is increasing in severity, will be considered an adverse event. Adverse events will be monitored until the event has cured or stabilized.

# _Reporting of adverse events_

For each possible adverse event identified and graded as moderate, severe or life threatening, an adverse event report form will be completed (Appendix 9). The following information will be recorded for all adverse experiences that are reported:

- Description of event

- Date of event onset

- Date event reported

- Maximum severity of the event

- Maximum suspected relationship of the event to study medication

- Is the event serious?

- Initials of the person reporting the event

- Was the event episodic or intermittent in nature?

- Outcome

- Date event resolved

Grading of events will be based on standard guidelines (Appendix 10).

# _Reporting of serious adverse events_

Guidelines for reporting of serious adverse events provided by the KEMRI, the London School of Hygiene & Tropical Medicine, and the data and safety monitoring board (DSMB) will be followed.

**xv) Quality control**

All members of the study team will be trained in the study objectives, methods of effective communication with study participants, and collection of high quality data. Study members will receive additional training specific to the tasks they will perform within the study including interviewing techniques, and clinical and laboratory measurements. A random sample of stool, urine and blood samples will be re-read by experienced technicians and any disparities corrected.

# **9. Data management**

# **Data entry and storage**

All questionnaires will be transferred to KIlifi for review, data entry, and storage. Data will be entered by two independent clerks, will be verified for data entry errors, and corrected from the original questionnaire using customized software (Microsoft Visual FoxPro® 6.0) and verified for accuracy. Study records will be stored securely in KEMRI facilities.

# **Data analysis**

All analyses will be on the basis of intention-to-treat. To assess the success of randomization baseline characteristics between the four randomization groups will be compared. To assess the impact of the interventions, methods appropriate for cluster-randomized trials will be used (Hayes & Bennett, 1999). The prevalence, or mean, in each school will be calculated and the unadjusted risk ratio (RR), or mean difference (intervention-control), estimated in each stratum. An overall estimate of the effect of IST will be obtained by taking a weighted average of the stratum-specific estimates, the weights proportional to the number of schools per stratum, and 95% confidence intervals will be adjusted for observed between-school variance. Formal hypothesis testing will be undertaken using stratified unpaired t-tests. The impact of each intervention will be estimated for education outcomes and health outcomes in separate multiple regression models. An interaction term will be included to identify any synergistic effects between the two interventions. Statistical analysis will be carried out using STATA<sup></sup> software, version 10.0. (Stata Corporation, Texas, USA).

# **10. Time Frame**

|**2008**|||||||||||Nov|Dec|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|Staff recruitment and training|||||||||||||
|Development and piloting of<br>educationassessment tools|||||||||||||
|**2009**|Jan|Feb|Mar|Apr|May|Jun|Jul|Aug|Sep|Oct|Nov|Dec|
|Development and piloting of<br>education assessment tools|||||||||||||
|Teacher training workshop|||||||||||||
|Baseline health and education<br>surveys|||||||||||||
|IST|||||||||||||
|Instruction intervention|||||||||||||
|Assessment of class behavior|||||||||||||
|**2010**|Jan|Feb|Mar|Apr|May|Jun|Jul|Aug|Sep|Oct|Nov|Dec|
|First follow-up health and<br>education surveys|||||||||||||
|IST|||||||||||||
|Instruction intervention|||||||||||||
|Assessment of class behavior|||||||||||||

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