Dan 1989.

Methods	Design: Randomised, double‐blind, parallel group trial Year: July 1987 to March 1988 Country: Japan
Participants	Patients: 73 patients were randomised to one of the following 2 groups: Buprenorphine suppository: N = 34, 15 females/19 males, age: < 60 years (14), 60‐70 years (11), ≥70 years (9); cancer type: stomach (8), hepato‐biliary‐pancreatic (7), colorectal‐uterine (4), breast‐prostate (5), oropharyngeal (2), lung (4), oesophageal (2), other (2); analgesic drugs: none (0) peripheral analgesic (25), peripheral+central analgesic (6), central analgesic (2), others (1); pain intensity at baseline: mild (17), moderate (17); ECOG performance status: 0 (2), 1 (3), 2 (11), 3 (13), 4 (5); number of patients excluded from the study = 2 (due to protocol violations consisting of treatment with other analgesic agents and/or severe pain). Buprenorphine injection: N = 35, 10 females/25 males, age: <60 years (20), 60≤ and <70 (9), 70≤ years (6); cancer type: stomach (10), hepato‐biliary‐pancreatic (7), colorectal‐uterine (4), breast‐prostate (3), oropharyngeal (5), lung (2), oesophageal (1), other (3); analgesic drugs: none (1) peripheral analgesic (22), peripheral+central analgesic (6), central analgesic (5), others (1); pain intensity at baseline: mild (17), moderate (18); ECOG performance status: 0 (1), 1 (6), 2 (10), 3 (17), 4 (2); number of patients excluded from the study = 1 (due to protocol violations consisting of treatment with other analgesic agents). Inclusion criteria: "Patient who have a cancer pain and pain intensity is 2 (mild) or 3 (moderate)". Exclusion criteria: None reported.
Interventions	Buprenorphine suppository: Drug: Buprenorphine suppository + placebo injection. Dose/dosing: 0.2 mg administered twice, with the second administration 6 to 8 hours after the first administration regardless of the presence or absence of pain. Formulation: Suppository. Route of administration: Intra‐rectal. Length of treatment: 12 to 16 hours. Titration schedule: No information reported. Rescue medication: Appears to be indomethacin suppository 50 mg. Study drug must be administered > 4 hours after using indomethacin suppository (no further information reported). Other medication: Other analgesics or suppositories should not be used, and the authors avoided the use of psychotropic drugs as they appear to affect the action of the experimental drugs." Buprenorphine injection: Drug: Buprenorphine injection + placebo suppository. Dose/dosing: 0.2 mg administered twice, with the second administration 6‐8 hours after the first administration regardless of the presence or absence of pain. Formulation: Injection. Route of administration: IM. Length of treatment: 12 to 16 hours. Titration schedule: No information reported. Rescue medication: Appears to be indomethacin suppository 50 mg. Study drug must be administered > 4 hours after using indomethacin suppository (no further information reported). Other medication: Other analgesics or suppositories should not be used, and the authors avoided the use of psychotropic drugs as they appear to affect the action of the experimental drugs."
Outcomes	Pain intensity: Assessed by patients at baseline and at 2, 4 and 6 hours in response to the question "How is your pain". It seems the patient answers were then coded into one of 4 categories: 1 = none or little pain ("I have no pain" "I have a little pain, but it does not bother me"), 2 = mild pain ("I can stand the pain, but it always bother me"), 3 = moderate pain ("I can barely stand the pain, it is quite painful"), and 4 = severe pain ("I have intolerable, quite painful pain that I cannot stand"). Pain relief: Assessed by patients at baseline and at 2, 4 and 6 hours in response to the question "How is the effect". It seems the patient answers were then coded into one of 3 categories: 1 = effective ("Drug has worked well" "I have a little pain, but drug has worked well"), 2 = minor response ("Drug has not worked much"), 3 = ineffective ("Drug has not worked at all"). Adverse events including appetite (assessed at baseline and study end), temper (assessed at baseline and study end), drowsiness,dizziness, feeling heavy‐headed, nausea, vomiting, sweating, thirst, urinary retention, euphoria, and fatigue (all assessed 12 hours after second experimental drug administration): Assessed by healthcare professional on a scale from 0 (no symptom) to 3 (severe; for dizziness, feeling heavy‐headed, nausea, vomiting, sweating, thirst, urinary retention, euphoria, and fatigue), and on a scale from 0 (no symptom) to 4 (severe; for drowsiness).
Notes	Study free of commercial funding? Not reported. Groups comparable at baseline? Yes, the groups appear to be comparable at baseline. ITT analyses undertaken? No, the analyses were conducted per‐protocol. This study is only published in Japanese, and was kindly translated by Dr. Maki Kawasaki, Japanese Branch of the Australasian Cochrane Centre.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information about randomisation sequence to make a judgement.
Allocation concealment (selection bias)	Unclear risk	Insufficient information about allocation to make a judgement.
Blinding of participants and personnel (performance bias) Pain	Low risk	Double‐blinded and placebo looks identical to the actual drug.
Blinding of participants and personnel (performance bias) Adverse events	Low risk	Double‐blinded and placebo looks identical to the actual drug.
Blinding of outcome assessment (detection bias) Pain	Low risk	Assessed by patients and they were blinded.
Blinding of outcome assessment (detection bias) Adverse events	Low risk	Assessed by healthcare professional and they were blinded.
Incomplete outcome data (attrition bias) Pain	High risk	Data reported for 28/35 IM patients and 33/34 rectal buprenorphine patients after the second administration of the study drug.
Incomplete outcome data (attrition bias) Adverse events	Low risk	Most of the adverse events appear to be reported for 34/34 rectal buprenorphine patients and for 35/35 IM buprenorphine patients.
Selective reporting (reporting bias)	Low risk	All the main expected outcomes are reported.
Other bias	Unclear risk	It is unclear whether the study is at risk of other bias(es)
Were the patients adequately titrated?	Unclear risk	It is unclear, but probably not.
For cross‐over trials: Are data available for both time periods?	Unclear risk	NA.