VNS Study Group 1995.
| Study characteristics | ||
| Methods | Randomised, prospective, double‐blind, active‐control study Pre‐randomisation baseline period: 12 weeks Duration of treatment: 14 weeks. Efficacy was determined at the 12‐week time point. At the end of the 14 week double‐blind phase, participants entered an extension phase in an open trial. |
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| Participants | A multicentre trial (USA, Canada, Sweden, and Germany) 114 people randomised High stimulation group: 54 participants; mean age 33.1 years; 61% male and 39% female; mean seizures/day 1.49; median seizures/day 0.73; mean duration of epilepsy 23.1 years; simple focal seizures 24 participants; complex focal seizures 50 participants; secondarily generalised seizures 38 participants Low stimulation group: 60 participants; mean age 33.5 years; 63% male and 37% female; mean seizures/day 1.71; median seizures/day 0.82; mean duration of epilepsy 20.0 years; simple focal seizures 25 participants; complex focal seizures 58 participants; secondarily generalised seizures 33 participants |
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| Interventions | Comparison of high (output current 0.25 to 3.0 mA, on/off time 30 to 90 s/5 to 10 min, frequency 20 to 50 Hz, pulse width 500 µs) and low (output current 0.25 to 1.75 mA, on/off time 30 s/60 to 180 min, frequency 1 to 2 Hz, pulse width 130 µs) stimulation in treatment of refractory focal seizures All participants had an identical implantation of the vagus nerve stimulation device (NeuroCybernetic Prosthesis, Cyberonics). |
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| Outcomes | Primary outcome: Seizure frequency (50% and 75% reduction of seizures) Secondary outcomes:
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| 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 tables were developed by an independent statistician with assignments, based on the participant's identification code. |
| Allocation concealment (selection bias) | Low risk | Assignments were made automatically by a look‐up table in the computer software used to program the generator. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Participants were blinded and one investigator for each site was unblinded. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | The interviewer remained blinded to treatment group. Identical implants used. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 57 participants were randomised to low stimulation. 3 participants allocated to high stimulation had their stimulator programmed for low stimulation in error. These participants were analysed in the low stimulation group according to the treatment they received rather than the treatment they were randomised to. This was not an intention‐to‐treat analysis. |
| Selective reporting (reporting bias) | Unclear risk | All outcomes stated in the methods section of the paper were reported in the results. There was no protocol available to check a priori outcomes. |
| Other bias | Unclear risk | All studies were sponsored by Cyberonics, the manufacturer of the device. |
µs: microseconds Hz: hertz IQ: intelligent quotient mA: milliampere min: minutes mo: month ms: milliseconds QOL: quality of life s: seconds VNS = vagus nerve stimulation y: year