1. Background
Lumos Diagnostics is a U.S.-listed in vitro diagnostics company commercialising FebriDx®, a qualitative, visually read, lateral-flow immunoassay that measures two host-response proteins — Myxovirus resistance protein A (MxA) and C-reactive protein (CRP) — from a fingerstick blood sample to differentiate bacterial from non-bacterial acute respiratory infection. The device is FDA-cleared for ages 12–64 in moderately complex and CLIA-waived settings.1
Protocol protocol was a prospective, multi-center, observational, blinded clinical method comparison study conducted across primary care, urgent care, and emergency settings. The primary outcome was the agreement of the FebriDx® result with the reference standard of clinical adjudication, performed by a panel of experts using a Clinical Reference Algorithm that incorporated multiplex respiratory PCR (BioFire Spotfire and Roche 6800), Brahms procalcitonin (PCT), CBC, and CRP testing alongside the clinical presentation.2 RDI was contracted as full-service CRO for the U.S. arm: site identification and contracting, IRB submission, kit production and shipment, central monitoring, reference-lab testing, and statistical-grade data delivery.
2. Constraints encountered
Four constraints shaped the execution plan:
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Bacterial-positive yield is seasonal
The primary endpoint was anchored on bacterial-etiology cases. The U.S. flu season of late 2024 and Q1 2025 produced a high volume of viral-etiology subjects, but bacterial-positive yield decelerated as respiratory illness prevalence dropped through April–May 2025. The protocol’s power calculation requires a minimum bacterial cohort, not a minimum total cohort.
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Heterogeneous practice settings
Sites included urgent care groups (Site A, Site H), emergency departments (Site B), and primary care/multi-specialty clinics (Site C, Site D, Site E, Site F, Site G, Site I). Each setting had distinct workflow, EMR, and patient-flow patterns; no single SOP could be deployed unmodified.
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Concurrent comparator-test logistics
Each enrolled subject required, in addition to the FebriDx® fingerstick: a combined mid-turbinate / oropharyngeal swab for multiplex PCR, and a venipuncture for PCT, CBC, and CRP. The reference-lab testing chain ran through RDI’s Van Nuys lab; specimen integrity (cold chain, time-to-spin, time-to-ship) was on the critical path.
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Investigational-Use blinding throughout
FebriDx® results were blinded to subjects, treating clinicians, and adjudicators; CRP results were blinded to adjudicators only. Site staff performed and read the device and uploaded a result photograph to the EDC immediately after documentation, with no clinician feedback. The blinding regime added per-subject staff burden and made operator drift hard to detect without central monitoring.
3. Methods
RDI executed the program as full-service CRO from a single program-management spine in Van Nuys, with central monitoring, in-house kit production, and reference-lab testing co-located in the same facility. Four operational moves are reported here in order of implementation.
3.1. Standard SIV at network of nine enrolling sites
Site initiation visits proceeded across nine enrolling sites between December 2024 and February 2025: Site B (ED), Site A (UC), Site I (PC), Site G, Site F, Site C, Site D, Site H (UC), and Site E. Each site received an SIV deck, regulatory binder, source documents, kits, and direct training on FebriDx® operation, sample handling, and EDC use.
3.2. Reference-lab integration in-house
Mid-turbinate / OP swabs were tested on BioFire Spotfire (BioFire Diagnostics) for the respiratory pathogen panel and Roche cobas 6800 for SARS-CoV-2 with quantification. PCT, CBC, and CRP were performed locally. Centralising the reference testing inside RDI removed the multi-vendor courier risk and compressed the time from sample receipt to data delivery.
3.3. Mid-study pivot to enriched-enrollment SIV (May–June 2025)
As bacterial-positive yield decelerated post-flu season, RDI introduced a second SIV format at active sites: an “enriched” second-encounter SIV that re-trained site staff on screening for elevated pre-test probability of bacterial etiology — sore throat without cough, productive cough with elevated WBC, otitis-media exclusion enforcement, and the standard-of-care prescription pattern that signals clinical suspicion. Sites received refreshed slide decks (May 14 at Site A; June 2 at Site E) and revised screening prompts in-clinic. The intent was to lift the proportion of qualified bacterial cases per screen, not to expand sites.
Pre-pivot (Mar–May 2025)
Standard FebriDx® SIV; sites screened broadly across all febrile ARI presentations. Yield dropped with seasonal incidence; total enrollment Mar–May = 162 subjects.
Post-pivot (Jun–Aug 2025)
Enriched-enrollment SIV deployed at active sites; screening focused on clinical signatures suggesting bacterial etiology and antibiotic prescription at index visit. Total enrollment Jun–Aug = 227 subjects (+40%).
3.4. Phased site close-out, Q1–Q2 2026
Site close-out proceeded in two waves following the August 2025 enrollment close. The Site I close-out report cleared sponsor review first and was used as the template for the second wave (Site E, Site H) issued late March 2025. The remaining sites — Site G (1 April 2026) and Site B (10 April 2026) — were closed against the same template. one of the lead sites device reconciliation completed October 2025; one subject record (one subject) was reconciled and exported post-billing in early autumn 2025 with sponsor-statistician sign-off.
4. Results
Cumulative enrollment crossed 173 by 31 January 2025, 402 by 30 April, 585 by 30 June (post-pivot), and reached 681 at active-enrollment close on 31 August 2025 (Fig. 1). The four top-performing sites — Site A (197), Site B (159), Site C (101), and Site D (97) — accounted for 554 enrollments, approximately 81% of the total (Table 1).
The post-pivot June 2025 month produced 131 enrollments — a 2.5× increase over May 2025 (52 enrollments) and the second-highest month of the program after January 2025 (161 enrollments) (Fig. 2). The June lift was concentrated at the same set of high-performing sites that had carried the program through Q1, indicating the pivot operated through site-level retraining rather than new site contribution.
The sponsor expanded scope twice mid-engagement: Change Order 1 (signed 20 May 2025) and Change Order 2 (signed 9 September 2025). Site close-out activities ran from October 2025 through April 2026; one of the lead sites unused-device reconciliation completed mid-October 2025, and the final monitoring reports cleared in April 2026.
Your statistician has confirmed she has no questions or concerns regarding the data received.
RDI/Lumos project update, October 2025
| Site | Setting | Enrolled |
|---|---|---|
| Site A | Urgent care | 197 |
| Site B | Emergency department | 159 |
| Site C | Primary care | 101 |
| Site D | Primary care | 97 |
| Top-4 subtotal | ~81% of enrollment | 554 |
| Site E | Urgent care | 57 |
| Site F | Primary care | 39 |
| Site G | Primary care | 15 |
| Site H | Urgent care | 9 |
| Site I | Primary care | 5 |
| Long-tail subtotal | 5 sites | 125 |
| RDI Van Nuys / test sites | Internal validation | 2 |
| All sites at active-enrollment close (31 Aug 2025) | 11 sites total / 9 enrolling | 681 |
5. Discussion
Three observations bear noting. First, bacterial-positive yield in respiratory-IVD method comparison is empirically seasonal, and the seasonality is asymmetric: peak flu drives total subject volume, but post-flu desaturation drives the ratio of bacterial to viral cases that the protocol’s power calculation actually depends on. The pivotal months were April–May 2025, when total volume held but bacterial yield decelerated.
Second, the operational lever that recovered the curve was not protocol amendment, not site expansion, and not contingency budget. It was a reformatted second-encounter SIV at the existing top sites. The premise of the enriched SIV was that site staff trained for broad screening — which is correct in flu season — required different prompts to identify bacterial pre-test probability post-season. Treating the SIV as an event rather than an artefact allowed yield recovery within the existing site network and contract envelope.
Third, the program demonstrates a recurring pattern across RDI rescue and method-comparison engagements: when execution confirms operational capacity, sponsors expand scope. CO 1 (May 2025) and CO 2 (September 2025) extended the program against the original SOW; the sponsor confirmed dataset acceptance at study close.
6. Conclusion
Enrollment for a host-response respiratory IVD method comparison is sensitive to the seasonal prevalence of bacterial etiology, not just to total respiratory volume. The standard CRO response — protocol amendment, additional sites, expanded eligibility — is not the only available lever. Mid-study reformatting of the SIV to refocus screening at the active sites recovered post-season yield without amendment or scope dilution. The program closed at 681 subjects across 9 enrolling sites and was followed by phased close-out through Q1–Q2 2026.