Health Ahead Comparative Effectiveness Study

Access to comprehensive preventive health screening is profoundly unequal. Geographic, economic, and systemic barriers leave medically underserved populations - including rural, frontier, and isolated communities - with little or no access to the depth of preventive screening that identifies disease before symptoms occur. The long-term aim of this work is a fully automated preventive screening system that can be deployed anywhere people live. Reaching that aim safely and credibly requires testing each change to the screening model one variable at a time, against current practice.

The Health Ahead Comparative Effectiveness Study is therefore designed as a standing sequential comparative-effectiveness platform. Each phase is a parallel two-arm comparison that isolates a single change while holding all other elements of the screening experience constant, and each is evaluated with the same core outcome set. As one comparison concludes, the next is opened by protocol amendment. Throughout, all participants are concurrently enrolled in the 100-Year Human Aging Study and the Human Observatory Study, so that short-horizon comparative findings are linked to lifelong individual and population-level outcomes.

Two design principles govern every comparison. First, allocation is randomized wherever randomization is feasible and non-randomized only where participant-level random assignment is not possible (for example, comparisons of screening location such as mobile versus fixed laboratory). Second, every comparison is registered with non-inferiority as the primary hypothesis: each evolutionary change toward a more automated and more broadly deployable model must demonstrate that it does not degrade outcomes relative to current practice, by more than a pre-specified margin. The unifying thesis is that quality is preserved as the platform evolves. Superiority is assessed as a pre-specified secondary in a hierarchical (gatekeeping) test and reported whenever non-inferiority is established and the data support a superiority claim. The same core outcome set is applied to every comparison to the greatest extent each comparison allows.

The planned comparison sequence is:

* Comparison 1: Static versus interactive personalized health report delivery. Both arms complete identical comprehensive multi-system screening and differ only in the report they receive. The interactive report allows participants to adjust their own behaviors and diagnostic inputs in real time and visualize the projected effect on their composite scores, estimated biological age, and aging trajectory. Assignment is randomized. The primary hypothesis is that the interactive report is non-inferior to the standard static report on health activation and behavior change. * Comparison 2: Mobile community screening versus fixed laboratory screening in medically underserved populations. The question is whether mobile delivery achieves engagement and outcomes equivalent or superior to a fixed laboratory setting (an equivalence/non-inferiority question). * Comparison 3: A hybrid delivery model combining medical droids, one registered nurse, and remote physician oversight, versus human-only screening. * Future: Fully automated screening performed by medical droids with remote physician review versus hybrid model.

The platform launches in Colorado, chosen as the founding geography for its exceptional diversity of medically underserved communities - high-altitude frontier towns, rural agricultural communities, mining corridors, and isolated mountain communities - within a well-characterized geography with established academic research infrastructure. Findings are designed to generalize to medically underserved populations nationally, internationally, and to inform federal health policy on mobile and automated preventive health delivery.

• Health Activation and Engagement (Superiority) [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Report Efficacy and Utilization [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Unintended Consequences and Psychological Impact [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Completion of Provider-Recommended Health Behavior Changes [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Primary Barrier to Non-Completion of Recommended Changes [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Participant Satisfaction - Longevity Metrics Post-Screening Satisfaction Questionnaire (6-item), Composite Score [Time frame: 1 to 2 weeks after health screening (at report delivery)]
• Complexity-Adjusted Cost-Effectiveness [Time frame: 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Participant Follow-up and Retention [Time frame: 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Longitudinal Health Outcomes and Mortality [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Operational Throughput and Screening Completion [Time frame: 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Data Quality and Test Validity [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]
• Population Characterization by Arm [Time frame: Baseline, 6-12-month follow-up, then periodically from enrollment until death, up to 100 years.]