Nature, Published online: 29 October 2025; doi:10.1038/s41586-025-09686-5

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

Background: Patient recruitment remains a critical challenge in clinical research. Although the integration of electronically collected patient-entered data within clinical practices enables innovative recruitment approaches, existing methods present challenges such as increased patient burden and potential violation of autonomy. A more nuanced approach involves identifying patient attributes associated with higher propensity for research participation, enabling research teams to efficiently prioritize outreach efforts. Objective: This study aims to (1) develop patient-reported questions reflecting perceptions about research participation and (2) determine whether patient responses are predictive of interest in joining a precision medicine registry. Methods: This mixed methods study used an exploratory sequential design in 2 phases. Phase 1 involved cognitive interviews with 32 patients recruited through the Cleveland Clinic Healthcare Partners program to develop “research perception” questions. Participants evaluated 9 candidate questions that were based on a literature review of research participation factors. Three questions were selected for implementation. Phase 2 was a cross-sectional cohort study incorporating these 3 questions into routine electronic questionnaires completed by primary care patients through the patient portal. The study population included 1077 patients who completed both “research perception” and “research recruitment” questions between August 2018 and April 2019. Diagnostic accuracy was assessed using receiver operating characteristic curve analysis, and multivariable logistic regression models evaluated associations while adjusting for demographic and health factors. Results: Phase 1 revealed strong research support among participants, with 97% (31/32) agreeing that research should be part of the institution’s mission and 100% (32/32) affirming that research enhances patient care. Phase 2 included 1077 patients (mean age 48.3, SD 16.3 years; 625/1065 female, 58.68%; 661/1005 White, 65.77%), of whom 278 (25.8%) expressed interest in being contacted about the precision medicine registry. Patients expressing interest were older and had worse self-reported health, more depressive symptoms, and greater social needs. “Strongly agree” and “very important” responses to any “research perception” question were significantly associated with study interest, with adjusted odds ratios ranging from 6.36 (95% CI 2.77-14.6) to 17.6 (95% CI 5.08-61.1; P<.001). The “research perception” questions demonstrated high sensitivity (>80%) but limited specificity (24%-31%). Conclusions: Patient-reported questions assessing research participation likelihood can help identify patients more likely to enroll in clinical studies. This approach enables effective recruitment prioritization while preserving patient autonomy and reducing patient burden. High sensitivity makes these questions valuable as screening tools, although limited specificity suggests use for prioritizing rather than excluding participants. Further validation across different trial types and populations is warranted.