Trial Design

As the clinical research landscape evolves, decentralized clinical trials (DCTs) have emerged as a foundational competency, enabling broader patient participation, increasing trial efficiency, and driving more inclusive, real-world data collection. However, the successful execution of DCTs requires more than just innovative technology—it demands a comprehensive strategy that addresses the unique challenges of decentralization.

Protocol complexity in clinical trials has risen for two decades, but the trend has not been comprehensively quantified by phase and sponsor across the full 2004–2025 window on ClinicalTrials.gov.

How sponsors can leverage both the EU Clinical Trials Regulation and UK’s reformed framework to achieve cost efficiencies, faster timelines, and stronger regulatory positioning.

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.

From planning one Phase III trial at a time to digital standardization on repeat.

In this Q&A, Adrelia Allen, executive director of clinical trial patient diversity at Merck, discusses how the company is embedding diversity into clinical trial execution—from protocol design and site selection to long-term community engagement that extends well beyond individual trial timelines.

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

FDA Commissioner Marty Makary’s departure caps a turbulent tenure marked by leadership instability, industry pushback, and a series of regulatory controversies that complicated drug development for sponsors and CROs.

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.

Behavioral science reveals how recruitment failures, site disengagement, and underrepresentation in clinical trials are rooted in early design decisions, and what sponsors can do to address them before they become costly problems.

In this Q&A, Jenna DiRito, PhD, COO and co-founder of Revalia Bio, discusses how earlier, human-relevant data is reshaping go/no-go decision-making in drug development and what a truly front-loaded workflow looks like in practice.

In this Q&A, Krishna Cheriath, VP and head of clinical research digital data and AI at Thermo Fisher Scientific, examines how AI is reshaping clinical operations—from case intake and trial design to site burden reduction and the emerging reality of agentic AI in the workforce.

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.

The April issue of Applied Clinical Trials delves into the priorities driving patient engagement approaches today from the technology, regulatory, and site operations fronts.

Real-world data is increasingly used to optimize trial design, reduce recruitment burden, and support regulatory decisions, but adoption remains uneven due to challenges around data quality, integration, and internal alignment across functional areas.

Digital twin technology can reliably simulate standard-of-care treatment outcomes using historical clinical trial data, offering a practical pathway to virtual control arms that reduce recruitment burden and address ethical concerns around placebo designs.

Moving beyond vendor evaluation to incentive design in Phase II/III rare and genetic disease trials.

In part 1 of this three-part series, behavioral science reveals how slow patient recruitment and enrollment challenges often stem from design and startup decisions made long before recruitment begins, but can be identified and resolved early when they still matter.

In the first months of 2026, the FDA has moved on multiple fronts to modernize how drugs are developed, evaluated, and approved, signaling a broader regulatory shift toward flexibility, mechanism-based evidence, and human-centric science.

In this video interview, Marc Buyse, ScD, founder and CEO of IDDI, reflects on the gap between sponsor expectations and statistical reality, drawing on lessons from the COVID era to argue for more pragmatic, cost-efficient trial execution and greater patient access to clinical research.

In this video interview, Marc Buyse, ScD, founder and CEO of IDDI, examines the most common threats to trial data reliability, including opaque methodologies, synthetic controls, and the limits of AI-driven analysis, while making the case for explainable, transparent trial design.

In this video interview, David Morton, PhD, director of biostatistics at Certara, reflects on the growing role of Bayesian approaches in modern drug development, emphasizing their potential to improve decision-making, efficiency, and overall trial success.

In this video interview, David Morton, PhD, director of biostatistics at Certara, explores the practical challenges of implementing Bayesian designs, including the need for simulation, cross-functional alignment, and clear communication with regulators.