Protocol Design

Patient-centricity remains largely consultative in most clinical research, yet rare disease communities demonstrate that genuine partnership from protocol inception improves feasibility, reduces unnecessary burden, and identifies outcomes that matter to patients themselves.

This pilot episode of The Human Side of Clinical Trials introduces a framework from Brian S. McGowan, PhD, FACEHP, chief learning officer and co-founder of ArcheMedX, Inc., exploring why operational failures in clinical trials often trace back to gaps in human readiness rather than process design alone.

Biomarker-informed trial enrollment appears straightforward for identifying responders and optimizing efficiency, but failures to account for demographic variation in cut-off selection, causality versus correlation, and composite biomarker complexity risk excluding viable patients and exacerbating disparities.

In this Q&A, Elizabeth Walsh, PMP, ACRP-CP, founder of Walsh Clinical Advisory and co-author of The Clinical Execution Blueprint, discusses the persistent misconceptions about sponsor accountability, why execution gaps originate long before study startup, and what genuine inspection readiness looks like when it is built in from the outset.

AI agents operate only within workflows, but most organizations lack unified workflow management systems, making it difficult to identify where agents should be deployed or ensure they integrate effectively across connected business processes in clinical research.

Clinical R&D modernization stalls through incremental optimization of individual workflows, but meaningful systemic change requires leaders to visualize structural relationships, understand hidden incentives, and identify leverage points that benefit the whole system rather than parts.

Experience sampling captures real-time signals of site burden and operational friction at the moment they occur, providing earlier and more actionable insight than retrospective assessments and revealing workarounds before they compound into protocol deviations.

Protocol assumptions about patients, visit schedules, timelines, and vendors are rarely tested against operational reality until startup, but early engagement of experienced execution strategists can identify and mitigate feasibility gaps before commitments harden into expensive course corrections.

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From rising costs and regulatory uncertainty to persistent vaccine hesitancy, sponsors face mounting pressure to standardize operations, build community trust, and develop the behavioral capabilities needed to run vaccine trials effectively in a rapidly shifting environment.

Optimization challenges spurring cultural, strategic, and organizational change.

Clinical development productivity improved in 2025, but gains remain fragile as end-to-end timelines lengthened again, signaling that future success depends less on individual trial execution and more on program-level orchestration, site engagement, and adaptive operating models.

Participant adherence depends on readiness—a combination of knowledge, calibrated confidence, and real-world mastery—not simply on digital tools, reminders, or education, which are forms of exposure rather than preparation for sustained performance.

Pediatric trial participation shapes children's and caregivers' long-term psychological outcomes, yet protocol design often overlooks experience as a variable affecting recruitment, retention, and data integrity—a gap increasingly recognized by regulators and quality standards

In this video interview, Del Smith, PhD, CEO and co-founder of Acclinate, explains how deep community relationships generate insights that improve protocol design, endpoint selection, and site placement, while building an on-ramp that compounds in value across future studies.

In this Q&A, Mark Freitas, managing director and life sciences practice lead at Alvarez & Marsal, discusses how clinical trial design has become a strategic business decision—and why small and midsize companies bear the greatest consequences when those decisions go wrong.

In this video interview, Mark Freitas, managing director and life sciences practice lead at Alvarez & Marsal, identifies governance inertia and review cycle lag as the most underappreciated risks when AI speeds up protocol development faster than organizations can act on the insights it generates.

In this video interview, Mark Freitas, managing director and life sciences practice lead at Alvarez & Marsal, offers a measured look at where AI is genuinely accelerating upstream protocol work and why proof points of faster approvals reaching patients are still limited.

In this video interview, Mark Freitas, managing director and life sciences practice lead at Alvarez & Marsal, discusses how crowded pipelines, compressed IP timelines, and competitive differentiation pressures are forcing smaller sponsors to treat protocol design as a core element of business strategy.

In this Q&A, Mwango Kashoki, MD, MPH, SVP and global head of regulatory strategy at Parexel, breaks down the FDA's plausible mechanism framework and what it means for sponsors developing individualized therapies in ultra-rare disease settings.

The execution translation gap—the failure to convert identified problems into coordinated, timely action—costs millions per trial through delayed amendments, persistent deviations, and slow site activation, yet remains addressable through aligned accountability and proactive execution management.

In this video interview, Mwango Kashoki, MD, MPH, senior vice president and global head of regulatory strategy at Parexel, examines the biological, dosing, and population-level considerations that sponsors must get right from the start when using basket and other master protocol designs to evaluate individualized therapies across multiple conditions.

In part 3 of this three-part series, behavioral science reveals that clinical trial diversity cannot be achieved through last-minute recruitment efforts, but requires designing protocols, sites, and enrollment strategies around the real barriers and needs of underrepresented communities from the outset.