are "fine" when asked.
Previous evidence reported fatigue in 1/5 to 1/2 of adults with ITP. 9

26%
Physicians were asked to rank their 3 most important treatment goals for your patients, other than a cure for ITP, with 1 being the most important (A) (B) F I G U R E 3 Top three treatment goals identified by A, patients and B, physicians. Most frequently selected treatment goals (patients and physicians were asked to select and rank their top three treatment goals) Previous evidence from a discussion group of 23 patients found that patients reported restrictions in their social activities due to bruising. 15 So, I-WISh also identified concerns about physical appearance, including bruising, as an issue in 35% of patients with ITP to the extent of wearing long-sleeve clothing. Health professionals working with patients with ITP need to consider the impact of physical appearance and fatigue on HRQoL, and adjust their management accordingly. Surprisingly, this was not different between males and females.
As initially reported using the ITP-PAQ, 15   This trial data availability is in accordance with the criteria and process described on www.clinicalstudydatarequest.com.