- Email: [email protected]
Emerging areas
C H A P T E R
17 Emerging areas Avani C. Modi1, 2, Ana M. Gutierrez-Colina1, Kimberly A. Driscoll3 1
Division of Behavioral Medicine and Clinical Psychology, Center for Adherence and Self-Management, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States; 2 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; 3 Department of Clinical & Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, United States The field of pediatric adherence and self-management has burgeoned throughout the past 25 years, with an increasing number of studies focusing on new methods of adherence assessment, novel developments in adherence and self-management interventions, and adoption of cutting-edge technology-based approaches to deliver evidence-based adherence and self-management tools. In addition to these areas of growth, several emerging issues are at the forefront of our field. In the sections that follow, we will discuss recommendations on adherence terminology and taxonomy, guidance about use of contemporary theoretical models, new adherence measurement approaches and novel targets for intervention, methodological innovations for trial design, and dissemination and implementation efforts to advance the impact of adherence science in clinical practice.
Taxonomy The terms used to describe adherence have changed across time and differed across disciplines, with ongoing debate about the terminology that most accurately captures the nuances of this behavior (Dickinson et al., 2017). The lack of consistent terminology, common measurement approaches, and unifying adherence taxonomies has hampered scientific progress, challenged study replication, and served as a barrier to the aggregate study of the adherence literature. Recognizing the critical need to
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harmonize and enhance the transparency of research reporting, the European Society for Patient Adherence, Compliance and Persistence (ESPACOMP) developed an empirical taxonomy that conceptualizes adherence as a complex, dynamic, and quantifiable process. This taxonomy comprises three distinct but interrelated phases, including initiation, implementation, and persistence (Vrijens et al., 2012). The initiation phase is the start of the adherence process and assesses whether or not an individual initiates treatment. The implementation phase evaluates dosing history, including dosing delays, omissions, or additions. Lastly, the persistence phase indicates the length of time between the initiation phase and the moment in which an individual discontinues treatment. This conceptual framework facilitates uniformity in the study and reporting of adherence-related science and addresses several limitations that affect scientific progress within the field of adherence and self-management. Therefore, we advocate for its adoption to facilitate progress, research replication, and future collaborations across disciplines and adherence scientists.
Theory The application of theory to guide research endeavors is an important step in promoting scientific progress within the field of psychology. Theoretical principles serve as the foundation for developing research aims and testable hypotheses. In pediatric adherence and self-management, several older theories have been applied to inform scientific inquiry (e.g., Health Belief Model, Transtheoretical Model of Change) (see Chapter 1: Introduction), but no theories have successfully applied or are fully supported empirically across pediatric chronic conditions. Furthermore, in some pediatric areas (see Chapter 15: Dermatological Conditions and Chapter 16: Sleep), there is a complete lack of theoretical guidance to inform adherence and self-management research efforts. One of the primary barriers to using these theories is that they were developed exclusively in adult populations, which neglects key developmental factors and the larger systems in which children exist (e.g., family, school, community). As a result, we advocate for the future use of pediatric-specific contemporary models, including the Pediatric Self-management Model (Modi et al., 2012) and the Revised Selfand Family Management framework (Gray, Knafl, & McCorkle, 2006; Gray, Schulman-Green, Knafl, & Reynolds, 2015; Ryan & Sawin, 2009). These frameworks can be applied across pediatric conditions and were intentionally developed to reflect the complexities that affect pediatric populations.
Measurement Adherence assessment via objective, reliable methodology is critical to address and understand adherence behaviors. Electronic monitoring and
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technology-focused tools are standard for the measurement of adherence across a number of diseases. These methods yield robust data on daily adherence patterns and shed light on new areas of intervention. For example, daily adherence data allow for the identification of time of day or days of the week that are particularly problematic. Older electronic monitors, such as MEMS TrackCaps or blood glucose meters, have the capability of recording adherence data across time but could only be downloaded at point of care or during a research visit. In contrast, new electronic monitors provide real-time adherence data to clinicians, researchers, and individuals and their family members. For example, SimpleMed pillboxes (Vaica; Israel) use 3G/4G networks to communicate with a portal that displays real-time adherence data. Similarly, AdhereTech bottles for oral medications and Propeller Health for inhalers allow for realtime adherence monitoring and increase the amount and precision of clinical data available for proactive intervention. “Smart packaging,” where microchips in blister packs monitor when doses are removed from the pack, is also being used successfully (Arnet, Walter, & Hersberger, 2013). In diabetes, blood glucose meters, continuous glucose monitors, and insulin pumps provide real-time data to smart phones and cloud-based applications so that immediate treatment adjustments can be made (see Chapter 3: Type 1 Diabetes). Some electronic monitors also have the ability to remind individuals to take their medications via texts, phone calls, or emails and can be tailored to align with their preferences. Moreover, strategies to improve adherence are embedded into the electronic devices with options for individual tailoring. Wearable and tracking devices such as smartwatches, fitness bracelets, and apnea machines are increasingly used to assess daily adherence to broader health behaviors (e.g., physical activity, sleep) and guide treatment course. With the exception of diabetes devices, it is unclear if these electronic devices are clinically useful and insurance companies rarely provide coverage for them significantly limiting dissemination and uptake in clinical practice. Thus, future advocacy efforts are needed to demonstrate the clinical benefits of measuring adherence to positively impact clinical care and health outcomes. Interestingly, a large number of adherence measurement tools (e.g., electronic monitors, pharmacy refills, self-report) are plagued by an inability to confirm if medications have actually been ingested. Newer approaches, such as patented mobile artificial intelligence (aICure; New York, NY) or digital pills with ingestible sensors (Proteus Digital Health) confirm drug ingestion and may be the future of adherence measurement. However, it is unclear if youth with chronic conditions and their families will be open to this “big brother” approach, particularly as new risks related to confidentiality, health data privacy, and cyber security are introduced. Furthermore, the extent to which insurance companies and third-party payers will support these innovative devices remains
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unknown. That being said, pharmacies are becoming more involved in medication therapy management, with high potential for reimbursement. Pharmacists may be in a unique and rare position to influence adherence behaviors in both inpatient and outpatient settings, and psychologists are encouraged to partner with pharmacists to further influence adherence at the systems level for youth with chronic conditions. Adherence biomarkers are also increasingly used in clinical practice, including standard deviations of medication levels (see Chapter 13: Solid Organ Transplant), metabolites (see Chapter 7: Cancer and Chapter 11: Inflammatory Bowel Disease and GI Disorders), or serum levels (see Chapter 9: Epilepsy). Bioassays enable clinicians to better understand whether individuals have medications in their body, but they may not provide the level of specificity needed to guide behavioral interventions. Newer biologically based methods, including hair samples, dried blood spot sampling, and saliva samples, are currently being tested in a number of pediatric conditions (see Chapter 9: Epilepsy and Chapter 12: HIV/ AIDS); however, it remains unknown if these methods are reliable and valid for clinical practice. Finally, it is notable that electronic monitors and medical devices, including continuous glucose monitoring or insulin pump therapies for type 1 diabetes, produce daily and even moment-by-moment adherence data, providing a wealth of health information. With the exponential availability of health data generated by these devices, healthcare providers, caregivers, and individuals with chronic conditions are progressively faced with new challenges related to data integration for clinical decision-making. Big data analytics and machine learning approaches and novel ways to provide individuals with user-friendly data may provide innovative avenues for leveraging the valuable information drawn from technology, while minimizing system inefficiencies, costs, and provider/patient burden. For example, efforts are underway to provide individuals with type 1 diabetes with summary statistics and recommendations to improve insulin pump adherence that are individually tailored and more understandable than reports generated by industry standard software (Driscoll et al., 2017).
Intervention Technology innovations have a profound impact on the development of adherence and self-management interventions. As highlighted by many of the chapters in this book, mobile health (mHealth), electronic health (e-Health), and telehealth are increasingly being used to address adherence and self-management. Despite the promise of these
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interventions, participant engagement across time with these approaches is a challenge. Because the power of technology-based solutions is limited by the extent to which individuals use them, mHealth content needs to be engaging and interactive, and perceived as beneficial. As such, researchers are encouraged to work with various disciplines with expertise in engagement, including education technology experts, graphic designers and programmers, videographers, as well as stakeholders (e.g., patients, families, providers). By engaging key players in the development process, mHealth tools will have higher uptake by individuals with chronic illness and caregivers, thereby increasing their reach and efficacy. As noted in several meta-analyses (Dayer et al., 2017; Fedele, Cushing, Fritz, Amaro, & Ortega, 2017), rigorous randomized controlled trials are still needed to evaluate the long-term efficacy of mHealth adherence interventions, but in an age of consumerism where medical care is provided virtually (e.g., digital therapeutics), groceries are delivered to homes, and most products can be obtained within 24 hours, tech-based solutions are likely to be an important piece of the future adherence landscape. The field of prescription digital therapeutics, a novel paradigm to treat illness and manage health-related challenges, is a related emerging area that capitalizes on technology. Rooted in evidence-based therapies (e.g., cognitive-behavioral therapy), prescription digital therapeutics use health technology and digital platforms to link behavioral interventions with physician prescription practices to treat or prevent the onset of health conditions. Prescription digital therapeutics can be prescribed independently or in conjunction with pharmacotherapy to provide a multipronged approach to treatment and prevention. Once the digital therapeutic prescription is filled, individuals obtain a code that gives them access to a digital platform where they receive the prescribed intervention from the comfort of their homes. Prescription digital therapeutics are moving toward approval by the Food and Drug Administration (FDA), with the first prescription digital therapeutic (for opioid use disorder) cleared by the FDA in late 2018 (i.e., reSET by Pear Therapeutics and Novartis), further establishing its future use and potential for adherence and self-management interventions. Lastly, the emergence of promising new targets for adherence and self-management interventions provides new frontiers for the treatment of nonadherence. Neurocognitive functions (e.g., executive functioning, self-regulation, attention) are increasingly recognized as playing a key role in the execution and implementation of self-management tasks across pediatric conditions. Cross-sectional studies demonstrate associations between executive functioning and adherence in children and adolescents with spina bifida (O’Hara & Holmbeck, 2013), solid organ transplantation (Gutie´rrez-Colina et al., 2016), and asthma (Sonney &
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Insel, 2019). Results from a literature review in youth with type 1 diabetes further support associations between executive functioning and adherence, as well as biomarkers such as A1C (Duke & Harris, 2014), suggesting that neurocognitive functions may have a role in shaping not only adherence and self-management behaviors but also biobehavioral outcomes. Longitudinal investigations replicated this pattern of findings and demonstrated that better executive functioning is associated with slower increases in A1C (Berg et al., 2018) and better glycemic control across time (Vloemans et al., 2019), indicating that assessment of executive functioning skills may help identify those at risk for suboptimal clinical outcomes. Recent attention to the role of parental executive functioning and the significant interactions between parental and child executive functioning in the prediction of adherence highlights the important role of neurocognitive functions, not just in youth but also in their caregivers (Goethals et al., 2018). Although traditionally conceptualized as a relatively stable variable, mounting evidence in pediatric research reveals that neurocognitive functioning can be feasibly targeted and effectively improved with training (Kurowski et al., 2014; Modi et al., under review; Wade et al., 2010). As such, neurocognitive functions are a promising new avenue for targeting many of the skills that underlie the successful execution of adherence and selfmanagement behaviors. Behavioral economics is another target for intervention that is receiving increased attention. Behavioral economics represents several scientific fields, including psychology, marketing, and economics, with the goal of understanding human decision-making. Four primary concepts from behavioral economics apply to adherence and self-management behaviors, including default bias (i.e., consumer’s tendency to choose preselected items that are nonmandatory), loss aversion (i.e., gaining a reward is perceived as better than losing something of equal value), overestimation of rare events (i.e., when individuals misinterpret the likelihood of a rare event occurring), and social norms (i.e., impact of feedback about another person’s performance/behavior on one’s own performance/behavior) (Stevens, 2014). Stevens (2014) urged pediatric psychologists to consider the role of these behavioral economic principles in improving adherence behaviors. For example, pharmacies can provide automatic refill reminders and delivery of medications via mail as default (default bias) or adolescents could lose 15 minutes from their allotted 150 daily minutes on their smartphone/tablet every time they miss their medicine (loss aversion). These are strategies that healthcare providers could recommend and/or caregivers could implement. Lottery-based systems of rewards are also being used via apps, including Mango Health, in which individuals have a chance at winning various prizes
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(e.g., gift cards, donation to a charity) depending on how well they complete their treatments (overestimation of rare events). Testing of these types of interventions at the population level is important. For example, a randomized clinical trial focused on loss aversion, BE IN CONTROL, provided adolescents and young adults with type 1 diabetes a virtual account of $60 each month, with $2 subtracted for every day the individuals did not meet their blood glucose monitoring goal (Wong & Wirrell, 2006). Participants in the intervention had greater adherence to blood glucose monitoring compared to controls (50% vs. 19%) during the active intervention arm, but this difference disappeared during follow-up when incentives were removed, suggesting loss aversion programs may be short-lived. Finally, comparing how youth adhere to treatment compared with those of similar age/sex and condition may nudge them to become more adherent (social norms). A social norms adherence intervention is currently being tested in a small NIH clinical trial (NCT03958331) in adolescents with epilepsy. Use of these principles could be an important future direction for pediatric adherence and selfmanagement interventions. Building on behavioral economic principles, increased attention is being given to incentivizing adherence behaviors. Companies around the United States incentivize employees in wellness programs to stop smoking, exercise more, and engage in healthy dietary behaviors. Incentive systems are effective for children and adolescents for decreasing marijuana use (Stewart, Felleman, & Arger, 2015), increasing activity (Christian et al., 2016), and making healthy food choices (McEvoy et al., 2014). A 2015 meta-analysis found financial incentive systems improve the odds of changing behavior fourfold when compared with controls, regardless of age, sex, or race (Haff et al., 2015). Thus, incentivizing treatment adherence is one possible solution to promote health, especially for youth with chronic conditions. As noted in BE IN CONTROL, which is both a financial incentive and loss aversion, effects of these programs may be short-lived. In addition, the ethical considerations of payment for treatment must be considered (Healy, Hope, Bhabha, & Eyal, 2017). One potential concern is the replacement of extrinsic motivation by intrinsic motivation, which may yield poorer adherence when incentives are removed and the adolescent is no longer motivated to adhere for their own health (e.g., intrinsic motivation). However, to our knowledge, no studies have examined the differential role of intrinsic and extrinsic motivation related to financial incentives for treatment adherence and self-management in youth. Research focused on behavioral economic principles is an important area for future research and warrants attention as a target for adherence promotion efforts.
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Methodology Study designs As noted in the introduction, several meta-analyses highlight that healthcare providerebased and multicomponent interventions produce the largest effects (Graves, Roberts, Rapoff, & Boyer, 2010; Kahana, Drotar, & Frazier, 2008; Pai & McGrady, 2014; Wu & Pai, 2014). Dismantling which strategies are most effective and for whom is an important next step in pediatric psychology to facilitate personalized treatment and optimal resource allocation. One way to answer these questions is the use of adaptive trials (Nanhum-Shani et al., 2012), such as Sequential Multiple Assignment Randomized Trials (SMART), in which several adherence strategies are embedded in the intervention, but responsiveness to the initial strategy determines the need for additional intervention components (Almirall, Nahum-Shani, Sherwood, & Murphy, 2014; Collins, Nahum-Shani, & Almirall, 2014). For example, Naar-King et al. (2016) employed a two-stage adaptive intervention design to test four different treatment components and optimize weight loss among African American adolescents with obesity (Naar-King et al., 2016). Youth and caregivers in this behavioral trial were randomized to either home-based or office-based motivation interviewing þ skills building (phase 1). After the initial treatment, nonresponders (weight change <3%) were rerandomized to an augmented treatment that included either continued skills or contingency management (phase 2). All responders completed relapse prevention during this trial phase. This example illustrates how the use of SMART designs allows researchers to examine the most effective and efficient interventions to improve clinical outcomes.
Transparent reporting Transparent reporting is recognized as a fundamental component of rigorous and high-quality scientific research, with important implications for the validity, reliability, replicability, and impact of research findings and conclusions (Simera et al., 2010). Throughout the past few decades, this growing recognition has led to the creation of transparent reporting guidelines for randomized and nonrandomized clinical trials (e.g., CONSORT, STROBE), an important step in promoting scientific transparency and providing guidance to the scientific community about best reporting practices. Consistent with this trend, the European Society for Patient Adherence, Compliance, and Persistence (ESPACOMP) developed Medication Adherence Reporting Guidelines (EMERGE) to provide complementary and specific direction regarding transparent reporting for adherence (De Geest et al., 2018, 2019). The EMERGE
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guidelines are conceptually grounded in the ESPACOMP taxonomy for medication adherence noted previously (Vrijens et al., 2012) and include a set of four items describing the minimum reporting criteria and additional 17 items with recommendations for more detailed adherence reporting. The minimum criteria include (1) reporting on specific phases of medication adherence studied (i.e., initiation, implementation, persistence); (2) providing a precise operational definition of each adherence phase; (3) specifying the measurement methods used to assess adherence at each phase; and (4) discussing research results for each of the adherence phases studied. We believe these basic reporting criteria should become the new standard for reporting adherence and advocate for its adoption to increase commitment to conducting rigorous and high-quality research in a transparent and consistent manner. We urge adherence researchers to consider the additional EMERGE recommendations for the most rigorous approach to adherence reporting methodology.
Dissemination and implementation science in adherence and self-management Dissemination and implementation of adherence measurement and interventions remains a critical need. Few adherence and selfmanagement interventions have been disseminated and implemented in clinical practice because it takes approximately 17 years for research to benefit patient care (Green, 2008). Scaling interventions for broad dissemination can be difficult, but improving patienteprovider communication about self-management is a powerful first step. In the past, this topic was often ignored or avoided by both medical staff and patients/families. A recent survey of adherence practices in pediatric gastroenterology care, for example, indicates that healthcare providers believe adherence monitoring in clinical practice is important, but only 25% systematically screen for adherence problems and only 21% perceive that they are able to modify adherence behaviors (Maddux et al., 2018). Pediatric psychologists are key healthcare providers trained in adherence and uniquely positioned to facilitate conversations about adherence and self-management. Unfortunately, most medical clinics do not have access to pediatric psychologists. Arming frontline healthcare providers with strategies to help their patients and families and advocating for the integration of pediatric psychologists in medical subspecialists is a critical first step and must become standard of care. Strategies to initiate discussion about adherence include normalizing and not criticizing families for adherence difficulties, assessing barriers
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to adherence, and asking very specific questions about how families fit medications into their daily routine (e.g., when they take it, last missed dose, barriers they experienced). A recent clinical initiative within a pediatric kidney transplant clinic focuses on a clinical adherence monitoring and intervention system, the Adherence Monitoring and Promotion Program, which was initiated and developed by adherence psychologists, individuals in need of a kidney transplant, and healthcare providers, in which the first step was training the healthcare team on ways to discuss adherence nonjudgmentally. Second, a simple adherence barriers checklist was developed based on the evidence-based literature regarding pediatric adherence barriers and administered to individuals (10 years and older) and their caregivers via a tablet every 6 months (Varnell et al., 2017). Third, a clinical algorithm and shared decision-making tools were developed to provide guidance to healthcare team members on next steps when a barrier is identified. These tools are used systematically by providers to engage families in discussion about strategies to overcome barriers. The Adherence Monitoring and Promotion Program is an exemplar for other chronic conditions of how to disseminate adherence promotion strategies into clinical practice, with preliminary data indicating that kidney rejection rates have decreased because of this initiative. To ensure support for adherence interventions in clinical practice, however, the value of these efforts should be demonstrated. For example, how does dissemination and implementation of adherence initiatives save individuals with chronic conditions and healthcare systems money? How does being proactive with adherence efforts differ from being reactive financially? Adult studies indicate that implementation of behavioral adherence promotion interventions in clinical practice is likely less costly than the indirect (e.g., productivity loss) and direct healthcare costs associated with suboptimal adherence (Chapman, Ferrufino, Kowal, Classi, & Roberts, 2010; Chapman, Kowal, et al., 2010; Desborough, Sach, Bhattacharya, Holland, & Wright, 2012). More pediatric studies need to quantify the impact of adherence interventions on healthcare charges, costs, and utilization. Pediatric nonadherence is linked to higher healthcare use, including emergency room visits and hospitalizations (McGrady & Hommel, 2013). Increasing nonadherence across time in individuals with IBD results in three times the healthcare costs compared with more adherent individuals, suggesting nonadherence is a driver of healthcare costs (Hommel et al., 2017). Similarly, individuals with nonadherence as measured by a biomarker (e.g., standard deviation of tacrolimus levels) in kidney transplant have higher healthcare utilization and charges compared to those with better adherence (Rich et al., 2018). These studies are beginning to shed light on the economic impact of pediatric nonadherence, but much work is yet to be done.
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Lastly, although treatment adherence is a key goal for the teams that care for youth with chronic conditions, it is important to recognize that optimal adherence may not be a priority for families. Teams must consider a family’s hierarchy of needs and recognize that essential needs in Maslow’s Hierarchy (e.g., food, shelter, safety) must be met first before adherence interventions become the focus of clinical care (Barnidge, LaBarge, Krupsky, & Arthur, 2017). Understanding how hospitals and clinics can provide financial assistance or connect families with resources in the community to meet these needs should be the first step of any adherence promotion intervention.
Conclusions It is clear from the content of each of the chapters in this book that decades of research have contributed significantly to our understanding of pediatric adherence and self-management. This is an extremely exciting time for pediatric psychologists as our contributions to medicine generally, and to improving adherence and self-management behaviors have never been stronger. Moreover, the need for our integration into routine medical care because of our specialized expertise and training in behavioral science is clearer than ever. However, as noted in multiple chapters, despite how vast our field is, there is still much work to be done. A consistent theme across all the chapters in this book, regardless of the condition of focus, is the great need for innovative intervention research that leads to improvements in pediatric adherence and self-management behaviors and health outcomes more generally. This research must not only capitalize on technological advances and the emerging areas highlighted in this chapter but must also be cost-effective to facilitate dissemination into clinical care of youth. The compilation of the extant pediatric adherence and self-management research in this book provides a solid foundation of accomplishments in the pediatric psychology field in the last several decades. In addition, we hope that the highlighted gaps in each chapter, combined with emerging topics of study, help to stimulate innovative research and clinical work for established pediatric psychologists, current trainees, and future generations of pediatric psychology researchers and clinicians. We are looking forward to seeing what the next several decades have in store.
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17 Emerging areas Avani C. Modi1, 2, Ana M. Gutierrez-Colina1, Kimberly A. Driscoll3 1
Division of Behavioral Medicine and Clinical Psychology, Center for Adherence and Self-Management, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States; 2 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; 3 Department of Clinical & Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, United States The field of pediatric adherence and self-management has burgeoned throughout the past 25 years, with an increasing number of studies focusing on new methods of adherence assessment, novel developments in adherence and self-management interventions, and adoption of cutting-edge technology-based approaches to deliver evidence-based adherence and self-management tools. In addition to these areas of growth, several emerging issues are at the forefront of our field. In the sections that follow, we will discuss recommendations on adherence terminology and taxonomy, guidance about use of contemporary theoretical models, new adherence measurement approaches and novel targets for intervention, methodological innovations for trial design, and dissemination and implementation efforts to advance the impact of adherence science in clinical practice.
Taxonomy The terms used to describe adherence have changed across time and differed across disciplines, with ongoing debate about the terminology that most accurately captures the nuances of this behavior (Dickinson et al., 2017). The lack of consistent terminology, common measurement approaches, and unifying adherence taxonomies has hampered scientific progress, challenged study replication, and served as a barrier to the aggregate study of the adherence literature. Recognizing the critical need to
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harmonize and enhance the transparency of research reporting, the European Society for Patient Adherence, Compliance and Persistence (ESPACOMP) developed an empirical taxonomy that conceptualizes adherence as a complex, dynamic, and quantifiable process. This taxonomy comprises three distinct but interrelated phases, including initiation, implementation, and persistence (Vrijens et al., 2012). The initiation phase is the start of the adherence process and assesses whether or not an individual initiates treatment. The implementation phase evaluates dosing history, including dosing delays, omissions, or additions. Lastly, the persistence phase indicates the length of time between the initiation phase and the moment in which an individual discontinues treatment. This conceptual framework facilitates uniformity in the study and reporting of adherence-related science and addresses several limitations that affect scientific progress within the field of adherence and self-management. Therefore, we advocate for its adoption to facilitate progress, research replication, and future collaborations across disciplines and adherence scientists.
Theory The application of theory to guide research endeavors is an important step in promoting scientific progress within the field of psychology. Theoretical principles serve as the foundation for developing research aims and testable hypotheses. In pediatric adherence and self-management, several older theories have been applied to inform scientific inquiry (e.g., Health Belief Model, Transtheoretical Model of Change) (see Chapter 1: Introduction), but no theories have successfully applied or are fully supported empirically across pediatric chronic conditions. Furthermore, in some pediatric areas (see Chapter 15: Dermatological Conditions and Chapter 16: Sleep), there is a complete lack of theoretical guidance to inform adherence and self-management research efforts. One of the primary barriers to using these theories is that they were developed exclusively in adult populations, which neglects key developmental factors and the larger systems in which children exist (e.g., family, school, community). As a result, we advocate for the future use of pediatric-specific contemporary models, including the Pediatric Self-management Model (Modi et al., 2012) and the Revised Selfand Family Management framework (Gray, Knafl, & McCorkle, 2006; Gray, Schulman-Green, Knafl, & Reynolds, 2015; Ryan & Sawin, 2009). These frameworks can be applied across pediatric conditions and were intentionally developed to reflect the complexities that affect pediatric populations.
Measurement Adherence assessment via objective, reliable methodology is critical to address and understand adherence behaviors. Electronic monitoring and
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technology-focused tools are standard for the measurement of adherence across a number of diseases. These methods yield robust data on daily adherence patterns and shed light on new areas of intervention. For example, daily adherence data allow for the identification of time of day or days of the week that are particularly problematic. Older electronic monitors, such as MEMS TrackCaps or blood glucose meters, have the capability of recording adherence data across time but could only be downloaded at point of care or during a research visit. In contrast, new electronic monitors provide real-time adherence data to clinicians, researchers, and individuals and their family members. For example, SimpleMed pillboxes (Vaica; Israel) use 3G/4G networks to communicate with a portal that displays real-time adherence data. Similarly, AdhereTech bottles for oral medications and Propeller Health for inhalers allow for realtime adherence monitoring and increase the amount and precision of clinical data available for proactive intervention. “Smart packaging,” where microchips in blister packs monitor when doses are removed from the pack, is also being used successfully (Arnet, Walter, & Hersberger, 2013). In diabetes, blood glucose meters, continuous glucose monitors, and insulin pumps provide real-time data to smart phones and cloud-based applications so that immediate treatment adjustments can be made (see Chapter 3: Type 1 Diabetes). Some electronic monitors also have the ability to remind individuals to take their medications via texts, phone calls, or emails and can be tailored to align with their preferences. Moreover, strategies to improve adherence are embedded into the electronic devices with options for individual tailoring. Wearable and tracking devices such as smartwatches, fitness bracelets, and apnea machines are increasingly used to assess daily adherence to broader health behaviors (e.g., physical activity, sleep) and guide treatment course. With the exception of diabetes devices, it is unclear if these electronic devices are clinically useful and insurance companies rarely provide coverage for them significantly limiting dissemination and uptake in clinical practice. Thus, future advocacy efforts are needed to demonstrate the clinical benefits of measuring adherence to positively impact clinical care and health outcomes. Interestingly, a large number of adherence measurement tools (e.g., electronic monitors, pharmacy refills, self-report) are plagued by an inability to confirm if medications have actually been ingested. Newer approaches, such as patented mobile artificial intelligence (aICure; New York, NY) or digital pills with ingestible sensors (Proteus Digital Health) confirm drug ingestion and may be the future of adherence measurement. However, it is unclear if youth with chronic conditions and their families will be open to this “big brother” approach, particularly as new risks related to confidentiality, health data privacy, and cyber security are introduced. Furthermore, the extent to which insurance companies and third-party payers will support these innovative devices remains
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unknown. That being said, pharmacies are becoming more involved in medication therapy management, with high potential for reimbursement. Pharmacists may be in a unique and rare position to influence adherence behaviors in both inpatient and outpatient settings, and psychologists are encouraged to partner with pharmacists to further influence adherence at the systems level for youth with chronic conditions. Adherence biomarkers are also increasingly used in clinical practice, including standard deviations of medication levels (see Chapter 13: Solid Organ Transplant), metabolites (see Chapter 7: Cancer and Chapter 11: Inflammatory Bowel Disease and GI Disorders), or serum levels (see Chapter 9: Epilepsy). Bioassays enable clinicians to better understand whether individuals have medications in their body, but they may not provide the level of specificity needed to guide behavioral interventions. Newer biologically based methods, including hair samples, dried blood spot sampling, and saliva samples, are currently being tested in a number of pediatric conditions (see Chapter 9: Epilepsy and Chapter 12: HIV/ AIDS); however, it remains unknown if these methods are reliable and valid for clinical practice. Finally, it is notable that electronic monitors and medical devices, including continuous glucose monitoring or insulin pump therapies for type 1 diabetes, produce daily and even moment-by-moment adherence data, providing a wealth of health information. With the exponential availability of health data generated by these devices, healthcare providers, caregivers, and individuals with chronic conditions are progressively faced with new challenges related to data integration for clinical decision-making. Big data analytics and machine learning approaches and novel ways to provide individuals with user-friendly data may provide innovative avenues for leveraging the valuable information drawn from technology, while minimizing system inefficiencies, costs, and provider/patient burden. For example, efforts are underway to provide individuals with type 1 diabetes with summary statistics and recommendations to improve insulin pump adherence that are individually tailored and more understandable than reports generated by industry standard software (Driscoll et al., 2017).
Intervention Technology innovations have a profound impact on the development of adherence and self-management interventions. As highlighted by many of the chapters in this book, mobile health (mHealth), electronic health (e-Health), and telehealth are increasingly being used to address adherence and self-management. Despite the promise of these
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interventions, participant engagement across time with these approaches is a challenge. Because the power of technology-based solutions is limited by the extent to which individuals use them, mHealth content needs to be engaging and interactive, and perceived as beneficial. As such, researchers are encouraged to work with various disciplines with expertise in engagement, including education technology experts, graphic designers and programmers, videographers, as well as stakeholders (e.g., patients, families, providers). By engaging key players in the development process, mHealth tools will have higher uptake by individuals with chronic illness and caregivers, thereby increasing their reach and efficacy. As noted in several meta-analyses (Dayer et al., 2017; Fedele, Cushing, Fritz, Amaro, & Ortega, 2017), rigorous randomized controlled trials are still needed to evaluate the long-term efficacy of mHealth adherence interventions, but in an age of consumerism where medical care is provided virtually (e.g., digital therapeutics), groceries are delivered to homes, and most products can be obtained within 24 hours, tech-based solutions are likely to be an important piece of the future adherence landscape. The field of prescription digital therapeutics, a novel paradigm to treat illness and manage health-related challenges, is a related emerging area that capitalizes on technology. Rooted in evidence-based therapies (e.g., cognitive-behavioral therapy), prescription digital therapeutics use health technology and digital platforms to link behavioral interventions with physician prescription practices to treat or prevent the onset of health conditions. Prescription digital therapeutics can be prescribed independently or in conjunction with pharmacotherapy to provide a multipronged approach to treatment and prevention. Once the digital therapeutic prescription is filled, individuals obtain a code that gives them access to a digital platform where they receive the prescribed intervention from the comfort of their homes. Prescription digital therapeutics are moving toward approval by the Food and Drug Administration (FDA), with the first prescription digital therapeutic (for opioid use disorder) cleared by the FDA in late 2018 (i.e., reSET by Pear Therapeutics and Novartis), further establishing its future use and potential for adherence and self-management interventions. Lastly, the emergence of promising new targets for adherence and self-management interventions provides new frontiers for the treatment of nonadherence. Neurocognitive functions (e.g., executive functioning, self-regulation, attention) are increasingly recognized as playing a key role in the execution and implementation of self-management tasks across pediatric conditions. Cross-sectional studies demonstrate associations between executive functioning and adherence in children and adolescents with spina bifida (O’Hara & Holmbeck, 2013), solid organ transplantation (Gutie´rrez-Colina et al., 2016), and asthma (Sonney &
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Insel, 2019). Results from a literature review in youth with type 1 diabetes further support associations between executive functioning and adherence, as well as biomarkers such as A1C (Duke & Harris, 2014), suggesting that neurocognitive functions may have a role in shaping not only adherence and self-management behaviors but also biobehavioral outcomes. Longitudinal investigations replicated this pattern of findings and demonstrated that better executive functioning is associated with slower increases in A1C (Berg et al., 2018) and better glycemic control across time (Vloemans et al., 2019), indicating that assessment of executive functioning skills may help identify those at risk for suboptimal clinical outcomes. Recent attention to the role of parental executive functioning and the significant interactions between parental and child executive functioning in the prediction of adherence highlights the important role of neurocognitive functions, not just in youth but also in their caregivers (Goethals et al., 2018). Although traditionally conceptualized as a relatively stable variable, mounting evidence in pediatric research reveals that neurocognitive functioning can be feasibly targeted and effectively improved with training (Kurowski et al., 2014; Modi et al., under review; Wade et al., 2010). As such, neurocognitive functions are a promising new avenue for targeting many of the skills that underlie the successful execution of adherence and selfmanagement behaviors. Behavioral economics is another target for intervention that is receiving increased attention. Behavioral economics represents several scientific fields, including psychology, marketing, and economics, with the goal of understanding human decision-making. Four primary concepts from behavioral economics apply to adherence and self-management behaviors, including default bias (i.e., consumer’s tendency to choose preselected items that are nonmandatory), loss aversion (i.e., gaining a reward is perceived as better than losing something of equal value), overestimation of rare events (i.e., when individuals misinterpret the likelihood of a rare event occurring), and social norms (i.e., impact of feedback about another person’s performance/behavior on one’s own performance/behavior) (Stevens, 2014). Stevens (2014) urged pediatric psychologists to consider the role of these behavioral economic principles in improving adherence behaviors. For example, pharmacies can provide automatic refill reminders and delivery of medications via mail as default (default bias) or adolescents could lose 15 minutes from their allotted 150 daily minutes on their smartphone/tablet every time they miss their medicine (loss aversion). These are strategies that healthcare providers could recommend and/or caregivers could implement. Lottery-based systems of rewards are also being used via apps, including Mango Health, in which individuals have a chance at winning various prizes
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(e.g., gift cards, donation to a charity) depending on how well they complete their treatments (overestimation of rare events). Testing of these types of interventions at the population level is important. For example, a randomized clinical trial focused on loss aversion, BE IN CONTROL, provided adolescents and young adults with type 1 diabetes a virtual account of $60 each month, with $2 subtracted for every day the individuals did not meet their blood glucose monitoring goal (Wong & Wirrell, 2006). Participants in the intervention had greater adherence to blood glucose monitoring compared to controls (50% vs. 19%) during the active intervention arm, but this difference disappeared during follow-up when incentives were removed, suggesting loss aversion programs may be short-lived. Finally, comparing how youth adhere to treatment compared with those of similar age/sex and condition may nudge them to become more adherent (social norms). A social norms adherence intervention is currently being tested in a small NIH clinical trial (NCT03958331) in adolescents with epilepsy. Use of these principles could be an important future direction for pediatric adherence and selfmanagement interventions. Building on behavioral economic principles, increased attention is being given to incentivizing adherence behaviors. Companies around the United States incentivize employees in wellness programs to stop smoking, exercise more, and engage in healthy dietary behaviors. Incentive systems are effective for children and adolescents for decreasing marijuana use (Stewart, Felleman, & Arger, 2015), increasing activity (Christian et al., 2016), and making healthy food choices (McEvoy et al., 2014). A 2015 meta-analysis found financial incentive systems improve the odds of changing behavior fourfold when compared with controls, regardless of age, sex, or race (Haff et al., 2015). Thus, incentivizing treatment adherence is one possible solution to promote health, especially for youth with chronic conditions. As noted in BE IN CONTROL, which is both a financial incentive and loss aversion, effects of these programs may be short-lived. In addition, the ethical considerations of payment for treatment must be considered (Healy, Hope, Bhabha, & Eyal, 2017). One potential concern is the replacement of extrinsic motivation by intrinsic motivation, which may yield poorer adherence when incentives are removed and the adolescent is no longer motivated to adhere for their own health (e.g., intrinsic motivation). However, to our knowledge, no studies have examined the differential role of intrinsic and extrinsic motivation related to financial incentives for treatment adherence and self-management in youth. Research focused on behavioral economic principles is an important area for future research and warrants attention as a target for adherence promotion efforts.
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Methodology Study designs As noted in the introduction, several meta-analyses highlight that healthcare providerebased and multicomponent interventions produce the largest effects (Graves, Roberts, Rapoff, & Boyer, 2010; Kahana, Drotar, & Frazier, 2008; Pai & McGrady, 2014; Wu & Pai, 2014). Dismantling which strategies are most effective and for whom is an important next step in pediatric psychology to facilitate personalized treatment and optimal resource allocation. One way to answer these questions is the use of adaptive trials (Nanhum-Shani et al., 2012), such as Sequential Multiple Assignment Randomized Trials (SMART), in which several adherence strategies are embedded in the intervention, but responsiveness to the initial strategy determines the need for additional intervention components (Almirall, Nahum-Shani, Sherwood, & Murphy, 2014; Collins, Nahum-Shani, & Almirall, 2014). For example, Naar-King et al. (2016) employed a two-stage adaptive intervention design to test four different treatment components and optimize weight loss among African American adolescents with obesity (Naar-King et al., 2016). Youth and caregivers in this behavioral trial were randomized to either home-based or office-based motivation interviewing þ skills building (phase 1). After the initial treatment, nonresponders (weight change <3%) were rerandomized to an augmented treatment that included either continued skills or contingency management (phase 2). All responders completed relapse prevention during this trial phase. This example illustrates how the use of SMART designs allows researchers to examine the most effective and efficient interventions to improve clinical outcomes.
Transparent reporting Transparent reporting is recognized as a fundamental component of rigorous and high-quality scientific research, with important implications for the validity, reliability, replicability, and impact of research findings and conclusions (Simera et al., 2010). Throughout the past few decades, this growing recognition has led to the creation of transparent reporting guidelines for randomized and nonrandomized clinical trials (e.g., CONSORT, STROBE), an important step in promoting scientific transparency and providing guidance to the scientific community about best reporting practices. Consistent with this trend, the European Society for Patient Adherence, Compliance, and Persistence (ESPACOMP) developed Medication Adherence Reporting Guidelines (EMERGE) to provide complementary and specific direction regarding transparent reporting for adherence (De Geest et al., 2018, 2019). The EMERGE
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guidelines are conceptually grounded in the ESPACOMP taxonomy for medication adherence noted previously (Vrijens et al., 2012) and include a set of four items describing the minimum reporting criteria and additional 17 items with recommendations for more detailed adherence reporting. The minimum criteria include (1) reporting on specific phases of medication adherence studied (i.e., initiation, implementation, persistence); (2) providing a precise operational definition of each adherence phase; (3) specifying the measurement methods used to assess adherence at each phase; and (4) discussing research results for each of the adherence phases studied. We believe these basic reporting criteria should become the new standard for reporting adherence and advocate for its adoption to increase commitment to conducting rigorous and high-quality research in a transparent and consistent manner. We urge adherence researchers to consider the additional EMERGE recommendations for the most rigorous approach to adherence reporting methodology.
Dissemination and implementation science in adherence and self-management Dissemination and implementation of adherence measurement and interventions remains a critical need. Few adherence and selfmanagement interventions have been disseminated and implemented in clinical practice because it takes approximately 17 years for research to benefit patient care (Green, 2008). Scaling interventions for broad dissemination can be difficult, but improving patienteprovider communication about self-management is a powerful first step. In the past, this topic was often ignored or avoided by both medical staff and patients/families. A recent survey of adherence practices in pediatric gastroenterology care, for example, indicates that healthcare providers believe adherence monitoring in clinical practice is important, but only 25% systematically screen for adherence problems and only 21% perceive that they are able to modify adherence behaviors (Maddux et al., 2018). Pediatric psychologists are key healthcare providers trained in adherence and uniquely positioned to facilitate conversations about adherence and self-management. Unfortunately, most medical clinics do not have access to pediatric psychologists. Arming frontline healthcare providers with strategies to help their patients and families and advocating for the integration of pediatric psychologists in medical subspecialists is a critical first step and must become standard of care. Strategies to initiate discussion about adherence include normalizing and not criticizing families for adherence difficulties, assessing barriers
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to adherence, and asking very specific questions about how families fit medications into their daily routine (e.g., when they take it, last missed dose, barriers they experienced). A recent clinical initiative within a pediatric kidney transplant clinic focuses on a clinical adherence monitoring and intervention system, the Adherence Monitoring and Promotion Program, which was initiated and developed by adherence psychologists, individuals in need of a kidney transplant, and healthcare providers, in which the first step was training the healthcare team on ways to discuss adherence nonjudgmentally. Second, a simple adherence barriers checklist was developed based on the evidence-based literature regarding pediatric adherence barriers and administered to individuals (10 years and older) and their caregivers via a tablet every 6 months (Varnell et al., 2017). Third, a clinical algorithm and shared decision-making tools were developed to provide guidance to healthcare team members on next steps when a barrier is identified. These tools are used systematically by providers to engage families in discussion about strategies to overcome barriers. The Adherence Monitoring and Promotion Program is an exemplar for other chronic conditions of how to disseminate adherence promotion strategies into clinical practice, with preliminary data indicating that kidney rejection rates have decreased because of this initiative. To ensure support for adherence interventions in clinical practice, however, the value of these efforts should be demonstrated. For example, how does dissemination and implementation of adherence initiatives save individuals with chronic conditions and healthcare systems money? How does being proactive with adherence efforts differ from being reactive financially? Adult studies indicate that implementation of behavioral adherence promotion interventions in clinical practice is likely less costly than the indirect (e.g., productivity loss) and direct healthcare costs associated with suboptimal adherence (Chapman, Ferrufino, Kowal, Classi, & Roberts, 2010; Chapman, Kowal, et al., 2010; Desborough, Sach, Bhattacharya, Holland, & Wright, 2012). More pediatric studies need to quantify the impact of adherence interventions on healthcare charges, costs, and utilization. Pediatric nonadherence is linked to higher healthcare use, including emergency room visits and hospitalizations (McGrady & Hommel, 2013). Increasing nonadherence across time in individuals with IBD results in three times the healthcare costs compared with more adherent individuals, suggesting nonadherence is a driver of healthcare costs (Hommel et al., 2017). Similarly, individuals with nonadherence as measured by a biomarker (e.g., standard deviation of tacrolimus levels) in kidney transplant have higher healthcare utilization and charges compared to those with better adherence (Rich et al., 2018). These studies are beginning to shed light on the economic impact of pediatric nonadherence, but much work is yet to be done.
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Lastly, although treatment adherence is a key goal for the teams that care for youth with chronic conditions, it is important to recognize that optimal adherence may not be a priority for families. Teams must consider a family’s hierarchy of needs and recognize that essential needs in Maslow’s Hierarchy (e.g., food, shelter, safety) must be met first before adherence interventions become the focus of clinical care (Barnidge, LaBarge, Krupsky, & Arthur, 2017). Understanding how hospitals and clinics can provide financial assistance or connect families with resources in the community to meet these needs should be the first step of any adherence promotion intervention.
Conclusions It is clear from the content of each of the chapters in this book that decades of research have contributed significantly to our understanding of pediatric adherence and self-management. This is an extremely exciting time for pediatric psychologists as our contributions to medicine generally, and to improving adherence and self-management behaviors have never been stronger. Moreover, the need for our integration into routine medical care because of our specialized expertise and training in behavioral science is clearer than ever. However, as noted in multiple chapters, despite how vast our field is, there is still much work to be done. A consistent theme across all the chapters in this book, regardless of the condition of focus, is the great need for innovative intervention research that leads to improvements in pediatric adherence and self-management behaviors and health outcomes more generally. This research must not only capitalize on technological advances and the emerging areas highlighted in this chapter but must also be cost-effective to facilitate dissemination into clinical care of youth. The compilation of the extant pediatric adherence and self-management research in this book provides a solid foundation of accomplishments in the pediatric psychology field in the last several decades. In addition, we hope that the highlighted gaps in each chapter, combined with emerging topics of study, help to stimulate innovative research and clinical work for established pediatric psychologists, current trainees, and future generations of pediatric psychology researchers and clinicians. We are looking forward to seeing what the next several decades have in store.
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