Adherence to anti diabetic medication among patients with diabetes in eastern Uganda; a cross sectional study
BMC Health Services Research volume 15, Article number: 168 (2015)
Lack of adherence to anti diabetic medication causes suboptimal blood sugar control among patients with diabetes and can lead to treatment failures, accelerated development of complications and increased mortality. This study assessed factors associated with adherence to anti diabetic medication in rural eastern Uganda.
A cross sectional study was conducted among 521 patients with diabetes in Iganga and Bugiri hospitals between October 2012 and January 2013. Respondents were patients who were18 years and above and had been on diabetic treatment for not less than a month. Pretested questionnaires were used. Variables that were collected included socio-demographic characteristics, possible barriers to adherence, and self management efforts. Adherence was assessed using self reports. Descriptive and inferential statistics were done to determine adherence to anti diabetic medication and the associated factors.
The level of adherence to anti diabetic medication was 83.3% and factors that were independently associated with adherence were; having been on anti diabetic drugs for at least three years (OR = 1.89, 95% CI = 1.11 - 3.22), availability of diabetic drugs (OR = 2.59, 95% CI = 1.54 - 3.70), and having ever had diabetic health education (OR = 4.24, 95% CI =1.15 - 15.60).
About four in five patients adhere to anti-diabetic treatment. Strategies aimed at improving anti diabetic drug availability and providing health education could improve adherence.
Diabetes Mellitus (DM) is a growing public health problem worldwide with an estimated 177 million people affected in 2003, 221 million by 2010 and is expected to rise to 300 million in 2025 with biggest increases in Asia and Africa [1-4]. By 2025, it is estimated that more than 75% of people with diabetes will reside in low income countries . Uganda is experiencing a marked upsurge of diabetes [5,6]. In a random sample from Kampala the capital city and its neighboring district Mukono, the prevalence was estimated to be up to 8.1% .
A key dimension of healthcare quality is adherence to prescribed medications. According to the World Health Organization (WHO), adherence is the extent to which a persons behavior; taking medication, following a prescribed diet, and/or executing lifestyle changes corresponds with agreed recommendations from the health care provider . However, non-adherence to medication is particularly common among patients with diabetes  and inadequate adherence compromises safety and treatment effectiveness, leading to increased mortality and morbidity. This ultimately translates into significant direct and indirect costs to the healthcare system [10-12]. It is also argued that, because the magnitude of non-adherence and the scope of its effect are high, more health benefits worldwide would result from improving adherence to existing treatments than by developing new medical treatments . Effective management of diabetes is associated with lower morbidity, mortality, and health care utilization hence reducing the cost and burden to government and the community. A study done in United States indicated that people with diabetes who did not adhere to treatment had significantly worse clinical outcomes compared to patients who adhered to treatment . Despite the emphasis put to patients on the importance of appropriate medication use, many patients poorly adhere to drugs especially for chronic diseases  and fall short of achievable health goals as a result. Non-adherence is associated with factors that are patient-centered, therapy-related, or healthcare system related [13,15]. The patient-centered factors can be demographic (age, gender, educational level, and marital status) and psychological (patients beliefs and motivation towards the therapy, negative attitude, patient-prescriber relationship, understanding of health issues, and patients knowledge) [16,17]. The therapy-related factors include route of medication, duration of treatment, complexity of treatment, type of medication and the side effects of the medicines. The factors linked to the healthcare system include availability and accessibility of health care, and the health provider-patient interactions .
Previously, numerous studies have explored potential risk factors of non adherence to medicines across a variety of conditions [12,18,19]. Frequently cited risk factors include age, sex, ethnicity, income, education, and co-morbidity though their relationship to adherence has been inconsistent due to variations in study designs and sample populations [9,20,21]. Medication related side effects are also associated with non-adherence . A study done in Uganda in an urban hospital indicated long time interval to a facility visit, patients not understanding the drug regimen and inability to afford the cost of the drugs as associated with non adherence . Use of a diet plan and being told why to control diet are also associated with adherence .
In Uganda, there is scarcity of literature on adherence to diabetic treatment in rural areas whose population is generally poorer with less access to health care. The number of patients with diabetes in rural areas is on the increase . Therefore there is a need to identify factors related to medication adherence. Furthermore, most of the studies have been carried out in developed countries , leaving a gap in knowledge about the prevalence and factors that may be associated with adherence to diabetic treatment in rural settings. In this study, we assessed factors associated with adherence to anti diabetic medication in eastern Uganda so as to guide interventions for improving drug adherence and optimal glycaemic control among patients with diabetes in rural areas.
The study was conducted in two general hospitals – Iganga and Bugiri. These hospitals operate out-patients diabetic clinics once a week and have in-patient facilities for the very ill patients. Patients attend the clinics at scheduled times for continuous monitoring and consultation regarding their illness. Medical care is provided throughout the week and patients receive free medical care including medicines and laboratory tests when available. A more detailed description of the study setting has already been described in a previous paper .
Study respondents and data collection
This was a cross sectional study. Respondents were all patients with diabetes, aged at least 18 years, attending the diabetic clinics who gave informed consent to participate in the study. We excluded those who were very ill and those who were newly diagnosed with diabetes (less than one month) from the study. Our outcomes were adherence to anti diabetic medication and the associated factors.
Out of the 575 registered patients with diabetes, a total of 521 patients who reported between October 2012 and January 2013 in these hospitals were recruited consecutively on diabetic clinic days. Both clinics were allocated 12 weeks for patient selection and data collection was done concurrently.
Trained interviewers used pretested semi-structured questionnaires to collect information on: age, gender, education level, marital status, and occupation. Other variables included perceived benefits of treatment, duration on drugs, type of drugs taken, availability of drugs, having had side effects, time since patient was last seen by health worker, use of alternative medicine, having ever had diabetic education, understanding the drug regimen and having received reminders to take drugs.
Assessment of adherence to anti diabetic medication
Therapeutic adherence means that the patient observes the medical recommendations, taking the medication, and maintaining a lifestyle as recommended by clinicians . In our study, we focused on medication adherence. Adherence to diabetic treatment was determined through self reports of how patients had been taking medication one week prior to the interview. Patients were specifically asked to recall if they missed any doses of medication on a day by day basis over a period of seven days. The number of times doses were missed was calculated basing on the patients medication regimen which was obtained from their medical forms.
Operational definition of adherence to anti diabetic medication
Data management and analysis
Data was entered using double data entry, cleaned to ensure completeness and consistency and checked for normality. Univariate analysis was used to summarize data, describe social demographic characteristics of study respondents and determine level of adherence. We used bivariate analysis to determine associations between adherence and various independent factors using STATA 10.0 statistical software (Stata, College Station, TX, USA). Crude odds ratios with their corresponding 95% confidence intervals were used to describe these associations. Independent variables with p-values less than 0.25 were used for multinomial analysis to determine variables which were independently associated with medication adherence. Independent factors were determined through a logistic regression analysis with stepwise elimination method while keeping known predictors of adherence from literature, in the multivariate model.
Ethical approval to conduct this study was obtained from Makerere University School of Public Higher Degrees Research and Ethics Committee and the Uganda National Council for Science and Technology. Permission was granted by Iganga and Bugiri district health authorities. Written informed consent was obtained from study participants. Data accruing was kept securely locked at all times and was only accessible to researchers.
A total of 521 diabetic patients were interviewed of whom 259 (49.7%) were female. The mean age was 50.9 years (standard deviation 14.6 years). Nearly three-quarters, 381 (73.1%) were married, and about half, 238 (45.7%) had no formal education. Details of the respondents background characteristics are summarized in Table 1.
Adherence to anti diabetic medication
Of the 521 participants, 433 (83.3%) were adherent to anti-diabetic medications based on an adherence index of 80% from self reports [12,23,27]. Respondents socio-demographic characteristics such as age, sex, education level and marital status were not associated with adherence to anti diabetic medication.
Factors associated with adherence to diabetic medication
At crude analysis, factors associated with adherence to medication were: being on anti diabetic drugs for at least three years (OR = 2.25, 95% CI = 1.38 – 3.66), receiving anti diabetic drugs in injection form (OR = 1.78, 95% CI = 1.07 – 2.96), availability of anti diabetic medication (OR = 2.56, 95% CI = 1.56 – 4.16), not using alternative medicine (OR = 2.26 95% CI = 1.33 – 3.83), having ever had diabetic education (OR = 3.33, 95% CI = 1.06 – 11.1) and having no reminders to take medication (OR = 0.25, 95% CI = 0.10 – 0.56). Details are summarized in Table 2.
Independent factors associated with adherence to diabetic medication
Factors independently associated with adherence to anti diabetic medication after adjusted analyses were: having taken medication for more than three years (OR = 1.89, 95% CI = 1.11 – 3.22), availability of anti-diabetic drugs (OR = 2.59, 95% CI = 1.54 – 3.70), and ever had diabetic education (OR = 4.24, 95% CI = 1.15 – 15.60). Details are summarized in Table 3.
In this study, adherence to anti diabetic medication was 83.3% and this was associated with duration on anti-diabetic treatment, drug availability and having ever had diabetic education.
About four in every five respondents adhered well to their diabetic medication based on self reports at an adherence index of 80% [12,23,27]. Since adherence information was based on patients recall, the actual adherence levels may be lower than what was found in our study. This is because self-reports usually overestimate patients adherence levels . Furthermore, patients may get problems recalling how they took medication but this was minimized by asking them to recall over a short period of only one week. Thirdly, potential response bias was minimized by asking non critical and non threatening questions when assessing for medication adherence. Similar rates of adherence have been reported previously [9,11,12,17]. However, low rates of adherence to diabetic medication have also been reported in India, Malaysia, Saudi Arabia and Korea [18,27-29]. The discrepancy in adherence levels may be attributed to differences in metrics to assess adherence, and/or differences in health care settings and socio economic status. With reference to our study, patients receive free anti diabetic drugs while in countries like India, Malaysia and Korea, patients pay for drugs and clinic consultations. These associated financial costs may deter or delay patients from re-filling prescribed medication and this negatively impacts on their adherence. Secondly the high costs of the prescribed oral hypoglycemic medications especially the relatively newer agents or scarcity of prescribed brands of medications further hinders optimal adherence [11,30]. Financial costs associated with diabetic care whether direct or indirect significantly reduce access to diabetic therapy and thus influence patients adherence in developing countries [18,31,32].
In our multivariate model, respondents who had been on anti diabetic medication for at least three years significantly had high levels of adherence (AOR 1.11 – 3.22). Similar results were observed from a study among diabetic patients in France, which showed that patients with poor adherence had been on diabetic treatment for less than five years . Patients with longer durations of diabetic medication are likely to have had more interactions with their health care providers, could have understood their regimen better and would be self motivated to take their medication. It is possible that patients who have been on treatment for a short duration may be less aware of their disease and are thus more likely to be non adherent. Alternatively, it could be that the adherence to treatment may be responsible for patients lasting longer than three years. A prospective study assessing adherence of patients with diabetes would be useful to determine to what extent adherence contributes to their survival.
Unavailability of anti diabetic medication was associated with non adherence (AOR 1.54 – 3.70). Nearly a third, 33.8% of the respondents reported having missed getting at least one of the drugs in their regimen from the hospitals in the previous two months. Other studies have reported anti diabetic drugs stock-outs as a major constraint in managing diabetes [23,34-37]. The situation is more critical for those needing insulin. Insulin is much less available and less affordable compared to the oral hypoglycemic medicines. Access to insulin remains poor in many regions of the world due to high prices, exposing patients to risk of serious complications and disease, such as blindness, amputation and death. Insulin prices in private pharmacies vary considerably between regions and between countries within the same region . These findings imply that many patients would go without drugs till they are able to purchase their medications or the next scheduled visit with their health care provider. Failure to afford medications is the most common reason for poor adherence . In our study the hospitals provide free medications for only one month. Sometimes appointments are longer than a month and thus patients are forced to refill their prescriptions from private drug shops and pharmacies. Unfortunately in rural areas, few patients can afford such price. There are also fewer facilities offering anti-diabetic medication in rural areas compared to urban areas. Some patients resort to taking traditional medicines [26,38,39]. Consequently this negatively impacts on their adherence. Irregular supply for anti diabetic drugs has been linked to underfunding and supply chain problems in most health care systems [35,40].
In this study diabetic health education was significantly associated with adherence to medication (AOR 1.15 – 15.60). This is in agreement with other studies that have reported similar associations in Europe, United States and Africa [31,41,42]. Sensitization about the disease, the diagnosis and management of diabetes is effective in improving recruitment of patients into treatment programs as well as improving drug adherence . Diabetes self-management education has the potential to improve diabetes care . Meeting with a diabetes educator for 30 minutes every three months before an office visit may help to achieve many goals . The use of educational materials, regular interviews, instructions from nurses and physicians about methods of incorporating drug administration into patients daily lives, a real partnership between physician and patient, and patient self management of diabetic treatment, have all been found to improve adherence . It is critical therefore that efforts be put in equipping diabetic clinics with adequate numbers of well trained health workers current with the new diabetic management guidelines and willing to spend reasonable time with patients [46,47].
The use of self reports has limitations as an estimate of patients adherence levels. Self reports might be subjective and may overestimate patients adherence status when compared to other methods such as pill counts, prescription claims or biological assays [48,49]. However, the assessments for adherence using self reports may make patients feel comfortable in telling the truth and may probably facilitate the identification of poor adherence [50,51], and thus, it is a reliable and cost-effective method. This method of assessing adherence has its benefits, since it helps health care providers to identify patients who are more likely to have poor adherence, and determine aspects of diabetes that they can focus on to improve patients management .
Our findings showed that only four out of every five patients adhered to anti diabetic medication in a rural setting. Adherence was associated with duration on anti diabetic medication, availability of drugs, and having received diabetic health education. Patients who had been in diabetic treatment for more than three years were more likely to adhere to treatment. Therefore strategies to improve anti diabetic drug availability, health education on diabetic care and self management may help in improving adherence levels among patients with diabetes.
Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med. 1997;14 Suppl 5:S1–85.
Hjelm K, Mufunda E, Nambozi G, Kemp J. Preparing nurses to face the pandemic of diabetes mellitus: a literature review. J Adv Nurs. 2003;41(5):424–34.
World Health Organization. The World Health Report 1997: Conquering Suffering, Enriching Humanity. Geneva: World Health Organization; 1997.
Perry M. Early detection of type 2 diabetes: the role of the community nurse. Br J Community Nurs. 2001;6(4):176–9.
Government of Uganda. National Health Policy. Kampala: Ministry of Health; 1999.
Government of Uganda. Health Sector Strategic Plan II 2005/06 - 2009/2010. Kampala: Ministry of Health; 2005.
Lasky D, Becerra E, Boto W, Otim M, Ntambi J. Obesity and gender differences in the risk of type 2 diabetes mellitus in Uganda. Nutrition. 2002;18(5):417–21.
WHO. Adherence to long term therapies, time for action. Geneva: World Health Organization. 221; 2003.
Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004;27(5):1218–24.
Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care. 2005;43(6):521–30.
Lee WC, Balu S, Cobden D, Joshi AV, Pashos CL. Prevalence and economic consequences of medication adherence in diabetes: a systematic literature review. Manag Care Interface. 2006;19(7):31–41.
Hutchins V, Zhang B, Fleurence RL, Krishnarajah G, Graham J. A systematic review of adherence, treatment satisfaction and costs, in fixed-dose combination regimens in type 2 diabetes. Curr Med Res Opin. 2011;27(6):1157–68.
Pollack MF, Purayidathil FW, Bolge SC, Williams SA. Patient-reported tolerability issues with oral antidiabetic agents: Associations with adherence; treatment satisfaction and health-related quality of life. Diabetes Res Clin Pract. 2010;87(2):204–10.
Lee WC, Balu S, Cobden D, Joshi AV, Pashos CL. Medication adherence and the associated health-economic impact among patients with type 2 diabetes mellitus converting to insulin pen therapy: An analysis of third-party managed care claims data. Clin Ther. 2006;28(10):1712–25.
van Bruggen R, Gorter K, Stolk RP, Zuithoff P, Klungel OH, Rutten GE. Refill adherence and polypharmacy among patients with type 2 diabetes in general practice. Pharmacoepidemiol Drug Saf. 2009;18(11):983–91.
Jin J, Sklar GE, Min Sen OV, Chuen Li S. Factors affecting therapeutic compliance: A review from the patients perspective. Ther Clin Risk Manag. 2008;4(1):269–86.
Wong MCS, Kong APS, So W-Y, Jiang JY, Chan JCN, Griffiths SM. Adherence to Oral Hypoglycemic Agents in 26 782 Chinese Patients: A Cohort Study. J Clin Pharmacol. 2011;51(10):1474–82.
Park KA, Kim JG, Kim BW, Kam S, Kim KY, Ha SW, et al. Factors that Affect Medication Adherence in Elderly Patients with Diabetes Mellitus. Korean Diabetes J. 2010;34(1):55–65.
Clifford S, Perez-Nieves M, Skalicky AM, Reaney M, Coyne KS. A systematic literature review of methodologies used to assess medication adherence in patients with diabetes. Curr Med Res Opin. 2014;30(6):1071–85.
DiMatteo MR. Variations in patients adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42(3):200–9.
Walker EA, Molitch M, Kramer MK, Kahn S, Ma Y, Edelstein S, et al. Adherence to preventive medications: predictors and outcomes in the Diabetes Prevention Program. Diabetes Care. 2006;29(9):1997–2002.
Chao J, Nau DP, Aikens JE. Patient-reported perceptions of side effects of antihyperglycemic medication and adherence to medication regimens in persons with diabetes mellitus. Clin Ther. 2007;29(1):177–80.
Kalyango JN, Owino E, Nambuya AP. Non-adherence to diabetes treatment at Mulago Hospital in Uganda: prevalence and associated factors. Afr Health Sci. 2008;8(2):67–73.
Travis T. Patient perceptions of factors that affect adherence to dietary regimens for diabetes mellitus. Diabetes Educ. 1997;23(2):152–6.
Reeve PA, Falkner MJ. Disease patterns in a rural black population. S Afr Med J. 1986;69(9):551–2.
Rutebemberwa E, Lubega M, Katureebe SK, Oundo A, Kiweewa F, Mukanga D. Use of traditional medicine for the treatment of diabetes in Eastern Uganda: a qualitative exploration of reasons for choice. BMC Int Health Hum Rights. 2013;13:1.
Khan AR, Al-Abdul Lateef ZN, Al Aithan MA, Bu-Khamseen MA, Al Ibrahim I, Khan SA. Factors contributing to non-compliance among diabetics attending primary health centers in the Al Hasa district of Saudi Arabia. J Family Community Med. 2012;19(1):26–32.
Sankar UV, Lipska K, Mini GK, Sarma PS, Thankappan KR. The Adherence to Medications in Diabetic Patients in Rural Kerala. India: Asia-Pacific Journal of Public Health; 2013.
Ahmad NS, Ramli A, Islahudin F, Paraidathathu T. Medication adherence in patients with type 2 diabetes mellitus treated at primary health clinics in Malaysia. Patient Prefer Adherence. 2013;7:525–30.
Karter AJ, Parker MM, Moffet HH, Ahmed AT, Schmittdiel JA, Selby JV. New prescription medication gaps: a comprehensive measure of adherence to new prescriptions. Health Serv Res. 2009;44(5 Pt 1):1640–61.
Yusuff K, Obe O, Joseph B. Adherence to anti-diabetic drug therapy and self management practices among type-2 diabetics in Nigeria. Pharm World Sci. 2008;30(6):876–83.
Wabe NT, Angamo MT, Hussein S. Medication adherence in diabetes mellitus and self management practices among type-2 diabetics in Ethiopia. N Am J Med Sci. 2011;3(9):418–23.
Bezie Y, Molina M, Hernandez N, Batista R, Niang S, Huet D. Therapeutic compliance: a prospective analysis of various factors involved in the adherence rate in type 2 diabetes. Diabetes Metab. 2006;32(6):611–6.
Gill G. Diabetes in Africa - Puzzles and challenges. Indian J Endocrinol Metab. 2014;18(3):249–51.
Beran D, Yudkin JS. Diabetes care in sub-Saharan Africa. Lancet. 2006;368(9548):1689–95.
Hogerzeil HV, Liberman J, Wirtz VJ, Kishore SP, Selvaraj S, Kiddell-Monroe R, et al. Promotion of access to essential medicines for non-communicable diseases: practical implications of the UN political declaration. Lancet. 2013;381(9867):680–9.
Goudge J, Gilson L, Russell S, Gumede T, Mills A. Affordability, availability and acceptability barriers to health care for the chronically ill: longitudinal case studies from South Africa. BMC Health Serv Res. 2009;9:75.
Aikins A-G. Healer shopping in Africa: new evidence from rural–urban qualitative study of Ghanaian diabetes experiences. BMJ. 2005;331(7519):737.
Matheka DM, Demaio AR. Complementary and alternative medicine use among diabetic patients in Africa: a Kenyan perspective. Pan Afr Med J. 2013;15:110.
Bailey GR, Barner JC, Weems JK, Leckbee G, Solis R, Montemayor D, et al. Assessing Barriers to Medication Adherence in Underserved Patients With Diabetes in Texas. Diabetes Educ. 2012;38(2):271–9.
Lorenzi GM, LaRue SM, Collins SE. Effects of a Patient Education Support Program on Pramlintide Adherence. Clinical Diabetes. 2011;29(1):17–24.
Rothschild SK, Martin MA, Swider SM, Tumialán Lynas CM, Janssen I, Avery EF, et al. Mexican American Trial of Community Health Workers: A Randomized Controlled Trial of a Community Health Worker Intervention for Mexican Americans With Type 2 Diabetes Mellitus. Am J Public Health. 2014;104(8):1540–8.
Rodondi N, Peng T, Karter AJ, Bauer DC, Vittinghoff E, Tang S, et al. Therapy modifications in response to poorly controlled hypertension, dyslipidemia, and diabetes mellitus. Ann Intern Med. 2006;144(7):475–84.
AmericanDiabetesAssociation. Standards of Medical Care in Diabetes—2009. Diabetes Care. 2009;32(Supplement 1):S13–61.
Mensing C, Boucher J, Cypress M, Weinger K, Mulcahy K, Barta P, et al. National Standards for Diabetes Self-Management Education. Diabetes Care. 2002;25 suppl 1:s140–7.
Schoenthaler AM, Schwartz BS, Wood C, Stewart WF. Patient and Physician Factors Associated With Adherence to Diabetes Medications. Diabetes Educ. 2012;38(3):397–408.
Nicolucci A, Rossi MC. Incretin-based therapies: a new potential treatment approach to overcome clinical inertia in type 2 diabetes. Acta Biomed. 2008;79(3):184–91.
Hays RD, Kravitz RL, Mazel RM, Sherbourne CD, DiMatteo MR, Rogers WH, et al. The impact of patient adherence on health outcomes for patients with chronic disease in the Medical Outcomes Study. J Behav Med. 1994;17(4):347–60.
Garber MC, Nau DP, Erickson SR, Aikens JE, Lawrence JB. The Concordance of Self-Report With Other Measures of Medication Adherence: A Summary of the Literature. Med Care. 2004;42(7):649–52.
Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive Validity of a Medication Adherence Measure in an Outpatient Setting. J Clin Hypertens. 2008;10(5):348–54.
Eraker SA, Kirscht JP, Becker MH. Understanding and improving patient compliance. Ann Intern Med. 1984;100(2):258–68.
Kravitz RL, Hays RD, Sherbourne CD, DiMatteo MR, Rogers WH, Ordway L, et al. REcall of recommendations and adherence to advice among patients with chronic medical conditions. Arch Intern Med. 1993;153(16):1869–78.
This study was funded in part by the Swedish International Development Cooperation Agency (Sida) and Makerere University. Its contents are solely the responsibility of the authors and do not reflect the views of Sida nor the authors institutions of affiliation. We thank hospital authorities of Iganga and Bugiri for their support, the research assistants for their dedicated work and the respondents for their valuable participation.
The authors declare that they have no competing interests.
JB, ER and WB participated in the conception, design, and implementation of the study, statistical analysis and interpretation of the data, and the drafting of the manuscript. All authors have seen and approved the final version of the manuscript.
About this article
Cite this article
Bagonza, J., Rutebemberwa, E. & Bazeyo, W. Adherence to anti diabetic medication among patients with diabetes in eastern Uganda; a cross sectional study. BMC Health Serv Res 15, 168 (2015). https://doi.org/10.1186/s12913-015-0820-5