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 Similar articles in PubMed 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 Trippoli, S. Articles by Hillner, B. E. Search for Related Content PubMed PubMed Citation Articles by Trippoli, S. Articles by Hillner, B. E.

Survival Gain in Cost-Effectiveness Studies

Drug Information Center, Policlinico Careggi Hospital Florence, Italy

To the Editor:In comparing treatment A (innovative treatment) with treatment B (reference treatment) in the context of a cost/effectiveness (C/E) study, the calculation of the C/E ratio is appropriate when A is more effective than B, ie, when the difference in clinical effectiveness between A and B is statistically significant.¹ When this demonstration is lacking, undertaking a C/E analysis is considered either questionable² or inappropriate.³

The publication of C/E studies wherein the C/E ratio (eg, cost per life year gained or cost per quality-adjusted life year gained) is calculated from situations in which primary data show no statistical difference between A and B in survival or quality-adjusted survival is becoming more and more frequent, as previously pointed out²; the rationale for publication is, however, unclear. In the Journal of Clinical Oncology, for example, Hillner et al⁴ published a C/E study comparing pamidronate with placebo in advanced breast cancer in which the C/E ratio was calculated in the absence of a significant difference in quality-adjusted survival between pamidronate and placebo (cost per quality-adjusted life year gained = $108,200 or $305,300, depending on the patient subgroup). Likewise, Hillner et al,⁵ in comparing temozolomide with dacarbazine for metastatic melanoma, found no statistical difference in unadjusted survival (primary data), but constructed a C/E ratio where the survival gain was 1.1 months per patient and the cost per life year gained was $36,990. A very similar problem applies to the study by Hlatsky et al,⁶ which has been criticized for the lack of a significant survival difference.⁷ Given that the C/E ratio assumes that there is a clinical difference between A and B, in our view, the calculation of this ratio is inappropriate when primary data show no statistical difference in effectiveness between A and B.

REFERENCES

1. Weinstein MC, Siegel JE, Gold MR, et al: Recommendations of the panel on cost-effectiveness in health and medicine. JAMA 276: 1253-1258, 1996[Abstract]

2. Trippoli S, Messori A: Cost-effectiveness analyses of statistically ineffective treatments. JAMA 280: 1992-1993, 1998[Free Full Text]

3. Società Italiana di Farmacoeconomia (SIFE): Linee-guida per la conduzione di studi sull’efficacia e sul costo dei trattamenti farmacologici. Farmacoeconomia 3: 147-153, 1999

4. Hillner BE, Weeks JC, Desch CE, et al: Pamidronate in prevention of bone complications in metastatic breast cancer: A cost-effectiveness analysis. J Clin Oncol 18: 72-79, 2000[Abstract/Free Full Text]

5. Hillner BE, Agarwala S, Middleton MR: Post hoc economic analysis of temozolomide versus dacarbazine in the treatment of advanced metastatic melanoma. J Clin Oncol 18: 1474-1480, 2000[Abstract/Free Full Text]

6. Hlatsky MA, Rogers WJ, Johnstone I, et al: Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. N Engl J Med 336: 92-99, 1997[Abstract/Free Full Text]

7. Jacobson MW: Cost-effectiveness of coronary bypass surgery versus angioplasty. N Engl J Med 336: 1840-1841, 1997 (letter)[Free Full Text]

Response

Virginia Commonwealth University Richmond, VA

In Reply:Trippoli et al have published frequent commentaries about limitations in a variety of published cost-effectiveness issues. Herein, they again question the appropriateness of doing a cost-effectiveness study of a trial without statistically significant results. As Hlatky¹ noted in his reply to Jacobson,² an ongoing debate is about how to distinguish between the concepts of statistically significant and clinically important.

Our article³ addressing the cost-effectiveness of pamidronate in advanced breast cancer was based on data from the two trials critical to the United States Food and Drug Administration approval that were statistically significant in the primary end point, skeletal-related complications due to bony metastases.^4,5 The determination of a quality-adjusted survival was done in our post-hoc analyses and determining a statistically significant difference in quality-adjusted survival was not possible.

In our article⁶ addressing the role of temozolomide in metastatic melanoma, we previously stated that the trial was underpowered or overly optimistic; that is, too few patients were enrolled. In this trial, the observed 7+ month median survival was almost identical to that of larger community cohorts.⁷ Therefore, the issue concerning the clinical importance of a 1.1-month survival benefit can be debated when observed in a negative trial. Although we disagree with Trippoli et al that all such analyses are inappropriate, we do hope that in the design of future clinical trials, sample sizes are determined realistically to avoid this debate.

REFERENCES

1. Hlatky MA: Reply to: Jacobson MW. N Engl J Med 336: 1840-1841, 1997

2. Jacobson MW: Cost-effectiveness of coronary bypass surgery versus angioplasty. N Engl J Med 336: 1840-1841, 1997 (letter)

3. Hillner BE, Weeks JC, Desch CE, et al: Pamidronate in prevention of bone complications in metastatic breast cancer: A cost-effectiveness analysis. J Clin Oncol 18: 72-79, 2000

4. Hortobagyi GN, Theriault RL, Lipton A, et al: Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group [see comments]. N Engl J Med 335: 1785-1791, 1996[Abstract/Free Full Text]

5. Hortobagyi GN, Theriault RL, Lipton A, et al: Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate: Protocol 19 Aredia Breast Cancer Study Group. J Clin Oncol 16: 2038-2044, 1998[Abstract]

6. Hillner BE, Agarwala S, Middleton MR: Post hoc economic analysis of temozolomide versus dacarbazine in the treatment of advanced metastatic melanoma. J Clin Oncol 18: 1474-1480, 2000

7. Barth A, Wanek LA, Morton DL: Prognostic factors in 1,521 melanoma patients with distant metastases [see comments]. J Am Coll Surg 181: 193-201, 1995[Medline]

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 Similar articles in PubMed 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 Trippoli, S. Articles by Hillner, B. E. Search for Related Content PubMed PubMed Citation Articles by Trippoli, S. Articles by Hillner, B. E.