Generation of data to externally validate treatment decision algorithms for tuberculosis in children

In March 2022, the World Health Organization (WHO) Global Tuberculosis Program published new consolidated guidelines on the management of tuberculosis in children and adolescents, as well as an operational manual .

One of the new recommendations in the consolidated guidelines relates to the use of integrated treatment decision algorithms in children with suspected pulmonary TB attending health facilities to diagnose pulmonary TB. Integrated treatment decision algorithms are flowcharts that assign evidence-based scores to microbiological, clinical, and radiological characteristics that help clinicians make decisions about initiating treatment for TB in children. For this recommendation, the Guidelines Development Group (GDG) convened by WHO reviewed the evidence on several treatment decision algorithms. The GDG made a generic recommendation on the use of treatment decision algorithms, given the important role these algorithms could play in closing the large case detection gap in children. Therefore, this recommendation has been made by WHO as interim, conditional recommendation, given the need for further evidence. Evidence will need to be produced to review the recommendation in the future.

Following the GDG meeting, two new integrated treatment decision algorithms were developed and validated in-house, using a database of individual patients from pediatric diagnostic studies from geographically diverse high-burden TB settings. . These algorithms have been included in the operational manual for the management of tuberculosis in children and adolescents (see chapter 4 from page 73 and appendix 5).

The WHO Global Tuberculosis Programme, together with the Special Program for Research and Training in Tropical Diseases (TDR), aim to facilitate the generation of evidence through external validation and studies to inform a future review of the generic recommendation in the 2022 WHO consolidated guidelines on the management of tuberculosis in children and adolescents.

The type of studies to generate the evidence includes the following:

1. External validation studies on the diagnostic accuracy of the two integrated treatment decision algorithms, including for specific subpopulations and in various settings. Ideally, these validation studies would also include:

a. qualitative or quantitative sub-studies, including on feasibility, acceptability and equity,

b. economic sub-studies to determine resource requirements and profitability.

Potential adaptations of the algorithms could also be considered based on epidemiological settings (such as settings with different TB burdens, different healthcare settings, including settings with limited access to chest X-ray) and subpopulations .

2. Modeling studies to determine the potential impact of newly developed treatment decision algorithms on case detection and treatment initiation.

Therefore, the WHO Global Tuberculosis Program and the Special Program for Research and Training in Tropical Diseases (TDR) are seeking expressions of interest from independent researchers/research groups, academic institutions or other entities with relevant expertise and experience in conducting research on pediatric TB diagnostic approaches. , to generate the data listed above. Research projects should be conducted over a relatively short period (no more than 2 years) to inform the revision of current guidelines.

The expression of interest must contain:

A concept note (max. 5 pages) of the proposed research, including objectives, research question(s), study plans, setting or countries where the proposed research will be conducted, a summary of the research team (including principal investigator(s)), expected impacts, budget (or proposed plan to raise funding) and timeline;

· The CV of the main researcher must also be attached.

Please note that the WHO Global Tuberculosis Program and the Special Program for Research and Training in Tropical Diseases (TDR) will not fund studies and applicants should outline their plans to fund the research if funds are not already available.

Please send your submissions to the WHO Global Tuberculosis Program at [email protected] by June 30, 2022.

After reviewing expressions of interest, the WHO Global Tuberculosis Programme, in collaboration with the Special Program for Research and Training in Tropical Diseases (TDR), will convene a meeting with selected researchers to harmonize research methods and data collection efforts.