Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis
BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2538 (Published 14 July 2009) Cite this as: BMJ 2009;339:b2538
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We read with interest the paper by Latimer et al on the cost
effectiveness of Cox-2 selective inhibitors (coxibs) and traditional
NSAIDs. The perspective of this study was stated to be that of the NHS in
England and Wales. However, Latimer et al did not test the external
validity of the data used in their modelling and whether these data are
generalisable to NHS patients. Their pivotal analyses used data from
randomised clinical trials (RCTs) on incidence rates of outcomes.1 We
recently evaluated the external validity of 33 published cost-
effectiveness studies of coxibs, including the study by Latimer et al.2
These studies typically used RCT data to obtain estimates on incidence
rates of outcomes and costs. We concluded that these published cost-
effectiveness analyses of coxibs lacked external validity, did not
represent patients in actual clinical practice and should not have been
used to inform prescribing policies. Exposure to coxibs and traditional
NSAIDs, incidence rates, costs and patients characteristics were
substantially different between RCTs and actual clinical practice (as
measured in the UK General Practice Research Database).2 The belief that
RCT data provide evidence with the least risk of bias, as stated by
Latimer, is flawed. Randomisation does indeed ensure that comparative
measures (such as relative rates) lack bias. However, it does not ensure
that exposure and patient characteristics, incidence rates and costs
reflect those of patients in actual clinical practice. The field of health
technology assessments and the National Institute for health and Clinical
Excellence should move from evaluating cost-efficacy in ideal
(hypothetical) populations with ideal interventions to cost-effectiveness
in real populations with pragmatic interventions.2 External validity
should be an explicit requirement for cost-effectiveness analyses.
Prescribing policies should be based only on cost-effectiveness analyses
with proven external validity.
Tjeerd-Pieter van Staa1-2, Hubert G Leufkens1, Liam Smeeth3
1Utrecht Institute for Pharmaceutical Sciences, Utrecht University,
Utrecht, the Netherlands
2General Practice Research Database, London, United Kingdom
3London School of Hygiene & Tropical Medicine, London, United Kingdom
References
1. Latimer N, Lord J, Grant RL, O'Mahony R, Dickson J, Conaghan PG;
National Institute for Health and Clinical Excellence Osteoarthritis
Guideline Development Group. Cost effectiveness of COX 2 selective
inhibitors and traditional NSAIDs alone or in combination with a proton
pump inhibitor for people with osteoarthritis. BMJ 2009 Jul 14;339:b2538.
doi: 10.1136/bmj.b2538.
2. van Staa TP, Leufkens HG, Zhang B, Smeeth L. A comparison of cost
effectiveness using data from randomized trials or actual clinical
practice: selective cox-2 inhibitors as an example. PLoS Med 2009
Dec;6(12):e1000194.
Competing interests:
The views expressed in this paper are those of the authors. GPRD receives funding from the MHRA, pharmaceutical companies, universities, and contract research organizations. The department of of Pharmacoepidemiology and Pharmacotherapy has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public funded Top Institute Pharma (www.tipharma.nl, includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. The authors declare that they have no other competing interest.
Competing interests: No competing interests
Re: external validity of cost-effectiveness analyses
Van Staa, Leufkens and Smeeth make an important point in their rapid
response to our paper on the cost-effectiveness of NSAIDs and COX-2
selective inhibitors with and without gastroprotection in osteoarthritis,
but we are concerned that they have not considered the observational data
we used. We had to bring together data on treatment efficacy alongside
risk of adverse events, and so found evidence from both randomised
controlled trials and observational studies. The pros and cons of these
two approaches in terms of bias are well known, but external validity to
an NHS setting is multi-dimensional and harder to judge objectively. For
this reason we took both designs into consideration and constructed the
same health economic model with RCT data, then again with observational
data as a sensitivity analysis. We feel this is a useful approach that
brought our discussion of bias and validity in the literature from being
opinion-based to evidence-based and would recommend it to others in the
field.
Where van Staa and colleagues describe the notion of RCTs offering
least bias as flawed, we can only assume they are referring to bias
compared to a post hoc application, in this case routine NHS practice. In
this way the argument seems to confuse bias and external validity. It may
be unrealistic to set a goal of synthesized evidence perfectly valid for
the NHS; the studies we found were the best available, yet differed in
terms of setting, design, outcomes, patient inclusion, dose regimen and
comparators, and even once these issues were considered there was residual
heterogeneity (for instance, stroke incidence in the CLASS study) that
warrants sensitivity analysis. For this reason we feel our approach is
more useful than refusing all but the purest data in terms of validity.
Competing interests:
All authors were members of the National Institute for Health and Clinical Excellence Osteoarthritis Guideline Development Group (PGC chaired the group, JD was the clinical adviser, RLG was project manager, NL was the health economist, JL was the National Institute for Health and Clinical Excellence technical adviser, and RO was the research fellow). During the guidelines process, PGC received travel grants to educational meetings and honoraria for joint injection tutorials from Merck, Sharp & Dohme, he has also been adviser to Novartis and Bristol Myers Squibb on imaging studies in rheumatoid arthritis. JD has received travel grants from Pfizer, Wyeth, Novartis, and Napp, and honoraria for tutorials from Pfizer and Novartis. He has also been on advisory boards for pharmaceutical companies including GlaxoSmithKline, Wyeth, and Novartis. After completing the guideline analysis but before its publication, NL joined Roche Products and has since moved to the University of Sheffield. RLG, JL, and RO have no competing interests.
Competing interests: No competing interests