Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa

Study Overview
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Brief Summary
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The purpose of this study is to compare three strategies for finding TB cases in a rural Sub-Saharan African setting: 1) Screening all attendees of primary care clinics for TB; 2) Conducting household contact investigations of newly diagnosed TB cases; 3) Providing incentives to newly diagnosed TB cases and their contacts to promote contact screening for TB. For each intervention, investigators will measure comparative effectiveness in terms of cases identified as well as the cost-effectiveness and feasibility of implementation.

Official Title
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Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa

Conditions
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Tuberculosis

Intervention / Treatment
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* Other: Active TB case finding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Facility-based screening arm Age 0-99 years Informed consent provided (or assent plus parent/guardian consent) Attending any of the study 28 study clinics in the facility-based screening arm Contact tracing arm- Index Case Age 0-99 years Informed consent provided (or assent plus parent/guardian consent) Newly diagnosed (last 2 months) with TB at any of the 28 study clinics in the contact tracing arm Contact tracing arm- Household Contact Age 0-99 years Informed consent provided (or assent plus parent/guardian consent) Living in the same household as an enrolled Index case (see above) Contact tracing arm- Non-household Close Contact Age 0-99 years Informed consent provided (or assent plus parent/guardian consent) Referred to the study as a close contact of an enrolled Index case (see above) Exclusion Criteria (all arms): Unable to provide informed consent.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Facility-based screening<br>This strategy will be implemented at all clinics (n=28) within this arm for 18 months. Study staff will encourage providers at each of the clinics to screen all consenting patients attending the clinic, regardless of the original reason for clinic presentation. Upon presenting for care (e.g., while waiting for their healthcare provider), patients will be informed about the study and screened for cough of any duration, fever, weight loss, or night sweats. Participants who are symptomatic and provide a sputum specimen (according to the clinic standard of care) will be given a study flyer informing them that they may be contacted by study staff, and a brief summary of the study. Per standard of care, all sputum samples will be sent to the local National Health Laboratory Service laboratory for Xpert testing. | Other: Active TB case finding<br>* Active TB case finding (ACF) refers to any number of strategies used to identify individuals with active TB disease, outside of passive case finding. In passive case finding, individuals with symptoms present at health centers for diagnosis. In active case finding, the health system makes an effort to identify TB cases before they present passively.<br>|
| Experimental: Contact screening<br>This arm is comprised of two sub-arms: In the household contact screening sub-arm, a mobile field team visits the household of each consenting newly diagnosed pulmonary TB index case. Each visit consists of a household census, consent of all eligible household members for TB screening, administration of a brief questionnaire, sputum collection for testing with Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) and the offer of HIV testing. In the incentive-based contact screening sub-arm, all consenting newly diagnosed active TB cases are provided with 10 coupons for free TB screening to give to close contacts. When a contact presents at clinic with a coupon, they and the index case each receive a small amount of money. If the contact is diagnosed with active TB and starts treatment, the index case receives an additional larger amount of money. Each contact receives a brief questionnaire, TB symptom screen, optional HIV testing, and sputum sample collection for Xpert MTB/RIF. | Other: Active TB case finding<br>* Active TB case finding (ACF) refers to any number of strategies used to identify individuals with active TB disease, outside of passive case finding. In passive case finding, individuals with symptoms present at health centers for diagnosis. In active case finding, the health system makes an effort to identify TB cases before they present passively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Initiation Ratio in Facility Versus Contact Investigation Clinics | The primary analysis was based on the facility- level rate ratio, and we first calculated an unadjusted ratio of the treatment initiation rates between the two arms and the corresponding 95% confidence interval (CI). We then adjusted for any residual confounding by district stratification and the historical annual number of people started on TB following a two-stage approach. The first step of this approach fits a Poisson regression to the facility-level counts and the district and historical volume covariates irrespective of study arm. The residuals ratios, calculated as the ratio of the observed over the expected counts, are then used in the second stage to estimate the between-arm rate ratio and the corresponding 95% CI. | 18 months | 
| Comparative Treatment Initiation Ratio in the Incentive-based Versus Household-based Contact Investigation Arms | The primary outcome of the study was the comparative number of people with incident TB diagnosed and started on treatment at study clinics in the two contact tracing arms, excluding the six-month washout period. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative Costs and Cost-effectiveness of Active TB Case Finding Strategies | The primary outcome for this analysis will be the incremental cost-effectiveness ratio, defined as (cost of ACF strategy 2 - cost of ACF strategy 1 [or no ACF])/(effectiveness of ACF strategy 2 - effectiveness of ACF strategy 1 [or no ACF]), where effectiveness is modeled as the number of disability-adjusted life years (DALYs) averted by the intervention. | 3.5 years | 
| Comparative Number of Secondary TB Cases Identified in Incentive-based Versus Household-based Contact Tracing | The pre-specified secondary study outcome was the number of Xpert-based TB diagnoses made among enrolled contacts (secondary cases) by arm. | 36 months |