Two scope expansions, one EDC migration, 244 subjects delivered

1. Background

The sponsor commissioned a multi-cohort therapeutic-drug specimen collection program to support a portfolio of mass-spectrometry assays for solid organ transplant recipients. The protocol covers five analyte families — mycophenolic acid (MPA), cyclosporine A (CSA), tacrolimus (TAC), sirolimus (SIR), and everolimus (EVR) — and three principal organ groups (heart, liver, kidney). For tacrolimus, the protocol distinguishes peak and trough draws as separate sub-cohorts, and an “ISD” (immunosuppressant drug pooled) cohort applies across organ groups for selected analytes. The data are inputs to assay verification on the sponsor’s mass-spectrometry platform.²

The program was structured into two collections: Collection I (the original 218-subject scope) and Collection II (a 350-subject incremental scope added 3 April 2026). Collection II expanded the analyte mix to include everolimus across liver and kidney organ groups and increased target counts on cyclosporine across all three organ groups.

2. Constraints encountered

Five constraints shaped the execution plan:

1. Multi-cohort, multi-organ eligibility envelope

   The protocol enrolls across 5 analytes × 3 organ groups, with peak/trough sub-cohorts for tacrolimus. Operationally each (analyte, organ) combination behaves as its own sub-study, with its own target count, its own clinical-screening signature, and its own visit logistics. Sites may be capable of one analyte×organ combination but not another.

2. Mass-spectrometry-grade specimen integrity

   Therapeutic drug levels at the analytical assay level require draw-time precision (peak/trough timing for tacrolimus), tube-type discipline (whole blood for CSA and TAC; serum for MPA), and cold chain maintained from draw to the testing site. Errors at any of these layers fall through to the analyte result.

3. Site density at the academic transplant center level

   Patients on these immunosuppressants are managed at academic transplant centers, not at primary care or urgent care. The set of viable U.S. sites is small (Tier-1 lead centers) and concentrated. Site contracting at academic medical centers is a multi-month process with subcontract / FCOI / IT-security overhead.

4. Paper CRF at program start

   The original Collection I started on paper CRF for sponsor compatibility. Paper CRF’s slow query cycle and limited data visibility were viable at the original 218-subject scope; they would have been a binding constraint on the Collection II expansion.

5. Re-enrollment risk on cohort change

   Once a subject contributes to one analyte×organ cohort, they are not re-eligible for the same combination. As cohorts close, sites need access to a different patient pool to support the next combination — a constraint that drove the activation of Tier-3 sites with broader patient mixes.

3. Methods

RDI executed the program as full-service CRO with tiered site engagement, central monitoring, and a single program-management spine in Van Nuys. Five operational moves are reported here in order of implementation.

3.1. Compressed IRB pursuit

The Advarra IRB application ([Pro number]) was filed 15 July 2025; IRB review cleared 30 July 2025 — 15 days end-to-end. Approval documents were posted 1 August 2025; site initiation visits at the lead Tier-1 centers began immediately, and the first month of enrollment (August 2025) produced 18 subjects.

3.2. Tiered site engagement

Sites were classified into three tiers and engaged in sequence. Tier-1 lead transplant centers (Site A, Site B, Site C, Site D) were activated first and produced the bulk of Collection I enrollment. Tier-2 sites (Site E, Site F, Site G) covered specific analyte-organ combinations not available at Tier-1. Tier-3 sites (Site H, Site I, Site J, Site K, Site L, Site M, with Site N, Site O, and Site P in active discussion) were brought online in 2026 to support Collection II analyte-organ combinations and to mitigate the re-enrollment-risk constraint described in §2(v).

3.3. Mid-program scope expansion (3 April 2026)

The sponsor confirmed a Collection II expansion on 3 April 2026 with a 350-subject incremental target. Collection II expanded the cyclosporine and everolimus cohorts across heart, liver, and kidney organ groups; opened the everolimus cohort for the first time (not yet open as of 1 May 2026); and revised the analyte-organ enrollment matrix shown in Table 1. A change order is being routed to reflect the expanded scope.

3.4. Paper CRF → Castor EDC migration

Sites were transitioned from paper CRF to Castor EDC mid-program to improve data visibility, accelerate query cycles, and integrate with the sponsor’s Medrio data-management environment. Sites completed Castor training in April 2026; subsequent enrollments are direct-entry into Castor. A sample dataset was shared with the sponsor data-management team to assess the Castor → Medrio integration.

3.5. Castor → Medrio integration handoff

RDI’s data-management workflow uses Castor for capture and the sponsor’s Medrio environment for downstream analytical use. A representative sample dataset was shared with the sponsor data-management team during the migration to validate the Castor-export → Medrio-import handshake. The intent of the EDC migration is operational visibility for Collection II without rework on the sponsor side at study close.

4. Results

Cumulative enrollment crossed 80 by end-September 2025, 192 by end-November 2025, 218 by end of Collection I (March 2026), and reached 244 at the 1 May 2026 reporting date with Collection II contributing 25 of those subjects (Fig. 1). The transition between Collections is visible as a flat segment from December 2025 through March 2026 — the Collection I targets were near close, paper-CRF transition activities were running, and Tier-3 sites were not yet on-line. April 2026 saw the first inflection in Collection II enrollment (+24 subjects).

Site distribution at the 1 May reporting date is concentrated at the lead Tier-1 sites: Site A (94 subjects), Site B (52), Site C (40), and Site D (24) account for 210 of 244 enrollments — approximately 89% of the program. The Tier-2 sites (Site E, Site F, Site G) contribute a further 34 subjects (Table 1; Fig. 2). Tier-3 sites (Site H, Site I, Site J, Site K, Site L, Site M) are activating against Collection II.

By cohort, MPA-Kidney and TAC-Kidney are close to closure at one lead site, with that site projecting closure in the next several weeks. Cortisol and aldosterone reference cohorts — running in parallel with the analyte cohorts under the same sponsor program — are tracking on the sister study’s timeline.

5. Discussion

Three observations bear noting. First, multi-cohort therapeutic drug specimen collection at academic transplant centers is operationally a tiered network problem, not a uniform site-network problem. The four Tier-1 lead sites carry ~89% of Collection I enrollment because they have the patient density and immunosuppressant therapeutic-drug-monitoring infrastructure; Tier-2 and Tier-3 sites unlock specific analyte-organ combinations not available at the leads, which is what makes the matrix structure of Collection II tractable.

Second, mid-program scope expansion is the dominant secondary observation, repeating the pattern documented in the sponsor’s healthy-volunteer rescue engagement.³ Once enrollment confirmed operational capacity through the lead-site network, the sponsor expanded the analyte-organ matrix by 350 incremental subjects — a 2.6× expansion of the original 218-subject Collection I scope. When recovery confirms operational capacity, sponsors expand.

Third, the paper-CRF to Castor EDC migration and the Castor → Medrio integration handshake should be read as scope-expansion infrastructure rather than as a documentation upgrade. Paper CRF was viable at the original Collection I scale; it would have been a binding constraint on Collection II’s 6–9 month enrollment window with seven additional Tier-3 sites. The migration was scheduled to complete before Collection II site activations, which it did.

6. Conclusion

Multi-cohort, multi-organ therapeutic drug specimen collection for a mass-spectrometry assay program is achievable through a tiered site-engagement model, with Tier-1 academic transplant centers carrying enrollment volume and Tier-3 sites unlocking analyte-organ combinations not available at leads. Collection I closed at the 218-subject target; Collection II added 350 incremental subjects with associated EDC migration and Tier-3 site activation, and is on track for completion within a 6–9 month window driven by site activation cadence.