Recommendations on How to Improve Medication Adherence Studies in the Field of Transplantation

In Brief

Nonadherence is frequent and deleterious after organ transplantation. The author comments on the beneficial influence of electronic medication dispenser use on nonintentional nonadherence but outlines thoughtfully the other aspects of nonadherence that would deserve an increased research effort towards a multidimensional approach that might lead to improved results.

Henriksson and colleagues¹ present a prospective study using an electronic monitoring device (EMD) to minimize unintentional nonadherence after kidney transplantation. The results showed that a pill bottle was opened within the allotted time window very accurately: 98% of the time. A critical note is that opening the bottle does not indicate ingestion of said pills, although EMDs are often used to measure adherence, and are considered by some as the gold standard. Nonadherence increased over the 1-year follow-up period which replicates findings from previous studies.^2-4 Furthermore, nonadherence varied according to the time of day and day of the week: evenings and Thursdays and Saturdays were more problematic. No significant differences were found between the experimental group (standard care plus an EMD) and control group (standard care without EMD) on renal function (P-creatinine level), blood concentration of tacrolimus, and outpatient visits. There was a trend for a higher biopsy-verified rejection rate in the control group, which may have arguably been significant if the sample had been larger.

The study has a number of strengths which contribute to the development of the field. First, the study addresses a pertinent issue in transplantation. Improvements in clinical outcomes have primarily been booked in the first year after transplantation; greater improvements in longer-term outcomes are still needed. One of the potential targets to realize these long-term improvements is medication adherence.⁵ Second, the study moves on from observation to intervention. Nonadherence after transplantation is a well-recognized and well-documented problem.^3,6 Patients who are nonadherent run the risk of losing their graft (eg, heart, lung, liver, kidney, and also face, or limb) and ultimately their lives. However, very few studies offer effective solutions to this issue.^7,8

Despite these strengths, there are also areas for improvement which are typical of research in this area. The aim of this commentary is thus to highlight these potential areas for improvement in research on medication adherence after transplantation, with the article of Henriksson merely as an illustration. In the introduction, the authors emphasize the fact that sufficient information and education is given on medication use, and despite this “carefully repeated information,” nonadherence persists. Two points can be made here.

First, behavior is determined by more than knowledge alone. Multiple factors (eg, emotional, cognitive, behavioral, social) influence health behavior. Models that attempt to predict change in health behavior (such as the Transtheoretical Model, Integrative Model of Behavioral Prediction, Social-Cognitive Theory, Self-Regulation Theory, and the Capability-Opportunity-Motivation Model) integrate factors, such as confidence in performing the behavior (self-efficacy), perceived norm, attitudes, beliefs, motivation, and intentions. Therefore, solely providing information to improve knowledge without addressing the aforementioned predictors is insufficient to bring about change in adherence behavior. Multidimensional interventions addressing these various contributing factors are likely to be the most effective in promoting adherence after transplantation.^7,8 Collaboration between medical professionals and behavioral scientists would greatly improve the work in this area because medication nonadherence is a behavioral issue rather than a medical one. Otherwise stated, it is a behavior that is performed (or not), which has consequences for medical outcomes. Health psychology has a long tradition of studying medication (non)adherence;⁹ however, this wealth of literature is poorly represented nor used in current studies on medication adherence after transplantation. The result is the development of interventions that are not informed by this body of literature, nor are they grounded in theories of behavioral change. To improve the quality of interventions, a multidisciplinary approach including allied health professionals is imperative. Involving patients themselves in intervention development is also recommended.¹⁰ An example of an initiative to stimulate such collaboration the stipulation by the Dutch Kidney Foundation that grant proposals submitted for funding in the Kolff Social Science Call must include a social scientist in the research team. This reflects the need to work together to improve the quality of research on clinical issues, such as medication adherence.

Second, this paper illustrates the tendency in medication adherence research to focus on patient-related and therapy-related factors. (I admit to being guilty of this myself [eg, 2]). Examples of patient-related factors include knowledge, attitudes, and beliefs. Examples of therapy-related factors include the number of pills, timing, and mode of delivery. Consequently, interventions are typically aimed at changing these factors. Henriksson and colleagues state “The reasons why patients do not take their medications vary from individual to individual”; however, reasons for nonadherence may also vary from situation to situation, family to family, or country to country. This narrow focus on the patient neglects factors on other ecological levels, such as interpersonal, organizational, community, health system, or societal, which have also been suggested to influence adherence.¹¹ We need to broaden our focus and critically assess how posttransplant care is organized, who is addressing nonadherence and are they trained to do so, whether interventions are evidence-based, whether factors on all ecological levels are addressed, and to what extent these strategies are effective.

Finally, we must appreciate that one size does not fit all. In the study by Henriksson and colleagues, they offer a standardized solution to nonadherence; however, it important to recognize that 10% of patients in the experimental group dropped out due to feelings of being monitored or finding the EMD stressful and worrying. Therefore, this approach was unsuitable for these individuals. This illustrates that interventions should be tailored to the goals, ideas on decision-making and responsibility for treatment, self-management support needs, and capabilities of each individual patient.⁷ Such tailored interventions are more likely to be effective than a one-size-fits-all approach.

In conclusion, more research is needed to move on from observation to developing and testing interventions to promote immunosuppressive medication adherence after transplantation. Such research would benefit from multidisciplinary authorship, involvement of patients, theoretical underpinning, tailoring, and a multidimensional and multilevel approach.

ACKNOWLEDGMENT

The authors thank Willem Weimar for reviewing the first draft.