. 2025 May 1;25(2):1–177.

Table A3:

GRADE Evidence Profile for the Comparison of nVNS and Control, Acute Use, Cluster Headache

Number of studies (design)	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Upgrade considerations	Quality
Pain relief: response
2 (RCTs)	Serious limitations (-1)^a	No serious limitations	No serious limitations^b	Serious limitations (-1)^c	Undetected	None	⊕⊕ Low
Pain relief: response in 50% or more of attacks
2 (RCTs)	Very serious limitations (-2)^a	No serious limitations^d	No serious limitations	Serious limitations (-1)^e	Undetected	None	⊕ Very low
Pain relief: sustained treatment response
1 (RCT)	No serious limitations	No serious limitations^f	No serious limitations	Very serious limitations (-2)^g	Undetected	None	⊕⊕ Low
Pain freedom
1 (RCT)	Serious limitations (-1)^a	No serious limitations^f	No serious limitations	Serious limitations (-1)^h	Undetected	None	⊕⊕ Low
Pain freedom in 50% or more of attacks
2 (RCTs)	Very serious limitations (-2)^a	No serious limitations	No serious limitations	Serious limitations (-1)ⁱ	Undetected	None	⊕ Very low
Headache intensity
2 (RCTs)	Serious limitations (-1)^a	No serious limitations	No serious limitations^b	Serious limitations (-1)^j	Undetected	None	⊕⊕ Low
Duration of headache attack
1 (RCT)	Serious limitations (-1)^a	No serious limitations^f	No serious limitations	Serious limitations (-1)^k	Undetected	None	⊕⊕ Low
Acute medication use
1 (RCT)	No serious limitations	No serious limitations^f	No serious limitations	Serious limitations (-1)^l	Undetected	None	⊕⊕⊕ Moderate
≥ 1 Adverse event
2 (RCTs)	Serious limitations (-1)^a	Serious limitations (-1)	No serious limitations^m	Serious limitations (-1)ⁿ	Undetected	None	⊕ Very low
≥ 1 Severe adverse event
2 (RCTs)	Serious limitations (-1)^a	No serious limitations	No serious limitations^m	Serious limitations (-2)^o	Undetected	None	⊕ Very low
≥ 1 Device-related adverse event
2 (RCTs)	Serious limitations (-1)^a	No serious limitations	No serious limitations^m	Serious limitations (-1)ⁿ	Undetected	None	⊕⊕ Low

Abbreviations: GRADE, Grading of Recommendations Assessment, Development, and Evaluation; nVNS, noninvasive vagus nerve stimulation; RCT, randomized controlled trial.

See Table A1.

Outcome measured differently by the 2 studies, but not downgraded.

Small sample sizes and very wide confidence intervals that crossed no effect in both studies.

Moderate inconsistency, but not downgraded.

Confidence intervals were very wide and crossed no effect or a moderate decrease in response.

Inconsistency could not be assessed because only 1 study contributed to the outcome.

Only 1 study included, with a very small sample size and wide confidence intervals that included a very large effect and a small, not clinically meaningful effect (absolute difference 1%). Given that no risk of bias was present, greater weight was placed on the severe imprecision, downgrading 2 levels.

Very small sample size with a confidence interval that crossed no effect (P > .05).

ⁱ

Extremely wide confidence intervals that included a very large increase in response and a decrease in response.

Very small sample sizes in both studies, with confidence intervals that included no effect in both studies.

Small sample size with a very wide confidence interval that included a large reduction in duration and a 6-minute increase in duration.

Small sample size with a confidence interval that crossed no effect.

No description of how adverse events and device-related adverse events were predefined.

ⁿ

Wide confidence interval that crossed no effect.

Extremely wide confidence interval that included very large harm and a reduction in adverse events. Further downgraded due to a very low number of events.