Increasing patient participation in oncology clinical trials.

AIM: Timely recruitment of eligible participants is essential for the success of clinical trials, with insufficient accrual being the leading cause for premature termination of both oncology and non-oncology trials. METHODS: In this paper we further elaborate on the challenges for patient participation in oncology trials from physician, patient, healthcare system, and some trial-related perspectives. RESULTS: We present strategies such as use of digital healthcare technologies, real-world data and real-world evidence, decentralized clinical trials, pragmatic trial designs, and supportive services to increase patient participation. CONCLUSIONS: Multifaceted measures are necessary to increase patient participation, especially for those who are under-represented in cancer trials.

Impact of COVID-19 pandemic on nonpharmacological pain management trials in military and veteran healthcare settings: an evaluation informed by implementation science.

The coronavirus disease (COVID-19) pandemic disrupted healthcare and clinical research, including a suite of 11 pragmatic clinical trials (PCTs), across clinics within the Department of Veterans Affairs (VA) and the Department of Defense (DOD). These PCTs were designed to evaluate an array of nonpharmacological treatments and models of care for treatment of patients with pain and co-occurring conditions. The aims of the study are to (a) describe modifications to PCTs and interventions to address the evolving pandemic and (b) describe the application of implementation science methods for evaluation of those PCT modifications. The project used a two-phase, sequential, mixed-methods design. In Phase I, we captured PCT disruptions and modifications via a Research Electronic Data Capture questionnaire, using Periodic Reflections methods as a guide. In Phase II, we utilized the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) taxonomy to develop a focus group interview guide and checklist that would provide more in-depth data than Phase I. Data were analyzed using directed content analysis. Phase I revealed that all PCTs made between two and six trial modifications. Phase II, FRAME-guided analyses showed that the key goals for modifying interventions were increasing treatment feasibility and decreasing patient exposure to COVID-19, while preserving intervention core elements. Context (format) modifications led eight PCTs to modify parts of the interventions for virtual delivery. Content modifications added elements to enhance patient safety; tailored interventions for virtual delivery (counseling, exercise, mindfulness); and modified interventions involving manual therapies. Implementation science methods identified near-real-time disruptions and modifications to PCTs focused on pain management in veteran and military healthcare settings.

Active-duty personnel and veterans often report pain and seek treatment in military and veteran healthcare settings. Nondrug treatments, such as self-care, counseling, exercise, and manual therapy, are recommended for most patients with chronic pain. The COVID-19 pandemic has affected clinical trials of these nondrug treatments in military and veteran populations. In this study, we explored how 11 research teams adapted study trials on pain to address COVID-19. Team members completed online questions, brief checklists, and a one-time focus group about how they modified their trials. Each of the 11 trials made 2 to 6 changes to their studies. Most paused or delayed recruitment efforts. Many shifted parts of the study to a virtual format. Goals for adapting treatments included improved feasibility and decreased patient exposure to COVID-19. Context or format changes increased virtual delivery of study treatments. Content changes focused on patient safety, tailoring treatments for virtual delivery, and offering varied manual therapies. Provider concerns about technology and patient willingness to seek in-person care during the pandemic also were factors driving changes. These findings may support the increased use of virtual care for pain management in military and veteran health settings.

The impact of COVID-19 on pragmatic clinical trials: lessons learned from the NIH Health Care Systems Research Collaboratory.

BACKGROUND: The COVID-19 pandemic has considerably disrupted nearly all aspects of daily life, including healthcare delivery and clinical research. Because pragmatic clinical trials are often embedded within healthcare delivery systems, they may be at high risk of disruption due to the dual impacts on the conduct of both care and research. METHODS: We collected qualitative data using multiple methods to characterize the impact of COVID-19 on the research activities of 14 active pragmatic clinical trials in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. A COVID-19 impact questionnaire was administered electronically to principal investigators in June 2020. Text responses were analyzed thematically, and qualitative summaries were subsequently reviewed by five independent reviewers, who made iterative revisions. Additional COVID-19-related impacts were identified during virtual meetings with trial teams during April-July 2020 and combined with questionnaire responses for analysis. RESULTS: Impacts of the pandemic were broadly classified into two main types: healthcare operations and social distancing. In some instances, trial delays created statistical challenges, particularly with trials using stepped-wedge designs, and necessitated changing data collection strategies or modifying interventions. The majority of projects used existing stakeholder-driven approaches to adapt interventions. Several benefits of these adaptions were identified, including expanded outreach capabilities and ability to study virtual intervention delivery. All trial teams were able to adapt to pandemic-related modifications. CONCLUSION: In a group of 14 ongoing pragmatic clinical trials, there was significant impact of COVID-19 on trial activities. Engaging appropriate stakeholders was critical to designing and implementing trial modifications and making continued safe progress toward meeting research objectives.

Assessing the impact of the COVID-19 pandemic on pragmatic clinical trial participants.

Characterizing the impacts of disruption attributable to the COVID-19 pandemic on clinical research is important, especially in pain research where psychological, social, and economic stressors attributable to the COVID-19 pandemic may greatly impact treatment effects. The National Institutes of Health - Department of Defense - Department of Veterans Affairs Pain Management Collaboratory (PMC) is a collective effort supporting 11 pragmatic clinical trials studying nonpharmacological approaches and innovative integrated care models for pain management in veteran and military health systems. The PMC rapidly developed a brief pandemic impacts measure for use across its pragmatic trials studying pain while remaining broadly applicable to other areas of clinical research. Through open discussion and consensus building by the PMC's Phenotypes and Outcomes Work Group, the PMC Coronavirus Pandemic (COVID-19) Measure was iteratively developed. The measure assesses the following domains (one item/domain): access to healthcare, social support, finances, ability to meet basic needs, and mental or emotional health. Two additional items assess infection status (personal and household) and hospitalization. The measure uses structured responses with a three-point scale for COVID-19 infection status and four-point ordinal rank response for all other domains. We recommend individualized adaptation as appropriate by clinical research teams using this measure to survey the effects of the COVID-19 pandemic on study participants. This can also help maintain utility of the measure beyond the COVID-19 pandemic to characterize impacts during future public health emergencies that may require mitigation strategies such as periods of quarantine and isolation.

The time is now: role of pragmatic clinical trials in guiding response to global pandemics.

Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research response. The slow and inefficient process of carrying out traditional randomized clinical trials led regulatory authorities to hastily approve treatments and tests without sufficient evidence of safety and efficacy.We here outline issues with the current research platform, summarize shortcomings of traditional randomized clinical trials particularly apparent at the time of pandemics, and highlight the advantages of pragmatic clinical trials as an alternative to rapidly generate the needed clinical evidence. We further discuss barriers and challenges to pragmatic clinical trials implementation and explore opportunities for research institutions and regulatory authorities to facilitate widespread adoption of this vital research tool.As a subsequent wave of COVID-19, and/or another epidemic, are all but inevitable in our lifetime, we must ensure that our research infrastructure is conducive to carrying out pragmatic clinical trials to expeditiously generate the needed evidence and blunt the epidemic's toll on human lives and livelihoods.

Learning health systems, embedded research, and data standards-recommendations for healthcare system leaders.

Learning health systems that conduct embedded research require infrastructure for the seamless adoption of clinical interventions; this infrastructure should integrate with electronic health record (EHR) systems and enable the use of existing data. As purchasers of EHR systems, and as critical partners, sponsors, and consumers of embedded research, healthcare organizations should advocate for EHR system functionality and data standards that will increase the capacity for embedded research in clinical settings. As stakeholders and proponents for EHR data standards, healthcare leaders should support standards development and promote local adoption to support quality healthcare, continuous improvement, innovative data-driven interventions, and the generation of new knowledge. "Standards-enabled" health systems will be positioned to address emergent and critical research questions, including those related to coronavirus disease 2019 (COVID-19) and future public health threats. The role of a data standards officer or champion could enable health systems to realize this goal.

Reflections on the IJHPR's article collection on dementia.

Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) constitute a worldwide public health crisis. In light of the AD/ADRD epidemic now existing within the global COVID-19 pandemic, the need for global action to improve dementia care is greater than ever. The article collection "Dementia- an Interdisciplinary Approach," in the Israeli Journal of Health Policy and Research (IJHPR) highlights the need for interprofessional approaches to improving outcomes for people living with dementia and their care partners, as well as the complexities of conducting dementia care research.

Certificates of confidentiality and unexpected complications for pragmatic clinical trials.

INTRODUCTION: The need to protect the confidentiality of research data has long been recognized. One means to help protect research data from use in civil or criminal matters in the United States is a Certificate of Confidentiality (CoC). Until recently, investigators applied for a CoC when conducting research that was sensitive, stigmatizing or where the disclosure of private information could possibly result in civil or criminal liability. However, effective October 1, 2017, CoCs are automatically issued for much research supported by the National Institutes of Health (NIH). While automatic issuance reduces administrative burden, it also poses some surprising unanticipated challenges for research in general and pragmatic clinical trials (PCTs) in particular, which are key elements of learning health systems. METHODS: We reviewed the new policy on CoCs to identify and analyze issues related to it that are potentially problematic for PCTs. RESULTS: We identified three relevant issues: (1) whether the EHR may be populated with research data that may be sensitive or stigmatizing without explicit consent from subjects; (2) incomplete protections for sensitive data in the EHR; and (3) requirements for notifying subjects about the CoC provisions. CONCLUSION: Formal guidance from the NIH is needed to address the application of CoCs to the setting of PCTs. In the meantime, it is essential for researchers designing and conducting PCTs, as well as health care systems in which this research is conducted, to be aware of the nuances inherent in CoCs so they can best adhere to their legal obligations regarding them. In the absence of guidance, special attention should be paid to pragmatic research that populates the electronic health record with research data as well as research conducted without explicit consent. Given the large amount of pragmatic research precipitated by the Coronavirus Disease 2019 pandemic, which has been accompanied by major efforts to share data, the need for such guidance is especially urgent.

Adapting to disruption of research during the COVID-19 pandemic while testing nonpharmacological approaches to pain management.

The COVID-19 pandemic has slowed research progress, with particularly disruptive effects on investigations of addressing urgent public health challenges, such as chronic pain. The National Institutes of Health (NIH) Department of Defense (DoD) Department of Veterans Affairs (VA) Pain Management Collaboratory (PMC) supports 11 large-scale, multisite, embedded pragmatic clinical trials (PCTs) in military and veteran health systems. The PMC rapidly developed and enacted a plan to address key issues in response to the COVID-19 pandemic. The PMC tracked and collaborated in developing plans for addressing COVID-19 impacts across multiple domains and characterized the impact of COVID-19 on PCT operations, including delays in recruitment and revisions of study protocols. A harmonized participant questionnaire will facilitate later meta-analyses and cross-study comparisons of the impact of COVID-19 across all 11 PCTs. The pandemic has affected intervention delivery, outcomes, regulatory and ethics issues, participant recruitment, and study design. The PMC took concrete steps to ensure scientific rigor while encouraging flexibility in the PCTs, while paying close attention to minimizing the burden on research participants, investigators, and clinical care teams. Sudden changes in the delivery of pain management interventions will probably alter treatment effects measured via PMC PCTs. Through the use of harmonized instruments and surveys, we are capturing these changes and plan to monitor the impact on research practices, as well as on health outcomes. Analyses of patient-reported measures over time will inform potential relationships between chronic pain, mental health, and various socioeconomic stressors common among Americans during the COVID-19 pandemic.