Background
Although randomised controlled trial (RCT) data indicate that it is possible to cure up to 95% of individuals with drug-sensitive tuberculosis (DS TB) using a standard 6-month drug regimen, anti-tuberculosis treatment (ATT) completion by 12 months in the UK is lower: only 82% of people notified with DS TB in 2019 completed treatment (treatment completion at 12 months is the measure used by national surveillance bodies – it excludes people with TB that involves sites where longer treatment is indicated, such as with central nervous system disease). Of those who did not complete treatment by 12 months (i.e. the remaining 18%), 5.2% were still on treatment, 4.2% had died, 3.9% were ‘not evaluated’ (a group that includes people where the outcome is unknown), 3.4% were lost to follow-up, and 1.3% stopped treatment. The figures for multidrug-resistant (MDR) TB are lower again, with only 62% of 50 individuals completing treatment by 24 months (based on 2018 notifications). Here, 12% were still on treatment at 24 months, 10% had been lost to follow-up, and 8% had died.1
Treatment regimen durations for TB are long in comparison to those for many other common bacterial infections, which are often curable after a few days or weeks of treatment with a single antimicrobial agent. Until recently, the standard treatment regimen for DS TB was 6 months (a 2-month ‘intensive phase’ of four antibiotics, followed by a 4-month ‘continuation phase’ of two antibiotics), and for MDR TB up to 24 months.2 Recent advances have resulted in the first ever successful RCT of a 4-month regimen that is non-inferior to the standard four drug 6-month regimen for DS TB in adults.3 The option to shorten the standard 6-month regimen to 4 months for DS TB in children and adolescents has also been recommended.4 Both are game-changing breakthroughs and add to advances that have reduced the time required for effective treatment of rifampicin-resistant TB to 6–9 months.5
Lengthy treatment regimens are a known cause of issues with adherence, which in turn is associated with failure to achieve cure for TB disease.6 Shorter treatment regimens, therefore, may result in improved adherence, although data in this area are minimal.7 Encouraging as this is, other regimen characteristics may also be important, such as the daily pill burden.
As well as the greater risk of a poor treatment outcome, non-adherence is also thought to contribute to drug-resistant (DR), which has implications for individuals on treatment as well as for public health and wider efforts at TB elimination.6
Most TB disease in the UK is seen in people who were born in TB endemic countries or have social connections with these locations through family, friends or travel.1 This is unlike many other parts of the world and introduces a further degree of social complexity when managing TB in the UK.
The chance of not completing treatment for TB disease is increased in men, younger and older adults compared to those in their 30s and 40s, people with pulmonary TB, and where someone is treatment centre is located.1 While these are mostly not directly modifiable, UK TB services focus on social complexity as potentially influencing adherence and treatment completion. People starting treatment for TB are therefore risk assessed using a standard checklist which asks about problem alcohol and drug use, mental health issues, history of imprisonment, immigration status, and homelessness.8
Rationale for research
The level of concern about non-adherence in people on treatment for TB has resulted in substantial global research and systems investment in interventions to improve adherence. Although both digital and other approaches have shown promise at increasing adherence, their impact on improving treatment outcomes is more complicated.9,10 Using digital and other approaches to enhance engagement between patients and healthcare providers is thought to be important but has proven to be complex to deliver within healthcare systems.11
In the UK, little is known about the burden of non-adherence, the types of non-adherence displayed (e.g. is early treatment discontinuation or sporadic missed doses more common?),6 or the causes of non-adherence as it unfolds across the treatment course. Limited research has been undertaken in this setting to understand the behavioural, social and cultural barriers to, and facilitators of, adherence to treatment for TB; or to develop and evaluate interventions to address poor adherence.12,13
At the time this study was conceived, the best way to support ATT adherence was unclear. Directly observed therapy (DOT) had been the recommended approach since the late 1990s,14 but more recent studies, including some in low TB incidence settings, had found mixed results for the effectiveness of DOT compared to self-administered therapy in improving ATT adherence.15–17 Specifically, the most recent Cochrane review by Karumbi and Garner demonstrated that DOT does not reduce the risk of not achieving a treatment cure versus self‐administered treatment once patients in the latter group have more than monthly contact with their healthcare providers.10 DOT is also resource-intensive and has been criticised for being overly rigid and paternalistic, sometimes creating a negative experience for patients.18–21
More recently, digital adherence technologies (DATs) have been recommended by World Health Organization (WHO): these include video-observed therapy (VOT – a remote version of DOT administered via a smartphone or other device),22 short message service (SMS)-based reminders and a range of ‘medication monitoring boxes’ (MMBs), which record every time the box is opened and relay this information to the health service (usually via SMS or the internet). These data can then be used as a proxy for the individual’s adherence. DATs are potentially cheaper, more acceptable, less burdensome than DOT or other standard care measures, and can provide healthcare professionals (HCPs) with regular, up-to-date information on how medication has been taken. However, they rely primarily on giving patients reminders to take their medication, and usually do little to address the psychosocial, structural, cultural, and health-systems factors that may influence adherence.23 The importance of considering these factors has been highlighted in recent guidance from the International Union Against TB and Lung Disease and by the WHO, which in 2024 published international guidance for enhancing social protection for people with TB.24,25 In the UK, the National Institute for Health and Care Excellence (NICE) has noted the lack of robust research into the wider determinants of non-adherence.2 Recent evidence also suggests that a person-centred approach, which tailors support to the individual’s needs, may be effective in improving adherence.16
Expressing this another way, DOT, VOT and other DATs essentially target the ‘practicalities’ (i.e. capability and resources) of adherence-related behaviour. However, patients’ perceptions of the necessity of treatment as well as their concerns about illness and treatment need to be addressed within a support package, not least to assist the individual to make informed choices about their own care.26,27 We therefore identified a need for an evidence-based, person-centred package of interventions to improve adherence to ATT, deliverable within the NHS, that accounted for the shortcomings of existing support measures such as DOT and DATs.
Aim and objectives
Aim
To develop, pilot, and evaluate process and interim outcomes for an effective manualised intervention package that improves the likelihood of treatment completion among NHS patients with TB who are at risk of poor adherence.
Objectives
- Synthesise current knowledge on (a) determinants of adherence to treatment for TB, and (b) interventions that can support adherence, with particular emphasis on social and cultural barriers.
- Apply a conceptual framework of adherence endorsed by NICE to elucidate and address the personal, socio-cultural, and health systems context, mechanisms, and pathways of poor adherence among NHS patients with TB.
- Develop a manualised intervention package with multiple components that can (a) identify NHS patients most at risk of non-adherence, (b) identify the salient modifiable barriers to adherence; and (c) tailor support mechanisms to meet individual needs by matching appropriate interventions to specific barriers, as recommended by NICE.
- Pilot the intervention package in people at risk of poor adherence to define how the components work in combination and separately.
- Evaluate the process of implementation of this intervention through (a) describing the challenges and facilitators in delivering the package as intended (fidelity, reach) and (b) assessing the impact of the intervention through evaluation of adherence indicators.
- Use the findings of the pilot to assess the costs of delivering the manualised intervention in an NHS setting, and to guide development of a proposal for a full RCT.