Rowbotham 2012.

Study characteristics
Methods	Design: parallel Duration: 8 weeks Assessment: baseline and post‐intervention Country: USA, Canada, France, Germany, Italy, Mexico, Puerto Rico
Participants	Pain condition: diabetic peripheral neuropathy Population: diabetic adults with diabetic peripheral neuropathic pain Minimum pain intensity: ≥ 4 on 0‐10 scale Inclusion criteria 18‐75 years of age with a diagnosis of diabetes mellitus Painful distal symmetric diabetic polyneuropathy for P6 months and a score of ≥ 3 on the physical assessment portion of the MNSI at the screening visit An average score ≥ 4 during the 7 days before the baseline visit on the 24‐hour average pain scale Exclusion criteria Cardiovascular and mental health conditions excluded Total participants randomised: 280 Age in years (mean, SD): NR Gender: 128/280 were female Pain duration in years (mean): 4.68
Interventions	Placebo n = 51 Inert Duloxetine 60 mg n = 57 SNRI Fixed dose ABT‐894 2 mg n = 61 Neuronal nicotinic acetylcholine receptor agonist Fixed dose ABT‐894 4 mg n = 56 Neuronal nicotinic acetylcholine receptor agonist Fixed dose ABT‐894 8 mg n = 55 Neuronal nicotinic acetylcholine receptor agonist Fixed dose
Outcomes	Pain intensity Physical function Mood Quality of life PGIC AEs Withdrawal
Missing data methods	ITT with LOCF
Funding source	Pharmaceutical: Abbott Laboratories: AbbVie (prior sponsor, Abbott)
Conflicts of interest	These studies were sponsored by Abbott Laboratories. Dr Rowbotham has served as a consultant to Abbott, Adynxx, Afferent Pharmaceuticals, Allergan, Arcion, Bristol Meyers Squibb, Cardiome, Flexion, Kyowa Hakko Kirin, Neurotherapeutics Pharma, NuvoResearch, Xenon, Xenoport, and Zalicus. Dr Stacey has received grant support from NeurogesX and Pfizer, and has served as a consultant to AstraZeneca, Boehringer Ingelheim, Endo Pharmaceuti‐cals, NeurogesX, and Pfizer. Dr Arslanian has no conflicts of interest to declare. Dr Zhou is an employee of Abbott. Drs Nothaft, Duan, Best, and Pritchett are employees of Abbott and hold Abbott stock and stock options.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomised 1:1 to each treatment arm using a randomisation schedule that was generated before study start.
Allocation concealment (selection bias)	Low risk	Patients were allocated to each treatment arm via an interactive voice response system.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not clear on blinding procedures regarding study drug appearance and dosing
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Self‐reported outcomes from participants, but unsure of blinding
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	States ITT but no methods reported Attrition Total: 43/280 (15.4%) Placebo: 7/51 (13.7%) Duloxetine 60 mg: 13/57 (22.8%) ABT‐894 2 mg: 8/61 (13.1%) ABT‐894 4 mg: 8/56 (14.3%) ABT‐894 8 mg: 7/55 (12.7%)
Selective reporting (reporting bias)	Low risk	Everything as listed in the protocol
Other bias	Low risk	No other sources of bias were identified.