Thibela TB Trisha Crawford James Lewis Katherine Fielding

Statistical analysis plan Measurement of the primary outcome Measurement of the primary outcome Sub-group analyses Sub-group analyses –Hostel dwellers or permanent employees –HIV prevalence amongst TB cases

Original plan for study 12 mths24 mths Max. of 3 mths recruitment 12 mths measurement period for primary outcome Final prevalence survey Baseline prevalence survey Staggered enrolment across regions

Revised plan for study 9 mths: last participant to start IPT completes IPT Recruitment Period: variable for each cluster (depending on cluster size) 12 mths: measurement period for primary outcome Final prevalence survey Date of cluster enrolment Baseline prevalence survey Extended recruitment and follow-up Co-enrol in regions

Definition of time period for primary outcome Start of measurement period Start of measurement period –cluster enrolment + cluster-specific recruitment period + 9 months Control clusters we define a cluster-specific recruitment period based on Control clusters we define a cluster-specific recruitment period based on –Size of cluster –Assuming recruitment 30/day, 5 recruitment days per mth For smaller clusters the measurement period starts a shorter time interval after cluster enrolment For smaller clusters the measurement period starts a shorter time interval after cluster enrolment

Adjustment Individual level Individual level –Age, gender, surface/underground, permanent/contractor Cluster level Cluster level –TB CNRs, ART/IPT coverage, radiological prevalence of TB, silicosis

Analyses planned- Baseline survey Baseline survey Baseline survey –RFs for being on TB Rx, radiological prevalence of TB Use of survey for cohort analysis Use of survey for cohort analysis –RFs for TB –Effect of secondary PT (restricted to those reporting prev hx of TB)

Analyses of data from intervention clusters TB case finding TB case finding Screening failures on IPT Screening failures on IPT Retention analysis Retention analysis –Report to DSMB

Final culture prevalence survey Sample size Sample size –750 per cluster –Based on 60% reduction in TB prevalence Clusters range in size from 1000 to 11,000 Clusters range in size from 1000 to 11,000 Longer FU of clusters would be beneficial (routine FU) Longer FU of clusters would be beneficial (routine FU) To minimize the impact survey on outcome - sample proportionally to cluster size? To minimize the impact survey on outcome - sample proportionally to cluster size?

TCAS – TB case ascertainment study Problems Problems –Differential up-take by intervention arm; information on refusals is documented –Compare counts by time period with TB register –Contractors? Case definitions for outcomes Case definitions for outcomes –? Compare across studies

Other data sources ART/IPT availability ART/IPT availability –Baseline & collected direct from company Health services (aggregate data at cluster level) Tolerability sub-study Tolerability sub-study –Add in more mixing questions? HR data HR data –Presented a crude summary of in and out- migration –More detailed analysis

Papers Pilot studies Pilot studies –TST & TB survey –INH urine testing Study design paper Study design paper TB case-finding TB case-finding MGIT demonstration study (incl. economics) MGIT demonstration study (incl. economics) Modelling Modelling Data management? Data management? AEs – short report? AEs – short report?