Dose-response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies

Abstract

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.

Figure 1

Individual studies with extractable data. L’Abbé plots of the proportions of patients improved on high and low doses for the individual direct comparisons with aspirin, ibuprofen and acetaminophen. The size of the circle representing a trial is proportional to the number of patients studied in the trial