Design and Implementation of a Randomized Controlled Trial of Genomic Counseling for Patients with Chronic Disease

Abstract

We describe the development and implementation of a randomized controlled trial to investigate the impact of genomic counseling on a cohort of patients with heart failure (HF) or hypertension (HTN), managed at a large academic medical center, the Ohio State University Wexner Medical Center (OSUWMC). Our study is built upon the existing Coriell Personalized Medicine Collaborative (CPMC®). OSUWMC patient participants with chronic disease (CD) receive eight actionable complex disease and one pharmacogenomic test report through the CPMC® web portal. Participants are randomized to either the in-person post-test genomic counseling—active arm, versus web-based only return of results—control arm. Study-specific surveys measure: (1) change in risk perception; (2) knowledge retention; (3) perceived personal control; (4) health behavior change; and, for the active arm (5), overall satisfaction with genomic counseling. This ongoing partnership has spurred creation of both infrastructure and procedures necessary for the implementation of genomics and genomic counseling in clinical care and clinical research. This included creation of a comprehensive informed consent document and processes for prospective return of actionable results for multiple complex diseases and pharmacogenomics (PGx) through a web portal, and integration of genomic data files and clinical decision support into an EPIC-based electronic medical record. We present this partnership, the infrastructure, genomic counseling approach, and the challenges that arose in the design and conduct of this ongoing trial to inform subsequent collaborative efforts and best genomic counseling practices.

Integrating clinical decision support systems for pharmacogenomic testing into clinical routine - a scoping review of designs of user-system interactions in recent system development

“…Pharmacogenomic information is usually gathered within the environment of a particular clinic or health care provider. Via patient letters [18, 31, 39, 42] and online portals [25], which contain the pharmacogenomic test results, this information can be transferred to other health care providers. For instance, patients can be advised to discuss their pharmacogenomic test results with physicians whenever a medication is prescribed which is affected by these pharmacogenomic results [42].…”

Outcomes of a Randomized Controlled Trial of Genomic Counseling for Patients Receiving Personalized and Actionable Complex Disease Reports

“…Participants were stratified by diagnosis (hypertension or heart failure) and enrolling physician ( n =20). All 199 individuals were block randomized to either the intervention arm (98 participants) or control arm (101 participants), with each arm receiving eight CPMC personalized disease reports [age related macular degeneration (AMD), coronary artery disease (CAD), type 1 diabetes (DM1), type 2 diabetes (DM2), hemochromatosis (HH), melanoma (MEL), prostate cancer (PRO), systemic lupus erythematosus (LUP)] (Sweet et al, 2014). These eight conditions were chosen given the relative high frequency of the genetic variant used to assess risk, varied effect size of each genetic variant on risk (RR 0.08 – >6.0), and because each condition is potentially actionable via lifestyle modification and/or medical intervention.…”

“…The genomic counseling session, which was scheduled for one hour but sometimes extended to 1.5 hours, included a review of results for all eight test reports, assessment of medical history, and, in accordance with the recommendations of the National Society of Genetic Counselors Task Force, construction of at least a 3-generation pedigree in order to provide a context in which the counselee could understand the test report risk information and risk assessment (National Society of Genetic Counselors’ Definition Task et al, 2006; Smerecnik et al, 2009). Given that participants have the potential for multiple “increased” risk variables (genetic variant, family history and health behaviors; Table SI), “decreased” risk variant(s) for DM1, and differing ranges of relative risk for each disease (0.08 – >6.0), we developed a tabular visual display for use in the genomic counseling intervention which synthesized each of the risk factors into a one-page document to provide an overall quick reference summary (Sweet et al, 2014). All individual increased risk variables were highlighted, and risk was also compared to the general population risk for each disease.…”

“…Baseline and follow-up measures included new items developed from a review of the literature, after review with the respective study authors, and modified items from existing CPMC surveys (Jenkins et al, 2007; Keller M, 2010; Sweet et al, 2014). Table I provides a list of questions for each of the survey measures discussed below.…”

“…Individuals with a chronic disease may also vary in their understanding and response to multiple actionable genomic risk reports, and may treat risk information related to their diagnosis differently than risk information for other diseases. The Ohio State University-Coriell Personalized Medicine Collaborative (OSU-CPMC) was designed as a randomized cohort study to measure the effects of in-person post-test genomic counseling on patients with chronic disease (heart failure; hypertension) receiving multiple personalized and potentially actionable complex disease reports through a web-based portal (Sweet et al, 2014). The primary aims of the randomized trial were to explore the following hypotheses: 1) Is genomic counseling associated with changes in causal attribution of disease risk and personal awareness of disease risk among participants with chronic disease following receipt of multiple genomic results online?…”