Setting Up a Phase 0 Trial: Teams, Sites, and Volunteer Management

Why Setup Matters in Phase 0 Trials

While Phase 0 studies are shorter and involve fewer participants than traditional trials, their setup requires meticulous planning and coordination. These trials often involve advanced technologies like microdosing, ultra-sensitive bioanalysis, and imaging endpoints, so having the right team, infrastructure, and subject management strategy is critical for success.

Key Team Roles and Responsibilities

1. Sponsor Team

• Project Manager: Oversees the trial timeline, budget, and coordination
• Clinical Scientist: Defines objectives, sampling schedules, and data use
• Regulatory Lead: Handles submissions to health authorities and ethics committees

2. Site Staff

• Principal Investigator (PI): Accountable for trial conduct and subject safety
• Sub-Investigators: Assist in dosing, assessments, and data collection
• Study Nurses: Manage drug administration, sample handling, and monitoring

3. Bioanalytical Team

• Bioanalytical Lead: Coordinates assay development and validation
• Sample Logistics Manager: Oversees chain of custody and storage

4. Pharmacokineticist / Statistician

• Responsible for data modeling and interpretation of PK/PD results
• Supports decision-making on dose escalation and study conclusions

5. Quality Assurance (QA)

Conducts audits and ensures that GCP and GLP standards are followed throughout the trial.

Criteria for Selecting the Right Study Site

Phase 0 trials often require specialized infrastructure. Site selection should be based on:

• Experience in early-phase research, especially with microdosing protocols
• Availability of intensive pharmacokinetic sampling capabilities
• On-site processing and storage (centrifuges, -80°C freezers, biohazard handling)
• Access to PET imaging or radiopharmacy, if applicable
• Emergency response capability, even for low-risk trials

Contract research organizations (CROs) may also be engaged for study conduct, data management, or central lab services.

Volunteer Management in Phase 0 Studies

1. Subject Selection

Healthy volunteers are typically enrolled. Inclusion/exclusion criteria should ensure:

• Low variability in PK parameters (e.g., similar BMI, age, sex)
• No history of drug abuse, smoking, or chronic medication use
• Willingness to follow fasting and activity restrictions

For oncology studies or targeted agents, terminally ill patients may be recruited under special ethical considerations.

2. Informed Consent Process

• Emphasize lack of therapeutic intent and purpose of microdosing
• Clearly explain risks, time commitments, and sample collection frequency
• Address confidentiality, insurance, and withdrawal rights

Consents should be available in the local language and approved by the Ethics Committee.

3. Dosing and Sample Collection

Phase 0 trials involve single doses with intensive sampling:

• Administer dose under fasting or standardized meal conditions
• Collect blood samples at multiple time points (e.g., pre-dose to 24h)
• Record vitals and adverse events meticulously, even if minimal

4. Safety Monitoring and Follow-Up

• Implement predefined stopping rules in case of unexpected reactions
• Ensure medical backup is available for emergencies
• Provide follow-up contact and lab assessments as per protocol

5. Compensation and Volunteer Experience

Offer fair compensation based on local ethical guidelines. Also:

• Ensure comfortable facilities for long sampling durations
• Communicate updates and provide results if applicable
• Respect volunteer dignity and reinforce the contribution to science

Logistics and Documentation

• Ensure SOPs are in place for every study procedure
• Train site staff on protocol and microdose handling
• Set up source documentation and CRF (Case Report Form) tools
• Implement drug accountability logs and reconciliation procedures

Case Example: Coordinated Setup for a 10-Volunteer Microdose Study

A CRO coordinated a single-center Phase 0 study involving 10 healthy volunteers. They ensured:

• Assay validation was completed before first dosing
• Site had -80°C storage, centrifuges, and rapid processing SOPs
• Each subject stayed for 24 hours post-dose under medical supervision
• PK samples were transferred on dry ice to the central lab within 12 hours

The trial was completed in 10 days with high compliance and usable PK profiles for all volunteers.

Summary for Clinical Research Students

Phase 0 studies may seem small in scale, but their precision and complexity make them a true test of clinical operations. As a student or early-career professional in clinical operations, pharmacology, or project management, understanding how to structure the right team, choose a capable site, and manage volunteers safely will help you build trials that succeed—even at the microdose level.

Execution excellence begins long before dosing—and continues until the last data point is captured.