Video-observed therapy (VOT) via smartphone improves adherence to tuberculosis (TB) therapy and is more cost-effective when compared with directly observed therapy (DOT), according to the first randomized controlled trial (RCT) of its kind.
Alistair Story, PhD, from the Institute of Health Informatics at the University College London (UCL) in London, England, and colleagues published their findings online February 21 in The Lancet.
The study, which is the first RCT to compare treatment adherence for DOT with VOT, found that more patients on VOT completed 80% or more scheduled treatment observations during the first 2 months than those on DOT.
Patients supported by VOT also sustained high levels of observed adherence throughout the treatment period, whereas observation rates of patients on DOT declined to less than half of scheduled doses after 6 months. VOT was also less expensive to deliver than DOT.
“Up until this trial, the evidence base for the impact of VOT in TB treatment has been weak,” senior author Andrew Hayward, MD, director of the UCL Collaborative Centre for Inclusion Health, told Medscape Medical News. “This trial provides the strongest evidence to date that technologies, sensitively integrated into care, can make a real difference to patients. Importantly this trial shows that technologies can improve the care of some of the most vulnerable and excluded people in our society.”
Story discussed the wider significance of the work. “TB is a disease that perfectly correlates with poverty and exclusion internationally. The global challenge to eliminate TB will ultimately be fought on this front. It’s here especially where innovative ways to reach and enable the most vulnerable patients to complete treatment without ‘catastrophic costs’ will be a game-changer. New drugs are necessary but not enough. We have to be able to deliver the treatment,” Story told Medscape Medical News.
“The reported results of this video-supported TB therapy trial is an important landmark towards improving the quality of evidence for a technology that is being scaled up in different settings worldwide,” Tereza Kasaeva, MD, PhD, director, Global TB Programme, World Health Organization (WHO), said in a news release.
VOT vs DOT
DOT has been the standard of care for tuberculosis since the early 1990s and is currently recommended by the WHO and the American Thoracic Society.
Poor adherence to TB treatment is one of the main barriers to effective disease control worldwide, Hayward told Medscape Medical News. “When patients do not take their medicine regularly, they are more likely to die, spread disease to others, and develop multidrug-resistant tuberculosis, which can become extremely hard to treat,” he said.
The major response to poor adherence internationally has been to recommend face-to-face DOT or even hospitalization to ensure adherence. “This is very inconvenient and can be costly both for patients and health services, whereas VOT allows patients to be observed using a smartphone recording so that their treatment doses can be confirmed without the need to travel,” Hayward pointed out.
Vulnerable Groups Likely to Benefit Most
Pilot studies have shown that VOT is an acceptable, flexible, cost-effective, and patient-friendly intervention. Two prior studies have compared treatment observation levels for DOT and synchronous or VOT (live video): one study in Australia showed that 87.9% of treatment events were observed for VOT and 68.9% for DOT, while another study in New York City reported 95% adherence for VOT and 91% for DOT. Until now, there have been no randomized comparative studies published for asynchronous (recorded) VOT or studies examining effectiveness in socially complex patients with histories of homelessness, mental health problems, imprisonment, and addiction.
Patients recruited in the multicenter, analyst-blinded, superiority RCT were drawn from 22 clinics across England, and were aged 16 years or older with active pulmonary or non-pulmonary TB. Overall, 58% of patients had a history of homelessness, imprisonment, drug use, alcohol problems, or mental health problems.
Homeless people are at increased risk for TB and have worse treatment outcomes, including mortality, than the general public. According to the WHO, in many industrialized countries, TB rates among the homeless can be up to 20 times higher than the general population.
“These vulnerable groups comprise around 20% of the TB patients in the UK. These patients are much more likely to transmit infection, develop drug-resistant disease, fail to take treatment, become lost to follow-up, and die from their disease. TB is a disease that perfectly correlates with poverty and exclusion internationally,” explained Story.
A total of 226 patients were randomly assigned to either VOT (daily remote observation using a smartphone app; 112 patients) or DOT (observations by a healthcare or lay worker three to five times per week in the home, community, or clinic settings with remaining doses self-administered; 114 patients). Patients in the VOT group were trained to record and send videos of every dose taken 7 days per week. Trained treatment observers viewed these videos through a password-protected website. Patients were provided with a smartphone and a data plan via University College London Hospital as well as free domestic calls and text messages.
The primary endpoint was completion of 80% or more scheduled treatment observations during the first 2 months following enrollment. The intent-to-treat analysis showed 70% (78/112) of patients on VOT met the primary endpoint compared with 31% (35/114) on DOT (adjusted odds ratio [OR], 5.48; 95% confidence interval [CI], 3.10 – 9.68; P < .0001). A big part of this effect was because many patients did not engage in DOT. Even among those patients who did engage with DOT, observation rates were significantly lower than in the VOT group (63% vs 77%) (adjusted OR, 2.52; 95% CI, 1.17 – 5.54; P = .017).
The authors write that VOT, as used in this study, has a wide range of components beyond just convenience. “The intervention included personal support, where patients met the VOT observer for training, and received regular personalized messages as reminders, confirmation of receipt of video clips, or to follow up when clips were not received.”
Stomach pain, nausea, and vomiting were the most common adverse events reported (14% on VOT and 8% on DOT). Patients reported adverse events and were referred for management of these events if necessary. The greater number of events in the VOT group compared to the DOT group was likely due to the systematic reporting, although it could also have resulted from better compliance, the authors note.
Although the WHO recommends DOT, their recent guidance now recommends VOT as a suitable alternative if appropriate technological infrastructure is in place. “We hope that this trial will allow them to recommend VOT as a preferable alternative to DOT as it is cheaper, more effective and more acceptable to patients,” remarked Hayward.
When asked how realistic it would be for some vulnerable groups to own a fully charged phone with a paid-up data plan and to continue supplying recordings to treatment observers, Hayward pointed out that, “In this study we provided mobiles and data plans, which are cheap compared to the cost of meeting with patients in person. We found that those on VOT had high levels of observation throughout the 6 months of their treatment.”
“Outside of the trial we have found very similar results with patients maintaining high levels of observation throughout treatment,” he continued. “For patients with multidrug-resistant tuberculosis we have used VOT to complete treatment courses of between 12 and 24 months. Outside the trial patients often use their own phones, but if they don’t have them then we provide them.”
Now, the challenge is to translate this success into high-burden settings, added Story. “We hope our results will enable TB control programs globally to incorporate VOT alongside other measures to support patients.”
The study was funded by the National Institute of Health Research Programme Grants for Applied Research scheme (RP-PG-0407-10340). Hayward has disclosed no relevant financial relationships. Story is clinical lead for the University College London Hospitals’ Find&Treat service, which manages video-observed therapy.
Lancet. Published online February 21, 2019. Full text