Changing costs and the impact on RSV prophylaxis

Abstract

Objective:

Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks’ gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.

Methods:

New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.

Results:

Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors.

Conclusions:

Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks’ GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.

Limitations:

There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.

Key words::

• Respiratory syncytial virus
• Palivizumab
• Cost analysis
• Cost-effectiveness analysis

Background

In the current era, respiratory syncytial virus (RSV) is still the most dominant viral pathogen that causes lower respiratory tract infection (LRTI) and hospitalization in children under 2 years of age. RSV hospitalization costs in Canadian children 1–4 years of age from 1993–1994 were calculated at (all costs are in Canadian dollars, unless otherwise specified) $18.5 million1. Palivizumab, a humanized monoclonal antibody shown to be effective at preventing RSV hospitalization in infants2, is currently approved in Canada for infants in several high risk categories. Due to its high acquisition cost, many cost-effectiveness analyses (CEAs) have been performed worldwide to determine both cost impact as well as target specific populations for palivizumab prophylaxis. While results vary, most analyses suggest that palivizumab may be cost effective in well-defined high-risk populations3. Risk factors for RSV hospitalization include bronchopulmonary dysplasia or chronic lung disease (BPD/CLD), congenital heart disease (CHD), and prematurity, and have been shown to have a strong influence on cost effectiveness4.

In the United States, the cost for palivizumab increased from approximately US$9005 for a 100 mg vial in 1999 to current prices of US$1073.88 and $2027.80 for 50 mg and 100 mg vials respectively6 (all prices represent Wholesale Acquisition Cost [WAC], cost to the payer). However, the 2.5% cost increase for prophylaxis has been much more modest in Canada from 2007 to 2010 in comparison to the US, with prices rising from $733.91 per 50 mg vial and $1467.81 per 100 mg vial to $752.26 and $1504.51, respectively. This larger price increase may impact the cost effectiveness of palivizumab in the US7. In light of the recent, more restrictive recommendations by the American Academy of Pediatrics (AAP) for RSV prophylaxis in 32–35 gestational age infants8 (limit three doses), it is important to examine the impact of the relatively modest Canadian price increase on local cost analyses in order to reassess cost effectiveness of the product based on our published model.

In 2007, Lanctôt et al.9 used a decision analytic model to compare direct and indirect costs and benefits of palivizumab prophylaxis for RSV in a sub-group of infants of gestational age (GA) 32–35 weeks. The primary analysis was performed from the payer's perspective (Canadian provincial Ministries of Health) and the secondary analysis from the societal perspective, including indirect costs. Sub-analyses indicated that the results varied based on the number of risk factors and risk level (low to high) utilizing a risk-scoring tool (RST)10. Incremental cost-effectiveness ratios (ICERs) were $31,618 per quality-adjusted life-year (QALY) excluding asthma costs and $20,924/QALY including them. Given the change in medication prices, the objective of this report was to re-evaluate palivizumab cost effectiveness in Canada with updated 2010 values in order to assess the effect of local cost changes.

Methods

Model details were described in Lanctôt et al.9 This model was updated to reflect 2010 prices in order to examine the effects of changing healthcare costs on palivizumab cost effectiveness. The 2007 and updated 2010 model values are summarized in Table 1. Palivizumab prices are from Abbott Laboratories Ltd, Canada. Per diem costs for paediatric ward and paediatric intensive care unit (ICU) were adjusted for inflation from 2007 values using the Bank of Canada's online inflation calculator (original values from the Ontario Case Costing Initiative11). The 2010 per diem general ward costs were from Health Canada12. GP office visits, paediatric consultation, and house call assessment costs were obtained from the Ontario Ministry of Health Schedule of Benefits13. The analysis was performed from the perspective of the publicly funded healthcare system for infants 32–35 weeks’ GA in Canada, as well as for select sensitivity to changes in mortality rate of infants hospitalized due to RSV infection. Risk level analyses were conducted to compare changes in cost effectiveness across groups of infants. A risk-scoring tool10 was therefore employed to predict the risk of RSV hospitalization in premature infants, where a score of 0–48, 49–64, and 65–100 represents low, moderate and high risk, respectively.

Table 1.  Costs of RSV prophylaxis and treatment.

Item	2007 value (CAN$)	2010 value (CAN$)	Change (%)
50 mg vial palivizumab	734	752	3
100 mg vial palivizumab	1,468	1,505	3
Paediatric ward (per diem)	957	993	4
Paediatric ICU (per diem)	2,335	2,422	4
General ward (per diem)	799	1,037	30
GP office visit	31	32	5
Paediatrics consultation	142	165	16
Community care contact	42	42	0

Results

From 2007 to 2010, the average cost for an RSV hospitalization increased from $4820 to $5001. ICERs from Lanctôt et al. (2007) and the 2010 cost update are found in Table 2. Given that the causal relationship between RSV infection and asthma has not yet been fully elucidated, direct costs are reported both including and excluding costs of asthma (Table 2). For infants 32–35 weeks’ GA, 2010 ICERs were $20,814/QALY for direct medical costs including asthma and $31,360/QALY excluding asthma, slightly higher than the 2007 values. By contrast, the mortality rates assessed in a sensitivity analysis in the 2007 publication had a much larger impact on ICERs. Even between two relatively similar mortality rates, 1.0% from IMpact2 and 1.2% from Joffe et al.5, the impact of changing mortality on cost effectiveness far outweighs that of changing healthcare costs.

Table 2.  Cost effectiveness of palivizumab prophylaxis.

Analysis	2007 ICER/QALY (CAN$)	2010 ICER/QALY (CAN$)
Base case
Direct medical costs, including asthma	20,924	20,814
Direct medical costs, excluding asthma	30,618	31,360
Select sensitivity analyses
Mortality rate – Joffe et al. (1.2%)	48,751	48,495
Mortality rate – IMpact-RSV (1.0%)	50,701	50,434
Number of risk factors
Zero risk factors	801,297	820,701
One risk factors	143,267	146,218
Two risk factors	81,331	82,732
Three risk factors	26,667	26,701
Four or more risk factors	808	192
Risk-scoring tool10
Low risk (score of 0–48)	179,669	183,561
Moderate risk (score of 49–64)	34,215	34,438
High risk (score of 65–100)	5765	5274

ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

The ICER for the lowest-risk group, those with zero risk factors, increased the most from $801,297/QALY in 2007 to $820,701/QALY in 2010, while the ICER/QALY for the highest-risk group of infants with four or more risk factors, fell from $808 to $192. The smallest increase in ICERs from 2007 to 2010 was in the group of infants with three or more risk factors, and the smallest decrease in ICERs occurred in the total group of infants 32–35 weeks’ GA, which included costs for asthma in 2010.

Discussion

Changes from 2007 to 2010 in cost effectiveness of palivizumab for Canadian infants of 32–35 weeks’ GA were minimal across all analyses. Variation in ICERs from model parameters such as mortality rate or asthma cost inclusion far outweighs the minimal changes over time. The proportionally greater increase in medical costs than in drug costs led to differential changes in ICERs, with additional cost savings per hospitalization avoided, outweighing additional drug costs in high risk groups and lowering ICERs in 2010. ICERs correspondingly increased over time in low-risk groups. Overall, ICERs changed minimally in either direction. As a result, recommendations that palivizumab prophylaxis is cost effective from the perspective of the healthcare system in infants born between 32 and 35 weeks’ GA with two or more risk factors inclusive of those in the moderate and high risk categories as assessed by the risk scoring tool, did not change.

Cost-effectiveness analyses vary between countries even when the same model and parameters are included, in part because of differences between countries in hospitalization costs for an RSV infection3. Thus, palivizumab CEAs are most useful when targeted to specific countries and populations. This update suggests that the cost effectiveness of palivizumab is fairly stable given the modest increases in healthcare and medication costs in Canada. This is an important consideration in light of significant palivizumab price increases in the United States, where even from 2007 costs of US$712.20 and US$1344.80 for 50 mg and 100 mg vials7 there has been an approximate 50% increase. This likely impacted cost effectiveness and usage guidelines, especially in groups of infants such as those between GA 32–35 weeks who constitute approximately 5–7% of the North American birth cohort14. No evidence was found in this analysis for any change in the cost effectiveness of palivizumab that would impact its present indications for use in this sub-population as stipulated by the Canadian Paediatric Society in Canada15. The minimal changes in palivizumab ICERs shown here underscore the need to consider country-specific factors in re-assessing cost effectiveness over time as well as developing a well-defined original analysis.

There are some limitations to this analysis. First, the palivizumab and healthcare costs used in this model are representative of the Canadian economy and healthcare setting. These costs can vary widely between countries; thus conclusions about cost effectiveness can only be drawn for infants residing in Canada. Second, as with the 2007 analysis, there is considerable uncertainty regarding relative mortality rates after RSV infection due to limited data. Only one, nested case-control Canadian study by Sampalis et al.16 was available to report mortality in this group and was used in the primary analysis. The select sensitivity analysis was performed using lower mortality rates reported by Joffe et al. and the IMpact-RSV study.

Conclusion

The 2010 update to this palivizumab cost-effectiveness model demonstrates that the recent increase in Canadian prices for the drug have had no notable impact on ICERs. As healthcare and drug prices change over time in individual countries, it is necessary to re-evaluate the cost effectiveness profile of palivizumab in a local setting in order to ensure accurate and efficient allocation of healthcare resources.

Transparency

Declaration of funding

No funding was provided for this analysis.

Declaration of financial/other relationships

K.S. reports no relevant financial relationships. B.P. and K.L. have disclosed that they are Co-principal Investigators of ‘CARESS’ (Canadian Registry of Synagis), a multicenter investigator initiated research study supported by a research grant by Abbott Laboratories Ltd. The principal investigators maintain control over the rights to publish, as well as any presentations or abstracts composed using the data collected in the study. B.P. and K.L. are also co-investigators on a research study funded by Abbott International entitled ‘Surveillance and cost analysis for Respiratory Syncytial Virus hospital admissions in the Arctic communities in Canada’.