A cost-effectiveness analysis comparing the originator follitropin alfa to its biosimilars in patients undergoing a medically assisted reproduction program from a French perspective

Figures & data

Figure 1. Decision-tree.

Table 1. Model input data: clinical background.

Clinical efficacy outcomes	Gonal-FO^a	Gonal-FBb	Gonal-FP^a^b	Ovaleap^a	Bemfolab	BioS^a^b
Oocytes retrieval	97.9%	100.0%	98.9%	99.3%	100.0%	99.8%
Embryo transfer	93.7%	92.7%	93.2%	92.8%	90.0%	91.0%
Pregnancy	36.6%	44.7%	40.3%	29.8%	37.5%	34.5%
Miscarriage	4.1%	2.0%	3.0%	2.4%	4.8%	4.0%
Birth	95.9%	98.0%	97.0%	97.6%	95.2%	96.0%
Live birth rate per woman	32.0%	41.0%	36.0%	27.0%	32.0%	30.0%
Mild/moderate OHSS	2.1%	12.2%	6.7%	3.9%	21.3%	14.7%
Severe OHSS	0.7%	0.8%	0.7%	0.7%	0.8%	0.7%
r-hFSH mean dose	1,614.3	1,569.2	1,593.7	1,535.8	1,555.7	1,548.1

BioS, Pooled biosimilar data from both clinical trials; Gonal-FB, Gonal-F data from clinical trial vs Bemfola; Gonal-FO, Gonal-F data from clinical trial vs Ovaleap; Gonal-FP, Gonal-F pooled data vs both biosimilars; OHSS, ovarian hyperstimulation syndrome; r-hFSHα, recombinant human follicle-stimulating hormone alfa.

^a Strowitzki et al.¹³

^b Rettenbacher et al.¹²

Table 2. All estimated costs with assumptions.

Phase	Assumptions	Costs (€)	Sources
Induction stage (without treatment induction)		484.91	Ameli French database^19 KOL
Blocking phase Ovulation trigger phase Monitoring Bioassays	LA: 48%, SA: 52%, RN: 100 Decapeptyl: 10%, Ovitrelle: 90%, RN: 30% 3 ultrasounds 4 LH, progesterone and estradiol assays	124.97 33.74 110.40 215.80
Oocytes retrieval		1,670.81	Ameli French database^18 KOL DRG Tariff: PMSI-MCO^20
Pre-anesthesia consultation Oocyte retrieval Spermatozoid retrieval Spermatozoid preparation Standard IVF ICSI IVF	10% of patients concerned 91% by masturbation/9% transcutaneous 100% of patients 40% of patients 60% of patients	27 861.87 918.29 135.00 418.50 702.00
Embryo transfer		131.58	Ameli French database^19 Modalités de FINANCEMENT 2016 des activités d’AMP et de CPDPN^33
Intrauterine transfer Transfer fees b-hCG bioassay	Applied for 100% of patients eligible for embryo transfer	51.25 58.78 21.55
Pregnancy resulting in miscarriage		1,040.66	Ameli French database^19 DRG Tariff: PMSI-MCO^20
Bioassays Consultation >6 months Ultrasound Miscarriage	2 b-hCG bioassays 3, 4, and 5 month consultations 11AS, 1T, 2T ultrasounds	43.1 55.80 135.12 806.63
Pregnancy giving live birth		2,873.40	Ameli French database^19 DRG Tariff: PMSI-MCO^20 KOL (questionnaire)
Bioassays Consultation <6 months Ultrasound Consultation >6 months Delivery	2 b-hCG bioassays 3, 4, and 5 month consultations 11AS, 1T, 2T ultrasounds 6, 7, 8, and 9 month consultations 75% natural delivery/25% cesarean delivery	43.1 55.80 235.32 112.00 2,427.17
Ovarian Hyperstimulation Syndrome: mild and moderate		235.32	Ameli French database^19 KOL
Ultrasound	4 ultrasounds performed during gynecologist consultations (as it can occur anytime, this is a mean cost of all ultrasounds performed during pregnancy). As ultrasound costs are more expensive, this tariff will be taken into account instead of consultations	58.83
Ovarian Hyperstimulation Syndrome: severe		1,391.72	Ameli French database^19 KOL DRG Tariff: PMSI-MCO^20
Ultrasound Hospitalizations	1 ultrasound 1 hospitalization	58.83 1,332.89

b-hCG, beta-human chorionic gonadotropin; DRG, Diagnosis-Related Group; ICSI, Intra Cytoplasmic Spermatozoid Injection; IVF, in vitro fertilization; KOL, key opinion leader; LA, Long agonist; PMSI, Programme de médicalisation des systèmes d'information; SA, Short Antagonist; RN, Registered Nurse.

Table 3. Results of the base case cost-effectiveness analysis.

Strategy	Cost (€)	Incremental cost (€)	Efficacy	Incremental efficacy	ICER (€)	Cost per live birth (€)
Gonal-F vs Ovaleap
With OHSS
Gonal-F	3,825.90	259.17	0.32	0.05	4,804.41	1,866.82
Ovaleap	3,566.71	—	0.27	—	—	1,522.53
Without OHSS
Gonal-F	3,811.51	263.13	0.32	0.05	4,877.76	1,862.19
Ovaleap	3,548.39	—	0.27	—	—	1,517.62
Gonal-F vs Bemfola
With OHSS
Gonal-F	4,121.81	279.07	0.40	0.08	3,274.80	2,367.76
Bemfola	3,842.74	—	0.32	—	—	1,857.76
Without OHSS
Gonal-F	4,081.80	298.68	0.40	0.08	3,504.89	2,351.50
Bemfola	3,783.12	—	0.32	—	—	1,838.60
Gonal-F pooled vs BioS
With OHSS
Gonal-F	3961.50	259.56	0.36	0.06	4,352.17	2,095.56
BioS	3701.94	—	0.30	—	—	1,718.15
Without OHSS
Gonal-F	3 935.40	278.39	0.36	0.06	4,667.90	2,086.15
BioS	3 657.02	—	0.30	—	—	1,704.63

ICER, incremental cost-effectiveness ratio; OHSS, ovarian hyperstimulation syndrome/

Figure 2. Tornado diagram depicting the sensitivity analysis for Gonal-FP vs BioS.

Table 4. Results of one-way sensitivity analyses for the comparison of Gonal-F with its biosimilars.

Reference analyses	Main variables of one-way sensitivity analysis	ICER Lower bound	ICER Upper bound
Gonal-FO vs OvaleapICER with OHSS: 4,804.41 ICER without OHSS: 4,877.76	Birth rate [± 20%]	Gonal-FO is dominated	4,112.24
	OHSS (mild-to-moderate) [± 20%]	4,786.49	4,822.34
	OHSS (severe) [± 20%]	4,769.07	4,839.75
	Dosage [663.7; 2,564.9]	Gonal-FO is dominant	11,922.79
	Treatment cost [± 20%]	2,501.1	—
Gonal-FB vs Bemfola ICER with OHSS: 3,274.80 ICER without OHSS: 3,504.89	Birth rate [± 20%]	42,456.71	3,110.34
	OHSS (mild-to-moderate) [± 20%]	3,207.44	3,342.15
	OHSS (severe) [± 20%]	3,248.24	3,301.35
	Dosage [1061.2; 2,077.2]	1,262.02	5,200.11
	Treatment cost [± 20%]	1,816.79	—
Gonal-FP vs BioS ICER with OHSS: 4,352.17 ICER without OHSS: 4,667.90	Birth rate [± 20%]	Gonal-FP is dominated	3,884.92
	OHSS (mild-to-moderate) [± 20%]	4,299.36	4,404.98
	OHSS (severe) [± 20%]	4,317.47	4,386.87
	Dosage [864.4; 2,323]	Gonal-FP is dominant	9,043.00
	Treatment cost [± 20%]	2,268.78	—

ICER, incremental cost-effectiveness ratio; OHSS, ovarian hyperstimulation syndrome.

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