Fassoulaki 2000.

Methods	Triple‐blinded (participants, providers, outcome assessors) randomized placebo‐controlled clinical trial Sequence generation was randomized but not described Follow‐up: 3 months
Participants	Participants: 46 female participants at a university hospital in Athens, Greece Operation: modified radical mastectomy or lumpectomy and axillary lymph node dissection 2 groups, size: 23/22 (completed) Age ± SD (group 1, 2): 49 ± 6, 49 ± 8 All female participants Exclusion criteria: age > 60 years Remarks: participants undergoing modified radical mastectomy with axillary node dissection/lumpectomy (group 1, 2): 10/13, 7/15. Participants undergoing chemotherapy post‐op (group 1/2): 16/16. Participants undergoing radiotherapy post‐op (group 1/2): 13/8
Interventions	Group 1 (EMLA): 5 g EMLA to sternal area 5 min before induction. Immediately after extubation 5 g EMLA on supraclavicular area, 10 g around axilla (away from site of incision), then covered with Tegaderm. Same total dose of cream (20 g) applied daily on the 4 days after surgery. Group 2 (control/placebo): exactly the same as above, only placebo cream was used. Both groups received premedication with droperidol and metoclopramide and the same GA technique with thiopental and propofol, sevoflurane and nitrous oxide in O2 with rocuronium. No analgesics were given to either group during surgery. Post‐op analgesia in all participants: 75 mg propoxyphene and 600 mg paracetamol IM as needed x 24 h, then paracetamol oral or paracetamol/codeine oral ± hydroxyzine Adjuvants: propoxyphene Immediate post‐op pain control: no significant improvement in post‐op pain or analgesic consumption. Time to first analgesic requirement was significantly longer in EMLA group
Outcomes	Dichotomus: pain/no pain at 3 months (also broken down by site, including chest wall, arm, axilla) Continous: verbal intensity scale of 0 = no pain to 3 = severe pain at 3 months Other reported: absent/decreased sensation, home analgesic use at 3 months
Notes	We acknowledge the response by the study author providing details on allocation concealment, blinding, and sources of support and conflict of interest statement. Funding sources: study author replied, "the study was funded from Departmental sources only." Conflicts of interest: study author replied, "none of the authors has conflict of interest relevant to the study,"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients were randomized before induction of anesthesia using sealed opaque envelopes containing code A or B"
Allocation concealment (selection bias)	Low risk	Quote: study author responded "sealed opaque envelopes containing code A or B" were used
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "the EMLA or the placebo cream was applied by an anaesthesiologist who was not involved in patients' anaesthesia or data collection. All other anaesthesiologists, anaesthetic or ward nurses, as well as the patient, were not aware of the group of assignment"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "an independent observer who was not involved in patient randomization or anaesthesia administration was assessing and recording pain scores"
Incomplete outcome data (attrition bias) All outcomes	Low risk	One participant in the EMLA group with cutaneous allergy was excluded and not replaced. Otherwise no other participants lost. No ITT analysis was done, only per‐protocol.
Selective reporting (reporting bias)	Low risk	No protocol available for review but pre‐specified outcomes within manuscript were reported on.
Null bias	High risk	Quote: "The VAS scores at rest and after movement recorded 0, 3, 6, 9, and 24 h, as well as 2, 3, 4, 5, and 6 days postoperatively did not differ significantly between the 2 groups"