Implementing universal Lynch syndrome screening (IMPULSS): protocol for a multi-site study to identify strategies to implement, adapt, and sustain genomic medicine programs in different organizational contexts

BACKGROUND: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS screening program implementation and improvement. This toolkit will promote effective implementation of LS screening in various complex health systems. METHODS: This study includes eight healthcare systems with 22 clinical sites at varied stages of implementing LS screening programs. Guided by the Consolidated Framework for Implementation Research (CFIR), we will conduct in-depth semi-structured interviews with patients and organizational stakeholders and perform economic evaluation of site-specific implementation costs. These processes will result in a comprehensive cross-case analysis of different organizational contexts. We will utilize qualitative data analysis and configurational comparative methodology to identify facilitators and barriers at the organizational level that are minimally sufficient and necessary for optimal LS screening implementation. DISCUSSION: The overarching goal of this project is to combine our data with theories and tools from implementation science to create an organizational toolkit to facilitate implementation of LS screening in various real-world settings. Our organizational toolkit will account for issues of complex coordination of care involving multiple stakeholders to enhance implementation, sustainability, and ongoing improvement of evidence-based LS screening programs. Successful implementation of such programs will ultimately reduce suffering of patients and their family members from preventable cancers, decrease waste in healthcare system costs, and inform strategies to facilitate the promise of precision medicine. TRIAL REGISTRATION: N/A

Evaluation of a multidisciplinary lipid clinic to improve the care of individuals with severe lipid conditions: A RE-AIM framework analysis

BACKGROUND: Individuals with complex dyslipidemia, or those with medication intolerance, are often difficult to manage in primary care. They require the additional attention, expertise, and adherence counseling that occurs in multidisciplinary lipid clinics (MDLCs). We conducted a program evaluation of the first year of a newly implemented MDLC utilizing the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to provide empirical data not only on program effectiveness, but also on components important to local sustainability and future generalizability. METHODS: The purpose of the MDLC is to increase the uptake of guideline-based care for lipid conditions. Established in 2019, the MDLC provides care via a centralized clinic location within the healthcare system. Primary care providers and cardiologists were invited to refer individuals with lipid conditions. Using a pre/post-study design, we evaluated the implementation outcomes from the MDLC using the RE-AIM framework. RESULTS: In 2019, 420 referrals were made to the MDLC (reach). Referrals were made by 19% (148) of the 796 active cardiology and primary care providers, with an average of 35 patient referrals per month in 2019 (SD 12) (adoption). The MDLC saw 83 patients in 2019 (reach). Additionally, 50% (41/82) had at least one follow-up MDLC visit, and 12% (10/82) had two or more follow-up visits in 2019 (implementation). In patients seen by the MDLC, we found an improved diagnosis of specific lipid conditions (FH (familial hypercholesterolemia), hypertriglyceridemia, and dyslipidemia), increased prescribing of evidence-based therapies, high rates of medication prior authorization approvals, and significant reductions in lipid levels by lipid condition subgroup (effectiveness). Over time, the operations team decided to transition from in-person follow-up to telehealth appointments to increase capacity and sustain the clinic (maintenance). CONCLUSIONS: Despite limited reach and adoption of the MDLC, we found a large intervention effect that included improved diagnosis, increased prescribing of guideline-recommended treatments, and clinically significant reduction of lipid levels. Attention to factors including solutions to decrease the large burden of unseen referrals, discussion of the appropriate number and duration of visits, and sustainability of the clinic model could aid in enhancing the success of the MDLC and improving outcomes for more patients throughout the system

Implementation strategies to improve statin utilization in individuals with hypercholesterolemia: A systematic review and meta-analysis

BACKGROUND: Numerous implementation strategies to improve utilization of statins in patients with hypercholesterolemia have been utilized, with varying degrees of success. The aim of this systematic review is to determine the state of evidence of implementation strategies on the uptake of statins. METHODS AND RESULTS: This systematic review identified and categorized implementation strategies, according to the Expert Recommendations for Implementing Change (ERIC) compilation, used in studies to improve statin use. We searched Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from inception to October 2018. All included studies were reported in English and had at least one strategy to promote statin uptake that could be categorized using the ERIC compilation. Data extraction was completed independently, in duplicate, and disagreements were resolved by consensus. We extracted LDL-C (concentration and target achievement), statin prescribing, and statin adherence (percentage and target achievement). A total of 258 strategies were used across 86 trials. The median number of strategies used was 3 (SD 2.2, range 1-13). Implementation strategy descriptions often did not include key defining characteristics: temporality was reported in 59%, dose in 52%, affected outcome in 9%, and justification in 6%. Thirty-one trials reported at least 1 of the 3 outcomes of interest: significantly reduced LDL-C (standardized mean difference [SMD] - 0.17, 95% CI - 0.27 to - 0.07, p = 0.0006; odds ratio [OR] 1.33, 95% CI 1.13 to 1.58, p = 0.0008), increased rates of statin prescribing (OR 2.21, 95% CI 1.60 to 3.06, p \u3c 0.0001), and improved statin adherence (SMD 0.13, 95% CI 0.06 to 0.19; p = 0.0002; OR 1.30, 95% CI 1.04 to 1.63, p = 0.023). The number of implementation strategies used per study positively influenced the efficacy outcomes. CONCLUSION: Although studies demonstrated improved statin prescribing, statin adherence, and reduced LDL-C, no single strategy or group of strategies consistently improved outcomes. TRIAL REGISTRATION: PROSPERO CRD42018114952

Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging

C-B3-04: Media Analysis of Genetic Testing Information for Common Disease Presented to the Public

Background/Aims: With the advent of personalized medicine, consumers are routinely exposed to information and direct- to- consumer (DTC) advertising of various genetic tests. Specifically, 2007–2008 saw a return of the DTC advertisement for BRACAnalysis® in the eastern US, and the advent of three new companies offering DTC genetic screening for under $1000. This abstract presents the results of a media analysis for information presented to the general public on genetic testing for common diseases, such as cancer or heart disease, or for full genome scans for disease risk in general

PS1-09: Public Opinion of Family History and Genetic Testing for Common Diseases: Results from Focus Groups with Kaiser Permanente Colorado Members

Background and Aims: With the advent of personalized medicine, consumers are routinely exposed to information about new gene discoveries, family history, and direct-to-consumer (DTC) advertising of genetic tests. Since 2008, the BRACAnalsysis® test for breast cancer risk has been steadily advertised directly to consumers in different markets across the US, and at least 3 companies now offer DTC genetic screening for $300 –$1000, with more companies entering this burgeoning market. The specific aims of this project are to

Alternate service delivery models in cancer genetic counseling: a mini-review

Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state of science regarding service delivery models such as telephone counseling, telegenetics and group counseling. Research on comparative effectiveness of these models in traditional individual, in-person genetic counseling has been promising for improving access to care in a manner acceptable to patients. Yet, it has not fully evaluated the short- and long-term patient- and system-level outcomes that will help answer the question of whether these models achieve the same beneficial psychosocial and behavioral outcomes as traditional cancer genetic counseling. We propose a research agenda focused on comparative effectiveness of available service delivery models and how to match models to patients and practice settings. Only through this rigorous research can clinicians and systems find the optimal balance of clinical quality, ready and secure access to care, and financial sustainability. Such research will be integral to achieving the promise of genomic medicine in oncology

Formalizing and Optimizing Patient Engagement in a Large Health Care System

Background/Aims: Patient engagement and patient-centeredness have become catchphrases used as core principles in reference to the Affordable Care Act, the Learning Healthcare System workshop, value-driven care and the Patient-Centered Outcomes Research Institute. Patient engagement is not a new concept; in 2001, the Institute of Medicine defined patient- and family-centered care as care based on continuous healing relationships, customized according to patient needs and values, patient control, information equipoise, transparency and anticipation of patient needs. Increased attention is also being paid to include patient-defined outcomes, demonstrated shared decision-making and patient assessed value in their care as benchmarks for reimbursement. Methods: At Geisinger Health System, we have developed a framework to guide patient engagement across the continuum of care and in research and discovery to meet the strategic aim of enhancing the experience and quality of care for patients and their families. We have launched several initiatives and working groups to improve engagement of patients, families and clinical stakeholders to continue evolving as a learning health care system. Initiatives include assessment of existing expertise to assist in engagement across the research continuum, multiple advisory boards and development of purposeful community engagement activities. Workgroups developed include project-specific patient advisory committees, a patient engagement workgroup comprised of stakeholders across research and health care operations, and workgroups to design specific engagement tasks such as symposia and knowledge assessments regarding the learning health care system environment. Results: We will present the overarching framework and strategies developed by the patient engagement workgroup and share materials and strategies employed to encourage meaningful patient engagement in study design, measures, analysis and conclusions. Strategies include pre-engagement activities, identifying patient research partners, supporting patient partners and defining the role of patient partners in dissemination and implementation. Conclusion: Effective patient and family engagement in research depends on adequate technical, programmatic and human resources that collectively constitute an integral infrastructure

Returning Results in the Genomic Era: Initial Experiences of the eMERGE Network

A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE sites developed plans for three essential elements of the RoR process: Disclosure to the participant, notification of the health care provider, and integration of results into the electronic health record (EHR). Procedures and protocols around these three elements were adapted as appropriate to individual site requirements and limitations. Detailed information about the RoR procedures at each site was obtained through structured telephone interviews and follow-up surveys with the clinical investigator leading or participating in the RoR process at each eMERGE3 institution. Because RoR processes at each of the 10 sites allowed for taking into account differences in population, disease focus and institutional requirements, significant heterogeneity of process was identified, including variability in the order in which patients and clinicians were notified and results were placed in the EHR. This heterogeneity in the process flow for eMERGE3 RoR reflects the “real world” of genomic medicine in which RoR procedures must be shaped by the needs of the patients and institutional environments

The Geisinger MyCode® Community Health Initiative: Experiences in Patient Recruitment, Genomic Sequencing, and Patient Engagement in a Population-Based Biobank

Background/Aims: Geisinger’s MyCode® Community Health Initiative is a population-based biorepository that began in 2007. Participants give broad consent for research use of their samples and electronic health record data, including genomic analysis, and permission to re-contact for additional studies. Participation in MyCode is open to all Geisinger patients, with a goal to enroll 250,000 participants. In 2013, consent was revised to allow for return of medically actionable information discovered through genomic studies to patients and providers and to include the information in the electronic health record. In 2014, a collaboration was initiated with the Regeneron Genetics Center to perform whole exome sequencing on biobank samples. The Governing Board approves all research conducted on biobank specimens, the Return of Results Oversight Committee monitors the return of clinical findings, and the External Ethics Advisory Committee provides independent feedback on MyCode operations and the clinical return of results process. Community members are engaged through research focus groups, newsletters and as members of the two committees. Methods: MyCode is visible via signage throughout Geisinger clinics and system website. Approximately 20 MyCode consenters are stationed in outpatient clinics throughout the system. Samples are collected at the time of clinical blood draws. Consented participants who have not had clinical bloodwork may arrange to provide a MyCode sample if desired. Saliva collection may also be requested. In May 2015, an educational campaign was launched to ensure that all Geisinger employees can answer patient questions about biobank participation. Results: At this time, approximately 1,000 patients consent per week, 90,000 patients have consented (85% response rate), 55,000 have at least one sample in the biobank, and 50,000 exomes have been sequenced thus far. The population of consented patients is 97% white, 62% female and 50% aged 50–79 years. Conclusion: Whole exome sequence information combined with patient medical record data is allowing Geisinger researchers and research partners to investigate new approaches to prevention, diagnosis and treatment of disease. Strong community engagement programs maintain trust in the system, keep participants engaged in research and continue to guide the evolution of the MyCode program