Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States

Figures & data

Figure 1.  Structure of simple decision tree model. ICU = intensive care unit; RSV = respiratory syncytial virus.

Table 1.  Probabilities used in the model by palivizumab prophylaxis and no prophylaxis.

Variable	Infant population	Base case input for variable	Source for base case inputs	Sensitivity analysis range for base case input	Source for sensitivity analysis range
Placebo
Background risk of RSV hospitalization	<32 wGA, ≤6 mo CA	18.5%	*	9.4%–34.2%	9.4%: Boyce et al.15 34.2%: Boyce et al.15
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	13.4%	*	8%–34.2%	8%: Boyce et al.15 34.2%: Boyce et al.15
	32–35 wGA, ≤6 mo CA with 2006 AAP RF
	32–35 wGA, ≤6 mo CA with ≤1 RF	3.4%	*	1.7%–6.6%	1.7%: Sampalis et al.37 6.6%: Wegner et al.23
Background risk of ICU admission among infants with RSV hospitalization	<32 wGA, ≤6 mo CA	19.5%	Forbes et al.58	17.8%–48.4%	17.8%: Figueras-Aloy et al.32 48.4%: Horn et al.59
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	21.9%	Forbes et al.58	17.8%–48.4%	17.8%: Figueras-Aloy et al.32 48.4%: Horn et al.59
	32–35 wGA, ≤6 mo CA with 2006 AAP RF
	32–35 wGA, ≤6 mo CA with ≤1 RF
Mean wGA	<32 wGA, ≤6 mo CA	28.6	US Natality data64	–	–
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	33.3		–	–
	32–35 wGA, ≤6 mo CA with 2006 AAP RF	34.1		–	–
	32–35 wGA, ≤6 mo CA with ≤1 RF
Mean length of stay of RSV hospitalization, d	<32 wGA, ≤6 mo CA	7.0	Forbes et al.58	6.2–7.8	Forbes et al.58
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	10.4	Forbes et al.58	9.6–11.2	Forbes et al.58
	32–35 wGA, ≤6 mo CA with 2006 AAP RF
	32–35 wGA, ≤6 mo CA with ≤1 RF
Case fatality rate among infants admitted to pediatric ICU with RSV	<32 wGA, ≤6 mo CA	4.3%	Gunville et al.60	3%–8.11%	3%: Yount et al.75 8.11%: Sampalis et al.76
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	6.1%	Gunville et al.60	3%–8.11%	3%: Yount et al.75 8.11%: Sampalis et al.76
	32–35 wGA, ≤6 mo CA with 2006 AAP RF
	32–35 wGA, ≤6 mo CA with ≤1 RF
Number of hours lost – RSV hospitalization (per day)	All groups	8	Assumption	6.4–9.6	Assumption (±20%)
Palivizumab
RRR of RSV hospitalization	<32 wGA, ≤6 mo CA	75.1%	Post hoc analysis of IMpact-RSV Clinical Study20	27.2%–91.5%	Post hoc analysis of IMpact- RSV Clinical Study20
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	82.2%	Post hoc analysis of IMpact-RSV Clinical Study20	45.4%–94.2%	Post hoc analysis of IMpact- RSV Clinical Study20
	32–35 wGA, ≤6 mo CA with 2006 AAP RF
	32–35 wGA, ≤6 mo CA with ≤1 RF
RRR of ICU admission among hospitalized infants	All groups	63.0%	Post hoc analysis of IMpact-RSV Clinical Study20	0%–94.8%	Post hoc analysis of IMpact- RSV Clinical Study20

AAP = American Academy of Pediatrics; CA = chronologic age; ICU = intensive care unit; LRI = lower respiratory tract infection; RF = risk factor; RRR = relative risk reduction, RSV = respiratory syncytial virus; wGA = weeks gestational age.

*We first estimated the background RSV hospitalization rates for <32 wGA, ≤6 mo CA (10.7%); 32–34 wGA, ≤3 mo CA, 2009 AAP RF (7.1%); 32–35 wGA, ≤6 mo CA, 2006 AAP RF (7.1%); and 32–35 wGA, ≤6 mo CA, ≤1 RF (1.7%) from Checchia et al.55 (10.7%) and Sampalis et al.37 (7.1% and 1.7%). To obtain rates of RSV hospitalization for these cohorts covered by Medicaid, we converted these probabilities to odds (O = P/[1 − P], where O = odds and P = probability). We then multiplied the baseline odds by the odds ratio (OR) of 2.03 (95% CI, 1.99–2.06), the increased odds of RSV hospitalization among infants from the Medicaid California population compared with the non-Medicaid California population.9 Finally, we converted the transformed OR to probabilities of RSV hospitalization for Medicaid infants <32 wGA, ≤6 mo CA (18.5%); 32–34 wGA, ≤3 mo CA with 2009 AAP RF (13.43%); 32–35 wGA, ≤6 mo CA with 2006 AAP RF (13.43%); and 32–35 wGA, ≤6 mo CA with ≤1 RF (3.4%).

Table 2.  Cost of drug administration and RSV-related outcomes adjusted to 2010.

Variable	Infant population	Base case inputs	Source for base case inputs	Sensitivity analysis range	Source for sensitivity analysis range
Direct medical costs 12 mo after RSV infection compared with placebo	<32 wGA, ≤6 mo CA	$39,399	Shi et al24	$31,519–$47,279	Assumption (±20%)
	32–34 wGA, ≤3 mo CA with 2009 AAP RF	$20,160	Shi et al24	$16,128–$24,192	Assumption (±20%)
	32–35 wGA, ≤6 mo CA with 2006 AAP RF
	32–35 wGA, ≤6 mo CA with ≤1 RF
Cost of palivizumab	All groups	100 mg, $1190.97 50 mg, $631.10	Estimated average public spend for palivizuma20,27	100 mg, $952.77–$1429.16 50 mg, $504.88–$757.32	Assumption (±20%)
				For maximum value: WAC scenario, 100 mg, $2027.80 50 mg, $1073.88	Thomson Healthcare, Inc.77
Administration, prophylaxis	All groups	$38	CPT 96372	$30–$43	Range for CPT code
Average hourly cost for the time lost due to RSV infection (indirect cost)	All groups	$19	US Department of Labor62	$15–$23	Assumption (±20%)
Transportation costs	All groups	$6	Luce et al65	$5–$7	Assumption (±20%)

AAP = American Academy of Pediatrics; CA = chronologic age; CPT = current procedural terminology; RSV = respiratory syncytial virus; WAC = wholesale acquisition cost; wGA = weeks gestational age.

Note: owing to weight-based dosing of palivizumab, the model calculations are based on a cost-per-mg value that is derived from the average cost per mg for 50-mg and 100-mg vials of palivizumab, respectively.

Table 3.  Health utilities incorporated in the cost-effectiveness model.

Variable	Infant population	Base case inputs	Source for base case inputs	Sensitivity analysis range	Source for Sensitivity analysis range
Baseline utility	All groups	1	Assumption	–	–
Hospitalization disutility	All groups	− 0.3972	Leidy et al.66	−0.3534 to −0.4520	Leidy et al.66
Post-hospitalization recovery period disutility	All groups	−0.0911	Leidy et al.66	−0.0728 to −0.1093	Assumption (±20%)
Duration, post-hospitalization recovery period, d	All groups	60	Leidy et al.66	48–72	Assumption (±20%)
Age at time of RSV hospitalization, mo	All groups	2.4	Palmer et al.45	1.9–2.9	Assumption (±20%)
Average life expectancy of general US population, y	All groups	77.45	Centers for Disease Control and Prevention46	58.1–96.8	Assumption (±25%)

RSV = respiratory syncytial virus.

Figure 2.  Benchmark of palivizumab cost-effectiveness results with those of vaccines. AAP = American Academy of Pediatrics; DTaP = diptheris, tetanus, and acellular pertussis vaccine; HPV = human papillomavirus vaccine; RF = risk factor; TIV = trivalent inactivated influenza vaccine; wGA = weeks gestational age.

Table 4.  Net costs and QALYS between palivizumab prophylaxis and no prophylaxis among the 4 cohorts.

	<32 wGA, ≤6 mo CA*			32–34 wGA, ≤3 mo CA* with AAP 2009 RF^†			32–35 wGA, ≤6 mo CA* with AAP 2006 RF^‡			32–35 wGA, ≤6 mo CA* with ≤1 RF^$
	Palivizumab	No Prophylaxis	Difference	Palivizumab	No Prophylaxis	Difference	Palivizumab	No Prophylaxis	Difference	Palivizumab	No Prophylaxis	Difference
Prophylaxis costs	$3287	0	$3287	$3266	0	$3266	$4462	0	$4462	$4462	$0	$4462
RSV-related costs	$1867	$7493	−$5627	$519	$2921	−$2402	$519	$2921	−$2402	$132	$741	−$609
Total costs	$5154	$7493	−$2339	$3785	$2921	$864	$4981	$2921	$2060	$4594	$741	$3853
QALY	30.907	30.861	0.046	30.908	30.854	0.0539	30.908	30.854	0.0539	30.911	30.897	0.014
ICER	–	–	Dominant	–	–	$16,037	–	–	$38,244	–	–	$281,892

AAP = American Academy of Pediatrics; CA = chronologic age; ICER = incremental cost-effectiveness ratio calculated as incremental costs/incremental QALYs; QALY = quality-adjusted life-year; RF = risk factor; RSV = respiratory syncytial virus; wGA = weeks gestational age.

*Chronologic age at the start of the RSV season (November 1).

^†Having siblings <5 y of age and/or attending day care.

^‡Having 2 of the following: environmental air pollutants, congenital abnormalities of the airways, severe neuromuscular disease, school-aged siblings, or day care attendance.

^$Risk factors described in Sampalis et al37.

Table 5.  One-way sensitivity analysis for infants <32 wGA, ≤6 months CA.

	Baseline results		Dominant
	Input		ICER
	Minimum	Maximum	Input minimum	Input maximum
RRR of RSV hospitalization (75.1%)	27.2%	91.5%	$35,146	Dominant
Background risk of RSV hospitalization (18.5%)	9.4%	34.2%	$18,366	Dominant
Discount rate for outcomes (3%)	0%	5%	Dominant	Dominant
Average cost of palivizumab per mg* ($12.27)	$9.81^†	$14.72^† $20.88^‡	Dominant	Dominant Dominant
Increased direct medical costs 12 mo after RSV infection compared with placebo ($39,399)	$31,519	$47,279	Dominant	Dominant
Probability of case fatality in ICU (4.3%)	3.0%	8.11%	Dominant	Dominant
Background risk of ICU admission (19.5%)	17.8%	48.4%	Dominant	Dominant
RRR of ICU admission (63%)	0%	94.8%	Dominant	Dominant

CA = chronologic age; ICER = incremental cost-effectiveness ratio; ICU = intensive care unit; RRR = relative risk reduction; RSV = respiratory syncytial virus; wGA = weeks gestational age.

Dominant means that RSV prophylaxis administration is cost-saving and improves health outcomes compared to a no RSV prophylaxis strategy.

*Owing to weight-based dosing of palivizumab, the model calculations are based on a cost-per-mg value that is derived from the average cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^†Derived from ±20% of the average base case cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^‡Derived from the average 2010 wholesale acquisition costs for the 100-mg vial ($2027.80) and 50-mg vial ($1073.88), respectively.

Table 6.  One-way for infants 32–34 wGA, ≤3 months CA with 2009 AAP RF.

	Baseline results		$16,037
	Input		ICER
	Minimum	Maximum	Input minimum	Input maximum
Background risk for RSV hospitalization (13.4%)	8%	34.2%	$56,964	Dominant
Cost of palivizumab per mg* ($12.27)	$9.81^†	$14.72^† $20.88^‡	$5077	$26,997 $54,521
RRR of RSV hospitalization (82.2%)	45.4%	94.2%	$42,981	$9062
Discount rate for outcomes (3%)	0%	5%	$6539	$23,588
Increased direct medical costs 12 mo after RSV infection compared with placebo ($20,160)	$16,128	$24,192	$24,284	$7789
Background risk of ICU admission (21.9%)	17.8%	48.4%	$19,467	$7476
Probability of ICU death (6.1%)	3%	8.11%	$30,713	$12,149
RRR ICU admission (63%)	0%	94.8%	$18,088	$15,167

AAP = American Academy of Pediatrics; CA = chronologic age; ICER = incremental cost-effectiveness ratio; ICU = intensive care unit; RF = risk factor; RRR = relative risk reduction; RSV = respiratory syncytial virus; wGA = weeks gestational age.

Dominant means that RSV prophylaxis administration is cost-saving and improves health outcomes compared to a no RSV prophylaxis strategy.

*Owing to weight-based dosing of palivizumab, the model calculations are based on a cost-per-mg value that is derived from the average cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^†Derived from ±20% of the average base case cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^‡Derived from the average 2010 wholesale acquisition costs for the 100-mg vial ($2027.80) and 50-mg vial ($1073.88), respectively.

Table 7.  One-way for infants 32–35 wGA, ≤6 months CA with 2006 AAP RF.

	Baseline results		$38,244
	Input		ICER
	Minimum	Maximum	Input minimum	Input maximum
Background risk for RSV hospitalization (13.4%)	8%	34.2%	$94,162	Dominant
Cost of palivizumab per mg* ($12.27)	$9.81^†	$14.72^† $20.88^‡	$23,034	$53,455 $91,655
Probability of case fatality in ICU (6.1%)	3.0%	8.11%	$73,244	$28,974
Discount rate for outcomes (3%)	0%	5%	$15,594	$56,252
RRR of RSV hospitalization (82.2%)	45.4%	94.2%	$69,489	$30,157
Background risk of ICU admission (21.9%)	17.8%	48.4%	$46,425	$17,830
Increased direct medical costs 12 mo after RSV infection compared with placebo ($20,160)	$16,128	$24,192	$46,492	$29,997
RRR of ICU admission (63%)	0%	94.8%	$43,135	$36,170

AAP = American Academy of Pediatrics; CA = chronologic age; ICER = incremental cost-effectiveness ratio; ICU = intensive care unit; RRR = relative risk reduction; RSV = respiratory syncytial virus; wGA = weeks gestational age.

*Owing to weight-based dosing of palivizumab, the model calculations are based on a cost-per-mg value that is derived from the average cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^†Derived from ±20% of the average base case cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^‡Derived from the average 2010 wholesale acquisition costs for the 100-mg vial ($2027.80) and 50-mg vial ($1073.88), respectively.

Table 8.  One-way sensitivity analysis for infants 32–35 wGA, ≤6 months CA with ≤1 RF.

	Baseline results		$281,892
	Input		ICER
	Minimum	Maximum	Input minimum	Input maximum
Background risk of RSV hospitalization (3.4%)	1.7%	6.6%	$608,380	$123,595
Case fatality in the ICU (6.1%)	3%	8.11%	$539,866	$213,560
Discount rate for outcomes (3%)	0%	5%	$114,944	$414,623
Cost of palivizumab per mg* ($12.27)	$9.81^†	$14.72^† $20.88^‡	$221,945	$341,839 $492,392
Background risk of ICU admission (21.9%)	17.8%	48.4%	$342,188	$131,419
RRR of RSV hospitalization (82%)	45.4%	94.2%	$360,314	$261,592
Increased direct medical costs 12 mo after RSV infection compared with placebo ($20,160)	$16,128	$24,192	$290,140	$273,645
RRR of ICU admission (63%)	0%	94.8%	$317,941	$266,602

CA = chronologic age; ICER = incremental cost-effectiveness ratio; ICU = intensive care unit; RF = risk factor; RRR = relative risk reduction; RSV = respiratory syncytial virus; wGA = weeks gestational age.

*Owing to weight-based dosing of palivizumab, the model calculations are based on a cost-per-mg value that is derived from the average cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^†Derived from ± 20% of the average base case cost per mg for 100-mg and 50-mg vials of palivizumab, respectively.

^‡Derived from the average 2010 wholesale acquisition costs for the 100-mg vial ($2027.80) and 50-mg vial ($1073.88), respectively.

Figures 3 and 4.  Probabilistic analyses <32 wGA, ≤6 months CA. CA = chronologic age; QALY = quality-adjusted life-year; wGA = weeks gestational age.

Figures 5 and 6.  Probabilistic analyses for 32–34 wGA, ≤3 months CA with AAP 2009 RF. AAP = American Academy of Pediatrics; CA = chronologic age; QALY = quality-adjusted life-year; RF = risk factor; wGA = weeks gestational age.

Figures 7 and 8.  Probabilistic analyses 32–35 wGA, ≤6 months CA with AAP 2006 RF. AAP = American Academy of Pediatrics; CA = chronologic age; QALY = quality-adjusted life-year; RF = risk factor; wGA = weeks gestational age.

Figures 9 and 10.  Probabilistic analyses 32–35 wGA, ≤6 months CA with ≤1 RF. CA = chronologic age; QALY = quality-adjusted life-year; RF = risk factor; wGA = weeks gestational age.

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