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Using Evidence From Different Sources: An Example Using Paracetamol 1000 Mg Plus Codeine 60 Mg

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Review

Using Evidence From Different Sources: An Example Using Paracetamol 1000 Mg Plus Codeine 60 Mg

L A Smith et al. BMC Med Res Methodol.

Abstract

Background: Meta-analysis usually restricts the information pooled, for instance using only randomised, double-blind, placebo-controlled trials. This neglects other types of high quality information. This review explores using different information for the combination of paracetamol 1000 mg and codeine 60 mg in acute postoperative pain.

Results: Randomised, double-blind, placebo-controlled trials of paracetamol 1000 mg and codeine 60 mg had an NNT of 2.2 (95% confidence interval 1.7 to 2.9) for at least 50% pain relief over four to six hours in three trials with 197 patients. Computer simulation of randomised trials demonstrated 92% confidence that the simulated NNT was within +/- 0.5 of the underlying value of 2.2 with this number of patients. The result was supported a rational dose-response relationship for different doses of paracetamol and codeine in 17 additional trials with 1,195 patients. Three controlled trials lacking a placebo and with 117 patients treated with of paracetamol 1000 mg and codeine 60 mg had 73% (95%CI 56% to 81%) of patients with at least 50% pain relief, compared with 57% (48% to 66%) in placebo controlled trials. Six trials in acute pain were omitted because of design issues, like the use of different pain measures or multiple dosing regimens. In each paracetamol 1000 mg and codeine 60 mg was shown to be better than placebo or comparators for at least one measure.

Conclusions: Different designs of high quality trials can be used to support limited information used in meta-analysis without recourse to low quality trials that might be biased.

Figures

Figure 1
Figure 1
Relative efficacy: Numbers needed to treat for paracetamol/codeine combinations for at least 50 % pain relief over four to six hours for patients with moderate or severe post-operative pain. The number of patients in the comparison was the number given paracetamol 1000 mg plus codeine 60 mg together with the number given placebo in the data pooled from trials for each combination of paracetamol and codeine where there were at least two trials.
Figure 2
Figure 2
Efficacy of paracetamol/codeine combinations and active comparators in randomised, double-blind, active- and placebo-controlled trials in acute pain.

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