People-centred care versus clinic-based DOT for continuation phase TB treatment in Armenia: a cluster randomized trial
Vahe Khachadourian, Nune Truzyan, Arusyak Harutyunyan, Varduhi Petrosyan, Hayk Davtyan, Karapet Davtyan, Martin van den Boom, Michael E Thompson, Vahe Khachadourian, Nune Truzyan, Arusyak Harutyunyan, Varduhi Petrosyan, Hayk Davtyan, Karapet Davtyan, Martin van den Boom, Michael E Thompson
Abstract
Background: WHO's directly observed therapy (DOT) strategy for tuberculosis (TB) treatment depends upon a well-organized healthcare system. This study sought to evaluate the effectiveness of self-administered drug intake supported by a family member versus in-clinic DOT.
Methods: This open-label, nationally-representative stratified cluster randomized controlled non-inferiority trial with two parallel equal arms involved drug-susceptible pulmonary TB patients in the continuation treatment phase. We randomly assigned outpatient-TB-centres (52 clusters) to intervention and control arms. The intervention included an educational/counseling session to enhance treatment adherence; weekly visits to outpatient-TB-centres to receive medication, and daily SMS medication reminders and phone calls to track adherence and record side effects. Controls followed clinical DOT at Outpatient-TB-centres. Both groups participated in baseline and 4-5 months follow-up surveys. The trial's non-inferiority comparisons include: treatment success as the clinical (primary) outcome and medication adherence (self-reported), knowledge, depressive symptoms, stigma, quality of life, and social support as non-clinical (secondary) outcomes.
Results: Per-protocol analysis showed that the intervention (n = 187) and control (n = 198) arms achieved successful treatment outcome of 92.0 and 92.9%, respectively, indicating that the treatment success in the intervention group was non-inferior to DOT. Knowledge, depression, stigma, quality of life, and social support also showed non-inferiority, demonstrating substantial improvement over time for knowledge (change in the intervention = 1.05: 95%CL (0.49, 1.60); change in the control = 1.09: 95%CL (0.56, 1.64)), depression score (change in the intervention = - 3.56: 95%CL (- 4.99, - 2.13); change in the control = - 1.88: 95% CL (- 3.26, - 0.49)) and quality of life (change in the intervention = 5.01: 95%CL (- 0.64, 10.66); change in the control = 7.29: 95%CL (1.77, 12.81)). The intervention resulted in improved treatment adherence.
Conclusions: This socially empowering alternative strategy might be a preferable alternative to DOT available to patients in Armenia and in other countries. Further research evaluating cost effectiveness of the intervention and generalizability of the results is warranted.
Trial registration: Clinicaltrials.gov: NCT02082340, March 10, 2014.
Keywords: Counselling; Patient-Centreed care; Tuberculosis.
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
References
- World Health Organisation. Global tuberculosis report 2016. Geneva: World Health Organization; 2016.
- van der Werf MJ, Langendam MW, Huitric E, Manissero D. Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis. Eur Respir J. 2012;39(6):1511–1519. doi: 10.1183/09031936.00125711.
- Volmink J, Garner P. Directly observed therapy for treating tuberculosis. In: Volmink J, editor. Cochrane Database of Systematic Reviews. Chichester: Wiley; 2007. p. CD003343.
- Driver CR, Matus SP, Bayuga S, Winters AI, Munsiff SS. Factors associated with tuberculosis treatment interruption in new York City. J Public Health Manag Pract. 2005;11(4):361–368. doi: 10.1097/00124784-200507000-00017.
- Barnhoorn F, Adriaanse H. In search of factors responsible for noncompliance among tuberculosis patients in Wardha District, India. Soc Sci Med [Internet] 1992;34(3):291–306. doi: 10.1016/0277-9536(92)90271-Q.
- Aziz MA, Wright A. The World Health Organization/international union against tuberculosis and lung disease global project on surveillance for anti-tuberculosis drug resistance: a model for other infectious diseases. Clin Infect Dis. 2005;41(s4):S258–S262. doi: 10.1086/430786.
- Newell JN, Baral SC, Pande SB, Bam DS, Malla P. Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial. Lancet. 2006;367(9514):903–909. doi: 10.1016/S0140-6736(06)68380-3.
- World Health Organization. Treatment of Tuberculosis Guidelines: World Health Organization; 2010.
- Maciel ELN, Guidoni LM, Brioshi AP, Do Prado TN, Fregona G, Hadad DJ, et al. Household members and health care workers as supervisors of tuberculosis treatment. Rev Saude Publica. 2010;44(2):339–343. doi: 10.1590/S0034-89102010000200015.
- M’imunya JM, Kredo T, Volmink J. Patient education and counselling for promoting adherence to treatment for tuberculosis. Cochrane Database Syst Rev. 2012;5:CD006591.
- Morisky DE, Malotte CK, Choi P, Davidson P, Rigler S, Sugland B, et al. A patient education program to improve adherence rates with antituberculosis drug regimens. Health Educ Q. 1990;17(3):253–267. doi: 10.1177/109019819001700303.
- Akkslip S, Rasmithat S, Maher D, Sawert H. Direct observation of tuberculosis treatment by supervised family members in Yasothorn Province. Thailand Int J Tuberc Lung Dis. 1999;3(12):1061–1065.
- Guo N, Marra F, Marra CA. Measuring health-related quality of life in tuberculosis: a systematic review. Health Qual Life Outcomes. 2009;7:14. doi: 10.1186/1477-7525-7-14.
- World Health Organization. Global strategy and targets for tuberculosis prevention, care and control after 2015. Geneva; 2014.
- International Telecommunication Union: The World in 2014–ICT Facts and Figures [Internet]. 2014. Available from: ICTFactsFigures2014-e.pdf [cited 2018 Jul 15].
- Nglazi MD, Bekker L-G, Wood R, Hussey GD, Wiysonge CS. Mobile phone text messaging for promoting adherence to anti-tuberculosis treatment: a systematic review. BMC Infect Dis. 2013;13:566. doi: 10.1186/1471-2334-13-566.
- Bediang G, Stoll B, Elia N, Abena JL, Geissbuhler A. SMS reminders to improve adherence and cure of tuberculosis patients in Cameroon (TB-SMS Cameroon): a randomised controlled trial. BMC Public Health. 2018.
- Liu X, Lewis JJ, Zhang H, Lu W, Zhang S, Zheng G, et al. Effectiveness of electronic reminders to improve medication adherence in tuberculosis patients: a cluster-randomised trial. PLoS Med. 2015;12(9):e1001876.
- Mohammed S, Glennerster R, Khan AJ. Impact of a daily SMS medication reminder system on tuberculosis treatment outcomes: a randomized controlled trial. PLoS One. 2016;11(11):e0162944.
- Mohammed S, Siddiqi O, Ali O, Habib A, Haqqi F, Kausar M, et al. User engagement with and attitudes towards an interactive SMS reminder system for patients with tuberculosis. J Telemed Telecare. 2012;18(7):404–408. doi: 10.1258/jtt.2012.120311.
- Khachadourian V, Truzyan N, Harutyunyan A, Thompson ME, Harutyunyan T, Petrosyan V. People-centered tuberculosis care versus standard directly observed therapy: study protocol for a cluster randomized controlled trial. Trials. 2015;16:281. doi: 10.1186/s13063-015-0802-2.
- World Health Organization. Definitions and reporting framework for tuberculosis. WHO; 2014.
- Eldridge S, Kerry S. A practical guide to cluster randomised trials in health services research. Chichester: Wiley; 2012.
- Truzyan N, Crape B, Harutyunyan T, Petrosyan V. Family-based tuberculosis counseling supports directly observed therapy in Armenia: a pilot project. J Tuberc Res. 2018;06(02):113–124. doi: 10.4236/jtr.2018.62011.
- World Health Organization. Advocacy, communication and social mobilization for TB control: A guide to developing kno1. World Health Organization. Advocacy, communication and social mobilization for TB control: A guide to developing knowledge, attitude and practice surveys. World He. WHO. 2008.
- Movsisyan A. Diagnostic accuracy of post-traumatic stress disorder checklist-civilian version and modified versions of Center for Epidemiologic Studies Depression Scale among 1988 Spitak earthquake survivors: American University of Armenia; 2013.
- Demirchyan A, Petrosyan V, Thompson ME. Psychometric value of the Center for Epidemiologic Studies Depression (CES-D) scale for screening of depressive symptoms in Armenian population. J Affect Disord. 2011;133(3):489–498. doi: 10.1016/j.jad.2011.04.042.
- Van Rie A, Sengupta S, Pungrassami P, Balthip Q, Choonuan S, Kasetjaroen Y, et al. Measuring stigma associated with tuberculosis and HIV/AIDS in southern Thailand: exploratory and confirmatory factor analyses of two new scales. Tropical Med Int Health. 2008;13(1):21–30. doi: 10.1111/j.1365-3156.2007.01971.x.
- EuroQol--a new facility for the measurement of health-related quality of life. Health Policy [Internet]. 1990;16(3):199–208 Available from: [cited 2014 Dec 27].
- Schulz U, Schwarzer R. Soziale Unterstützung bei der Krankheitsbewältigung: Die Berliner Social Support Skalen (BSSS) Diagnostica. 2003;49(2):73–82. doi: 10.1026//0012-1924.49.2.73.
- Herman A, Botser IB, Tenenbaum S, Chechick A. Intention-to-treat analysis and accounting for missing data in Orthopaedic randomized clinical trials. J Bone Jt Surgery-American Vol. 2009;91(9):2137–2143. doi: 10.2106/JBJS.H.01481.
- Laird NM, Ware JH. Biometrics. 1982. Random-Effects Models for Longitudinal Data.
- Liang K-Y, Zeger SL. Biometrika. 1986. Longitudinal Data Analysis Using Generalized Linear Models.
- Bark CM, Furin JJ, Johnson JL. Approaches to clinical trials of new anti-TB drugs. Clin Investig (Lond) 2012;2(4):359–370. doi: 10.4155/cli.12.22.
- World Health Organization . A people-centred model of tuberculosis care: A blueprint for eastern European and central Asian countries. 1. Copenhagen: World Health Organization; 2017.
- Raza S, Sarfaraz M, Ahmad M. Practice of family and non-family based directly obseved treatment for tuberculosis in Pakistan: a retrospective cohort study. TheHealth. 2012;3(2):39–44.
- Truzyan N, Grigoryan R, Martirosyan H, Petrosyan V, Crape B, Melkomian DM, et al. Operational research on investigation of TB risk factors in Armenia: Center for Health Services Research and Development, American University of Armenia; 2012.
- Singal AG, Higgins PDR, Waljee AK. A primer on effectiveness and efficacy trials. Clin Transl Gastroenterol. 2014;5(1):e45. doi: 10.1038/ctg.2013.13.
- Otu AA. Is the directly observed therapy short course (DOTS) an effective strategy for tuberculosis control in a developing country? Asian Pacific J Trop Dis. 2013;3(3):227–231. doi: 10.1016/S2222-1808(13)60045-6.
- Vashishtha R, Mohan K, Singh B, Devarapu SK, Sreenivas V, Ranjan S, et al. Efficacy and safety of thrice weekly DOTS in tuberculosis patients with and without HIV co-infection: an observational study. BMC Infect Dis. 2013;13(1):468. doi: 10.1186/1471-2334-13-468.
- Mezzich JE, Appleyard J, Botbol M, Ghebrehiwet T, Groves J, Salloum I, et al. Summary Report of the Seventh Geneva Conference on Personcentered Medicine. Int J Person Centered Med. 2014;4(2):139–44.
- Munro SA, Lewin SA, Smith HJ, Engel ME, Fretheim A, Volmink J. Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research. Rylko-Bauer B, editor. PLoS Med. 2007;4(7):e238.
- Taylor SE, Kemeny ME, Reed GM, Bower JE, Gruenewald TL. Psychological resources, positive illusions, and health. Am Psychol. 2000;55(1):99–109. doi: 10.1037/0003-066X.55.1.99.
- Miller DE, Miller LT. Survivors : an oral history of the Armenian genocide: University of California Press; 1993. p. 242.
Source: PubMed