Preferences of Patients with Chronic Hepatitis B – A Discrete Choice Experiment on the Acceptability of Functional Cure

Figures & data

Table 1 DCE Attributes and Attribute Levels

Attributes	Levels	Explanation Given to Patients During Interview
Route of administration	Tablet(s), up to 2x daily	Electroporation is a quick electric pulse given during injection, increasing the permeability of the cells and increasing the delivery of the drug into muscle cells. The electric pulse has a momentary mild discomfort like a “pinch-punch” at the site of infection.
	Subcutaneous injection, weekly + tablet up to 2x daily
	Intramuscular (IM) injection with electric impulse (electroporation (EP)), 3x + tablet(s) up to 2x daily
The frequency of visiting physicians	Monthly visits	A visit might include, eg, a blood test to check your blood values, receiving your prescription, receiving an administration of your drug or just for a general check-up
	Half-yearly visits
Efficacy attribute (functional cure)^a	1% of patients achieving long-term disease remission	It is the % of patients, who (after 12 months on treatment) achieve a long-term disease remission such that no further treatment is necessary. Long-term disease remission means that during treatment, the virus is completely suppressed and the viral DNA and sAg are no longer detectable in the blood – but this is also sustainable after the completion of treatment.
	30% of patients achieving long-term disease remission
	50% of patients achieving long-term disease remission
Safety attribute (number of days with side effects in a month)	0 days per month	Side effects can disrupt daily activities and can include. eg, Dizziness, diarrhea, tiredness, headache, back and muscle pain or joint pain, stomachache, flulike symptoms, cough, inflammation of nose and throat, nausea, feeling week, skin rash or reactions on the injections site.
	1 day per month
	3 days per month
Distance to treating physician^b	15 mins	This is the commuting time required to travel to the physician.
	45 mins

Notes: This table presents the attributes and their levels considered in this DCE. ^aCurrent standard of care rarely achieves function cure, which is reported for about 1% of patients within 12 months of therapy. Therefore, this level was chosen to create comparability to current medications such as interferons and oral nucleos(t)ide analogues (NUCs).¹⁶ bThis attribute was included to capture the interviewees’ trade-offs (opportunity costs) based on a comprehensible unit of measurement.

Figure 1 Example choice card.

Table 2 Sociodemographic and Clinical Characteristics of Patients

Variables	All Patients Enrolled		Patients Successfully Completed DCE w/o Inconsistent DCE Responses
N	141		108
Sociodemographic characteristics
Mean/Median age in years (SD)	50.1/49.0	(13.3)	49.1/47.5	(13.1)
Mean/Median age at first HBV diagnosis (SD)	36.1/31.7	(15.0)	35.1/30.9	(14.1)
Mean/Median years since first HBV diagnosis (SD)	14.0/12.0	(9.3)	14.0/12.0	(9.6)
Female gender (%)	56	(39.7)	40	(37.0)
eAg status (as in EASL Guidelines)^Citation30
HBeAg-positive chronic HBV infection (%)	8	(5.7)	5	(4.6)
HBeAg-positive chronic hepatitis B (%)	11	(7.8)	7	(6.5)
HBeAg-negative chronic HBV infection (%)	51	(36.2)	38	(35.2)
HBeAg-negative chronic hepatitis B (%)	70	(49.6)	57	(52.8)
HBsAg-negative (%)	1	(0.7)	1	(0.9)
Treatment characteristics
Currently receiving medication – yes (%)	101	(72.3)	80	(74.1)
Current medication – Tenofovir (%)	71	(50.0)	61	(56.5)
Current medication – Lamivudine (%)	10	(7.1)	7	(6.5)
Current medication – Entecavir (%)	20	(14.2)	12	(11.1)
Previously received other CHB medication – yes (%)	32	(22.7)	28	(25.9)
Interferon used before – yes (%)	17	(12.1)	14	(13.0)
Interferon used before – no (%)	106	(75.2)	91	(84.3)
Interferon used before – patient does not know (%)	7	(5.0)	3	(2.8)
Interferon used before – no patient response (%)*	11	(7.8)	–	–
Experiences with adverse events/side effects
Side-effect experience – yes (%)	23	(16.30)	20	(18.5)
Side-effect experience – no (%)	106	(75.2)	87	(80.6%)
Side-effect experience – patient does not know (%)	1	(0.7)	1	(0.9)
Side-effect experience – no patient response (%)*	11	(7.8)	–	–

Notes: Patients’ sociodemographic characteristics (mean and standard deviation of age, age at first HBV diagnosis and years since first HBV diagnosis) and eAg status are based on information reported by physicians. *No patient response corresponds to patients who were initially enrolled but did not participate in phone interviews due to not being interested anymore or not reachable via phone.

Table 3 Estimated Conditional Logit Regression Model for the Entire Sample and Subgroups of Patients

	All Patients (n=108)	Female (n=40)	Male (n =68)	Age > 47.5 (n=54)	Age ≤ 47.5 (n=54)	Years Since First Diagnosis > 12 (n=50)	Years Since First Diagnosis ≤ 12 (n=58)
Efficacy (functional cure) (reference group: 1% of patients with remission sustained over 12 months)
30% of patients with remission sustained over 12 months	0.978 (0.000)	1.242 (0.000)	0.849 (0.000)	0.954 (0.000)	1.014 (0.000)	0.888 (0.000)	1.061 (0.000)
50% of patients with remission sustained over 12 months	1.457 (0.000)	1.882 (0.000)	1.248 (0.000)	1.378 (0.000)	1.548 (0.000)	1.362 (0.000)	1.545 (0.000)
Route of administration (reference group: EP +Tablets)
Tablets	0.430 (0.000)	0.461 (0.003)	0.420 (0.000)	0.473 (0.000)	0.386 (0.002)	0.461 (0.000)	0.403 (0.001)
SC injection + tablet	0.060 (0.495)	−0.068 (0.662)	0.118 (0.267)	0.175 (0.150)	−0.064 (0.611)	0.144 (0.253)	−0.017 (0.891)
Frequency of physician visits (reference group: monthly)
Every 6 months	0.287 (0.000)	0.285 (0.003)	0.289 (0.000)	0.207 (0.007)	0.372 (0.000)	0.315 (0.000)	0.262 (0.001)
Number of days with side effects (reference group: 3 days)
1 day	0.182 (0.013)	0.123 (0.343)	0.215 (0.016)	0.204 (0.045)	0.160 (0.131)	0.158 (0.137)	0.203 (0.046)
0 days	0.297 (0.001)	0.269 (0.081)	0.306 (0.004)	0.241 (0.046)	0.354 (0.005)	0.258 (0.039)	0.332 (0.006)
Distance to treating physician (reference group: 45 mins)
15 mins	0.065 (0.237)	0.122 (0.211)	0.043 (0.519)	0.012 (0.880)	0.124 (0.119)	0.069 (0.385)	0.062 (0.414)
Number of observations	3456	1280	2176	1728	1728	1600	1856
Log-likelihood	996.92	337.67	652.23	507.13	486.32	470.30	525.04

Notes: This table shows results of the analysis based on the conditional logit regression model. Shown values are utilities which do not have an own unit. P-values refer to utility differences between a specified attribute level and another reference level.

Figure 2 Relative importance of each attribute for patients’ hypothetical treatment choices (entire sample and 6 subgroups).

Figure 3 Relative utility associated with different treatment options (fixed attribute levels: 1 day with side effects, half-yearly physician visits, 15 mins of travel time to physician).

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