Better Treatments That Cost More: The Dilemma

Gynecologic Oncology 78, 1–2 (2000) doi:10.1006/gyno.2000.5885, available online at http://www.idealibrary.com on

EDITORIAL Better Treatments That Cost More: The Dilemma Laurie Elit,* ,§ ,1 Amiram Gafni,† ,‡ and Mark N. Levine§ *Departments of Obstetrics and Gynecology, †Medicine, and ‡Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; and §Cancer Care, Ontario Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada L8V 5C2

Radiation has been the standard treatment for locally advanced cancer of the cervix. A recent advance in the treatment of cervical cancer is the addition of concurrent chemotherapy to radiation [1– 6]. In this edition of Gynecologic Oncology, Rose and Lappas provide a pharmacoeconomic analysis for determining whether cisplatin-based chemoradiation is costeffective when compared to radiation alone [7]. When considering the results of a pharmacoeconomic study, we need to (1) judge the quality of the evidence concerning effectiveness, (2) critically appraise the methodology of the economic evaluation, and (3) study the health care policy implications of the results. The framework in Drummond et al. [8], which consists of 10 questions (Table 1), is helpful in critically appraising such studies. The study by Rose and Lappas satisfies Questions 1, 2, 6, 8, and 9. We wish to address issues raised by the remaining questions.

seen by agencies such as HMOs in the United States and the Ministries of Health in Canada. Consequences that were included were survival and treatment-related acute toxicity. Long-term morbidity of treatment and changes in quality of life of the patient and family were not evaluated. A preferable measure of outcome for these consequences could have been quality-adjusted life years (QALYs), health year equivalents (HYE), or willingness-to-pay (WTP) [8]. The authors assumed that the cost and consequences of recurrent disease and death are the same in both study arms. This may or may not be the case depending on whether there is a difference in time to recurrence between the groups and the difference in recurrence pattern.

Question 3: Was There Evidence That Effectiveness Has Been Established?

The authors chose not to assess the impact of discounting, which represents the decision-maker’s preferences regarding the timing of the costs and consequences of an intervention. For example, positive time preference implies that dollars spent or saved in the future should not weigh as heavily in program decisions as dollars spent/saved today. We agree with Rose and Lappas that the treatment and acute toxicities did not extend beyond a year; however, survival and long-term toxicities do extend beyond a year. Thus, it would be appropriate to evaluate the impact of discounting in a sensitivity analysis.

Question 7: Were Costs and Consequences Adjusted for Differential Timing?

Six randomized controlled clinical trials have been conducted to address the role of cisplatin chemotherapy in addition to radiation therapy [1– 6]. The chemotherapy plus radiation treatment provided a survival advantage in the first five studies [1–5], but not in the recent Canadian trial [6]. As is often the case with clinical trials, these studies raise a number of further questions, for example, the use of single-agent cisplatin versus multiple-agent cisplatin and 5FU chemotherapy, the optimal dose of cisplatin [5, 6], and the optimal fractionation schedule of radiation therapy [6].

Question 10: Did the Discussion of Results Include All Issues of Concern to Users? This brings us to our final two points of discussion: generalizability and the policy implications of this pharmacoeconomic evaluation. A concern emerging in the current economic literature relates to the generalizability of the costing data. There is evidence that hospital cost variation may be large both within countries and between countries [9]. The pharmacoeconomic evaluation is most useful in those environments where the costing and consequence units are valued the same as in the study. The authors correctly provide the reader with the incremental costs imposed by chemoradiation over radiation alone com-

Questions 4 and 5: Were All Important Costs and Consequences Identified and Measured? This study assumed the viewpoint of the third-party payer. The costs included were the direct costs associated with overhead, supplies, and physician visits. Indirect costs such as those borne by patients and their families for time off work or for travel were not included. Thus, we do not see the full impact of chemoradiation on cost, but rather we see a limited picture: that 1

Dr. Elit is a Career Scientist in the Health Research Personnel Development Programme, Ontario Ministry of Health. 1

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EDITORIAL

TABLE 1 Guide for Assessing the Quality of a Pharmacoeconomic Study [8] 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Was a well-defined question posed in answerable form? Was a comprehensive description of the competing alternatives given (i.e., can you tell who did what to whom where and how often)? Was there evidence that the program’s effectiveness had been established? Were all important and relevant costs and consequences for each alternative identified? Were costs and consequences measured accurately in appropriate physical units (i.e., number of physician visits) prior to valuation? Were costs and consequences valued credibly? Were costs and consequences adjusted for differential timing? Was an incremental analysis of costs and consequences of alternative performed? Was a sensitivity analysis performed? Did the presentation and discussion of the results of the study include all issues of concern to users?

pared with the additional survival the new therapy provides. The decision-maker must now determine whether this new therapy can be funded given current fiscal restraints. The cost ratio philosophy as discussed by Rose and Lappas is promoted by a threshold value approach. This approach suggests that all therapies that fall below a given cost per year survival be funded. We agree that patients and society will opt for increased survival, especially when toxicity is minimal. The difficulty in a fixed budget envelope (in which HMOs or publicly funded systems find themselves) is determining where the funds will come from to pay for the increased cost. The economic principle that is being addressed is called opportunity costs (i.e., what benefits will be foregone if money is shifted) [10]. The question to be answered is whether the benefits foregone (due to the shifting of resources) are smaller than the benefits gained. A major obstacle in practice is to find programs to cancel in order to free up resources for the new program. A practical approach that encourages departments to look first for inefficiencies in their own operation (i.e., “clean your own budget first”) is described by Elit et al. [11]. In other words, one would like to start with the gynecologic oncology budget and try to find at least one other intervention (or set of interventions) that, if eliminated, will free up enough resources to support the new intervention (i.e., chemoradiation) and result in a net gain in health outcome. The study by Rose and Lappas [7] seems to indicate that this might be possible.

There are few pharmacoeconomic evaluations in the gynecologic oncology literature. We congratulate the authors on undertaking this assessment of chemoradiation. REFERENCES 1. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stages IIB–IVA carcinoma of the cervix with negative paraaortic lymph nodes: A Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17:1339 –1348, 1999 2. Morris M, Eifel PJ, Lu J, Grisby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM: Pelvic radiation with concurrent chemotherapy versus pelvic and para-aortic radiation for high risk cervical cancer: A randomized Radiation Therapy Oncology Group clinical trial. N Engl J Med 340:1137–1143, 1999 3. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based chemotherapy and radiotherapy for locally advanced cervical cancer. N Engl J Med 340:1144 –1153, 1999 4. Peters WA III, Liu PY, Barrett RJ, Gordon W Jr, Stock R, Berek JF, DiSaia PJ, Souhami L, Grisby P, Alberts DS: Cisplatin and 5-fluorouracil plus radiation therapy are superior to radiation therapy as adjunctive in high-risk early stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: Report of a phase III intergroup study. Gynecol Oncol 72:443, 1999 5. Keys HM, Bundy BM, Stehman FB, Muderspach LI, Chafe WE, Suggs CL, Wlaker JL, Gersell D. A comparison of weekly cisplatin during radiation therapy versus irradiation alone each followed by adjuvant hysterectomy in bulky stage IB cervical carcinoma: A randomized trial of the Gynecologic Oncology Group. N Engl J Med 340:1154 –1161, 1999 6. Pearcey RG, Brundage MD, Crouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D: A clinical trial comparing concurrent cisplatin and radiation therapy versus radiation alone for locally advanced squamous cell carcinoma of the cervix carried out by the National Cancer Institute of Canada Clinical Trials Group. A0CO 19;2000 Abstract 1497 7. Rose PG, Lappas PT: Analysis of the cost effectiveness of concurrent cisplatin-based chemoradiation in cervical cancer: Implications from five randomized trials. Gynecol Oncol 78:3– 6, 2000 8. Drummond MF, O’Brien BJ, Stoddart GL, Torrance GW: Methods for the Economic Evaluation of Health Care Programmes, 2nd ed, Oxford Medical Publications, 1997, Chapter 5, pp. 96 –138 9. Hansen KK, Zwanzizer J: Marginal costs in general acute care hospitals: A comparison among California, New York and Canada. Health Econ 5:195–216, 1996 10. Gafni A: Economic evaluation. Journal of health care interventions: An economist perspective. ACP J Club 124:A12–A14, 1996 11. Elit L, Gafni A, Levine MN: Economic and policy implications of adopting paclitaxel as first-line therapy for advanced ovarian cancer: An Ontario perspective. J Clin Oncol 15:632– 639, 1997