Jodie Barden

Pain and analgesic response after third molar extraction and other postsurgical pain

&NA; There is uncertainty over whether the patient group in which acute pain studies are conducted (pain model) has any influence on the estimate of analgesic efficacy. Data from four recently updated systematic reviews of aspirin 600/650 mg, paracetamol 600/650 mg, paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model. Area under the pain relief versus time curve equivalent to at least 50% maximum pain relief over 6 h was used as the outcome measure. Event rates with treatment and placebo, and relative benefit (RB) and number needed to treat (NNT) were used as outputs from the meta‐analyses. The event rate with placebo was systematically statistically lower for dental than postsurgical pain for all four treatments. Event rates with analgesics, RB and NNT were infrequently different between the pain models. Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven, and, on balance, no major difference is likely.

Relative efficacy of oral analgesics after third molar extraction

Objectives To compare the relative efficacy of analgesics after third molar extraction from systematic reviews of randomised, double blind studies.Data sources Dental trials from systematic reviews of randomised, double-blind studies of analgesics in acute pain.Data selection Number of patients with moderate or severe pain achieving at least half pain relief over 4 to 6 hours after a single oral dose of analgesic.Data extraction Independently by two reviewers.Data synthesis Use of dichotomous information from active and placebo treatments, first to calculate the statistical significance using relative risk, and then to evaluate the clinical relevance using number needed to treat (NNT). Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors had the lowest (best) NNTs for the outcome of at least half pain relief over 4-6 hours compared with placebo. With the best performing analgesics, 50-70 patients out of 100 had good pain relief compared with about 10 out of 100 with placebo. Only paracetamol 600/650 mg plus codeine 60 mg was associated with any significant increase in any patient experiencing an adverse event.Conclusions NSAIDs and COX-2 inhibitors have the lowest (best) NNTs. They may also have fewer adverse effects after third molar surgery, though conclusive evidence is lacking. At least 80% of analgesic prescribing by UK dentists is in line with the best available evidence on efficacy and safety.

Oral valdecoxib and injected parecoxib for acute postoperative pain: a quantitative systematic review

BackgroundClinical trials suggest that cyclo-oxygenase-2 specific inhibitors (coxibs) are an effective treatment for acute postoperative pain. The aims of this systematic review were to examine the evidence for oral valdecoxib and injected parecoxib, and quantify efficacy and adverse effects.MethodsInformation from randomized, double-blind studies in acute postoperative pain was sought. The area under the pain relief versus time curve over four to six hours was dichotomized using validated equations to derive the proportion of patients with treatment and placebo with at least 50% pain relief over four to six hours and calculate the number-needed-to-treat (NNT). Information on duration of analgesia and adverse events was also collected.ResultsThe NNT for one patient to experience at least 50% relief over six hours following a single oral dose of valdecoxib 20 mg and 40 mg was 1.7 (1.4 to 2.0) and 1.6 (1.4 to 1.8) respectively. The NNT for one patient to have at least 50% relief over four to six hours with parecoxib 20 mg IV and 40 mg IV was 3.0 (2.3 to 4.1) and 2.3 (2.0 to 2.6) respectively. Mean time to remedication (weighted by trial size) was >24 hours with valdecoxib 40 mg, 8.7 hours with parecoxib 40 mg IV and 1.7 to 1.8 hours with placebo. There were no statistical differences between treatment and placebo for any adverse effect.ConclusionBoth oral valdecoxib and injected parecoxib are effective treatments for acute postoperative pain.

Bias from industry trial funding? A framework, a suggested approach, and a negative result

Abstract Bias from funding sources of trials would threaten their validity. Meta‐analyses of high quality acute pain and migraine trials were used to explore the hypothesis that industry funding of clinical trials produced more favourable results than non‐profit sponsorship. Analyses were planned to evaluate whether industry‐sponsored trials had different results from trials funded by academic or other non‐profit sources, but of 176 trials, only two were supported by non‐profit sources, while 31 provided no statement of support. An alternative method is proposed within industry‐sponsored trials, looking at conflicting industry interests for the same drug, used either as test or comparator treatment. Fifty‐three trials used an analgesic as test and 90 as comparator, allowing comparisons to be made for aspirin 600/650 mg, ibuprofen 400 mg, paracetamol (acetaminophen) 1000 mg, rofecoxib 50 mg and sumatriptan 50 and 100 mg. Only for sumatriptan 50 and 100 mg, with the outcome of headache response at 2 h, was there any significant difference between the drug used as a test or as a comparator. The direction was for higher (worse) NNTs with sumatriptan as comparator. Investigating potential industry bias through the funding source of trials is unlikely to be adequate because of a dearth of trials funded by non‐profit organisations. We propose a method based on potential conflict of interest within industry‐sponsored trials. Using this method, established clinical trial results in acute pain and migraine appear to be unbiased.

Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review

BackgroundRofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic review of rofecoxib in acute pain examined studies in adults of analgesic efficacy over six hours, the amount and quality of the evidence on extended duration of analgesia, and the quality and quantity of evidence on adverse events.MethodsCochrane Library (issue 4, 2001), Biological Abstracts (March 2002), MEDLINE (March 2002) and PubMed (March 2002) were searched using rofecoxib as a free text term. The area under the pain relief versus time curve was dichotomized using validated equations to derive the proportion of patients on rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was used to calculate the number needed to treat for at least 50% pain relief over six hours for rofecoxib compared with placebo. Information on duration of analgesia and adverse events was also collected.ResultsFive included trials investigated 1,118 patients, of whom 211 received placebo and 464 received rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0 to 2.6). The weighted mean remedication time was 1.9 hours for placebo (126 patients), 7.4 hours for ibuprofen 400 mg (97 patients) and 13.6 hours for rofecoxib 50 mg (322 patients).ConclusionRofecoxib at 2–4 times the standard daily dose for chronic pain is an effective single dose oral analgesic in acute pain. Limitations in trial reporting constrain conclusions about longer duration of analgesia and adverse event profile.

Outcomes in acute pain trials: systematic review of what was reported?

&NA; Single‐dose clinical trial methods for evaluating analgesics have been used successfully for over 50 years. The aims of this review were to examine which pain measurement scales have been used in high quality acute pain trials, to investigate other common measurements or characteristics, to confirm that different scales used by standard methods give the same estimate of analgesic effect, to investigate remedication methodologies and the potential of ‘time to remedication’ as a standard outcome. Published reports of randomised, double blind, placebo‐controlled trials, investigating at least 20 adult patients (10 patients per treatment arm) experiencing moderate or severe pain using at least one standard pain intensity or pain relief scale were sought. Key design features, outputs and outcomes were catalogued for each report. The main outcomes reported were misleading, detailing only the mean values of data with a demonstrably skewed distribution. After 50 years, the reporting of results from acute pain trials warrants a fresh look. Possible improvements include reporting the number of patients with certain levels of pain relief, or the actual number (percentage) of patients with a certain level of pain relief at a certain time, or more useful information on remedication from trials of at least 12 h duration. Most useful would be all three. Further exploration would only be possible from analysis at the individual patient level.

Ibuprofen 400 mg is effective in women, and women are well represented in trials

BackgroundA recent article in the New Scientist argued that women were under-represented in clinical trials which, until now, had masked the finding that ibuprofen 400 mg was ineffective in women.MethodsMeta-analysis of randomised, double-blind placebo-controlled trials of ibuprofen 400 mg in acute pain, and use of individual patient information were planned to test the hypothesis that ibuprofen is ineffective in women. For each trial the proportion of women participating, the number of patients with at least 50% pain relief and the overall event rate for ibuprofen 400 mg and placebo was calculated. For each patient percentage pain relief was calculated, and the numbers of women and men achieving at least 50% pain relief used to calculate number-needed-to-treat (NNT) for ibuprofen 400 mg compared to placebo.ResultsThirty-seven included trials had 3,577 patients, 67% of whom were women. The proportion with at least 50% pain relief was unaffected by how many women were included. In an analysis of 678 individual patients the proportion of women and men with at least 50% pain relief was the same, NNT 3.4 (2.6 to 4.6) and 2.5 (2.0 to 3.3) respectively.ConclusionThere is no clinically meaningful difference in the efficacy of ibuprofen 400 mg between men and women experiencing moderate to severe postoperative pain and women were well represented.