Health state utility values in congenital thrombotic thrombocytopenic purpura (cTTP): A vignette-based valuation Study in the UK general population

Abstract Introduction The aim of this UK study was to estimate health-related quality of life (HRQoL) in patients with congenital thrombotic thrombocytopenic purpura (cTTP) by eliciting utility values via a general population proxy approach. Vignette-based health states (HS) represented varying disease severities and treatments, including recombinant ADAMTS13 (rADAMTS13), plasma-based therapy (PBT) prophylaxis, and no prophylaxis. HS were defined based on literature and expert input and are summarized in the vignettes used for valuation. Methods Eight HS vignettes were developed based on a targeted literature review and validated by three UK clinical experts with experience in cTTP, in line with National Institute for Health and Care Excellence best practices. These vignettes reflected chronic HS in cTTP and captured associated utility values, which are numerical measures of HRQoL on a scale from 0 (death) to 1 (full health). Utilities were elicited using composite time trade-off (cTTO), combining conventional and lead-time TTO techniques, via an online, self-complete survey. Participants were not patients, but members of the UK general public recruited via an online panel. Direct patient input was not feasible due to the ultra-rare nature of cTTP. Of the 1,237 survey respondents, 1,102 (89%) passed quality control checks and were included in the analysis. All valuations, including those for a child and young person HS, were completed by adult respondents. Vignettes representing acute/subacute events were not included, as these transient states are considered unsuitable for valuation via cTTO. Results Utility values ranged from 0.33 to 0.71 across eight HS in cTTP: (1) Adult (≥18 years), non-overt symptoms (i.e. mild or less visible), PBT: 0.33; (2) Adult, no symptoms, PBT: 0.39; (3) Adult, no symptoms, no prophylaxis: 0.44; (4) Adult, no symptoms, rADAMTS13: 0.65; (5) Young person (12–17 years), no symptoms, no prophylaxis: 0.63; (6) Young person, no symptoms, rADAMTS13: 0.64; (7) Child (<12 years), no symptoms, no prophylaxis: 0.70; (8) Child, no symptoms, rADAMTS13: 0.71. The lowest mean utility (0.33) was elicited for the adult HS with non-overt symptoms receiving PBT prophylaxis, reflecting the perceived highest symptom burden and treatment complexity compared with other HS. The highest utility value (0.71) was for the child HS with no non-overt symptoms, receiving rADAMTS13, suggesting respondents were less willing to trade life years for children compared to adults. Among adult HS, rADAMTS13 prophylaxis was associated with significantly higher utility than no prophylaxis (mean difference +0.19, p<0.01), a trend also observed in younger age groups suggesting that participants valued the availability of a recombinant treatment option and its potential to improve disease control. PBT prophylaxis was rated lower than no prophylaxis, potentially due to the perceived treatment burden and adverse side effects. Notably, utility scores were low even in asymptomatic states (e.g., 0.44 for adult, no prophylaxis), indicating that respondents may have considered long-term prognosis and uncertainty, not only daily symptoms. This underscores the psychological burden of living with a chronic, life-threatening condition. Conclusions This study provides novel utility values for cTTP, with rADAMTS13 showing the highest scores across all age groups (up to 0.71), suggesting that a treatment that reduces both symptom and administration burden may meaningfully improve HRQoL. Several limitations should be noted: low scores even in asymptomatic states may reflect perceived long-term burden; and the online self-complete format may have limited participant understanding of treatment complexity. These values support the use of HRQoL in future evaluations of cTTP therapies.