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Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review |
Barden J, Edwards J E, McQuay H J, Moore R |
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Authors' objectives To examine the efficacy of single-dose rofecoxib for acute post- operative pain in adults.
Searching The Cochrane Library (Issue 4, 2001), Biological Abstracts (March 2002), MEDLINE (March 2002) and PubMed (March 2002) were searched using the terms: 'rofecoxib', 'vioxx', 'cox-2 selective inhibitor', 'specific cyclooxygenase-2 inhibitor', analgesi*', 'pain*', 'postoperative', 'post-operative', 'surgical', 'postsurgical' 'post-surgical', 'dental', 'molar' and 'extraction', along with search terms relating to study type. The reference lists and review articles were examined for relevant references, and in-house databases were also searched. Only full journal publications were included in the review.
Study selection Study designs of evaluations included in the reviewDouble-blind, randomised controlled trials (RCTs) with at least 10 patients per group.
Specific interventions included in the reviewTo be included, the studies had to use single-dose treatments of oral rofecoxib and a placebo or active comparator. Of the studies included in the review, the patients analysed received rofecoxib 50 mg; the comparator analgesics included ibuprofen (400 mg), celecoxib (200 mg), paracetamol (600 mg) plus codeine (60 mg), or naproxen sodium (550 mg).
Participants included in the reviewAdults with acute post-operative pain. To be included, the baseline post-operative pain had to be of moderate to severe intensity, and the patients had to be over 15 years of age. The characteristics of the participants were not reported.
Outcomes assessed in the reviewTo be included, the studies had to have pain outcomes measures of total pain relief (TOTPAR) or summed pain intensity difference (SPID) over 4 to 6 hours, or sufficient data to allow their calculation. The pain measures allowed for the calculation of TOTPAR or SPID were a standard 5-point pain relief scale, a standard 4-point pain intensity scale, or a standard visual analogue scale for pain relief or intensity. Time to remedication, and adverse events were also of interest.
How were decisions on the relevance of primary studies made?Two authors were involved in the searches. Abstracts were examined for possible inclusion.
Assessment of study quality Validity was assessed using the 3-item, 5-point scale of Jadad et al. (see Other Publications of Related Interest no.1). Three authors independently assessed the validity of the studies, and consensus was achieved. The authors were not blinded to the study details.
Data extraction Three authors were involved in the data extraction process. The data tabulated were: study identification, study design, dosages, sample sizes, outcomes, analgesic results, adverse events, and quality score. For each trial, the outcome values for each treatment group were converted into a percentage of the maximum (%max) TOTPAR. The proportion of patients who achieved at least 50% maxTOTPAR (i.e. at least 50% pain relief) was then calculated. The authors used an intention to treat analysis.
Methods of synthesis How were the studies combined?The relative benefit and relative risk (RR) estimates were calculated along with 95% confidence intervals (CIs) using a fixed-effect model (see Other Publications of Related Interest no.2). The authors then calculated the number-needed-to-treat or harm.
How were differences between studies investigated?The authors explicitly state that they did not conduct statistical tests for heterogeneity, or assess publication bias. Instead, heterogeneity was examined visually using a L'Abbe plot.
Results of the review Five RCTs with 1,118 patients (211 received placebo, 443 received comparator analgesics, and 464 received rofecoxib 50 mg) were included in the review.
Four of the five studies were in a dental pain setting after third molar extraction, and one was after orthopaedic surgery.
The quality scores were 4 for four trials and 5 for one trial.
At least 50% pain relief.
Based on data from all five trials, 56% of the patients given rofecoxib 50 mg had at least 50% pain relief over 6 hours, compared with 11% of the patients with placebo (RR 4.8, 95% CI: 3.3, 7.2). The number-needed-to-treat was 2.3 (95% CI: 2.0, 2.6).
Remedication time.
The median time to remedication was given in three studies. For placebo, the weighted mean time to remedication was 1.9 hours (n=126), compared with 13.6 hours for rofecoxib 50 mg (n=322) and 7.4 hours for ibuprofen 400 mg (n=97).
Adverse events.
Based on the results from two studies, an adverse event was reported by 33% of the patients on placebo and 28% of those on rofecoxib 50 mg, but the results were not significantly different (RR 0.69, 95% CI: 0.44, 1.08). Nausea and vomiting were reported separately in three dental trials, and both occurred significantly less frequently in the treatment group than in the placebo group; however, there were few (71) events.
Authors' conclusions Rofecoxib at a dose of two to four times the standard daily dose for chronic pain is an effective single-dose oral analgesic in acute pain. Conclusions relating to longer duration of analgesia and the adverse event profile were constrained by limitations in the way the trials were reported.
CRD commentary The inclusion and exclusion criteria were detailed regarding the study design, participants, intervention and outcomes of interest. The authors searched four databases and the search terms were provided. The authors appear to have restricted their search to English language publications, and only included full-journal publications in their review. It would have been beneficial to state whether or not the manufacturer of rofecoxib had any unpublished studies on file (all of the included studies were funded by Merck, the manufacturer of rofecoxib). It is therefore possible that some studies may have been missed, introducing retrieval bias.
The validity of the included studies was adequately assessed by three authors. Details of the individual studies were tabulated although some information was lacking, e.g. the participants' characteristics. In addition, the number of patients with at least 50% pain relief differs in the table and in the text. It appears the authors could have made more direct comparisons between rofecoxib and other analgesics, as well as comparing rofecoxib and placebo.
The conclusions follow from the results.
Implications of the review for practice and research Practice: The authors state that rofecoxib at a dose of two to four times the standard daily dose for chronic pain is an effective single-dose oral analgesic in acute pain.
Research: The authors did not state any implications for further research.
Funding Pain Research Funds, supported by the Oxford Pain Relief Trust.
Bibliographic details Barden J, Edwards J E, McQuay H J, Moore R. Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review. BMC Anesthesiology 2002; 2:4 Other publications of related interest 1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12. 2. Morris JA, Gardner MJ. Calculating confidence intervals for relative risk, odds ratios and standardised ratios and rates. In: Gardner MJ, Altman DG, editors. Statistics with confidence confidence intervals and statistical guidelines. London: British Medical Journal; 1989. p. 50-63.
Indexing Status Subject indexing assigned by CRD MeSH Lactones /therapeutic use; Pain, Postoperative /drug therapy /prevention & control AccessionNumber 12002008328 Date bibliographic record published 30/11/2002 Date abstract record published 30/11/2002 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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