Assessing methods of measuring medication adherence in chronically ill children–a narrative review

Figures & data

Table 1 Validated questionnaires of each chronic disease with characteristics of the concerning studies

	Authors	Year	Sample size	Mean age of the children ± SD(if provided)	Adherence assessment	Filled in by/ persons being interviewed	Medicine
Asthma
	Martinez, Sossa, and Rand^Citation57	2007	64	3.6±2.2 years	Pediatric Inhaler Adherence Questionnaire (PIAQ)	Parents/caregivers	Not mentioned (metered-dose inhaler, MDI)
	Tiggelman, van de Ven, van Schayck, Engels^Citation73	2015	139	11.8±1.0 years	Medication Adherence Report Scale for Asthma (MARS-A) A Dutch translation of the MARS-A is described in this article. The MARS-A was first described by Cohen et al (2009)^Citation74	Children (adolescents)	Not mentioned Cohen et al (2009)^Citation74 reported self-reported adherence with inhaled corticosteroids (ICS)
	Garcia-Marcos, Brand, Kaptein, and Klok^Citation75	2016	133	6 years (with a range of 2–12 years)	Medication Adherence Report Scale (MARS-5)^a	Parents	Inhaled corticosteroids (ICS) (low-to-moderate doses of fluticasone propionate)
	McQuaid, Walders, Kopel, Fritz, and Klinnert^Citation76	2005	115	11.5 years (with a range of 7–16 years)	Family Asthma Management System Scale (FAMSS) Revised version	(Older) children and parents	Not mentioned
HIV/AIDS
	Farley, Hines, Musk, Ferrus, and Tepper^Citation77	2003	26	6.9±3.2 years (with a range of 21 months to 12.5 years)	Pediatric AIDS Clinical Trials Group (PACTG) (Module 1 and 2) This questionnaire is also mentioned by Van Dyke et al (2002)^Citation78	Caregivers	(Three or more) highly active antiretroviral therapy (HAART) medications
Epilepsy
	Modi, Monahan, Daniels, and Glauser^Citation59	2010	119	7.2±2.9 years	Pediatric Epilepsy Medication Self-Management Questionnaire (PEMSQ)	Caregivers	Antiepileptic drugs—AED (carbamazapine/carbatrol, valproic acid, levetiracetam, oxcarbazepine, ethosuximide, gabapentin, lamotrigine, topiramate)
Diabetes mellitus
	Lewin, LaGreca, Geffken, Williams, Duke, Storch, and Silverstein^Citation79	2009	164	14.6±2.9 years (with a range of 11–18 years)	Selfcare inventory (SCI)	Adolescents and parents	Intensive regimens, continuous subcutaneous insulin infusion and glargine regimens
	Lewin, Storch, Williams, Duke, Silverstein, and Geffken^Citation80 The DSMP was described firstly by Harris et al (2000)^Citation81 b	2010	275 parents along with their child (1 parent per child) 105 (families of youths)	13.3±2.7 years 11.6±1.2 years (with a range of 6.1–15.8 years)	Diabetes Self-management Profile (DSMP)	Youth and parents, administered by a trained clinician	Insulin (various delivery methods)
	Markowitz, Laffel, Volkening, Anderson, Nansel, Weissberg-Benchell, and Wysocki^Citation82	2011	338	12.5±1.7 years (with a range of 9–15 years)	Diabetes Self-management Questionnaire (DSMQ)	Children and their parents (two parallel versions)	All insulin regimens (by injections and by pump therapy)
ADHD
	Charach, Gajaria, Skyba, and Chen58	2008	19	11.85±2.1 years (with a range of 8.2–15.5 years)	Stimulant adherence measure	Parents and children	Psychostimulant medication for DSM-IV attention-deficit/hyperactivity disorder (ADHD)

Notes: ^aThe MARS-5 is a shortened version of the MARS-A questionnaire. ^bThe search strategy originally retrieved the article by Lewin et al.⁸⁰ However, as it is not the purpose of this article to examine the validity of the DSMP, but to provide normative data, information originating from the article by Harris et al⁸¹ has been mentioned in the Tables 1 and 2.

Abbreviations: PIAQ, Pediatric Inhaler Adherence Questionnaire; MARS-A, medication adherence report scale for asthma; MARS-5, medication adherence report scale; EMD, electronic monitoring devices; FAMSS, family asthma management system scale; PACTG, Pediatric AIDS Clinical Trials Group; MEMS^®, medication event monitoring system; PEMSQ, pediatric epilepsy medication self-management questionnaire; SCI, selfcare inventory; DSMP, diabetes self-management profile; DSMQ, diabetes self-management questionnaire; ICC, intraclass correlation coefficient.

Table 2 Clinical relevant characteristics of all the validated questionnaires

Adherence Assessment	Amount of questions	Optional: comparison with	Validation	Main advantages of the questionnaire	Main limitations of the study or specific disadvantages of the concerning questionnaire
Asthma
Pediatric Inhaler Adherence Questionnaire (PIAQ)^Citation57	6 questions (last 2 questions can be omitted in clinical practice)	The weight of inhaler canisters	Spearman’s rho: 0.42 (significant) Sensitivity: 50–75% Positive predictive value: 23.1–66.7% Likelihood ratio to detect nonadherent patients: 1.5–5.5 (nonsignificant CIs)	Brief and easy (required time to fill in: 1–3 minutes)	Validated only in a Spanish-speaking population The chosen gold standard (change in canister weight) is vulnerable to deceit as well Adherence has been assessed during a short period of time (15 days), which however minimizes memory and social biases
Medication adherence report scale for asthma (MARS-A)a,^Citation73,Citation74	10 questions	Cohen et al (2009): electronic adherence (an MDI-log monitor)	Cronbach’s α: 0.80 Cohen et al (2009): Cronbach’s α: 0.85 (English language) and 0.86 (Spanish language) Test-retest reliability: r=0.65 (significant) Significant correlation between continuous MARS-A scores and continuous electronic adherence: r=0.42 Dichotomized high self-reported adherence predicts high electronic adherence significantly: OR=10.6	Cohen et al (2009): Strong overall psychometric properties (good internal, criterion and construct validity)	Cohen et al (2009): The criterion validity test has been performed in a relatively small sample of patients (n=53) Unknown generalizability of the results to other settings (for example populations with a lower burden of asthma) Further validation in Spanish-speaking populations is needed
Medication adherence report scale (MARS-5)^Citation75	5 questions	Validated electronic monitoring devices (EMD): Smartinhaler^® and SmartDisk^® EMDs	Spearman’s rho: 0.47 (significant); however, a variation of adherence rates at every MARS-5 score is shown by a scatter plot in the article Area under the ROC curve: 0.7188 and likelihood ratios which are too small to be clinically useful	Avoids social desirable answers/bias by its anonymity Long (12 months) real-life study without intervention	Poor accuracy and reliability compared with electronic monitoring (not a useful adherence measure in clinical practice) Unknown generalizability, as the study only included a sample from a Caucasian middle-class population without follow-up
Family asthma management system scale (FAMSS)^Citation76	7 core and 2 additional scales	MDILog electronic medication monitor	Cronbach’s α: 0.84 Relationship between FAMSS summary score and MDILog medication adherence: 0.29 (significant) Relationship between Medication adherence (one of the subscales) and MDILog medication adherence: 0.30 (significant)	FAMSS places adherence in a larger setting, as it includes the management of asthma in a family context—resulting in the provision of rich clinical data The FAMSS summary score is related to (prospective) asthma morbidity	FAMSS is semi structured and costs more labour to implement than standardized self-reports The authors used a small sample participating in the MDILog electronic medication monitor assessment Research on the utility of the (translation of) FAMSS in a Spanish-speaking population has not been performed
HIV/AIDS
Pediatric AIDS Clinical Trials Group (PACTG) (Modules 1 and 2)^Citation77 Note: the PACTG is a measure which consists of an (oral) interview	Module 1: 7 questions Module 2: 4 questions^b	Viral load/virological response (and medication event monitoring system (MEMS^®))	Sensitivity: 90% Specificity: 43% Positive predictive value: 69%	Not mentioned	Not mentioned
Epilepsy
Pediatric Epilepsy Medication Self-Management Questionnaire (PEMSQ)^Citation59	27 items, consisting of 4 scales	MEMS^® TrackCap and self-reported adherence (a particular question answered by caregivers about the amount of missed AED doses in the past week)	Cronbach’s α of the scale “adherence to medications and clinic appointments”: 0.87 Association of the scale “adherence to medications and clinic appointments” with adherence measured by MEMS^®: r=0.22 (significant) Association of the scale “adherence to medications and clinic appointments” with self-reported adherence: r=0.28 (significant)	Strong psychometric properties The PEMSQ also measures knowledge and expectations (perceptions) of epilepsy treatment, next to barriers to adherence and beliefs about the efficacy of medication^c Brief measure and easy to perform and interpret	Limitations in the chosen population of the study: solely children below 14 years have been included from only one hospital, who also were within the first 2 years of their diagnosis
Diabetes mellitus
Self-care inventory (SCI)^Citation79	14 items	HbA1c assay in blood (and the hereafter mentioned diabetes self-management profile (DSMP))	Cronbach’s α: 0.72 (parent) and 0.80 (adolescent) Agreement between parent and adolescent: ICC (intraclass correlation coefficient) =0.47 Test-retest reliability: r=0.91 (adolescent, significant) and r=0.86 (parent, significant)	Strong psychometric properties The SCI assesses different key aspects of the regimen and adherence behaviors in diabetics SCI can be applied to a variety of insulin regimens Time (and cost) effective	Limited generalizability, due to the restricted sample characteristics (mostly Caucasian, wide age range, from the low to lower-middleclass)
Diabetes Self-Management Profile (DSMP),d^Citation80 Note: the DSMP is a measure which consists of an (oral) interview First mentioned by Harris et al (2000)^Citation81	23 items with 5 domains	Harris et al (2000): HbA1c assay in blood	Cronbach’s α: 0.78 (parent) and 0.75 (child) Harris et al (2000): Cronbach α=0.76 Test-retest reliability (Pearson correlation) over 3 months: r=0.67 Agreement between parent and adolescent (Pearson correlation): r=0.61	Strong psychometric properties (acceptable construct validity and reliability) Relatively convenient to administer and interpret The DSMP includes different components and dimensions concerning self-management of the disease (next to the administration of insulin) It predicts additional variance in metabolic control (HbA1c) Includes two versions, distinguishing different treatment regimens	DSMP requires quite some effort from staff and patients (20–30 minutes)
Diabetes Self-Management Questionnaire (DSMQ)e82	9 items	HbA1c assay in blood Also: frequency of blood glucose monitoring in blood and the dose of insulin (next to other measures which are correlated with adherence and control of the blood glucose levels, for example the DSMP)^f	Cronbach’s α: 0.59 for children (with Cronbach’s α: 0.56 for children <11 years and with Cronbach’s α: 0.60 for children ≥11 years) and 0.57 for parents Significant correlation with HbA1c for children ≥11 years (r= −0.22) Significant correlation with the frequency of blood glucose monitoring for children <11 years (r=0.22) and for children ≥11 years (r=0.44)	Short questionnaire (can be completed in <10 minutes) Requires not a lot of staff (labour/resources) Advantages of the chosen population in this study: DSMQ is validated in a diverse and younger population (diverse geographical origins and ethnic backgrounds, aged 9–15 years)	Compared with the DSMP, the shortness of the DSMQ might negatively impact its internal consistency Does not include two versions to take the different regimes into account, which might lead to loss of adherence information related to these regimes
ADHD
Stimulant Adherence Measure^Citation58 Note: the Stimulant Adherence Measure consists of a semi-structured telephone interview	Parent version:^g first section: 9 questions second section: 4 questions third section: 1 question Child version:^h first section: 14 questions, second section: 3 questions, third section: 1 question	MEMS^®	Significant intraclass correlations (ICCs), varying from 0.663–0.907, between data derived from MEMS^® and reports from parents in week 1, 2 and 3 and in the months 1, 2 and 3 Significant ICC’s between data derived from MEMS^® and reports from children in week 1 (ICC=0.773), week 2 (ICC=0.542) and week 3 (ICC=0.606) Significant inter-rater reliability (ICC=0.956)	Valid and reliable questionnaire, as shown by the results Results show comparable adherence measurements of the questionnaire, administered at monthly intervals, compared with MEMS^® The stimulant adherence measure offers the opportunity to explanation (of behavior)	More accurate for adherence ratings from parents than from children Limitations of the sample: small sized and derived from a clinical setting (it is not a community-based research population)

Notes: ^aTiggelman et al⁷³ have translated the MARS-A to a Dutch population of adolescents, as this questionnaire was first described in adults by Cohen et al.⁷⁴ Therefore, Table 2 describes the main characteristics of MARS-A according to Cohen et al.⁷⁴ bAccording to the available questionnaires with the form date in November 2004, which can be found at: https://www.frontierscience.org/apps/cfmx/apps/common/QOLAdherenceForms/index.cfm?project=IMPAACT. ^cAlthough questionnaires which measure (subjective) perceptions of the disease have been an exclusion criterion, the presence of these additional scales might lead to a better understanding of parental beliefs and (deficiencies of) knowledge, which contribute to self-management and the therapy of the child. Therefore, this is considered to be an advantage.⁵⁹ dThe DSMP is an update of the self-care adherence inventory (SCAI).⁸⁰ eThe DSMQ is a shortened version of the DSMP, which also reflects the medication adherence of a broader age range. ^fBoth questionnaires show a significant correlation; however, these correlations have not been mentioned or elaborated on in the tables. ^gAccording to the version published at: https://www.sickkids.ca/pdfs/Psychiatry/SAM/8621-sam_parent.pdf ^hAccording to the version, published at: https://www.sickkids.ca/pdfs/Psychiatry/SAM/8620-sam_child.pdf

Abbreviations: PIAQ, pediatric inhaler adherence questionnaire; MARS-A, medication adherence report scale for asthma; MARS-5, medication adherence report scale; EMD, electronic monitoring devices; FAMSS, family asthma management system scale; PACTG, Pediatric AIDS Clinical Trials Group; MEMS^®, medication event monitoring system; PEMSQ, pediatric epilepsy medication self-management questionnaire; SCI, self-care inventory; DSMP, diabetes self-management profile; DSMQ, diabetes self-management questionnaire; ICC, intraclass correlation coefficient.

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