Appendix 1. MEDLINE search strategy
Database: Ovid MEDLINE(R) <1946 to January Week 4 2019>*
Search Strategy:
1 PRN.mp. [mp=title, abstract, original title, name of substance word, subject heading word, floating sub‐heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (1175)
2 pro re nata.mp. (425)
3 patient‐controlled.mp. (5311) 4 self‐administration.mp. (10550) 5 PCA.mp. (26678)
6 opioid.mp. (71422) 7 opiate.mp. (11771) 8 morphine.mp. (29878) 9 methadone.mp. (9227) 10 oxycodone.mp. (2764) 11 hydromorphone.mp. (1282) 12 codeine.mp. (3198)
13 fentanyl.mp. (12491) 14 buprenorphine.mp. (4860) 15 alfentanil.mp. (1276) 16 remifentanil.mp. (4092)
17 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 (101201) 18 cancer.mp. (1089129)
19 malig*.mp. (334427) 20 carcinoma.mp. (473820) 21 neoplasm.mp. (471596) 22 18 or 19 or 20 or 21 (1619968) 23 (as adj required).mp. (647647) 24 (as adj needed).mp. (401190)
25 1 or 2 or 3 or 4 or 5 or 23 or 24 (1058392) 26 17 and 22 and 25 (1276)
27 limit 26 to "all adult (19 plus years) and /humans and/ yr="1987 ‐Current" (961)
Appendix 2. Assessment of risk of bias methodology.
We assessed risk of bias for each included study using criteria outline in the Cochrane Handbook for Systematic Review of Intervention.
Selection bias
1. Random sequence generation (selection bias) methods were assessed as low risk of bias (e.g. random number table; computer random number generator), high risk of bias (non‐
random process, for example, odd or even date of birth; hospital or clinic record number) or unclear risk of bias (e.g. study reports that participants were randomised but does not give details of the method used).
2. Allocation concealment (selection bias) methods were assessed as low risk of bias (e.g.
telephone or central randomisation), high risk of bias (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth, case record numbers) or unclear risk of bias (e.g. study does not report any concealment approach, or only states that a list or table was used).
Performance bias
3a + 3b. Blinding of participants or study personnel methods assessed as low risk of bias (e.g. study participants and/or personnel were blinded, high risk (e.g. no attempt of blind study participants or personnel) or unclear risk of bias.
Detection bias
4 Blinding of outcome assessment methods were assessed as low risk of bias (e.g. blinding of assessor described), high (e.g. no blinding of assessor attempted) or unclear risk of bias.
Incomplete outcome data bias
5. Incomplete outcome data (bias due to incomplete outcome data) was assessed as low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups), high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; greater than 20% drop‐out).
Reporting bias
6. Selective reporting (reporting bias) was assessed as low risk of bias (e.g. clear description of all the study’s pre‐specified outcomes have been reported), high risk of bias (e.g. where not all the study’s pre‐specified outcomes have been reported) or unclear risk of bias.
Other bias
7. Sample size
We classified studies as being at low risk of bias (200 participants or more per treatment arm); unclear risk of bias (50 to 199 participants per treatment arm); or high risk of bias (fewer than 50 participants per treatment arm).
Appendix 3. Opioid conversion ratios
https://www.rcoa.ac.uk/faculty-of-pain-medicine/opioids-aware/structured-approach-to- prescribing/dose-equivalents-and-changing-opioids
Opioid Potency equivalent to oral
morphine sulphate
Morphine sulphate (mg/day)
Codeine 0.01
Hydromorphone 7.5
Tapentadol 25
Buprenorphine 35 microgram/hr TDS
84mg
Buprenorphine 70 microgram/hr TDS
168mg
Buprenorphine 0.2mg 16mg
Appendix 4.
Prospero registration: CRD42019133463
Accessed at https://www.crd.york.ac.uk/PROSPERO/
