DeGiorgio 2005.

Study characteristics
Methods	Randomised, prospective, active‐control study Pre‐randomisation baseline period: 4 weeks Duration of treatment: 3 months. This period included month 1, month 2, and month 3 time points.
Participants	A multicentre trial (USA) 64 people randomised Group A (rapid cycle): 19 participants; mean output current at completion of study 0.87 mA Group B (mild cycle): 19 participants; mean output current at completion of study 0.80 mA Group C (low cycle): 23 participants; mean output current at completion of study 0.93 mA
Interventions	Randomised comparison of three distinct duty‐cycles in treatment of refractory focal seizures: Group A: on/off time 7 s/18 s, duty‐cycle 28%, frequency 20 Hz, pulse width 500 sec rapid cycle; Group B: on/off time 30 s/30 s, duty‐cycle 50%, frequency 20 Hz, pulse width 250 seconds mild cycle; Group C: on/off time 30 s/3 min, duty‐cycle 14%, frequency 30 Hz, pulse width 500 seconds slow cycle. All participants had an identical implantation of the vagus nerve stimulation device (NeuroCybernetic Prosthesis, Cyberonics).
Outcomes	Primary outcome: Seizure frequency (50% and 75% reduction of seizures) Secondary outcomes: Treatment withdrawal Adverse events
Notes	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 occurred in blocks of six (2 for each group), with a unique predetermined randomisation schedule for each site.
Allocation concealment (selection bias)	Unclear risk	No details of concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Identical implants used, but no details of method of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	3 out 64 participants exited early: one developed a device infection, so the device had to be removed; one could not tolerate rapid cycle stimulation, so was converted to a standard duty‐cycle and removed from the study; and one participant was lost to follow‐up. No intention‐to‐treat analysis was performed.
Selective reporting (reporting bias)	Unclear risk	Protocol unavailable, but it appeared all expected and prespecified outcomes were reported.
Other bias	Unclear risk	All studies were sponsored by Cyberonics, the manufacturer of the device.