Elicitation of health state utilities associated with the mode of administration of drugs acting on the prostacyclin pathway in pulmonary arterial hypertension

Figures & data

Table 1 Final health states

Mode of administration	Agent
Twice-daily oral drug	• Selexipag (Uptravi^®)
Nebulization	• Iloprost (Ventavis^®)
Continuous subcutaneous infusion	• Treprostinil (Remodulin^®)
Continuous intravenous infusion with a permanent cathetera	• Epoprostenol non thermostable (Flolan^®)
	• Epoprostenol thermostable (Veletri^®, Flolan pH12^®)
	• Treprostinil (Remodulin^®)

Notes:

a Three different products are available via this mode of administration. There are minor differences between the three formulations. Epoprostenol thermostable was used as the reference case for development of the health state.

Table 2 Example health state

∆
Disease	• You have a condition which means you have high blood pressure in your lungs. This puts a strain on the right side of your heart as it has to work harder to push blood through the lungs to pick up oxygen.
Main symptoms	• You often feel tired.
	• You find it difficult to breathe (experience shortness of breath) when you climb stairs and cannot keep up with others when walking on the flat.
	• You often feel light-headed (dizzy) when you stand up.
	• You can sometimes experience pain and a feeling of tightness in your chest when undertaking exercise such as walking at the same pace as others on the flat (level ground) or carrying shopping.
Impacts	• You cannot do things in the house that need a lot of physical effort such as vacuuming, carrying shopping, or gardening.
	• You are able to work, but you cannot do anything at work that involves a lot of physical exertion, such as carrying heavy objects.
	• You are able to socialize, but you cannot do sports or physical activities that involve a lot of physical exertion.
	• You are able to travel for work or holidays but this needs to be planned in advance and routes that involve stairs and a lot of walking will be more difficult.
Treatment	• Every 3 months you have a medical assessment involving blood tests. This takes about half a day.
	• To stabilize your symptoms and to prevent your condition from getting worse, you are treated with medication.
	• You need to take 2 types of tablets each day.
	• Tablet 1 needs to be taken twice a day.
	• Tablet 2 needs to be taken three times a day.
	• You also take a medication that is delivered directly into your bloodstream through a narrow, flexible tube called a catheter. This is inserted under local anesthetic into a vein leading to your heart.
	• The catheter is linked with a thin tube to a plastic container of the drug fixed to a pump, which you need to carry with you at all times. The pump is about the size of a calculator and weighs approximately 400 g (about the weight of a tin of beans).
	• To have the catheter inserted, and to learn how to prepare the plastic containers and use the pump, you stay in hospital for 7 days.
	• You should not get the pump wet, so you should protect this with a waterproof covering when showering. You should not go swimming with the pump.
	• Once you have learnt how to get the medication ready, you can fill seven plastic containers needed for a week on the same day, and store them in the fridge. This takes you about one hour.
	• You need to change the medication plastic container daily. This takes about 10 minutes.
	• The catheter site needs to be cleaned carefully at least once a week so that it does not get infected. The cleaning takes about 5–10 minutes.

Table 3 Sociodemographic and EQ-5D-5L results

Demographic	Study sample (n=150)	UK populationa
Sex (%)
Male	56 (37.3%)	49.2%
Female	94 (62.7%)	50.8%
Median age (mean, SD), years	33.5 (37.2, 14.3)	40.0
Range, years	18–74	–
Ethnicity (%)b
White	107 (71.3%)	85.9%
Mixed race	11 (7.3%)	2.2%
Asian	14 (9.3%)	7.5%
Black	15 (10.0%)	3.4%
Other/Middle Eastern	2 (1.3%)	0.6%
Prefer not to answer	1 (0.7%)	–
Employment status (%)
Employed full time	55 (36.7%)	55.2%
Employed part time	32 (21.3%)	19.7%
Student	22 (14.7%)	4.9%
Seeking work	6 (4%)	–
Unemployed	5 (3.3%)	6.3%
Retired	7 (4.7%)	–
Self-employed	16 (10.67%)	13.9%
Stay at home	4 (2.7%)	–
Other	3 (2%)	–
Qualifications (%)
No qualifications	3 (2.0%)	22.7%
Qualifications (non-university)	63 (42.0%)	50.2%
Qualifications (university)	84 (56.0%)	27.2%
Marital status (%)
Single	65 (43.3%)	34.6%
Partner/married	76 (50.7%)	46.8%
Divorced/separated/widowed	9 (6.0%)	18.6%
Children, n (%)
Yes – have children	59 (39.3%)	–
No – do not have children	91 (60.7%)	–
Median number of children as dependents (SD)	1 (0.95)	–
Other dependents, n (%)
Yes – have other dependents	7 (4.7%)	–
No – do not have other dependents	143 (95.3%)	–
EQ-5D-5L scoresc
Dimension scores, n (%) > none
Mobility	17 (11.3%)	623 (18.4%)
Self-care	6 (4.0%)	144 (4.3%)
Usual activities	23 (15.3%)	551 (16.3%)
Pain/discomfort	45 (30.0%)	1,117 (33.0%)
Anxiety/depression	37 (24.7%)	710 (21.0%)
EQ-5D index score, mean (SE)	0.90 (0.01)	0.86 (<0.01)
EQ VAS score, mean (SE)	81.5 (1.25)	82.8 (0.4)

Notes:

a Sex and age data from Overview of the United Kingdom (Office for National Statistics 2015).⁴¹ Ethnicity, qualifications, marital status, and religious status data from UK Census data (Office for National Statistics, 2011).⁴² Employment data from UK Statistical Bulletin (Office for National Statistics, 2016).⁴³

b One participant was both Black/African/Caribbean/Black British – African and Black/African/Caribbean/Black British – Caribbean. One participant was both White – English and Black/African/Caribbean/Black British – Caribbean (and categorized as being of mixed race).

c Study sample using the EQ-5D-5L. UK norms using the EQ-5D-3L.⁴⁰

Abbreviations: SD, standard deviation; SE, standard error; VAS, visual analog scale.

Figure 1 Mean TTO utility scores for each PAH health state.

Notes: *p-value vs oral health state; p<0.001; mixed model F = 92.4, p<0.001.
Abbreviations: PAH, pulmonary arterial hypertension; SD, standard deviation; TTO, time trade-off.

Figure 2 Mean VAS utility scores for each PAH health state.

Notes: *p-value vs oral health state; p<0.001; mixed model F = 326.5, p<0.001.
Abbreviations: PAH, pulmonary arterial hypertension; SD, standard deviation; VAS, visual analog scale.

Figure 3 Mean disutilities of TTO utility scores for each non-oral vs oral PAH health state.

Notes: *p-value vs oral health state; p<0.001.
Abbreviations: PAH, pulmonary arterial hypertension; SD, standard deviation; TTO, time trade-off.

Table 4 Results from the univariable and multivariable mixed effects regression models of TTO utility scores, with p-values significant at p<0.05 indicated in bold

TTO scores (N=150)	Univariable β (SE)	p-value	Multivariable Adj β (SE)	p-value
Sex
Female vs male	0.065 (0.038)	0.088	0.037 (0.040)	0.360
Age group		0.042		0.290
43–74 vs 18–28 years	0.109 (0.044)	0.015	0.094 (0.055)	0.092
29–42 vs 18–28 years	0.026 (0.044)	0.551	−0.004 (0.053)	0.941
Ethnicity
White vs non-White	0.024 (0.041)	0.568	−0.004 (0.045)	0.932
Employment status
Employed vs not	−0.041 (0.040)	0.304	−0.087 (0.045)	0.054
Education		0.169
No qualifications vs university	0.232 (0.132)	0.082	–	–
School/college vs university	−0.019 (0.037)	0.612	–	–
No/school/college vs university	−0.008 (0.037)	0.838	−0.053 (0.041)	0.205
Marital status		0.141		0.783
Divorced/separated/widowed	0.110 (0.080)	0.169	0.012 (0.090)	0.893
vs single
Married/partner vs single	0.066 (0.038)	0.084	0.032 (0.046)	0.493
Religious status		0.603		0.822
Prefer not to answer vs no	−0.064 (0.083)	0.443	−0.051 (0.090)	0.570
Yes vs no	−0.034 (0.045)	0.458	−0.018 (0.049)	0.715
Child dependents
Yes vs no	0.116 (0.042)	0.006	0.103 (0.049)	0.035
Other dependents
Yes vs no	−0.018 (0.088)	0.838	−0.057 (0.092)	0.538

Abbreviations: SE, standard error; TTO, time trade-off.

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