Guidance
4 Efficacy
4 Efficacy
This section describes efficacy outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
4.1 In a multicentre randomised controlled trial (RCT) of 74 patients with respiratory failure caused by amyotrophic lateral sclerosis (ALS), non-invasive ventilation (NIV) plus diaphragm pacing (n=37) was compared with NIV alone (n=37). Overall survival (defined as the time from randomisation to death from any cause) was statistically significantly shorter in the NIV plus pacing group than in the NIV-alone group (median 11.0 months; 95% confidence interval [CI] 8.3 to 13.6, compared with 22.5 months; 95% CI 13.6 to not reached, adjusted hazard ratio 2.27; 95% CI 1.22 to 4.25, p=0.009). Tracheostomy-free survival (defined as the time to death or tracheostomy) was also statistically significantly shorter in the NIV plus pacing group than in the NIV-alone group (median 11.0 months; 95% CI 8.3 to 13.6, compared with 22.5 months; 95% CI 13.6 to not reached, adjusted hazard ratio 2.42; 95% CI 1.28 to 4.59, p=0.007). Median survival from symptom onset was 28 months (95% CI 22 to 45) for NIV plus pacing patients and 45 months (95% CI 32 to not reached) for those having NIV alone.
4.2 In another multicentre triple-blind RCT in 74 patients with probable or definite ALS, active stimulation (n=37) was compared with sham stimulation (n=37). The NIV-free survival in the intention-to-treat population was statistically significantly shorter in the active stimulation group than in the sham stimulation group (median 6.0 months; 95% CI 3.6 to 8.7, compared with 8.8 months; 95% CI 4.2 to not reached, adjusted hazard ratio 1.96; 95% CI 1.08 to 3.56, p=0.02). The cumulative incidence of NIV did not differ between the 2 groups (since randomisation: median 6; 95% CI 5.1 to 12, compared with 8.8; 95% CI 4.7 to not reached, p=0.42; since symptom onset: median 40; 95% CI 33.6 to 61.7, compared with 34.1; 95% CI 26.4 to not reached, p=0.81). A statistically significant difference in overall tracheostomy-free survival in favour of the sham survival group was seen in the final analysis (49% [18/37] of patients died in the active stimulation group compared with 19% [7/37] in the sham stimulation group; adjusted hazard ratio 3.14; 95% CI 1.31 to 7.53). Overall survival from randomisation was statistically significantly shorter in the active stimulation group than in the sham stimulation group (median 15.6 months; 95% CI 9 to 27, compared with not reached [more than 33], p=0.007). This was also true for overall survival from symptom onset (median 51 months; 95% CI 39 to 74.1, compared with not reached [more than 133], p=0.03).
4.3 In the multicentre RCT of 74 patients with respiratory failure caused by ALS, there were no statistically significant differences between the NIV plus pacing group and the NIV-alone group in patient or carer pre-planned quality-of-life measures. These included the health questionnaires SF-36 (physical health score p=0.78, mental health score p=0.11), Sleep Apnoea Quality of Life (SAQLI, p=0.11) and Caregiver Burden Inventory (CBI, p=0.55). The patient health utility (measured using the EQ-5D-3L) was slightly lower in the NIV plus pacing group than in the NIV-alone group (p=0.056), and the differences were statistically significant when a score of 0 was assigned to the EQ-5D-3L following death. Differences between groups were modest at any individual time point (at 12 months the mean difference was −0.12; 95% CI −0.24 to −0.00, p=0.056), but longitudinal analysis demonstrated statistically and clinically significant differences on all patient EQ-5D-3L questionnaires (mean difference −0.14; 95% CI −0.24 to 0.04, p=0.001).
4.4 The specialist advisers listed key efficacy outcomes as reduction in dependency on external mechanical ventilation, survival and quality of life.