Jain 1988

Methods	Multi‐arm RCT – 3 groups.
Participants	Women with moderate to severe pain following episiotomy at a clinical research centre, New Orleans. Women with known hypersensitivity to NSAID agents, history of allergy to aspirin, ibuprofen or caffeine, history of asthma, clinically significant renal, hepatic, endocrine, pulmonary, cardiac, neurologic, or cerebral dysfunction or with a history of peptic ulcer disease or gastrointestinal blood loss, uncontrolled diabetes, drug abuse or alcoholism, were excluded. Use of caffeine, anti‐inflammatory agent, tranquilliser or sedative was prohibited during the 4 hours prior to administration of test medication as well as during the study period.
Interventions	Intervention: caffeine 100 mg + ibuprofen 200 mg (N = 50) and ibuprofen 400 mg (N = 49). Comparison: placebo (N = 48).
Outcomes	Pain intensity (0 = none, 1 = slight, 2 = moderate and 3 = severe). Pain relief (0 = none, 1 = slight or 25%, 2 = some or 50%, 3 = a lot or 75% and 4 = complete or 100% relief). Rescue/additional medication (only included if requested after 2 hours of receiving study drug). Side effects. Global impression and overall evaluation of study medication. Pain assessed at baseline and 30 minutes after and thereafter hourly up to 6 hours. Only 6‐hour data used in this review (4‐hour data could not be extracted).
Notes	Caffeine 100 mg + ibuprofen 200 mg combination therapy not include in the review as not pure NSAID.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation schedule.
Allocation concealment (selection bias)	Unclear risk	Supplied in unit dose bottles containing identical tablets; no information if sequentially numbered and sealed.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No clear statement.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of 161 women selected, 14 (9%) were excluded from the analysis; 11 due to rescue medication before the 2‐hour follow‐up (4 in the ibuprofen 400 mg group, 4 in the placebo group (and 3 in the ibuprofen 200 mg + caffeine group which was not included in this review), 2 due to use of confounding agents and 1 because she was under 18 years old (not specified from which group). Attrition rates could not be calculated due to non‐report of the exact number of participants in each group at the start of the study.
Selective reporting (reporting bias)	Low risk	Pre‐specified outcomes were all reported.
Other bias	Low risk	No statistical differences across groups in terms of demographic variables and baseline pain intensity measures.