Aims: Establishing the dose-response relationship for clinically useful doses of aspirin, ibuprofen and paracetamol has been difficult. Indirect comparison from meta-analysis is compromised by too little information at some doses.
Methods: A systematic review of randomized, double-blind trials in acute pain comparing different doses of aspirin, ibuprofen and paracetamol was therefore undertaken.
Results: Fifty trials were found. Numerical superiority of higher over lower dose was found by the original authors in 37/50 trials (74%) and statistical superiority in 11/50 (22%). Twenty-eight trials had design, quality and data reporting characteristics to allow pooling of common doses; in 3/28 (11%) of the individual trials our calculations showed statistical superiority of higher over lower dose. Pooled comparison of 1000/1200 mg aspirin over 500/600 mg was statistically superior, with a number-needed-to-treat (NNT) for higher over lower dose of 16 (8 to > 100). Pooled comparison of 400 mg ibuprofen over 200 mg was statistically superior, with an NNT for higher over lower dose of 10 (6-23). Pooled comparison of 1000 mg paracetamol over 500 mg was statistically superior, with an NNT for higher over lower dose of 9 (6-20).
Conclusions: Use of trials making direct comparison of two different doses of target drugs revealed the underlying dose-response curve for clinical analgesia.