4 Crucial Differences Between Early-Phase And Late-Phase Trial Site Selection

By Jeff de Leon, M.D.

The success of a clinical trial hinges on many factors, but few are as foundational as the choice of the clinical trial site tasked in executing the study protocol. While the overarching goal of any clinical trials — whether early-phase or late-phase — is to generate reliable data to advance a therapeutic candidate, the operational and strategic priorities differ significantly between these phases. Early-phase trials, typically Phase 1 and sometimes Phase 2a, prioritize safety, pharmacokinetics, and proof-of-concept, often in small, tightly controlled cohorts. Late-phase trials i.e. Phase 2b onwards, shift focus to efficacy, broader patient populations, and statistical power. These distinctions demand different site capabilities, expertise, and infrastructure.

Here, I’ll share the differences, focusing on what makes an ideal site for early-phase trials, where speed, precision, and adaptability are non-negotiable.

Early-Phase Trials: Start With The Investigator

For early-phase trials, the PI, preferably a physician, is the cornerstone of site selection. This individual must bring not only clinical expertise but also full availability at the site to oversee a trial’s unique demands. Early-phase trials require hands-on leadership from the PI. Why? These studies often involve first-in-human dosing or complex dose-escalation protocols, where real-time decisions — sometimes within hours — can determine whether to proceed, adjust, or halt the trial, on top of constant and frequent communications with counterparts at pharma companies and CROs. A PI who is stretched across multiple studies or unavailable during critical windows risks delays or compromised safety. Needless to say, additional investigators to act as sub-investigators are needed to ensure coverage.

Feasibility by sponsors and CROs should vet investigators not just for their CVs and active medical license but also their schedules and commitments, ensuring they can be present for dosing days, safety reviews, unscheduled escalations, and monitoring visits.

Recruitment: The Power Of An Active And Diverse Patient Database

Recruitment challenges affect all clinical trials, but early-phase studies face heightened pressure due to tight timelines. Unlike late-phase trials, which can use advertising or multi-site networks to enroll patients over months or years, early-phase trials lack that flexibility — delays can disrupt fast-paced schedules and stall subsequent studies awaiting results. An active, current patient database is a game changer here.

The ideal early-phase site maintains a roster of potential participants, updated within the last year, with detailed medical histories and, ideally, recent lab results. For instance, a Phase 1 trial for a metabolic disorder drug requires patients with specific biomarkers (e.g., elevated fasting glucose) readily available in records. Diversity among participants is also critical, ensuring the data reflects varied demographics and reduces bias in early findings. Similarly, an ethnically diverse clinical staff brings broader perspectives, enhancing patient trust and protocol execution. Relying on advertisements to recruit from scratch is risky — slow, expensive, and uncertain —while a pre-screened, diverse database speeds startup and keeps the trial on track.

SOPs Tailored To Early-Phase Precision

Standard operating procedures (SOPs) are the backbone of any clinical trial site, but early-phase trials demand a specialized subset. These studies often involve intricate protocols — think multiple blood draws for pharmacokinetics/pharmacodynamics over 24 hours with no to minimal windows, strict dosing decision flow, or continuous monitoring for adverse events. A site accustomed to late-phase trials where procedures might be more standardized and less frequent, may falter under the intensity of early-phase requirements.

For instance, a Phase 1 trial testing a drug’s bioavailability might require pharmacokinetic sampling at precise intervals (e.g., 15 minutes, 30 minutes, and one hour post-dose). The site’s SOPs should outline how staff are trained to hit these marks, how equipment is calibrated, and how deviations are documented and addressed. Generic SOPs won’t cut it — there’s no room for ambiguity when every data point shapes dose-escalation decisions. Sites with a track record of early-phase trials will have these processes dialed in, often with dedicated staff who understand the nuances of small-cohort, high-stakes research.

Feasibility assessments should evaluate SOPs or related documents (e.g., working practices, guidelines) to confirm both meticulous attention to detail and proactive mitigation strategies.

Bedspace And Facility Flexibility: Adapting To Shifting Timelines

Facility requirements also diverge sharply between early- and late-phase trials. Early-phase studies often require overnight stays, continuous monitoring by trained staff, or unscheduled interventions, making bedspace availability a critical factor. A site with limited beds or rigid scheduling can’t accommodate the fluid timelines inherent in these trials. Imagine a Phase 1 dose-escalation study where a safety signal emerges, prompting an unplanned 48-hour observation period. If the site’s beds are booked or its staff can’t pivot, the trial stalls.

The ideal early-phase site offers dedicated inpatient capacity — think roughly 40 beds for a small trial and 100 or more for larger ones — with the flexibility to scale up or down as needed. This might mean reserving space for potential dose cohorts or accommodating healthy volunteers for a bioavailability study, even over the holidays. Also important are the procedure areas the facility has — expecting to do the study procedures in their own room is not advisable — there should be assigned areas with adequate space.

Sites must have access to a medical emergency facility, ideally within 10 minutes, with immediate availability of medical records for the investigator. Equipment access is equally critical: on-site labs for real-time sample processing, infusion suites for complex biologics, and telemetry for cardiac monitoring can determine a site’s suitability for early-phase trials.

Strategic Implications For Sponsors And CROs

These differences should assist in the site selection strategy. Early-phase trials call for a “quality over quantity” approach — fewer sites, but each a precision instrument. Late-phase trials favor a “breadth and depth” model, leveraging multiple sites to cast a wide net. Misaligning these priorities risks delay, additional cost, and ultimate failure.

The takeaway? Early-phase site selection needs to have a different approach than the usual feasibility geared for late-phase trials. It starts with fully available physician-investigators, hinges on an active and diverse patient database (not ads), demands phase-specific SOPs that show sites’ robust experience in execution and mitigation, and requires flexible bedspace and facilities to accommodate compressed and changing study timelines. By tailoring their criteria to the trial’s phase, sponsors and CROs maximize efficiency, protect timelines, and, ultimately, bring therapies to patients faster.

About The Author:

Jeff de Leon, M.D. serves as the chief operating officer of an early-phase site in a leading clinical research network. With two decades of research experience, primarily in leadership, he has driven a 300% growth for his organization over five years. Opinions expressed are his own.