Palivizumab and the importance of cost effectiveness
BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b1935 (Published 11 June 2009) Cite this as: BMJ 2009;338:b1935
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
"Palivizumab. An extremely expensive drug that reduces
hospitalisation from respiratory syncytial virus". Not if it is used
efficiently?
One of the papers I was invited to deliver at the World Congress of
Critical Care held in Madrid in 1993 was on the potential for gastric
tonometry to improve cost-effectiveness. I believe it was there that I
first made the case for using measurements of intramucosal pH to select
patients who needed added treatment and might benefit from a monoclonal,
Centoxin made by Centocor being in contention at that time. A few months
later I made the same case, at a meeting I believe was supported partly
or wholy by Pfizer, for the monoclonal antibody that had been developed
against TNF alpha. The proposal had the potential to improve cost-
effectiveness by restricting administration to those with a persistently
low gastric intramcuosal pH that had failed to respond to treatment. By
eliminating unnecessary usage in the majority of patients the proposal
also had the potential to reduce the market potential for the costly
drugs. The same means could be used to select patients for ECMO. The value
of gastric intramucosal pH in prediciting weaning success or failure
demonstrates the credibility of these unadopted proposals.
"Measurement of gastric intramucosal pH (pHim)represents a simple and
accurate index to predict weaning outcome...During mechanical ventilation,
pHim was < or = 7.30 in patients who failed weaning and > 7.30 in
patients who were successfully weaned (p < 0.001; 100% sensitivity and
specificity)" (1).
This study, in which the pHim was derived from measurements of pCO2
made with silicone balloon tonometers, improved upon those in an earlier
study in which the measurements had been made in samples of raw gastric
juice (2). In the earlier study, "Patients who were successfully weaned
from mechanical ventilation showed no change in pHi [pHim](7.45 during
mechanical ventilation compared with 7.46 during weaning [difference,
0.01; CI, –0.01 to 0.03; P = 0.29]). The sensitivity and specificity of
pHi [pHim] in predicting weaning success or failure were both 100% (CI, 81
to 100 and 72 to 100, respectively).
The predictive value of the pCO2-gap, which fails to take into
account the additive benefit of the arterial [HCO3-] demonstrated in the
prediction of bleeding from stress ulceration(3), was not as good but a
stress test "increased specificity of [DELTA]Pg-aco2 from 0.45 to 0.94 and
positive predictive value from 0.85 to 0.97" (4).
1. G Bouachour, MP Guiraud, JP Gouello, PM Roy, and P Alquier.
Gastric intramucosal pH: an indicator of weaning outcome from mechanical
ventilation in COPD patients. Eur Respir J 1996; 9: 1868-1873.
2. Z. Mohsenifar; Angela Hay; Jeffrey Hay; Michael I. Lewis; and
Spencer K. Koerner. Gastric Intramural pH as a Predictor of Success or
Failure in Weaning Patients from Mechanical Ventilation. Annals Internal
Medicine 15 October 1993 | Volume 119 Issue 8 | Pages 794-798.
3. Fiddian-Green RG, McGough E, Pittenger G, Rothman E. Predictive
value of intramural pH and other risk factors for massive bleeding from
stress ulceration. Gastroenterology. 1983 Sep;85(3):613-20.
4. Chittock, Dean R. MD; Russell, James A. MD; Walley, Keith R.
Stress test and gastric-arterial Pco2 measurement improve prediction of
successful extubation. Critical Care Medicine. 28(7):2313-2319, July 2000.
Competing interests:
Tonometric patents issued in my name
Competing interests: No competing interests
Alison Teale and colleagues argue eloquently for cost-effectiveness
of drugs to be considered when making decisions about funding. (1) The
example they use, of palivizumab, is a classic illustration of indication
creep. An extremely expensive drug that reduces hospitalisation from
respiratory syncytial virus (RSV), but has not been shown to save lives or
to be cost-effective in multiple economic analyses, has crept into use
around the world. The mechanism used has been to emphasize the relative
reduction in hospitalisation of about 50%, rather than the absolute risk
reduction of about 6%, which means that about 17 babies have to be treated
all winter to prevent one hospital admission.
Teale et al quote the Birmingham study as showing that palivizumab is
cost-effective for some high-risk groups, but the Birmingham authors are
far more circumspect than this. They identify some highly selected
children, such as those born very pre-term with chronic lung disease and
with siblings in day care, whose base-case cost per quality-adjusted life-
year (QALY) is in the range usually acceptable to NICE. They do not give
sensitivities around these QALYs and are careful to conclude only that
palivizumab "may" be cost-effective for these high-risk children. (2)
We in Australia will not use palivizumab until the price is dropped
sufficiently to make the drug truly cost-effective.
References
1. Teale A, Deshpande S, Burts A. Palivizumab and the importance of
cost effectiveness. BMJ 2009; 338: 1474-6.
2. Wang D, Cummins C, Bayliss S, Sandercock J, Burls A.
Immunoprophylaxis against respiratory syncytial virus (RSV) with
palivizumab in children: a systematic review and economic evaluation.
Health Technol Assess. 2008; 12: 1-86.
Competing interests:
None declared
Competing interests: No competing interests
Long term outcomes following admission for RSV bronchiolitis in children
Respiratory syncitial virus (RSV) bronchiolitis remains the most
common cause of serious lower respiratory tract infection in infants
worldwide.(1) Teale et al. describe the cost effectiveness of Palivizumab
prophylaxis following acute infection, currently only recommended in high
risk infants.(2) Emerging evidence from the United States (US) suggests
there is considerable long-term respiratory burden following an episode of
RSV bronchiolitis and most affected infants are previously healthy.(3)
With a RSV vaccine currently recruiting in global trials, the impact of
RSV infection on the long term health of children and future healthcare
utilisation needs to be considered, to establish whether vaccination would
be best targeted at high risk infants or given wider population coverage.
We estimated the five year healthcare burden following hospital admission
for bronchiolitis in England.
We used the Hospital Episode Statistics database to follow up all
children admitted to English hospitals where the primary diagnosis (main
reason for admission) was bronchiolitis or RSV bronchiolitis (ICD-10 codes
J21 and J210 respectively), during the index year 2000/01. We examined
subsequent significant health outcomes over the following 5 years,
including readmissions to hospital (by primary cause), outpatient
consultations, length of stay and mortality.
In 2000/01, 11463 children aged between 4 weeks and 6 months were
admitted with bronchiolitis (2% of all infants aged <1), 4207 of these
with confirmed RSV-associated bronchiolitis. Over the next five years,
42.4% of the overall cohort had one or more further admissions, 25% had
one or more outpatient attendances and 68 children died (6 per 1000
children admitted). Almost half of all further hospital admissions were
for respiratory conditions (48.1%), 15.9% of the overall cohort were
readmitted with bronchiolitis, 7% with asthma and 6% with wheezing.
Further admissions for bronchiolitis had longer hospital stays than
further admissions for other causes (median = 2 days) compared with the
median length of stay for all other which was 1 day (p<0.001).
Our observational study supports the findings of Hall et al., which
showed long-term illness burden and subsequent healthcare utilisation
costs following childhood bronchiolitis are considerably greater than
previously reported(3,4) and not limited to high risk infants.(3) The
next step in the UK is to undertake a full health economic review of the
population burden of RSV disease in children. Development of a live
attenuated vaccine against RSV is progressing rapidly and an improved
prophylactic drug Motavizumab has completed phase III trials.(5) To
assess the clinical and cost effectiveness of these interventions, we now
need to utilise a broad range of data including paediatric intensive care
units, to enhance our understanding of the long-term cost and disease
burden of RSV infection.
References
(1) Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ.
Bronchiolitis-associated hospitalizations among US children, 1980-1996.
JAMA 1999; 282(15):1440-1446.
(2) Teale A, Deshpande S, Burls A. Palivizumab and the importance of
cost effectiveness. BMJ 2009; 338(jun11_1):b1935.
(3) Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA
et al. The Burden of Respiratory Syncytial Virus Infection in Young
Children. N Engl J Med 2009; 360(6):588-598.
(4) Greenough A, Alexander J, Burgess S, Bytham J, Chetcuti PA,
Hagan J et al. Health care utilisation of prematurely born, preschool
children related to hospitalisation for RSV infection. Arch Dis Child
2004; 89(7):673-678.
(5) Handforth J, Friedland JS, Sharland M. Inhaled corticosteroids
after respiratory syncytial virus infection. BMJ 2009; 338(mar31_2):b164.
Competing interests:
Abbott Laboratories provided funding for this study.
Competing interests: No competing interests