22.1 Specimens, Diagnostic Results and Rater Quality

Specimens, Diagnostic Results and Rater Quality

A specimen can be collected correctly yet become unusable through misidentification, processing, storage or shipment. A valid diagnostic result can still fail to protect a participant if it never reaches a qualified reviewer. The ECO covers sample/diagnostic collection, shipment, verification, reporting and storage, including laboratories, imaging and raters. Monitoring should follow the complete process and its clinical consequences.

Use the actual protocol and laboratory/diagnostic instructions. Collection timing, containers, processing, temperature and shipping conditions depend on the analyte and method. There is no universal centrifuge speed, freezing temperature or shipping interval for all clinical samples. A monitor verifies the specified process rather than improvising technical parameters from memory.

Traceable collection and processing

Confirm participant code, required visit/time point, actual collection time and relevant preconditions. Record deviations honestly. A planned time and actual time answer different questions, especially for timed pharmacokinetic or safety assessments. A requisition preprinted with the planned time does not prove when collection occurred.

Relevant processing records should establish what happened, by whom and when, using suitable equipment and supplies. Labelled aliquots and storage locations should remain traceable to the original sample without inappropriate identifying information. If a label is unclear, follow a controlled investigation and correction process. Do not guess the participant or overwrite identifiers to match a convenient manifest.

Storage and shipment

Shipping must follow applicable biosafety and transport requirements, using appropriately trained personnel. The CCRA lesson is to verify the authorised instructions, traceability and response to a problem; it is not to memorise one dangerous-goods category for every specimen. The study team should arrange the correct technical process for the actual material and destination.

A courier delay may affect sample suitability. Preserve the known collection, processing and shipping conditions and ask the responsible laboratory/sponsor function to evaluate the impact. A tracking status saying delivered does not establish the sample was accepted or analysed. Check rejections, missing tests and any need for a permitted repeat with the investigator.

Critical laboratory results

The investigator should have timely access to relevant external results affecting eligibility, treatment or safety and should review them appropriately. A portal timestamp can show a report became available; it may not establish that the treating team reviewed the critical finding. Confirm the alert and escalation process, including nights, weekends and absent primary contacts.

If a significant result lacks documented review, promptly involve qualified site staff and the sponsor as appropriate. The CRA should not diagnose the participant, prescribe treatment or wait for the next routine monitoring cycle. Determine whether medical assessment, an AE record, a dose decision or safety reporting is required under the protocol. Not every out-of-range result is automatically an AE; the investigator's assessment and collection instructions matter.

Imaging and raters

Diagnostic and endpoint quality can depend on acquisition methods, software, equipment, scoring conventions and rater training. Verify required certification and approved manuals, including changes. An otherwise clear image can be unsuitable if it omits a required view or uses the wrong acquisition method. A subjective rating can be biased if the assessor sees treatment information intended to remain concealed.

Preserve original outputs and relevant metadata. Where central review is used, clarify whether the local result, central result or both guide care and analysis. The investigator must receive clinically necessary information through an appropriate route; maintaining a scientific blind does not justify withholding urgent participant-safety information. Address the access boundary in the protocol and plans.

A reconciliation example

An EDC visit lists a completed safety panel, the shipment log shows two samples sent and the central laboratory reports one rejected specimen. Review whether the EDC records actual results, a planned collection or a completion assumption. Trace sample identifiers, rejection reason, investigator review and any permitted repeat. Correct the supported record with an audit trail; do not enter normal values because the participant looked well.

At closure reconcile unresolved samples, results and retained material under the protocol, consent and applicable requirements. Clarify storage or destruction authorisation and retain necessary records. The sample's physical disposition and the retention of associated clinical data are related but different decisions; completing one does not automatically complete the other.

Official sources

Checked October 18, 2026: ICH E6(R3), Principles and Annex 1, ICH E8(R1).