1. Background

The sponsor commissioned a specimen collection program to support immunoassay verification work on chronic Hepatitis C virus (HCV) markers in two populations where HCV prevalence runs materially above the general-population baseline: subjects co-infected with HIV, and subjects with current or recent intravenous drug use.2 Verification work for assays intended to perform across the full clinical population requires representative specimen sourcing from the populations where the marker is most prevalent — not just from the general-population enrollment frame.

The two populations are operationally distinct from the chronic-Hepatitis-B population reported in this engagement series.3 Where chronic Hepatitis B subjects are followed in primary-care and community-hepatology panels, chronic-HCV subjects in the target populations are primarily reached through HIV-care clinics and harm-reduction programs — a different community-clinic profile with a different operational requirement at the site level.

2. Constraints encountered

Three constraints shaped the execution plan:

  1. Population access through clinical relationships, not recruitment

    HIV-positive subjects and current or recent intravenous-drug-using subjects are not reached through general-population recruitment channels (advertising, community outreach, clinical-trial registries). They are reached through ongoing clinical care relationships at HIV-care clinics, harm-reduction programs, and federally-qualified community clinics. Site selection had to begin from the patient-panel side, not the recruitment-volume side.

  2. Eligibility documentation requires chart confirmation

    The protocol required documented chronic HCV status (HCV RNA positive or anti-HCV positive with confirmatory testing) plus the population-defining criterion. Confirming the chronic-HCV status from medical-record review during screening is the dominant lever for the qualified-subject ratio; sites without ready access to the subject’s clinical chart cannot run an efficient screening front door. Both program sites had direct access to subject charts as part of their primary clinical relationship.

  3. Subject-relationship continuity through draw

    Subjects in the target populations are more likely to be lost to follow-up between consent and specimen collection than general-population subjects. The protocol was structured as a single-visit specimen draw to compress the consent-to-collection window; both sites scheduled draws same-day or next-day from consent where feasible. The compressed window is the principal operational driver of the high-throughput months.

Monthly cadence formed a near-symmetric bell curve: +39, +89, +90, +71, +31. The peak two months coincide with both sites running at full screening capacity; the tail months reflect the natural close-out as eligible-subject pools drew down.

3. Methods

RDI executed the program as full-service CRO from the same Van Nuys operational spine as the rest of this engagement series. Three operational moves are reported here in order of implementation.

3.1. Compressed IRB pursuit

The Advarra IRB application was filed in early November 2025; IRB review cleared 7 days later. Approval documents posted shortly thereafter, and site initiation visits at both sites ran in mid- to late-November 2025; first-subject-in followed in early December 2025.

3.2. Two-site community-clinic anchor

Two community-clinic sites were activated as the program network. Site A (the lead site, 221 of 320 enrollments) is a federally-qualified community-health-center system with established HIV-care and harm-reduction patient panels. Site B (99 of 320 enrollments) is a standalone clinical research center with established access to the target populations through pre-existing care relationships. Both sites had subject-chart access at screening, allowing eligibility confirmation in the screening window rather than at the laboratory back door.

3.3. Single-visit specimen draw with same-day collection

The protocol was structured as a single-visit specimen draw against documented chronic-HCV status plus the population-defining criterion. Both sites scheduled the consent-to-draw window as tightly as feasible — same-day or next-day where the subject was on-site for clinical care, within a few days otherwise. The compressed window is the principal operational driver of the high-throughput months (February: +90, January: +89).

General-population recruitment frame

Advertising, community outreach, registry recruitment. Multi-week consent-to-draw windows. Eligibility verified at the laboratory back door. Operational losses concentrated at the recruitment-to-consent and consent-to-draw transitions.

Hard-to-reach-population frame (this program)

Subjects identified through ongoing clinical-care relationships at the site. Same-day or next-day consent-to-draw window where feasible. Eligibility verified from the medical chart during screening. Operational losses minimised by relationship continuity through the draw window.

4. Results

Cumulative enrollment crossed 39 by end-December 2025, 128 by end-January 2026, 218 by end-February 2026, 289 by end-March 2026, and reached 320 at the 30 April 2026 reporting date (Fig. 1). The program target was attained in April 2026 and the program is now in closeout.

Monthly cadence formed a near-symmetric bell curve across the 5-month enrollment window. The first month (December: +39) reflects the time required for both sites to identify and consent the first wave of subjects from their pre-existing clinical relationships. The peak two months (January: +89, February: +90) reflect both sites running at full screening capacity simultaneously. The tail months (March: +71, April: +31) reflect the natural draw-down as the eligible-subject pools at each site approached saturation.

Site distribution was approximately 70/30 between the two community-clinic sites: Site A (federally-qualified community-health-center system) 221 of 320 enrollments, Site B (standalone clinical research center with target-population access) 99 of 320 enrollments (Table 1; Fig. 2). The asymmetric site contribution reflects the underlying patient-panel size: Site A’s HIV-care and harm-reduction panel is approximately twice the size of Site B’s.

Table 1 Enrollment by site at the 30 April 2026 reporting date. The two community-clinic sites contributed approximately 70/30 to total program enrollment, reflecting the underlying patient-panel-size asymmetry.
Site Setting Enrolled Share
Site AFederally-qualified community-health-center system; established HIV-care and harm-reduction panels22169%
Site BStandalone clinical research center; access to target populations through pre-existing care relationships9931%
All sites at 30 Apr 2026 reporting date2 sites; both active throughout the enrollment window320100%
0 100 200 300 400 CUMULATIVE ENROLLMENT (n) · MONTHLY BARS (n) Dec 2025 Jan 2026 Feb 2026 Mar 2026 Apr 2026 Calendar month, Dec 2025 – Apr 2026 +39 +89 +90 +71 +31 320 · TARGET MET PEAK MONTH both sites at full capacity
Fig. 1 Cumulative enrollment (orange line) and monthly enrollment cadence (gray bars) across the 5-month enrollment window. The monthly cadence forms a near-symmetric bell curve (+39, +89, +90, +71, +31) with the February peak coinciding with both sites running at full screening capacity. Cumulative enrollment reached 320 by 30 April 2026, attaining the program target. Source: RDI Salesforce enrollment dashboard at 30 April 2026.
SITE CONTRIBUTION (n = 320) Site A 221 subjects · 69% Site B 99 subjects · 31% federally-qualified community-health-center system standalone clinical research center
Fig. 2 Site contribution at 30 April 2026. The two community-clinic sites contributed approximately 70/30 to total program enrollment. The asymmetry reflects the underlying patient-panel-size difference between the federally-qualified community-health-center system (Site A) and the standalone clinical research center (Site B) — not a difference in operational performance. Source: RDI Salesforce enrollment dashboard at 30 April 2026.

5. Discussion

Three observations bear noting. First, hard-to-reach-population specimen collection is fundamentally a different operational problem than general-population specimen collection. The general-population recruitment funnel — advertising through to consent through to draw — does not transfer to populations reached through ongoing clinical care. Site selection has to begin from the patient-panel side, not the recruitment-volume side; sites without existing clinical relationships to the target population deliver low enrollment volume regardless of total patient throughput.

Second, the bell-curve monthly cadence is a marker that both sites operated at the same operational tempo. A program with site mismatch typically shows a flatter enrollment curve dominated by one site’s ramp; the symmetry of the monthly cadence here (+39, +89, +90, +71, +31) reflects both sites running at concurrent full capacity through January and February.

Third, the 320-subject delivery in 5 months from 2 sites is comparable on a per-site-per-month basis to general-population specimen collection programs in this engagement series. The hard-to-reach-population framing did not impose a per-site-per-month penalty — it imposed a site-selection penalty that has to be paid once at program start, in the form of partnering with sites that have the right clinical relationships. Once those sites were identified and activated, throughput ran at general-population rates.

6. Conclusion

Specimen collection from hard-to-reach populations is operationally a community-clinic-partnership problem rather than a recruitment-funnel problem. A two-site network of community clinics with established clinical relationships to the target populations — HIV-positive subjects and intravenous-drug-using subjects — delivered 320 subjects in 5 months against a 7-day IRB cycle and a near-symmetric monthly cadence. The same operational frame — pre-existing clinical relationships rather than recruitment outreach — transfers to other hard-to-reach-population specimen collection programs.