The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial.

BACKGROUND AND AIMS: Smoking cessation medications are effective, but often underutilized because of costs and side effects. Cytisine is a plant-based smoking cessation medication with more than 50 years of use in central and eastern Europe. While cytisine has been found to be well-tolerated and more effective than nicotine replacement therapy, direct comparisons with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost-effectiveness of cytisine compared with varenicline. DESIGN: Two-arm, parallel group, randomized, non-inferiority trial, with allocation concealment and blinded outcome assessment. SETTING: Australian population-based study. PARTICIPANTS: Adult daily smokers (n = 1266) interested in quitting will be recruited through advertisements and Quitline telephone-based cessation support services. INTERVENTION AND COMPARATOR: Eligible participants will be randomized (1 : 1 ratio) to receive either cytisine capsules (25-day supply) or varenicline tablets (12-week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10-12-minute sessions). MEASUREMENTS: Assessments will be undertaken by telephone at baseline, 4 and 7 months post-randomization. Participants will also be contacted twice (2 and 4 weeks post-randomization) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self-reported 6-month continuous abstinence from smoking, verified by carbon monoxide at 7-month follow-up. We will also evaluate the relative safety and cost-effectiveness of cytisine compared with varenicline. Secondary outcomes will include self-reported continuous and 7-day point prevalence abstinence and cigarette consumption at each follow-up interview. COMMENTS: If cytisine is as effective as varenicline, its lower cost and natural plant-based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives world-wide.

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation.

BACKGROUND: Tobacco smoking is one of the leading causes of deaths worldwide. Nearly one-fifth of adults in the UK regularly smoke cigarettes. The ill-health associated with smoking costs the NHS over £3B every year. A number of pharmacological interventions are available that can help people to quit smoking. These include nicotinic receptor partial agonists such as varenicline or cytisine. Varenicline is a synthetic product licensed for use in the UK, while cytisine is derived naturally from the seeds of the plant Cytisus laborinum L. (golden rain acacia). OBJECTIVES: To review the evidence on the clinical effectiveness and safety of cytisine from smoking cessation compared with varenicline; to develop an economic model to estimate the cost-effectiveness of cytisine and varenicline; and to provide recommendations based on value of information analyses as to whether or not a head-to-head trial of cytisine and varenicline would represent effective use of resources. DATA SOURCES: Efficacy and adverse events data were sourced from a recent Cochrane review. These data were supplemented with an updated search of twelve electronic databases, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and The Cochrane Library, for the period from December 2011 to January 2013. The review included randomised controlled trials (RCTs) of adult smokers attempting to quit using varenicline or cytisine. Further interventions were considered (placebo, nicotine replacement therapy, bupropion) to allow an indirect comparison between varenicline and cytisine. The primary outcome was abstinence at a minimum of 6 months' follow-up. Secondary outcomes were common adverse events such as abnormal dreams, headache, nausea, insomnia and serious adverse events. REVIEW METHODS: A systematic review and network meta-analysis of the clinical evidence was undertaken. A random-effects model was used to allow for heterogeneity between studies. The economic model structure was based on a published model. Probabilistic sensitivity analyses were undertaken to estimate the treatment expected to be most cost-effective given current information. Formal expected value of perfect information, perfect partial information and of sample information were performed. RESULTS: Twenty-three (RCTs) were included in the systematic review, comprising a total of 10,610 participants. Twenty-one trials of varenicline of differing dosing schedules and two trials of cytisine at standard dose met the inclusion criteria. No head-to-head trials comparing varenicline with cytisine were identified. The methodological quality of the studies was judged to be moderate to good. Cytisine was more efficacious than placebo [hazard ratio (HR) 4.27, 95% credible interval (CrI) 2.05 to 10.05], as was standard-dose varenicline (HR 2.58, 95% Crl 2.16 to 3.15). Standard-dose varenicline treatment was associated with significantly higher rates of headache, insomnia and nausea than placebo; there was no significant difference in the rates of abnormal dreams. There were no significant differences in the rates of headache or nausea between cytisine and placebo; data were identified for neither abnormal dreams nor insomnia. Using expected values, cytisine is anticipated to dominate varenicline, in that it produces more quality-adjusted life-years at a lower associated cost. This occurred in approximately 90% of the scenarios performed. However, owing to the large number of people who wish to quit smoking (estimated to be 3 million over a 10-year period), the implications of making an incorrect decision is large. The expected value of sample information indicated that conducting a head-to-head trial of cytisine and varenicline was worthwhile, and that 1000 smokers per arm was an appropriate number to recruit. CONCLUSIONS: On the basis of the evidence included in this review, varenicline and cytisine are both effective interventions to aid smoking cessation when compared with placebo. Cytisine is estimated to be both more clinically effective and cost-effective than varenicline. However, there is uncertainty in the decision, and a head-to-head trial of cytisine and varenicline would appear to be an effective use of resources. STUDY REGISTRATION: The study was registered as PROSPERO CRD42012003455. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme.

[Dolasetron and shivering. A prospective randomized placebo-controlled pharmaco-economic evaluation]. / Dolasetron und "shivering". Eine prospektive, randomisierte, placebokontrollierte pharmakoökonomische Evaluation.

BACKGROUND AND GOAL: Forced by the current economical situation, German hospitals have to reconsider their clinical productivity. When caregivers introduce new therapeutic concepts medical quality should either be improved without increasing costs or when reducing costs medical quality should be maintained. In the surgical field postoperative shivering reduces both patient comfort and medical quality. We therefore investigated the clinical pathway prevention of shivering with dolasetron in a prospective, randomized, placebo-controlled analysis of cost-effectiveness. MATERIAL AND METHODS: After written informed consent we randomized 40 patients scheduled for lumbar disc hernia repair or head and neck surgery into two groups: patients of group D received dolasetron 1 mg/kg body weight during surgery whereas patients of group K received 100 ml saline as placebo. Primary endpoints were the incidence of shivering, the length of stay in the postanesthesia care unit and process-associated costs. Secondary endpoint was the influence on perioperative thermoregulation. RESULTS: We observed postanesthetic shivering in 5 patients belonging to group D in comparison to 15 patients receiving the placebo (p<0.05). The length of stay in the postanesthesia care unit was shorter in patients allocated to dolasetron (mean+/-SD; group D: 43+/-16 min, group K 62+/-18 min, p<0.05). There was a significant saving in process-associated personnel costs (personnel costs in group D EUR 41.26+/-14, personnel costs in group K EUR 53.15+/-15) but in contrast the process-associated material costs were significantly increased (group D EUR 17.16+/-3, group K EUR 0.73+/-1, p<0.05). CONCLUSIONS: The optimization of the clinical process and medical quality induced by a prophylaxis against shivering and postoperative nausea and vomiting compensates for the increased use of pharmaceutical resources in our setting.

Dolasetron versus ondansetron for the treatment of postoperative nausea and vomiting.

The management of postoperative nausea and vomiting (PONV) remains a persistent problem. Despite the use of prophylactic antiemetics, breakthrough nausea and vomiting still frequently occur. There have been no published studies comparing dolasetron and ondansetron for the treatment of PONV. This was a prospective, randomized, double-blind, active-controlled study in adult outpatient surgery patients. We screened 559 consecutive adult surgery patients, with 92 patients randomized to either ondansetron or dolasetron. The objectives of the study were 1) to determine whether treatment of PONV with ondansetron 4 mg IV or dolasetron 12.5 mg IV would result in better outcomes in patients undergoing day surgery and 2) to compare the cost of drugs used for treating PONV. Thirty-three (70%) of 47 patients given ondansetron required rescue medication, compared with 18 (40%) of 45 patients given dolasetron (P < 0.004). Dolasetron was approximately 40% less expensive than ondansetron, and the costs of the study drug plus rescue antiemetics were 30% less in the dolasetron group than in the ondansetron group. Dolasetron provided greater efficacy for antiemetic treatment because of the need for less rescue therapy. Because of the decreased use of rescue antiemetics and acquisition cost at our hospital, costs in the dolasetron group were less than costs in the ondansetron group.

Ondansetron versus dolasetron: a comparison study in the prevention of postoperative nausea and vomiting in patients undergoing gynecological procedures.

The purpose of this study was to determine if 4 mg of ondansetron and 12.5 mg of dolasetron were equally effective in preventing postoperative nausea and vomiting (PONV) in patients undergoing gynecological procedures. While the overall incidence of PONV appears to be 25% to 35%, the incidence among this patient population is considerably higher. Patients were assigned to 1 of 2 antiemetic treatment groups. Patients in group 1 received 4 mg of ondansetron at the end of surgery, while patients in group 2 received 12.5 mg of dolasetron at the end of surgery. Data collection occurred perioperatively and in the 24 hours following surgery. chi 2 determined there was no statistical difference between groups related to emesis in the postanesthesia care unit (PACU), emesis in the 24 hours following surgery, and side effects. Results of this study showed there was no statistically significant difference between 4 mg of ondansetron or 12.5 mg of dolasetron when administered at the end of surgery for preventing PONV in patients undergoing gynecological procedures. Given the cost difference between these 2 antiemetics, there is a potential for significant cost savings in this high-risk patient population.

A comparison of the costs and efficacy of ondansetron and dolasetron in the prophylaxis of postoperative vomiting in pediatric patients undergoing ambulatory surgery.

UNLABELLED: Postoperative vomiting (POV) after ambulatory surgery remains a major problem. We designed this study to determine the smallest dose of dolasetron equivalent to the Food and Drug Administration approved dose of ondansetron 100 micro g/kg IV, for the prophylaxis of POV in children undergoing surgery. In this double-blinded controlled study, 204 healthy ASA I-II children aged 2-12 yr, undergoing superficial ambulatory (day-case) surgery, were randomized to receive either ondansetron 100 micro g/kg IV, or dolasetron 45, 175, 350, or 700 micro g/kg IV during a standardized perioperative regimen. The primary end-point was the incidence of complete response, defined as the absence of POV symptoms. Costs were calculated from the perspective of the hospital using a previously described model. The incidence of early (0-6 h) and 24-h emesis was more frequent in the dolasetron 45 micro g/kg group compared with the dolasetron 350 and 700 micro g/kg groups and with the ondansetron group. Repeated POV occurred more often when dolasetron was used in a dose <350 micro g/kg. There were no significant differences in emesis rates between the dolasetron 175, 350, and 700 micro g/kg groups or between these groups and the ondansetron 100 micro g/kg group. The smallest dose of dolasetron with acceptable equivalent efficacy and patient satisfaction scores to ondansetron 100 micro g/kg was 350 micro g/kg. Institutional costs for managing POV were less with dolasetron 350 micro g/kg than with ondansetron. IMPLICATIONS: This randomized double-blinded dose-ranging study concluded that dolasetron, 350 micro g/kg IV, was the smallest dose that provided acceptable equivalent efficacy and patient satisfaction scores to ondansetron, 100 micro g/kg IV, for the prophylaxis of postoperative vomiting in children undergoing outpatient surgery. However, with this dose, the costs to the institution for managing postoperative vomiting were less.

A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis.

UNLABELLED: The optimal dose and timing of 5-HT(3) antagonist administration for prophylaxis against postoperative nausea and vomiting (PONV) remains controversial. Although 5-HT(3) antagonists seem to be most effective when administered near the end of surgery, there are no data on the comparative efficacy or costs associated with the 5-HT(3) antagonists dolasetron and ondansetron when administered at the end of the operation. In this double-blinded study, 200 outpatients undergoing otolaryngologic procedures with a standardized general anesthetic received 4 (O4) or 8 mg (O8) of ondansetron or 12.5 (D12.5) or 25 mg (D25) of dolasetron IV within 30 min before the end of surgery. A blinded observer recorded the emetic episodes, maximum nausea score, recovery room resource and drug use, nursing time spent managing PONV, times to achieve discharge criteria from the Phase 1 and 2 recovery units, postdischarge emesis, and patient satisfaction. Total costs were calculated by using the perspective of a free-standing surgicenter. There were no differences in patient demographics, incidence of PONV, need for rescue medications, time spent in the recovery areas, unanticipated hospital admissions, or patient satisfaction among the four treatment groups. The mean total costs (95% confidence intervals) to prevent PONV in one patient were lowest in the D12.5 group: $23.89 (17.18-28.79) vs $37.81 (30.29-45.32), $33.91 (28.92-39.35), and $75.18 (61.13-89.24) for D25, O4, and O8, respectively. Excluding nursing labor costs did not alter this finding: $18.51 (14.18-22.85), $34.77 (28.03-41.49), $31.77 (28. 92-39.35), and $71.76 (58.17-85.35) for D12.5, D25, O4, and O8, respectively. We conclude that 12.5 mg of dolasetron IV is more cost effective than 4 mg of ondansetron IV for preventing PONV after otolaryngologic surgery and is associated with similar patient satisfaction. IMPLICATIONS: When administered at the end of surgery, 12.5 mg of dolasetron IV is as effective as 25 mg of dolasetron IV, 4 mg of ondansetron IV, and 8 mg of ondansetron IV in preventing emetic symptoms after otolaryngologic surgery and was associated with similar patient satisfaction at a reduced cost. There were no differences in the antiemetic efficacy of the 4 and 8 mg doses of ondansetron.

Cost-effectiveness of prophylactic dolasetron or droperidol vs rescue therapy in the prevention of PONV in ambulatory gynecologic surgery.

PURPOSE: To assess the cost-effectiveness of prophylactic therapy (1.25 mg droperidol or 50 mg dolasetron i.v.) vs no prophylaxis (rescue therapy) for the prevention of post-operative nausea and vomiting (PONV) from a Canadian hospital perspective. DESIGN: A predictive decision analytic model using previously published clinical and economic evaluations, and costs of medical care in Canada. SUBJECTS: Ambulatory gynecology surgery patients. INTERVENTIONS: Three strategies administered prior to emergence from anesthesia were compared: 1.25 mg droperidol i.v., 50 mg dolasetron i.v.; and no prophylaxis (rescue therapy). RESULTS: The base case mean cost per patient receiving dolasetron prophylaxis was $28.08 CAN compared with $26.88 CAN per patient receiving droperidol prophylaxis, resulting in a marginal cost of $1.20 CAN. This difference translated in an additional cost of $12.00 CAN for the dolasetron strategy per adverse event avoided over the droperidol strategy. The base case mean cost per patient not receiving prophylaxis was $26.92 resulting in marginal costs of $1.16 CAN and $0.04 CAN when compared to dolasetron and droperidol, respectively. Compared with the no prophylaxis strategy, dolasetron prophylaxis resulted in an incremental cost-effectiveness ratio of $5.82 CAN per additional PONV-free patient. The mean costs incurred per PONV-free patient were calculated to be $48.41 for the dolasetron strategy, $46.34 for the droperidol strategy and $70.83 for the no prophylaxis strategy. CONCLUSIONS: Dolasetron and droperidol given intraoperatively were more cost-effective than no prophylaxis for PONV in patients undergoing ambulatory gynecologic surgery. The difference between the two agents was small and favoured droperidol. The model was robust to plausible changes through sensitivity analyses.