Tuberculosis Research in Tibet Soars to New Heights, Improving Treatment Adherence and Outcomes
February 22/2024
Professor Xiaolin Wei, the Dalla Lana Chair of Global Health Policy, in Clinical Public Health and Institute of Health Policy, Management and Evaluation at DLSPH, and his co-authors recently had their tuberculosis research in Tibet published in The Lancet. The article is titled ‘Effectiveness of a comprehensive package based on electronic medication monitors at improving treatment outcomes among tuberculosis patients in Tibet: a multicentre randomised controlled trial.’ The article is based on the trial they ran for 5 years in Shigatse, Tibet with tuberculosis (TB) patients. This is the first study in the world demonstrating a positive impact of electronic monitors on TB treatment outcomes. The evidence is valuable for TB programs and the World Health Organization to inform policies in bring the benefits of electronic medicine monitors to patients.
Tuberculosis in Tibet
Professor Xiaolin Wei in Tibet with patients and village doctors
The research team chose Tibet as the location for their trial because it has one of the highest rates of TB patients stopping their medications, also known as ‘loss to follow up.’ TB patients must be treated daily for at least six months, but if they stop taking their pills, they become resistant to the medication, and it is harder and more expensive to treat. But if there’s no support for the patient, they often stop their treatments, which has been a challenge for patients of many chronic diseases, worldwide, for centuries. Patients have to renew their medications every two months at the TB dispensary at the county centres in Tibet, but this is often challenging because of the high altitude, long travel distance, and harsh weather and road conditions.
There are four medications for tuberculosis patients that they must take at once for two months, then two medications for another four months, which are packaged in blister packs. Just as TB has its own symptoms such as coughing, fever, etc., so too does the medication. Side effects from the medication include loss of appetite, orange urine (which sometimes scares the patients), and nausea. After being on the medication for one week, the TB symptoms often go away, making it even more challenging for patients, as they often think that since their symptoms have gone away, why should they suffer the side effects of taking the medications. Many patients stop treatment in the middle of their treatment plans for this reason.
“Given the limited human resources in Tibet, I believe the supervision and support patients received was minimum. Many of us have been exploring different ways to improve treatment adherence,” says Xiaolin Wei.
How the E-health Innovation was Implemented
Directly Observed Treatment
This is the usual care in Tibet and the most widely implemented option in China and other countries, which is called directly observed treatment (DOT), meaning the patients go to a clinic to swallow the pills in front of a health worker in the morning, so they can see that the patient is getting their medication. It is intended to improve the treatment adherence, but there are logistical and financial challenges with this option, as it is not always possible, so most patients self-administer their medications – especially those living in remote areas.
Electronic Medication Monitors
The electronic monitors are small boxes that can code the medications for up to two months for patients. The box has a few functions; one function serves as an alert to the patients to take their medications when it is time. Another critical function with the monitors is that they have a chip on the cap of the box, that once the box is opened, sends a signal to the cloud that the box has been opened. The assumption is that the patient has now taken the medications out of the box and swallowed them. They have been set so that if a patient opens the box excessively, the monitor will just record it as being opened once. That signal is then shared through an app with the patient, the treatment support provider in the village, and the treatment supervisors in the TB centre. This helps ensure that the patients are taking their medications on time. If there is no signal that the box has been opened for three days, the village doctor will conduct video observed treatment (VOT) with the patient through the app.
Success of the study would not be possible without a consortium that combined the best cutting-edge knowledge in implementation science and local lived experience. The team, led by Prof. Xiaolin Wei, collaborated closely with a team led by Dr. Jun Hu and Pande Pasang, the then directors of the Shigatse Centre for Disease Control, China, and a team led by Prof. John Walley and Dr. Joseph Hicks from the University of Leeds, UK. Interventions were co-designed with patients, village doctors and TB doctors, to improve the efficiency and quality of TB care at each level. For example, village doctors, who are paramedics, who are responsible for managing TB patients in their villages, can access real-time information regarding patient adherence, and intervene remotely using DOT when needed.
Research Challenges of Remote Areas
The research team faced several challenges in their research – both physically and mentally – as their location was remote, and the altitude was so high. They had to go through intensive physical training before they went to Tibet to prepare for the challenges in altitude. Many of them who visited Shigatse experienced altitude sickness, despite their training and the fact that they were regulating their breathing and travelling with large containers of oxygen wherever they went. They also had to walk slowly once they reached their destination. Despite these challenges, the researchers say that it was extremely rewarding in working with patients and health providers in Tibet.
Research Impact on Public Health
The team used implementation science theory and frameworks to design the intervention so the e-health innovation would be embedded into routine care to improve the care quality. For example, they looked at the local context and barriers, and they conducted intensive training for village doctors. This had never happened before, but it is essential to improving patient care. The process evaluation, which will be published soon, will illustrate how the package of interventions improved quality of care, and how the different contextual factors influenced the results. The trial went beyond just applying the new technology, as that wouldn’t have worked on its own.
“While this technology has been used before, the trials before ours haven’t been successful. To my knowledge, this is the first trial in the world to show that the digital adherence technology works. This is going to be a big contribution towards the development of guidelines for treatment adherence for TB patients,” says Professor Wei. “The implication is not only for the electronic medical records, but that this will be a way to put research to practice and policy in a way that will really matter to these patients and their families.”
Gratitude
Within DLSPH, Zhitong Zhang, a DLSPH Research Associate, managed most of the day-to-day work of the trial, and spent considerable time in Tibet to ensure that the operation went smoothly. Victoria Haldane, a DLSPH PhD student graduating in June 2024 was actively engaged with several students to conduct the process evaluation.
The research team worked closely with their partners in the Shigatse Centre for Disease Control (CDC) from Tibet, China. They credit the Shigatse CDC for the work they do, and for how much the research team learned from them. The Shigatse CDC oversees all the public health activities in the prefecture. They then worked with the research team to train all of the TB medical professionals at the village, township, and county levels. Professor Wei also thanks the input from Dr. Joseph Hicks and Prof. John Walley from the University of Leeds, in the UK, both of whom he has been working with on implementation science to change health practice and policies over two decades. The project is supported by TB REACH, a special initiative of Stop TB Partnership.
Additionally, Professor Wei is grateful to Professors Ross Upshur, Elizabeth Rea and others who co-teach the course ‘Integrating Public Health and Clinical Care: The Case of TB’ (CHL5631) with him. Students will find more resources regarding TB control and how to improve public health systems in this course.
To learn more about Dr. Wei’s research in Tibet, please visit the Global Implementation Lab website.