Training the Workforce to Conduct Embedded Pragmatic Clinical Trials to Improve Care for People Living with Dementia and Their Caregivers

The National Institute on Aging IM bedded P ragmatic A lzheimer's Disease and Alzheimer's Disease–Related Dementias C linical T rials (IMPACT) Collaboratory serves as a national resource for the conduct of embedded pragmatic clinical trials to improve the care of people living with dementia (PLWD) in partnership with the healthcare systems that serve them. Inherent in this objective is the need to train and support a cadre of investigators prepared to conduct this work now and in the future. The Training Core of the IMPACT Collaboratory supports the training of investigators to become experts in this field through three objectives: (1) curricula development and dissemination; (2) network generation and navigation; and (3) a career development award program. The innovative approach of the Training Core will require developing content and providing training experiences that recognize the unique challenges of research at the intersection of health systems, pragmatic trials, and PLWD and their caregivers. Ultimately, we seek to build the nation's capacity to conduct research that bridges the gaps between efficacy studies to effectiveness research to implementation science. Although foundational resources in the methods of each of these areas are already available, few actually focus on pragmatic trials embedded within healthcare systems that focus on PLWD. To bring new interventions for PLWD from efficacy to widespread implementation, researchers must build diffusability, adaptability, heterogeneity, and scalability into the design of the intervention. In achieving these objectives, the Training Core will utilize the network of investigators, institutions, and stakeholders represented in the IMPACT Collaboratory. J Am Geriatr Soc 68:S21–S27, 2020 .     

Selecting Outcomes to Ensure Pragmatic Trials Are Relevant to People Living with Dementia

Outcome measures for embedded pragmatic clinical trials (ePCTs) should reflect the lived experience of people living with dementia (PLWD) and their caregivers, yet patient- and caregiver-reported outcomes (PCROs) are rarely available in large clinical and administrative data sources. Although pragmatic methods may lead to use of existing administrative data rather than new data collected directly from PLWD, interventions are truly impactful only when they change outcomes prioritized by PLWD and their caregivers. The Patient- and Caregiver-Reported Outcomes Core (PCRO Core) of the IM bedded P ragmatic A lzheimer's Disease (AD) and AD-Related Dementias C linical T rials (IMPACT) Collaboratory aims to promote optimal use of outcomes relevant to PLWD and their caregivers in pragmatic trials. The PCRO Core will address key scientific challenges limiting outcome measurement, such as gaps in existing measures, methodologic constraints, and burdensome data capture. PCRO Core investigators will create a searchable library of AD/AD-related dementias (ADRD) clinical outcome measures, including measures in existing data sources with potential for AD/ADRD ePCTs, and will support best practices in measure development, including pragmatic adaptation of PCROs. Working together with other Cores and Teams within the IMPACT Collaboratory, the PCRO Core will support investigators to select from existing outcome measures, and to innovate in methods for measurement and data capture. In the future, the work of the IMPACT Collaboratory may galvanize broader embedded use of outcomes that matter to PLWD and their care partners in large health systems. J Am Geriatr Soc 68:S55–S61, 2020 .     

Transforming Dementia Care Through Pragmatic Clinical Trials Embedded in Learning Healthcare Systems

The current evidence base for testing nonpharmacological interventions for people living with dementia (PLWD) and their caregivers is limited, especially within care settings such as ambulatory care, assisted living communities, nursing homes, hospitals, and hospices. There has been even less attention to translation of effective interventions for PLWD into delivery of care. Thus, there is an urgent need for researchers to partner with these care settings, especially those that follow a learning healthcare systems (LHSs) model, and vice versa to conduct embedded pragmatic clinical trials (ePCTs). These trials are conducted within sites that offer routine care and are designed to answer important, relevant clinical questions and leverage existing electronic health and administrative data. ePCTs set in LHSs create a unique opportunity for researchers, healthcare providers, and PLWD and their families to work and learn together as potentially effective interventions are studied and stress tested in real-world situations. Healthcare settings that embrace research or quality improvement as part of a culture of continuous learning are ideal settings for ePCTs. In this article, we summarize what we have learned from the National Institutes of Health's Health Care Systems Research Collaboratory–funded ePCTs, discuss challenges of ePCTs within settings that serve PLWD, and describe the work of the Health Care Systems Core within the National Institute on Aging's IMbedded Alzheimer's Disease and Related Dementias Clinical Trials Collaboratory that will occur over the next 5 years. J Am Geriatr Soc 68:S43–S48, 2020 .     

Building a National Program for Pilot Studies of Embedded Pragmatic Clinical Trials in Dementia Care

Sixteen million caregivers currently provide care to more than 5 million persons living with dementia (PLWD) in the United States. Although this population is growing and highly complex, evidence-based management remains poorly integrated within healthcare systems. Therefore, the National Institute on Aging IMPACT Collaboratory was formed to build the nation's ability to conduct embedded pragmatic clinical trials (ePCTs) for PLWD and their caregivers. The pilot core of the IMPACT Collaboratory seeks to provide funds for upward of 40 pilots for ePCTs to accelerate the testing of nonpharmacologic interventions with the goal that these pilots lead to full-scale ePCTs and eventually the embedding of evidence-based care into healthcare systems. The first two challenges for the pilot core in building the pilot study program were (1) to develop a transparent, ethical, and open nationwide process for soliciting, reviewing, and selecting pilot studies; and (2) to begin the process of describing the necessary components of a pilot study for an ePCT. During our initial funding cycle, we received 35 letters of intent, of which 17 were accepted for a full proposal and 14 were submitted. From this process we learned that investigators lack knowledge in ePCTs, many interventions lack readiness for an ePCT pilot study, and many proposed studies lack key pragmatic design elements. We therefore have set three key criteria that future pilot studies must meet at a minimum to be considered viable. We additionally discuss key design decisions investigators should consider in designing a pilot study for an ePCT. J Am Geriatr Soc 68:S14–S20, 2020 .     

Using Healthcare Data in Embedded Pragmatic Clinical Trials among People Living with Dementia and Their Caregivers: State of the Art

Embedded pragmatic clinical trials (ePCTs) are embedded in healthcare systems as well as their data environments. For people living with dementia (PLWD), settings of care can be different from the general population and involve additional people whose information is also important. The ePCT designs have the opportunity to leverage data that becomes available through the normal delivery of care. They may be particularly valuable in Alzheimer's disease and Alzheimer's disease-related dementia (AD/ADRD), given the complexity of case identification and the diversity of care settings. Grounded in the objectives of the Data and Technical Core of the newly established National Institute on Aging Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory (IMPACT Collaboratory), this article summarizes the state of the art in using existing data sources (eg, Medicare claims, electronic health records) in AD/ADRD ePCTs and approaches to integrating them in real-world settings. J Am Geriatr Soc 68:S49–S54, 2020 .     

Embedded Pragmatic Trials in Dementia Care: Realizing the Vision of the NIA IMPACT Collaboratory

Close to 6 million Americans have Alzheimer's disease (AD) or Alzheimer's disease and related dementia (AD/ADRD). These high-need, high-cost patients are vulnerable to receiving poor quality uncoordinated care, ultimately leading to adverse health outcomes, poor quality of life, and misuse of resources. Improving the care of persons living with dementia (PLWD) and their caregivers is an urgent public health challenge that must be informed by high-quality evidence. Although prior research has elucidated opportunities to improve AD/ADRD care, the adoption of promising interventions has been stymied by the lack of research evaluating their effectiveness when implemented under real-world conditions. Embedded pragmatic clinical trials (ePCTs) in healthcare systems have the potential to accelerate the translation of evidence-based interventions into clinical practice. Building from the foundation of the National Institutes of Healthcare Systems Collaboratory, in September 2019 the National Institute on Aging Imbedded Pragmatic AD/ADRD Clinical Trials (IMPACT) Collaboratory was launched. Its mission is to build the nation's capacity to conduct ePCTs within healthcare systems for PLWD and their caregivers by (1) developing and disseminating best practice research methods, (2) supporting the design and conduct of ePCTs including pilot studies, (3) building investigator capacity through training and knowledge generation, (4) catalyzing collaboration among stakeholders, and (5) ensuring the research includes culturally tailored interventions for people from diverse backgrounds. This report presents the rationale, structure, key activities, and markers of success for the overall NIA IMPACT Collaboratory. The articles that follow in this special Issue describe the specific work of its 10 core working groups and teams. J Am Geriatr Soc 68:S1–S7, 2020 .     

Career development in pragmatic clinical trials to improve care for people living with dementia

The growing number of people living with dementia (PLWD) requires a coordinated clinical response to deliver pragmatic, evidence-based interventions in frontline care settings. However, infrastructure to support such a response is lacking. Moreover, there are too few researchers conducting rigorous embedded pragmatic clinical trials (ePCTs) to make the vision of high quality, widely accessible dementia care a reality. National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease and Related Dementias Clinical Trials (IMPACT) Collaboratory seeks to improve the pipeline of early career researchers qualified to lead ePCTs by funding career development awards. Even with support from the Collaboratory, awardees face practical and methodological challenges to success, recently exacerbated by the COVID-19 pandemic. We first describe the training opportunities and support network for the IMPACT CDA recipients. This report then describes the unique career development challenges faced by early-career researchers involved in ePCTs for dementia care. Topics addressed include challenges in establishing a laboratory, academic promotion, mentoring and professional development, and work-life balance. Concrete suggestions to address these challenges are offered for early-career investigators, their mentors, and their supporting institutions. While some of these challenges are faced by researchers in other fields, this report seeks to provide a roadmap for expanding the work of the IMPACT Collaboratory and initiating future efforts to recruit, train, and retain talented early-career researchers involved in ePCTs for dementia care.     

Engaging Stakeholders in the Design and Conduct of Embedded Pragmatic Clinical Trials for Alzheimer’s Disease and Alzheimer’s Disease–Related Dementias

Embedded pragmatic clinical trials (ePCTs) of nondrug interventions for Alzheimer’s disease and Alzheimer’s disease–related dementias (AD/ADRD) are conducted in real-world clinical settings and designed to generate an evidence base to inform clinical and policy decisions about care for this vulnerable population. The ePCTs exist within a complex ecosystem of relationships between researchers, payors, policymakers, healthcare systems, direct care staff, advocacy groups, families, caregivers, and people living with dementia (PLWD). Because the rapid increase of the number of Americans with AD/ADRD outpaces curative treatments, there is an urgent need to mobilize the power of these relationships to improve dementia care and address a mounting public health crisis. Stakeholder engagement in ePCTs is essential to generate research questions, establish the relevancy of trials to the intended end users, and understand the factors that influence dissemination and implementation in real-world clinical settings. The process of including stakeholders in ePCTs for dementia is similar to stakeholder engagement in ePCTs for other diseases and conditions; however, the unique nature of embedded research, prevalence of caregiver and provider burden, and the progressive worsening of cognitive impairment in PLWD must be approached with additional strategies. This article presents key considerations of stakeholder engagement for ePCTs in AD/ADRD and main activities of the stakeholder engagement team in the National Institute on Aging IMPACT Collaboratory to move the field forward. J Am Geriatr Soc 68:S62–S67, 2020 .     

Ethical and Regulatory Issues for Embedded Pragmatic Trials Involving People Living with Dementia

Embedded pragmatic clinical trials (ePCTs) present an opportunity to improve care for people living with dementia (PLWD) and their care partners, but they also generate a complex constellation of ethical and regulatory challenges. These challenges begin with participant identification. Interventions may be delivered in ways that make it difficult to identify who is a human subject and therefore who needs ethical and regulatory protections. The need for informed consent, a core human subjects protection, must be considered but can be in tension with the goals of pragmatic research design. Thus it is essential to consider whether a waiver or alteration of informed consent is justifiable. If informed consent is needed, the question arises of how it should be obtained because researchers must acknowledge the vulnerability of PLWD due in part to diminished capacity and also to increased dependence on others. Further, researchers should recognize that many sites where ePCTs are conducted will be unfamiliar with human subjects research regulations and ethics. In this report, the Regulation and Ethics Core of the National Institute on Aging Imbedded Pragmatic Alzheimer’s disease (AD) and AD-related dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory discusses key ethical and regulatory challenges for ePCTs in PLWD. A central thesis is that researchers should strive to anticipate and address these challenges early in the design of their ePCTs as a means of both ensuring compliance and advancing science. J Am Geriatr Soc 68:S37–S42, 2020 .     

Achieving Health Equity in Embedded Pragmatic Trials for People Living with Dementia and Their Family Caregivers

Embedded pragmatic clinical trials (ePCTs) advance research on Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD) in real-world contexts; however, health equity issues have not yet been fully considered, assessed, or integrated into ePCT designs. Health disparity populations may not be well represented in ePCTs without special efforts to identify and successfully recruit sites of care that serve larger numbers of these populations. The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease (AD) and AD-Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory's Health Equity Team will contribute to the overall mission of the collaboratory by developing and implementing strategies to address health equity in the conduct of ePCTs and ensure the collaboratory is a national resource for all Americans with dementia. As a first step toward meeting these goals, this article reviews what is currently known about the inclusion of health disparities populations of people living with dementia (PLWD) and their caregivers in ePCTs, highlights unique challenges related to health equity in the conduct of ePCTs, and suggests priority areas in the design and implementation of ePCTs to increase the awareness and avoidance of pitfalls that may perpetuate and magnify healthcare disparities. J Am Geriatr Soc 68:S8–S13, 2020 .     

Dissemination and Implementation of Evidence-Based Dementia Care Using Embedded Pragmatic Trials

There are many nonpharmacologic interventions tested in randomized clinical trials that demonstrate significant benefits for people living with Alzheimer's disease (AD) and AD-related dementia, their care partners, or professional care providers. Nevertheless, with few exceptions, proven interventions have not been translated for delivery in real-world settings, such as home care, primary care, hospitals, community-based services, adult day services, assisted living, nursing homes, or other healthcare systems (HCSs). Using embedded pragmatic clinical trial (ePCT) methods is one approach that can facilitate dissemination and implementation (D&I) of dementia care interventions. The science of D&I can inform the integration of evidence-based dementia care in HCSs by offering theoretical frameworks that capture field complexities and guiding evaluation of implementation processes. Also, D&I science can suggest evidence-based strategies for implementing dementia care in HCSs. Although D&I considerations can inform each stage of dementia care intervention development, it is particularly critical when designing ePCTs. This article examines fundamental considerations for implementing dementia-specific interventions in HCSs and how best to prepare for successful dissemination upstream in the context of ePCTs, thereby illustrating the critical role of the D&I Core of the National Institute on Aging Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory. The scientific premise of the D&I Core is that having the “end” in mind, upfront in the design and testing of dementia care programs, can lead to decision-making that optimizes the ultimate goal of wide-scale D&I of evidence-based dementia care programs in HCSs. J Am Geriatr Soc 68:S28–S36, 2020 .     

Ethical analysis of vulnerabilities in cluster randomized trials involving people living with dementia in long-term care homes

Cluster randomized trials (CRT) of non-pharmacological interventions are an important means of improving the quality of care and quality of life of people living with dementia (PLWD) in long-term care (LTC) homes. PLWD in LTC homes are, however, vulnerable in manifold ways. Therefore, researchers require guidance to ensure that the rights and welfare of PLWD are protected in the course of this valuable research. In this article, we introduce a framework for identifying vulnerabilities in randomized trials and apply it to three CRTs involving PLWD in LTC homes. CRTs may render PLWD in LTC homes vulnerable to three autonomy wrongs: inadequately informed consent, inadequately voluntary consent, and invasions of privacy; two welfare wrongs: risks of therapeutic procedure exceed potential benefits, and excessive risk of non-therapeutic procedures; and one justice wrong: unjust impact of research activities on care. We then discuss appropriate, feasible additional protections that can be implemented to mitigate vulnerability while preserving the scientific validity of the CRT. Corresponding additional protections that can be feasibly implemented include capacity assessments, substitute decision-makers, assent, insulation from LTC home employees during the consent process, patient advocates, utilizing LTC home employees for data collection, stakeholder engagement, additional supervision during study procedures, using caregivers to complete questionnaires by proxy, and gatekeeper permission. Reassuringly, many of these additional protections promote, rather than imperil, the scientific validity of these trials.     

Pragmatic Trials in Long-Term Care: Implementation and Dissemination Challenges and Opportunities

Randomized controlled trials are considered the most rigorous research design in efficacy and effectiveness research; however, such trials present numerous challenges that limit their applicability in real-world settings. As a consequence, pragmatic trials are increasingly viewed as a research design that overcomes some of these barriers with the potential to produce findings that are more reproducible. Although pragmatic methodology in long-term care is receiving increasing attention as an approach to improve successful dissemination and implementation, pragmatic trials present complexities of their own. To address these complexities and related issues, experts with experience conducting pragmatic trials, developing nursing home policy, participating in advocacy efforts, and providing clinical care in long-term care settings participated in a virtual consensus conference funded by the National Institute on Aging in Spring 2021. Participants identified 4 cross-cutting principles key to dissemination and implementation of pragmatic trial interventions: (1) stakeholder engagement, (2) diversity and inclusion, (3) organizational strain and readiness, and (4) learn from adaptations. Participants emphasized that implementation processes must be grounded in the perspectives of the people who will ultimately be responsible for implementing the intervention once it is proven to be effective. In addition, messaging must speak to long-term care staff and all others who have a stake in its outcomes. Although our understanding of dissemination and implementation strategies remains underdeveloped, this article is designed to guide long-term care researchers and community providers who are increasingly aware of the need for pragmatism in disseminating and implementing evidence-based care interventions.     

Development and Preliminary Examination of the Psychometric Properties of the Behavior Problem Checklist

ABSTRACT

Objective: Clinical settings require an efficient and informative approach to the assessment of caregiving situations to help providers decide how to focus interventions. Providers serving caregivers need to know about care recipients, who may not be available in the same clinical setting where the caregiver is being served, so checklists have been developed to elicit the caregivers’ perceptions of the problem (e.g., symptoms, functional challenges, and attributions for the problem). The purpose of this study was to conduct a preliminary test of reliability and validity of an assessment tool designed for use in clinical settings that serves caregivers of persons with physical illness as well as dementias.Methods: Informal family caregiver clients in a counseling program (N = 502) completed assessment questionnaires, including a new measure, the Behavior Problem Checklist, during intake, prior to intervention. The sample was divided into a development sample (N = 400) and a verification sample (N = 102) in order to examine the psychometric properties of the Behavior Problem Checklist.Results: The Behavior Problem Checklist exhibited item-total internal reliability, test-retest reliability, and convergent validity with another measure of behavior problems.Conclusions: The Behavior Problem Checklist appears to be a valid tool to assess problem behaviors. At its current level of development, it is deemed to be appropriate for use in research settings. With further study, the BPC may prove to be a useful clinical tool for use with caregivers to help identify care recipient problem areas that can assist providers with selection of interventions.     

Improving Heart Failure Therapeutics Development in the United States: The Heart Failure Collaboratory

The current heart failure clinical trial environment is strained by increasing complexity and cost, regulatory requirements, competing demands on stakeholders, implementation challenges, and decreasing patient and investigator participation. To begin the process of developing potentially effective strategies and tactics, stakeholders including patients; investigators; academic leaders; pharmaceutical and device industry representatives; society representatives; third-party payers; and government representatives from the U.S. Food and Drug Administration, National Institutes of Health, and Centers for Medicare and Medicaid Services convened in March of 2017. This paper summarizes the discussions, outlines current challenges and actionable opportunities, and makes targeted recommendations to achieve the goals of improving efficiency in clinical trials and speeding the development of effective heart failure therapies, including the formation of an organized Heart Failure Collaboratory.     

Treatment strategies for acid reflux: EncomPASSing practical solutions for primary care

Despite a steady diet of randomized controlled trials (RCTs) for over three decades, nearly all of our routine clinical decisions remain incompletely supported, or even totally unaddressed, by the burgeoning pile of RCT data. The biomedical literature tends to focus on explanatory RCTs that compare new agents with placebo; it is less common to find pragmatic clinical trials (PCTs) that test the risks, benefits, and costs of competing active therapies within the context of usual practice settings. In this issue of the American Journal of Gastroenterology, Moayeddi and colleagues report the results of the EncomPASS study-a novel PCT for the primary care management of reflux disease. In this editorial, the results of EncomPASS are discussed, and the study is highlighted as a model for investigators to follow as we continue to emphasize pragmatic trials that address everyday challenges in clinical care.     

Impact,Challenges, and Future Projections of Vaccine Trials in Africa

Immunization remains the most cost effective method for the control of infectious diseases. Therefore, there is a global effort to deploy new vaccines for disease control and eradication. These new vaccines must be tested in the settings in which they will be used. This necessity has required the conduct of many vaccine trials in Africa, where several infectious diseases with significant public health impact are prevalent. However, these areas have peculiarities and are just beginning to gain expertise in the conduct of such trials. The vaccine developers and sponsors of these trials may also not be conversant with some issues unique to the trial site. The understanding gap from both partners can result in challenges if not addressed during the planning phase of the trial. This review seeks to highlight the issues surrounding the conduct of clinical trials in resource-constrained settings and suggests some ways of circumventing them.     

Cardiovascular outcome trials for anti-diabetes medication: A holy grail of drug development?

Since the time questions arose on cardiovascular safety of Rosiglitazone, FDA has suggested guidelines on conduct of studies on anti-diabetic drugs so as to prove that the cardiovascular risk is acceptable. Based on the cardiovascular risks of pre-approval clinical trials, guidelines have been made to conduct cardiovascular safety outcome trials (CVSOTs) prior to the drug approval or after the drug has been approved. Unlike the trials comparing the efficacy of antidiabetic agents, the CVSOTs examine the cardiovascular safety of a drug in comparison to standard of care. These trials are expensive aspects of drug development and are associated with various technical and operational challenges. More cost effective models of assessing cardiovascular safety like use of biomarkers, electronic medical records, pragmatic and factorial designs can be adopted. This article critically looks at the antidiabetic drug approval from a cardiovascular perspective by asking a few questions and arriving at answers.