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Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease |
Elhassan N O, Sorbero M E, Hall C B, Stevens T P, Dick A W |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study investigated the use of palivizumab as an intervention for the primary prevention of respiratory syncytial virus (RSV). This intervention was compared with no prophylaxis.
Study population The study population comprised a hypothetical cohort of premature infants born at 26 to 32 weeks' gestation discharged from the neonatal intensive care unit at 36 weeks' post-conception age.
Setting The study setting was secondary or tertiary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were derived from studies published between 1982 and 2003. The price year was 2002.
Source of effectiveness data The effectiveness data were derived from a review and synthesis of published studies and government documents.
Modelling The authors developed two decision analytic models. One model included the effects of asthma on costs and outcomes, the other model did not. Analyses without asthma had a time horizon of 1 year post-conception age. The model with asthma had a time horizon of 8 years and included time-dependent Markov processes to allow the risk of asthma to vary with the age of the cohort.
Outcomes assessed in the review The outcomes assessed were:
the average probability of RSV hospitalisation in the no prophylaxis group;
the efficacy of palivizumab in infants without chronic lung disease;
the average probability of RSV hospitalisation in the prophylaxis group;
the length of RSV hospitalisation;
the probability of asthma;
the duration of increased risk of asthma following RSV infection during infancy; and
the quality of life for children with and without asthma.
Study designs and other criteria for inclusion in the review Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Approximately 14 primary studies were included in the review of the literature.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The average probability of RSV hospitalisation in the no prophylaxis group ranged from 0.064 at 31 to 32 weeks' gestation to 0.206 at 26 weeks' gestation.
The average probability of RSV hospitalisation in the prophylaxis group ranged from 0.011 at 32 weeks' gestation to 0.052 at 26 weeks' gestation.
The efficacy of palivizumab in infants without chronic lung disease was 0.747 at less than 32 weeks' gestation and 0.820 at 32 weeks' gestation.
The length of RSV hospitalisation was 6.8 days.
The probability of asthma in the control group was 0 at age 1 year, 1.0 at age 3 years, and 3.0 at age 7.5 years.
The probability of asthma in the RSV group was 11 at age 1 year, 23 at age 3 years, and 30 at age 7.5 years.
The duration of increased risk of asthma following RSV infection during infancy was 7.5 years.
The quality of life estimate for children with symptomatic asthma was 0.89. The absolute difference in quality of life with and without asthma was 0.03.
Measure of benefits used in the economic analysis The measure of benefits used was the quality-adjusted life-years (QALYs) gained. Quality of life estimates, with and without considering the effects of asthma, were derived from articles and measured using the Health Utility Index.
Direct costs The direct costs to the health care system were included in the analysis. These were for drugs, drug injections, hospitalisation and emergency department visits. The drug costs were derived from published wholesale prices, while the cost of a drug injection was assigned the lowest reimbursement rate applicable to local private insurers. The hospitalisation costs were derived from a published study (Stang et al. 2001, see 'Other Publications of Related Interest' below for bibliographic details). The costs of emergency department visits were derived from local estimates in Rochester, USA. In the model that did not include the effects of asthma, the costs were incurred over 1 year and discounting was therefore not relevant. In the model that did include the effects of asthma, the costs were incurred over 8 years and discounting was therefore relevant. Discounting was appropriately performed at an annual rate of 3%. The average and incremental costs were reported. The price year was 2002.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs The indirect costs included in the analysis were those associated with lost productivity of the parents. The authors assumed that one parent lost an average of 8 hours of work per day during RSV hospitalisation. It was also assumed that an average of 3 hours of work per day was required for palivizumab injection visits and emergency department visits. The costs of time lost from work were derived from US Bureau of Labour Statistics data. In the model that did not include the effects of asthma, the costs were incurred over 1 year and discounting was therefore not relevant. In the model that did include the effects of asthma, the costs were incurred over 8 years and discounting was therefore relevant. Discounting was appropriately performed at an annual rate of 3%. The average and incremental costs were reported. The price year was 2002.
Sensitivity analysis A series of one-way sensitivity analyses were undertaken to test the robustness of the results. The parameters used in the model were varied over plausible ranges derived from the literature. In addition, the authors generated estimates for a target best-case scenario for the use of palivizumab prophylaxis.
Estimated benefits used in the economic analysis The authors only reported the QALYs generated by each intervention for the model that included the effects of asthma.
The incremental QALYs gained when palivizumab prophylaxis was compared with no prophylaxis for children born at different gestational ages were:
0.0060 at 26 weeks;
0.0042 at 27 and 28 weeks;
0.0036 at 29 and 30 weeks;
0.0023 at 31 weeks; and
0.0018 at 32 weeks.
Cost results For the model that did not include the effects of asthma, the incremental costs of palivizumab prophylaxis compared with no prophylaxis, at different gestational ages were:
$5,114 at 26 weeks;
$5,589 at 27 weeks;
$6,452 at 28 weeks;
$2,527 at 29 and 30 weeks;
$2,852 at 31 weeks; and
$3,414 at 32 weeks.
For the model that did include the effects of asthma, the costs of palivizumab prophylaxis versus no prophylaxis at different gestational ages, were:
$7,435 and $2,493 at 26 weeks;
$7,257 and $1,790 at 27 weeks;
$8,120 and $1,790 at 28 weeks;
$3,852 and $1,403 at 29 and 30 weeks;
$3,711 and $925 at 31 weeks; and
$4,185 and $829 at 32 weeks.
Synthesis of costs and benefits The costs and benefits were combined using an incremental cost-utility ratio (i.e. the additional cost per QALY gained when palivizumab prophylaxis was compared with no prophylaxis). The authors only reported the incremental cost-utility ratios for the model that included the effects of asthma. The results showed that the incremental cost-utility ratios were higher than $200,000 per QALY for all gestational ages and reached a maximum of $1.85 million per QALY gained for infants born at 32 weeks' gestation. The results of the sensitivity analysis showed that reductions in palivizumab costs to 25% of current values resulted in an incremental cost-utility ratio of less than $100,000 per QALY for infants born at 26 and 29 weeks' gestation.
Authors' conclusions The model supports the implementation of more restrictive guidelines for palivizumab prophylaxis as it was not cost-effective at a threshold of $200,000 per quality-adjusted life-year (QALY).
CRD COMMENTARY - Selection of comparators Although no explicit justification was given for using no prophylaxis for RSV as the comparator, it would appear to represent current practice in the authors' setting. You should decide if the comparator used represents current practice in your own setting.
Validity of estimate of measure of effectiveness The authors did not report that a systematic review of the literature had been undertaken to identify relevant research and minimise biases. The authors provided very few details of the methods used in their review, and did not report how the results from different studies were combined, or if differences between them were compared. The authors only reported that the data were derived from secondary sources, including publications and government documents.
Validity of estimate of measure of benefit The estimation of benefits was modelled using a Markov model. This was appropriate for the study question.
Validity of estimate of costs All the cost categories relevant to the societal perspective adopted were included in the analysis. In addition, all the relevant costs appear to have been included. The costs and the quantities were not reported separately, which will limit the generalisability of the authors' results. The costs were derived from published sources. Appropriate sensitivity analyses of the costs were conducted. All future costs in the model, up to 8 years in the future, were appropriately discounted. The price year was reported, which will aid any future inflation exercises.
Other issues The authors reported that their study was the first cost-effectiveness analysis of RSV prophylaxis by specific gestational age, to evaluate the implication of the possible increased risk of asthma on the economic analysis of RSV prophylaxis and to integrate measures of morbidity. The issue of generalisability to other settings was partly addressed through the sensitivity analysis. The authors do not appear to have presented their results selectively. However, they used a very high threshold ($200,000 per QALY) to determine if prophylaxis was cost-effective in comparison with no prophylaxis. Despite this high threshold, prophylaxis with palivizumab was not found to be cost-effective.
The authors reported a number of further limitations to their study. First, cost and hospital stay were assumed to be equal for all gestational ages. Second, the costs of asthma were derived from data collected between 1985 and 1994. Third, a modelling assumption biased the results towards improved cost-effectiveness of RSV prophylaxis. The authors also assumed that the weights of the infant at the time of discharge and the time of injections were at 10% of the growth curve.
Implications of the study The authors reported that current American Academy of Pediatrics' recommendations for the use of palivizumab as RSV prophylaxis in premature infants without chronic lung disease are not cost-effective at present.
Bibliographic details Elhassan N O, Sorbero M E, Hall C B, Stevens T P, Dick A W. Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease. Archives of Pediatrics and Adolescent Medicine 2006; 160(10): 1070-1076 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.
Stang P, Brandenburg N, Carter B. The economic burden of respiratory syncytial virus-associated bronchiolitis hospitalizations. Arch Pediatr Adolesc Med 2001;155:95-6.
American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV. Pediatrics 1998;102:1211-6.
Joffe S, Ray GT, Escobar GJ, et al. Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants. Pediatrics 1999;104:419-27.
Indexing Status Subject indexing assigned by NLM MeSH Antibodies, Monoclonal /economics /therapeutic use; Antibodies, Monoclonal, Humanized; Antiviral Agents /economics /therapeutic use; Asthma /economics /epidemiology /prevention & Comorbidity; Cost of Illness; Cost-Benefit Analysis; Decision Support Techniques; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases /economics /epidemiology /prevention & Length of Stay; Palivizumab; Quality-Adjusted Life Years; Respiratory Syncytial Virus Infections /epidemiology; control; control AccessionNumber 22006002048 Date bibliographic record published 30/04/2007 Date abstract record published 30/04/2007 |
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