A cost-effectiveness evaluation of the originator follitropin alpha compared to the biosimilars for assisted reproduction in Germany

Figures & data

Figure 1 Cost-effectiveness model decision-tree structure.

Table 1 Transition probabilities

Transition probability of oocyte retrieval
Analysis	Intervention	Total number of women in each arm	Number of women with oocyte retrieval	Probability of oocyte retrieval	Reference
Originator vs Biosimilar 1	Originator	123	123	100%	Rettenbacher et al 2015^Citation14
Biosimilar 1	249	249	100%
Originator vs Biosimilar 2	Originator	146	143	97.9%	Strowitzki et al 2016^Citation15
Biosimilar 2	153	152	99.3%
Originator vs pooled biosimilars	Originator	269	266	98.9%	Rettenbacher et al and Strowitzki et al^Citation14,Citation15
Pooled biosimilars	402	401	99.8%
Transition probability of embryo transfer
Analysis	Intervention	Number of women with successful oocyte retrieval	Number of women that had embryo transfer	Probability of embryo transfer conditional upon oocyte retrieval	Reference
Originator vs Biosimilar 1	Originator	123	114	92.7%	Rettenbacher et al 2015^Citation14
Biosimilar 1	249	224	90.0%
Originator vs Biosimilar 2	Originator	143	134	93.7%	Strowitzki et al 2016^Citation15
Biosimilar 2	152	141	92.8%
Originator vs pooled biosimilars	Originator	266	248	93.2%	Rettenbacher et al and Strowitzki et al^Citation14,Citation15
Pooled biosimilars	401	365	91.0%
Transition probability of pregnancy
Analysis	Intervention	Number of women with embryo transfer	Number of pregnant women	Probability of pregnancy conditional upon embryo transfer	Reference
Originator vs Biosimilar 1	Originator	114	51	44.7%	Rettenbacher et al 2015^Citation14
Biosimilar 1	224	84	37.5%
Originator vs Biosimilar 2	Originator	134	49	36.6%	Strowitzki et al 2016^Citation15
Biosimilar 2	141	42	29.8%
Originator vs pooled biosimilars	Originator	248	100	40.3%	Rettenbacher et al and Strowitzki et al^Citation14,Citation15
Pooled biosimilars	365	126	34.5%
Transition probability of live birth
Analysis	Intervention	Number of pregnant women	Number of women with a live birth	Probability of live birth conditional upon pregnancy	Reference
Originator vs Biosimilar 1	Originator	51	50	98.0%	Rettenbacher et al 2015^Citation14
Biosimilar 1	84	80	95.2%
Analysis	Intervention	Number of pregnant women	Number of women with a live birth	Probability of live birth conditional upon pregnancy	Reference
Originator vs Biosimilar 2	Originator	49	47	95.9%	Strowitzki et al 2016^Citation15
Biosimilar 2	42	41	97.6%
Originator vs pooled biosimilars	Originator	100	97	97.0%	Rettenbacher et al and Strowitzki et al^Citation14,Citation15
Pooled biosimilars	126	121	96.0%

Notes: Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg.

Table 2 Mild–moderate and severe OHSS event rates

Analysis	Intervention	Mild–moderate OHSS			Severe OHSS			Reference
		n	N	%	n	N	%
Originator vs Biosimilar 1	Originator	15	123	12.2	1	123	0.8	Rettenbacher et al 2015^Citation14
	Biosimilar 1	53	249	21.3	2	249	0.8
Originator vs Biosimilar 2	Originator	3	146	2.1	1	146	0.7	Strowitzki et al 2016^Citation15
	Biosimilar 2	6	153	3.9	1	153	0.7
Originator vs pooled biosimilars	Originator	18	269	6.7	2	269	0.7	Rettenbacher et al and Strowitzki et al^Citation14,Citation15
	Pooled biosimilars	59	402	14.7	3	402	0.7

Notes: Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg.

Table 3 Daily dosing inputs for normal, hyper- and poor responders

Analysis	Intervention	Mean normal responder dose	Mean hyper-responder dose	Mean poor-responder dose	Duration (days)	Reference
Originator vs Biosimilar 1	Originator	147 IU	122 IU	171 IU	11	Rettenbacher et al 2015^Citation14
	Biosimilar 1	147 IU	119 IU	174 IU	11
Originator vs Biosimilar 2	Originator	166 IU	116 IU	216 IU	10	Strowitzki et al 2016^Citation15,a
	Biosimilar 2	165 IU	112 IU	218 IU	9

Notes: Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg. ^aFor the pooled biosimilars analysis, dosing for each arm was assumed to equal that from Strowitzki et al 2016.

Table 4 Unit cost: assisted reproduction and birth

Cost component	Cost (EUR €)	Reference
Preparation
General treatment, treatment plan	22.59	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Serological tests (HIV, Hbc, HCV, Hbs)	50.60
Total	73.19	Calculated
Oocyte retrieval
ICSI consultation for couples	8.63	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Outpatient surgery visit, including post-procedure surveillance	101.10	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Preparation of sperm and processing medium	42.40	Kassenärztliche Bundesvereinigung (KBV), Federal Association of Centres for Reproductive Medicine^Citation11,Citation13
Ovum pick-up and biopsy needle	114.72	Kassenärztliche Bundesvereinigung (KBV), Federal Association of Centres for Reproductive Medicine^Citation13,Citation28
Anesthesia, including monitoring	119.17	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Total	463.95	Calculated
No oocyte retrieval
Discontinuation before ovum pickup	212.13	Kassenärztliche Bundesvereinigung (KBV)^Citation13
ICSI consultation for couples	8.63	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Anesthesia, including monitoring	119.17	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Total	417.86	Calculated
Embryo transfer
ICSI and embryo transfer	1,316.66	Kassenärztliche Bundesvereinigung (KBV)^Citation13
IVF and embryo transfer	932.60
Total (weighted)	1,224.33	Calculated (based on proportion of IVF [24%]/ICSI [76%])
No embryo transfer
ICSI, no embryo transfer	1,179.11	Kassenärztliche Bundesvereinigung (KBV)^Citation13
IVF, no embryo transfer	932.60
Total (weighted)	1,119.85	Calculated (based on proportion of IVF [24%]/ICSI [76%])
Pregnancy/no pregnancy
Blood test for beta human chorionic gonadotropin (pregnancy test)	6.10	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Live birth
Live birth	3,686.12	Fallpauschalen-Katalog: Weighted average of vaginal and C-section births,^14 Statistisches Bundesamt^Citation30
Miscarriage
Miscarriage	302.90	Kassenärztliche Bundesvereinigung (KBV)^Citation13

Abbreviations: HIV, human immunodeficiency virus; Hb_c, hepatitis B_c antigens; HCV, hepatitis C virus; Hb_s, hepatitis B surface antigen; ICER, incremental cost-effectiveness ratio; ICSI, intracytoplasmic sperm injection; IVF, in-vitro fertilization.

Table 5 Unit cost: mild to moderate and severe OHSS

Cost component	Cost (EUR €)	Reference
Mild–moderate OHSS
Hematology test (x2)	0.25	Kassenärztliche Bundesvereinigung (KBV)^Citation13
Hematocrit test (x2)	0.25
Creatinine test (x2)	8.45
Electrolyte test (x2)	1.00
Hepatic test (x2)	10.25
Total	20.20	Calculated
Severe OHSS
Poisoning/toxic effects of drugs	1,900.75	GKV- Spitzenverband, DRG X62Z^Citation36

Abbreviation: OHSS, ovarian hyper-stimulation syndrome.

Table 6 Unit cost: gonadotropin vial

Vial strength (FSH IU)	Originator (EUR €)	Biosimilar 1 (EUR €)	Biosimilar 2 (EUR €)	Reference
FSH 900 IU	537.26^a	-	430.01^a	Lauer-Fischer GmbH WEBAPO^® InfoSystem^Citation29
FSH 450 IU	274.13^a	227.64	220.00^a
FSH 300 IU	186.41^a	151.78	150.00^a
FSH 225 IU	-	116.50	-
FSH 150 IU	-	78.83	-
FSH 75 IU	53.69	42.95	-

Notes: ^aMulti-dose vial. Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg.

Abbreviation: FSH, follicle stimulating hormone.

Table 7 Gonadotropin costs for normal, poor and hyper-responders for one fresh cycle based on daily dosing

Comparison	Normal responder cost (EUR €)	Poor responder cost (EUR €)	Hyper-responder cost (EUR €)	Weighted cost (EUR €)^a	∆ Cost Originator vs biosimilar (EUR €)
Originator vs Biosimilar 1^Citation14
Originator	972.46	1,128.21	811.39	994.19	42.12
Biosimilar 1	867.13	1,281.50	867.13	952.08
Originator vs Biosimilar 2^Citation15,b
Originator	1,074.52	1,348.65	811.39	1,114.06	222.23
Biosimilar 2	860.02	1,080.02	650.01	891.83

Notes: Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg. ^aWeighted by the proportion of different responder types; ^bFor the pooled biosimilar comparison, dosing for each arm and costs were assumed to equal those reported in the Biosimilar 2 trial.¹⁵

Table 9 Key clinical and cost-effectiveness results for Originator versus Biosimilar 2

	Originator	Biosimilar 2	Difference
Live birth rate	32.2%	26.8%	5.4%
Total costs (€)^a	4,053	3,646	407
Gonadotropin costs (€)	1,114	892	222
Adverse event costs (€)	13	13	0
Assisted reproduction costs (€)	1,735	1,751	−17
Birth costs (€)	1,191	990	201
Cost per live birth (€)	12,590	13,606
ICER (€)	7,540

Notes: Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg. ^aCost breakdowns were estimated as the average cost for women within each treatment arm.

Abbreviation: ICER, incremental cost-effectiveness ratio.

Figure 2 Cost per live birth for Originator versus Biosimilar 1, Biosimilar 2 and pooled biosimilars.Notes: Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. Biosimilar 2: Ovaleap^®; CVC Capital Partners, Luxembourg.

Table 8 Key clinical and cost-effectiveness results for Originator versus Biosimilar 1

	Originator	Biosimilar 1	Difference
Live birth rate	40.7%	32.1%	8.5%
Total costs (€)^a	4,272	3,917	355
Gonadotropin costs (€)	994	952	42
Adverse event costs (€)	18	20	−2
Assisted reproduction costs (€)	1,759	1,756	3
Birth costs (€)	1,501	1,189	312
Cost per live birth (€)	10,510	12,192
ICER (€)	4,168

Notes: Biosimilar 1: Bemfola^®, Gedeon Richter UK Ltd, London, UK. ^aCost breakdowns were estimated as the average cost for women within each treatment arm.

Abbreviation: ICER, incremental cost-effectiveness ratio.

Table 10 Key clinical and cost-effectiveness results for Originator versus pooled biosimilars

	Originator	Pooled biosimilars	Difference
Live birth rate	36.0%	30.1%	5.9%
Total costs (€)^a	4,207	3,777	430
Gonadotropin costs (€)	1,114	892	222
Adverse event costs (€)	15	17	−2
Assisted reproduction costs (€)	1,746	1,754	−8
Birth costs (€)	1,332	1,113	218
Cost per live birth (€)	11,676	12,547
ICER (€)	7,256

Note: ^aCost breakdowns were estimated as the average cost for women within each treatment arm.

Abbreviation: ICER, incremental cost-effectiveness ratio.

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