Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Use of JYNNEOS® (orthopoxvirus) vaccine heterologous for those who received ACAM2000 primary series

Table 1: Policy Question 5 and PICO

Table 2: Outcomes and Rankings

Appendix 1: Studies Included in the Review of Evidence

Table 3a: Summary of Studies Reporting Outcome A – Prevention of Disease

Table 3b: Summary of Studies Reporting Outcome B – Severity of Disease

Table 3c: Summary of Studies Reporting Outcome C – Serious Adverse Events (SAE)

Table 3d: Summary of Studies Reporting Outcome D – Myo/pericarditis

Table 5: Summary of Evidence for Outcomes of Interest

Explanations

1. Risk of bias due to lack of comparison data.
2. Seroconversion rate is an indirect measure of prevention.
3. Small sample size, no comparison.
4. Attrition rate was variable across study groups. One group lost 17% of participants.
5. Small sample size, fragility of estimate.
6. In the protocol it is unclear how serious adverse events were assessed.
7. Sample size is small, too small to detect rare adverse events.
8. Observational data was included in the evidence profile for this outcome because the effect estimate for the randomized trials was not estimable.
9. Single-arm studies contribute data to the intervention, but no available data for the comparison from the systematic review. Downgraded for indirectness because historical data was used for comparison.
10. Intervention data was drawn from 3 observational studies included in the systematic review. 0/349 (0.00 %) participants from 3 studies developed vaccine related serious adverse events.
11. Comparison data was drawn from historical data. In a phase III clinical trial for ACAM2000 enrolling participants with previous smallpox vaccination 3/1371 (0.22%) developed vaccine related serious adverse events after ACAM2000 administration. No smallpox vaccine-specific serious adverse event was recorded.
12. Assessment of myo-/pericarditis was initiated late in the study at the request of FDA. Very few subjects could be evaluated at that point. It was unclear how many subjects were evaluated.
13. Sample size is small, too small to detect rare events of myopericarditis after JYNNEOS®.
14. Intervention data was drawn from 3 observational studies included in the systematic review. 0/349 (0.00 %) participants developed myo-/pericarditis.
15. Comparison data was drawn from historical data. In a phase III clinical trial for ACAM2000 enrolling participants with previous smallpox vaccination, 0/1371 (0.00%) developed myo-/pericarditis after ACAM2000 administration.

References

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