Investigation of a Novel Approach to Improve Treatment Success Rates for Tuberculosis Patients in Senegal
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 4

Summary: 
      Tuberculosis (TB) patients who receive inadequate treatment or do not complete therapy are
      more likely to remain infectious, thus contributing to the continuous spread of TB infection
      in communities. Despite the widespread use of Directly Observed Therapy, defaulters remain an
      important problem in TB control programmes. In Sénégal, defaulters rate reach 30%, which is
      hampering dramatically the effectiveness of control. New strategies to deliver treatment to
      TB patients and ensure proper adherence that are adapted to the local situations are urgently
      needed.

      Objectives

      The overall objective of the project is to improve tuberculosis treatment success rates in
      Sénégal. The specific objectives are:

        1. to assess the current situation of tuberculosis (TB) in Sénégal

        2. to identify the determinants of cure,

        3. to develop measures to improve patient's compliance with the treatment that are adapted
           to the local situation, acceptable, affordable and sustainable

        4. to evaluate the impact of these measures on TB control.

      Methods

      The proposed research seeks to develop and test innovative methods to improve cure rates in
      TB patients. It will explore the factors of success of TB treatment using inter-disciplinary
      approach, integrating social sciences and economic analyses into TB research. The project is
      composed of 3 comprehensive phases:

        -  Phase 1: baseline assessment of the TB situation.

        -  Phase 2: anthropological study, investigating various domains contributing to patients
           cure using a range of qualitative research methods. At the end of this investigation, it
           is expected that determinants of care will be clearly identified. On this basis,
           suitable methods for improving patients' adherence to treatment will be tailored and
           developed.

        -  Phase 3: these methods will be tested and compared using a cluster randomised controlled
           trial design, in populations served by defined health centres. Their efficacy will be
           measured in terms of improvement of the classical TB control programme indicators (cure
           rate, defaulter rate, failure rate, death rates). The methods will also be evaluated on
           their acceptability by the TB patients and the communities and on their feasibility
           (duration : 24 months).

      Expected results:

      Methods to improve patients' adherence to treatment that are affordable, acceptable and
      sustainable will be developed and tested according to qualitative and quantitative criteria.
    

Detailed description: 
      General Project Methods

      The proposed research seeks to develop and test innovative methods to improve treatment
      success rates in TB patients in Senegal. It will explore the factors of success of TB
      treatment using inter-disciplinary approach, integrating social sciences and economic
      analyses into TB research. The project is composed of 3 comprehensive phases, that will be
      run concurrently and complement each other:

        -  Phase 1: baseline assessment of the TB situation. It is first proposed to assess the
           magnitude of the TB problem and of the means to control it through a standard baseline
           assessment (6 months).

        -  Phase 2: anthropological study, investigating various domains contributing to patients
           cure (the patients, the community, the general health services, the policy makers and
           the TB control staff), using a range of qualitative research methods (12 months). At the
           end of this investigation, it is expected that determinants of care will be clearly
           identified with a comprehensive understanding of their relation/interface. On this
           basis, suitable methods for improving patients' adherence to treatment will be
           developed.

        -  Phase 3: these methods will be tested and compared using a cluster randomised controlled
           trial design, in populations served by defined health centres. Their efficacy will be
           measured in terms of improvement of the classical TB control programme indicators (cure
           rate, defaulter rate, failure rate, death rates). The methods will also be evaluated on
           their acceptability by the TB patients and the communities and on their feasibility (24
           months).

      Methods of the Intervention Trial:

      The intervention is intended to improve access to care and increase adherence to treatment,
      targeting simultaneously DHC staff, TB patients and communities, and includes four
      components:

        1. improving communication between health personnel and patients through appropriate
           training;

        2. decentralising treatment to remote health posts and involving community health workers
           (CHW);

        3. strengthening the DOT strategy by giving patients the opportunity to choose their
           treatment supporter; and

        4. reinforcing supervision of health posts by the DHC team.

      The intervention is applied at the District Health Centre (DHC) level, which is the unit of
      randomisation.

      Sample Size:

      Based on the detection of an average of 100 new TB cases per DHC per year, an estimated
      coefficient of variability k=0.12, an estimated success rate in the control arm of 65% using
      conventional TB control programmes procedures, with 80% power and a type I error of 5%, the
      required sample size aiming to detect a difference of at least 15% in the treatment success
      rate between the intervention and control arms is eight DHCs per arm. In order to take into
      account the variation in recruitment of TB patients between the DHCs, the randomisation is
      stratified on baseline detection rate of sputum smear positive cases in 2001, that were
      classified as less than 60/100 000 and more than or equal to 60/100 000.

      Patients and follow-up DHCs with a functional TB diagnosis and treatment unit, where no other
      research projects were being undertaken, were eligible for inclusion. The study population
      consisted of all individuals presenting to the DHC between June 2003 and May 2004 with newly
      diagnosed sputum-smear positive pulmonary TB (at least two positive specimens), aged 15 years
      or more, and living in the district served by the DHC. Written informed consent was obtained
      at recruitment and patients were followed-up during the course of their eight month treatment
      regimen, with the last patients seen in January 2005.

      Smear-negative and extra-pulmonary tuberculosis cases, as well as re-treatment cases, were
      not eligible for the study. Patients were recruited into the study between June 2003 and May
      2004 and followed up till January 2005.

      Endpoints:

      Primary endpoints are both the proportion of recruited patients experiencing treatment
      success (those cured + those completing treatment), and the proportion of patients defaulting
      from treatment before completion. A "cured" patient is defined by a negative sputum-smear at
      eight months and on at least one previous occasion. Patients "completing treatment" are those
      missing smear results but who had finished their treatment regimen. A "defaulter" is defined
      as a patient who definitely stopped treatment before completion.
    

Intervention name(s): Comprehensive package of activities
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: tuberculosis; control; treatment; adherence