Cost minimisation analysis of 12 or 24 weeks of peginterferon alfa-2b + ribavirin for hepatitis C virus

Figures & data

Figure 1.  Diagnostic and therapeutic pattern according to the study protocol.

Table 1a.  24-week diagnostic/therapeutic scheme followed by patients during the clinical trial.

Week	24-week standard group (n=70)
	Study therapy	Therapy for AEs	Medical consultation	Diagnostic tests
T0	PG, RB	-	1 OPH, 1 PSY	1 Set A*
T2	PG, RB	-	1 GE	1 Ha
T4	PG, RB	-	1 GE	1 Set B
T8	PG (68 + 2^†), RB (64 + 6^‡)	PX (9), LT (9)	1 GE	1 Set B
T12	PG (68 + 2^†), RB (64 + 6^‡)	PX (9), LT (9)	1 GE	1 Set B
T16	PG (68 + 2^†), RB (64 + 6^‡)	PX (9), LT (9)	1 GE	1 Set B
T20	PG (68 + 2^†), RB (64 + 6^‡)	PX (9), LT (9)	1 GE	1 Set B
T24	PG (68 + 2^†), RB (64 + 6^‡)	PX (9), LT (9)	1 GE	1 Set B
T28	-	LT (9)	1 GE	1 Set C
T32	-	LT (9)	1 GE	1 Set C
T36	-	LT (9)	1 GE	1 Set C
T40	PG (2 rel), RB (2 rel)	LT (9)	1 GE	1 Set B (2 rel), 1 set C (68)
T44	PG (2 rel), RB (2 rel)	LT (9)	1 GE	1 Set B (2 rel), 1 Set C (68)
T48	PG (2 rel), RB (2 rel)	LT (9)	1 GE	1 Set B (2 rel), 1 set C (68)
T49 – T60	PG (2 rel), RB (2 rel)	LT (9)	3 GE (2 rel)	3 sets B (2 rel)
T61 – T72	-	LT (9)	3 GE (2 rel)	3 sets C (2 rel)
T73 – T84	-	LT (9)	3GE (2 rel)	3 sets C (2 rel)

AE, adverse event; PG, peginterferon alfa-2b (1 µg/kg weekly); RB, ribavirin (1 g/day); PX, paroxetine (20 mg/day); LT, levothyroxine (100 µg/day); OPH, ophthalmologist; PSY, psychiatrist; GE, gastroenterologist; Ha, haemochrome; ^{rel, relapses; HCV, hepatitis C virus; TSH, thyroid-stimulating hormone; APh, alkaline phosphatise; GGT,} γ^-glutamyl antibody; 1 anti-smooth muscle antibody; 1 electrocardiogram; 1 oesophagogastroduodenoscopy; 1 free thyroxine; 1 free triiodothyronine; 1 hepatic biopsy; 1 HCV genotype; 1 quantitative HCV RNA; 1 thoracic radiography; 1 TSH. Set B = 1 APh; 1 GGT; 1 GOT; 1 GPT; 1 haemochrome; 1 qualitative HCV RNA examination in polymerase chain reaction; 1 TSH.

Set C = 1 APh; 1 GGT; 1 GOT; 1 GPT.

*These tests were done on hospital admission at recruitment, so their costs are included in the diagnosis-related group tariff.

^†Peginterferon alfa-2b reduction (0.5 µg/kg weekly) for neutropenia.

^‡Ribavirin reduction (0.8 g/day) for anaemia.

Table 1b.  12-week diagnostic/therapeutic scheme followed by patients during the clinical trial.

Week	12-week variable group (n=133)
	Study therapy	Therapy for AEs	Medical consultation	Diagnostic tests
T0	PG, RB	-	1 OPH, 1 PSY	1 Set A*
T2	PG, RB	-	1 GE	1 Ha
T4	PG, RB	-	1 GE	1 Set B
T8	PG (132 + 1^†), RB (129 + 4^‡)	PX (8), LT (8)	1 GE	1 Set B
T12	PG (132 + 1^†), RB (129 + 4^‡)	PX (8), LT (8)	1 GE	1 Set B
T16	-	LT (8)	1 GE	1 Set C
T20	-	LT (8)	1 GE	1 Set C
T24	-	LT (8)	1 GE	1 Set C
T28	PG (13 rel), RB (13 rel)	LT (8)	1 GE	1 Set B (13 rel), 1 Set C (120)
T32	PG (13 rel), RB (13 rel)	LT (8)	1 GE	1 Set B (13 rel), 1 Set C (120)
T36	PG (13 rel), RB (13 rel)	LT (8)	1 GE	1 Set B (13 rel), 1 Set C (120)
T40	PG (13 rel), RB (13 rel)	LT (8)	1 GE (13 rel)	1 Set B (13 rel)
T44	PG (13 rel), RB (13 rel)	LT (8)	1 GE (13 rel)	1 Set B (13 rel)
T48	PG (13 rel), RB (13 rel)	LT (8)	1 GE (13 rel)	1 Set B (13 rel)
T49 – T60	-	LT (8)	3 GE (13 rel)	3 Sets C (13 rel)
T61 – T72	-	LT (8)	3 GE (13 rel)	3 Sets C (13 rel)
T73 – T84	-	-	-	-

AE, adverse event; PG, peginterferon alfa-2b (1 µg/kg weekly); RB, ribavirin (1 g/day); PX, paroxetine (20 mg/day); LT, levothyroxine (100 µg/day); OPH, ophthalmologist; PSY, psychiatrist; GE, gastroenterologist; Ha, haemochrome; ^{rel, relapses; HCV, hepatitis C virus; TSH, thyroid-stimulating hormone; APh, alkaline phosphatise; GGT,} γ^-glutamyl antibody; 1 anti-smooth muscle antibody; 1 electrocardiogram; 1 oesophagogastroduodenoscopy; 1 free thyroxine; 1 free triiodothyronine; 1 hepatic biopsy; 1 HCV genotype; 1 quantitative HCV RNA; 1 thoracic radiography; 1 TSH. Set B = 1 APh; 1 GGT; 1 GOT; 1 GPT; 1 haemochrome; 1 qualitative HCV RNA examination in polymerase chain reaction; 1 TSH.

Set C = 1 APh; 1 GGT; 1 GOT; 1 GPT.

*These tests were done on hospital admission at recruitment, so their costs are included in the diagnosis-related group tariff.

^†Peginterferon alfa-2b reduction (0.5 µg/kg weekly) for neutropenia.

^‡Ribavirin reduction (0.8 g/day) for anaemia.

Table 1c.  24-week diagnostic/therapeutic scheme followed by patients during the clinical trial

Week	24-week variable group (n=80)
	Study therapy	Therapy for AEs	Medical consultation	Diagnostic tests
T0	PG, RB	-	1 OPH, 1 PSY	1 Set A*
T2	PG, RB	-	1 GE	1 Ha
T4	PG, RB	-	1 GE	1 Set B
T8	PG (78 + 2^†), RB (72 + 8^‡)	PX (10), LT (10)	1 GE	1 Set B
T12	PG (78 + 2^†), RB (72 + 8^‡)	PX (10), LT (10)	1 GE	1 Set B
T16	PG (78 + 2^†), RB (72 + 8^‡)	PX (10), LT (10)	1 GE	1 Set B
T20	PG (78 + 2^†), RB (72 + 8^‡)	PX (10), LT (10)	1 GE	1 Set B
T24	PG (78 + 2^†), RB (72 + 8^‡)	PX (10), LT (10)	1 GE	1 Set B
T28	-	LT (10)	1 GE	1 Set C
T32	-	LT (10)	1 GE	1 Set C
T36	-	LT (10)	1 GE	1 Set C
T40	PG (3 rel), RB (3 rel)	LT (10)	1 GE	1 Set B (3 rel), 1 Set C (77)
T44	PG (3 rel), RB (3 rel)	LT (10)	1 GE	1 Set B (3 rel), 1 Set C (77)
T48	PG (3 rel), RB (3 rel)	LT (10)	1 GE	1 Set B (3 rel), Set set C (77)
T49 – T60	PG (3 rel), RB (3 rel)	LT (10)	3 GE (3 rel)	3 Sets B (3 rel)
T61 – T72	-	LT (10)	3 GE (3 rel)	3 Sets C (3 rel)
T73 – T84	-	LT (10)	3 GE(3 rel)	3 Sets C (3 rel)

AE, adverse event; PG, peginterferon alfa-2b (1 µg/kg weekly); RB, ribavirin (1 g/day); PX, paroxetine (20 mg/day); LT, levothyroxine (100 µg/day); OPH, ophthalmologist; PSY, psychiatrist; GE, gastroenterologist; Ha, haemochrome; ^{rel, relapses; HCV, hepatitis C virus; TSH, thyroid-stimulating hormone; APh, alkaline phosphatise; GGT,} γ^-glutamyl antibody; 1 anti-smooth muscle antibody; 1 electrocardiogram; 1 oesophagogastroduodenoscopy; 1 free thyroxine; 1 free triiodothyronine; 1 hepatic biopsy; 1 HCV genotype; 1 quantitative HCV RNA; 1 thoracic radiography; 1 TSH. Set B = 1 APh; 1 GGT; 1 GOT; 1 GPT; 1 haemochrome; 1 qualitative HCV RNA examination in polymerase chain reaction; 1 TSH.

Set C = 1 APh; 1 GGT; 1 GOT; 1 GPT.

*These tests were done on hospital admission at recruitment, so their costs are included in the diagnosis-related group tariff.

^†Peginterferon alfa-2b reduction (0.5 µg/kg weekly) for neutropenia.

^‡Ribavirin reduction (0.8 g/day) for anaemia.

Table 2.  Italian National Health Service tariffs and drugs prices (Euros).

	€
Drugs*
Peginterferon alfa-2b (1 μg × kg)	2.8
Ribavirin (1 g)	21.0
Paroxetine (20 mg)	0.8
Levothyroxine (100 μg/day)	1.8
Laboratory tests^†
Glutamic–oxalacetic transaminases	1.14
Glutamic–pyruvic transaminase	1.14
γ-glutamyl transferase	1.24
Alkaline phosphatase	1.39
Haemochrome	3.2
Thyroid-stimulating hormone	7.8
Qualitative HCV RNA test in PCR	63.0
Medical consultations^†
Gastroenterologist	20.66
Psychiatrist	19.37
Ophthalmologist	20.66
Hospitalisation^†
Chronic hepatitis	638.34

HCV, hepatitis C virus; PCR, polymerase chain reaction.

* Source: Prontuario Farmaceutico, 2003.

^† Source: ‘Prestazioni di assistenza specialistica ambulatoriale erogabili nell’ambito del Servizio Sanitario Nazionale e relative tariffe’—D.M. 22 July 1996.

^† Source: ‘Prestazioni di assistenza ospedaliera per acuti erogate in regime di ricovero ordinario e diurno’—D.M. 30 June 1997.

Table 3.  Average cost per patient by group (Euros).

	Standard group (n=70)		Variable group (n=213)
	€	(%)	€	(%)
Study drug therapy*	8,292.5	(84.7)	6,180.7	(82.3)
Admissions	638.3	(6.5)	638.3	(8.5)
Diagnostic tests	520.1	(5.3)	395.0	(5.3)
Medical consultations	313.9	(3.2)	283.9	(3.8)
AEs drug therapy	20.1	(0.2)	10.3	(0.1)
Total cost	9,784.9	(100.0)	7,508.2	(100.0)
Relapsed patients	254.8	(2.6)	669.7	(8.9)
Not relapsed patients	9,530.1	(97.4)	6,838.5	(91.1)

AE, adverse event.

*Costs of dose reduction for anaemia or neutropenia were deducted.

Table 4.  Sensitivity analysis.

	Standard group mean (n=70)	Variable group mean (n=213)	Incremental cost
Base case	9,784.9	7,508.2	+2,276.7
Multiway analysis*
+10%	10,761.3	8,259.0	+2,502.3
+20%	11,737.7	9,009.8	+2,727.9
+50%	14,667.0	11,262.3	+3,404.7
–10%	8,808.5	6,757.4	+2,051.1
–20%	7,832.0	6,006.6	+1,825.5
–50%	4,902.8	3,754.1	+1,148.7

* Unit costs of medical consultations, diagnostic tests, drugs and hospitalisation were varied simultaneously.