Objectives: Decision analysis is commonly used to perform economic evaluations of new pharmaceuticals. The outcomes of such studies are often reported as an incremental cost per quality-adjusted life year (QALY) gained with the new agent. Decision analysis can also be used in the context of estimating drug cost before market entry. The current study used neurokinin-1 (NK-1) receptor antagonists, a new class of antiemetics for cancer patients, as an example to illustrate the process using an incremental cost of $Can20,000 per QALY gained as the target threshold.

Methods: A decision model was developed to simulate the control of acute and delayed emesis after cisplatin-based chemotherapy. The model compared standard therapy with granisetron and dexamethasone to the same protocol with the addition of an NK-1 before chemotherapy and continued twice daily for five days. The rates of complete emesis control were abstracted from a double-blind randomized trial. Costs of standard antiemetics and therapy for breakthrough vomiting were obtained from hospital sources. Utility estimates characterized as quality-adjusted emesis-free days were determined by interviewing twenty-five oncology nurses and pharmacists by using the Time Trade-Off technique. These data were then used to estimate the unit cost of the new antiemetic using a target threshold of $Can20,000 per QALY gained.

Results: A cost of $Can6.60 per NK-1 dose would generate an incremental cost of $Can20,000 per QALY. The sensitivity analysis on the unit cost identified a range from $Can4.80 to $Can10.00 per dose. For the recommended five days of therapy, the total cost should be $Can66.00 ($Can48.00–$Can100.00) for optimal economic efficiency relative to Canada's publicly funded health-care system.

Conclusions: The use of decision modeling for estimating drug cost before product launch is a powerful technique to ensure value for money. Such information can be of value to both drug manufacturers and formulary committees, because it would facilitate negotiations for optimal pricing in a given jurisdiction.

Background and objective Female patients undergoing gynaecological procedures, especially laparoscopically, are at high risk of postoperative nausea and vomiting. No available antiemetic is entirely effective. This double-blinded randomized trial examines the efficacy and safety of tropisetron and metoclopramide in combination and compares the results with metoclopramide alone in laparoscopic gynaecological surgery.

Methods One hundred and twenty female patients scheduled for minor gynaecological laparoscopy, aged 27–43 years, were randomly allocated to receive pretreatment with metoclopramide 10 mg intravenously (n = 57) or tropisetron 5 mg with metoclopramide 5 mg (n = 63).

Results Fewer patients in the combined treatment group experienced postoperative nausea and vomiting (14% vs. 37%, P = 0.008) or needed rescue antiemetic treatment (3% vs. 16%, P = 0.038). No significant adverse events were observed.

Conclusions The combination of the antiemetics was superior, which is probably explained by the fact that the two drugs have different sites of action, thus preventing emesis by blocking different pathways.

Background and objective In a randomized, placebo-controlled, double-blind trial, we compared the efficacy of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in women undergoing hysterectomy.

Methods Patients were allocated randomly to one of three groups: group A (n =50) received 50 mg dolasetron orally, group B (n =50) received 20 mg metoclopramide intravenously and placebo orally, group C (n =50) received placebo orally. If patients complained of retching or vomiting, or if patients demanded an antiemetic, 1.25 mg droperidol was administrated intravenously. To quantify postoperative nausea and vomiting the following score was used: 0 =no nausea, 1 =nausea, 2 =retching, 3 =single vomiting, 4 =multiple vomiting. The Raatz test was used to analyse postoperative nausea and vomiting (PONV) scores.

Results Dolasetron reduced the postoperative nausea and vomiting score significantly (P <0.02 vs. metoclopramide; P <0.0001 vs. placebo). Metoclopramide also reduced the postoperative nausea and vomiting score (P <0.02 vs. placebo). Fisher's exact test showed a significant reduction of vomiting in the dolasetron group compared with metoclo-pramide-treated patients (P <0.007) and placebo-treated patients (P <0.000006) and a significantly lower rate of nausea in comparison to the placebo group (P <0.009). There were no significant differences between the metoclopramide and the placebo groups (in Fisher's exact test). The use of postoperative droperidol per patient was significantly lower in the dolasetron group (P <0.04 vs. metoclopramide; P <0.0001 vs. placebo) than in the metoclopramide (P <0.02 vs. placebo) and in the placebo groups.

Conclusions Oral dolasetron is more effective than either metoclopramide given intravenously or placebo for preventing vomiting after hysterectomy. It also was significantly superior to either metoclopramide or placebo concerning the PONV score and the need for droperidol rescue.

We conducted a prospective, randomized, double-blind clinical trial comparing droperidol 1.25 mg intravenously (i.v.) (group 1, n = 30), ondansetron 4 mg i.v. (group 2, n = 30), or both (group 3, n = 30) in the prevention of postoperative nausea and vomiting (PONV) in the first 24 h following major gynaecological procedures under combined general and epidural anaesthesia. PONV was analysed by a linear nausea/vomiting score, incidence of nausea and vomiting, and the need for antiemetic rescue. Our results showed a similar incidence of nausea and vomiting in all groups (G1 33%, G2 40%, G3 43%). However, when comparisons were made according to the time of assessment, combination therapy resulted in significantly lower PONV than droperidol in the first hour (0% vs. 13%, P < 0.05) and second hour (0% vs. 13%, P < 0.05), and than ondansetron on the first hour (0% vs. 13%, P < 0.05). A trend persisted up to the fourth hour but was not statistically significant in either group. In conclusion, droperidol and ondansetron are effective agents in the prevention of PONV, and their combination seems to provide slightly better results than either drug alone.

Postoperative nausea and vomiting (PONV) is a common adverse phenomenon following breast surgery. The efficacy of ondansetron and droperidol in preventing post–operative nausea and vomiting in women undergoing breast surgery was compared in this randomized, double–blind, placebo–controlled study. Altogether 207 women were randomly assigned to receive either a single intravenous dose of droperidol (1.25 mg) (n = 69), ondansetron (8 mg) (n = 67) or saline (n = 71) immediately after induction of general anaesthesia with thiopental, fentanyl, atracurium, nitrous oxide in oxygen and isoflurane. Complaints of nausea, vomiting and requests for rescue antiemetics were recorded during a 24-h period postoperatively. During the initial 2 h in the postanaesthesia care unit, the incidence of postoperative nausea and vomiting was 15%, 6% and 12% in the placebo, droperidol and ondansetron groups, respectively (NS). The incidence of post–operative nausea and vomiting during the first 24 h was 61%, 48% and 45% in the placebo, droperidol and ondansetron treatment groups, respectively (NS). Postoperative analgesic requirements and the length of stay in the post–anaesthesia care unit were equal in all three treatment groups. It is concluded that the intravenous pretreatment with single doses of ondansetron or droperidol did not substantially prevent postoperative nausea and vomiting after breast surgery.

Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. This study was undertaken to evaluate the efficacy of granisetron/dexamethasone combination for preventing postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy (LC). In a prospective, randomized, double-blind manner, 120 patients (83 females), aged 25–65 years, were assigned to receive granisetron 40 μg kg−1 alone or granisetron 40 μg kg−1 plus dexamethasone 8 mg (n=60 of each) intravenously immediately before the induction of anaesthesia. A standardized general anaesthetic procedure and postoperative analgesia were used. A complete response, defined as no PONV and no need for another rescue antiemetic, during 0–3 h after anaesthesia was 83% with granisetron and 98% with granisetron plus dexamethasone, respectively (P=0.008); the corresponding incidence during 3–24 h after anaesthesia was 83% and 98% (P=0.008). No clinically important adverse events were observed in any of the group. In conclusion, prophylactic therapy with granisetron/dexamethasone combination is more effective than granisetron alone for the prevention of PONV after LC.

The anti-emetic efficacy of prophylactic ondansetron and tropisetron in combination with a low dose of droperidol in patients with high probability for post-operative nausea and vomiting undergoing gynaecological laparoscopy was compared. Patients were randomly allocated in a double-blind manner to receive either ondansetron 8 mg (n=45) or tropisetron 5 mg (n=43) at the end of surgery. A standardized general anaesthetic technique was used, including droperidol 0.75 mg. The incidence of nausea was 36% and 49% (P=0.28), and vomiting occurred in 13% and 14% of the patients in the ondansetron and tropisetron groups, respectively. The onset time for rescue medication was significantly sooner after tropisetron than ondansetron (3 h 18min vs. 6 h 25min; P=0.007). There were no statistically significant differences in efficacy between prophylactic ondansetron and tropisetron combined with droperidol in a high-risk population. However, ondansetron appeared to be more effective in preventing post-operative nausea and vomiting in the early hours after surgery compared with tropisetron.

This study was undertaken to compare the efficacy and safety of granisetron, a 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone and each drug alone for the prevention of post-operative vomiting by children, with no history of motion sickness and/or previous post-operative vomiting, undergoing general inhalational anaesthesia for surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 150 children, ASA physical status I, aged 4–10 years, were assigned to receive granisetron 40 mg kg−1, dexamethasone 150 mg kg−1, or granisetron 40 mg kg−1 plus dexamethasone 150 mg kg−1 intravenously immediately after inhalation induction of anaesthesia (n=50 of each). A complete response, defined as no emesis and no need for another rescue anti-emetic during the first 24 h after anaesthesia, was 86% with granisetron, 68% with dexamethasone and 98% with granisetron plus dexamethasone, respectively (P< 0.05; overall Fisher's exact probability test). No clinically serious adverse events were observed in any of the groups. In conclusion, prophylactic therapy with combined granisetron and dexamethasone was more effective than was each anti-emetic alone for the prevention of vomiting after paediatric surgery.

Dimenhydrinate is an inexpensive antihistaminic drug, that is frequently used as an anti-emetic during anaesthesia. The popularity of the drug is contrasted by the lack of modern studies concerning its efficacy in reducing the incidence of post-operative nausea and vomiting. Thus, dimenhydrinate was compared with placebo in this prospective, randomized, double-blind study. One hundred and thirty-three female in-patients were studied. They were stratified according to the type of surgery (laparoscopic cholecystectomy, thyroid resection or knee arthroscopy) to ensure an homogenous distribution in both groups. General anaesthesia was induced with etomidate, fentanyl, vecuronium and maintained with enflurane in N2O/O2. Neuromuscular block was reversed with pyridostigmine/atropine. Patients in the dimenhydrinate group (n=67) received 62 mg dimenhydrinate intravenously after induction of anaesthesia. Placebo patients (n=66) received saline. Administration of dimenhydrinate (and placebo) was repeated three times during the 48-h study to mitigate the short half-life of the drug. Post-operative analgesia and anti-emetic rescue medication was standardized. Episodes of vomiting, retching and the need for additional anti-emetics were recorded. Nausea was assessed using a 10-cm visual analogue scale. Post-operative nausea and vomiting was rated as ‘none’, ‘mild’, ‘moderate’ and ‘severe’ using a fixed scoring algorithm. There were no differences between the two groups with regard to biometric data, type of surgery and distribution of risk factors for developing post-operative nausea and vomiting. In the dimenhydrinate group, more patients remained completely free from post-operative nausea and vomiting compared with placebo (dimenhydrinate: 38.8%; placebo:15.1%; P=0.004). The incidence of severe post-operative nausea and vomiting was also reduced from 39.4% to 14.9%. No relevant side effects were observed. Intra-operative dimenhydrinate, followed by three further administrations after surgery, reduces the incidence and the severity of post-operative nausea and vomiting without side effects. However, there still remained an unacceptable high number of patients who were not prevented completely from experiencing post-operative nausea and vomiting.

We have compared the efficacy of granisetron with perphenazine in the prevention of vomiting after tonsillectomy with or without adenoidectomy in children. In a prospective, randomized, double-blind study, 90 paediatric patients, ASA I, aged 4–10 years, received granisetron 40 mg kg−1 or perphenazine 70 mg kg−1 (n=45 each) intravenously immediately after an inhalation induction of anaesthesia. A standard general anaesthetic technique was employed throughout. A complete response, defined as no emesis with no need for another rescue antiemetic, during the first 3 h (0–3 h) after anaesthesia was 87% with granisetron and 78% with perphenazine (P=0.204). The corresponding incidence during the next 21 h (3–24 h) after anaesthesia was 87% and 62% (P=0.007). No clinically serious adverse events were observed in any of the groups. We conclude that granisetron is a better anti-emetic than perphenazine for the long-term prevention of post-operative vomiting in children undergoing general anaesthesia for tonsillectomy.

This study was undertaken to determine the minimum effective dose of granisetron, 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of post-operative vomiting in children undergoing general inhalational anaesthesia for surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 120 children, ASA physical status I, aged 4–10 years, were assigned to receive placebo (saline) or granisetron at three different doses (20 μg kg−1, 40 μg kg−1, 100 μg kg−1) intravenously immediately after inhalation induction of anaesthesia (n=30 of each). A complete response, defined as no emesis and no need for another rescue antiemetic during the first 24 h after anaesthesia, occurred in 57% with placebo, 67% with granisetron 20 μg kg−1, 90% with granisetron 40 μg kg−1 and 90% with granisetron 100 μg kg−1 respectively (P<0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups. Our results suggest that granisetron 40 μg kg−1 is the minimum effective dose for the prevention of emesis after paediatric surgery, and that increasing its dose to 100 μg kg−1 provides no demonstrable benefit.

This study was undertaken to determine the minimum effective dose of granisetron, a selective 5-hydroxy-tryptamine type 3 receptor antagonist, for the prevention of post-operative nausea and vomiting (PONV) in female patients undergoing elective laparoscopic cholecystectomy. In randomized, placebo-controlled, double-blind study, 120 women were assigned to receive either placebo (saline) or granisetron at three different doses (20 μg kg−1, 40 μg kg−1 or 80 μg kg−1) intravenously immediately before the induction of anaesthesia. All patients received standardized aesthesia consisting of isoflurane and nitrous oxide in oxygen. The incidence of PONV during the first 24 hours after anaesthesia was 43, 40, 13 and 13% after administration of placebo and granisetron 20 μg kg−1, 40 μg kg−1 and 80 μg kg−1, respectively (P<0.05, overall Fisher's exact probability test). Adverse effects post-operatively were not different among the groups. In conclusion, granisetron 40 μg kg−1 is the minimum effective dose in the prevention of PONV after laparoscopic cholecystectomy.

Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post-operative nausea and emesis in in-patients undergoing major gynaecological surgery in this double-blind, randomized, placebo-controlled, multicentre study. A total of 1044 patients received a single intravenous (i.v.) injection of study medication immediately before induction of anaesthesia. Nausea and emesis were assessed over the 24 h post-operative period. Significantly more patients who received ondansetron experienced no emetic episodes (44%) compared with those who received metoclopramide (37%, P=0.049) or placebo (25%, P<0.001). No nausea was experienced by significantly more patients who received ondansetron (32%) than with patients who received metoclopramide (24%, P=0.009) or placebo (16%, P<0.001). In addition, fewer emetic episodes, less severe nausea and a reduced need for rescue antiemetics were also observed with ondansetron (P<0.05 vs. metoclopramide and placebo). Metoclopramide and placebo-treated patients were also 1.5 times (95% CI 1.5–4.2) and 2.5 times (95% CI 1.1–2.0) more likely, respectively, to experience nausea post-operatively. Overall, ondansetron was the most effective antiemetic in this patient population.

Nausea and vomiting remain unpleasant side effects of intrathecal (i.t.) morphine and of the numerous therapies tried, only prophylactic intravenous (i.v.) metoclopramide has been reported to be promising. Seventy-three patients, scheduled for orthopaedic prosthesis surgery of the hip or knee were studied. They received 4mL of plain bupivacaine and 0.3 mg of preservative-free morphine i.t. for anaesthesia. The test drugs given in a double-blind and randomized fashion, were either metoclopramide 20 mg, three times, at 6 h intervals (23 patients), ondansetron, 8 mg, twice, at 12 h intervals (25 patients), or 0.9% saline three times, at 6 h intervals (25 patients). The occurrence of nausea, vomiting and pain was followed for 24 h. The incidences of nausea and vomiting were 60% (15/l25) and 56% (14/25) in the saline group, 52% (12/23) and 48% (11/23) in the metoclopramide group, and 52% (13/25) and 40% (10/25) in the ondansetron group. Incidences of severe vomiting were 24, 35 and 12%, respectively. Eight patients in the saline group, seven in the metoclopramide and 10 in the ondansetron group did not need additional opioids for post-operative pain relief. We conclude that, metoclopramide and ondansetron were not better than saline in the prevention of post-operative emesis induced by intrathecal morphine.

The efficacy of ondansetron 4 mg was compared with metoclopramide 10 mg for the prevention of post-operative nausea and vomiting in patients after major gynaecological abdominal surgery. Anaesthesia was standardized using thiopentone, atracurium and methadone for induction followed by isoflurane in nitrous oxide-oxygen mixture. Fifty patients were randomized in a double-blind fashion to either receive intravenous(i.v.) ondansetron 4 mg or metoclopramide 10 mg during closure of the pelvic peritoneum. The incidence and frequency of vomiting, and the incidence of severe nausea was recorded for 24 h after surgery. One patient was excluded because of respiratory depression. In the first 4 h after surgery, five patients (20%) in the ondansetron group (n = 25) and eight patients (33%) in the metoclopramide group (n = 24) vomited, whereas at 4–12 h, this increased to 11 patients (44%) and nine patients (37.5%) respectively. The incidence was 52 and 37.5% respectively in the subsequent 12–24 h. The highest incidence of nausea was in the first 4 h after surgery, being 56 and 37.5% in the ondansetron and the metoclopramide groups respectively. This decreased to less than 25% in both groups in the 12–24 h period. Ondansetron 4 mg and metoclopramide 10 mg had similar but short lasting efficacy for the prevention of vomiting in patients who received continued opioid analgesia after major gynaecological surgery.