Digital health for treatment adherence in people with tuberculosis: a systematic review

Saúde digital para a adesão ao tratamento da pessoa com tuberculose: uma revisão sistemática

Salud digital para la adherencia al tratamiento en personas con tuberculosis: una revisión sistemática

Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.

Tuberculosis (TB) is a serious global public health problem, affecting vulnerable countries and groups, with an estimated 1/3 of the world’s population infected by Mycobacterium tuberculosis. To combat the disease, the World Health Organization (WHO) launched the End TB Strategy, based on three pillars: person-centered care; integrated and robust health systems covered by social protection programs; and research and innovation.^1-2

According to the WHO report released in 2021, in Brazil, only 71% of people diagnosed with TB complete treatment, a rate below the goal established by the WHO of at least 85%³. Several factors can influence the decision-making of people with TB, such as socioeconomic aspects, access to health services, social protection actions and lack of information or knowledge about the disease⁴.

TB treatment typically requires daily supervision and use of a combination of medications, which can cause adverse reactions and negatively affect the treatment experience. This can lead to non-adherence or abandonment of treatment.^4-5 Therefore, care focused on sick individuals’ well-being, as recommended by person-centered care, is essential for supporting and ensuring the completion of TB treatment⁴.

The introduction of Directly Observed Treatment Short Course (DOTS) substantially increased cure rates and reduced dropouts, being considered a blueprint strategy.^4-6 However, a study developed in 2020 estimates that physical distancing measures contribute to an increase in 6.3 million additional cases of TB between the years 2020 and 2025, in addition to 1.4 million deaths from TB due to the reduction in coverage of TB DOTS strategy⁷.

Even before the COVID-19 pandemic, Video Directly Observed Treatment (VDOT) was already encouraged as an alternative to traditional DOTS, since digital resources are viable and have long reach, minimizing barriers cultural, organizational, economic and geographic issues faced by people with TB.^8-9

The WHO supports a configuration of the strategy based on digital health, person-centered care and Unique Therapeutic Projects. However, this recommendation still needs to be thoroughly assessed against the strengths of evidence available for advanced DOTS in digital health. Although a systematic review has been observed in the literature, many other studies may have been produced, and a new analysis with more evidence is needed.^10-11 Considering the above, the study aims to describe the use of digital health technologies to assist with adherence to TB treatment through a systematic literature review with a rapid review approach.

This is a systematic literature review with a rapid review approach registered in PROSPERO under number CRD42022364841. The review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions methodological items, in addition to using the Guidance from the Cochrane Rapid Reviews Methods Group of 2020. The presentation of results was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.^12-13

Studies without language restrictions were included, published between January 1, 2020 and September 15, 2022. The time frame was carried out following the rapid review methodology developed by Cochrane, in cases where there is a need for a rapid synthesis of evidence. This approach simplifies systematic review components, such as limiting search time. Furthermore, the time frame was carried out to identify which technologies are the most recent and which remain up to date.¹³

Quantitative, experimental, quasi-experimental studies and clinical trials were included. The study population was made up of people aged 18 years or over, with all types of TB (pulmonary, extrapulmonary TB, latent TB, active TB, sensitive TB or extrapulmonary TB), as proven by the study analyzed. Technologies included were smartphone apps, synchronous and/or asynchronous videos, phone reminders, ingestible sensors, SMS (Short Message Service) reminders, and other digital health interventions that aim to improve medication adherence and TB treatment outcomes.

The primary outcome was medication adherence, i.e., treatment completion, adherence rate and missed doses. Adherence can be measured through the patient’s medical record and/or self-report on the device, through asynchronous or synchronous video, responding to phone calls and SMS text messages. There is no “gold standard” in the literature to measure adherence behavior, as there are a variety of strategies used.¹⁴

Studies were included, within the eligibility aspects, to address the following question: what is the evidence of use of telemedicine in adherence to TB treatment? The question was formulated following the PIO acronym structure (P = Population, I = Intervention or exposure, O = Outcome) (Chart 1).¹⁵

Chart 1
Components of research question according to the acronym “PIO” (P = Population, I = Intervention or exposure, O = Outcome)

The following databases were used for the research: US National Library of Medicine (PubMed); Virtual Health Library (VHL); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Trial; Scientific Electronic Library Online (SciELO); Scopus; and Embase.

The search strategies were developed in collaboration with a specialized librarian, using the Boolean operators AND and OR in combination with the Medical Subject Headings (MeSH), Health Sciences Descriptors (DeCS) and Emtree Terms descriptors, in accordance with each database. The general strategy included the descriptors “Tuberculosis” AND “Telemedicine” AND “Treatment Adherence”, combined with keywords.

Throughout the text, the term used was “digital health”, but in the search term, it was replaced by the synonym “telemedicine”, as it is a descriptor considered more appropriate to cover the broad search in databases.¹² It is important to highlight that access to the electronic databases was carried out through the content services (Proxy) of the Universidade de São Paulo (USP) - Campus Ribeirão Preto via USP’s VPN (Virtual Private Network).

Retrieved records were imported into the Rayyan^® software,16 and duplicate records were eliminated. The remaining records were grouped according to titles and abstracts to identify potentially eligible studies. During screening, 24 studies could not be read in full, as they were absent from online platforms, only having their abstracts. E-mails were sent to the authors requesting full access to the article, but there was no response until the completion of this study.

Records’ titles and abstracts were assessed by two independent reviewers (AFT, RVSS) and a third reviewer (JSTA) who arbitrated any disagreements. Potentially eligible records were read in full by two independent reviewers (AFT, RVSS), again, with third reviewer (JSTA) refereeing. The study selection process was outlined according to the PRISMA diagram.¹²

Data were collected independently by two reviewers (AFT, RVSS), and all disagreements were discussed by the team until a consensus was reached. A standardized extraction form based on the Cochrane Consumer and Communication Review Group Data Extraction Template (2015) was used. The information extracted included: 1) author; 2) year of publication; 3) country of publication; 4) study design; 5) study objective; 6) sample characteristics; and 7) results.

The Mixed Methods Appraisal Tool (MMAT) assesses according to the percentage of development of each domain, using the descriptor “*”, which is equivalent to 25%, with the maximum quality score with 100% development expressed by the descriptor “****”. Based on the results found, study quality was classified as “high quality” evidence (100% = “****”), “moderate quality” (75% = “***”); and “low quality” (< 50% = “**”; “*”).¹⁷

According to Resolutions 466/2012 and 510/2016, “all research involving human beings must be assessed by a Research Ethics Committee (REC)”, even those that use secondary data, through the CEP-CONEP System. However, if the research uses only public domain data without identifying the participants or if it is a bibliographic review without the involvement of human beings, it does not need to be approved by REC-CONEP. Therefore, as this study uses public domain data, it was not necessary to submit it for REC assessment.

In literature, a total of 300 articles were found in the searched databases, of which 157 articles were excluded after selection, as they were duplicates, based on the detection of Rayyan^®.¹⁶ After exclusion, 149 articles remained for analysis. After reading titles, abstracts and reading in full, only 9 eligible articles were identified (Figure 1).

Figure 1
PRISMA 2020¹² flow diagram for new systematic reviews that included only database and record searches

As shown in Chart 2, of the studies included, three^18-20 studies (33.3%) were carried out is America (North and South America), five,^21-25 (55.5%) in Asia, and one,²⁶ (11.1%) in Africa. The countries where the studies were carried out were: one¹⁷ (11.1%) in Peru; two^21.24 (22.2%) in China; one²² (11.1%) in Saudi Arabia; two^19-20 (22.2%) in the United States of America; one²⁶ (11.1%) in Ethiopia; and two^23-25(22.2%) in India. Regarding design, five^{20-22, 25.26} studies (55.5%) were defined as clinical trials; two^23-24 studies (22.2%) were quasi-experimental clinical trials; one¹⁸ studies (11.1%) were descriptive; and one¹⁹ study (11.1%) was a prospective cohort. The publication period of each study covered 2020 to 2022, with two^24-25 studies (22.2%) published in 2020, four^20.22-23.26 studies (44.4%) published in 2021 and three^18-19.21 studies (33.3%) published in 2021.

Six^19-23.26studies (66.6%) used text messages (applications) and SMS as strategies; and three^19-21studies (33.3%) presented the name of the technological application used in the study, namely WeChat. and Emocha Mobile Health.. Six^18-21,24,25studies (66.6%) used videos ranging between synchronous and asynchronous; two^22.26studies (22.2%) used only SMS; and one²³ studies (11.1%) used voice calls. The majority^20-26 of study participants were men (77.7%) aged 18 or over (77.7%).

The sample size of studies^18,25varied between 10 and 405 participants with a confirmed diagnosis of TB. Samples were collected differently across studies, with participants divided into control and intervention groups. However, there were also studies in which participants, as in previous studies, were divided into two groups, control and intervention, with the difference that the sample of participants in the control group was collected from retrospective data. In both situations, the intervention concerned the use of digital health. Video and SMS technologies gained prominence in studies, being the most used strategies both together and separately.

Among the studies, the samples were diverse, as were the approaches and sample characteristics. Participants were found who received TB treatment for the first time or who had previously received treatment (retreatments). People with TB were classified as having pulmonary TB, extrapulmonary TB, or both.

Regarding objectives, five^18-20,23,26 studies (55.5%) verified adherence to treatment by controlling missed doses; three^22,24,25studies (33.3%) analyzed adherence to treatment through completion of drug treatment (cure); and one²⁰ article (11.1%) demonstrated that, even with a higher percentage of doses not ingested in the technological intervention, there was an increase in treatment completion rates.

The studies had similar objectives related to the following categories: assess and compare adherence to treatment using digital health compared to conventional treatment in people diagnosed with TB; describe the characteristics of VDOT implementation; and assess the cost-benefit of applying technology in the treatment of people with TB.

Chart 2
Characteristics of studies included in the review according to author, year, country, study design, study objective, population and results (2020 – 2022)

The quality and evidence of studies were assessed using MMAT¹⁷, as described in Table 1. Among the randomized controlled studies, four^21,22,24-25were suspected of high quality, except for one²⁶ study, which did not report blinding sample allocation. Among the non-randomized quantitative studies, two^23-24 studies were considered to be of high quality, while one²⁰ studies were considered to be of moderate quality. Two^20,24 studies have shown inconsistencies in sample selection (selection bias), inconsistencies in the measurements used (measurement bias) and confounding factors related to the sample conduct. The quantitative descriptive studies^18-19 were classified as suspect of moderate quality, due to weaknesses in sampling strategy that was not relevant to address the quantitative research question as well as the sample size that was not representative of the population.

Table 1
Assessment of quality of evidence of included studies according to MMAT 20202022

Scores ranging from 25% (*)-one criteria met- to 100% (****)-all criteria met.

This study aimed to describe the use of digital health technologies to assist with adherence to TB treatment. It was observed that technologies, such as reminders via SMS, synchronous and asynchronous videos, and voice calls, are resources that can effectively contribute to TB treatment, increasing medication adherence rates and, consequently, improving disease cure rates.

In the systematic review, the technological strategies used in the interventions included automatic text messages to remind users of appointments and medication times as well as motivating phrases. Conversation channels were also used to answer questions about the side effects of medications, voice calls with healthcare professionals and asynchronous videos to observe medication taking. These strategies are aligned with what the literature demonstrates about the use of technologies.^28-29

Medication self-management is a fear of many health professionals, who are resistant to adopting technologies within health services. However, the results of Perry’s study²⁰ contradict these concerns, since, even with a higher incidence of missed doses using the combined SMS and video strategy, cure rates in the intervention group were better in relation to treatment completion. Likewise, the study by Bachina¹⁹ showed different results, with greater medication adherence in the technological intervention group that used the same strategy. This indicates that the same technology can present different results depending on the context.

Technologies contain resources that can be considered a strategic approach to overcome nonadherence to TB treatment, which is one of the main predictors of resistant forms of the disease and treatment relapse. These factors make the process of healing and containing the disease difficult, damaging people’s quality of life.³¹ However, the use of technological resources has shown significant results in the persistence of drug treatment, with all articles demonstrating that adherence was equal or better than in the control group that used DOT, as in Bao’s article²¹, in which the DOT group has a tendency to gradually stop monitoring until abandoning it completely.

Several factors can influence the decision-making of people with TB, such as socioeconomic factors, access to health services, social protection actions and lack of information or knowledge about the disease.. In this sense, technology can also be a resource to assist in the decision-making process of a person diagnosed with TB to adhere to treatment. It was observed that, whenever there was an option to choose between the approach with digital technology or traditional DOT, the preference was for the technological approach. Furthermore, an important factor in choosing VDOT was the optimization of time, avoiding waiting for care and/or transportation when traveling to the reference health unit to receive DOTS.

The technologies used in the studies were mainly synchronous VDOT, with only one study, which used asynchronous videos and SMS. VDOT has been shown to be a viable approach to supporting TB medication adherence, even in situations where the Internet is not regularly available.^28-29 This approach allows for person-centered care as well as safety, as it allows visualization of medication intake through recordings, allowing the professional to guide the correct form of administration, as recommended by DOT, but remotely.^28-29

Although strategies that use only SMS do not demonstrate in the literature that they increase adherence compared to traditional treatment, it is a strategy that has important functions, such as scheduling appointments, remembering medication times and appointments already scheduled as well as signaling problems, if they arise, from adverse effects to delays.^28-29Another advantage is its simplicity, low cost and popularity, as it is available on all cell phones.^28-29

In the study by Guo et al. (2020),²⁵ the strategy used was SMS, and graphics and images were sent in these messages, in order to also include illiterate people. Inclusion strategies are extremely important, given that TB is a disease that mostly affects people in socially vulnerable situations, and is associated with low education.^28-29

Three^18,23,26studies (33.3%) included in the review originate from countries considered emerging and developing, which demonstrates an interest on the part of low-income countries in implementing digital health as a strategy to overcome access barriers to health services, improving quality of care provision and advancing improvements in health indicators, as recommended by the End TB Strategy.^1,28

It should be noted that, among the studies found in the literature review, developed countries, such as the United States of America and China, also demonstrated that they seek to understand the adoption of digital technology in TB treatment, thus aiming to better serve the population with TB.^1,29

Some studies^24-25have shown that the use of digital technologies significantly reduced transportation costs for users, since in these countries the health service does not offer free transportation or tickets.³⁰ In a scenario of global economic crisis, further aggravated by the COVID-19 pandemic, where social inequalities have become even more exacerbated, the use of digital resources to monitor cases becomes essential. Therefore, the use of digital technologies for the sustainability of DOT is considered a valid, safe and effective strategy, bringing several benefits to both users and the health service, highlighting cost reduction and time optimization for professionals and people with TB.³⁰

It is noteworthy that only three studies described in detail which technologies were being applied, using Emocha Mobile Health^®19-20 and WeChat.²¹. The technology used in each study was little discussed, which raises an important gap in knowledge, as better exploring available technologies and relying on examples and experience reports can help managers define strategies and devices to ensure quality of care and adherence to treatment.

The plurality of approaches that technology allows us to explore is wide, and studies show that, in general, technologies are a way of bringing users and health professionals closer together and considering people with TB, considering their autonomy, believing that they want to be treated. This involves working with mutual responsibility and making them the protagonist of their treatment.^1,2,28-29

Despite the great potential for adherence to medications and achieving a cure outcome, scientific evidence is still limited, and there is a need for further investigations as well as more assertive criteria. Furthermore, it is important to define the names of the applications used and assess the cost of implementing the technology. It is also noteworthy that the grouping of heterogeneous studies did not allow for a qualitative synthesis.

Digital health is not intended to replace conventional treatment, and it is crucial that the strategy used in treatment is centered on people with TB, respecting their needs and, above all, their preferences.^28-29 The use of digital health among people diagnosed with TB can be a great complementary strategy to health services, with the aim of increasing adherence to treatment and impacting the disease’s epidemiological data in the country.^28-29

CONCLUSION

The use of health technologies as well as conventional treatment appears to be complementary and fundamental for TB control, based on the evidence found in the study countries. It is important to give greater visibility and encouragement to social issues related to understanding the particularities of each person living with the disease, aiming to contemplate and complete treatment.

The systematic review highlighted the relevance of using digital health for TB treatment and its contribution to improving adherence. These results are aligned with the Sustainable Development Goals of the 2030 agenda, especially goal 3.3, which seeks to promote person-centered care rather than just controlling them.

Digital health involves strengthening the bond, the use of an intercultural language, co-responsibility and individuals’ leading role in their health-disease process. Digital health does not consist of robotization and mechanization of care, but rather the complementation of the essential basis of care, which is based on human relationships.