The cost-effectiveness of palivizumab in infants with cystic fibrosis in the Canadian setting: A decision analysis model

Figures & data

Table 1. Base case results for palivizumab treated infants compared to no palivizumab treated infants by risk for severe RSV disease.

Outcome	No Palivizumab	Palivizumab
All CF < 2 years
Life Expectancy (years)
Undiscounted	35.92	35.95
Discounted 3%	21.12	21.14
Discounted 5%	16.09	16.12
Quality-adjusted life years
Undiscounted	32.72	32.82
Discounted 3%	19.51	19.56
Discounted 5%	14.96	14.99
Net costs (PMB + Healthcare)
Undiscounted	C$780,364	C$801,085
Discounted 3%	C$394,845	C$414,599
Discounted 5%	C$275,125	C$294,702
ICER
Undiscounted		C$207,207
Discounted 3%		C$395,095
Discounted 5%		C$652,560
High risk CF <2 years
Life Expectancy
Undiscounted	35.78	35.89
Discounted 3%	21.17	21.24
Discounted 5%	16.16	16.29
Quality-adjusted life years
Undiscounted	32.27	32.62
Discounted 3%	19.29	19.46
Discounted 5%	14.81	14.92
Net costs
Undiscounted	C$778,970	C$800,512
Discounted 3%	C$398,111	C$416,090
Discounted 5%	C$279,233	C$296,539
ICER
Undiscounted		C$61,550
Discounted 3%		C$105,757
Discounted 5%		C$157,332
	The authors for references [6, 9, 14, 18, 24, 27, 28, 29, 33, 37] have been inserted using data from CrossRef

Table 2. Variables used in the model along with associated ranges used for the sensitivity analyses.

			Range
Variable Type	Description	Base Case	Low	High
Probabilities	Palivizumab effectiveness	55% reduction^5	38%	72%
	Probability of hospitalization for RSV	0.038 for children<2^9,13,26-28 0 otherwise	0.01	0.08
	Relative risk of hospitalization for RSV in high risk CF patients	3.6^16	2.5	12.9
	Relative risk of progression if hospitalized with RSV	5^14,15,24,25	1	15
Utilities
	Death	0	NA
	Mild disease	0.96^29	0.76	1
	Moderate disease	0.91^29	0.88	1
	Severe disease	0.8^29	0.59	1
	Lung transplant	0.8^29,30	0.59	1
	Disutility of being hospitalized for RSV (caregiver perspective)	−0.07^31	−0.15	0
Costs
	Palivizumab (per mg)	C$15.05	C$9.78^34	C$15.05
	Median weight at 6 months	7.6^40	5.8	9.8
	Median weight at 18months	10.55^40	8.2	13.6
	Total cost per admission for RSV (x1.05 for physician costs)	C$3617^32	C$1151	C$6084
	Average^* cost of mild CF disease (FEV1 ≥ 70%)	C$12,640^21	NA	NA
	Average^* cost of moderate CF disease (40%≤FEV1<70%)	C$27,847^21	NA	NA
	Average^* cost of severe CF disease (FEV1 <40%)	C$41,552^21	NA	NA
	Average^* cost of Heart and/or Lung Transplant	C$40,677^21	NA	NA

* Average over all ages. Include CF-related costs from health-care payer perspective including; medications, clinic visits, hospitalizations, diagnostic testing, home IV therapy, home oxygen therapy, and transplantation costs. As adapted from Van Gool et al.²¹ and converted to 2013 Canadian dollars. For age-specific breakdown of costs, please see Table S1.

RSV = respiratory syncytial virus, CF = cystic fibrosis, FEV₁ = forced expiratory volume in 1 second

Figure 1. Tornado diagram of the relative impact on the ICER of each of the variables included in the model for a) All CF infants and b) the high risk CF infants only. The x-axis represents the range of the ICER when the parameters are varied by the ranges shown in brackets. The vertical line indicates the base-case ICER for PMB immunoprophylaxis among a) All CF infants (C$652,560 per QALY gained) and b) the high risk CF infants (C$157,332 per QALY gained).

Figure 2. Two-way sensitivity analyses of they key parameters identified in one-way sensitivity analyses for the high-risk CF infants. Analyses were conducted using net benefit with a willingness to pay threshold of $50,000 per QALY. These graphs show the change in the optimal decision strategy over values of 2 variables: A) probability of RSV hospitalization vs. relative risk of progression if hospitalized with RSV, B) probability of RSV hospitalization versus effectiveness of PMB, C) cost of PMB per mg of body weight vs. PMB effectiveness, and D) cost of PMB per mg body weight versus probability of RSV hospitalization. The light gray region represents combinations of the variables for which the “No PMB” strategy is preferred while the dark gray region represents combinations of the variables for which the “PMB” strategy is preferred. The dotted lines represent the base-case values used in the analyses.

Figure 3. Model schematic for both the high risk and All CF groups. (HS1 = Mild Disease (FEV₁ ≥ 70%), HS2 = Moderate Disease (40% ≤ FEV₁ <70%), HS3 = Severe Disease 3 (FEV₁ < 40%), HS4 = Heart and/or Lung Transplant).

Figure 4. Comparison between model output (dashed line) and CF Canada statistics ⁴¹ (solid line) on cumulative probability of death for each age group.

Figure 5. Health state distributions over the lifetime of the natural history cohort of All CF patients in the model. (HS1= Mild Disease (FEV₁ ≥ 70%), HS2 = Moderate Disease (40%≤FEV₁ < 70%), HS3 = Severe Disease 3 (FEV₁ < 40%), HS4 = Heart and/or Lung Transplant).

Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics 1998; 102(3 Pt 1):531-7.

 Google Scholar

Paes B, Steele S, Janes M, Pinelli J. Risk-Scoring Tool for respiratory syncytial virus prophylaxis in premature infants born at 33–35 completed weeks' gestational age in Canada. Curr Med Res Opin 2009; 25(7):1585-91; PMID:19469698; http://dx.doi.org/10.1185/03007990902929112

 PubMed Web of Science ®Google Scholar

Yi MS, Britto MT, Wilmott RW, Kotagal UR, Eckman MH, Nielson DW, Kociela VL, Tsevat J. Health values of adolescents with cystic fibrosis. J Pediatr 2003; 142(2):133-40; PMID:12584533; http://dx.doi.org/10.1067/mpd.2003.51

 PubMed Web of Science ®Google Scholar

Chirico G, Ravasio R, Sbarigia U. Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants. Ital J Pediatr 2009; 35(1):4; PMID:19490659; http://dx.doi.org/10.1186/1824-7288-35-4

 PubMed Web of Science ®Google Scholar

Calo-Fernandez B, Martinez-Hurtado JL. Biosimilars: company strategies to capture value from the biologics market. Pharmaceuticals (Basel). 2012; 5(12):1393-408; PMID:24281342

 PubMedGoogle Scholar

Dieticians of Canada. WHO Growth Charts for Canada. Birth to 24 Months: Boys. 2010.

 Google Scholar

The Ontario Case Costing Initiative. http://www.occp.com/mainPage.htm. Accessed Nov 15, 2013.

 Google Scholar

van Gool K, Norman R, Delatycki MB, Hall J, Massie J. Understanding the costs of care for cystic fibrosis: an analysis by age and health state. Value Health 2013; 16(2):345-55; PMID:23538187; http://dx.doi.org/10.1016/j.jval.2012.12.003

 PubMed Web of Science ®Google Scholar

Cystic Fibrosis Canada. Canadian Cystic Fibrosis Patient Data Registry Report. Toronto, ON: Cystic Fibrosis Canada, 2010.

 Google Scholar