A Mixed-Method Study of Medication-Related Burden Among Multi-Drug Resistant Tuberculosis Patients in West Java, Indonesia

Introduction

Tuberculosis (TB) remains a global health problem, especially in lower- and middle-income countries. In 2023, Indonesia had the second-highest prevalence of TB in the world.¹ This infectious disease requires patients to take several medicines over a long period. Moreover, in multidrug-resistant (MDR) conditions, the patient must take multiple medications for an even longer duration of treatment. The treatment duration should be 9–11 months for a short-term regimen and usually 18–20 months for a long-term regimen (LTR).²

The chronic condition is quite challenging due to the need for self-management regarding the treatment and the illness itself. Although the use of medicine is the main intervention in MDR-TB treatment, it helps in relieving the symptoms; prolonged medication often comes with several consequences that require extra time, effort, and finances for patients.^3–5 These challenges can be unbearable for several patients and are perceived as a burden. The medication-related burden may affect how patients perceive the need for medicine, regardless of other factors such as background and clinical condition, which are related to day-to-day difficulties.^4,6 Medication-related burden is a complex phenomenon that involves different components and elements interacting with each other.⁷ It could lead to treatment non-adherence and affect the quality of life.⁶ Meanwhile, adherence to TB treatment is critical in achieving success, controlling disease spread, and minimizing the aggravation of drug resistance.⁸

Since medication-related burdens threaten treatment success and well-being, it is essential to evaluate the perception of patients regarding their own experiences and treatment outcomes.⁴ This study aimed to deeply understand the medication-related burden in MDR-TB patients by combining qualitative and quantitative methods (mixed methods). The quantitative section used a validated questionnaire to measure medication-related burden as the impact of long-term treatment. The qualitative section (in-depth interviews) captured a broader and deeper narrative of medication-related burdens, which cannot be fully described with a quantitative study.^9,10 This research is expected to improve MDR-TB patient care and help patients connect treatment routines with the expectations of their daily life.¹¹

Materials and Methods

Study Setting and Population

Participants were recruited from the MDR-TB clinic of Hasan Sadikin General Hospital, a tertiary referral hospital in West Java, Indonesia. All participants or their guardians gave written informed consent to participate in this research before data collection process (either for interview or filling questionnaire, or both). Patients were attending the hospital for monthly follow-ups between February and March 2021. The following were the inclusion criteria for qualitative and quantitative study participants: (1) Patients diagnosed with MDR-TB, (2) aged above 18 years old, (3) completed the first months of therapy, and (4) had no treatment interruptions (missed monthly-scheduled follow-ups) in the current regimen. Seventy-four patients participated in this study. Among them, 71 completed the questionnaire for the quantitative study. A one-month total sampling technique was used for quantitative data collection. For the qualitative section, data reached saturation after 36 patients were interviewed to explore the burden related to long-term medication use. Twenty-seven patients were interviewed privately, while others were accompanied by their caregivers due to communication difficulties caused by their health conditions.

Qualitative Data Collection and Analysis

Prior to participant recruitment, a key informant interview was conducted with an internist who is an expert in TB care, to gather preliminary information about the medication-related burden in MDR-TB patients. The in-depth interview guide was developed from a previous study on issues regarding long-term medicines by Krska et al, 2013^12,13 and adjusted to the local context based on the information from the key informant.

Semi-structured in-depth interviews were then conducted with patients and/or their caregivers to understand their experiences, beliefs, and perceptions of the burden associated with MDR-TB treatment and how they deal with it. The interviews were conducted by a research member who was trained in qualitative methods. Participants were recruited until data saturation was reached, with a total of 36 participants. The interviews lasted for 15–20 minutes in Bahasa Indonesia, and the audio was digitally recorded. The recordings were transcribed verbatim, and the transcript data were managed using NVivo12 software for thematic analysis.

Quantitative Data Collection and Analysis

The medication-related burden was quantitatively measured using the Living with Medicine Questionnaire version 3 (LMQ-3), developed by Katusiime et al, 2018.¹⁴ The LMQ-3 consists of 41 items and covers eight domains (1) interference with day-to-day life (6 items); (2) patient-doctor relationships (5 items); (3) perceived effectiveness (6 items); (4) general concern about medicine (7 items); (5) side effect burden (4 items); (6) practical difficulties (7 items); (7) cost-related burden (3 items); (8) autonomy over medicine (3 items). The LMQ-3 scores were transformed from ordinal data to numeric data (person measure/logit) using Winsteps software and classified into lower and higher burdens based on the mean and standard deviation values. Higher person measure reflected higher medication-related burden. Sociodemographic and clinical characteristics were also collected from patient forms and medical records. Patients’ characteristics data were presented as n (%). The association between patients’ characteristics and medication-related burden was analysed using chi-square for bivariate analysis and binary logistic regression for multivariate analysis, with SPSS v.25 (α = 0.05, CI 95%).

Results

Seventy-one patients agreed to fill out the questionnaire, and 36 agreed to be the informant of the interview.

Qualitative Result

Four themes of medication-related burdens have been identified from in-depth interviews with 36 participants, namely: personal beliefs, regimen burdens, socioeconomic burdens, and healthcare burdens (Table 1).

Table 1 Result of Thematic Analysis in Medication-Related Burden Among MDR-TB Patients

Regimen Burden

MDR-TB treatment leads to several regimen-related concerns. In terms of physical characteristics, the taste of the pill was very bitter, the size was too big, and the odor was very strong. Moreover, patients had to take a large number of pills with all these distinct characteristics every day, for a long time. However, the main concern about the regimen is mainly side effects. The inevitable consequence of therapy interrupts day-to-day life. Some patients perceived the symptoms as terrible and not worth the benefit or even worse than the illness itself. The worst side effect period was during the first three months of therapy.

The side effect outweighs the benefit. That is the truth (a female patient)

I was so sad. Medicine made her get worse instead of getting better (a male family member of the patient)

Manifestation of side effects varied from mild to debilitating effects. Nausea, vomiting, and lethargy were the most complained about side effects that interrupted daily activities. Other side effects included loss of appetite, abdominal pain, dizziness, tingling, and numbness in limbs, myalgia, arthralgia, dry, and scaly skin, hearing impairment, blurred vision, palpitations, restlessness, irritability, and hallucinations. Some patients claimed they lost consciousness for several hours after taking the medicine.

This medication is very terrible. He (pointing to someone) said that it feels like more than taking the drugs (psychotropics). That is true, just like being drunk, slurring. (a male patient)

I cried and said to the nurse, ‘I cannot do this. How come a person has to be injected every day with this kind of side effect? I’m dying, I’m going crazy’. (a female patient)

The worry about worse consequences made the patient seek alternative therapy.

One day, I looked for alternative medicine. The therapist said, ‘You better not take medicine anymore because we have another treatment’. We (my husband and I) decided to stop the medicine. We thought we had already got over it. But when I arrived home at night, I had a cough again. My husband was worried and said, ‘You’d better continue to take the medicine again’ (a female patient)

Personal Beliefs

Bad experiences with taking medicine resulted in negative perceptions of their medication. These perceptions in the patient’s mind guided their thoughts, feelings, or behavior. For example, when the time to take medicine was approaching, the patient felt the side effects symptoms, such as nausea, or nervousness. Other patients experienced similar sensations just by looking at something that reminded them of taking medicine.

I just told my son, ‘Do you want to take your medicine here right now?’ And then he suddenly vomited. (father of a patient)

Regardless of their personal experiences, some patients believed that medicine is a chemical that may cause long-term effects and dependence. This belief results in a hesitancy to continue therapy.

A worry does exist. If we take the medication and have certain diseases in our body, such as high uric acid and stomach disorders, it will come up. Our heart, kidney, and stomach will also be triggered. Those are what I am worrying about. (a male patient)

Two patients perceived the medicine to have low effectiveness. This perception of low effectiveness made the patients feel unsatisfied with the therapy.

Socioeconomic Burden

MDR-TB patients should have a daily visit to the community health center for Directly Observed Therapy and a monthly visit to a tertiary referral hospital for clinical follow-up. This induced three social and economic-related issues. First, although the direct medical costs are covered by health insurance, the indirect costs, such as travel expenses, may become a barrier for them in accessing healthcare facilities.

Last night, I had no money to afford the travel cost to get here. Yesterday, I tried to look for a loan, but no one could help me. This morning, I asked somebody else about it, and praise God, finally, I received a loan. (a male patient)

In the social context, side effects also cause a loss of productivity and a lack of socializing.

In the beginning (of therapy), (my husband) usually sleeps after taking medicine, gets some rest, and cannot do regular activities (a woman family member of the patient)

I rarely meet up with my friends because it is difficult to find the right time. I feel unwell after taking medicine. (a female patient)

Healthcare Burden

There were two concerns of patients related to healthcare: the distance to seek healthcare and daily visits to community health centers or hospitals. In addition, in terms of service, patients expected to have the same doctor for their monthly follow-ups. A patient also said that he was upset with the community health center service because he found it difficult to get spare medicine when the community health center was closed.

Last day, I was very upset with the healthcare service in the community health center. On that day, the pill was not taken properly due to vomiting, so I went to the community health center which was closed, and asked, the security officer whether I could get any spare medicine. The security officer said, ‘Today is a day off; it would be better to come here again tomorrow.’ Then, I answered, ‘No! The dose must not be skipped. Missing one dose will make the therapy restart. The pills are supposed to be ready.’ (a male family member of the patient)

Each burden category was an inseparable part of the other burdens. One perceived barrier may induce or exacerbate other problems. Figure 1 represents the interaction among the types of burdens in this study.

Figure 1 TB medication-related burdens. Abbreviation: TB, Tuberculosis. Notes: The arrow (→) means one burden worsens another burden.

Quantitative Result

Seventy-one patients were included in this study. They were mainly male, at a productive age (below 40 years old), had income below the regional minimum wage, had lower educational backgrounds, and had family members as their caregivers. More than half of the patients received short-term regimens with various durations of treatment. Nine out of 10 patients experienced at least one side effect. The details of patients’ characteristics can be seen in Table 2.

Table 2 Sociodemographic and Clinical Characteristics of Patients

Based on LMQ-3 response result, the mean value for person measure is −0.28 ± 0.52 (see Table 3). Among 71 patients, 58 (81.7%) had person measure above −0.8, which were considered to have a higher medication-related burden (Table 4). This study observed associations between higher levels of burden and younger age: 18–30 years (OR 7.303, 95% CI: 1.045–51.034) and 31–40 years (OR 6.53, 95% CI: 1.077–39.607). The study also found an association between higher levels of burden and experienced side effects (OR 46.602, 95% CI: 2.825–768.894) as shown in Table 5.

Table 3 Descriptive Statistics of LMQ-3 Result Person Measure

Table 4 Result of Bivariate Analysis Between Level of Medication-Related Burden with Sociodemographic and Clinical Characteristics Using Chi Square

Table 5 Result of Multivariate Analysis Between Level of Medication-Related Burden and Sociodemographic and Clinical Characteristics Using Binary Logistic Regression

Among the 8 domains in LMQ-3, domain 2 (patient-doctor relationships) had the lowest mean of person measure (see Table 3; Figure 2). This implies that the relationship with healthcare professionals induced a minimum burden compared with other domains. In contrast, domain 8 (lack of autonomy over medicine) had the highest mean of person measure, implying that a lack of autonomy toward medicine use was perceived as the most burdensome issue.

Figure 2 Person measure of medication-related burden which is assessed using Living with Medicine Questionnaire-3 (LMQ-3). Notes: outlier; Domain 1: Interference of day-to-day life; Domain 2: Patient-doctor relationships; Domain 3: Perceived effectiveness; Domain 4: General concern about medicine; Domain 5: Side effect burden; Domain 6: Practical difficulties; Domain 7: Cost-related burden; Domain 8: Autonomy over medicine.

Discussion

This study found that medication induces multidimensional responses that are subjectively perceived by each patient. One issue may lead to or aggravate other issues. This corresponds with previous studies which suggest that medication-related burden is a complex phenomenon that involves different components and elements interacting with each other.^7,15 The qualitative study helps in understanding the different components of patient concern and enables the caregiver to identify the personal burden to make a better approach. In contrast, more generalized issues can be better described with the quantitative method, which is valuable in formulating policies related to patient-centered care. Both methods contribute to identifying any burdens that may interrupt optimal health outcomes.¹⁶

The treatment regimen was perceived as the most dominant burden, related to the characteristics of the medicine package and the rules of MDR-TB therapy, which were complex, and strict. Similarly, autonomy over medicine domain showed the highest mean measure, which indicated there were an issue about patient’s control of medicine dose and schedule that affects patients overall. One of the most complained-about problems was side effects. Not surprisingly, the presence of side effects also showed a significant association with the severity of medication-related burden in quantitative analysis. It is known that the MDR-TB regimen causes various side effects, ranging from mild to those that cause disability and threaten life.^17,18 Consequently, patients lost their daily functionality and social interaction. The results of this study correspond with a previous study that found adverse reactions or side effects of drug-resistant TB medications are associated with the quality of life of patients.^19,20 For example, vomiting, as one of the most frequent side effects, not only caused discomfort but also potentially reduced the drug dose taken by the patients.

Personal belief represents individual internal factors. Treatment expectation depends on treatment experiences,^21,22 verbal suggestions,²² and the learning process.^22,23 This study shows that the experience of treatment constructs specific ideas about the medication. These ideas might generate a belief that controls their reaction toward therapy. For example, side effects may emerge before taking medicine, which are called anticipatory symptoms. The symptoms of side effects sometimes also occur when patients think about taking medication, which is called associative symptoms. Restlessness and feeling of distress sometimes arise before taking drugs and are called behavioral symptoms.²⁴ However, these anticipatory, associative, and behavioral symptoms are not clinically evident. Yet, they are burdensome and make patients avoid therapy.²⁵

A solid cultural factor also contributed to how patients avoid undesirable effects. Some people tried to seek another option of therapy instead of conventional medicine. Alternative therapy and traditional remedies are popular in Indonesia. People believe that conventional synthetic medicine treatment causes more side effects and leads to drug dependence than alternative therapy or traditional medications.⁹

Socioeconomic burdens represented workloads regarding their economic condition and social functioning. TB medication side effects made patients feel isolated due to the decline in their social function.²⁶ In terms of finances, patients found constraints because they still had to pay several indirect costs in addition to medical expenses covered by national health insurance. Besides, patients are more likely to suffer income loss in this condition. This gap results in a substantial financial burden on the patient. The quantitative finding showed an association between age and burden level. It may be because different age groups perceive diverse perceptions of health.^27,28 The burden of illness and medicine in MDR-TB also resulted in economic and social dependence. Consequently, the family also experiences the caregiver burden of MDR-TB therapy.

Healthcare-related burdens arise from frequent visits to healthcare facilities. Patients expect convenient and accessible services. This finding implies that the role of healthcare professionals matters a lot, either in providing appropriate treatment or in giving emotional support to patients.

Healthcare professionals are supposed to provide responsive care and respect patients as whole persons with multidimensional needs and values.^29,30 A pharmacist is a healthcare professional with extensive knowledge and skills in clinical medication management.³¹ Since medicine use seems to be one of the major concerns of tuberculosis, pharmacists hold the potential to contribute to overcoming the medication-related burden.^32–34 Intensive monitoring, counseling, and education about the disease, appropriate drug use, management of side effects, and medication therapy reviews are needed.^34–37 These measures may increase self-efficacy and awareness of the severity and susceptibility of diseases. Information about side effects should be communicated with positive framing, by avoiding negative verbal suggestions.³⁸

The ability of patients to bear workloads depended on their perception. The health belief model (HBM) explains the reasons for patients’ health behaviors that primarily arise from their health perceptions.³⁶ When the perceived benefits outweigh the burdens, patients will continue adhering to treatment regardless of the burdens. In addition, the HBM explains that awareness about the risk of severity and susceptibility to diseases, self-efficacy, and specific cues that trigger better health behavior also matter.^39,40 Therefore, assistance from a healthcare professional is recommended by providing patient-centered care, educational support, and psychological intervention.⁴¹ Psychological interventions, such as cognitive-behavioral therapy, were also recommended as non-pharmacological interventions.⁴² There are three domains as modifiable targets of psychological intervention: (1) knowledge, beliefs, and related cognitive constructs; (2) emotional distress and well-being; and (3) behavioral skills and coping.⁴³

Moreover, patients also need support from family and the community. The family, as caregivers, supervises medication, and encourages patients. Peers and the TB survivor community may also provide support.^44,45 This approach may create a sentimental attachment and give hope to patients. Finally, financial support from the government may be a solution to relieving the burden, especially in low-, and middle-income countries.

Limitations of this study were as follows: (1) The one-month total sampling technique, while time saving, may limit the generalizability of the data, and (2) there was no comparison of drug-sensitive TB (DS TB) patients to confirm the severity of burden in MDR-TB care. Further research is required to analyse and provide a more comprehensive understanding of the condition of MDR-TB patients compared to DS TB patients.

Conclusion

In qualitative section, side effect was identified as the major concern of the treatment. Similarly, in quantitative section, presence of side effect and younger age were associated with higher burden. Based on joint analysis, regimen-related burden was inferred as the most common issue observed in MDR-TB patients. By understanding perspective of patient, healthcare professionals are expected to provide tailored care to alleviate burdens. The findings about the burden of medication side effects also highlight the necessity for more tolerable MDR-TB medication. An extensive quantitative study over extended period will enable more findings.