Re: Wolfe et al. Do rheumatology cost-effectiveness analyses make sense?

A. Brennan and N. Bansback

Operational Research, School of Health and Related Research, University of Sheffield, UK

Correspondence to: A. Brennan. E-mail: a.brennan{at}sheffield.ac.uk

SIR, Wolfe et al. [1] provides a valuable editorial into the field of economic evaluation in rheumatology. The editorial focuses first on the relation between observational and randomized controlled trial (RCT) data on improvement in health assessment questionnaire (HAQ) disability score and second on the realism of using the disease activity score (DAS28) as the clinical criterion for judging successful response. We would like to extend the thinking in both these areas and discuss a further important issue relating to the timing of policy decisions.

The first key point questions the use of HAQ score improvements from RCT versus observational data. In considering this further, we believe the apparent incompatibility between data sources is a function of timing of measurement and patient group. Indeed the explanations below suggest that these data might be reconciled. The reported HAQ changes from the US National Data Bank for Rheumatic Diseases (NDB) show a change over a 6-monthly period from 1.22 to 1.15 in ‘785 RA [rheumatoid arthritis] patients who were not receiving etanercept when the HAQ was first measured but who were receiving it 6 months later and who had a duration of etanercept therapy of 3 months or more’. Therefore the first measurement of HAQ does not take place at the point of the clinical decision but prior to it. At some point after this first measurement, each of the 785 patients was switched to etanercept for clinical reasons; reasons that probably include a significant worsening in disability. If the measurement of HAQ was made at the point when therapies were switched (X2), one would expect to see a greater HAQ improvement (X2 X3), instead of the rates reported (X1X3) (see Fig. 1). We would argue that the washout of treatments before a clinical trial is a reflection of worsening of the HAQ seen at the switch between treatments in clinical practice.



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FIG. 1. Illustration of possible measurement and pathway discrepancy.

 
The second key point refers to the criteria for successful response and hence continuation. In RCT and observational trials of etanercept [24] and other biological therapies of severely affected patients, the mean HAQ score at baseline was 1.6. After treatment with etanercept monotherapy the overall mean HAQ score was 1.0—not too dissimilar to the 1.15 seen in the NDB. These figures are made up of both responders and non-responders (see Fig. 2). We therefore believe that the results presented in our paper [5] are an accurate reflection of the cost-effectiveness, provided that the successful response criteria specified by the British Society for Rheumatology [6] are strictly adhered to in clinical practice. There is a question as to whether these guidelines will be followed. Importantly, the cost-effectiveness of the treatments is directly correlated to how stringent the definition of success is. To continue etanercept in patients where the treatment shows only minor efficacy will add little benefit [in terms of quality adjusted life years (QALYs)] at great cost, therefore worsening the cost-effectiveness. Modelling could be used now to calculate the implied worsening in cost-effectiveness based on assumptions about clinical adherence, or later when audit/observational data are available. However, if rheumatologists do not follow the guidelines, as these data emerge refinement of the cost-effectiveness calculations could indeed show the treatments to be less cost-effective.



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FIG. 2. Example of HAQ changes from Moreland et al. [2].

 
Finally, the purpose of economic models is to inform decision making at a particular point in time. The rationale is that a better decision will be made at time t by using a model than by not using it. At a later point in time, t + 1, the model can be updated using additional clinical data from, say, long-term observational studies and then better-informed decisions can be made in the future [7]. At the time of the decision (2001), the National Institute for Clinical Excellence (NICE) made a judgement informed by the model results [5] with the limited data available to them. NICE proposed that the British Biologics Registry (http://www.arc.man.ac.uk/webbiologicsreg.htm) monitor side-effects and evaluate longer-term efficacy to monitor the reappraisal in 2005.

We do not want to ignore the potential problems of validity when using RCT data to predict real-life events in economic evaluation. We strongly agree that observational evidence will provide essential information on long-term efficacy, safety and resource use in biologics. We conclude that the apparent differences between RCT and observational evidence reported by Wolfe et al. might be reconciled when issues of timing of measurement and patient group are taken into account. Further, the cost-effectiveness results presented are reasonable estimates provided that clinical guidelines for response criteria are followed.

The authors have declared no conflicts of interest.

References

  1. Wolfe F, Michaud K, Pincus T. Do rheumatology cost-effectiveness analyses make sense? Rheumatology Advance Access published October 1, 2003, 10.1093/rheumatology/keh034.
  2. Moreland L, Schiff MH, Baumgartner SW et al. Etanercept therapy in rheumatoid arthritis. A randomized controlled trial. Ann Intern Med 1999;130:478–86.[Abstract/Free Full Text]
  3. Weinblatt ME, Kremer JM, Bankhurst AD et al. A trial of etanercept, a recombinant tumor necrosis factor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340(4):253–9.[CrossRef]
  4. Geborek P, Crnkic M, Petersson IF, Saxne T. Etanercept, infliximab and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden. Ann Rheum Dis 2002;61:793–8.[Abstract/Free Full Text]
  5. Brennan A, Bansback N, Reynolds A, Conway P. Modelling the cost-effectiveness of etanercept in adults with rheumatoid arthritis in the UK. Rheumatology 2004;43:62–72. First published July 30, 2003: 10.1093/rheumatology/keg451.[Abstract/Free Full Text]
  6. British Society for Rheumatology. Guidelines for Prescribing TNF-{alpha} Blockers in Adults with Rheumatoid Arthritis. London: British Society for Rheumatology, 2001. https://www.msecportal.org/portal/editorial/PublicPages/bsr/536883013/1.doc
  7. Sculpher M, Fenwick E, Claxton K. Assessing quality in decision analytic cost-effectiveness models: a suggested framework and example of application. Pharmacoeconomics 2000;17(5):461–77.
Accepted 7 November 2003