for the main comparison.

Analgesic plus caffeine compared with analgesic alone for acute pain
Patient or population: adults with acute pain Settings: community Intervention: analgesic plus caffeine Comparison: same dose of analgesic alone
Outcomes	Outcome with analgesic alone	Outcome with analgesic plus caffeine	RR and NNT (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
Effective pain relief	41%	48%	RR 1.2 (1.1 to 1.3) NNT 14 (9.9 to 24)	4262 (27 separate comparisons)	High	Small effect size but large numbers of participants contributing. There is a large amount of data that cannot be incorporated into this review, but this result is robust to analysis assuming all missing data show no effect. In fact, the results of this review are consistent with an almost completely different analysis in 10,000 participants demonstrating the effect of caffeine to have a similar effect size
Serious adverse events	1 event	1 event	Not calculated	Not calculated	Very low	Neither event judged related to study medication. Single dose studies are not powered to assess serious adverse events
CI: confidence interval; NNT: number needed to treat to benefit; RR: risk ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.