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Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery |
Issioui T, Klein K W, White P F, Watcha M F, Skrivanek G D, Jones S B, Hu J, Marple B F, Ing C |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Selective non-steroidal anti-inflammatory drugs (NSAIDs) given alone, or in combination, prior to outpatient otolaryngologic surgery were considered. The NSAIDs studied were rofecoxib (a cyclooxygenase-2 inhibitor; 50 mg) and acetaminophen (2 mg).
Type of intervention Secondary prevention and treatment.
Study population The study population comprised healthy outpatients aged between 18 and 75 years who were undergoing ENT surgery and who gave written consent. Patients were excluded if they had received any analgesic medication within 12 hours of the operation, or were pregnant or breast-feeding. They were also excluded if they had a history of drug abuse, clinically significant neurologic, cardiovascular, renal, hepatic, or gastrointestinal disease.
Setting The setting was secondary care (outpatient surgical centre). The economic study was carried out in the USA.
Dates to which data relate The authors did not explicitly state the dates to which the effectiveness evidence related. However, it was reported that the costs of acquiring the oral drugs for the study in 2001 were used for the cost analysis study.
Source of effectiveness data The effectiveness data were derived from a single study.
Link between effectiveness and cost data The resource use data for the interventions were collected prospectively from the same patient sample as that used in the effectiveness analysis.
Study sample Power calculations were used to determine the sample size. It was estimated that 35 patients would be required in each of the four groups when assuming the following:
the log transformation of the mean and standard deviation of the peak pain score in the placebo group would be similar to a published study;
a relative reduction of 33% in the peak verbal pain score rating was of clinical importance;
a type I error of 0.05 not adjusted for multiple comparisons; and
a power of 90%.
This sample size would have an 80% power at the 0.01 level of significance to detect a change in the proportion of patients requiring rescue analgesia in the postanaesthesia care unit (PACU) from 82% in the placebo group to 40% in the treatment group. This incidence of rescue therapy in the treatment and placebo groups was reported to follow the trend of published studies. The study sample comprised 143 patients, who were divided into four groups. There were 36 patients in the placebo group, 35 in the acetaminophen group, 37 in the rofecoxib group and 35 in the acetaminophen-rofecoxib combination group. The method used to select the sample was not reported. Also not reported were whether any patients refused to participate and the number of patients excluded.
Study design The study was a randomised, double-blind placebo-controlled trial that was carried out in a single centre. Randomisation was conducted using a computer-generated random number generator. Patients, observers and those involved in direct patient care were blinded to the treatment allocation. A follow-up period of 48 hours was reported. No loss to follow up was reported.
Analysis of effectiveness Although not explicitly reported, it appears that the basis of the analysis was intention to treat. All four groups were shown to be comparable in terms of baseline characteristics. The primary end point of the study was the peak postoperative pain score. The secondary end point was the proportion of patients requiring rescue analgesic medication. Verbal rating scales (VRS) were used to measure pain and nausea, with scores ranging from 0 (none) to 10 (worst imaginable).
Effectiveness results The baseline pain and nausea VRS scores were shown to be similar in all four groups.
The numbers of patients with severe pain, and the cumulative proportion of patients requiring rescue medications at 15 to 150 minutes after arrival in the PACU, were not significantly different between the placebo and acetaminophen groups.
Peak pain scores, the number of patients requiring more than one dose of parenteral opioid rescue medication, and the cumulative number of patients requiring rescue analgesic therapy at the end of the first 3 hours postoperatively were significantly higher in the placebo group than in the other three groups. The peak pain score was 6 (range: 3 - 9) in the placebo group, 5 (range: 1 - 9) in the acetaminophen group, 3 (range: 0 - 8) in the rofecoxib group and 3 (range: 0 - 9) in the acetaminophen-rofecoxib group. Twenty-three patients (64%) in the placebo group required more than one dose of parenteral opioid rescue medication, compared with 15 (43%) in the acetaminophen group, 6 (16%) in the rofecoxib group and 10 (29%) in the acetaminophen-rofecoxib group. However, there were no significant differences between the four groups in the incidence of nausea, vomiting, or the requirement of antiemetic rescue medication.
The patients who had received placebo reported higher peak post discharge pain scores than those in the three active drug treatment groups. The score was 6 (range: 3 - 9) in the placebo group, 4 (range: 0 - 8) in the acetaminophen group, 0 (range: 0 - 1) in the rofecoxib group and 0 (range: 0 - 3) in the acetaminophen-rofecoxib group. In addition, the post discharge pain score and the oral analgesic requirements were higher in the acetaminophen group than the two rofecoxib groups. However, there were no differences between the four groups in the incidence of nausea, vomiting, or the peak nausea scores after discharge.
Clinical conclusions Rofecoxib, 50 mg administered orally, decreased postoperative pain and the need for analgesic rescue medication after otolaryngologic surgery. The addition of 2 g oral acetaminophen failed to improve its analgesic efficacy.
Measure of benefits used in the economic analysis The number-needed-to-treat (NNT) for complete satisfaction with pain control was used in the economic analysis. This was calculated as the reciprocal of the absolute difference in the incidence of complete satisfaction between the two groups.
Direct costs The direct costs included in the economic analysis were those of rescue drugs for the treatment of postoperative pain and emetic symptoms. The costs of the anaesthetic drugs that every patient received, drug preparation and administration, and nurse labour were not included in the cost analysis as they were common for all groups. Discounting was not relevant due to the short period of follow-up. The quantities and the costs were not analysed separately. The hospital acquisition price was used to cost the drug. The price year was 2001.
Statistical analysis of costs It appears that the costs have been treated stochastically, as it was stated that the Fieller theorem was used to compute the 95% confidence interval (CI) due to a sampling error. No statistical tests appear to have been used.
Indirect Costs No indirect costs were included in the study.
Sensitivity analysis The study did not report any sensitivity analysis. However, the authors discussed the fact that the results were sensitive to some of the parameters. This suggests that, although not reported, some sensitivity analyses may have been conducted.
Estimated benefits used in the economic analysis Compared with the placebo group, the NNT for complete satisfaction with pain control was 1.6 (95% CI: 1.4 - 2.5) in the rofecoxib group and 2.2 (95% CI: 1.8 - 4.3) in the rofecoxib-acetaminophen group.
Compared with the acetaminophen group, the NNT for complete patient satisfaction with pain control was 3.0 (95% CI: 1.8 - 13.4) in the rofecoxib group and 5.8 (95% CI: 2.48 - infinity) in the rofecoxib-acetaminophen group.
Cost results A total cost per patient was not reported. Only the additional expenditures to achieve total patient satisfaction with pain management for patients in different groups were reported
Synthesis of costs and benefits An additional expenditure of $16.76 (95% CI: 7.89 - 21.03) was needed for a patient in the placebo group to obtain total pain management satisfaction.
An additional expenditure of $30.24 (95% CI: 5.25 - 54.24) was needed for one additional patient in the acetaminophen group to obtain complete pain satisfaction with rofecoxib.
Authors' conclusions Oral premedication with rofecoxib (50 mg) decreased postoperative pain and the need for rescue medication, thereby improving patient satisfaction with their pain management and the quality of recovery after outpatient ear, nose and throat (ENT) surgery. However the addition of acetaminophen (2 g administered orally) failed to enhance the analgesic efficacy of rofecoxib in this outpatient surgical population.
CRD COMMENTARY - Selection of comparators The comparators were explicitly stated and the reason for their choice was clear. However, it was stated that the new drugs could have been compared with more traditional NSAIDs (e.g. ketorolac and diclofenac), although not for this patient population as the more traditional NSAIDs are reported to be relatively contraindicated for ENT surgery. You should decide if the comparators selected represent valid comparators in your own setting.
Validity of estimate of measure of effectiveness The basis of the analysis was a randomised, double-blind placebo-controlled trial, which was well conducted and appropriate given the study question. The study sample appears to have been representative of the study population, although it would have been useful to know how the sample had been selected. In addition, the four patient groups were shown to be comparable at analysis. The method of randomisation, length of follow-up and blinding were all reported, which suggests that the internal validity is likely to be high. The authors did not state whether the outcomes had been analysed on the basis of intention to treat or treatment completers only, although it would appear to have been the former. Power calculations were performed and an appropriate sample size used, although the authors stated that the sample size was not powered to detect statistically significant differences in the secondary outcome measure.
Validity of estimate of measure of benefit The authors adopted the NNT to achieve total satisfaction with pain management as the measure of benefit. This was derived directly form the effectiveness results, as the reciprocal of the absolute difference in the incidence of complete satisfaction between the two groups.
Validity of estimate of costs The perspective of the analysis was not reported. However, it appears to have been that of the hospital and, as such, only the direct costs were included. In addition, all costs that were likely to be equivalent in the four groups were excluded. Thus, the only costs included were for the oral study drugs and the incremental costs of the rescue drugs for treating postoperative pain. The costs were specific to the authors= setting and may not be generalisable to other settings. Given the limited detail reported, it was difficult to ascertain whether the costing was conducted in an efficient and credible manner. These facts also mean that it is not possible to judge the quality of the results obtained. Sensitivity analyses may have been conducted but, if so, they were not reported.
Other issues The authors made good and extensive comparisons of their results with those of published studies. However, they did not explicitly address the issue of generalisability to other settings. In addition, a more detailed costing exercise would have been more informative for the decision-maker. A detailed description of resource use, including those items described as common for the four groups (and which were not included in the economic analysis), would have enhanced the generalisability to other settings. The results of the study should be considered with some caution because of the scope of the costing, and the sensitivity of the cost estimates to a number of assumptions (e.g. nausea, vomiting).
Implications of the study The results suggested that oral premedication with rofecoxib (50 mg) decreases postoperative pain and the need for rescue medication, thereby improving efficacy. However, the cost-effectiveness analysis should be treated with caution. More studies reporting detailed resource use and costing are needed.
Source of funding Supported by an educational grant from Merck, West Point (NY), USA.
Bibliographic details Issioui T, Klein K W, White P F, Watcha M F, Skrivanek G D, Jones S B, Hu J, Marple B F, Ing C. Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. Anesthesiology 2002; 97(4): 931-937 Other publications of related interest Malmstron K, Daniels S, Koety P, Seidenberg PC, Desjardins PJ. Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: A randomized, placebo and active-comparator-control clinical trial. Clinical Therapeutics 1999;21:1653-63.
Morison BW, Fricke J, Brown J, Yuan W, Kotey P, Mehlisch D. The optimal analgesic dose of rofecoxib: overview of six randomized controlled trials. Journal of the American Dental Association 2000;131;1729-37.
Issoui T, Klein KW, White PF, Watcha MF, Coloma M, Skrivanek GD, et al. The efficacy of premedication with celecoxib and acetaminophen in preventing pain after otolaryngolic surgery. Anesthesia and Analgesia 2002;94:1188-93.
Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307-14.
Scuderi PE, James RL, Harris L, Mims GR. Antiemetic prophylaxis does not improve outcomes after outpatient surgery when compared to symptomatic treatment. Anaesthesiology 1999;90:360-71.
Indexing Status Subject indexing assigned by NLM MeSH Acetaminophen /economics /therapeutic use; Adolescent; Adult; Aged; Ambulatory Surgical Procedures; Analgesics, Non-Narcotic /economics /therapeutic use; Anti-Inflammatory Agents, Non-Steroidal /economics /therapeutic use; Cost-Benefit Analysis; Costs and Cost Analysis; Double-Blind Method; Female; Humans; Lactones /economics /therapeutic use; Male; Middle Aged; Otorhinolaryngologic Surgical Procedures; Pain Measurement /drug effects; Pain, Postoperative /drug therapy /economics; Patient Satisfaction; Postoperative Nausea and Vomiting /epidemiology /prevention & Sulfones; control AccessionNumber 22002001853 Date bibliographic record published 31/12/2004 Date abstract record published 31/12/2004 |
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