Multidrug-resistant tuberculosis (MDR-TB) is one of the most serious public health problems in the world today—and the global burden is growing. That’s why we are delighted to announce that UNITAID has awarded Partners In Health a grant that will change how MDR-TB is treated throughout the world.
Partnering with Médecins Sans Frontières and Interactive Research & Development, PIH will use the four-year, $60 million grant to bring two new drugs to 17 countries in which MDR-TB poses a significant burden. Called “END-TB,” this project is designed to dramatically expand access to these new drugs globally. It will lead to the development of new treatment regimens for MDR-TB and ultimately improve the quality of life for countless patients. Here’s everything you need to know about this innovative program:
What’s UNITAID and why is it funding END-TB?
UNITAID is a global health financing system that works to expand access to drugs and diagnostics for TB, HIV, malaria, and other infectious diseases that disproportionally affect low-resource countries. About half of UNITAID funding comes from a small fee on airline tickets. The projects it funds are often aimed at sustainably reshaping markets so that new drugs and medical technologies are available to more people at a lower price, which is a major focus of END-TB.
Who is PIH partnering with on this project?
The project consists of a consortium with two other partners. Our first partner is Médecins Sans Frontières, or Doctors Without Borders, which you’ve probably heard of. The group does amazing work in countries where armed conflict, epidemics, natural disasters, and other challenges limit access to health care.
Our second partner is Interactive Research & Development, or IRD, a global health delivery and research organization based in Dubai that works in 15 countries, including high-burden MDR-TB countries such as Pakistan, Indonesia, and Bangladesh. The IRD team leverages process and technology innovations to address global health delivery gaps, including the use of health market innovations such as social business models to engage private providers in lung health and diabetes care, as well as the use of performance-based incentives for community screeners and treatment supporters, patient incentives to enable treatment compliance, and the use of open-source information technology platforms to allow close monitoring of patient care and program quality.
The project will also work with many other “non-consortium” partners, such as national TB programs and local nongovernmental organizations and stakeholders in the END-TB countries, as well as other international partners such as the World Health Organization (WHO) and MSF Access Campaign.
In what countries is END-TB going to be implemented?
Patients from 17 different countries—most of which are designated by the WHO as high-burden MDR-TB countries—will be enrolled in the program. In some countries, only patients from the END-TB partner site will be enrolled initially, to gain “in-country experience.” In other countries, patients will be enrolled countrywide from the start.
The 17 countries are: Armenia, Bangladesh, Belarus, Ethiopia, Georgia, India, Indonesia, Kazakhstan, Kenya, Kyrgyzstan, Lesotho, Myanmar, Nepal, North Korea, Pakistan, Peru, and Swaziland. Here’s a map to help you get a better understanding:
Why were these countries selected?
These are all countries where the END-TB partners have active projects and established systems for treatment delivery and monitoring and evaluation. For example, PIH has been supporting large MDR-TB treatment projects in Peru, Lesotho, and Kazakhstan for years. This expertise will allow us to figure out the best ways to use these new TB drugs, and provide a model for other sites and countries.
And what’s the difference between TB and MDR-TB?
As Carole Mitnick, PIH’s longtime partner and renowned TB expert, explained, “The distinction lies in the drugs that are useful to treat this bacterial disease.” TB is usually treated with a four-drug, six-month regimen.
MDR-TB is caused by bacteria that are resistant to the two most important drugs in the standard regimen, isoniazid and rifampicin. It is highly infectious; each untreated MDR-TB patient can infect three to six people each year. Treating MDR-TB is grueling for patients. It often requires a minimum of 20 months, consisting of daily regimens containing at least five drugs, one of which is given as a daily injection for at least eight months. Some of the drugs carry the potential for severe adverse effects, including psychiatric disorders, kidney damage, liver toxicity, and hearing loss. It can be an isolating and painful process for patients, even when treatment is delivered through community-based platforms with comprehensive social support.
And still, only about half of the people who endure the full two-year treatment are cured. Eighty percent of patients who fail MDR-TB treatment die within three years.
How serious a problem is MDR-TB?
Drug-resistant TB is one of the most serious public health problems in the world today. Unfortunately, it appears that the global burden of MDR-TB is growing. The WHO estimated that there were 450,000 new cases of MDR-TB in 2012. That same year, approximately 170,000 people died from MDR-TB. Tuberculosis—drug-resistant strains and drug-susceptible strains combined—kills more than 1 million people every year. That’s equivalent to the entire population of Hawaii dying every year from a treatable disease.
What are the new drugs END-TB will deliver? And why are they so important?
Bedaquiline and delamanid are the first new drugs approved for TB in 40 years. They have the potential to shorten the course of treatment, improve cure rates, and minimize side effects.
The problem is that these drugs aren’t getting to the patients who need them most. There are two principal reasons for this: 1) They are new and many countries are reluctant to use them because of limited safety profiles and they have no experience in their use; 2) They are not licensed in many places, or only have conditional approval. Often the only way to access them is through what’s called “compassionate use” programs, which can be cumbersome, slow, and are not an option in all countries. This all leads to a "chicken-and-egg" phenomenon, where countries are reluctant to administer the new drugs because they are not widely used, and we can’t improve our understanding of their safety because countries aren’t using them.
How will END-TB change that?
END-TB is designed to specifically spur early adoption of these drugs. By buying bedaquiline and delamanid for 3,200 patients across 17 countries, PIH will create a network of sites that can demonstrate the best way to use these drugs. The first patients to use these drugs at the END-TB sites will likely be the ones with highly resistant strains of TB, such as extensively drug-resistant TB. These patients have very few treatment options and have the most to gain.
PIH and its partners will collect an enormous amount of data in this first group of patients. We want to make sure these drugs do not cause any unexpected side effects, and that they are as effective as initially thought. This data will then immediately be made available to the WHO to inform future policy recommendations. Showing that these new TB drugs are both effective and safe will go a long way in convincing more countries to use them. The rigorous monitoring of patients and careful delivery of drugs is possible in experienced MDR-TB treatment sites, such as those run by PIH and its partners.
Why is a clinical trial part of END-TB?
A major goal of END-TB is to simplify the treatment of MDR-TB by finding new treatment regimens. This will be done through a clinical trial that will take place at a subset of the END-TB sites. Getting the new TB drugs to the patients who need them—especially those with highly resistant TB—will certainly save many lives. But the clinical trial component, which will employ an innovative design never used to evaluate TB regimens, has the potential to be a true "game-changer" by discovering shorter, safer, all- oral, and more effective regimens that could be used in all MDR-TB patients.
Is that typical for a PIH project?
A multicenter clinical trial may not be what usually comes to mind when people think of PIH. But PIH has a long history of research in the area of TB, though of course not on this scale. PIH will draw on clinical trial experts from our partners at Harvard Medical School, the Division of Global Health Equity at Brigham and Women's Hospital, and the epidemiological centers at Médecins Sans Frontières.
Furthermore, much of the work will be done by our experienced and dedicated doctors and nurses at our country sites, many of whom have years of experience caring for MDR-TB patients and who have been longing for better drugs and regimens. END-TB will not receive any funding from pharmaceutical companies. This ensures complete objectivity when evaluating the safety and efficacy of the new drugs.
This sounds like a massive project. How long will it take?
It is quite large, but we plan to move swiftly so these drugs can get to patients as soon as possible. As previously mentioned, END-TB is spread over four years. We expect to start enrolling patients this fall. This is a historic opportunity to tackle the escalating MDR-TB public health emergency.