Table 3.

Model inputs (continued), Results and Sensitivity Analyses reported in the included studies

Authors (Year), Countries	Discount rate	Utilities (QALYs) and outcomes			Results/ICER	Willingness-to-pay threshold	Sensitivity analyses
		Preference based measure used to estimate utilities	Whose utility values?	Other outcomes
Journal Articles
Batty AJ, et al. (2013), United Kingdom [16]	3.5%	Migraine Specific Quality of Life Questionnaire v2.1 (MSQ) was used to collect Health-Related Quality of Life (HRQoL) information at baseline and 24 weeks after the intervention. The MSQ scores were mapped to EQ-5D to produce utility values.	Utility values from the participants of PREEMPT trial	Headache per day/year, cost per headache day avoided	At 2 years, Botox treatment was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with Botox reduced headache days by 38 days per year at a cost of £18 per headache day avoided.	£20,000– £30,000/QALY	Both deterministic and probabilistic sensitivity analyses (PSA) were performed
Giannouchos TV, et al. (2019), Greece [17]	None	Quality-adjusted life years (QALYs) were calculated by using the health utility data (MSQ to EQ-5D) for participants with chronic migraine (CM) from 10 countries obtained from the International Burden of Migraine Study (IBMS)	General public	Number of migraines avoided	CM treatment with Erenumab compared to Botox resulted in ICERs of €218,870 and €231,554 per QALY gained and €620 and €656 per migraine avoided, from the societal and the payer’s perspective, respectively. Using a cost-effectiveness threshold equal to three times the local gross domestic product (GDP) per capita (€49,000), for Erenumab the ICERs fall below this threshold.	EURO 49,000/QALY	Both PSA and deterministic sensitivity analyses were performed
Hansson-Hedblom A, et al. (2020), Norway and Sweden [18]	3%	The IBMS study was used to map EQ-5D scores from MSQ score.	Utility values from the participants of PREEMPT trial		In Sweden, Botox was associated with 0.223 additional QALYs at an additional cost of EUR 4126 compared to placebo, resulting in an ICER of EUR 18,506. In Norway, Botox was associated with 0.216 additional QALYs at an additional cost of EUR 4301 compared to placebo, resulting in an ICER of EUR 19,954.	SEK 280,000 (Sweden) and NOK 495,000 (Norway)	Both PSA and deterministic sensitivity analyses were performed
Hollier-Hann G, et al. (2020), United Kingdom [19]	3.5%	Utility values were directly obtained from the EQ-5D data collected in the REPOSE study. EQ-5D was administered at baseline and each follow-up visit (at intervals of approx. 12 weeks)	UK tariff	Headache per day/year, cost per headache day avoided	Botox treatment resulted in incremental costs of £1204 and an incremental QALY gain of 0.07 compared with placebo in CM participants who have previously failed three or more preventive treatments, corresponding to an ICER of £16,306 per QALY gained	£20,000– £30,000/QALY	Both PSA and deterministic sensitivity analyses were performed
Lipton RB, et al. (2018), United States of America [20]	3%	MSQ responses from the Erenumab EM and CM pivotal studies were mapped to the EQ-5D-3L, then pooled to generate one complete migraine dataset.	General public		Erenumab resulted in incremental QALYs of 0.185 vs supportive care (SC) and estimated cost offsets due to reduced monthly migraine days (MMD) of $8482 over 10 years, with an average duration of treatment of 2 years	$100,000–$200,000/ QALY	Both PSA and deterministic sensitivity analyses were performed
Mahon R, et al. (2021), Sweden [21]	3%	Two trials included in this study used the MSQ score which was mapped onto EQ-5D.	Not stated	Cost per migraine day avoided	Erenumab treatment resulted in ICERs of Swedish krona (SEK) 34,696 and SEK 301,565 per QALY gained in the total migraine and episodic migraine (EM) populations, respectively. Erenumab was dominant in the CM population.	SEK 300,000/ QALY	Both PSA and deterministic sensitivity analyses were performed
Ruggeri et al. (2013), Italy [22]	3%	The IBMS study was used to map EQ-5D scores from MSQ score	UK tariff	Headache per day/year, cost per headache day avoided	Botox compared with placebo gained an incremental 0.04 more QALYs per participant; the incremental cost per participant was €208; the ICER was €4899 per QALY gained	€20,000 - €30, 000/QALY	Both PSA and deterministic sensitivity analyses were performed
Sussman M, et al. (2018), United States of America [23]	3%	EQ-5D scores were used	Not stated	Headache-related disability, lost work productivity, anxiety and depression	From a societal perspective treatment with Erenumab compared with no preventive treatment ranges from a dominant strategy among CM participants to an ICER of $122,167 for EM participants. When excluding indirect costs (i.e., payer perspective), the ICERs are cost-effective among CM participants ($23,079 and $65,720 versus no preventive treatment and Botox, respectively), but not among EM participants.	USD 50,000/ QALY	Both PSA and deterministic sensitivity analyses were performed
Vekov (2019), Bulgaria [24]	5%	EQ-5D scores were used	Not stated	Headache Impact Test (HIT-6), Migraine Disability Assessment, (MIDAS)	Erenumab was not cost-effective compared to placebo (standard prevention therapy) with ICER of 637,000 BGN/QALY.	Three times the national annual GDP per capita	PSA
Other reports
CADTH (Botox) (2019, Canada [25]	3%	MSQ was used to collect HRQoL information at baseline and 24 weeks after the intervention. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values from the participants of PREEMPT trial were used	Headache per day/year, cost per headache day avoided	ICER was CAD 134,601/QALY gained for Botox vs BSC. At a WTP of CAD 50,000 per QALY, Botox was associated with a 9% probability of being the optimal intervention. A price reduction of more than 75% is required to achieve an ICER of less than CAD 50,000/QALY.	CAD 50,000	Sensitivity analysis showed that utility values had the greatest influence on model results.
CADTH (Erenumab) (2019, Canada [26]	3%	MSQ was used to collect HRQoL information at baseline and 24 weeks after the intervention. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values from the participants of PREEMPT trial were used	Headache per day/ year, cost per headache day avoided	Erenumab dominated Botox in the population for whom the previous treatment including Botox was failed.	CAD 50,000	Sensitivity analyses involved analysing different time horizon and with Scenarios were performed.
ICER (2018), United States of America [27]	3%	MSQ was used to collect HRQoL information at baseline and 24 weeks after the intervention. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values from the participants of PREEMPT trial were used	Headache per day/year, cost per headache day avoided	The ICER for Erenumab vs no preventative treatment was USD 86,000/QALY and Fremanzenumab vs no preventative treatment was USD 115,000/QALY, both way above the baseline WTP of USD 50,000/QALY.	USD 50,000	Sensitivity analyses were performed using topiramate as the alternative treatment to Botox and this resulted in an estimated ICER of USD 28,960/QALY.
NICE: Erenumab (2019), United Kingdom [29]	3.5%	MSQ was used to collect HRQoL information at baseline and 24 weeks after the intervention. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values obtained from Erenumab trials (Study 295, STRIVE and ARISE) data.	Headache per day/year, cost per headache day avoided	The blended dose of Erenumab was cost-effective in treating CM population vs Botox and vs best supportive care with a ICER of £18,893 and an ICER of £17,212 per QALY gained, respectively. Erenumab 140 mg is cost-effective treatment vs both Botox and best supportive care, with an ICER of £17,832 and an ICER of £13,340 per QALY gained, respectively.	£20,000– £30,000/QALY	Both PSA and deterministic sensitivity analyses were performed including using the whole migraine population and a societal perspective.
NICE: Fremenzumab (2019), United Kingdom [28]	3.5%	MSQ was used to collect HRQoL information. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values obtained from patient level MSQ data from FOCUS trial	Headache per day/year, cost per headache day avoided	Fremanezumab had higher costs, but also gained more QALYs than both best supportive care and Botox. The ICERs showed that Fremanezumab was a cost-effective treatment compared to best supportive care (£11,825/QALY gained) and Botox (£16,227/QALY gained)	£20,000– £30,000/QALY	Both PSA and deterministic sensitivity analyses were performed
NICE: Galcenzenumab (2020), United Kingdom [30]	3.5%	MSQ was used to collect HRQoL information. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values obtained from patient level MSQ data from CONQUER trial	Headache per day/ year, cost per headache day avoided	The actual ICERS were confidential and masked. However, the report indicated that ICER for Galcanezumab fall below the lower threshold (£20,000/QALY gained) as defined by standard WTP for United Kingdom.	£20,000– £30,000/QALY	Both PSA and deterministic sensitivity analyses were performed
Warwick Evidence (2011), United Kingdom [31]	3.5%	MSQ was used to collect HRQoL information. The MSQ scores then were mapped into to EQ-5D to produce utility values.	Utility values obtained from patient level MSQ data from PREEMPT Trial	Headache per day/year, cost per headache day avoided	The reported ICER was £5828/QALY gained.	£20,000– £30,000/QALY	Both PSA and deterministic sensitivity analyses were performed

CM Chronic migraine, EM Episodic migraine, EQ-5D European-Quality of Life Five dimensions, HRQoL Health-Related Quality of Life, GDP Gross domestic product, IBMS International Burden of Migraine Study, ICER Incremental cost-effectiveness ratio, HIT-6 Headache Impact Test, MIDAS Migraine Disability Assessment, MSQ Migraine specific questionnaire, MMD Monthly migraine days, NOK Norwegian Krone, PREEMPT Patients in The Phase III REsearch Evaluating Migraine Prophylaxis Therapy, PSA Probabilistic sensitivity analyses, QALY Quality-adjusted life year, SEK Swedish Krona, SC Supportive care