What a Companion Diagnostic Actually Means for Your Role
A companion diagnostic (CDx) is a laboratory test that the drug label states is required before a patient can receive a specific treatment. In a biomarker-selected oncology trial, this means the CDx result must be obtained, reviewed, and filed before the patient can be confirmed eligible — regardless of how suitable they appear clinically.
For CRAs, coordinators, and research nurses, the CDx is not a background regulatory issue — it is a core operational responsibility. Errors in specimen collection, labelling, or shipping are among the leading causes of screen failures and protocol deviations at oncology trial sites. Understanding the workflow end-to-end is part of the job.
The CDx Workflow from First Contact to Enrolment
The CDx process runs in parallel with — and often before — other eligibility assessments. Knowing where each step sits in the overall timeline prevents the most common cause of delay: discovering too late that a specimen was rejected or a result is not back in time for the screening visit.
Read the protocol eligibility section and lab manual before scheduling a screening visit. Note which CDx assay is required, what specimen type is needed (tissue block, slides, plasma, whole blood), whether archival tissue is acceptable, and whether a fresh biopsy is required if archival tissue is unavailable or fails QC.
The CDx specimen collection must occur after the patient has signed the informed consent form. Collecting a screening biopsy or blood draw before consent — even if the patient agrees verbally — is a protocol deviation and a common FDA inspection finding. Document the consent date and specimen collection date clearly.
If archival tissue is permitted: request the tissue block or unstained slides from the pathology department where the original biopsy was stored. Allow 1–3 weeks for this — start early. If a fresh biopsy is required: coordinate with the proceduralist, confirm the correct collection tubes or containers per the lab manual, and arrange for the sample to reach the lab within the protocol-specified time window.
Label specimens with the patient's trial ID (not name), site ID, collection date and time, and specimen type. Package at the temperature specified in the lab manual — most tissue specimens ship at ambient or with cold packs; plasma ctDNA samples often require dry ice. Complete the shipping manifest and retain a copy. Notify the central lab that a shipment is en route.
Log the shipment tracking number. Know the typical turnaround for the central lab (usually 7–14 business days for tissue NGS; 5–7 days for plasma assays). If the result is delayed and the patient's screening window is running short, contact the sponsor/CRO immediately — do not wait until the window closes. Some protocols allow a window extension if the delay was caused by the central lab.
When the CDx report arrives — by portal notification, email, or fax — print or save it immediately and give it to the PI or sub-investigator for review. The PI must confirm the result and document their review. A coordinator or nurse reviewing a CDx report without PI countersignature and confirming eligibility is a regulatory finding.
File the original CDx lab report in the patient's source record. Document in the eligibility assessment the specific result (e.g., "EGFR exon 19 deletion detected — eligible"), the assay name, the laboratory, the date the result was received, and the PI's countersignature. Enter the CDx data fields in the eCRF per the sponsor's data entry instructions.
If the CDx result is negative, the patient does not meet the key eligibility criterion. Check the protocol for reflex testing options (e.g., tissue biopsy if plasma was negative). If no reflex option exists, document the screen failure reason in the source record and screen failure log, and notify the sponsor per the trial's reporting requirements.
Specimen Collection: What the Lab Manual Is Really Telling You
The lab manual is the operational specification for the CDx test. It defines exactly what is acceptable and what is not — and a specimen that does not meet the spec will be rejected, meaning the patient cannot be confirmed eligible until a new specimen is obtained (if that is even possible).
| Specimen Type | Common CDx Use | Key Requirements | Common Errors |
|---|---|---|---|
| FFPE tissue block | Tissue NGS panels (e.g., FoundationOne CDx); IHC-based assays (HER2, PD-L1) | ≥20–30% viable tumour cells; block age within protocol limit (commonly 3–5 years); original pathology report required | Block too old; insufficient tumour content; wrong block sent (benign tissue or normal margin) |
| Unstained FFPE slides | When block is unavailable or must be preserved; IHC assays | Typically 10–25 unstained slides, 4–5 μm thickness; must be from same block as original diagnosis; mounted on charged slides | Slides re-cut from wrong block; slides dried out; too few slides provided |
| Plasma (ctDNA) | Liquid biopsy CDx (e.g., Guardant360 CDx for EGFR); T790M detection | Two × 10 mL Streck BCT tubes (cell-free DNA preservation); collect before any treatment; process within 96 hours or ship immediately; no EDTA tubes | Wrong tube type (EDTA); not shipped cold; delay >96 h before processing; sample collected after start of prior systemic treatment |
| Whole blood (germline) | Germline BRCA testing; MSI-H/dMMR confirmation | EDTA tube; 8–10 mL; ambient shipping; no haemolysis | Haemolysed sample; wrong tube; mislabelled with name instead of trial ID |
| Fresh biopsy (core needle) | When archival tissue unavailable or fails QC; serial biopsy protocols | Placed in formalin immediately; ≥2 cores recommended; notify pathology in advance for rush processing; preserve remaining cores for translational research per protocol | Placed in saline instead of formalin; biopsy taken before consent; tumour content insufficient |
Local Lab vs Central Lab: Knowing the Difference
Many sites assume they can use their own pathology department to run CDx assays. This is sometimes permitted — but the protocol and lab manual are the definitive guide. Using a local lab when the protocol requires a central, sponsor-designated laboratory is a protocol deviation that can affect eligibility determinations.
Central Lab (Sponsor-Designated)
Performs the validated, FDA-approved CDx assay on the protocol-specified platform. Required for eligibility in most biomarker-selected trials. Turnaround: typically 7–14 business days for tissue NGS, 5–7 days for plasma. Ship per lab manual; central lab result is the eligibility-determining result.
Local Lab (Site Pathology)
May be permitted for pre-screening to assess rough biomarker status before committing a patient to a full screening visit. The local result cannot substitute for the central lab CDx result for eligibility. Confirm with the protocol whether any local testing is permitted and how it must be documented.
Eligibility Decision: Who Does What
The CDx result feeds directly into the eligibility determination, but the decision-making roles are clearly defined. Coordinators and nurses often receive the CDx report first — but confirming eligibility is the PI's responsibility.
Coordinator / Research Nurse
Receives CDx report → files in source record → notifies PI or sub-I that result is available → enters raw data in eCRF per sponsor instructions → does not confirm eligibility independently.
Sub-Investigator (Delegated)
Reviews CDx result → confirms it meets the protocol eligibility criterion → countersigns eligibility assessment → communicates decision to coordinator for documentation. Must be listed on the delegation log for eligibility review.
Principal Investigator
Ultimate responsibility for confirming eligibility and the accuracy of all eligibility data. Reviews and signs the eligibility checklist. Ensures the CDx result, its date, and the assay are accurately recorded before authorising enrolment.
Screen Failures: Documentation When CDx Is Negative
A negative CDx result is one of the most common reasons for screen failure in biomarker-selected oncology trials. How you document it matters — both for the trial data and for your site's screen failure rate, which sponsors and CRAs review during monitoring visits.
When a patient screens out due to a negative CDx, document: the specific CDx result and date received; the eligibility criterion that was not met (cite the protocol section number); whether a reflex test was considered or attempted and the outcome; the screen failure date; the PI's review and sign-off. Notify the sponsor using the screen failure notification process in the protocol.
The Six Most Common CDx Errors at Trial Sites
These errors appear repeatedly at sponsor monitoring visits and FDA inspections. All are preventable with careful protocol review and structured workflows.
| # | Error | Risk Level | How to Prevent It |
|---|---|---|---|
| 1 | CDx specimen collected before informed consent | Critical | Always verify consent date vs. specimen collection date in the source record. Consent must precede any screening procedure. |
| 2 | Wrong assay used (local lab instead of central CDx) | Critical | Confirm with the lab manual which laboratory and which assay is required for eligibility. Do not substitute. |
| 3 | CDx report not filed in source documents | High | Print or save the CDx report immediately on receipt. File it in the source record before the patient's next visit. |
| 4 | Archival tissue outside the permitted age window | High | Check the original pathology report date against the protocol's age limit before requesting the block. If marginal, contact the sponsor before shipping. |
| 5 | Plasma sample collected in EDTA tubes instead of Streck | Medium | Keep Streck BCT tubes physically separate from EDTA tubes in the collection area. Label the Streck tube storage clearly. Train all phlebotomy staff on protocol-specific tube requirements. |
| 6 | Eligibility confirmed by coordinator without PI countersignature | Medium | Establish a site workflow where CDx results go directly to the PI inbox with a specific flag. Never enter enrolment confirmation in the eCRF until the PI has signed the eligibility form. |
Source Documentation Requirements
A clear, complete source record for a CDx test should contain everything a monitor or inspector would need to verify that the right test was run, the right result was obtained, and the right person made the eligibility decision. Use this as a mental checklist for every CDx-related record you create.
CDx Source Documentation — Site Checklist
Archival Tissue Requests: A Practical Timeline
Requesting archival tissue from an outside hospital is consistently the longest step in the CDx pre-screening process — and the one most likely to be started too late. A realistic timeline is 1–3 weeks from request to receipt of slides or block. Build this into your scheduling.
Week 1 — Initiate the Request
Contact the pathology department where the biopsy or surgery was performed. Obtain the required tissue request form (your site may have a template; the outside hospital may require their own). Submit with the patient's consent to release records and medical information. Include the trial protocol number and the specific block or slides needed.
Week 1–2 — Pathology Review
The outside pathology department retrieves the block, reviews tumour content, and prepares unstained slides or releases the block. This step is often delayed if the original case is old, the pathologist is unavailable, or the tumour block has been used extensively for prior testing. Follow up proactively — a single phone call often accelerates the process by days.
Week 2–3 — Shipping and Receipt
Once released, ship to the central lab per the lab manual. Notify the lab of the incoming shipment. Retain the tracking number and shipping manifest. Upon receipt, the central lab will assess tumour content before proceeding with CDx testing — if content is insufficient, you will need a fresh biopsy. Know this possibility in advance.