Self-reported barriers to medication adherence among chronically ill adolescents: a systematic review.

Journal of Adolescent Health 54 (2014) 121e138

www.jahonline.org Review article

Self-Reported Barriers to Medication Adherence Among Chronically Ill Adolescents: A Systematic Review Signe Hanghøj, M.A., M.P.H., and Kirsten A. Boisen, M.D., Ph.D. * Center of Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Article history: Received April 12, 2013; Accepted August 15, 2013 Keywords: Adolescence; Barriers; Adherence; Chronic illness; Self-reported; Synthesis

A B S T R A C T

Purpose: To investigate self-reported barriers to medication adherence among chronically ill adolescents, and to investigate whether barriers are unique to specific chronic diseases or more generic across conditions. Methods: A systematic search of Web of Science, PubMed, Embase, PsycINFO, and CINAHL from January 2000 to May 2012 was conducted. Articles were included if they examined barriers to medication intake among chronically ill adolescents aged 13e19 years. Articles were excluded if adolescent’s views on barriers to adherence were not separated from younger children’s or caregiver’s views. Data was analyzed using a thematic synthesis approach. Results: Of 3,655 records 28 articles with both quantitative, qualitative, and q-methodology study designs were included in the review. The synthesis led to the following key themes: Relations, adolescent development, health and illness, forgetfulness, organization, medicine complexity, and financial costs. Most reported barriers to adherence were not unique to specific diseases. Conclusion: Some barriers seem to be specific to adolescence; for example, relations to parents and peers and adolescent development. Knowledge and assessment of barriers to medication adherence is important for both policy-makers and clinicians in planning interventions and communicating with adolescents about their treatment. Ó 2014 Society for Adolescent Health and Medicine. All rights reserved.

Chronic illness among adolescents is an important and increasing global public health concern. It is estimated that around 10% of adolescents suffer from a chronic disease affecting daily life [1]. Living with a chronic condition encompasses many complex behaviors that the patient has to add to daily routines including taking medication, following a diet, and/or executing lifestyle changes, as well as monitoring symptoms and attending outpatient clinical controls [2]. Insufficient adherence to long-term medical treatment is a major global health-threatening problem, and treatment adherence seems to be a larger challenge to chronically ill adolescents compared with children and adults [3,4]. * Address correspondence to: Kirsten A. Boisen, M.D., Ph.D., Center of Adolescent Medicine, 4101, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail address: [email protected] (K.A. Boisen).

IMPLICATIONS AND CONTRIBUTION

Insufficient adherence to medical treatment is a common health-threatening problem in chronic illness. This review contributes with adherence barriers across a range of chronic conditions from the adolescents’ own perspective. Some barriers seem to be specific to adolescence and knowledge of these barriers may improve clinical interventions.

Exploring barriers to medication adherence among chronically ill adolescents is important for several reasons. First of all, missing medical treatment can have serious consequences for health and result in increased morbidity and mortality [5]. Also, the economic burden of patient nonadherence is enormous [6,7]. Knowledge of barriers to medical treatment may improve the planning of interventions as well as an individual approach to young patients. Disease-specific reviews have been undertaken to clarify adolescents’ own perceptions of barriers to treatment; for example, in asthma [8,9], diabetes type 1 [10], and HIV [11]. To our knowledge, only a few reviews have focused on comprehensive insight of adolescents’ perceptions of barriers to treatment. For example, Kyngäs [12] who included asthma, type 1 diabetes mellitus, arthritis, and epilepsy. Our systematic review seeks to address this gap by examining self-reported barriers to

1054-139X/$ e see front matter Ó 2014 Society for Adolescent Health and Medicine. All rights reserved. http://dx.doi.org/10.1016/j.jadohealth.2013.08.009

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S. Hanghøj and K.A. Boisen / Journal of Adolescent Health 54 (2014) 121e138

medication adherence among chronically ill adolescents among a broad range of chronic diseases. The review question was: Which barriers to medication adherence do chronically ill adolescents perceive? We also wanted to highlight the most common perceived barriers across chronic diseases in order to investigate whether they are unique to specific diseases or can be characterized as disease-independent. To emphasize the adolescents’ voice we decided to focus on so-called “views studies,” which look solely at the barriers perceived by the adolescents. Views studies can be characterized as “people’s views in their own words, as well as questionnaires that use frequencies to quantify the proportion of people with a particular view or preference” [13]. Method Search strategy The following databases were searched for the period January 2000 to May 2012: Web of Science, PubMed, Embase, PsycINFO, and CINAHL. Google Scholar was searched for additional articles. Also, reference lists of all the identified articles were assessed for eligibility and reviews about adolescence and adherence were screened for additional relevant studies. The search strategy utilized both MeSH and non-MeSH terms. The following general search strategy was developed: Chronic disease OR chronic* AND adolescents OR adolescence OR teenage* OR youth AND adherence OR compliance OR self-management OR concordance. The full search strategy is available from the first author (S.H.) on request.

qualitative studies [14]. Thus, given that this review contains a significant portion of qualitative studies, we found it appropriate to use a quality checklist without a ranking score. S.H. and K.A.B. did the quality assessment individually and later discussed the results of the assessment together. We used a checklist developed by Mills [15,16] inspired by the Critical Appraisal Skills Program [17]. This quality assessment gives a thorough overview of the trustworthiness and transparency of each study. It is available from the authors on request. Data extraction and synthesis We used a thematic synthesis based on an interpretive, inductive approach in order to synthesize the findings. Included studies were extracted in a predesigned template (Table 1). In the qualitative studies, barriers were all presented descriptively, whereas barriers in the quantitative studies were presented as percentages. In the column “barriers” we reproduced outcome as it was presented in each article to strengthen the transparency of the synthesis. We were inspired by the tools and techniques for thematic synthesis to compare and contrast themes on barriers [18e20]. S.H. wrote the final synthesis, while all themes were continuously discussed with K.A.B until consensus was reached to ensure a common understanding of the themes. Then each article was reread to ensure that all barriers mentioned were included in the synthesis, so that all adolescent views were integrated. Results Study characteristics

Inclusion and exclusion criteria The inclusion criteria were: chronically ill adolescents aged 13e19 years. If a study had a wider age span, we decided to include the study if the mean age of the participants was between 14 and 18 years. Only somatic illness was included. Included studies had to have focused on exploring the views of adolescents, and had to have contained barriers to medication adherence in terms of medication intake as a main objective. Studies were only included if they were published in English and were of a western origin. To include the adolescent’s views, only qualitative studies, survey studies, and q-methodology studies where barriers were presented either descriptive or in percentages were included. Epidemiologic studies, intervention studies, and reviews were not included. The exclusion criteria were: studies on children and adults (unless data on adolescents were also included), participants being mentally ill, and studies where barriers were reported by parents or healthcare providers, or studies that did not clearly separate answers given by parents/ healthcare providers and adolescents, or between age groups, for example, children and adolescents. Studies focusing on adherence in terms of behavior such as adherence to treatment appointments, following special diets, and making lifestyle changes were not included except for studies also focusing on adherence to medication intake.

Studies retrieved. The database search led to 3,486 published English-language titles and after identifying additional records through other sources, 3,655 records were ready for an initial screening (Figure 1). From these records, 293 abstracts were selected for an in-depth screening. S.H. and K.A.B. screened the abstracts individually and discussed inclusion until consensus was reached. Duplicates were identified, and studies that did not meet the inclusion criteria were excluded. Then 73 full-text articles were assessed for eligibility. Any disagreements about including or excluding a study were resolved by discussion until consensus was reached. In this stage of the process 45 articles were excluded for specific reasons, and 28 relevant articles were left for inclusion in the review: 11 qualitative, 15 quantitative, and two using a q-methodology [21]. Sample and participants characteristics. Sample sizes for the quantitative studies varied from 31 to 1,061, while the sample sizes in the qualitative studies varied from 4 to 49. Counting the participants of all studies, this review embedded 2,501 participants suffering from at least one of the following chronic conditions: diabetes, asthma, cystic fibrosis, inflammatory bowel disease, chronic kidney disease, epilepsy, rheumatoid arthritis, sickle cell disease, hemophilia, cancer, and Pierre Robin syndrome, or participants had undergone a solid organ transplantation (kidney, liver, or heart).

Quality assessment Barriers found It has been discussed whether it is meaningful to assess study quality of qualitative studies. Furthermore, there is a lack of guidance on quality criteria applicable to both quantitative and

Synthesis. The synthesis led to the following key themes with subcategories in brackets:

Table 1 Studies included in the review Age þ mean

Country

Aim of the study

Survey Studies Dziuban [27]

Diagnosis

United States

1. Identifying barriers 12e20.9 (16.3 þ/ 2.1) Cystic fibrosis to treatment adherence and attitudinal patterns 2. Exploring ways to improve adherence

Gray [39]

United States

1. Examine barriers to adherence 2. Examine anxiety/ depressive symptoms on adolescent adherence

Greenley [47]

United States

Kyngäs [22]

Finland

1. Describe barriers to 11e18 adherence 2. Examine demographic, disease-related, and treatment regimenrelated correlates of adherence barriers 3. Examine relationships between frequencies of barriers and level of nonadherence 1) Describe factors 13e17 that affect compliance 2) Compare compliance and factors connected to compliance between adolescents with

13e17 (15.5 þ/ 1.4) Inflammatory bowel disease

Inflammatory bowel disease

Number

Design method and data analysis

n ¼ 60 35 females 25 males

Survey study Method: A specially designed questionnaire including 10 questions related to nonadherence. Data analysis: A total barrier score was calculated. Furthermore the result of the questionnaire was combined with objective measures of disease severity.

n ¼ 79 55.6% females 44.4% males

n ¼ 64 50% females 50% males

Asthma, epilepsy, n ¼ 1,061 rheumatoid 534 females arthritis, insulin 527 males dependent diabetes mellitus

Barriers identified

- Forgetting or lost medication 53% - Too busy or takes too much time 38% - Too many treatments 18% - Embarrassing 13% - Wanting to be normal 12% - Treatment issues: Taste, price, etc. 12% - Side effects 7% - Unsure treatment is needed/ useful 7% - Running out of medications 7% Survey study - Just forget 84.8% Method: - Wasn’t home 43% Medication Adherence Measure - Interferes with activity 34.2% (MAM). The questionnaire - Ran out/didn’t fill 15.3% consists of one open-ended - Hate the taste 12.7% question and seven forced - Not feeling well 12.7% choices. - Refused to/defiant 11.4% Data analysis: - Don’t think necessary 10.1% A total barrier score was calculated. - Hard to swallow pills 7.6% Pearson product correlations - Don’t like the side effects 6.4% between disease severity, - Other reasons: barriers to adherence, depressive - Fell asleep/was sleeping 3.9% symptoms, and adherence were - Too busy 2.6% calculated. - Tired 3.9% - Pharmacy ran out of medicine 1.3% - Did not fill pill box 1.3% - Lazy 1.3% - Lost medicine 1.3% Survey study - Lack of time 33% Method: Questionnaire with six - Medication side effects 14% questions - Feeling well 16% Data analysis: A total barrier score - Belief medication was ineffective was calculated. Furthermore 14% sample t-test was conducted to - Pharmacy barriers (e.g., pharmacy examine whether the number of did not stock medication, barriers differed between those difficulty accessing pharmacy) reporting perfect vs. imperfect 8% adherence. - Insurance barriers (e.g., no insurance, insurance did not cover medication) 5% Survey study Method: Questionnaire (based on a theoretical model and on a literature review). Data analysis: Relationship between variables and disease groups were analyzed by cross tabulation, and significance


Reference

All diseases: - Motivation - Sense of normality - Attitude - Energy and will-power - Experience of results - Support from the parents - Support from nurses 123

(continued on next page)

Reference

124

Table 1 continued Country

Aim of the study

Age þ mean

Diagnosis

Number

asthma, epilepsy, and rheumatoid arthritis.

Design method and data analysis levels were assessed with chisquare test.

Finland

1) Describe compliance 13e17 2) Analyze factors connected to compliance

Epilepsy


Modi [44]

United States

1) Examine barriers to 13e18 SCD treatment adherence and strategies to facilitate adherence across multiple regimen components 2) Determine intrafamily convergence of adherence barriers and strategies using caregiveradolescents dyads.

Sickle cell disease


de Moerloose [40]

Switzerland/ Netherlands/ UK

1) Assess the level of adherence 2) Assess the factors that influence adherence

Severe hemophilia

n ¼ 45 No gender description

13e19

Survey study Method: Questionnaire (based on a theoretical model of compliance of adolescents with diabetes and on a literature review). Data analysis: Relationship between variables (e.g., compliance, sense of normality, subjective outcomes, attitude, and parental support) were analyzed by cross tabulation, and significance levels were assessed with chisquare test. Survey study Method: 1) DMI-SCD (disease management and barriers interviewdsickle cell disease) a 60-item self-report 2) A list of 22 barriers identified in the literature from where the adolescents should choose any relevant barriers 3) An open-ended question to generate their own response to barriers Data analysis: Descriptive analyses were conducted to identify caregiver and adolescent endorsements of barriers and strategies for each treatment component along with their frequencies.

Survey study Method: Individual in-depth interviews Data analysis: A total barrier score was calculated. Furthermore

- Support from physicians - Threat to social well-being Epilepsy: - Support from friends - Emotional well-being IDDM: - Physical well-being - No motivation 55% - Weak sense of normality 67% - Negative subjective outcomes 60% - No energy and will power 59% - No support from parents 68% - No support from physician 60% - No support from nurses 59% - Negative attitude 68% - Threat to social well-being 63% - Threat to emotional well-being 56% - Fear of complications 41% - Fear of seizures 41% Pain management (n ¼ 25): - Forgetting or lost 58% - Taste aversions or side effects 38% - Desire to be normal 25% Oral antibiotics (n ¼ 6): - Taste aversions or side effects 50% - Difficulty swallowing 33% - Desire to be normal 33% - Medication efficacy 33% Transfusion (n ¼ 9): - Treatment pain or discomfort 33% - Taste aversion or side effects 22% - Multiple medications 22% Chelation therapy (n ¼ 5): - Treatment pain or discomfort 50% - Forgetting or lost 43% Hydroxyurea (n ¼ 2): - Forgetting or lost 100% Hydration (n ¼ 13): - Taste aversion or side effects 31% - Time management 23% Vitamin and mineral supplements (n ¼ 13): - Forgetting or lost 58% - Taste aversions or side effects 33% - Equipment broken or missing 25% - Forgetfulness > 55% - Lack of time 35% - Reduction, fluctuation, disappearance of symptoms 25% - Convenience 25%


Kyngäs [23]


3) Analyze reasons for noncompliant behavior 4) Identify unmet needs or patient problems and also to provide recommendations

United States

Develop a measure of 12e17 psychosocial barriers to adherence and examine relationships to patient characteristics, adherence, and hemoglobin A1C.

Rhee [29]

United States

1) Explore barriers to self-management 2) Examine the associations between barriers and psychosocial factors

Diabetes 1

13e20 (15.5 þ/ 1.7) Asthma

n ¼ 123 47.8% females 52.2% males


125



Mulvaney [24]

a multivariate logistic regression - Social/family stresses 25% analysis and a univariate - Travelling 25% regression analysis were - Failure to access peripheral vein performed. 22% - Differing perceptions of problem 20% - No faith in drug effectiveness 14% - Central venous access difficulties 11% - Decision making from parents to teenagers 11% - Availability of factor 10% - Concerns of adverse effects 7% - Refusal to try prophylaxis 5% - Misunderstanding of prescription 3% Survey study Stress and burn out 36% Method: 33 items were developed Time pressure and planning 23% through a literature review to Social support 22% create a questionnaire Stigma 16% Data analysis: Factor analysis Parental autonomy support 10% resulted in a 21-item fivecomponent solution. Furthermore the prevalence of barriers was calculated as percentages. Survey study - I hate the idea of giving up the Method: The illness management things the doctors say I have to survey consisting of 27 items give up 63% Data analysis: Factor analysis - I believe that if I take care of The barriers listed in percentages myself and follow my regimen, were received from the first my health will improve (R) 8% author on request. - I try to forget that I have an illness 50% - My regimen takes a lot of time and work 14% - Sometimes I can’t remember everything I’m supposed to do about my illness 53% - I don’t want my friends to know about my illness 10% - When there are changes to my regimen I sometimes get confused 33% - When I feel nervous or worried, it’s hard to follow my regimen 20% - None of my friends have to deal with this, why do I? 18% - My illness is easier to take care of than a lot of other illnesses (R) 15% - I understand what I am supposed to do to care for my illness (R) 6% - The doctors treat me like a little kid who can’t take care of her/ himself 10%

Reference

Country

Australia

Aim of the study

Age þ mean

1) Explore psychosocial 12e18 (mean: functioning females 14.6 2) Beliefs about males 14.3) treatment adherence 3) Difficulties with adherence 4) Concerns about living with a chronic illness

Diagnosis

Cancer (n ¼ 6) Pierre Robin syndrome (n ¼ 1) Cystic fibrosis (n ¼ 2)

Number




Survey study Method: Questionnaire called “Managing your health” consisting of seven written questions, the one related to adherence barriers was openended. Data analysis: The open-ended question was analyzed thematically, and themes were counted.

- I don’t always trust the doctors and nurses 14% - Following my regimen causes me physical pain or discomfort 4% - Nothing bad would happen to me if I didn’t follow my regimen 10% - My doctors are friendly and easy to talk to (R) 6% - It’s hard for me to plan things out carefully, so sometimes I don’t get around to following my regimen 27% - My regimen has side effects that I really don’t like 18% - My family doesn’t understand what it’s like to live with my illness 21% - I don’t mind if my friends bring up my illness or ask me questions about it (R) 6% - The doctors don’t seem to understand how much my regimen gets in the way of important things in my life 18% - My family gives me a lot of support to help me follow my regimen (R) 19% - The doctors do a good job of explaining things to me (R) 6% - It’s hard for me to stay organized enough to keep track of medications or other things related to my illness 21% - I refuse to give up time with friends to take care of my illness 18% - It feels like the doctors are too busy or rushed to talk to me about my illness and my regimen 7% - My regimen causes changes to my body that I don’t like 9% [(R) ¼ Reverse coded.] Control: - Too many restrictions - I don’t do it, they (i.e., mother and staff) do it - Time control when in hospital - Hard when working - Can’t remember them all the time - Takes over your life Aversions: - Hate it - Side-effects worse than disease


Rosina [41]

126

Table 1 continued

United States

Examine selfmanagement behaviors and glycemic control

12e21 (15.4 þ/ 2.1) Type 2 diabetes


Simons [35]

United States

1) Create Parent and adolescent Medication Barriers Scale (PMBS and AMBS) 2) Assess barriers to medication adherence

11e21 (15.8 þ/ 2.4) Solid organ transplant recipients


Survey study Method: Telephone survey consisting of 85 questions related to diabetes selfmanagement. Open-ended questions were included to ascertain adolescents’ perceptions about barriers. Data analysis: Open-ended questions were coded and bivariate analyses were performed to compare most recent values with patient characteristics and survey responses. Survey study Method: A barrier scale based on PEDS-TX, version 1 designed by Rodrigue (2004) to make the Adolescent Medication Barriers Scale (AMBS) Data analysis: Factor analysis. The barriers listed in percentages were received from the first author on request.

Disease frustration/adolescents issues: I don’t like to take the medicine at school 22.1% I feel that it gets in the way of my activities 9.9% I am forgetful and I don’t remember to take the medicine every time 38% I do not want other people to notice me taking the medicine 15.5% I sometimes just don’t feel like taking the medicine 15.5% I don’t like what the medication does to my appearance 25.4% I am tired of taking medicine 32.4% I am tired of living with a medical condition 32.4% Ingestion issues: I believe that the medicine is hard to swallow 14.1% I believe that I have too many pills to take 26.8% I don’t like how the medicine tastes 28.2% I believe the medicine has too many side-effects 16.9% I get confused about how the medicine should be taken (with or without food, with or without water, etc.) 7% Regimen adaption/cognitive I am not organized about when and how to take the medicine 8.5%

127



Rothman [48]

- Information overload, they expect you to remember, can they? - Too many pills - Painful Financial: - Expensive Emotional: - No point, you die anyway Denies nonadherence 12% Forgets or lack of motivation 53% Distracted by competing interests 17% Other 18%

Reference

128


Aim of the study

Age þ mean

Diagnosis

Number

United States

Identify barriers to medication adherence



Simons [36]

United States

1) Validate the Parent and Adolescent Medication Barrier Scale (PMBS and AMBS). 2) Examine the relations of perceived barriers to medication adherence



Survey study Method: Medication Adherence Measure (MAM). The questionnaire consists of one open-ended question and seven forced choices. Interviewed by telephone. Data analysis: For barrier coding inter-rated agreement and Kappa coefficients were calculated between rates. Survey study Method: The Adolescent Medication Barriers Scale (AMBS). interviewed by telephone. Data analysis: Factor analysis. The barriers listed in percentages were received from the first author on request.

Barriers identified I find it hard to stick to a fixed medication schedule 15.5% Sometimes I don’t realize when I run out of pills 29.6% Sometimes it’s hard to make it to the pharmacy to pick up the prescription before the medicine runs out 11.3% Forgot/distracted 28.8% Poor planning/scheduling problems 57.5% Physical barriers/medication issues (tired, sick, hard to swallow pills, taste) 9.6% Voluntary resistance/attempt to be normal 4.1%

Disease frustration/adolescent issues: I don’t like to take the medicine at school 15.2% I do not want other people to notice me taking the medicine 17.6% I feel that it gets in the way of my activities 27.5% I am forgetful and I don’t remember to take the medicine every time 52.9% I sometimes just don’t feel like taking the medicine 33.3% I don’t like what the medication does to my appearance 31.4% I am tired of taking medicine 35.3% I am tired of living with a medical condition 33.3% Regimen adaption/cognitive issues: I am not very organized about when and how to take the medication 3.9% I find it hard to stick to a fixed medication schedule 13.7% Sometimes I don’t realize when I run out of pills 23.5% Sometimes it’s hard to make it to the pharmacy to pick up the prescription before the medicine runs out 25.5% Ingestion issues: - I believe that the medicine is hard to swallow 5.9% I believe that I have too many pills to take 19.6%


Simons [45]


I believe the medicine has too many side-effects 27.5% I don’t like how the medicine tastes 25.5% I get confused about how the medicine should be taken 9.8% Just forgot 56.4% Wasn’t at home 20% Interferes with activity 18% Hate the taste 16% Ran out 7% Refused 5% Not feel well 3% Hard to swallow 1%

Renal transplant patients


Survey study Method: Medication Adherence Measure (MAM). The questionnaire consists of one open-ended question and seven forced choices. Data analysis: Overall average adherence scores were calculated across all medications.

United States

Identify psychosocial resources and barriers to selfmanagement

Type 2 diabetes

n ¼ 10 9 females 1 male

Buston [26]

UK

Understand the reasons for nonadherence

Asthma


van Dellen [38]

Nether-lands

Asthma

n ¼ 14 0 females 14 male

Hommel [37]

United States

1) Explore and compare 13e17 EM (explanatory model) in etiology of the condition, onset of symptoms, course of illness and treatment of the mothers and children from Moroccan, Turkish, Surinamese and Dutch backgrounds. 2) Gain more insight into the groups’ beliefs about causes, consequences, symptoms and the self-management of asthma Examine themes of 13e17 patient and parent- (15.75 þ/ 1.08) reported factors that impact treatment

Qualitative - Comorbidity. For example, having Method: Semistructured interviews asthma and managing blood Data analysis: A modified grounded glucose is difficult because of theory approach was used medications currently taken. - Dietary (not relevant in relation to medication adherence) - Fitting with peers. For example, feeling different from their peers, embarrassed to tell friends. Qualitative - Forgetfulness Method: In-depthinterviews - Ineffective medication Data analysis: Grounded theory - Denial approach - Difficulty using inhaler - Inconvenience - Embarrassment - Fear of side effects - Laziness Qualitative - Mothers interrupting Method: 4 focus groups - Only take medicine when feeling Data analysis: Descriptive codes to symptoms compare and look for common - Want to manage the medication themes. Theory of Kleinman. myself

Inflammatory bowel disease


Qualitative Studies Auslander [25]

14e19 (16.4 þ/ 1.4)

14e20 (15.6)

Qualitative - Forgetting (hanging out with Method: Semistructured interviews friends, sleepovers, change of Data analysis: NVivo software was plans) used for coding and analyses. - Activities (e.g., travelling/ (continued on next page)

129

Examine potentially 11e18 modifiable barriers (14.27 þ/ 2.2) related to adherence


United States

Zelikovsky [46]

Reference

130


Aim of the study

Age þ mean

Diagnosis

Number

adherence: 1) Challenges to adherence 2) Factors that facilitate treatment adherence

United States

1) Elucidate conceptions about disease process, expression, and treatment 2) Perceived access to care barriers 3) Potential barriers for treatment nonadherence

13e19

Chronic kidney disease


Mulvaney [28]

United States

To document barriers and facilitators of self-management

13e19 (15.2 þ/1e 2.2)

Type 2 diabetes


Naimi [34]

United States

1. Describe adherence 15e18 to preventive asthma medications 2. Explore relevant beliefs and barriers to adherence

Asthma



vacation) - Parent-child conflicts (especially mother-child) - Poor understanding of the purpose of prescribed medication - Regimen complexity (number of medications, number of pills per dose) - Swallow pills Qualitative Method: Semistructured - Inconvenient timing requirements interviews - Taste and size of pills Comparison between Latinos (n ¼ - Side effects, including effects on 13) and non-Latinos (n ¼ 6) physical appearance (and being living in San Diego, California teased) Data analysis: Coding consensus, - Not take pills in front of everybody co-occurrence, and comparison (when out with friends) outlined by Willms and rooted in - Not wanting to have medicine in grounded theory. purse -“Not normal” - Positive and negative effect of social support and extended social networks Qualitative Adolescent psychosocial Method: six focus groups development: Data analysis: Themes were - Embarrassment/lack of normalcy analyzed using the framework - Rebellion (unwilling to accept approach elucidated by Pope. what adults were telling them) - Peers (peers asking questions, fear of rejection) Role of others with diabetes: - Others with poor selfmanagement habits affecting them - No friends with diabetes ¼> coping is difficult Environmental/contextual: - School (unhealthy food, teachers reaction) - Health care (doctors’ ignorance) - Home (the parents’ handling) Qualitative - Medication unnecessary Method: Semistructured face-to- No difference in symptoms face interviews without medication Data analysis: Content analysis with - Ambivalent about the benefit focus on common themes using - Forgetting a grounded theory structure. - No symptoms - Dislike the taste - Fear of addiction to medication - Medication affects appearance - Difficulty in organizing time - Prescribed too many medications - Losing the F/S inhaler - Staying with friends/family and left the medications behind


Johnson [33]


Epilepsy

n¼4 2 females 2 males

Liver transplant patients

n ¼ 14 Qualitative No gender description Method: Semistructured interviews Data analysis: Framework analysis (Ritchie & Spencer) in five stages using a series of matrices.

United States

Explore experiences and behaviors related to the selfmanagement of teens with asthma

14e18

Asthma


United States

Examine beliefs, feelings, and behaviors about inhaled asthma controller medication

12e20 (15.3 þ/ 1.9)

Asthma


United States

Taylor [32]

UK

Velsor-Friedrich [49]

Wamboldt [30]

Qualitative Method: One focus group Data analysis: Content analysis.

Impact of side-effects: - Feeling different from friends - Pain - Growth Responsibility for taking medication: - Conflicts with parents - Forgetting medication leads to normal life - Self-care (responsibility) is stressful Adherence to medication (other barriers): - Spontaneous activities - Parent’s anxiety - Rejection - Rebellion (a way of exerting control over parents) - Simply forget Qualitative - Ran out of medicine Method: Focus groups - Not carrying an inhalator on Data analysis: Ethnographic regular basis approach (Morgan, 1988 and - Medicine is not necessary when Kruger, 1998). you feel healthy - Asthma is not a serious condition Qualitative Beliefs and feelings: Method: Six focus groups - Being less adherent to test the Data analysis: The “long-table” asthma status strategy where exact statements - Medication is a sign of weakness are sorted into thematic - Fathers says “real men don’t take categories and subcategories. medications” - Medication only when needed (being sick) - Embarrassment - Friends afraid that asthma can infect them Behaviors: - Routines difficult - Activities disrupt medication routines - Forgetfulness - Being inactive so the asthma does keep steady Roles of parents and providers: - Missing information about the medication from the doctors - Bad communication with the doctor - Parental monitoring starts

131



Understand patient 13e17 (15.0) attitudes about treatment of medically intractable epilepsy and to document potential barriers Explore people’s lived 12e18 experience of life after transplantation

Swarztrauber [42]

- Conflicts at home - Uncomfortable taking asthma medications in front of friends - Side effects (dulling, fall asleep) - Simply forgetting - Frustration with the information from doctors

Reference

132


Aim of the study

Age þ mean

Diagnosis

Number


Barriers identified conflicts - Parents don’t care - Parental disagreement (mother vs. father) - Cannot afford

Q-methodology studies Bullington [31]

Identify, categorize and understand the opinions regarding not taking medications as prescribed

Netherlands

To uncover 12e19 preferences for self- (15.3 þ/ 2.1) management and hospital care of adolescents with various chronic conditions

13e17 (15.3)

Kidney transplant patients

n¼9 6 females 3 males

Q-methodology Method: Phase 1: Unstructured interviews Phase 2: Patients’ statements sorted into a questionnaire with nine categories ranging from “most like my feelings” to “most unlike my feelings” Data analysis: Analyzing data followed three statistical procedures: (1) correlation; (2) factor analysis; (3) computation of factor scores

Different chronic conditions


Q-methodology Method: Used semistructured interviews and rank-ordered 37 statements Data analysis: (1) Q-sorts were subjected to by-person factor analysis; (2) factors were interpreted and described as preference profiles.

If a study consists of more than one aim, the relevant sub-aim about barriers to adherence is highlighted (bold) in the table.

Most important barriers: - Forget to take medicine - Medicines do not taste good - Medicines make them feel bad - They have to take medicines too many times a day - They do not like to carry medicines with them - Forget to take medicine - Home life is not good - They feel depressed - Too much to remember about transplant thing - They have to take medicines too many times a day - Forget to take medicine - More attention from parents for missing medications - They have options if something goes wrong - They worry a lot about being “sick” - More attention from doctors for missing medications - They do not know who to ask if they have a problem with their medications Factors: 1) Medication issues 2) Troubled adolescent 3) Deliberate nonadherer Major themes represented in the Q-set: 1) Clinical environment/ organization of care 2) Physician/patient communication 3) Information provision 4) Self-management/independence 5) Therapeutic regimen 6) Disease perception 7) Contact with fellow patients Preference profiles: A) Conscious & compliant B) Backseat patient C) Self-confident & autonomous D) Worried & insecure


Jedeloo [43]

United States


133

Figure 1. Flow diagram.

(1) Relations (peers, parents, health professionals); (2) Adolescent development (strive for normality, freedom vs. control); (3) Health and illness (physical well-being, mental wellbeing, treatment perceptions, and worries); (4) Forgetfulness (forgetting because of activities, forgetting by coincidence); (5) Organization; (6) Medicine complexity; (7) Financial costs. A Top-5 of common perceived barriers across chronic diseases is highlighted in Table 2: forgetting by coincidence, physical wellbeing, strive for normality, peers, and parents (all subcategories). Relations Peers. Relations with peers appeared to be critical to adherence. In one study, a statistically significant association between adherence and threat to social well-being was found [22], and a statistically significant association between adherence and support from friends was found for adolescents with epilepsy [22,23]. Another study found that females reported larger overall psychosocial barriers to adherence related to social support. The study concluded it indicated that “girls look to friends for support more often than boys” [24]. Other studies found that many adolescents felt embarrassed telling peers about their disease [24e30] and it worried them to feel different from their peers [25,31,32]. Stigma in terms of social deviance was reported by 16% of adolescents with diabetes [28]. Also, taking medication in front of peers was a major issue to some [24,31,33e36], and some adolescents feared that their peers would learn about their disease [28,32]. On the other hand, some adolescents also expressed fear of rejection from peers if they were no longer ill due to the creation of a special identity through their disease. To

avoid rejection from peers, the adolescents may thus be less adherent [31]. Finally, a single study found that having friends with poor self-management affected the adolescent to lower adherence, while not having friends with the same chronic disease also could hamper coping [28]. Parents. Conflicts between adolescents and their parents seemed to be a major reason for nonadherence [32,34,37]. Factors such as “family stress” and a“bad home life” were listed as indicators of a conflictive environment [33,38,39]. The studies included pointed to the following two main reasons for conflicts: (1) parents’ difficulty in delegating treatment responsibility; and (2) lack of support from parents. Parents’ difficulty in delegating treatment responsibility may obstruct the shift in the decision-making process from parents to adolescent, and hinder the adolescents’ strive for autonomy and self-determination in relation to caring for his/her own medical regimen [24,28,30,32,40]. One study described how difficult it was for some parents to “let go” and let their children find their own routines [32]. Two studies found mothers’ interruption playing a role in nonadherence, as especially mothers are responsible for monitoring their child’s treatment [37,38]. One study indicated being monitored by parents was related to discomfort, but also that not being monitored was interpreted as a sign of parents who “don’t care” [30]. Some adolescents reported that their parents did not support them sufficiently [22,23,28]. In one study as many as 68% of adolescents reported “no support from parents” [23]. Some adolescents reported they were afraid to ask their parents for help with their medication [31]. Another study found that 21% of

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Table 2 Top 5 common reported barriers across diseases Asthma

Cancer

CKD

CF

Diabetes

Epilepsy

IBD

PRS

SH

SCD

SOT

Total

Physical well-being

[26] [29] [30] [34] [38]

[41]

[33]

[27] [41]

[22]

[42]

[37] [39] [47]

[41]

[40]

[44]

11 conditions 21 studies

Forgetting by coincidence

[26] [29] [30] [34] [49]

[41]

[27] [41]

[28] [48]

[39]

[41]

[40]

[44]

Strive for normality

[22] [29] [30] [22] [26] [29] [30] [34] [22] [29] [30] [34] [38]

[33]

[27]

[22] [28]

[22] [23]

[22]

[31] [32] [35] [36] [45] [46] [31] [32] [35] [36] [45] [46] [32] [45]

[33]

[27]

[22] [24] [25] [28]

[22] [23]

[22]

[22] [24] [28]

[22] [23]

Peers

Parents

[37]

RA

[22]

[44]

[40]



[31] [32] [35] [36]


[31] [32]


CF ¼ cystic fibrosis; CKD ¼ chronic kidney disease; IBD ¼ inflammatory bowel disease; PRS ¼ Pierre Robin syndrome; RA ¼ rheumatoid arthritis; SCD ¼ sickle cell disease; SH ¼ severe hemophilia; SOT ¼ solid organ transplant patients (kidney, liver, heart).

adolescents with asthma felt that the family did not understand what it was like to live with a chronic illness [29]. An example of unhelpful behavior was “not listening to the adolescent” [28]. Some fathers even encouraged their sons not to take medication at all because: “real men don’t take medications” [30].

dependent diabetes mellitus, and rheumatoid arthritis there was a statistically significant correlation between sense of normality and adherence [22]. As many as 25% of adolescents with sickle cell disease reported a desire to be normal [44]. One study found that the desire to be seen as normal interlinked all themes in the interviews with liver transplanted adolescents, and that the desire to achieve normality was so strong that the adolescents occasionally neglected things they knew they should do to remain healthy, for example, adhere to medical treatment [32] or carry along the medicine [33]. This is in line with a study of adolescents with asthma where 50% of adolescents with asthma tried to forget their illness. This study also found that 18% skipped their treatment as they felt it was unfair that they had to deal with a chronic condition when their peers did not have to do so [29].

Health professionals. One study found a statistically significant correlation between support from health professionals and adherence for both asthma, epilepsy, insulin-dependent diabetes mellitus, and rheumatoid arthritis [22]. Not getting support from health professionals seems to be related to poor communication with doctors especially [22,23,28,30,32,38,41,42]. Poor communication was expressed either as lack of information from doctors or as inadequate communication with doctors. In a study of adolescents with asthma, 18% reported that doctors did not understand how much the regimen got in the way of important things in life; 14% did not trust the doctor; and 10% felt that the doctor treated them like a little child [29]. This is in line with a study of adolescents with various chronic conditions where some expressed their wish to be treated as adults by health professionals, because they did not feel like children anymore [43]. One study found that doctors did not provide the adolescents with an adequate understanding of the expectations of their treatment and the nature of their disorder [42]. One of the most frequently heard complaints about the doctor was that he was very impersonal, cold, and communicated to the computer and not to the patient [38]. Some adolescents also reported that they got more attention from doctors, when they skipped their medication [31].

Freedom versus control. Some adolescents felt that the disease controlled their lives, and in one study of asthma patients as much as 63% reported that they “hate to give up the things the doctor says they have to give up” [29]. Adolescents with cancer felt that their treatment included too many restrictions and that the treatment took over their lives [41]. Several adolescents found it difficult to follow a scheduled treatment program accurately, and some preferred to manage their treatment themselves and thus change the treatment if it suited them better [38,43]. Some adolescents even declared that “living easy now is more important than being completely treatment compliant” [43]. Refusing to take any medication, interpreted as an ultimate desire for freedom, was reported to be an adherence barrier across several diseases [26,32,39,40,46].

Adolescent’s development

Health and illness

Strive for normality. Chronically ill adolescents often connect chronic illness to a feeling of not being normal [22,23,27,28,44,45]. In the study of adolescents with asthma, epilepsy, insulin

Physical well-being. Side effects were a common theme across most diseases [26,27,29,33,35,36,39e42,44,47]. A total of 38% with sickle cell disease reported having side effects [44], 17% and


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28% of transplant patients were afflicted with side effects [35,36], while side effects were a barrier for 6% and 14% with inflammatory bowel disease [39,47], and for 7% with cystic fibrosis [27]. Two studies found that insufficient adherence was induced by medication weight gain [31,33], hinder of normal growth [32], and some studies found that medication made the adolescents feel ill [32,41,46]. Among adolescents with a solid organ transplant, 25% and 31% felt uncomfortable about what the medicine did to their appearance [35,36]. Adolescents with insulin dependent diabetes mellitus reported treatment to be a threat to physical well-being and this showed significant correlation to low adherence [22]. Several studies found that adolescents who experienced a reduction of symptoms also perceived a reduced need for medication [30,31,34,38,40,47]. In a study of asthma, 10% of the adolescents argued that“nothing bad would happen to me, if I do not follow my regimen” [29]. Among adolescents with severe hemophilia, 25% reported that reduction, fluctuation, or disappearance of symptoms was a barrier to medication adherence [40], while 16% of the adolescents with inflammatory bowel disease reported that feeling well was a reason for not taking their medication [47]. Finally, physical aversions to medicine were perceived as a barrier to adherence.“Taste aversions”were reported as a barrier in a large minority of adolescents with a solid organ transplant [35,36,46], in12% of adolescents with cystic fibrosis [27], and in 13% of adolescents with inflammatory bowel disease [39]. It seemed to be a general barrier across diseases [27,31,33,34,39,41,45,46]. Also difficulty swallowing pills was perceived as a barrier across diseases [31,37,39,44e46]. Some adolescents sometimes felt too tired to take their medicationd4% and 10% respectively [39,45], while only few reported“laziness”as a barrier [26,39].

a statistically significant gender difference, counting 24% males and 3% females [27]. “It is okay not taking medicine, because the illness is not serious”was also a barrier to some [30]. Furthermore, some adolescents were afraid of being addicted to medicine [34], and some worried about being “sick” [31]. Some adolescents were worried about their disease in terms of consequences if things went wrong. One stated:“For example, I might get a heart disease or die earlier” [43]. However, others pretended that nothing was wrong with them in order to be like the rest. They thought that living an easy life was preferable over therapy compliance [43]. Also some adolescents interpret medication as a sign of weakness [30].

Mental well-being. Living with a chronic disease can be a stressful experience due to (1) the chronic disease itself; (2) the treatment burden; and (3) potential difficulties attending to a medical treatment. Adolescents with diabetes reported feelings of stress, anxiety, and being overwhelmed as a result of their disease [24]. Chronic illness could also lead to anger, depression, and despair, which all may have a limiting effect on adherence. As many as 33% of adolescents with a solid organ transplant felt tired of living with a chronic condition [35,36], or being angry or depressed by being ill [31]. A total of 56% of adolescents with epilepsy reported treatment to be a threat to emotional wellbeing [23]. In a study of adolescents with cancer, Pierre Robin syndrome, and cystic fibrosis some argued there was no point in taking the medication, because “you will die anyway” [41]. Adolescents with a solid organ transplant were stressed and anxious about the treatment responsibility [31,32]. And adolescents with asthma had a hard time following their regimen when they felt nervous or worried [29].

Coincidences. “Just forgetting” was reported as a barrier across almost all diseases [24,26,27,29e32,34e36,39e41,45,46,48], counting for a major part of the response rates in the survey studies. It was reported by almost 85% with inflammatory bowel disease [39], by 53% of adolescents with cystic fibrosis, asthma, and type 2 diabetes [27,29,48], by more than 55% with severe hemophilia [40], and by 30%e56% in studies of adolescents with a solid organ transplant [35,36,45,46]. “Not carrying medicine on regular basis” or “forgetting to carry supplies” were also reported as barriers [24,31,49].

Perceptions and worries about illness and treatment. Obviously, the adolescents’ own treatment beliefs can affect adherence. Among adolescents with inflammatory bowel disease, 14% reported having “no faith in drug effectiveness” [40] while 14% believed that the medicine was ineffective [47]. Among adolescents with cystic fibrosis, 7% reported they were“unsure that treatment is useful” [27], while some adolescents with asthma thought that “medicine was unnecessary” and they were also “ambivalent about the benefit” [34]. Some adolescents reported that “missing a few doses does not hurt as long as you take the medicine before testing” [27,31], and in one study this had

Forgetting Activities. Forgetting the medication was the second most reported barrier across a range of studies and illnesses (Table 2). Activities seem to be a frequent explanation of forgetfulness. More than 34% of adolescents with inflammatory bowel disease reported “interferes with activity” [39], 18% of adolescents with a renal transplant reported spontaneous activity as a reason for forgetting [46], while 10% and 28% of adolescents with a solid organ transplant felt that the medicine got in the way of activities [35,36]. These findings were supported by three other studies, which found that “change of plans is a reason for forgetting” [30,32,37]. The reason “wasn’t home” was reported as a barrier by 20% and 43% [39,46], and “distracted by other interests” was a barrier to 17% of adolescents with type 2 diabetes [48]. Among specific activities, “travelling/vacation” [37,40],“staying or sleepovers at friends” [34,37], and“parties and social gathering” [24] were mentioned.

Organization In a study of adolescents with a solid organ transplant, 58% perceived problems with planning their treatment [45]. This finding was underpinned by a study of adolescents with sickle cell disease, where 23% experienced barriers related to time management [44]. Two studies offered “lack of time” as a reason for nonadherence in their studies, which one third of adolescents with inflammatory bowel disease and severe hemophilia reported as a barrier [40,47]. Several studies found that scheduling problems or inconvenient time requirements were a barrier to medication adherence [24e27,31,33,34,39,40]. One study of kidney transplanted adolescents had some specific examples regarding how some of them perceived treatment plans as a hassle. For example, treatment interrupted other routines, such as sleep, and some felt it was a hassle to go to the school nurse for medicine [31]. “Lost medication” [34,39,44] was reported as a barrier in only 1% of adolescents with inflammatory bowel disease, but in 58% of adolescents with sickle cell disease [39,44].

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“Running out of medication” was also reported as a barrier [27,31,39,46,49], as well as “fell asleep” and “did not fill pill box” [39]. Medicine complexity Confusion about how to take the medicine was a barrier to 7% and 10% of adolescents living with a solid organ transplant [35,36] and some asthma patients reported difficulty using an inhalator [26]. Confusion about changes in regimen was a barrier to 33% with asthma [29]. Number of pills per dose [34,37,41] and the perception of taking medicine too many times a day [27,31] were also reported as a problem to some adolescents. Other adolescents did not understand the purpose of the prescribed medicine [31,37,40], or did not know whom to ask about medication problems [31]. Financial costs Financial barriers did not seem to be a comprehensive problem to chronically ill adolescents. Nevertheless, “price” was a barrier to 12% of adolescents with cystic fibrosis [27], and to adolescents with cancer, Pierre Robin syndrome, and cystic fibrosis [41]. The reason “can’t afford” was also a barrier to some [30,31]. Among adolescents with inflammatory bowel disease, 5% reported “insurance did not cover medication” as a barrier [47]. Discussion Many of the findings in this study are in line with results from studies on young adults and studies where barriers have been reported by parents or healthcare providersd for example, forgetting [39,50e56]. Physical issues, such as feeling well or feeling ill, were also found in other studies [54e59]. An absence of perceived health benefits or not believing the medication is necessary have been reported by parents as well as young adults as an argument for not taking medication [50,52,54e57,60]. Also, side effects and ingestion issues (e.g., taste, size) have been reported as barriers by young adults, parents, and healthcare providers [52,54e57,59e62]. However, some issues seem to be related specifically to adolescence. Striving for normality was not reported as a barrier by young adults or by parents and healthcare providers in any of the studies we identified in the reviewing process. Peers were only reported as a factor that could influence adherence of young adults in one study [51], though some studies mention “stigma” and “social barriers” in relation to “other people” as barriers [50,52,54]. Also, conflicts with parents seem to be less relevant for young adults with a chronic disease. One study [63] mentioned “parental support” as an issue for young adults with cancer, while another study [52] mentioned “lack of familial support” as an issue for young adults with HIV. In studies of chronically ill adolescents with parents or healthcare providers reporting, we could only identify one study mentioning parentchild conflicts as a reason for nonadherence [55]. Studies of chronically ill adults suggest that barriers to medical treatment are to a large extent the same as for adolescents; for example, forgetting, physical discomfort, and stigma. However, barriers linked to adulthood are by nature more predominant; for example, financial costs and health insurance, relationship to work, and looking after family [2,64e67].

A cautious interpretation of our findings indicates that central barriers such as normality, peers, and parents are specific to adolescents, and that these issues become more insignificant in adulthood. The findings might also indicate that parents and healthcare providers are not always aware of the crucial role relation to peers and parents plays, and that adolescents’ sense of normality as a part of their construction of identity is worth paying special attention to in order to strengthen adherence in the chronically ill adolescent. As chronic conditions vary in severity and complexity, demands for treatment adherence vary significantly. Some treatments intrude into multiple contexts of the adolescents’ life; while for other chronic conditions adherence to treatment can be privately carried out at home. Also, the complexity of cognitive demands required for adherence to different chronic diseases varies significantly between regimens. Some treatment regimens require complex cognitive abilities such as executive functioning or delay of gratification, behavior that may be difficult for the average adolescent. Furthermore, nonadherence can have very different effects on the adolescent’s physical functioning and quality of life depending on the disease; for example, type 1 versus type 2 diabetes. However, despite these substantial contextual differences, the reported barriers were surprisingly alike across diseases and treatment regimens. Our review has limitations. The barriers identified are colored by the amount of quantitative studies often asking the same range of questions. This means that barriers such as costs and organization are highly represented, even though these barriers often count for only a little when looking at the percentages documented in each study. Because the thematic synthesis is based on a qualitative approach, there is also a risk that other researchers would interpret the themes differently. It is always a challenge to split themes that are interrelated and it is clear that reasons for nonadherence are multiple, complex, and interwoven. In this review, we focused only on chronically ill adolescents’ self-perceived barriers to medical treatment. This approach does not include how to solve problems regarding adherence, and we could have created a wider perspective on adherence if we had also examined facilitators. A study of chronically ill adolescents’ owns perspectives on facilitators to adherence may advantageously be the target of a future review. Although our review contains various chronic conditions all barriers were not coupled to each condition. Thus, we cannot be sure that the themes generated by the synthesis can be generalized and applied to all chronic conditions. Also, because chronic conditions differ in terms of severity and treatment burden, barriers are not necessarily of equal importance. Furthermore, some barriers are probably more common in specific settings; for example, “financial costs,” which were identified in studies from mainly the United States [27,30,41,47]. There is an urgent need for interventions targeted specifically to chronically ill adolescents in order to strengthen medication adherence. Even though several interventions have been targeted to adolescents with chronic conditions most of them are not randomized, consist of small sample sizes, and unfortunately show only minor or no adherence improvement [68e71]. The need for interventions is supported by the World Health Organization, which argues that access to medications is necessary, but insufficient in itself to solve the adherence challenge [72]. Although we found similar barriers in a variety of chronic conditions, individual adolescents and settings differ significantly and there is probably no global “one size fits all” strategy


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