Cost-effectiveness and quality of life evaluation of ondansetron and metoclopramide for moderately emetogenic chemotherapy regimens in breast cancer

Critical Reviews in Oncology/Hematology 32 (1999) 105112 www.elsevier.com/locate/critrevonc Cost-effectiveness and quality of life evaluation of ondansetron and metoclopramide for moderately emetogenic chemotherapy regimens in breast cancer Jean Lachaine a *, Claudine Laurier a, Adrian Langleben b, Linda Vaillant b a Faculty of Pharmacy, Uni ersity of Montreal, P.O. Box 6128, Centre-Ville Station, Montreal Que, H3C 3J7 Canada b Royal Victoria Hospital, Montreal Que, Canada Accepted 24 February 1999 Contents 1. Introduction... 106 2. Patients and Methods... 106 3. Results... 107 3.1. Clinical Effectiveness... 108 3.2. Quality of Life.... 109 3.3. CostEffectiveness Analysis... 110 3.4. Sensitivity Analysis... 110 4. Discussion... 110 5. Reviewers... 111 Acknowledgements... 112 References... 112 Biography... 112 Emesis represents a major obstacle to cancer chemotherapy. To improve emesis control, serotonin antagonists such as ondansetron have been developed. These agents are considered more effective, but are more expensive than traditional, metoclopramidebased, antiemetic regimens. The purpose of this study was to measure, in the context of current practice, the economic and quality of life impact of ondansetronbased regimens, compared with metoclopramide-based regimens in moderately emetogenic chemotherapy. Female patients with breast cancer who were naive to chemotherapy and scheduled to receive a cyclophosphamide-based chemotherapeutic regimen at a teaching * Corresponding author. hospital in Montreal, Canada, were eligible for this study. They received either an ondansetron or a metoclopramide-based antiemetic regimen. The selection of the regimen was left to the attending physician and represented current practice at the institution. Episodes of vomiting were recorded daily in a patient diary for 5 days following chemotherapy. Effectiveness was measured in terms of complete control (0 vomiting episodes) and major control (two or fewer vomiting episodes). Quality of life was measured using the EORTC QLQ-C30 questionnaire. Resource usage related to emesis (medications, devices, pharmacy and nursing time), were collected. Results for 52 patients (22 metoclopramide and 30 ondansetron) were analyzed. Emesis control was significantly better in the ondansetron group: 77% had complete control the first day and 77% over the 5-day period, compared with 32% 1040-8428/99/$ - see front matter 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S1040-8428(99)00025-6

106 J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 (P=0.002) and 27% (P=0.001) respectively for metoclopramide. Global quality of life decreased more with metoclopramide than with ondansetron, but the difference was not statistically significant. For complete control of acute emesis (day 1) the incremental cost-effectiveness ratio was $57 per additional case of emesis avoided with ondansetron. Results of this analysis of antiemetic treatments in the context of current practice indicates that, from a hospital perspective, ondansetron-based regimens would be preferable over metoclopramide-based regimens for controlling acute emesis in breast cancer patients receiving a moderately emetogenic chemotherapy, assuming $57 per emesisfree case to be a reasonable cost. 1. Introduction Emesis is a major obstacle in cancer chemotherapy. Patients indicate that nausea and vomiting are a major concern when receiving chemotherapy [1]. It is estimated that 1015% of patients who should be treated with chemotherapy refuse it because of nausea and vomiting [2]. For patients who could benefit from chemotherapy, treatment interruption may lead to a progression of the disease, and may result in an increase of mortality and morbidity [3]. In recent years, 5-HT 3 antagonists have been developed. Ondansetron was the first drug of this class to be made commercially available. It has been shown to offer better control of emesis than metoclopramide during the first 24 h following chemotherapy (acute emesis). However, evidence of its superiority in preventing emesis after the first 24 h following chemotherapy (delayed emesis) has been less convincing [4]. Ondansetron is generally more expensive than the traditional metoclopramide-based antiemetic regimen. This is particularly the case when the highest recommended dosages are used. There have been few economic evaluations of ondansetron. Most of these looked at the impact of antiemetics in patients treated with highly emetic chemotherapies [5 9], with the exception of the study by Cox et al. [10] of patients receiving cyclophosphamide chemotherapy (moderately emetogenic). All economic evaluation were retrospective, except the study by Cunningham et al. [6], which was conducted prospectively. In general, cost efficacy ratios for ondansetron and traditional regimens were evaluated as similar, the superior efficacy of ondansetron compensating for its higher acquisition cost. However, results of a cost utility analysis with highly emetic chemotherapies were somewhat unfavorable to ondansetron with an incremental cost per QALY of $168 139, although the measure of utility has been criticized [9]. All of these studies relied on data collected during clinical trials, and thus reflect efficacy rather that effectiveness. It is known that efficacy and effectiveness can differ [11]. Treatment decisions should consider effectiveness. Therefore, the purpose of this study was to compare the economic and quality of life impacts of ondansetronbased regimens with those of metoclopramide-based regimens in a real-life context. To do so, antiemetic treatment modalities were not subject to any protocol constraint. Treatment outcomes were compared in women with breast cancer receiving moderately emetogenic chemotherapy. The economic analysis was carried out from the perspective of the hospital which has to pay for the antiemetic treatments, and for the costs related to the preparation and administration of these treatments by the pharmacy and nursing staff. The measure of effectiveness is the control of emesis, while quality of life is looked at as a secondary measure. 2. Patients and methods This study was conducted between February 1995 and July 1997 in a university hospital in Montreal, Canada. Female patients with breast cancer, naive to chemotherapy and scheduled to receive, as outpatients, a cyclophosphamide-based chemotherapeutic regimen were eligible for this study. Cyclophosphamide had to be administered intravenously in a single dose not exceeding 1 g. These chemotherapeutic regimens are considered moderately emetogenic according to standard classification. Patients received either an ondansetron or a metoclopramide-based antiemetic regimen. The selection and dosage of the antiemetic regimen were left to the physician. Because patients were chemotherapy-naive, selection of the antiemetic did not rest on predisposition to emesis, but depended on physicians preference, patient request, and hospital policies regarding the selection of antiemetics. These policies evolved during the course of the study, shifting from discouraging the use of ondansetron for moderately emetogenic chemotherapy to wider access to this product. Eligible patients were identified by the oncology pharmacists from the daily list of patients scheduled to attend the oncology outpatient clinic. The study manager met with each patient and asked their consent to participate in the study. The study protocol and consent form were approved by the hospital s ethics committee. Recruitment of 30 subjects per group was planned. With this sample size, a statistically significant difference between efficacy rates of 75 and 45% can be shown with a significance level of 5% and a power of 80% [12]. These effectiveness rates, for the complete control of acute emesis, are based on a previous study with similar patients and treatment modalities [13].

J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 107 Data on chemotherapy and antiemetics prescribed, patient age and body surface were taken from the patient s record. All other data were provided by the patient in a daily diary. Using the daily diary, patients recorded their incidence of vomiting and nausea for 5 days following chemotherapy. Effectiveness was measured in terms of complete control (0 vomiting episodes) and major control (two or fewer vomiting episodes) (a) during the first day following chemotherapy; (b) for days 25, and c) for the total 5-day period following chemotherapy. In keeping with previous studies [13 16], effectiveness for days 25 and for the 5-day period was based on the results of the worst day during the relevant period. Quality of life was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. This instrument has been shown to be valid and reliable in multicultural clinical research setting [17]. It has been used extensively in cancer trials, including Canadian trials, and is available in both French and English. It incorporates five functional scales (physical, role, cognitive, emotional and social) three symptom scales (fatigue, pain and nausea and vomiting), a global health status/quality of life (QoL) scale, and a number of single items assessing additional symptoms commonly reported by cancer patients. Scores for each scale range from 0 to 100. A high score represents a higher response level. Thus, a high score for a functional scale represents a high/ healthy level of function, a high score for the global health status/qol represents a high quality of life, and a high score for a symptom scale represents a high level of symptomatology/problems [18]. Authorization to use the QLC-C30 for this study was granted by the Table 1 Characteristics of evaluable patients Ondansetron (n=30) Metoclopramide (n=22) Average age 53.6 57.9 (S.D.=10.9) (S.D.=10.1) Average body surface 1.68 m 2 1.68 m 2 (S.D.=0.22) (S.D.=19.8) Average dose of cyclophosphamide 973 mg 1014 mg (S.D.=130) (S.D.=194) French/English-speaking 9/21 (30/70%) 14/8 (64/36%) Cyclophosphamide 20 (66%) 13 (59%) +doxorubicin CMF* 8 (27%) 6 (27%) FAC** 1 (3%) 1 (4%) Cyclophosphamide +carboplatin 1 (3%) 1 (4%) Cyclophosphamide 0 (0%) 1 (4%) +epirubicin * Cyclophosphamide+methotrexate+5-fluorouracil. ** 5-fluorouracil+doxorubicin+cyclophosphamide. EORTC. Three copies of the quality of life questionnaire were included in the daily diary. Patients were instructed to complete one prior to chemotherapy, another at 24 h after chemotherapy and the third at 72 h. In accordance with the hospital perspective, only direct antiemetic treatments costs were considered. These included the acquisition cost of antiemetics, administration devices, and those associated with pharmacy and nursing time for preparing and administering injectable antiemetics. The time required by nurses was estimated using a time motion approach, while time for preparation in the pharmacy was estimated by interviewing pharmacy staff. Costs of antiemetics and devices were those paid by the hospital in January 1998. Pharmacy and nursing costs were calculated by multiplying the time required for the task by the average salary and benefits at the hospital for each of these groups of professionals. Costs of alternative treatments prescribed when the initial treatment failed were added to the costs of the initial treatment. Cost related to emesis, such as cleaning, were not considered. Cost-effectiveness ratios were computed considering the proportion of patients with complete emesis control during the first 24 h and for the total study period (days 15). Statistical analyses were carried out using Fisher s exact test (two-sided) for effectiveness and the t-test for quality of life scores. 3. Results A total of 58 subjects were initially selected. Data were not collected for three patients because one refused to participate and two were unable to read English or French adequately. Data for three patients were not included in the analysis, one because of an inappropriate diagnosis (ovarian cancer rather than breast cancer) and the remaining two because they had not received cyclophosphamide i.v. Results for 52 patients (22 metoclopramide and 30 ondansetron) were analyzed. There were no difference between the two groups of patients in term of mean age, mean body surface or the mean dose of cyclophosphamide. Seventy percent of patients who received ondansetron spoke English as opposed to 36% in the metoclopramide group (Table 1). The most frequent chemotherapies were the combination of cyclophosphamide and doxorubicin (64%), and the combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) (27%). Two patients received cyclophosphamide, doxorubicin and 5-fluorouracil (FAC); two received cyclophosphamide and carboplatin; and one received cyclophosphamide and epirubicin. The type of chemotherapy was not significantly different between the two groups. Patients in the metoclopramide group received an average dose of 306 mg of metoclopramide on day 1

108 J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 Table 2 Antiemetic treatments Ondansetron (n=30) Metoclopramide (n=22) No. of patients Average dose Minmax No. of patients Average dose Minmax (mg) (mg) (mg) (mg) Day 1 (including prechemotherapy) Ondansetron 30 (100%) 20.7 832 Metoclopramide 22 (100%) 306.4 110520 Dexamethasone 29 (97%) 19.2 1032 20 (91%) 10.5 1020 Diphenydramine 22 (100%) 123.87 25250 Lorazepam 16 (53%) 1 11 2 (9%) 1 11 Prochlorperazine 1 (3%) 40 Subsequent days Ondansetron 18 (60%) 21.3 832 Metoclopramide 17 (77%) 295.9 150600 Dexamethasone 21 (70%) 16.8 1224 Diphenydramine 10 (45%) 280 100500 Lorazepam Prochlorperazine 30 (100%) 313.3 100400 19 (86%) 127.4 100400 (including the pre-chemotherapy dose). All these patients received diphenhydramine at an average dose of 124 mg. Dexamethasone was given to 91% of patients at an average dose of 10.5 mg and two patients received 1 mg lorazepam. On subsequent days, metoclopramide was prescribed to 77% of patients at an average dose of 296 mg, with prochlorperazine for 86% of patients and diphenhydramine for 45% of patients. Those in the ondansetron group received an average dose of 21 mg of ondansetron on day 1. A total of 91% of patients also received dexamethasone at an average dose of 19 mg, 53% received lorazepam at a dose of 1 mg, and one patient was administered 40 mg of prochlorperazine. For the following days, prochlorperazine was prescribed to all these patients at an average dose of 313 mg. Subsequent doses of ondansetron were prescribed to 60% of patients at an average dose of 21 mg, and dexamethasone was prescribed to 70% at an average dose of 17 mg (Table 2). Major control was also superior with ondansetron at 93% compared with 59% with metoclopramide (P=0.005). For the control of delayed emesis (days 25) (Fig. 2), complete control was achieved with 83% of patients Fig. 1. Control of acute emesis (day 1). 3.1. Clinical effecti eness In the metoclopramide group, four patients suffered serious side effects which required the cessation of the antiemetic and use of an alternative treatment. These patients were considered metoclopramide-treatment failures. There were no instances of serious side effects requiring cessation of treatment in the ondansetron group. Control of acute emesis was significantly better in the ondansetron group (Fig. 1): for the first 24 h following chemotherapy, 77% had complete control compared with 32% for metoclopramide (P=0.002). Fig. 2. Control of delayed emesis (days 25). Fig. 3. Control of emesis (days 15).

J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 109 Fig. 4. Quality of life (differences between score on day 1 and before chemotherapy). QLQ-C30 scores; score for each scale range from 0 to 100. Fig. 5. Quality of Life (difference between scores on day 3 and before chemotherapy). QLQ-C30 scores; score for each scale range from 0 to 100. receiving ondansetron compared with 55% for those receiving metoclopramide (P=0.032). Major control of emesis was 100 and 82% for ondansetron and metoclopramide, respectively (P=0.027). In addition, for the 5-day period following chemotherapy, ondansetron showed higher effectiveness (Fig. 3), with 77% having complete control and 93% having major control compared with metoclopramide, with 27% (P=0.001) and 59% (P=0.005), respectively. The total dose of ondansetron given on day 1 varied from 8 to 32 mg (median =24 mg). Difference in dosage did not yield significant changes in emesis control. Complete control for day 1 was 73% with ondansetron at doses lower than 24 mg and 79% with doses equal to or greater than 24 mg (P=1.00). For both groups, dosages of antiemetics were within dosage ranges used in clinical trials. 3.2. Quality of life As proposed by Osoba [19], quality of life scores on days 1 and 3 are presented in terms of differences from the scores prior to chemotherapy. Scores were calculated for the five functional scales, the global health status/qol scales and for the symptom scale on nausea and vomiting. With both antiemetic regimens, levels of quality of life 1 day after chemotherapy were lower than prior to chemotherapy on all the five functional scales, except the emotional scale (Fig. 4). On average, patients who received ondansetron had a better score on day 1 than prior to chemotherapy on this scale. The differences between groups were not statistically significant on any of the functional scales. Global health status/qol decreased more with metoclopramide than with ondansetron, but the difference was not statistically significant ( 24 vs. 17, P=0.28). Difference scores on the nausea and vomiting scale coincide with the results observed for the control of emesis. Patients in the ondansetron group had better scores than those on metoclopramide. The difference between day 1 and pre-chemotherapy scores was 19 for ondansetron and 45 for metoclopramide (P = 0.035). On day 3, all scores, except the emotional dimension, were lower than prior to chemotherapy, but to a lesser extent than on day 1 (Fig. 5). For both groups, scores on the emotional dimension were better on day 3 than before chemotherapy. Change in scores on global quality of life were similar for both groups. For the role functioning scale, change in scores were significantly better for ondansetron (P=.002). The differences between groups for the four other functional scales were not statistically significant. On day 3, scores on the nausea and vomiting scale were similar in both groups, with 13 for ondansetron and 11 for metoclopramide.

110 J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 3.3. Cost-effecti eness analysis Costs of antiemetic treatments on day 1 include the cost of antiemetics administered prior to chemotherapy and those prescribed for the first 24 h following chemotherapy. Costs of antiemetic treatments for the whole period include costs incurred on day 1 and those related to antiemetics prescribed for subsequent days. All costs are in Canadian dollars. Average cost of antiemetics per patient for the ondansetron-based regimen was $61 ($24 115) for the first day and $96 ($30 198) for the whole treatment period, while it was $36 ($10 108) and $50 ($13 179), respectively, for metoclopramide. The average cost of administration devices was $1.28 per injection. Pharmacy time required for preparing an i.v. injection dose was 2.5 min at an average hourly rate of $25. Nursing time to administer each i.v. injection was estimated at 1 min, at an average rate of $23 per hour. Thus, for each injectable dose, an amount of $2.71 was added. When metoclopramide and diphenhydramine were simultaneously administered intravenously, cost for only one injection was added, since the two medications were combined in the same mini-bag. For the complete control of acute emesis (day 1) the incremental cost-effectiveness ratio was $57 per additional case of emesis avoided (Table 3). For the 5-day period, the incremental cost-effectiveness ratio was $93 per case of emesis avoided (Table 4). 3.4. Sensiti ity analysis In order to test the robustness of the results, some sensitivity analyses were performed on the results for the whole treatment period (days 1 5). Since dollar amounts allocated to the preparation and administration of injectable antiemetics may not result in real savings at the hospital level and because their estimation may be subject to error, these figures were suppressed in one sensitivity analysis. The cost of therapy varied significantly depending on the type of combination of antiemetics and the dose used. To observe the impact of these variations on the results, sensitivity analyses were done with the cost of antiemetic treatment at 50% less and 50% more than the average cost used in the base case while assuming equivalent effectiveness (Table 5). In all of these analyses, the cost-effectiveness ratio for ondansetron was lower than that for metoclopramide, except when the average cost of metoclopramide was reduced by 50% or the average cost of ondansetron increased by 50%. 4. Discussion Unlike most other studies focussing on efficacy, this study provides effectiveness data, which more closely reflects the impact of treatments in current practice. Nevertheless, the effectiveness rates for complete and major control of emesis are comparable with efficacy results of other studies comparing ondansetron and metoclopramide in combination with a steroid in the context of moderately emetogenic chemotherapies [13 16]. Although, assignment of patients to each treatment group was not randomized but rather based on physician preference, the risk that antiemetic treatment selection was subject to patient predisposition to emesis could not be completely avoided. However, it was minimized by selecting naive patients. Also, both Table 3 Cost-effectiveness analysis a Effectiveness (proportion of emesis-free cases) Incremental effectiveness Cost ($Can) Incremental cost (proportion of emesis-free ($Can) cases) Incremental cost-effectiveness ratio (Incr. $Can per Incr. case of emesis-free) Metoclopramide 0.318 34 Ondansetron 0.767 0.449 61 26 57 a Complete control of acute emesis (day 1). Table 4 Cost-effectiveness analysis a Effectiveness (proportion of emesis-free cases) Incremental effectiveness (proportion of emesis-free cases) Cost ($Can) Incremental cost ($Can) Incremental cost-effectiveness ratio (Incr. $Can per Incr. case of emesis-free) Metoclopramide 0.273 50 Ondansetron 0.767 0.494 96 46 93 a Complete control of emesis (days 15).

J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 111 Table 5 Sensitivity analysis on results for days 15 Cost-effectiveness Incremental cost-efratio ($) fectiveness ratio ($) Metoclopramide 169.08 ( cost for preparation and administration) Ondansetron ( cost 122.88 97.35 for preparation and administration) Metoclopramide (aver- 91.90 age cost 50%) Ondansetron (average 125.61 144.23 cost) Metoclopramide (average cost +50%) 275.71 Ondansetron (average 125.61 42.65 cost) Metoclopramide (aver- 183.81 age cost) Ondansetron (average 62.80 4.07 cost 50%) Metoclopramide (aver- 183.81 age cost) Ondansetron (average 188.41 190.95 cost +50%) Metoclopramide (aver- 91.90 age cost 50%) Ondansetron (average 62.80 46.72 cost 50%) Metoclopramide (aver- 275.71 age cost +50%) Ondansetron (average 188.41 140.16 cost +50%) Metoclopramide (aver- 91.90 age cost 50%) Ondansetron (average 188.41 241.74 cost +50%) Metoclopramide (aver- 275.71 age cost +50%) Ondansetron (average 62.80 54.86 cost 50%) groups were similar in terms of age, body surface, chemotherapeutic regimen and dose of cyclophosphamide. The only difference was in terms of first language, which might be reflected in the greater demand for ondansetron among English-speaking patients. Treatment modalities were not limited to only ondansetron or metoclopramide, but also included other antiemetics. Results reflect the effectiveness of the whole regimen and not only a single antiemetic. Ondansetron regimens included a larger average dose of dexamethasone than the metoclopramide regimen on day 1. Also, dexamethasone was prescribed for subsequent days to a majority of patients in the ondansetron group, while it was not prescribed after day 1 to patients receiving the metoclopramide regimen, and patients in the ondansetron group were more likely to receive lorazepam. This was mainly due to practice guidelines which recommend ondansetron in combination with dexamethasone and lorazepam. There were no statistical differences between groups on most difference scores of the QLQ-C30, except on day 1 for the nausea and vomiting scale and on day 3 for the role functioning scale. Since the sample size was determined with respect to the proportion of emesis freedom, it may not have been large enough to achieve the expected difference on the quality of life scores. The use of an ondansetron-based regimen led to a higher average cost compared with a metoclopramidebased regimen. However, its effectiveness in complete emesis control was significantly higher. The incremental cost-effectiveness ratio for the first day was $57 and 93 for the 5-day period. This means that each additional emesis-free case obtained using the ondansetron-based regimen cost $57 for the first day or $93 for the 5-day period. These costs have to be judged in light of the severe burden on patients experiencing emesis and the risk that they decide to discontinue chemotherapy. The greater efficacy of the ondansetron regimen in controlling delayed emesis (days 25) may be largely due to dexamethasone, since during this period dexamethasone was prescribed to a majority of patient receiving ondansetron but not to those receiving metoclopramide. Since dosage reduction of ondansetron has not led to a significant decrease in emesis control, as has been confirmed by other authors [20,21], the use of lower dosages could lead to cost-effectiveness ratios that are even more attractive. The antiemetic regimens compared in this evaluation represent the current practice at the teaching hospital where the study was conducted for chemotherapy-naive patients. Therefore, the conclusions of this study may not apply to different antiemetic combinations, different settings or different patient populations. Results of this analysis of antiemetic treatments in the context of current practice indicates that, from a hospital perspective, ondansetron-based regimens would be preferable over metoclopramide-based regimens for controlling acute emesis in breast cancer patients receiving a moderately emetogenic chemotherapy, assuming $57 per emesis-free case to be a reasonable cost. 5. Reviewers This paper was reviewed by Drs Linda D. MacKeigan (Assistant Professor) and Thomas R. Einarson, Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto Ont., Canada M5S 2S2; Dr Isabelle Gautier, Pharm.D., Pharmacy Department, Ottawa General Hospital, 501 Smyth Road, Ottawa, Ont., Canada K1H 8L6.

112 J. Lachaine et al. / Critical Re iews in Oncology/Hematology 32 (1999) 105112 Acknowledgements The authors wish to thank Mr Gabriel Gazze, Ms Elisabeth Letendre and Ms Sophia Panopalis, pharmacists at the Royal Victoria Hospital in Montreal, Canada. References [1] Coates A, Abraham S, Kaye S, et al. On the receiving end patient perception of the side effects of cancer chemotherapy. Eur J Cancer Clin Oncol 1983;19:2038. [2] Penta J, Poster D, Bruno S. The pharmacological treatment of nausea and vomiting caused by cancer chemotherapy. In: Laszlo J, editor. Antiemetics and cancer chemotherapy. Baltimore: Williams & Wilkins, 1983:5392. [3] Lindley CM, Bernard S, Fields AM. Incidence and duration of chemotherapy-induced nausea and vomiting in the outpatient oncology population. J Clin Oncol 1989;7(8):11429. [4] Markham A, Sorkin E. Ondansetron, an update of its therapeutic use in chemotherapy-induced and postoperative nausea and vomiting. Drugs 1993;45(6):93152. [5] Buxton MJ, O Brien BJ. Economic evaluation of ondansetron: preliminary analysis using clinical trial data prior to price setting. Br J Cancer 1992;66:S647. [6] Cunningham D, Gore M, Davidson N, et al. The real cost of emesis An economic analysis of ondansetron vs metoclopramide in controlling emesis in patients receiving chemotherapy for cancer. Eur J Cancer 1993;29A(3):3036. [7] Sands R, Roberts JT, Marsh M, et al. Low dose ondansetron and dexamethasone: a cost-effective alternative to high dose metoclopramide/dexamethasone/lorazepam in the prevention of acute cisplatin induced emesis. Clin Oncol 1992;4:678. [8] Johnson NE, Nash DB, Carpenter CE, et al. Ondansetron, cost and resource utilisation in a US teaching hospital setting. Pharmacoecon 1993;3(6):47181. [9] Zbrozek AS, Cantor SB, Cardenas MP, et al. Pharmaoceconmic analysis of ondansetron versus metoclopramide for cisplatin induced nausea and vomiting. Am J Hosp Pharm 1994;51:1555 63. [10] Cox F, Hirsch J. Ondansetron: a cost-effective advance in antiemetic therapy. Oncology 1993;50:18690. [11] O Brien B. Economic evaluation of pharmaceuticals. Frankenstein monster or vampire of trials? Med Care 1996;34(Suppl. 12):DS99DS108. [12] Cochran WG, Cox GM. Experimental designs, 2nd edition. New York: Wiley, 1957. [13] Campora E, Giudici S, Merlini L, Rubagotti A, Rosso R. Ondansetron and dexamethasone versus standard combination antiemetic therapy. A randomized trial for the prevention of acute and delayed emesis induced by cyclophosphamide-doxorubicin chemotherapy and maintenance of antiemetic effect at subsequent courses. Am J Clin Oncol 1994;17(6):5226. [14] du Bois A, McKenna CJ, Andersson H, Lahousen M, Kitchener H, Pinter T, Capstick V, Wilkinson JR. A randomised, doubleblind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy. Oncology 1997;54(1):714. [15] Jorgensen M, Victor MA. Antiemetic efficacy of ondansetron and metoclopramide, both combined with corticosteroid, in malignant lymphoma patients receiving non-cisplatin chemotherapy. Acta Oncol 1996;35(2):15963. [16] Soukop M, McQuade B, Hunter E, Stewart A, Kaye S, Cassidy J, Kerr D, Khanna S, Smyth J, Coleman R, et al. Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer. Oncology 1992;49(4):295304. [17] Aaronson NK, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: A quality of life instrument for use in International clinical trials in oncology. J Natl Cancer Inst 1993;85(5):36576. [18] Fayers P, Aaronson N, Bjordal K, Sullivan M. EORTC QLQ- C30, Scoring manual. EORTC Quality of Life Study Group: Brussels; 1995. [19] Osoba D, Zee B, Warr D, et al. Quality of life studies in chemotherapy induced emesis. Oncology 1996;53(Suppl. 1):925. [20] Dicato MA, Kaasa S, Campora E, et al. Efficacy of twice daily versus three times daily oral ondansetron in the prevention of chemotherapy induced emesis. A randomized, single blind, multicenter study. Clin Oncol 1992;4:2759. [21] Brown GH, Paes D, Bryson J, et al. The effectiveness of a single intravenous dose of ondansetron. Oncology 1992;49:2738. Biography Jean Lachaine is presently completing a Ph.D degree in the field of pharmacoeconomics at the Faculty of Pharmacy, University of Montreal. He is involved with the research group at the Faculty of Pharmacy. His research projects focus on economic evaluation of heath care interventions, primarily on pharmaceuticals. He gives courses on methodologies for economic evaluation at the Faculty of Medicine, University of Montreal. He holds a Bachelors s degree in Pharmacy, a Master s degree in Hospital Pharmacy and a Masters degree in Pharmaceutical Sciences (Pharmacoeconomics)..