Fassoulaki 2001.

Methods	Double‐blinded, placebo‐controlled randomized clinical trial Sequence generation via "coded envelopes", but not explicitly described Follow‐up: 3 months
Participants	Participants: 100 adult women at a university hospital in Athens, Greece Operation: breast cancer surgery (modified radical mastectomy or lumpectomy + axillary node dissection) 4 groups, size: 23/24/25/24 (completed) Age, group 1, 2, 3,4 (SD not reported): 46, 46, 44, 44 All female participants Exclusion criteria: women over 59 years of age or those who received radiotherapy or chemotherapy preoperatively Number of participants who underwent modified radical mastectomy (group 1, 2, 3, 4): 8, 10, 11, 7. Number of participants who underwent radiotherapy post‐op (group 1, 2, 3, 4): 9, 9, 4, 12. Number of participants who underwent chemotherapy post‐op (group 1, 2, 3, 4): 18, 15, 23, 18
Interventions	Group 1 (ropivacaine and mexiletine): mexiletine 200 mg by mouth evening before surgery and 200 mg twice daily for first 6 post‐op days, brachial plexus infiltrated 12 mL ropivacaine 10 mg/mL and 6 mL 3rd‐5th intercostal spaces after axillary dissection. Group 2 (ropivacaine and placebo): placebo tablet oral evening before surgery and twice daily for first 6 post‐op days, brachial plexus infiltrated 12 mL ropivacaine 10 mg/mL and 6 mL 3rd‐5th intercostal spaces after axillary dissection. Group 3 (placebo and mexiletine): mexiletine 200 mg by mouth evening before surgery and 200 mg twice daily for first 6 post‐op days, brachial plexus infiltrated 12 mL saline and 6 mL 3rd‐5th intercostal spaces after axillary dissection. Group 4 (placebo and placebo): placebo tablet oral evening before surgery and twice daily for first 6 post‐op days, brachial plexus infiltrated 12 mL saline and 6 mL 3rd‐5th intercostal spaces after axillary dissection. All groups received IV metoclopramide and droperidol 5 min before induction. Standardized GA regimen with thiopental, propofol, recouronium, sevoflurane, nitrous oxide in O2. All groups received same post‐op analgesia regimen of 75 mg propoxyphene + 600 mg paracetamol IM every 5 h as needed x first 24 h then post‐op day 2, oral tablet of 10 mg codeine + 400 mg paracetamol every 5 h as needed. Adjuvants: mexiletine (2/4 groups), propoxyphene (4/4 groups) Immediate post‐op pain control: significantly improved, significantly reduced analgesic consumption in group 2 compared with all other groups
Outcomes	Dichotomous: pain/no pain at 3 months (also reported by site, including chest, axilla) Continuous: VAS at 3 months Other: absent/decreased sensation, analgesic use at 3 months
Notes	We acknowledge the response by the study author providing details on randomization, allocation concealment, blinding of participants, personnel and outcome assessors as well as sources of support and conflicts of interest. Funding sources: study author responded, "The study was funded from Departmental sources only." Conflicts of interest: study author responded, "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	The study author stated, "twenty five opaque envelopes were prepared for each group, each containing a note with [a] code...The night before surgery the anaesthesiologist pulled out one envelop from the bag containing the 100 envelops and according to the code inside administered to the patient the capsule from the jar with the same code"
Allocation concealment (selection bias)	Low risk	The study author stated: "twenty five opaque envelopes"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The study author stated: "patients surgeons and anaesthesiologists ALL were blinded except for an anaesthesiologist not participating in the study"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Study author responded that the outcome assessors were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "four patients failed to complete the protocol and were not replaced. Data are unavailable for chronic follow up of two others". Does not state which group specifically the participants belonged to, but can see the numbers of attrition in each group. Overall low numbers and fairly balanced.
Selective reporting (reporting bias)	Low risk	No available protocol but primary outcome specified in manuscript completely reported on
Null bias	Low risk	Quote: "regional block reduced the number of intramuscular (IM) injections required the first 24 hours (P = 05), the R +PL group requiring less injections versus the PL + M group (P = .037). Three hours postoperatively, the R +PL group had less pain at rest when compared with all other groups"