Biomedical subjects

Marc Clausen

Publications and source records attributed to Marc Clausen.

6 recordsLinked to original sources

PubMed2026

Non-invasive screening in hereditary cancer: a randomized controlled trial to test cell-free DNA-based early detection in the CHARM consortium.

Individuals with hereditary cancer syndromes are born with germline genetic variants that significantly increase their lifetime risk of developing multiple cancers. Cancer rates and overall mortality can be reduced with intensive surveillance to facilitate early cancer detection. However, participating in diagnostic imaging and endoscopy surveillance programs is often time-consuming, overwhelming, inconvenient, and anxiety-inducing. To improve this, multi-cancer early detection tests are being developed using cell-free DNA (cfDNA) sequencing analysis to detect cancers with more sensitivity than conventional screening methods. Our community (the CHARM consortium: Cell-free DNA in Hereditary And high-Risk Malignancies) has been exploring the use of cfDNA sequencing in hereditary cancer, and has launched the CHARM2 prospective randomized controlled trial, which is enrolling 1000 participants with Hereditary Breast and Ovarian Cancer, Lynch syndrome, Li-Fraumeni syndrome, Neurofibromatosis type 1 and Hereditary Diffuse Gastric Cancer to improve equitable access, early detection and surveillance for high-risk individuals. All participants will have screening as per conventional syndrome-specific surveillance recommendations. Half the participants (experimental cohort) will also have cfDNA analysis at least three times a year, with abnormal results triggering dedicated clinical imaging and diagnostic evaluation, and heightened surveillance. Vetted by our patient advisors, validated patient-reported outcome and experience measures assessing participant psychosocial outcomes, engagement, and test preferences will be administered to both arms. Our goal is to inform if and how cfDNA analysis could be implemented into routine clinical care and offer a path to equitable and more convenient cancer screening for all high-risk Canadians.

Female↗

PubMed2026

Pilot Evaluation of a Digital Pretest Education Platform for Genomic Counseling: Perspectives of Health Care Providers and Patients.

Traditional in-person consultations for genetic services create access barriers. We hypothesized that the Genetics Adviser platform-a web-based digital platform delivering clinical genomic services-could reduce these barriers. Focusing on pretest education and counseling, we tested a pilot version of the platform in medical genetics and pediatric endocrinology group practices. The multimethod design consisted of quantitative patient and caregiver surveys, Google Analytics data, and qualitative healthcare provider interviews. Surveys included validated measures of acceptability and empowerment. Transcribed interviews were thematically coded and analyzed using NVivo. Of the 102 patients and caregivers targeted for this study, 85/102 (83%) accessed the platform, 71/102 (70%) proceeded beyond the landing page, and 60/102 (59%) completed the post-module survey. Users expressed high confidence in genetic understanding and empowerment (Genomics Outcome Scale [GOS]: 77/100), and providers noted potential benefits and highlighted technological and content-related limitations. Further research is needed to validate effectiveness across diverse populations and to evaluate long-term impacts on patient outcomes and healthcare efficiency.

Humans↗

PubMed2025

Opportunistic screening for broad range of medically relevant secondary findings: Laboratory benefits and burdens.

PURPOSE: Exome and genome sequencing enable opportunistic screening for secondary findings (SFs). We report on exome analysis for a broad range of medically relevant SFs in the setting of the Incidental Genomics randomized clinical trial (NCT03597165). METHODS: Participants had exome sequencing and were randomized to receive only primary cancer findings (control) or cancer findings and a choice of SFs (intervention). RESULTS: Across 279 participants, there were 4441 unique variants in SF genes: 5.0% (221) were reportable pathogenic/likely pathogenic variants, and 81.4% (3615) were nonreportable variants of uncertain significance (VUS). Intervention arm participants had on average 2.6 (SD 1.66, range 0-9) pathogenic/likely pathogenic variants and 29.5 VUS (SD 13.2, range 2-74). SFs for monogenic disease risk were reported in 35.3% (49/139) of participants (American College of Medical Genetics and Genomics non-cancer subset in 1.4%) and carrier status in 89.3% (117/131). In the intervention arm, variant filtration was 7.7 times longer per case (95% CI 5.3 to 11.3, P < .0001), variant classification was 13.3 times longer (95% CI 10.6 to 16.5, P < .0001), and report preparation was 3.3 times longer (95% CI 2.6 to 4.1, P < .0001). CONCLUSION: Although the yield of reportable SFs was high, this was accompanied by many nonreportable VUS and increased efforts for exome analysis.

Humans↗

PubMed2025

The development and usability of 'The Genetics Navigator': a digital solution for adult and paediatric clinical genetics services.

Clinical genetic services address diverse genetic testing needs, but there is no comprehensive digital solution to meet this variety. We aimed to develop and test the usability of the Genetics Navigator (GN), a platform designed to enhance genetic services for paediatric and adult patients. The GN prototype was created with input from a patient and clinician advisory board, informed by prior research. Usability testing involved genetics patients (N = 14), parents of paediatric patients (N = 4), and the general public (N = 10). Participants provided feedback using the 'think aloud' method when using the platform. We used the System Usability Scale (SUS) for quantitative evaluation. Qualitative data were coded by platform section, item, and identified key areas for improvement. Building on the Genetics Adviser platform, we added video and written content for various genetic conditions and patient groups, including pre-test education, counselling, decision support, history collection, post-test result disclosure, and management. Key feedback during rounds of usability testing emphasized the need for a supportive design, seamless workflow, and engaging experience of the tool. The tool was modified to reflect the feedback, and the GN achieved an average SUS score of 87.7 ± 10.9 (N = 28), indicating above-average usability. Future research will evaluate its clinical and cost-effectiveness in a randomized trial.

Humans↗

PubMed2024

Offering complex genomic screening in acute pediatric settings: Family decision-making and outcomes.

PURPOSE: Families of children in pediatric acute care who are offered ultrarapid genomic sequencing are making complex decisions during a high-stress period. To reduce complexity for families and clinicians, we offered genomic screening for the child and parents after the completion of diagnostic testing. We evaluated uptake, understanding, and service delivery preferences. METHODS: A cohort of 235 families who had completed ultrarapid diagnostic genomic sequencing at 17 Australian hospitals were offered up to 3 screens on their genomic data: pediatric-onset, adult-onset, and expanded couple carrier screening. We investigated decision making, understanding, and service delivery preferences using surveys at 3 time points (pre counseling, post counseling, and post result) and performed inductive content analysis of pretest genetic counseling transcripts. RESULTS: A total of 119 families (51%) attended genetic counseling with 115 (49%) accepting genomic screening. Survey respondents were more likely to find decisions about couple carrier screening easy (87%) compared with adult (68%; P = .002) or pediatric (71%; P = .01) screening decisions. All respondents with newly detected pathogenic variants accurately recalled this 1 month later. A delayed offer of screening was acceptable to most respondents (78%). CONCLUSION: Separating genomic screening from the stressful diagnostic period is supported by families who demonstrate good knowledge and recall. Our results suggest delaying genomic screening should be trialed more widely.

Humans↗

PubMed2024

Opportunistic genomic screening has clinical utility: An interventional cohort study.

PURPOSE: Practice is shifting toward genome-first approaches, such as opportunistic screening for secondary findings (SFs). Analysis of SFs could be extended beyond medically actionable results to include non-medically actionable monogenic disease risks, carrier status, pharmacogenomic variants, and risk variants for common complex disease. However, evidence on the clinical utility of returning these results is lacking. We assessed the outcomes of opportunistic screening for a broad spectrum of SFs by evaluating the yield, impact on clinical management, and consistency between SFs and participants' clinical features and family history. METHODS: Adult cancer patients had exome sequencing with the option to learn multiple categories of SFs. Outcomes data were collected through chart review and participant-reported measures up to one year after return of results. RESULTS: All participants (n = 139, 85.6% female, average 54.6 years old) who elected to learn SFs had ≥1 variant reported (100% [139/139]). The yield of reportable findings was highest for pharmacogenomic variants (97.8% [135/138] of participants), followed by common disease risk variants (89.4% [118/132]), carrier status (89.3% [117/131]), and variants related to Mendelian (27.2% [34/125]), medically actionable (15.2% [21/138]), and early-onset neurodegenerative (2.6% [3/117]) disease risks. SFs from the American College of Medical Genetics and Genomics list (v3.2, noncancer genes) were reported in 1.4% (2/138) of participants. SFs across all categories demonstrated clinical utility by prompting management changes in 28.1% (39/139) of participants. Moreover, a considerable proportion of participants had suggestive clinical features (49.0% (24/49)]) or family history (21.8% (27/124)) potentially related to their SFs. CONCLUSION: Our findings indicate there are potential benefits from opportunistic screening for a broad range of SFs.

Humans↗