Handforth 1998.

Methods	Randomised, prospective, double blind, active‐control study. Pre‐randomisation baseline period: 12‐16 weeks. Duration of treatment: 16 weeks. This period included 2‐12‐16 week time‐points.
Participants	A multi‐centre trial (USA). 198 people randomised. High stimulation group: 95 participants; mean age 32.1 years; 51.6% male and 48.4% female; mean seizures/day 1.59; mean duration of epilepsy 22.1 years. Low stimulation group: 103 participants; mean age 34.2 years; 42.7% male and 57.3% female; mean seizures/day 0.97; mean duration of epilepsy 23.7 years.
Interventions	Comparison of high (on/off cycles of 30 seconds every 5 minutes, each "on" period consisting of 500 µs duration pulses at 30 Hz frequency) and low stimulation (on/off cycles of 30 seconds every 3 hours, each "on" cycle of 130 µs duration pulse at 1 Hz frequency) in treatment of refractory partial seizures. All patients had an identical implantation of the vagus nerve stimulation device (NeuroCybernetic Prosthesis, Cyberonics).
Outcomes	Primary outcome: Seizure frequency (50% reduction of seizures). Secondary outcomes: a) Dropouts. b) Adverse events. c) Cognitive impact (reported in Dodrill 2000 paper). d) Quality‐of‐life (QOL) impact (reported in Dodrill 2000 paper).
Notes	DODRILL 2000 Epilepsy and Behavior and AMAR A.P. 1998 Neurosurgery are linked to this study. Supported by a grant from Cyberonics, Inc., Webster, TX.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation schedule was generated by a statistical consultant before study initiation.
Allocation concealment (selection bias)	Low risk	Telephone communication to obtain randomised treatment assignment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study personnel and participants are blinded. Identical implants used.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The study data were analysed by a blinded interviewer. Identical implants used.
Incomplete outcome data (attrition bias) All outcomes	Low risk	4 patient withdrawals, but the reasons for exclusion are reported.
Selective reporting (reporting bias)	Unclear risk	All outcomes stated in methods section of paper were reported in the results. There was no protocol available to check to priori outcomes.
Other bias	Unclear risk	All studies are sponsored by Cyberonics, the manufactures of the device.