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. 2022 Jun 16;16(5):803–819. doi: 10.1111/irv.13002
Planned approach Updated approach Reason for change
Meta‐analyses would be undertaken to produce pooled hSAR and hSCAR estimates. No pooled estimates of hSAR or hSCAR were produced. A 95% prediction interval was produced. There was substantial heterogeneity in estimated hSAR. We anticipated that we may be able to explain these sources of heterogeneity through several pre‐specified subgroup analyses and provide pooled estimates at a finer resolution (i.e., by subgroup).
The primary meta‐analysis produced a high I2 value of 99.7%, indicating a high degree of heterogeneity as anticipated. The high degree of heterogeneity was also reflected in the wide range of reported hSAR estimates (2%–90%) and prediction interval (3%–71%). Substantial heterogeneity was still present within these pre‐specified subgroups, as well as a number of post‐hoc subgroups.
Given our understanding of the differences in the source of the estimated hSAR in each investigation, and the residual heterogeneity that was present upon meta‐analysis within subgroups, it was decided it was not appropriate to report any pooled estimates. Instead, we added in the estimated 95% prediction interval to help illustrate the large variation in results.
A beta‐binomial mixed‐effects model would be fit for primary meta‐analysis and a binomial‐normal model would be fit for sensitivity analysis. A binomial‐normal mixed‐effects meta‐analysis model was used for the primary meta‐analysis. Both methodologies have been demonstrated to be appropriate for the chosen outcome measures, 24 , 28 and we intended to utilise the beta‐binomial model for the primary analysis and the binomial‐normal sensitivity analysis.
The binomial‐normal model had existing implementations in our chosen statistical package, 31 and so we decided to utilise this as for the primary analysis. No sensitivity analysis was undertaken due to the decision not to pool hSAR or hSCAR estimates, as described above.
We would assess reporting biases through (1) visual inspection of funnel plots of the effect size, and; (2) using Eggers test to evaluate bias due to small study effect. No assessment of reporting biases was made. Because we chose not to produce pooled estimates any of the outcomes of interest, there was no need to assess the impact of reporting biases on these pooled estimates.
Pre‐specified subgroups: (1) Income setting; (2) Predominantly circulating variant at the time of investigation; (3) Secondary case ascertainment methods and (4) Methodological quality of investigation. Additional post‐hoc subgroups: (1) Duration of follow‐up of household contacts; (2) Stricter adherence to the Unity protocol, and (3) Use of serological testing to ascertain secondary cases. The high heterogeneity between hSAR estimates (I 2 value of 99.7%) was not reduced in pre‐specified subgroup analyses (I 2 values ranging between 99.4%–99.6%).
To address this, we defined three additional post‐hoc subgroups we anticipated may account for heterogeneity.