Gan 2012.

Study characteristics
Methods	Multicenter, multiple‐dose, multiple‐day, randomized, double‐blind, active‐ and placebo‐controlled, parallel‐group phase 3 study. Efficacy assessed through Day 5 or discharge. Safety assessed 30 days postbaseline. Intervention administered when participant reported moderate to severe postoperative pain within 6 hours of completing surgery.
Participants	Type of surgery: abdominal or pelvic (hysterectomy, general abdominal, inguinal hernia, myomectomy, partial colectomy, general pelvic, salpingo‐oophorectomy, ventral hernia, other) Mean baseline VAS 67 to 70/100 and comparable among groups; paracetamol/opioids/other NSAIDs/PCA not permitted; short‐acting barbiturates or benzodiazepines were allowed with sufficient washout prior to assessment; rescue medication was available (IV morphine 5 to 7.5 mg). Diclofenac group Entered/completing: 87/68 Age (mean, SD): 43.3 ± 10.83 Sex (male, %): 19 (21.8%) Placebo group Entered/completing: 76/57 Age (mean, SD): 42.8 ± 9.66 Sex (male, %): 15 (19.7%) Ketorolac group Entered/completing: 82/67 Age (mean, SD): 42.9 ± 11.42 Sex (male, %): 15 (18.3%)
Interventions	Diclofenac: 37.5 mg/1 mL IV bolus administered when participant reported moderate to severe postoperative pain within 6 hours of completing surgery. Doses repeated every 6 h until end of study or participant withdrawal. Placebo: as with diclofenac. Nature of placebo not specified. Ketorolac: 30 mg/1 mL as with diclofenac
Outcomes	Primary (as specified in study): SPID 0 to 48 h post‐first dose of study drug Secondary: SPID over 0 to 24 h TOTPAR for the 0‐ to 24‐ and 0‐ to 48‐hour intervals (0 to 72, 0 to 96, and 0 to 120 hours as well, if data permitted) Proportion of patients with clinically meaningful (≥ 30%) reduction in pain intensity (vs baseline, using 0‐to‐100‐millimeter VAS) PID at each scheduled assessment Time from administration of study drug to administration of rescue medication Frequency and amount of rescue medication Patient‐reported global evaluation of the study drug at 24 and 48 hours on a 5‐point categorical scale (“excellent,” “very good,” “good,” “fair,” and “poor”) Safety: physical exam, labs, vitals, ECG, thrombophlebitis, AEs
Source of funding	Javelin Pharmaceuticals, Inc., Cambridge, MA (manufacturers of IV diclofenac, now Hospira, Inc., Lake Forest, IL following acquisition in 2010)
Were treatment groups comparable at baseline?	Yes: demographic (age, sex, ethnicity, height, weight) and surgical (time to first doses of intervention, surgical procedure, baseline pain intensity) variables
Notes	Rescue medication (bolus IV morphine 5 mg, titrated up to 7.5 mg after 30 min if analgesia was inadequate) was available upon patient request, up to once every 3 hours any time after administration of the initial dose of study drug, but participants were encouraged to wait at least 1 hour after study medication injection. Data from 37.5 mg diclofenac dose (highest in the study) chosen for all outcomes.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random code
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants, personnel and outcome assessors	Unclear risk	“Clinical staff and patients were blinded to study drug assignment”. No further details
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat population. For pain intensity and pain relief, if rescue medication was administered within 3 h of the next scheduled assessment, WOCF from the preceding 6 hours. If the assessments needed to do this were unavailable, assessments were imputed using BOCF. For withdrawals due to AEs or lack of efficacy, BOCF.
Selective reporting (reporting bias)	Unclear risk	Protocol available on ClinicalTrials.gov. All prespecified outcomes reported in full except PID for each stated time point and grade of thrombophlebitis.
Sample size	Unclear risk	Diclofenac N = 87 Placebo N = 76 Ketorolac N = 82