Decision‐making under conditions of uncertainty–what can we learn from palivizumab?

When we make healthcare decisions, whether it be about the treatment of an individual or a policy decision about what should be provided by a health service, there are always uncertainties in the information available. Uncertainties can include: What is the true effectiveness of a proposed treatment? Are there important adverse effects? Is the evidence applicable to this patient? What are the true costs? What is the opportunity cost? Making sensible and responsible decisions where significant uncertainty exists poses a challenge for clinicians and managers trying to optimize outcomes for their patients or populations. Palivizumab use in premature infants represents just such a challenge and is interesting to observe the evolving policy response where it has taken nearly 10 years from launch for national-level recommendations to reflect cost-effectiveness. In this journal, there is an economic evaluation by Neovius et al. (1) that uses Swedish cohort data to address this question. Palivizumab (Synagis ) is a monoclonal antibody that provides passive immunity against respiratory syncytial virus (RSV) infection. It is given by intramuscular injection once a month for five months during the RSV season. There is little doubt that palivizumab is effective at reducing the risk of serious disease from RSV infection as shown in the original trials in high-risk infants(2,3) and confirmed in clinical practice (4,5). The problem is RSV is common, nearly all children have been infected by the age of two, and palivizumab is expensive. Neovius et al.(1) estimate the mean drug acquisition cost per child treated to be 29k SEK (approximately £3k at current exchange rates). This average figure is of the same order as estimates from other economic evaluations (6,7). Since its launch palivizumab has been used extensively and worldwide sales exceeded US$ 1 billion in each of the last 3 years(8), but does using palivizumab in premature infants represent a good use of money or an irresponsibly high opportunity cost? We were first asked to address the issue of its cost-effectiveness by local (West Midlands) health service managers, shortly after palivizumab’s launch in 1999. We calculated that the cost per hospital admission prevented was around £43k (9). There was no direct evidence that palivizumab saved lives – a good example of the uncertainty that decision makers face: the trials were not powered to detect mortality differences, but, is it not reasonable to expect a reduction in deaths if we can reduce the incidence of serious illness and hospital admissions? We thought so, and modelled a reduction in mortality mirroring the reduction in hospital admissions which gave an estimated incremental cost per life-year gained (LYG) of £96k when used in all children who meet the licensed indication (well above the level considered to represent good value for money in the UK). Palivizumab is used prophylactically and cost is incurred for all children treated not just those who would have been seriously ill. It follows, therefore, that the cost-effectiveness will vary according to the probability that a child will Invited Commentary for Kristian Neovius et al. Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden, pages 1306–1314. Acta Pædiatrica ISSN 0803–5253