Editor,—I recently saw the UK guidance for the use of synagis (Palivizumab) brought out by the manufacturer and contributed to (?endorsed) by a number of UK experts. My interpretation of the IMpact-RSV (respiratory syncytial virus) study1appears to be at variance to the conclusions drawn and the recommendations of the “guidance”.

To me, in the above mentioned study,1 compared to placebo, Palivizumab: (a) did not (the trial lacked the power to demonstrate) reduce death or need for mechanical ventilation; (b) reduce RSV related hospitalisation by 55%—the primary outcome of interest.

Based on (b), the “guidance” recommends Palivizumab for premature infants of < 36 weeks' gestation who are < 6 months old at the start of RSV season as well as those with bronchopulmonary dysplasia < 2 years old who have required medical treatment within six months of the RSV season beginning.

Looking at the data in another way, one would need to treat 16 suggested “at risk” babies (20 for babies with bronchopulmonary dysplasia) to prevent one RSV related hospitalisation. Is it worth it in clinical or economic costs?

Clinical—There was no evidence that RSV illness was less severe among hospitalised Palivizumab recipients than among hospitalised placebo recipients. (The paper provides figures for secondary efficacy end points as per 100 treated children. I suppose they are clinically more relevant than for per 100 hospitalised children.) Although statistically insignificant, both the RSV related deaths occurred in the Palivizumab recipients. Three per cent of placebo recipients (but 15 of 53 hospitalised placebo recipients) and 1.3% of Palivizumab recipients (but 13 of 48 hospitalised Palivizumab recipients) had RSV intensive care unit admissions. Only 0.2% (one of 500 treated or 53 hospitalised) placebo recipients and 0.7% (seven of 1002 treated or 48 hospitalised) Palivizumab recipients required mechanical ventilation. Similar conclusions can be drawn for total ventilator days. In other words, reduction in hospitalisation rates does not necessarily equate with reduction in severity of illness.

Economic—As 16 at risk infants need to be treated to prevent one hospitalisation, and as the infants would receive five monthly injections of the antibody costing between £424 (US$680) and £706 (US$1130) per injection (depending on their weight), the cost of preventing one hospitalisation from RSV related illness is at least £32 000 (US£51 000). I do not know the latest figures for a paediatric inpatient stay but analogies from neonatal “special care” category days would suggest that a six to eight day admission (calculated figures from the IMpact-RSV trial) should not cost more than £1800 to £2500 (US$2880–4000).

So I see very little clinical benefit to those “at risk” children who receive Palivizumab and get RSV illness nor do I see any economic advantage to prevention of RSV related hospitalisations. Indeed both the PREVENT2 and Impact-RSV1studies show much lower rates of hospitalisation among the placebo infants than for historic data, which has been attributed among other things to “extensive education”. The valid conclusion then should be that education is the most important tool for prophylaxis against RSV hospitalisation.

The “guidance” suggests drawing conclusions from local RSV hospitalisation rates but these are affected by geographic and social factors as much as clinical ones. Moreover, would local figures have any meaningful value if a large multinational study fails conclusively to prove clinical or economical benefits of the treatment? I do not dispute that there will be an occasional baby with such severe lung disease that any help, however proved, would be welcome. But a generalised preventive measure such as this will be difficult to justify.

Have I got it all wrong?