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Genomic medicine holds great promise for improving health care, but integrating searchable and actionable genetic data into electronic health records (EHRs) remains a challenge. Here we describe Neptune, a system for managing the interaction between a clinical laboratory and an EHR system during the clinical reporting process. We developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis, and EHR integration. Neptune has been applied for the generation and delivery of over 15,000 clinical genomic reports. This work spans two clinical tests based on targeted gene panels that contain 68 and 153 genes respectively. These projects demanded customizable clinical reports that contained a variety of genetic data types including single-nucleotide variants (SNVs), copy-number variants (CNVs), pharmacogenomics, and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. Methods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open source and available at https://gitlab.com/bcm-hgsc/neptune .

Engaging communities in research planning and implementation can enhance recruitment and retention (RR) of racial and ethnic groups historically excluded and underrepresented in clinical research; however, most studies do not use community-informed approaches. This paper describes the formative research process used to design a Community-Informed Recruitment Plan Template for racial and ethnic groups historically excluded and underrepresented in clinical research.Using an existing RR template as a starting point, we iteratively developed and refined the community-informed template through a 3-phase process to achieve cultural-appropriateness. Phase 1 included a literature review, 34 community engagement (CE) studios to review recommendations, community advisory board (CAB) review, and survey data from minority recruitment experts. Phase 2 involved integration of content into existing RR template. Phase 3 was a final review and revision using input of the CAB and researchers' panel. Survey data collected in Phase 1 were analyzed using descriptives (i.e., frequencies and percentages). Open-ended survey responses were analyzed using inductive, qualitative thematic analysis.The final 8-section template can help develop effective grant or proposal language where study RR plans are requested. They include: 1) Recruitment Strategy; 2) A Stakeholder Communication Plan; 3) Evidence of Recruitment Feasibility; 4) Recruitment and Retention Team; 5) Recruitment and Retention Methods; 6) Recruitment and Retention Timeline; 7) Evaluation; and 8) Budget.Incorporating multiple perspectives into this formative research process enhances the cultural appropriateness of this community-informed RR template to help research teams achieve RR goals for individuals historically excluded and underrepresented in clinical research.

The Recruitment Innovation Center (RIC) has created a toolkit of novel strategies to engage potential participants in response to recruitment and retention challenges associated with COVID-19 studies. The toolkit contains pragmatic, generalizable resources to help research teams increase awareness of clinical trials and opportunities to participate; produce culturally sensitive and engaging recruitment materials; improve consent and return of results processes; and enhance recruitment of individuals from populations disproportionately impacted by COVID-19. This resource, the “RIC COVID-19 Recruitment and Retention Toolkit,” is available free online. We describe the toolkit and the community feedback used to author and curate this resource.

Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Network piloted three novel mechanisms in the trial titled Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multi-site, randomized, double-blind, placebo-controlled trial in the pediatric intensive care setting.The three novel start-up mechanisms included: 1) competitive activation; 2) use of trial start-up experts, called site navigators; and 3) supplemental funds earned for achieving pre-determined milestones. After sites were activated, they received a web-based survey to report perceptions of the DOSE start-up process. In addition to perceptions, metrics analyzed included milestones met, time to start-up, and subsequent enrollment of subjects.Twenty sites were selected for participation, with 19 sites being fully activated. Across activated sites, the median (quartile 1, quartile 3) time from receipt of regulatory documents to site activation was 82 days (68, 113). Sites reported that of the three novel mechanisms, the most motivating factor for expeditious activation was additional funding available for achieving start-up milestones, followed by site navigator assistance and then competitive site activation.Study start-up is a critical time for the success of clinical trials, and innovative methods to minimize delays during start-up are needed. Milestone-based funds and site navigators were preferred mechanisms by sites participating in the DOSE study and may have contributed to the expeditious start-up timeline achieved.gov #: NCT03938857.

The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.

Background Financial incentives may aid recruitment to clinical trials, but evidence regarding risk/burden-driven variability in participant preferences for incentives is limited. We developed and tested a framework to support real-world decisions on recruitment budget. Methods We included two phases: an Anchoring Survey, to ensure we could capture perceived unpleasantness on a range of life events, and a Vignette Experiment, to explore relationships between financial incentives and participants' perceived risk/burden and willingness to participate in high- and low-risk/burden versions of five vignettes drawn from common research activities. We compared vignette ratings to identify similarly rated life events from the Anchoring Survey to contextualize ratings of study risk. Results In our Anchoring Survey (n = 643), mean ratings (scale 1 = lowest risk/burden to 5 = highest risk/burden) indicated that the questions made sense to participants, with highest risk assigned to losing house in a fire (4.72), and lowest risk assigned to having blood pressure taken (1.13). In the Vignette Experiment (n = 534), logistic regression indicated that amount of offered financial incentive and perceived risk/burden level were the top two drivers of willingness to participate in four of the five vignettes. Comparison of event ratings in the Anchoring Survey with the Vignette Experiment ratings suggested reasonable concordance on severity of risk/burden. Conclusions We demonstrated feasibility of a framework for assessing participant perceptions of risk for study activities and discerned directionality of relationship between financial incentives and willingness to participate. Future work will explore use of this framework as an evidence-gathering approach for gauging appropriate incentives in real-world study contexts.

OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.

Objective: In many hospitals, nurse-led "safety huddles" are used to relay patient safety information, although whether this effectively identifies patients at risk for harm has not been determined. New electronic risk assessment tools are designed to identify patients at risk for harm during hospitalization, based on specific markers in the electronic health record. This study sought to compare the results of both methods. The findings may help to enhance decision making at the level of care delivery.A nonexperimental correlational study was conducted over a three-week period in 2015 in a large metropolitan acute care community hospital. Nurses on three units-a medical-surgical unit, a progressive care unit, and an orthopedic unit-constituted the convenience sample. Designated safety huddle leaders collected data using the daily census sheet to record the nurses' perceived risk of harm for each patient and the reason for risk concern. Separately, designated advanced practice nurses collected the electronic risk assessment tool's reports from the same units. Data were paired as they were entered into the database and analyzed to determine correlation. Perceptions of harm from the nurses, recorded as yes or no responses, were compared with the electronic tool's identification of high risk or moderate-to-low risk.In 746 data pairs, differences between the nurses' harm risk perceptions and the electronic tool's harm risk reports were statistically significant, supporting our prediction that there would be no correlation. The most significant difference was seen in instances when a nurse identified a patient as being at higher risk than the electronic tool did, often citing behavioral or psychosocial issues as the reason for concern.Nurses perceived harm risk differently than the electronic tool did. In situations when the electronic tool cited risk and the nurse perceived no risk, the risks were currently being addressed in the plan of care. In situations when the nurse perceived higher risk than the electronic tool did, the nurse often cited behavioral or psychosocial issues (which frequently lacked defined data points in the electronic health record and thus were not available to the tool). Changes in data mining algorithms must incorporate and weight the impact of psychosocial and behavioral elements together with other risk factors in order to provide meaningful practice recommendations.

Background: Transitioning from hospital to home is a common failure point in care delivery and patient adherence to a plan of care. Our post-discharge phone calls helped identify gaps (especially related to medications) and assign accountability for addressing issues. Method: We reached more than 200 patients with Acute Coronary Syndrome and Congestive Heart Failure by phone 24-48 hours after discharge between 8/2011 - 1/2012. We tested two operating models: hospital nurse with knowledge of admission (n=200) vs. clinic nurse with ongoing responsibility for managing patient (n=10 and ongoing). Callers used a standardized script and documentation form with “teach-back” methodology. Outcomes (Figure): Medications issues (65%, 107 of 165) included errors in discharge meds lists that contributed to patient misunderstandings and lack of adherence. Most (63%, 89 of 142) patients left the hospital without a scheduled follow-up appointment (revealing systematic improvement need). Callers provided teaching and reinforcement and triaged issues, avoiding at least 3 - 4 probable readmissions. Comparing two delivery models (hospital vs. clinic nurse) yielded notable differences. For both groups, calls took ∼15+ minutes (min=6, max=48). However, prep time, documentation and follow-up were significantly longer for hospital nurses (35 mins) than clinic nurses (15 mins). The hospital nurse spent more time “mining” records to understand each patient story; clinic nurses could prioritize calls and personalize content based on prior relationships with patients. Issues were quickly handled by clinic nurses in face-to-face provider interactions, whereas the hospital nurse frequently became mired in lengthy back-and-forth clinical communication. Conclusion: Analysis of post-discharge phone calls shows that some patients (new diagnoses, complicated medications regimen) may particularly benefit; however, the call represented a valuable reinforcement opportunity for all patients we reached. Optimally efficient, effective calls require: 1) Reliable patient contact information; 2) Clear record of plan of care, including accurate medications list; 3) Follow-up appointments scheduled; 4) Caller expertise with diagnoses; and 5) Caller prior relationship with the patient. Going forward, our team will continue to test clinic-based post-discharge phone calls, evaluating several key metrics including ability of patients to successfully articulate their medications and follow-up plans, % of patients who attend their follow-up appointments, readmission rates, et al.

The story of mediators in sepsis syndrome is developing extremely rapidly and continues to unfold. This discussion has focused on those areas most studied and those that have the greatest clinical implications in the context of current knowledge. There are a number of mediators under active investigation that have not been reviewed here because their discussion is beyond the scope of this article. Just how all the pieces of the intricate cascade of events ultimately fit together is yet to be seen. However, the availability of important probes, such as cyclooxygenase inhibitors, TNF, anti-TNF, IL1, anti-IL1, anti-proteases, antioxidants, and antiendotoxin, is allowing major progress to be made in a short period of time. Transferring this knowledge to the bedside and everyday clinical practice is a slower process, but the prospects are bright for innovative new therapies for sepsis syndrome, septic shock, and the multiple organ failure associated with these clinical entities.