Clinical and technical evidence

A literature search was carried out for this briefing in accordance with NICE's interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting

Published evidence

There are 2 studies summarised in this briefing. These include a randomised controlled trial (Mekhail et al. 2020) of 134 people and an observational study (Russo et al. 2020) of 50 people.

The clinical evidence and its strengths and limitations is summarised in the overall assessment of the evidence.

Overall assessment of the evidence

The evidence base is small but includes comparative evidence of good methodological quality. The population and clinical outcome of pain rating are relevant to the NHS. The studies also reported system-related secondary outcomes including use of pain medication and number of follow-up visits related to reprogramming. Neither study included in the evidence base compares Evoke with a spinal cord stimulation device routinely used in the NHS. Evidence showing equivalence between the open-loop Evoke used in the randomised controlled trial and open-loop spinal cord stimulation devices used as standard care would be useful. However, experts have stated the device is likely to be comparable. Both studies were funded by the company.

Mekhail et al. (2020)

Study size, design and location

Randomised controlled trial of 134 patients with chronic and intractable back and leg pain comparing the safety and efficacy of the closed-loop Evoke system with conventional open-loop spinal cord stimulation using Evoke in the US.

Intervention and comparator

The intervention arm of the trial used closed-loop spinal cord stimulation. The comparator arm of the trial used fixed-output, open-loop spinal cord stimulation. Both the intervention and comparator devices use the same device (that is, Evoke).

Key outcomes

The primary outcome was to achieve 50% or greater reductions in back and leg pain without an increase in pain medication. Out of the 125 people included in the study at 3 months, more people in the closed-loop group had a 50% or more reduction in pain compared with the open-loop group (82% and 60%, respectively). This shows statistically significant non-inferiority (p<0.0001) and superiority (p<0.005). Similarly, of the 118 people included in the study at 12 months, 83.1% of people in the closed-loop group had a 50% or more reduction in pain compared with 61.0% of people in the open-loop group (non-inferiority, p<0.0001; superiority, p=0.006). At 12 months, opioid use was reduced or eliminated in 55% of people in the closed-loop group and 40% of the open-loop group.

Strengths and limitations

This was a well-designed double-blinded study with a computerised randomisation sequence for group allocation. Patient demographics were well matched between groups. The study was powered to detect non-inferiority and superiority between the 2 groups. The same device was used in both arms but only the interventional arm used the closed-loop system. The open-loop Evoke system has not been proven to be equivalent to commercially available open-loop spinal cord stimulation devices, but experts advised it is likely to be comparable. The study was funded by the company and done outside of the UK.

Russo et al. (2020)

Intervention and comparator

Evoke closed-loop system.

No comparator.

Key outcomes

After 12 months, a reduction of 50% or more from baseline in pain rating was reported by 76.9% and 79.3% of people with back pain and people with leg pain, respectively. A reduction of 80% or more from baseline was reported in 56.4% and 58.6% of people with back and leg pain, respectively. At 12 months, mean overall pain reduced from a baseline of 81.3 mm on the visual analogue scale (plus or minus 1.6 mm) to 21.0 mm (plus or minus 3.4 mm, p<0.001). The proportion of people who reported 50% or more reduction from baseline in overall pain rating was 81.4%. There were 53.5% of people who reported 80% or more reduction in overall pain rating. The stimulation was in the therapeutic window 84.9% of the time and opioid intake was reduced or eliminated by the 12‑month visit in 68.8% of people. The mean number of unscheduled programming visits per person was 2.41 (n=49) between month 0 and 1 and reduced to 0.14 between months 6 and 12 (n=43).

Strengths and limitations

The study is multicentred and reported using Evoke in a relevant patient population. Clinical outcome measures were relevant and follow-up time was reasonable. The lack of comparator limits the usefulness of the findings. The study was powered to show that 90% of people could have programming with closed-loop stimulation. The study may be underpowered to detect a difference from baseline in pain ratings. It was funded by the company and the primary author has previously served as a consultant to the company. The study was done outside of the UK.


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Recent and ongoing studies