# Strengthening evidence on optimal multidrug-resistant tuberculosis treatment regimens through improved epidemiologic methods

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2022 · $685,092

## Abstract

PROJECT SUMMARY/ABSTRACT
In 2017, more than 550,000 people became sick with a strain of tuberculosis (TB) that was resistant to rifampin
and isoniazid, the two most potent drugs in the standard first-line TB regimen. Historically, treatment for patients
with multidrug-resistant (MDR) TB has been long, toxic, and ineffective: on average, only 55% of treated patients
were cured at the end of the conventional 18- to 24-month regimen, which included a daily injection for
approximately eight months. In 2012 and 2013 regulatory authorities conditionally approved the first new TB
drugs in fifty years, bedaquiline (BDQ) and delamanid (DLM), offering hope for more effective and less toxic
MDR-TB treatment. In early 2019, based on the best available evidence, the World Health Organization (WHO)
issued new guidelines for MDR-TB treatment. These guidelines included a new priority drug ranking for the
composition of MDR-TB regimens, which established BDQ as an anchor of an injectable-free 18- to 24-month
regimen and endorsed a standardized nine-month regimen containing an injectable.
Although conventional injectable-free and shortened injectable-containing MDR-TB regimens represent
enormous improvements, these new guidelines deferred guidance on a number of key questions for which
evidence is lacking, leaving many national TB programs uncertain about how to implement MDR-TB treatment.
For example, although recommendations guide the overall duration of treatment, there was no recommendation
on the optimal duration of use of each drug. Moreover, there is no data on the safety or effectiveness of the
regimen comprising the five top priority drugs. A lack of high quality MDR-TB cohort data also prevented
guidance on other urgent questions, including (1) the safety and effectiveness of common off-label uses of BDQ
and DLM, (e.g., co-administration and extended use of the drugs); and (2) whether BDQ or DLM could be
substituted into the recommended nine-month regimen. In the absence of clinical trial data to address these
questions, robust, valid causal inference from observational MDR-TB cohort data is of paramount importance to
guaranteeing optimal treatment—and minimizing death, morbidity, and disease transmission—for MDR-TB
patients throughout the United States and the world.
The endTB initiative, implemented by our group, offers a unique opportunity to generate high-quality evidence
to inform MDR-TB treatment and care. The endTB observational cohort of 2,600 MDR-TB patients treated with
BDQ and/or DLM in 17 countries—the largest, systematically-collected prospective dataset of its kind. Detailed
longitudinal data will permit robust analyses to inform lingering, critical questions, prioritized by the World Health
Organization. We will exploit this unique resource, strong partnerships in high-MDR-TB-burden countries, and
advanced expertise in epidemiologic methods to identify optimal MDR-TB regimens; inform optimal use of and
adverse event monitoring for BDQ and ...

## Key facts

- **NIH application ID:** 10397702
- **Project number:** 5R01AI146095-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Molly Forrest Franke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $685,092
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397702

## Citation

> US National Institutes of Health, RePORTER application 10397702, Strengthening evidence on optimal multidrug-resistant tuberculosis treatment regimens through improved epidemiologic methods (5R01AI146095-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10397702. Licensed CC0.

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