Course 7: Issues in Medication Management

Introduction to Adherence and Compliance Issues

Adherence, compliance, and failure are value-judgment words often used by medical practitioners to signify the ability of a patient to follow medical directions for treatment and follow-up. Debate has surrounded the use of these terms as they may indicate a lack of acknowledgment of obstacles that can prevent patients from following directions. It has been noted that “compliance” is not an appropriate term to describe what it takes to follow medical instructions for tuberculosis recovery in Haiti because the poor unfairly bear the burden of the disease and are then told to adhere to programs that are not structured to meet their needs. The term “compliance” unfairly places the blame on the patient for the inability to complete treatment.(1) In resource-poor settings, noncompliance should primarily be looked at as a program failure, and only after the program has been shown to be optimally designed for delivering care to the patient in question should noncompliance be considered a patient's fault.(2)

The debate around adherence issues began before 2003, when many arguments were raised to justify not treating people living with HIV/AIDS in resource-poor settings. Such arguments centered on the price of therapy compared to the poverty of the patient, the lack of health infrastructure, and the lack of trained health care providers. Additionally, many believed that the complexity of the intervention would be an impediment to effective therapy. In order to achieve an undetectable viral load and prevent the development of drug resistance, a person on anti-retroviral therapy needs to take at least 95% of the prescribed doses on time.(3) For many people, this means taking a regimen of three anti-retrovirals twice per day—on both occasions, they are usually taking several pills.(4) An oft-toted argument was that Africans did not have the same conception of time as Westerners, which would prevent them from adhering to the strict drug regime that HIV therapy requires.

Yet the claim that adherence barriers are insurmountable in poor settings is not grounded in evidence. In fact, adherence rates in poor settings are proving to be equal to or higher than adherence in the Global North.(5)(6)(7) That HIV patients in Africa achieve close to 90% adherence rates—far exceeding those achieved in North America—is remarkable given the "formidable obstacles in the poorest regions of the world."(8) These facts dispel early scale-up concerns that adherence would be inadequate in settings of extreme poverty.

Effects of Non-Adherence

Yet a large reason for the high HIV treatment adherence rates in some locations is that global health organizations and policymakers have learned from the past. Years of poor adherence rates for drugs targeted at tuberculosis, malaria, and HIV have led to the emergence of wide-spread resistance. For example, multidrug-resistant tuberculosis (MDR-TB) is a type of tuberculosis that does not respond to the two most effective anti-TB drugs. In 2015, 480,000 people developed MDR-TB worldwide. These resistant strains emerged due to poor medication management, such as patient non-adherence to treatment. Because it is difficult to obtain the limited and expensive drugs required to treat MDR-TB, a mere 52% of global MDR-TB patients receive effective treatment.(9) Ensuring that patients are adhering to drug regimens can prevent the further emergence of destructive drug-resistant parasites.

In addition to stopping the spread of resistance, high adherence rates can prevent the transmission of disease. When patients fail to take appropriate doses at regular time intervals, they increase the chance that they will remain infectious and thus spread the disease to their family and friends. “For individuals living in extreme poverty, adhering to antiretroviral medicine regimens helps them protect the relationships they rely upon to survive.”(10)

Lastly, non-adherence has detrimental effects to patient outcomes. As mentioned in the previous module, new research data supports the importance of adherence in post-operative eye-health.(11) Patients who faithfully instilled their non-steroidal anti-inflammatory eye drops after surgery were more comfortable than those who did not use their drops. In addition, those who used eye drops were far less likely to develop Cystoid Macular Edema, a common cause of vision loss after cataract surgery.(12)

Adherence Rates and Treatment Outcomes

While substantial research has been conducted around adherence rates in the Global North, more research is needed to identify these rates in the Global South. This can be accomplished by replicating previous studies, such as the Travatan Dosing Aid Study.(13) This research, based at the University of Pennsylvania, assessed patient adherence to a topical once-daily therapy for glaucoma using an electronic monitoring device on patients’ medication. Nearly 45% of patients who knew they were being monitored used their drops less than 75% of the time. Additionally, patients reported far higher medication use than their actual behavior, and ability of the physician to identify poor-adherers was poor. The first step in solving the issue of adherence is to similarly investigate the adherence rates of patients from villages who may have never before used medication.

It is clear that adherence is a factor in the outcome of medical treatment, but the strength and moderators of the adherence-outcome association have not been systematically assessed. A meta-analysis of 63 studies was conducted in order to measure the correlation between adherence and an objective measure of treatment outcomes.(14) Overall, the outcome difference between high and low adherence was 26%. According to this meta-analysis, adherence is most strongly related to outcomes in studies of non-medication regimens, where measures of adherence are continuous, and where the disease is chronic (particularly hypertension, hypercholesterolemia, intestinal disease, and sleep apnea). For patients with serious chronic eye-diseases, adherence to medications may prove to have an even greater effect on health outcomes, although future research is needed to establish this causal link.

Barriers to Adherence

Many barriers to adherence have been documented in the literature regarding community eye-health in the Global South. Knowing the predictors of poor adherence can help identify patients who need individualized strategies to improve follow-up and inform the structure of global health interventions to address adherence obstacles.

In Southern India, a survey was conducted on 243 glaucoma patients who were on at least one glaucoma medication. Researchers found that 42% of patients reported one or more problems in using their glaucoma medications. Approximately 6% of patients reported being less than 100% adherent in the past week. Unmarried patients and patients who reported difficulty squeezing the bottle and difficulty opening the bottle were significantly more likely to report non-adherence.(15) These findings suggest that elderly persons and those without sufficient social support networks may have unique barriers to adherence. Another study found multiple obstacles to adherence including poor education, lack of motivation, forgetfulness, drop application, and other practical issues.(16)

In addition to empirical research that identifies impediments to adherence, a biosocial lens is needed in order to fully understand the reasons behind non-compliance. For example, because of the enormous stigma surrounding AIDS in much of the Global South, the advent of effective therapy had social repercussions that altered rates of adherence. Preliminary data from rural Haiti suggests that the introduction of quality HIV care can lead to a rapid reduction in stigma, with resulting increased uptake of testing.(17) Thus, an overemphasis on identifying the characteristics and “markers” of poor-adherers can limit our understanding of adherence as a complex process embedded in societal conceptions of disease.

“An approach to adherence that combines both biological and social knowledge and that relies on qualitative and quantitative methodologies is more likely to move us closer to a better understanding of adherence and, eventually, to improving adherence rates.”(18)

Evidence-Based Methods to Increase Adherence

The global health community today faces a gap between the knowledge of barriers to adherence and the implementation of that knowledge for the delivery of health care, especially in poor countries. Governments and organizations have the tools to decrease the morbidity and mortality caused by many diseases throughout the world but have not sufficiently put this knowledge to action. This wastes resources, time, and money, as failing to use available science is costly and harmful and leads to overuse of unhelpful care, underuse of effective care, and errors in execution.(19)

Further research is needed to document adherence rates, the link between these rates and treatment outcomes, and barriers to adherence. In addition, research on effective ways to overcome adherence barriers can help close this knowledge-action gap. Several studies have documented evidence-based methods for increasing adherence. One study summarized the effects of interventions for improving adherence to ocular hypotensive therapy in people with ocular hypertension or glaucoma and found that interventions involving simplified dosing regimens, reminder devices, education, and individualized care planning could improve adherence.(20)

Other research findings suggest that doctor-patient communication and health-related beliefs of patients contribute to adherence. Patients who are less concerned about the future effects of glaucoma and the risks of not taking medications have lower adherence. Specifically, knowledge about potential vision loss from glaucoma is a critical element that tends to be missed by more passive patients, who then tend to be poorly adherent.(21) These findings suggest that educational efforts and improved physician-patient communication may increase patient adherence to medical therapies.

Also, because reasons for non-adherence may often be found outside the individual responsibility of patients, solutions may require the provision of social support, such as bringing community health workers closer to patients. In fact, community health workers have proven essential in achieving high adherence rates to HIV and TB drug regimens. Not only can community health workers provide a system of accountability, they can also educate patients on the importance of timeliness and appropriate dosages.

Given the complexity of barriers to adherence and the dearth of empirical research regarding evidence-based solutions, addressing the multifaceted causes of non-adherence must be advanced through research. For example, qualitative studies may uncover the nature of adherence and non-adherence in particular locations. Only by understanding the interrelated factors that promote or impede adherence can we hope to overcome the real causes behind non-adherence.

Footnotes

(1) Farmer, P., Robin, S., Ramilus, S. L., & Kim, J. Y. (1991, December). Tuberculosis, poverty, and" compliance": lessons from rural Haiti. In Seminars in respiratory infections (Vol. 6, No. 4, pp. 254-260).

(2) Ibid.

(3) Paterson, D. L., Swindells, S., Mohr, J., Brester, M., Vergis, E. N., Squier, C., ... & Singh, N. (2000). Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Annals of internal medicine, 133(1), 21-30.

(4) Partners In Health. The PIH guide to the community-based treatment of HIV in resource-poor settings. Boston: Partners In Health; 2004.

(5) Coetzee, D., Boulle, A., Hildebrand, K., Asselman, V., Van Cutsem, G., & Goemaere, E. (2004). Promoting adherence to antiretroviral therapy: the experience from a primary care setting in Khayelitsha, South Africa. Aids, 18, S27-S31.

(6) Katzenstein, D., Laga, M., & Moatti, J. P. (2003). The evaluation of the HIV/AIDS drug access initiatives in Cote d'Ivoire, Senegal and Uganda: how access to antiretroviral treatment can become feasible in Africa. Aids, 17, S1-S4.

(7) Koenig, S. P., Leandre, F., & Farmer, P. E. (2004). Scaling-up HIV treatment programmes in resource-limited settings: the rural Haiti experience. Aids, 18, S21-S25.

(8) Ware et al. Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study. PLoS Medicine, 2009; 6 (1): e11.

(9) Burattini, M. N., E. Massad, and F. A. B. Coutinho. 1993. Malaria transmission rates estimated from serological data. Epidemiology and Infection 111, (3) (Dec.): 503-23.

(10) Ware, N. C., Idoko, J., Kaaya, S., Biraro, I. A., Wyatt, M. A., Agbaji, O., ... & Bangsberg, D. R. (2009). Explaining adherence success in sub-Saharan Africa: an ethnographic study. PLoS medicine, 6(1).

(11) Henderson, B.A., Kim, J.Y., Ament, C.S., Ferrufino-Ponce, Z.K., Grabowska, A., and Cremers, S.L. “Clinical pseydophakic cystoids macular edema: Risk factors for development and duration after treatment.” Journal of Cataract & Refractive Surgery. 33.9 (2007): 1550-1558.

(12) Lloyd, B. “The Power of Postoperative Eye drops.”Eye On Vision, WebMD, Sept. 2007, https://blogs.webmd.com/.

(13) Okeke, C. O., Quigley, H. A., Jampel, H. D., Ying, G. S., Plyler, R. J., Jiang, Y., & Friedman, D. S. (2009). Adherence with topical glaucoma medication monitored electronically: the Travatan Dosing Aid study. Ophthalmology, 116(2), 191-199.

(14) DiMatteo, M. R., Giordani, P. J., Lepper, H. S., & Croghan, T. W. (2002). Patient adherence and medical treatment outcomes a meta-analysis. Medical care, 794-811.

(15) Sleath, B. L., Krishnadas, R., Cho, M., Robin, A. L., Mehta, R., Covert, D., & Tudor, G. (2009). Patient-reported barriers to glaucoma medication access, use, and adherence in southern India. Indian journal of ophthalmology, 57(1), 63.

(16) Lacey J, Cate H, Broadway DC. Barriers to adherence with glaucoma medications: a qualitative research study. Eye. 2009 Apr;23(4):924-32.

(17) Castro A, Farmer P. Understanding and addressing AIDS-related stigma: From anthropological theory to clinical practice in Haiti. Am J Public Health. 2005;95:53–59.

(18) Ibid.

(19) Berwick, DM. Disseminating innovations in health care. JAMA 2003;289,1969-1975.

(20) Gray TA, Orton LC, Henson D, Harper R, Waterman H. Interventions for improving adherence to ocular hypotensive therapy. Cochrane Database Syst Rev. 2009 Apr 15;(2).

(21) Friedman DS, Hahn SR, Gelb L, Tan J, Shah SN, Kim EE, Zimmerman TJ, Quigley HA. Doctor-patient communication, health-related beliefs, and adherence in glaucoma: results from the Glaucoma Adherence and Persistency Study. Ophthalmology. 2008 Aug;115(8):1320-7, 1327.