Table 4. Summary of findings.
Statistically significant outcomes from the review graded for risk of bias and imprecision using GRADE.
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) |
No of Participants (studies) |
Quality of the evidence(GRADE) |
|
|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | ||||
| Placebo | Lacosamide | ||||
|
50% Responder Rate (ITT) - Lacosamide (all) vs. placebo Follow-up: 16–18 weeks |
223 per 1000 |
374 per 1000 (303 to 463) |
RR 1.68 (1.36 to 2.08) |
1308 (3 studies) |
⊕ ⊕ ⊕ ⊖ moderate a b c |
|
Discontinuation of Study Drug due to Adverse Effects (ITT) - Lacosamide (all) vs. placebo Follow-up: 16–18 weeks |
49 per 1000 |
155 per 1000 (96 to 250) |
RR 3.13 (1.94 to 5.06) |
1308 (3 studies) |
⊕ ⊕ ⊕ ⊖ moderate a b c d |
|
Ataxia Follow-up: 16–18 weeks |
16 per 1000 |
83 per 1000 (37 to 187) |
RR 5.03 (2.23 to 11.37) |
1308 (3 studies) |
⊕ ⊕ ⊕ ⊖ moderate a b c d e |
|
Dizziness Follow-up: 16–18 weeks |
80 per 1000 |
278 per 1000 (194 to 399) |
RR 3.49 (2.43 to 5.01) |
1308 (3 studies) |
⊕ ⊕ ⊕ ⊖ moderate a b c d |
|
Fatigue Follow-up: 16–18 weeks |
42 per 1000 |
86 per 1000 (46 to 163) |
RR 2.04 (1.08 to 3.85) |
903 (2 studies) |
⊕ ⊕ ⊕ ⊖ moderate a b c d |
|
Nausea Follow-up: 16–18 weeks |
44 per 1000 |
104 per 1000 (54 to 201) |
RR 2.36 (1.22 to 4.58) |
1308 (3 studies) |
⊕ ⊕ ⊕ ⊖ moderate a b c d |
Notes.
GRADE Working Group grades of evidence (Guyatt et al., 2008): High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.Very low quality: We are very uncertain about the estimate.
The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).CI: Confidence interval; RR: Risk ratio.
Trials all had selective reporting of outcomes - outcomes reported in the protocol documents found in the FDA files did not match the outcomes reported in the peer-review publication.
All 3 trials stated “double-blind” without further explanation given. Blinding was assessed as per Akl et al. Journal of Clinical Epidemiology. 2012; 65: 262–267.
None of the 3 trials adhered to the intention-to-treat (ITT) principle - but performed “ITT” analysis with all patients who received at least one dose of study medication.
Ben-Menachem trial provided no explanation with regards to their random sequence generation.
Total number of events less than 300, based on Mueller et al. Annals of Internal Medicine 2007; 146: 878–881.
Wide confidence intervals suggest a degree of imprecision.