The 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. To 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. In 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. A 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.

Objectives: Residential proximity to pesticide-treated farmland is an important pesticide exposure pathway. Methods: In-person interviews and biological samples were collected from 100 farmworker and 100 non-farmworker adults and children living in Eastern Washington State. We examined the relationship of residential proximity to farmland to urinary metabolite concentrations of dimethylphosphate (DMTP) and levels of pesticide residues in house dust. Results: DMTP concentrations were higher in farmworkers than non-farmworkers (71 μg/L vs 6 μg/L) and in farmworker children than non-farmworker children (17 μg/L vs 8 μg/L). Compared to non-farmworker households, farmworker households had higher levels of azinphos-methyl (643 ng/g vs 121 ng/g) and phosmet (153 ng/g vs 50 ng/g). Overall, a 20% reduction in DMTP concentration was observed per mile increase in distance from farmland. Conclusions: Lower OP metabolite concentrations correlated with increasing distance from farmland.

Interventions to improve fecal testing for colorectal cancer (CRC) exist, but are not yet routine practice. We conducted this systematic review to determine how implementation strategies and contextual factors influenced the uptake of interventions to increase Fecal Immunochemical Tests (FIT) and Fecal Occult Blood Testing (FOBT) for CRC in rural and low-income populations in the United States. We searched Medline and the Cochrane Library from January 1998 through July 2016, and Scopus and clinicaltrials.gov through March 2015, for original articles of interventions to increase fecal testing for CRC. Two reviewers independently screened abstracts, reviewed full-text articles, extracted data and performed quality assessments. A qualitative synthesis described the relationship between changes in fecal testing rates for CRC, intervention components, implementation strategies, and contextual factors. A technical expert panel of primary care professionals, health system leaders, and academicians guided this work. Of 4218 citations initially identified, 27 unique studies reported in 29 publications met inclusion criteria. Studies were conducted in primary care (n = 20, 74.1%), community (n = 5, 18.5%), or both (n = 2, 7.4%) settings. All studies (n = 27, 100.0%) described multicomponent interventions. In clinic based studies, components that occurred most frequently among the highly effective/effective study arms were provision of kits by direct mail, use of a pre-addressed stamped envelope, client reminders, and provider ordered in-clinic distribution. Interventions were delivered by clinic staff/community members (n = 10, 37.0%), research staff (n = 6, 22.2%), both (n = 10, 37.0%), or it was unclear (n = 1, 3.7%). Over half of the studies lacked information on training or monitoring intervention fidelity (n = 15, 55.6%). Studies to improve FIT/FOBT in rural and low-income populations utilized multicomponent interventions. The provision of kits through the mail, use of pre-addressed stamped envelopes, client reminders and in-clinic distribution appeared most frequently in the highly effective/effective clinic-based study arms. Few studies described contextual factors or implementation strategies. More robust application of guidelines to support reporting on methods to select, adapt and implement interventions can help end users determine not just which interventions work to improve CRC screening, but which interventions would work best in their setting given specific patient populations, clinical settings, and community characteristics. In accordance with PRISMA guidelines, our systematic review protocol was registered with PROSPERO, the international prospective register of systematic reviews, on April 16, 2015 (registration number CRD42015019557 ).

The Plan-Do-Study-Act (PDSA) cycle is a commonly used improvement process in health care settings, although its documented use in pragmatic clinical research is rare. A recent pragmatic clinical research study, called the Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), used this process to optimize the research implementation of an automated colon cancer screening outreach program in intervention clinics. We describe the process of using this PDSA approach, the selection of PDSA topics by clinic leaders, and project leaders’ reactions to using PDSA in pragmatic research. STOP CRC is a cluster-randomized pragmatic study that aims to test the effectiveness of a direct-mail fecal immunochemical testing (FIT) program involving eight Federally Qualified Health Centers in Oregon and California. We and a practice improvement specialist trained in the PDSA process delivered structured presentations to leaders of these centers; the presentations addressed how to apply the PDSA process to improve implementation of a mailed outreach program offering colorectal cancer screening through FIT tests. Center leaders submitted PDSA plans and delivered reports via webinar at quarterly meetings of the project’s advisory board. Project staff conducted one-on-one, 45-min interviews with project leads from each health center to assess the reaction to and value of the PDSA process in supporting the implementation of STOP CRC. Clinic-selected PDSA activities included refining the intervention staffing model, improving outreach materials, and changing workflow steps. Common benefits of using PDSA cycles in pragmatic research were that it provided a structure for staff to focus on improving the program and it allowed staff to test the change they wanted to see. A commonly reported challenge was measuring the success of the PDSA process with the available electronic medical record tools. Understanding how the PDSA process can be applied to pragmatic trials and the reaction of clinic staff to their use may help clinics integrate evidence-based interventions into their everyday care processes. Clinicaltrials.gov NCT01742065 . Registered October 31, 2013.

Background The Community Preventive Services Task Force recommends multi-component interventions, including patient reminders, to improve uptake of colorectal cancer screening. Objective We sought to compare the effectiveness of different forms of reminders for a direct-mail fecal immunochemical test (FIT) program. Design Patient-randomized controlled trial. Participants 2772 adults aged 50–75, not up to date with colorectal cancer screening recommendations, with a clinic visit in the previous year at any of four participating health center clinics. Intervention Participants were mailed an introductory letter and FIT. Those who did not complete their FIT within 3 weeks were randomized to receive (1) a reminder letter, (2) two automated phone calls, (3) two text messages, (4) a live phone call, (5) a reminder letter and a live phone call, (6) two automated phone calls and a live phone call, or (7) two text messages and a live phone call. Patients with a patient portal account were sent two email reminders, but were not randomized. Main Measures FIT return rates for each group, 6 months following randomization. Key Results A total of 255 (10%) participants returned their FIT within 3 weeks of the mailing. Among randomized participants (n = 2010), an additional 25.5% returned their FITs after reminders were delivered (estimated overall return rate = 32.7%). In intention-to-treat analysis, compared to the group allocated to receive a reminder letter, return rates were higher for the group assigned to receive the live phone call (OR = 1.51 [1.03–2.21]) and lower for the group assigned to receive text messages (OR = 0.66 [0.43–0.99]). Reminder effectiveness differed by language preference. Conclusions Our data suggest that FIT reminders that included a live call were more effective than reminders that relied solely on written communication (a text message or letter). Trial Registration: ClinicalTrials.gov/ctc2/show/NCT01742065.