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In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems. The Collaboratory has a unique opportunity to draw on the Demonstration Project experiences to generate lessons learned related to ePCTs and the dissemination and implementation of interventions tested in ePCTs. In this article, we use case studies from six completed Demonstration Projects to summarize the Collaboratory's experience with post-trial interpretation of results, and implications for sustainment (or de-implementation) of tested interventions. We highlight three key lessons learned. First, ineffective interventions (i.e., ePCT is null for the primary outcome) may be sustained if they have other measured benefits (e.g., secondary outcome or subgroup) or even perceived benefits (e.g., staff like the intervention). Second, effective interventions-even those solicited by the health system and/or designed with significant health system partner buy-in-may not be sustained if they require significant resources. Third, alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions. Our experiences point to several recommendations to aid in considering post-trial sustainment or de-implementation of interventions tested in ePCTs: (1) include secondary outcome measures that are salient to health system partners; (2) collect all appropriate data to allow for post hoc analysis of subgroups; (3) collect experience data from clinicians and staff; (4) engage policy-makers before starting the trial.

Embedded pragmatic clinical trials (ePCTs) and quality improvement (QI) activities often occur simultaneously within healthcare systems (HCSs). Embedded PCTs within HCSs are conducted to test interventions and provide evidence that may impact public health, health system operations, and quality of care. They are larger and more broadly generalizable than QI initiatives, and may generate what is considered high-quality evidence for potential use in care and clinical practice guidelines. QI initiatives often co-occur with ePCTs and address the same high-impact health questions, and this co-occurrence may dilute or confound the ability to detect change as a result of the ePCT intervention. During the design, pilot, and conduct phases of the large-scale NIH Collaboratory Demonstration ePCTs, many QI initiatives occurred at the same time within the HCSs. Although the challenges varied across the projects, some common, generalizable strategies and solutions emerged, and we share these as case studies. KEY LESSONS: Study teams often need to monitor, adapt, and respond to QI during design and the course of the trial. Routine collaboration between ePCT researchers and health systems stakeholders throughout the trial can help ensure research and QI are optimally aligned to support high-quality patient-centered care.

While conducting a set of large-scale multi-site pragmatic clinical trials involving high-impact public health issues such as end-stage renal disease, opioid use, and colorectal cancer, there were substantial changes to both policies and guidelines relevant to the trials. These external changes gave rise to unexpected challenges for the trials, including decisions regarding how to respond to new clinical practice guidelines, increased difficulty in implementing trial interventions, achieving separation between treatment groups, and differential responses across sites. In this article, we describe these challenges and the approaches used to address them. When deliberating appropriate action in the face of external changes during a pragmatic clinical trial, we recommend considering the well-being of the participants, clinical equipoise, and the strength and quality of the evidence associated with the change; involving those charged with data and safety monitoring; and where possible, planning for potential external changes as the trial is being designed. Any solution must balance the primary obligation to protect the well-being of participants with the secondary obligation to protect the integrity of the trial in order to gain meaningful answers to important public health questions.

BackgroundLong-term adherence to colorectal cancer (CRC) screening is particularly important for fecal testing. Some U.S. studies report that only 25% of individuals repeat fecal testing annually. The purpose of this qualitative study was to identify barriers and facilitators reported by patients with suboptimal screening adherence to refine interventions for starting ongoing adherence to CRC screening. We also explored whether participants, particularly never screeners, would be willing to do a CRC screening blood test.MethodsForty-one patients who previously enrolled in the Systems of Support to Increase CRC Screening (SOS) trial were interviewed 4-5 years later. Participants were purposively selected to include men and women with diverse race/ethnicities who had either been inconsistent screeners or had never screened during the first three years of SOS despite receiving at least two rounds of mailed fecal tests. Two interviewers conducted 30-min telephone interviews using a semi-structured interview guide. An iterative thematic analysis approach was used.ResultsThemes related to screening barriers were more pervasive among never screeners including: (1) Avoidance (inattention, procrastination) (2) Concerns about handling stool; (3) Health concerns; (4) Fear of a cancer diagnosis or positive test results. Themes related to screening facilitators were more often mentioned by participants who screened at least once including: (1) Use of a simpler 1-sample fecal test; (2) Convenience of mailings and doing the test at home; (3) Salience of prevention, especially as one got older; and (4) Influence of recommendations from providers, family and friends. Participants had diverse preferences for the number (3 on average) and types (phone, mail, text) of screening reminders. Some participants did not prefer e-mail links to the patient shared electronic health record because of difficulties remembering their password. It was acceptable for a nurse or medical assistant not from their clinic to call them as long as that person was knowledgeable about their records and could communicate with their physician. Participants, especially never screeners, were generally very enthusiastic about the potential option of a CRC screening blood test.ConclusionFuture CRC screening programs should be designed to minimize these barriers and maximize facilitators to improve long-term screening adherence.Trial registrationPrimary Funding Agency: The National Cancer Institute of the National Institutes of Health (R01CA121125). Registered at clinicaltrials.gov NCT00697047 .

BackgroundThe clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped.MethodsTo strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design.ResultsIn this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs.ConclusionA planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.

ObjectiveThe patient-centered medical home (PCMH) includes comprehensive chronic illness and preventive services, including identifying patients who are overdue for colorectal cancer screening (CRCS). The association between PCMH implementation and CRCS during the Systems of Support to Increase Colorectal Cancer Screening Trial (SOS) is described.MethodsThe SOS enrolled 4664 patients from 21 clinics from August 2008 to November 2009. Patients were randomized to usual care, mailed fecal kits, kits plus brief assistance, or kits plus assistance and navigation. A PCMH model that included a workflow for facilitating CRCS was implemented at all study clinics in late 2009. Patients enrolled early had little exposure to the PCMH, whereas patients enrolled later were exposed during most of their first year in the trial. Logistic regression models were used to assess the association between PCMH exposure and CRCS.ResultsUsual care patients with ≥8 months in the PCMH had higher CRCS rates than those with ≤4 months in the PCMH (adjusted difference, 10.1%; 95% confidence interval, 5.7-14.6). SOS interventions led to significant increases in CRCS, but the magnitude of effect was attenuated by exposure to the PCMH (P for interaction = .01).ConclusionExposure to a PCMH was associated with higher CRCS rates. Automated mailed and centrally delivered stepped interventions increased CRCS rates, even in the presence of a PCMH.

BackgroundThe US Preventive Services Taskforce (USPSTF) recommends routine lipid screening beginning age 35 for men [1]. For women age 20 and older, as well as men age 20-34, screening is recommended if cardiovascular risk factors are present. Prior research has focused on underutilization but not overuse of lipid testing. The objective is to document over- and under-use of lipid testing in an insured population of persons at low, moderate and high cardiovascular disease (CVD) risk for persons not already on statins.MethodsThe study is a retrospective cohort study that included all adults without prior CVD who were continuously enrolled in a large integrated healthcare system from 2005 to 2010. Measures included lipid test frequency extracted from administrative data and Framingham cardiovascular risk equations applied using electronic medical record data. Five year lipid testing patterns were examined by age, sex and CVD risk. Generalized linear models were used to estimate the relative risk for over testing associated with patient characteristics.ResultsAmong males and females for whom testing is not recommended, 35.8 % and 61.5 % received at least one lipid test in the prior 5 years and 8.4 % and 24.4 % had two or more. Over-testing was associated with age, race, comorbidity, primary care use and neighborhood income. Among individuals at moderate and high-risk (not already treated with statins) and for whom screening is recommended, between 21.4 % and 25.1 % of individuals received no screening in the prior 5 years.ConclusionsBased on USPSTF lipid screening recommendations, this study documents substantial over-testing among individuals with low CVD risk and under-testing among individuals with moderate to high-risk not already on statins. Opportunity exists to better focus lipid screening efforts appropriate to CVD risk.

Background: Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling. Methods: Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019. We determined prevalence of unsatisfactory FIT and categorized reasons hierarchically. We used multivariable logistic regression models to identify factors associated with: (i) unsatisfactory FIT; and (ii) subsequent testing within 15 months of the unsatisfactory FIT. Results: Of 56,980 individuals completing an index FIT, 10.2% had an unsatisfactory FIT. Reasons included inadequate specimen (51%), incomplete labeling (27%), old specimen (13%), and broken/leaking container (8%). Unsatisfactory FIT was associated with being male [OR, 1.10; confidence interval (CI), 1.03-1.16], Black (OR, 1.46; CI, 1.33-1.61), Spanish speaking (OR, 1.12; CI, 1.01-1.24), on Medicaid (OR, 1.42; CI, 1.28-1.58), and received FIT by mail (OR, 2.66; CI, 2.35-3.01). Among those with an unsatisfactory FIT, fewer than half (41%) completed a subsequent test within 15 months (median, 4.4 months). Adults aged 50-54 years (OR, 1.16; CI, 1.01-1.39) and those who received FIT by mail (OR, 1.92; CI, 1.49-2.09) were more likely to complete a subsequent test. Conclusions: One in ten returned a FIT that could not be processed, mostly due to patient-related reasons. Fewer than half completed a subsequent test after unsatisfactory FIT. [ABSTRACT FROM AUTHOR]