27.3 Queries, Coding and Supported Clinical Meaning

Queries, Coding and Supported Clinical Meaning

A clinical trial may successfully enroll participants and execute every protocol-required procedure, but if the resulting data are plagued by uncodable medical terms, unresolved discrepancy queries, or discrepancies between the clinical database and the safety repository, the responsible team must assess and address the impact before planned analysis/reporting. Database Lock represents a controlled operational milestone restricting routine editing and defining a controlled dataset version for its intended use.

The Clinical Data Query Lifecycle

A Data Query (also termed a Data Clarification Form [DCF] or Discrepancy Note) is a formal communication generated within an Electronic Data Capture (EDC) platform requesting that the investigative site clarify, confirm, or correct clinical data entered on a Case Report Form.

The Three Origins of Data Queries

1. System/Automated Queries: Fired automatically by programmatic validation logic programmed into the EDC system. These operate according to the configured system workflow when values violate range boundaries, when mandatory fields are omitted, or when cross-form dates conflict.
2. Data Management (DM) Queries: Generated manually by sponsor or CRO Clinical Data Managers reviewing data listings for clinical plausibility, missing documentation across visits, or ambiguous medical descriptions.
3. CRA / Monitoring Queries: Generated manually by the CRA during on-site or remote Source Data Verification (SDV) and Source Data Review (SDR) when the monitor detects discrepancies between the primary source records and transcribed eCRF fields.

Regulatory Rules Governing Query Resolution

• Strict DOA Authorization: Under ICH E6(R3), the Principal Investigator is responsible for the accuracy, completeness, and timeliness of all trial data reported to the sponsor. While the PI may delegate query resolution tasks to qualified clinical research coordinators via the Delegation of Authority (DOA) log, responses and corrections should be made by appropriately authorised personnel under the documented workflow.
• Preserve the authorised workflow: A monitor must not answer for the site or make ad hoc data changes simply because staff are busy or a deadline is close. E6(R3) permits sponsor changes to investigator-entered data only when justified, agreed upon in advance by the investigator and documented. Use the actual controlled allocation of responsibilities; never impersonate site staff. Reviewing and closing a monitor query after a supported site response is distinct from supplying that response yourself.
• Prohibition of "Fudge Factors": Site personnel must never fabricate explanations or alter source documents retroactively to satisfy a query. If an automated edit check flags an out-of-range pulse of 42 bpm in an athletic subject, the site must not artificially alter the source record to 60 bpm. Instead, the site confirms that 42 bpm was the true measured value and enters an explanatory note: "Confirmed correct: Subject is a marathon runner; baseline resting bradycardia clinically evaluated by PI."
• Query Aging Metrics: Sponsors monitor Query Aging (the elapsed calendar days between query issuance and site resolution). The trial procedures define that sites resolve routine queries within specified deadlines, with urgent safety issues escalated promptly. The CRA tracks aging metrics and intervenes when site query backlogs exceed acceptable operational thresholds.

Medical coding and faithful clinical meaning

Coding groups varying clinical language for consistent review and analysis. Common dictionaries include MedDRA for events/medical conditions and WHODrug for medicines. Their detailed hierarchies are not additional references on ACRP's current CCRA list. A monitor's priority is clear, supported source and verbatim information, not changing a diagnosis to make a preferred code available.

Record an unambiguous term, relevant dates, medical assessment and the information requested by the protocol. If an abbreviation or compound phrase is unclear, seek qualified clarification. Do not assume every symptom must always be split or always absorbed into a diagnosis; apply the collection and coding conventions with medical review. Preserve what the investigator actually assessed and document any change.

For a medicine, exact product name, dose, unit, route, frequency, dates and indication can support interpretation. A trade name may refer to different formulations or combinations. Query missing information neutrally rather than substituting a familiar product. Coding is normally performed/reviewed by the assigned sponsor function; the CRA facilitates supported clarification through the investigator/site.

Serious Adverse Event (SAE) Reconciliation

In modern clinical trial execution, participant safety data are maintained in two parallel, independent databases:

The SAE Reconciliation Mandate

Because the clinical EDC database and the pharmacovigilance safety database ingest data through different pathways (routine eCRF entry vs. immediate SAE report forms), discrepancies can occur.

• SAE Reconciliation is the formal, periodic, cross-functional auditing process conducted jointly by Clinical Data Management, Drug Safety, and Clinical Operations to identify and resolve discrepancies between the two repositories.

Official sources

Checked October 18, 2026: ICH E6(R3), Principles and Annex 1, ICH E9(R1).