Originally published as JCO Early Release 10.1200/JCO.2008.19.8499 on November 10 2008

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In Reply

Edit Remák

Health Care Analytics, United Biosource Corp, London, United Kingdom

We thank Drs Trippoli and Messori for their comments on our publication.¹ The authors are correct in noting that the issue of application of statistical methods in economic evaluation has long been debated. However, the conclusion is not as clear as the authors of this letter would have us believe.

Lack of evidence of difference between the treatment arms is not evidence of lack of difference. Furthermore, Drs Trippoli and Messori cite an excerpt from the original clinical report of a randomized phase III study published in New England Journal of Medicine² to suggest that the criterion for evidence of prolonged survival was not met, but this was taken out of context. The primary analysis of the results was based on the progression-free survival, which was the primary end point. The overall survival was the secondary end point, and at the time of the analysis, the medians were not reached in either treatment group and therefore did not meet the prespecified level of significance; thus, no conclusion could be made regarding survival.

However, this has no bearing on the economic evaluation itself. We share the view with many other health economists that "rules of inference are arbitrary and entirely irrelevant to the decisions which clinical and economic evaluations claim to inform."³ Decisions should be based on the mean net benefit of the treatment. Cost-minimization analysis, which the authors of this letter seem to call for, has been shown to be an appropriate method of analysis only under rare circumstances (eg, a randomized trial has been designed to test the explicit hypothesis of equivalence in outcome between two therapies), and "the analytic focus should be on the estimation of the joint density of cost and effect differences, the quantification of uncertainty surrounding the incremental cost-effectiveness ratio and the presentation of such data as cost-effectiveness acceptability curves".⁴ All of this has been performed, taking into account all statistical properties of the survival curves reported by the clinical trial, and results have been presented accordingly.

The noninferiority assumption of long-term survival with sunitinib was applied in the extrapolation of survival, and is actually a conservative assumption that works against sunitinib and is, therefore, not biased against the comparator in this trial. Without this assumption, the projected overall-survival curves would cross at 174 weeks. The majority of patients are projected to be dead by this point in time, and the decrease in mean overall survival compared with the base case presented in the paper is outweighed by the decrease in cost of best supportive care, making sunitinib more effective and less costly than interferon alfa.

We feel that the data and analyses performed were presented clearly, following all recommendations on good practices in modeling and reporting of economic evaluations using modeling,^5,6 irrespective of affiliation of the authors. The authorship reflects contribution to the paper, and rightly "JCO makes its editorial decisions based on scientific quality and importance, not authorship."⁷

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

NOTES

published online ahead of print at www.jco.org on November 10, 2008.

REFERENCES

1. Remák E, Charbonneau C, Négrier S, et al: Economic evaluation of sunitinib malate for the first-line treatment of metastatic renal cell carcinoma. J Clin Oncol 26:3995-4000, 2008[Abstract/Free Full Text]

2. Motzer RJ, Hutson TE, Tomczak P, et al: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115-124, 2007[Abstract/Free Full Text]

3. Claxton K: The irrelevance of inference: A decision-making approach to the stochastic evaluation of health care technologies. J Health Econ 18:341-364, 1999[CrossRef][Medline]

4. Briggs AH, O’Brien BJ: The death of cost-minimization analysis? Health Econ 10:179-184, 2001[CrossRef][Medline]

5. Consensus Conference in Guidelines on Economic Modelling in Health Technology Assessment: Decision analytic modelling in the economic evaluation of health technologies. Pharmacoeconomics 17:443-444, 2000[CrossRef][Medline]

6. Nuijten MJC, Pronk MH, Brorens MJA, et al: Reporting format for economic evaluation. Part II: Focus on modelling studies. Pharmacoeconomics 14:259-268, 1998[CrossRef][Medline]

7. Levine MN. In reply. J Clin Oncol 25:614-616, 2007[Free Full Text]

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Related Correspondence

• Cost Effectiveness of Sunitinib
  Sabrina Trippoli and Andrea Messori
  JCO 2008 26: 5829 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Remák, E. Search for Related Content PubMed Articles by Remák, E. Related Articles Related Correspondence Social Bookmarking                            What's this?