Psychological and Educational Intervention to Improve Tuberculosis Treatment Adherence in Ethiopia Based on Health Belief Model: A Cluster Randomized Control Trial

Background Treatment non-adherence results in treatment failure, prolonged transmission of disease and emergence of drug resistance. Although the problem widely investigated, there remains an information gap on the effectiveness of different methods to improve treatment adherence and the predictors of non-adherence in resource limited countries based on theoretical models. This study aimed to evaluate the impact of psychological counseling and educational intervention on tuberculosis (TB) treatment adherence based on Health Belief Model (HBM). Methodology A cluster randomized control trial was conducted in Addis Ababa from May to December, 2014. Patients were enrolled into study consecutively from 30 randomly selected Health Centers (HCs) (14 HCs intervention and 16 HCs control groups). A total of 698 TB patients, who were on treatment for one month to two months were enrolled. A structured questionnaire was administered to both groups of patients at baseline and endpoint of study. Control participants received routine directly-observed anti-TB therapy and the intervention group additionally received combined psychological counseling and adherence education. Treatment non-adherence level was the main outcome of the study, and multilevel logistic regression was employed to assess the impact of intervention on treatment adherence. Results At enrollment, the level of non-adherence among intervention (19.4%) and control (19.6%) groups was almost the same. However, after intervention, non-adherence level decreased among intervention group from 19.4 (at baseline) to 9.5% (at endpoint), while it increased among control group from 19.4% (baseline) to 25.4% (endpoint). Psychological counseling and educational interventions resulted in significant difference with regard to non-adherence level between intervention and control groups (Adjusted OR = 0.31, 95% Confidence Interval (CI) (0.18–0.53), p < 0.001)). Conclusion Psychological counseling and educational interventions, which were guided by HBM, significantly decreased treatment non-adherence level among intervention group. Provision of psychological counseling and health education to TB patients who are on regular treatment is recommended. This could be best achieved if these interventions are guided by behavioral theories and incorporated into the routine TB treatment strategy. Trial Registration Pan African Clinical Trials Registry PACTR201506001175423


Abstract
This study intends to determine psychosocial and behavioral determinants of TB treatment nonadherence, and to evaluate psychological and educational intervention to improve treatment adherence among TB patients on treatment based on Heath Belief Model (HBM) concept. HBM is recommended as effective and useful model to understand and explain health behavior including treatment adherence as healthy practice by patients. It is a psychological model which constructs from six domains. These domains are perceive susceptibility to and perceived severity of the condition, perceived benefits of the recommended behavior, perceived psychological/ tangible barriers to perform recommended behavior, cue to action (motivator) to perform the behavior and self-efficacy on performing the recommended behavior correctly. Patients in treatment are likely adheres to their medical regimen under specific five sets of conditions according to the concept of HBM. First, patients must have some minimal health knowledge and motivation towards staying free of TB. Second, patients must perceive themselves as vulnerable to TB disease and they must also believe that TB and consequences of non-adherence are clearly a serious medical and health problem. Third, patients must also be convinced that current treatment TB is effective, that it is indeed possible to obtain control over the problems at an acceptable psychological or tangible social, psychological barriers and that the barrier does not outweigh the benefits. Fourth, the presence of an internal or external stimulus, referred as "cue to action," the trigger the health behavior of patients such as taking medication regularly. Finally, patients' self-efficacy belief on performing the recommended behavior should be maintained till the final treatment period. Therefore, based on HBM, the main outcome variable planned to be measured is level of treatment non-adherence. The key independent variables that are thought to be influencing the outcome variable and that will be assessed are six HBM domains; and as the main influencing factors, psychological variables (depression, anxiety and fear of stigma), social factors (demographic variables, economic problems and social support), and behavioural factors (knowledge, feeling better after few weeks of treatment, alcohol and tobacco use).
The cluster randomized control trial preceded by cross sectional study will be conducted in Addis Ababa from March to October, 2014 at selected health care facilities. Three hundred forty two (342) eligible TB patients will be enrolled consecutively from randomly selected 30 health centers which selected by random cluster sampling method. The health centers will be randomly allocated into control and intervention group. Researcher developed and standard questionnaires will be used for data collection after validated for reliability. The questionnaire will be administered by trained health professional at TB clinic of each health centers at baseline and endpoint. After, baseline information collected psychological and educational intervention will be implemented for intervention group, while control group followed under conventional TB treatment strategy. At the end of follow up similar data will be collected from both groups. Association factors and the impact of intervention will be assessed by multiple logistic regression, at 5% level of precision using SPSS ver.21.0.
Ethical approval will be obtained from the research ethical review board, Tehran University of Medical Sciences, Research and ethical review committee of Ethiopian Public Health Institute and Addis Ababa Health Bureau. Both oral and written informed consent will be obtained from each study participant. The experience and information gained from this study should help to improve TB prevention and control program; and to enhance TB treatment adherence.

Background
Adherence to long term treatment like Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) is very challenging because of its long term and drug related side effects [1]. As known treatment adherence is very important for effective treatment outcome and prevention of drug resistant TB bacilli strain. However, TB treatment non-adherence has several socioeconomic and health consequences [1][2][3][4][5]. From several consequences, occurrence of multi drug resistant TB (MDR-TB) is one of serious consequence that challenging global TB control program. For instance the odds of having interrupted the treatment at least for one day among those who developed (MDR-TB) are 13 times than among those not interrupted at all [6].
According to evidences, several psychosocial and behavioral factors are responsible for TB treatment non-adherence. For instance, depression [7], fear of stigma [8] and individual negative emotional condition [9] are the main psychological factors that associated with TB treatment non-adherence. In addition, lack of transportation cost and food, lack of social support, unemployment, lack of permission from job place and lack of shelter are some of social factors that influence TB treatment non-adherence [10][11][12][13][14][15]. Beside psychosocial factors, individual behavioral factors like individual TB disease and its treatment knowledge, feeling better after few weeks of treatment and forgetfulness are factors associated with treatment non-adherence [15][16][17][18]. Furthermore, alcohol consumption and tobacco smoking are the two individual behavioral factors that associated with TB treatment non-adherence [12,17,[19][20].
Beside psychosocial and behavioural factors lack of support from health care workers, and health care worker poor communication, distance from health care centre, insufficient and interrupted TB medication and laboratory logistic supply are health care worker and facility related factors that associated with TB treatment non-adherence [10,11,14]. In addition, TB patient's HIV and anti retroviral therapy (ART) status are association with TB treatment non-adherence [11].
However, contrarily other studies are reported that HIV sero positive and on ART are preventive factors of TB treatment non-adherence and lost to follow up among TB patients with HIV [11,14]. perceive themselves as vulnerable to TB disease and they must also believe that TB disease and the consequences of non-adherence is clearly a serious medical and health problem. Third, patients must also be convinced that current TB treatment is effective, that it is indeed possible to obtain control over the problems at an acceptable psychological or tangible social barriers and that the barrier does not outweigh the benefits. Fourth, the presence of an internal or external stimulus, referred as "cue to action," the trigger the health behavior of patients such as taking medication. Finally, patients' self-efficacy belief on regular follow up of treatment should be maintained till the final treatment period. Figure 1 shows the relationship between six HBM domains and individual participants baseline characteristics. for intervention) by simple random sampling technique. Randomizing of health facility is to control socioeconomic differences of each sub-city, and to control information contamination between control and intervention group on educational and psychosocial intervention will be applied. Participants will be enrolled from health center selected as a control will be control group and participants recruited from health center selected as intervention group will be intervention group of the study. Also, we assume, as we will be able to enroll at least one participant per day at each selected primary health care facility to achieve our target sample size (34) at single health center.
Researcher designed and standardized questionnaire will be used for data collection after evaluating for validity by a group of experts and for reliability by pilot study at study area. Then baseline/cross-sectional study data on psychosocial and behavioural determinants of TB treatment non-adherence will be collected thoroughly.
The intended psychological and educational intervention will be provided every week for the first month of enrollment, every two weeks during the second month, and then every month until At the end of treatment completion, similar questionnaire with baseline will be applied to both groups, and the endpoint data will be collected to see the impact intervention.
Data collected under intensive supervision of principal investigator and other members of the study team will be entered into double spread sheet data bases, checked for quality and will be analyzed with Statistical Package for Social Sciences (SPSS) version 21.0 at 5% precision level; and the result will be disseminated through oral presentation on different events and publication on peer reviewed journal.

Study Population
Study population is all TB patients who are diagnosed for all types of TB based on national TB treatment guideline and on first line and MDR-TB treatment regimens under DOTS strategy and MDR-TB treatment protocol [36]. Treatment adherence will be considered as the extent to which the patient's history of therapeutic medication-taking coincides with the prescribed treatment [1].
Accordingly, we will consider treatment adherent patient as a patient's attendance at the scheduled visit and regular medication with over 90% of doses prescribed based on WHO adherence definition [1].

Sampling and Sample Size Determination
As clearly demonstrated in figure 2 bellow; from 53 health center found in Addis Ababa, we will select 30 health centers from 10 sub-city administrations by random cluster sampling method.
Then 30 health centers will be divided into 15 control and 15 intervention groups by simple random assignment while considering control and interventional sites are far from each other to prevent information contamination.
To estimate précis proportion of non-adherence level; TB treatment non-adherence determinant factors; and the mean deference of two groups (control and interventional groups) on treatment non-adherence will be used two population proportion estimation formula to determine the required sample size.
Where Z α/2 is the critical value of the normal distribution at α/2, Z β is the critical value of the normal distribution at β, p 1 and p 2 are the expected sample proportions of the two groups. Because, our study is cluster randomized trial, we assumed design effect 1.5 by cluster sampling method to overcome the design effect. Then, the sample size will be: 207 X 1.5 = 3110.5 ≈ 311 Finally, sample size further increased by 10% to account for contingencies such as non-response or recording error, i.e. 311 X 10/100 + 311= 3342.1 ≈ 342. Therefore, the final sample size will be 342 TB patients on first line treatment for each group. As clearly shown in figure 2 bellow, we will be divided 2*342 participants into equal 34 participants at 20 each health center. Smoking Assessment Check list (39) are standard questionnaires will be used to collect data for psychological disorder, alcohol consumption and tobacco smoking respectively. The cutoff point will be considered according to standard questionnaire guideline and previous similar studies.
For socio-demographic data and participants' TB disease and its treatment knowledge level related information and adherence level literature based designed questionnaire will be used.
Health professional at TB clinic of selected health facilities will be applied the questionnaire after 4 days intensive training on questionnaire and good clinical practice. Finally, educational and psychological intervention will be provided by appropriate professional according scheduled.

Data Entry and Analysis
Data will be double interred in standard spreadsheets separately for quality purpose. Then, it will be analyzed using Statistical Package for Social Sciences (SPSS) version 20.0. Descriptive information will be determined to describe the socio-demographic data. Data will be checked for normality and homogeneity distribution before assessment of association by using Kolmogorov-Smirnov or Shapiro-Wilk.
Associations between psychosocial and behavioral factors, HBM constructs (perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cue to action and perceived self-efficacy) and TB medication non-adherence will be assessed by regression analysis at level of precision 5%, i.e. P value less than 0.05 will be considered as significant.

Data Collection Management and Safety Consideration
As we were tried to explain in the sampling method, health facility for control and interventional groups will be selected randomly while considering the optimum distance between control and intervention group to prevent information contamination and to distribute socioeconomic variables difference between sub-cities. The instrument designed based on literature review will be approved for validity and reliability. Psychological and educational intervention will be designed by the research team who are professional and experienced in the field of health education and promotion and applied by thoroughly trained appropriate professionals. Data collection will be supervised and checked before electronic data entry by principal investigator and other study team member closely to assure the maximum quality level. Then, double data entry method will be employed in separated spread sheet and data accessibility will be restricted to data manager and study principal investigator. Before analysis, data will be check for normality and homogeneity, then analyzed & interpreted with health education and promotion expert and senior biostatistician. Finally, quality scientific report will be developed and disseminated.

Ethical Consideration
Ethical approval will be obtained from the research ethical review board (RERB), Tehran University of Medical Sciences (TUMS), the Research and ethical review committee (RECC) of Ethiopian Public Health Institute (EPHI) and Addis Ababa City Administration Health Bureau.
Both oral and written informed consent will obtain from each study participant after thoroughly explaining objectives and benefits of the study. To ensure confidentiality, any personal identifying information on participants will not be collected. Benefits, compensation mechanism will be strictly respected for all participants equally for the time they will expend with us during interview and intervention implementation. Data will be collected for this study will not be used for other study without approval of each participant. All international and institutional randomize control trial research ethics conventions will be strictly obeyed during our study process.

Benefits of the Study Results
The benefits of this study are clear; because it will generate comprehensive information on determinants of TB treatment non-adherence and evaluate the intervention for implementation to minimize TB treatment non-adherence, which is the main challenge for global TB control program. Therefore, it will be helpful in terms of treatment cost reduction, policy direction and quality life improvement for the patients. In addition, the implementation of study result will be simple, because it implemented alongside with previously in system TB treatment strategy (DOTS).  Additionally, all information you will give us are confidential and used only for this study.

Implementation of the Study by Phases S/No Activities by phases for both drug susceptible and MDR types of TB
Dear participant, thank you for your cooperation in advance; and now I will read to you or you can read this written consent form; and you will sign for me as you agreed to participate in this study with your full will, after you understand the objective of the study, all procedures will be taken, and your benefits and rights.

Perceived Susceptibility
Please ask the participant and circle the selected level number, to what extent he/she agree or disagree with the following statement (where strongly disagree =1, disagree =2, Neutral =3, agree =4, strongly agree = 5) 1. All human are at risk of acquiring medication resistant or susceptible TB type germ at any time.

Perceived severity
Please ask the participant and circle the selected level number, to what extent he/she agree or disagree with the following statement (where strongly disagree =1, disagree =2, Neutral =3, agree =4, strongly agree = 5) 1. Please ask the participant to guess and put capital "X" in the box below based on how much he/she has been taken his/her anti-TB medication correctly (without missing) in the past 30 days. Also, tell the participant 0% means he/she has not taken his/her anti-TB medication, 50% means he/she has taken half of his/her anti-TB medication and 100% means he/she has taken every single dose of his/her anti-TB medication.

. Written Informed Consent Sheet
Dear participant, if you are agreed to take part in this study based on the information given to you, please listen or read this form one by one and tick every box to show your agreement on each points and sign the consent sheets at the end of this form. If there is any unclear point, don't hesitate to ask question until you understand it to make your decision by your own interest.
1. I know the objective and procedure of this study after I have read, or it was read to me, the information sheet concerning this study and I understand what will be required of me if I take part in the study.
2. I understand that being participation on this study is voluntary; confidentiality of my personal information is guaranteed; and as I have the right to get full treatment/care without participating on this study for my TB disease.
3. I understand that at any time I have the right to withdraw from this study without giving a reason and without affecting my normal treatment/care. 4. I know as data collector, collects information regarding TB disease and its treatment from me after he/she explain for me the procedure of collection, and as it takes 30 minutes to complete the whole procedure.
5. I know the potential benefit of this study for national and international TB control program through enhancing treatment adherence, that is important to prevent medication resistant types of TB and treatment failure 6. The interviewer explain for me as there is no any risk or discomfort, and extra treatment rather than normal TB treatment which I am taking 7. I understand that as information collected from me are confidential, and they will be reported with my approval and the information will be reported are only the result without my personal  This form and informed consent will be filled and signed in two copies, and then one copy will be provided for participant and the other for project manager.