Development and Reliability of a Correction Factor for Family-Reported Medication Adherence: Pediatric Inflammatory Bowel Disease as an Exemplar

Poor adherence to prescribed medical regimens can lead to a number of negative consequences, including suboptimal symptom management, increased disease severity, risk of relapse, and greater health care utilization (Higgins, Rubin, Kaulback, Schoenfeld, & Kane, 2009; Hommel, Denson, & Baldassano, 2011; Kane, Huo, Aikens, & Hanauer, 2003; Rapoff, 2010; Sokol, McGuigan, Verbrugge, & Epstein, 2005). Of central importance to understanding medication adherence and its effects is accurate assessment of adherence to the medical regimen in the context of clinical care. There are a number of available adherence assessments, each with advantages and disadvantages, such as feasibility for use in clinical practice (Hommel, Mackner, Denson, & Crandall, 2008b). For example, although bioassays are clinically feasible and provide objective data on medication levels, they are subject to bias due to white coat compliance (i.e., patients more conscientiously taking medication prior to medical appointments) and do not provide information on patterns of non-adherence (i.e., when medication was taken or not taken), which is essential for informing intervention. Electronic monitoring (EM), which some consider a gold standard assessment method (Cramer, 1995), provides more specific, real-time information on when doses were removed from pill bottles; however, EM is costly to implement and may rely on patients to bring pill bottles to clinic appointments so that adherence data can be downloaded. In clinical practice, patient- and/or parent-report of medication adherence is likely the most feasible method of adherence assessment. For instance, a recent survey of gastroenterology clinicians found that of those respondents who reported screening for medication adherence, 81% relied on patient-report (i.e., clinical interview; Trindade, Morisky, Ehrlich, Tinsley, & Ullman, 2011). Within the context of pediatric practice, parent-report (versus patient-report) of adherence is often used because of the high level of parent involvement in implementing prescribed regimens (e.g., medication administration). Subjectively reported adherence (e.g., parent-report), however, provides higher estimates of medication adherence as demonstrated across multiple patient populations, relative to other methods of assessing adherence such as EM (Hommel et al., 2008b; Rapoff, 2010). Subjectively reported adherence can lead to overestimates of medication adherence due to factors such as recall bias and social desirability. The current manuscript examines the issue of accurate adherence assessment and illustrates methodologies for correcting parent-reported adherence. These methodologies could be applied across chronic illness populations; however, we chose to use pediatric patients with inflammatory bowel disease (Otley et al., 2006) as an exemplar because this population demonstrates substantial variance (16–88%) in nonadherence to prescribed medication regimens (Hommel, Davis, & Baldassano, 2009; Mackner & Crandall, 2005; Oliva-Hemker, Abadom, Cuffari, & Thompson, 2007; Ooi, Bohane, Lee, Naidoo, & Day, 2007). Overestimation of adherence is also likely an issue among children with IBD and their families. For example, in a sample of adolescents with IBD, on average, patients overestimated their EM adherence by 7.8%, and there was wide variability in individuals’ overestimation of adherence (e.g., 2.3–23.2%; Greenley et al., 2012). Subjective reports of adherence could, however, be used with greater confidence if a correction factor based on objective adherence assessment was applied to adjust for inflated subjectively reported adherence estimates. Such a correction factor would be a cost-effective, easily implemented, and a more accurate method of assessing adherence in pediatric IBD based on caregiver-report. Better identification of patients and families who have adherence problems could enable clinicians to deliver targeted interventions to promote adherence and improve child health outcomes. Correction factors for self-reported medication adherence have previously been developed for children with epilepsy (Modi, Guilfoyle, Morita, & Glauser, 2011), adults with HIV (Liu et al., 2001), and low-income pregnant women (Jasti, Siega-Riz, Cogswell, & Hartzema, 2006). However, each population has a unique treatment regimen (e.g., dosing schedule, number of medications, medication side effects), which may differentially impact adherence. Further, adherence in pediatric populations is qualitatively different from adherence in adults because caregivers and family members are highly involved in administering the prescribed treatment regimen for children. As a result, correction factors for subjectively reported adherence may differ across illness populations and age groups. For pediatric patients with IBD, no studies have examined the relationship between medication adherence assessed via parent-report versus a more objective method such as EM or developed a correction factor for parent-reported adherence. Only one study has compared EM and subjectively reported adherence among children with IBD, but used adolescent-report of adherence. That study also compared the two methods of adherence assessment using sensitivity and specificity analyses at one adherence cut-point (i.e., indicating what percent of medication doses taken constitutes “adherent” versus “non-adherent”; Greenley et al., 2012). Although continuous data (e.g., adherence on a 0–100% scale) leads to a more detailed understanding of patient adherence, the dichotomous labels “adherent” and “non-adherent” are often used in clinical practice to guide treatment decisions. Because sensitivity and specificity may vary across different adherence cut-points, an important next step is to identify cut-points that yield the highest specificity and sensitivity. Building on the one prior study comparing EM and subjectively reported adherence in the pediatric IBD population (Greenley et al., 2012), the first aim of the current study was to examine the specificity and sensitivity of parent-reported versus EM adherence using different cut-points for adherence. Exploratory analyses were also conducted to examine the relationship between parent-reported and EM adherence below and above the cut-point which had the highest specificity and sensitivity. Also, to obtain more accurate assessments of adherence when parent-report may be an overestimation, the second aim of the current study was to develop a correction factor for parent-reported adherence that could be feasibly used in clinical practice. Consistent with prior findings (Greenley et al., 2012; Modi et al., 2011; Shi et al., 2010), we hypothesized that subjectively reported adherence would be higher than EM adherence and positively correlated, and that higher adherence cut-points would yield better sensitivity and specificity when comparing these adherence assessment methods.