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Clinical Research Coordinator Analysis

Intensive Pharmacokinetic (PK) Sampling Schedule

Finding: The protocol (Section 8.2.3, Table 11) mandates intensive pharmacokinetic (PK) sampling on Day 1, Week 4, and Week 24, requiring participants to be on-site for blood draws at pre-dose, and 2, 4, 8, and 12 hours post-investigational product (IP) administration. Section 6.5.1 further specifies that IP should be administered under fasted conditions (at least 8 hours) on PK sampling days. This results in participants needing to be at the clinic for well over 12 hours, starting with a fasted state. This extended duration presents a significant burden for participants (especially those with SCD who may be prone to pain crises), potentially impacting recruitment, willingness to continue, and compliance with the demanding sampling schedule. It also poses considerable logistical challenges for site staffing (requiring personnel coverage for extended hours), resource allocation (e.g., dedicated space, chairs/beds for participants), and coordination. Recommendation: To enhance feasibility and participant experience:

1. The Sponsor should provide clear, standardized guidance and adequate budget for sites to offer comfort measures for participants during these long PK days, such as private resting areas, meal provisions (after the fasting period and relevant samples are complete), and potentially travel or childcare reimbursement.

2. Explore and clarify if any flexibility exists for the later PK samples (e.g., the 12-hour sample). For instance, could a home health nursing visit be an option for suitable participants, or could participants who live locally be permitted to leave the site and return for the final draw(s) if this does not compromise sample integrity or data quality?

3. During site feasibility and selection, proactively discuss these intensive PK days to ensure sites have the infrastructure, staffing capacity, and experience to manage them effectively.

4. Develop a participant-facing information sheet specifically explaining the requirements and support available for these long PK visit days to manage expectations upfront.

Rationale: Addressing these logistical and participant burden aspects proactively will likely improve participant recruitment and retention, reduce the risk of missed PK samples leading to protocol deviations, ensure higher quality data, and contribute to smoother overall trial operations by ensuring sites are well-prepared and resourced.