Table 2.
Assumptions, parameters, and sample size estimations for the longitudinal cohorts in Mali, Kenya, and Zambia
| Mali | Kenya | Zambia | |
|---|---|---|---|
| Clusters per arm (overall) | 38 (76) | 35 (70) | 35 (70) |
| Trial duration in calendar years (seasonality of FU) (total FU per participant time in months) | 2 years (8-month seasons) (16 months FU) | 2 years (12-month seasons) (24 months FU) | 2 years (6-month seasons) (12 months FU) |
| α (type 1 error probability for 2-year trial) | 0.05 (Haybittle-Peto with one interim analysis) | 0.05 (Haybittle-Peto with two interim analyses at approx. 50% and 75%) | 0.05 (Haybittle-Peto with one interim analysis) |
| Power | 88% | 80% | 80% |
| Baseline incidence of clinical malaria in the target age group | 0.40 events per person year (based on 0.6 incident events during an 8-month malaria season) (5y–<15y) | 0.845 events per person year during a 12-m malaria transmission season (1y–<15y)a | 0.50 events per 6-month malaria season (Jan–Jun) (1y–<15y) |
| Reduction in baseline incidence (incidence rate ratio = 0.70) | 30% | 30% | 30% |
| Coefficient of variation | 0.40 | 0.40 | 0.40 |
| Assumed loss of person-time, including true LTFU plus loss due to exclusion of person-time following each treatment with AL | 20% | 20% | 34% |
| Total person-years required (number enrolled per cluster before loss to follow-up) | 3850 person-years (obtained by enrolling 38 individuals per cluster to account for loss to follow-up, followed for total of 16 months) | 1260 person-years (obtained by enrolling 13.5 individuals per cluster to account for loss to follow-up, followed for total of 24 months) | 1610 person-years (obtained by enrolling 35 individuals per cluster to account for loss to follow-up, followed for total of 12 months) |
aThe observed event rate in this age group was 1128 per 1000 person-years in the control arm of a recently completed mass test-and-treat trial in this area. A more conservative event rate of 845/1000 will be used to account for an anticipated 25% reduction in clinical malaria in children 1–<5 years of age (28.6% of the sample study cohort) due to the implementation of the RTS,S/AS01E vaccine in two-thirds of the study area (resulting in an estimated 7.4% reduction in event rates in children 1–<15 years), plus a further 17.6% reduction in malaria due to unforeseen changes in environmental factors, or boosting of other malaria control measures such as the scaling up of integrated community-based case management