Action and coping plans related to the behavior of adherence to oral anti-diabetic medication

Study Design:
Study Design: This mixed-methods study. Objective: To describe action plans related to the behavior of adherence to oral antidiabetic medications produced by people with type 2 diabetes mellitus and identify the challenges and coping strategies for the establishment of this behavior. Methods: The study followed-up 44 people with type 2 diabetes mellitus who used oral antidiabetic medications from southeast Brazil. Adults were invited to build action and coping plans based on the Implementation Intention Theory. The plans were quantitative and qualitatively analyzed. Results: Action plans included three major themes: (1) binding oral antidiabetic medication to time markers or the sleep/wake cycle; (2) in specific environments; (3) associated with daily life activities. The motivation for coping with the perceived barriers focused on placing the pills in visible places, asking for help from family members, establishing a routine and feeding properly. Conclusions: The most effective way to manage satisfactory oral antidiabetic medication adherence seems to be recognizing the perceived barriers by patients. The implementation of specific and individualized action and coping plans to overcome perceived barriers was the stark difference.


INTRODUCTION
Adherence to drug treatment is considered a determining factor for the successful treatment of non-communicable diseases (NCDs), although studies indicate that 17% up to 60% of patients -of all ages, sexes and ethnicities, and different health problems -do not adhere to their medications as prescribed 1,2 . Studies have presented great variation regarding oral antidiabetic medications (OADs), both in developed and developing countries (from 38.5% up to 89.7%), about its adherence [3][4][5][6][7] . Discontinuance of medication treatment can be considered a frequent problem in Type 2 Diabetes Mellitus (T2DM) patients and, consequently, contribute to inadequate glycemic control and to higher chances of disease complications 8 .
Several studies have highlighted the need for identifying determinants and barriers related to OAD adherence 3,6,7 . In this sense, the Theory of Planned Behavior (TPB) 9 is an extensively used theoretical reference in the study of health behaviors, including adherence to OADs 3,6,7,10 . This theory assumes that the intention (motivation) is the main determinant of behavior and that people with positive intention have higher chances of performing the desired behavior 9 .
However, studies show that people, even with positive intention, often fail in accomplishing the desired behavior when difficult or complex barriers/ obstacles are found [11][12][13] even in the adherence to OADs 7 . Therefore, interventions must be planned and implemented with aims to help motivated people performing the desired behavior 14 .
Considering this perspective, Gollwitzer 15 proposed the "Implementation Intentions" as a theory to help people with positive intention to accomplish desired behaviors. This theory allows the individual to establish a relationship between specific situations that may prevent the behavior from being performed and the possible planned responses to these situations 15 . The Implementation Intentions can be performed through action planning, in which the person identifies where, how and when he/she will perform the behavior and through coping planning, focused on risk situations or barriers that may prevent, interfere or impede the accomplishment of the target behavior or the implementation of the planned actions. This strategy is an independent cognitive planning and comprises the mental connection between the anticipation of possible risk situations for the noncompletion of the planned behavior, as well as the possible coping responses to overcome these risk situations or barriers 11,15 .
A previous studies 10, 16 showed the effects of the Implementation Intentions theory in promoting adherence to OADs in people with T2DM under primary health care, evidencing an increase in adherence after the intervention. However, the action and coping plans that were raised were not described previously elsewhere. These plans can be considered guiding and introductory to encourage people with T2DM, alone or together with family or friends, to plan the taking of OADs in a way that is possible in their reality and to repeat this behavior in order to become a habit and, consequently, reduce glycemic levels. Knowing these plans by health professionals and managers, mainly nurses, doctors, and pharmacists, can enable these professionals to address these strategies in consultations with people with T2DM and promote adherence in practical scope.
Thus, this study aims to present the action plans related to the adherence behavior to oral antidiabetic medicines prepared by T2DM patients under follow-up in primary health care and to describe the perceived barriers and their coping strategies to accomplish this behavior. To the best of our knowledge, there are no studies that have presented action and coping plans to promote of adherence to OADs, especially in people with T2DM under primary health care.

Design, population and study location
This mixed-methods study is derived from a previously single-blind randomized controlled study (RCT) with parallel groups (Trial registration -REBEC -RBR-439f77), which assessed the effect of the Implementation Intentions Theory on the promotion of adherence to OADs among people with T2DM under follow-up in primary health care 16 . Participants were recruited in two primary health care units in the southeastern region of Brazil, between February and December 2016. Inclusion criteria were: age ≥ 18 years; to be under continuous OADs use for at least six months; positive score to adhere to T2DM treatment in the intention scale (≥ to 4) and have the ability to read and write in Brazilian Portuguese. Cognitive status was assessed through a 10-item questionnaire adapted from a previous study 17 . This study had two groups -intervention group (IG) and control group (CG) -throughout 15 weeks, with six data collection steps. The detailed methodology can be assessed elsewhere 10,16 . Only participants from the IG were included in the analysis of the present study, since the action and coping plans were filled only by this subsample.

Action and coping planning
The construction of plans was based on theoretical assumptions of Implementation Intentions 15 , through the elaboration of action planning and coping planning, considering their respective overcoming strategies. Participants were asked to fill out, with the help of the researcher, a form in which up to three action plans about when, where and how (action planning) it was intended to take the OADs for the next two months. Up to three possible obstacles for the accomplishment of the behavior and one to three coping strategies (coping planning) were also raised. Both the action and copping plans were manually recorded in a spreadsheet by the researcher and individually filed for further reference throughout the monitoring process.
Variables and instruments 1. Sociodemographic and clinical data: identification variables were collected, sociodemographic profile (sex, age, marital status, educational level, employment status, family arrangement, individual and family income) and clinical characterization (comorbidities, time of diagnosis of T2DM, prescribed treatment, measurement of glycated hemoglobin (A1c), current medical prescription, use of OADs and access to the medicines) were made through interviews in a restricted environment.

2.
Behavior of adherence to OADs: was measured through an instrument created and used in a previous study 7 based on the TPB 9 . The instrument is composed of a single question and a four-point Likert-type scale and the answers vary from 1 (rarely or never) up to 4 (every day or almost every day of the week).

3.
Measurement of adherence to OADs: was obtained through the Brazilian instrument Global Evaluation of Medication Adherence (GEMA) 7 , which classifies adherence proportions as appropriate dose (≥ 80% of the prescribed dosage) or insufficient dose (< 80% of the prescribed dosage). The overall evaluation of adherence was made in four groups considering medical prescription: (Group I), adequate doses and care procedures; (Group II), adequate doses and inadequate care procedures; (Group III), inadequate doses and adequate care procedures; (Group IV), inadequate doses and care procedures.

4.
Intention: measured through an instrument composed of six questions with a five-point Likert-type scale, which was previously created 7 and based on the TPB 9 . The arithmetic mean of the scores measured in six items was calculated to obtain the mean of intent. Participants with a mean score greater than or equal to 4 were considered as having a positive intention.

Sample size
Sample estimation was performed for the RCT 16 . The Chi-square test was used for such, adopting 80% power and 1.25% significance level. The significance level was determined after applying the Bonferroni criterion. The estimated sample was of 37 individuals for each group. Considering a 20% loss rate, the final sample size was at least 44 individuals for each group.

Data analysis
The characterization data of the participants was submitted to descriptive statistical analyses. The developed plans were analyzed according to recommendations for content analysis in the context of theories on the study of behavior, being subjected to qualitative and quantitative analyses corresponding to the elaboration of one list for the action plans, one for the anticipated obstacles and one for coping plans 18 . Following, they were grouped by similarity of themes or ideas, enabling the frequency with which they were reported.

Ethical aspects
The study was approved by the local Research Ethics Committee (Document n. 47962915.4.0000.5404). The main study that originated this one followed the recommendations of the Consolidated Standards of Reporting Trials (CONSORT) 19 and was registered in the International Clinical Trials Registration Platform (ICTPR) via the Brazilian Clinical Trials Registry (ReBec), under the record RBR-439f77.

Sample characterization and characterization of adherence to oral antidiabetic medicines
Study participants were 44 people with T2DM under primary health care. The sample was composed mainly of women, with low education and in the use of polypharmacy. At baseline, only 27.3% of participants were considered as adherents from the overall adherence assessment (Table 1). Table 1 Sociodemographic and clinical characteristics.

Description of action and coping planning
Considering the plans related to taking the medicine, these were associated with taking the medicines at certain time counters, such as before or after meals (breakfast, lunch and dinner) or associating them to the sleep/wake cycle (waking up and before going to sleep). Regarding where to take the OADs, most plans were built by referencing specific home location (bedroom or kitchen). Regarding how to take the medicines, plans associated with activities of daily living (ADL) were the most common, such as during toothbrushing or bathing, and taking the medicines with a glass of water, juice or tea ( Table 2).
Different situations that may occur in everyday life, during work or leisure, were related to the obstacles of accomplishing the behavior. In daily life, the most frequently reported barriers were forgetfulness and the presence of adverse events (AEs). Coping plans designed to overcome obstacles in daily life were: placing pills in strategic locations, feeding every three hours in small portions, establishing a routine for meals and associating it to taking the OADs (Table 3). Table 2 Presentation of action plans elaborated by people with type 2 diabetes mellitus.

When (time markers)
Associate the taking of medicines after meals (breakfast, lunch and dinner) 43 97.7 Associate the taking of medicines before meals (breakfast, lunch and dinner) 25 56.8 Associate the taking of medicines to the sleep/wake cycle (e.g., fasting or before going to sleep) 24 54.5

Where (in which place)
Bedroom (e.g., next to the nightstand) 16 36.4 Home kitchen (e.g., next to the fridge or cupboard or water fountain) 10  Before walking the pets 4 9.1 Table 3 Perceived barriers and coping plans elaborated by patients regarding daily life, work and leisure activities. Only being able to read block letters 3 6.8 Asking the doctor or nurse to rewrite the prescription in a clearer manner and using block letters 3 6.8

Perceived obstacles/barriers
Use of polypharmacy and change of medicines 3 6.8 Asking for help from a family member to organize the medicines Organizing each of the doses in pill organizers everyday 2 1 4.5

Unawareness of the treatment
Difficulty to understand the reason/ purpose of the prescribed drug 5 11.4 Searching for a health care professional from the unit or participating in diabetes groups and understanding the reason for taking each drug and how they act on the body Self-stimulating to control diabetes 4 1 9.1 2.3 Believing that diabetes will be cured without any intervention 1 2.3 Understanding that diabetes has no cure and needs treatment to avoid complications

Emotional aspects
Sadness caused by the death of spouse or family issues 2 4.5 Increasing the bond with friends and family 2 4.5

Other barriers
Unavailability of the drug in the health unit 4 9.1 Searching in another close health unit or going to a popular pharmacy with the prescription and personal documents 4 9.1 Difficulty to swallow the pill due to its large aspect (metformin)

DISCUSSION
This study aimed to describe the action plans related to the behavior of adherence to OADs produced by T2DM patients under follow-up in primary health care, as well as to identify perceived barriers and their coping strategies to accomplish this behavior. Our results suggest that the most effective way to manage OADs adherence is recognizing the barriers perceived by patients and the development of strategies to improve the management of drug-taking, focusing on the patients' routine, activities of daily living, work and leisure was fundamental to improve their adherence.
The implementation of specific strategies to overcome these barriers, instead of the classic approach of simplifying a complex medication regimen, was the difference in our study, corroborating with the recommendations of the latest diabetes care guidelines 20 .
Previous TPB-based studies 3,6,7 showed that the low adherence to OADs by people with T2DM may be related to behavioral, normative and control beliefs. Thus, the preparation of action plans and planning based on the Implementation Intention strategy was crucial to assist participants and enable a positive intention on effective behavior and promotion of OADs adherence.
Despite the low level of education found in this study, both action and coping plans and the identification of barriers were designed by participants in conjunction with the researcher in a non-directive manner, following previous recommendations 14 . Evidence points that involving and valuing the patient's preferences for optimizing strategies in drug therapy management may increase engagement and motivation and, consequently, may increase the adherence to drug therapy 21,22 .
In several studies [23][24][25] , barriers such as forgetfulness, the presence of adverse events and difficulty establishing routines were some of the main reasons for non-adherence to medication in different scenarios, populations and health conditions. A previous study 23 showed that people with T2DM do not take their medications when they feel ill, are too busy, and cannot follow a previous routine, especially when they have meals in appropriate times.
Barriers such as forgetfulness, lack of routine to have meals and coping with emotional situations were also present in our study in daily living situations, at work and during leisure. For such, the coping strategies proposed by the patients themselves focused on placing the pills in strategic places, asking for help from family members to remind them, eating every three hours, drinking at least two liters of water a day, standardizing meal times, increasing the bond with friends and relatives and keeping the medicines in the purse or wallet when running errands or performing leisure activities. In this sense, nurses must be mediators and facilitators for constructing these plans, significantly contributing to the management of T2DM and continuity of care for the disease.
Another relevant barrier found in this study was adverse events, such as hypoglycemia, dry mouth, thirst or diarrhea. This barrier seems to be very specific to the use of AODs and T2DM patients, and points to the need for health professionals to build a stronger relationship with patients and working closely in the monitoring of therapeutic plans to improve adherence rates, especially in people with comorbidities and in use of polypharmacy.
The findings showed that most action plans were associated with binding the taking of AODs to time markers or the sleep/wake cycle. Forgetfulness, the establishment of a routine and the presence of adverse events were the most prevalent barriers raised by patients. Coping plans were designed to consider daily activities, such as placing the pills in easy to spot places, establishing a routine and feeding properly. These were the most reported strategies to overcome the existing gap to accomplish the behavior. Targeted interventions that encourage reflection about changing behaviors are beneficial and meaningful to promoting adherence to OADs and as strategies to be used in clinical practice.
Although this study provides new evidence about the importance of strategies to promote adherence to OADs, there are some limitations. Our findings are not generalizable to other scenarios, such as tertiary services that care for more complex patients; a subjective measure was used, i.e., selfreport to evaluate adherence to OADs, despite using a validated instrument (GEMA) that, in addition to measuring the adherence proportion, also considers the overall evaluation of adherence. Future studies could incorporate objective adherence measures, such as monitoring serum levels of medicines, evaluating biochemical laboratory tests and directly quantifying the therapeutic plan.
Thus, efforts to understand the adherence to drug treatment can be considered daily challenges to be achieved, since the mechanisms involved in this behavior are still complex 25 . Future studies on the effectiveness of these behavioral strategies should be conducted with T2DM patients to refine these interventions, seeking their replication in clinical practice.

CONCLUSION
The most effective way to manage satisfactory OADs adherence seems to be recognizing the perceived barriers by patients, and the development of strategies to improve drug-taking management; with focus on people's routine, daily living activities, work and leisure. The implementation of specific and individualized action and coping plans to overcome perceived barriers, instead of the classic approach of simplifying a complex medication regimen, was the stark difference in this study, corroborating with worldwide recommendations for managing T2DM.
In conclusion, involving and valuing people with T2DM when managing strategies for adhering drug to therapy may increase engagement and motivation and, consequently, may increase the adherence to drug therapy; which leads to a better quality of life and more prolonged survival.