Life Years Gained From Palivizumab

Abstract

Reply: In children younger than 5 years of age and particularly in those less than 1 year old, respiratory syncytial virus (RSV) is the most common viral cause of death, resulting in an estimated RSV-associated mortality rate of 3.2 per 100,000 person-years for the 1990/1991 through 1998/1999 seasons in the United States.1 Information about RSV-specific mortality was provided in 36 of 173 studies reviewed by Stensballe et al2 and was zero in 20 of them and 0.1%–12% in the remaining ones. Mortality caused by RSV infection was observed in 33% of the studies in developed countries and in 52% of the studies in developing countries. No difference could be detected when comparing mortality in field- and hospital-based studies or when studies conducted before 1980 were compared with those conducted after 1980.2 During a study period covering 8 consecutive RSV seasons, Thorburn3 reported on 406 RSV-positive patients admitted to the pediatric intensive care unit. Eighteen patients died due to RSV bronchiolitis resulting in an intensive care unit mortality rate of 4.4% and a total hospital RSV mortality rate of 1.7%. All of the RSV deaths were reported to have preexisting medical conditions including chronic lung disease in 12%. In infants and children with congenital heart disease, mortality rates of up to 37% have been reported in the early 1980s with rates ranging from 0% to 16.6% between 1992 and 2010.4 The study of Sampalis5 addressed the issue of health care utilization and morbidity subsequent to RSV hospitalization in non-bronchopulmonary dysplasia premature infants born between 32 and 35 weeks of gestation occurring during the first year of life in Canada. Between 1997 and 2000, a total of 2415 preterm infants hospitalized for proven or probable RSV were matched to 20,254 control infants. Data were impressive for the RSV cohort and control infants, respectively, regarding mean subsequent hospitalizations (2.96 versus 1.28), special care unit visits (0.67 versus 0.40), respiratory therapy visits (0.31 versus 0.13), physician consults (3.61 versus 0.89), in-hospital procedures (1.05 versus 0.81), outpatient visits (18.4 versus 7.54) and mean inpatient days (14.71 versus 5.04), with all differences being statistically significant (P < 0.001). Diagnoses for the RSV and control cohorts were respiratory conditions (64% versus 13%), fever (2.7% versus 0.7%), anorexia (2.2% versus 0.6%), lack of normal physiologic development (2.8% versus 1.1%; P < 0.05), overall deaths (8.1% versus 1.6%; P < 0.001) and sudden death (6.1% versus 0.3%; P < 0.001). In view of the above-mentioned remarkable RSV-related mortality rates reported in high-risk infants throughout the last decades, it seems to be highly justified to use the Sampalis5 data for calculating life years gained by palivizumab. We tried to use the Impact data6 to calculate life years gained for this patient group and obtained a similar result of 0.47 life years gained. The problem is that it is not possible to distinguish mortality rates between patients with need for hospitalization or not. But, nevertheless, results affirm our base case results. It is an interesting phenomenon that many authors criticize the so-called missing effect of palivizumab on the reduction of RSV-related mortality in the 2 placebo controlled trials that led to the license of the product6,7, but neither the Impact study6 in preterm infants with and without bronchopulmonary dysplasia nor the Feltes study7 in infants and children with hemodynamically significant congenital heart disease was powered to detect differences in rates of mortality. In addition, palivizumab still has to be seen in the light of the absence of specific treatment modalities and missing successful vaccine trials instead of research over half a century. Bernhard Resch, MD Research Unit for Neonatal Infectious Diseases and Epidemiology Division of Neonatology, Department of Pediatrics Medical University of Graz Graz, Austria Evelyn Walter, PhD Institute for Pharmaeconomic Research Vienna, Austria Mark J.C. Nuijten, MD, PhD Ars Accessus Medica Amsterdam, The Netherlands