Opportunity to Establish Consortium for Design of TB Drug Regimens

Funding News Edition: October 19, 2022
See more articles in this edition

Tuberculosis (TB) is currently a leading cause of death by an infectious disease and, according to the World Health Organization, 9.9 million people became ill with TB and 1.5 million died of TB in 2020. Annually, approximately 3.3 percent of new cases and 18 percent of previously treated cases are rifampin-resistant TB. Around one-quarter of the world’s population has latent TB, and CDC estimates that as many as 13 million latently infected people live in the United States.

To address this pandemic, NIAID’s 2018 Strategic Plan for Tuberculosis Research supports research to improve treatment for all forms of TB in all populations and age groups, including research to develop less toxic regimens of shorter duration for safe and effective treatment.

In recent years, the global scientific community has focused on applying cutting-edge science and technologies to understanding the physiology and pathogenesis of Mycobacterium tuberculosis (Mtb) and translating the knowledge gained into targeted therapy. However, limited pharmaceutical industry engagement in antimicrobial drug development has slowed the translation of these discoveries into effective treatment regimens.

NIAID invites applications to establish a Consortium of TB preclinical and clinical experts to systematically refine preclinical models by analyses of relevant preclinical and clinical data through the funding opportunity announcement (FOA) Consortium for Design of TB Drug Regimens (UM1, Clinical Trial Not Allowed).

Consortium Research Objectives

The Consortium will establish a collaborative, multidisciplinary research platform to systematically evaluate new candidate agents in combination. These agents may originate from academic, public-private partnerships, or pharmaceutical industry research efforts, and the Consortium will evaluate them for their potential for incorporation into new TB drug regimens across the human lifespan, including young children.

By generating adequate and comparable preclinical data on regimen efficacy, pharmacometrics, toxicities, drug-drug interactions, and other factors, the Consortium will increase efficiency, accelerate development of new combinations, and identify the most promising regimens for future clinical testing to effect shorter, relapse-free cures of pulmonary TB in adults, children, and persons being treated for HIV.

The TB Drug Regimen Consortium will take the following actions:

  • Provide an open platform to unite preclinical and clinical TB experts (U.S. and international) in the systematic analysis of available preclinical and clinical efficacy and safety data to identify preclinical research projects, scientific needs/gaps, and set an agenda of cooperative goals and research priorities.
  • Optimize preclinical models with back-translation of clinical data from recent trials into animal and other model development.
  • Facilitate communication, coordination, and planning of preclinical research to inform NIH-supported clinical trial networks (both adult and pediatric focused) and other sponsors/investigators by review and discussion of all available information on new agents/combinations and ongoing and anticipated research.
  • Incorporate pediatric-focused research to stimulate preclinical, translational activities that can enable accelerated clinical testing and earlier introduction of new TB drugs and regimens in pediatric populations, with an emphasis on young children (aged 6 years or younger).
  • Perform preclinical evaluations of mechanisms of action of individual and combination drug candidates.
  • Perform preclinical animal model studies (with emphasis on new drug combination efficacy comparisons) identified as needed by the Consortium leadership executive committee after review and approval by NIAID.
  • Provide compiled data and analyses on evaluated combination regimens with priority ranking assessment for consideration by clinical trial networks to guide optimized and coordinated choices of new regimens for phase 2 and 3 trials.
  • Assess evolving clinical research challenges and opportunities for potential inclusion of special populations, new technologies (including biomarkers), and the broader spectrum of TB disease into the Consortium research agenda.

The Consortium will use a strategic planning process for its scientific and translational activities. In establishing and refining research for treatment of TB diseases, the Consortium will actively engage major sponsors, researchers, and communities within and outside of the Consortium. The Consortium Scientific Leadership Group Executive Committee (SLG Ex Com) will ensure that the research is coordinated and complementary to other TB drug research enterprises.

TB Consortium Organizational Structure

The Consortium’s structure will facilitate coordinated and efficient TB drug regimen development. It will include a Scientific Leadership Group (SLG) including a Pediatric Focus Committee, led by SLG Ex Com, a Preclinical Laboratory Group (PLG), a Data Science and Modelling Group (DSMG), and an Administrative Group (AG). These functional areas will be integrally connected to all aspects of the research agenda for the treatment of TB diseases, focusing primarily on pulmonary TB in both adults and children.

Below are some characteristics of the TB Consortium. For full descriptions of each required committee, refer to the FOA linked at the beginning of the article.

SLG Executive Committee (SLG Ex Com) will be responsible for final decisions on prioritized research to be performed, ensuring progress, and providing administrative oversight. This group includes the Consortium program directors and principal investigators (PDs/PIs), the leaders of Preclinical Laboratories and the Data Science and Modelling Group, the chair of the Pediatric Focus Committee, NIAID clinical trial network representatives, and NIAID scientific representatives.

Pediatric Focus Committee (PFC) will ensure that pediatric populations benefit from research by the Consortium, including suggesting additional research needed to extend the impact of Consortium activities towards pediatric populations (especially related to pediatric pulmonary TB). The PFC will formulate plans to initiate relevant key pediatric translational and preclinical activities early during clinical testing of TB drug/combination drug regimens in adults, including those prioritized by SLG or by the Report of the meeting to review the WHO’s Paediatric Antituberculosis Drug Optimization priority list.

Preclinical Laboratory Group (PLG) consists of Preclinical Laboratories (PLs) and will be responsible for designing and implementing in vitro and in vivo studies of efficacy, mechanisms of action, safety, and pharmacometrics of drugs/combinations approved by the SLG Ex Com. At least two PLs will operate mouse models of TB pulmonary disease with pharmacology/pharmacodynamic capabilities for each drug tested and will have experience in successfully informing clinical trial design. Additional PLs may focus on other small animal models of disease, lesion-centric evaluations and rankings, novel quantitative measures of mycobacterial burden/response to therapy, biomarkers, drug effects on mycobacterial metabolism, or other areas supportive of drug regimen evaluation.

Data Science and Modelling Group (DSMG) will summarize and model data for the Consortium to review. The DSMG will also be responsible for collecting, organizing, validating, and analyzing existing preclinical and clinical data from completed studies and trials, from across the published literature, and from clinical trial meta data provided by associated networks/sponsors of adult and pediatric studies.

In conjunction with the Administrative Group, the DSMG will compile reports for the SLG (e.g., assembling dossiers on candidate drug’s history, chemistry, manufacturing and controls, preclinical efficacy and toxicity data, and clinical trial data across the human lifespan, including children). The DSMG will maintain a public chemical structure-based database of known drugs and new candidate compounds with links to public chemical databases and PubMed abstracts.

Administrative Group (AG) provides administrative support, organizes meetings, compiles summaries, facilitates communications, and prepares reports. The AG will coordinate research and data sharing agreements and organize experimental results in formats suitable for regulatory filings, as well as develop and prepare effective legal agreements between participating parties for maximizing disclosure of data to protect intellectual property.

After award, NIAID will form an External Advisory Board to evaluate and comment on scientific progress to the SLG Ex Com of the Consortium.

Note: The FOA lists several research areas that NIAID considers nonresponsive and if you include any of them in your application, NIAID will not review it. For the full list of nonresponsive research areas, go to the FOA linked at the beginning of the article.

Administrative Details and Due Date

Application budgets are not limited but need to reflect the actual needs of the proposed project.

Your proposed project period cannot exceed 5 years. All applications are due February 7, 2023, by 5 p.m. local time of the applicant organization.

Direct any inquiries to Dr. Barbara Laughon at 240-627-3302 or blaughon@mail.nih.gov. Direct questions specific to the pediatric component to Dr. Tania Lombo at 301-761-7612 or tania.lombo@nih.gov.

For matters concerning peer review, contact Dr. Yong Gao at 240-669-5048 or yong.gao@nih.gov.

Contact Us

Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.

Content last reviewed on