Abstract
Introduction
Pulmonary arterial hypertension (PAH) is a rare, incurable disease associated with decreased life expectancy and a marked impact on quality of life (QoL). There are three classes of drugs available for treatment: endothelin receptor antagonists (ERA), drugs acting on nitric oxide pathway (riociguat and phosphodiesterase type 5 inhibitors [PDE5i]), and drugs acting on prostacyclin pathway. The latter have widely different modes of administration – continuous intravenous infusion, continuous subcutaneous infusion, inhaled, and oral – each associated with variable treatment burden, and implications for health economic assessment. This study aimed to establish utility values associated with different modes of administration of drugs acting on the prostacyclin pathway for use in economic evaluations of PAH treatments.
Methods
A UK general public sample completed the EQ-5D-5L and valued four health states in time trade-off interviews. The health states drafted from literature and interviews with PAH experts (n=3) contained identical descriptions of PAH and ERA/PDE5i treatment, but differed in description of administration including oral (tablets), inhaled (nebulizer), continuous subcutaneous infusion, and continuous intravenous infusion.
Results
A total of 150 participants (63% female; mean age 37 years) completed interviews. Utilities are presented as values between 0 and 1, with 0 representing the state of being dead and 1 representing being in full health. The mean (SD) utility for oral health state was 0.85 (0.16), while all other health states were significantly lower at 0.74 (0.27) for inhaled (p=0.001), 0.59 (0.31) for subcutaneous (p<0.001) and 0.54 (0.32) for intravenous (p<0.001), indicating that there are disutilities (negative differences) associated with non-oral health states. Disutilities were −0.11 for inhaled, −0.26 for subcutaneous, and −0.31 for intravenous administration.
Conclusion
The results demonstrate quantifiable QoL differences between modes of administration of drugs acting on the prostacyclin pathway. QoL burden should be considered for economic evaluation of drugs for PAH treatment.
Acknowledgments
This work was funded by Actelion Pharmaceuticals Ltd. This study was conducted by ICON plc under a consulting agreement with Actelion Pharmaceuticals Ltd. The authors would like to acknowledge the participants of the study and the field-based TTO interviewers who were sub-contracted to ICON plc (Sophie Coates, Nell Ellison, Zoe Given-Wilson, Rosie McColl, Eleanor Parker, Nicola Tutt, and Christine Wilson). We would also like to thank Rainer Zimmermann (Actelion Pharmaceuticals Ltd.) and Diane Moran (Mater Misericordiae University Hospital) for clinical input and critical review of the health states and support document; Rachel Ballinger (ICON plc) for contribution to the development of the health states and support document; Sarah Corden (Medi-Ink Ltd.) for editorial assistance in preparing the manuscript; and Alexandra Kitt (Actelion Pharmaceuticals Ltd.) for assistance with literature searching and final manuscript review. The abstract of this paper was presented at the British Thoracic Society Winter Meeting 2017 (6–8 December 2017) as a spoken presentation. The presentation’s abstract was published in Thorax, volume 72, supplement 3 (https://doi.org/10.1136/thoraxjnl-2017-210983.55).
Author contributions
EWD and AB contributed to study design, data analysis and interpretation, and drafting or revising of the manuscript. SL, CEK, and HAD contributed to study design, data collection, data analysis and interpretation, and drafting or revising of the manuscript. WGS contributed to study design and drafting or revising of the manuscript. All authors approved the final version of the manuscript for publication, and agree to be accountable for all aspects of the work.
Disclosure
HAD, CEK, and SL are employees of ICON plc. AB and EWD are employees of Actelion Pharmaceuticals Ltd. AB owns stock or options. WGS has received honorarium for speaking and consultancy from Actelion Pharmaceuticals, Bayer AG, GlaxoSmithKline, and United Therapeutics. The authors report no other conflicts of interest in this work.