Multi-cohort transplant immunosuppressant collection for a mass-spectrometry assay program

An operations report on a multi-organ, multi-analyte therapeutic-drug specimen collection program for a top-tier global diagnostics manufacturer, with mid-study scope expansion to a second collection wave.

Abstract

Constraints encountered

Five constraints shaped the execution plan, reported in the order they bound the program.

1 · Multi-cohort, multi-organ eligibility envelope

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

2 · Mass-spectrometry-grade specimen integrity

Therapeutic drug levels require draw-time precision, tube-type discipline, and cold chain maintained from draw to the testing site. Errors at any layer fall through to the analyte result.

3 · Site density at the academic transplant center level

These patients are managed at academic transplant centers, not primary or urgent care. The set of viable U.S. sites is small and concentrated, and contracting at academic medical centers is a multi-month process.

4 · Paper CRF at program start

Collection I started on paper CRF for sponsor compatibility. The slow query cycle was viable at 218 subjects; it 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 — a constraint that drove the activation of lower-tier sites with broader patient mixes.

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.

Compressed IRB pursuit

The Advarra IRB application was filed 15 July 2025; review cleared 30 July 2025 — 15 days end-to-end. Site initiation visits at the lead centers began immediately, and the first month of enrollment produced 18 subjects.

Tiered site engagement

Sites were classified into three tiers and engaged in sequence. Tier-1 lead transplant centers were activated first and produced the bulk of Collection I enrollment. Tier-2 sites covered specific analyte-organ combinations not available at Tier-1. Tier-3 sites were brought online in 2026 to support Collection II and to mitigate the re-enrollment-risk constraint.

Mid-program scope expansion

The sponsor confirmed a Collection II expansion on 3 April 2026 with a 350-subject incremental target, expanding the cyclosporine and everolimus cohorts across all three organ groups and opening the everolimus cohort for the first time.

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 training in April 2026; subsequent enrollments are direct-entry.

Results

Cumulative enrollment reached 244 at the 1 May 2026 reporting date, with Collection II contributing 25 of those subjects. The transition between collections is visible as a flat segment from December 2025 through March 2026 — Collection I targets were near close, the paper-CRF transition was running, and Tier-3 sites were not yet online. April 2026 saw the first inflection in Collection II enrollment.

Site distribution is concentrated at the lead Tier-1 sites: four sites account for 210 of 244 enrollments — approximately 89% of the program.

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 monitoring infrastructure; lower-tier sites unlock specific combinations not available at the leads.

Second, mid-program scope expansion is the dominant secondary observation, repeating the pattern documented in the sponsor's healthy-volunteer rescue engagement. Once enrollment confirmed operational capacity through the lead-site network, the sponsor expanded the matrix by 350 incremental subjects — a 2.6× expansion of the original scope.

When recovery confirms operational capacity, sponsors expand.

Third, the paper-CRF to Castor EDC migration should be read as scope-expansion infrastructure rather than a documentation upgrade. Paper CRF was viable at the original scale; it would have been a binding constraint on Collection II's enrollment window. The migration was scheduled to complete before Collection II site activations, which it did.

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 lower-tier sites unlocking analyte-organ combinations not available at the leads. Collection I closed at the 218-subject target; Collection II added 350 incremental subjects and is on track for completion within a 6–9 month window.