FOREST Trial: Revolutionary Electronic Tool Transforms Hereditary Cancer Risk Assessment

Is FOREST Revolutionizing Hereditary Cancer Risk Assessment?

The Family History and Cancer Risk Study (FOREST) has launched a pragmatic clinical trial to evaluate a novel approach for systematic hereditary cancer risk assessment in diverse clinical settings. The study, registered as NCT05079334, deploys MeTree, a patient-facing electronic family health history (FHH) tool integrated with electronic health records (EHRs) via SMART on FHIR standards, aiming to improve identification of individuals eligible for genetic counseling services.

Hereditary cancer syndromes affect approximately 1-2 in 200 people and confer high lifetime risks for multiple cancer types that often develop earlier and demonstrate more aggressive behaviors. Despite guideline recommendations to assess family health history in primary care, many clinicians struggle to implement these frequently revised guidelines amid increasing time constraints and limited genetics knowledge. This systematic care gap disproportionately impacts medically marginalized populations. The FOREST study addresses these barriers by leveraging patient portal recruitment, validated electronic FHH collection, and clinician-targeted clinical decision support to provide guideline-concordant recommendations for at-risk patients. The study operates at two distinctly different health systems: Vanderbilt University Medical Center (VUMC), a comprehensive academic healthcare facility, and Meharry Medical College (MMC), one of the nation's oldest historically Black academic health science institutions serving predominantly underserved populations. This diversity in recruitment settings allows researchers to evaluate implementation feasibility across varied healthcare environments with different resource levels and patient demographics. The study employs the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework to guide implementation strategies and ensure external validity and sustainability in real-world settings.

What Innovative Strategies Identify Hereditary Cancer Risks?

The study methodology follows a systematic recruitment approach tailored to each site. At VUMC, recruitment leverages the My Health at Vanderbilt (MHAV) patient portal to identify and message adult patients with recent visits and active portal accounts. At MMC, a hybrid approach combines in-clinic recruitment by research coordinators with patient portal-based messaging. Following electronic consent and baseline survey completion, participants enter their family health history into MeTree, which generates a personalized risk assessment report. The platform evaluates risk for 143 conditions, including 20 hereditary cancer syndromes, and provides clinical decision support for both patients and providers. For participants identified as at-risk for hereditary cancer syndromes, genetic counseling referrals are facilitated. Post-completion surveys assess participant experience, health behaviors, and information sharing with providers and family members. The study's primary outcome evaluates whether MeTree improves identification of at-risk individuals compared to usual care, with secondary outcomes exploring impact on genetic counseling efficiency and downstream care utilization.

The FOREST study represents the first large-scale evaluation of a SMART on FHIR-based FHH application that allows vendor-agnostic integration with patient portals and EHRs. Dr. Alanna Rahm, lead investigator at the Genomic Medicine Institute at Geisinger, who is not involved in the study, noted in a recent publication that "systematic family history collection tools that integrate with EHRs represent a critical advancement in precision medicine implementation." This approach addresses multiple structural barriers in the traditional genetics services delivery model, which is labor-intensive and strains the overburdened primary care and genetic counseling workforce. By automating and systematizing patient identification and risk assessment, MeTree reduces the time burden on clinicians while providing guideline-concordant recommendations directly in the EHR. The study also examines whether pre-populated family history data streamlines genetic counseling appointments, potentially addressing workforce shortages in genetic services. The investigators hypothesize at least a 5-minute reduction in pre-test counseling appointments due to the extensive family history gathering and pedigree generation by MeTree.

Key Innovation: The FOREST study (NCT05079334) deploys MeTree, a patient-facing electronic family health history tool that integrates with electronic health records via SMART on FHIR standards. This vendor-agnostic approach evaluates risk for 143 conditions including 20 hereditary cancer syndromes, automatically generating personalized risk assessments and clinical decision support. Unlike proprietary tools, MeTree's interoperable design aligns with 21st Century Cures Act requirements and can work across diverse EHR systems, potentially revolutionizing how healthcare systems identify patients eligible for genetic counseling services while reducing clinician burden.

How Are Regulatory Changes Influencing Risk Assessment Tools?

Unlike proprietary genetic risk assessment tools marketed by companies such as Myriad Genetics and Invitae, MeTree's SMART on FHIR integration offers vendor-agnostic compatibility with diverse EHR systems. This approach aligns with recent regulatory requirements in the 21st Century Cures Act and the Federal Interoperability and Patient Access Final Rule, which mandated SMART on FHIR support for all certified health IT by the end of 2022. The study's findings could influence how healthcare systems approach genetic risk assessment integration, potentially accelerating adoption of similar interoperable solutions. For healthcare systems considering implementation of family history tools, FOREST provides a valuable model for evaluating both technological and workflow considerations across diverse clinical environments. The study's dual-site implementation strategy offers particular insights for health systems serving medically marginalized populations, where alternative approaches may be necessary when technical infrastructure is limited.

What Are the Prospects for Advancing Genomic Medicine?

The FOREST team plans to analyze study outcomes through 2023, with potential for expanded implementation if results demonstrate improved risk identification and clinical efficiency. Future directions may include adaptation for additional hereditary conditions beyond cancer syndromes and integration with emerging genomic screening approaches. The study represents an important step toward more equitable, scalable genomic medicine implementation that could significantly impact how hereditary cancer risk assessment is conducted in diverse healthcare settings.

The study team anticipates that the sample size of 500 participants completing MeTree will provide 80% power to detect significant differences between MeTree and EHR-based risk identification. This power calculation assumes that 10% of participants will be identified as at-risk by MeTree but not by EHR review, while 5% might be identified by EHR but not by MeTree. Participants receive financial incentives at each stage of completion, with total possible compensation ranging from $40-50 at VUMC to $60-70 at MMC, reflecting the additional support needed for participants at the MMC site.

For participants who elect genetic counseling, the study evaluates not only appointment efficiency but also tracks uptake of and adherence to appropriate risk management strategies through EHR data. Additionally, the study monitors family sharing by tracking how many times participants share their unique family resource web link, whether the link was accessed, and the number of family members who subsequently enroll in the study.

Important Study Design: FOREST addresses critical healthcare disparities by conducting research at two distinctly different sites:

Vanderbilt University Medical Center (comprehensive academic facility)
Meharry Medical College (historically Black institution serving underserved populations)

With 500 participants, the study uses the RE-AIM framework to evaluate whether automated family history collection improves identification of at-risk individuals compared to usual care. Investigators expect at least a 5-minute reduction in genetic counseling appointments and aim to demonstrate that technology-enabled approaches can reduce systematic barriers that disproportionately impact medically marginalized populations.

How Does FOREST Compare in Today's Competitive Landscape?

Industry Context: The FOREST study emerges amid growing recognition that traditional genetic counseling models cannot meet increasing demand for hereditary risk assessment. With expanded testing guidelines and rising consumer awareness of genetic testing, healthcare systems face mounting pressure to identify efficient, scalable approaches to risk stratification. This study addresses the "identification gap" in precision medicine implementation, where patients who could benefit from genetic services remain unidentified due to systematic barriers. By focusing on technology-enabled, patient-centered approaches that reduce clinician burden, FOREST aligns with broader healthcare trends toward digital health solutions that extend specialist expertise while addressing workforce limitations. If successful, this model could influence how genetic screening services are deployed across diverse healthcare settings, potentially reducing disparities in access to cancer prevention and early detection interventions.

Summary

The Family History and Cancer Risk Study (FOREST), a pragmatic clinical trial registered as NCT05079334, evaluates MeTree—a patient-facing electronic family health history tool integrated with electronic health records through SMART on FHIR standards—to improve identification of individuals at risk for hereditary cancer syndromes. Conducted at Vanderbilt University Medical Center and Meharry Medical College, the study addresses systematic barriers in hereditary cancer risk assessment that disproportionately affect medically marginalized populations. MeTree evaluates risk for 143 conditions including 20 hereditary cancer syndromes, generating personalized risk assessment reports and clinical decision support for patients and providers. The study's vendor-agnostic SMART on FHIR integration aligns with recent regulatory requirements from the 21st Century Cures Act, offering compatibility with diverse EHR systems unlike proprietary genetic risk assessment tools. With 500 participants, the study employs the RE-AIM framework to evaluate implementation feasibility, effectiveness in identifying at-risk individuals compared to usual care, and impact on genetic counseling efficiency. The approach automates patient identification and risk assessment, potentially reducing clinician time burden while providing guideline-concordant recommendations directly in the EHR. Investigators hypothesize at least a five-minute reduction in pre-test genetic counseling appointments due to MeTree's automated family history gathering and pedigree generation. The dual-site implementation strategy provides insights for healthcare systems serving diverse populations with varying resource levels and technical infrastructure. Results are expected to influence how healthcare systems approach genetic risk assessment integration and could accelerate adoption of interoperable solutions for hereditary cancer screening, potentially reducing disparities in access to cancer prevention and early detection interventions.