13.1 Product Accountability and Adherence Calculations

Product Accountability and Adherence Calculations

The Master Drug Accountability Log tracks aggregate product inventory at the site level, documenting:

• Protocol number, investigative site number, and Principal Investigator name.
• Product trade or code name, dosage form, and strength.
• Lot or batch numbers, kit identification serial numbers, and shipment tracking numbers.
• Date of shipment receipt and physical condition of containers upon delivery.
• Total quantity received, cumulative balance on hand, and initials of the authorized recipient.

The Subject Dispensing Log

The Subject Dispensing Log records individual subject exposure, documenting:

• Subject screening/randomization identification number and subject initials.
• Date of dispensing and visit number (e.g., Visit 2 / Week 4).
• Kit number(s) dispensed and number of dosage units (tablets, capsules, or vials) provided.
• Dose prescribed and dose modification details.
• Date the subject returned empty, partially used, or unused containers.
• Quantity of dosage units returned by the subject.
• Signature or initials of the dispensing pharmacist or authorized study coordinator.

Estimating participant adherence without confusing inventory

For a simple fixed-tablet regimen, an illustrative estimate is (units dispensed minus units returned) / units expected to be taken × 100%. This estimates disappearance from the participant's supply, not observed ingestion. Record lost tablets, hospital doses, partial containers and interruptions before interpreting the result. Protocol-specific rules determine the expected dose count and how to address non-adherence; 80–120% is not a universal GCP acceptance range.

Example: 60 tablets were dispensed for 30 days at two tablets daily. A documented three-day medical hold reduces expected use to 54 tablets. Nine tablets are returned, so 51 are unreturned: 51/54 × 100 = 94.4%, rounded to one decimal. If the site instead divides by 60, it obtains 85.0% and ignores the authorised interruption. Both calculations can be arithmetically correct for different denominators, but only the protocol-defined denominator answers the intended question.

For devices, preserve model/configuration, lot/serial identifiers and participant-use traceability as required by the protocol and instructions. A malfunction, use error or labelling issue needs documented assessment even when no injury occurred. Follow the study's escalation and return instructions. Do not clean or alter an explant in a way that destroys evidence; clinical safety, biosafety and the specified investigation process control its handling.

Do not infer a universal UDI requirement or 24–48-hour device deadline from ICH medicinal-product guidance.

CRA IP Reconciliation Responsibilities: The Triangulation Method

During routine interim and close-out monitoring visits, the CRA does not merely glance at pharmacy logbooks. The CRA must execute a rigorous, three-way Triangulation Audit Methodology:

Triangulation Audit Steps

1. Physical Inventory Audit: The CRA physically counts all unopened kits, intact blister cards, vials, returned empty bottles, and partially used boxes stored in the pharmacy or research storage room.
2. Log Verification: The CRA compares the physical count directly against the Master DAL and Subject Dispensing Logs, verifying mathematical totals and unit balances.
3. Source and EDC Cross-Check: The CRA cross-checks dispensed kit IDs against doctor progress notes, nursing administration records, electronic Case Report Forms (eCRFs), and Interactive Response Technology (IRT) records to confirm that the correct kit was dispensed to the correct randomized participant.

Resolving Discrepancies and Missing Product

If a discrepancy is identified (e.g., two tablets missing, broken vial, unreturned bottle):

• The CRA must never quietly adjust numbers or alter logs.
• The CRA must interview pharmacy personnel, trace physical disposal receptacles, and audit subject visit charts.
• Document the investigation, evidence, conclusion and follow-up through the applicable controlled records.
• If investigational product was dispensed incorrectly (wrong dose or wrong randomized kit), the event must be reported as a major protocol deviation to the sponsor and IRB.

Closing the accountability record

Use mutually exclusive categories for final disposition. One useful site-stock balance is:

Opening site stock + receipts + participant returns = dispensing + depot returns + authorised destruction + closing site stock + documented losses.

A participant-returned tablet enters stock again; it is not also counted as consumed. Keep dispensing and participant administration separate. Example: the site receives 200 tablets, dispenses 120, receives 20 back, and returns 100 to the depot. The balance is 200 + 20 = 120 + 100, with zero closing stock.

Participant-level records separately explain the 100 tablets not returned. An equation that adds all 120 dispensed tablets and all 100 depot-returned tablets against only 200 received would double-count the 20 tablets returned by participants.

Verify discrepancies and their supporting evidence, preserve traceability, and follow sponsor-authorised return or destruction procedures. A note to file may document an investigation but cannot prove the location of missing product. Do not alter accountability totals to force balance or discard unexplained containers before review. A destruction record identifies the product, quantities and disposition under the authorised procedure.

Official sources

Checked October 18, 2026: ICH E6(R3), Principles and Annex 1, ICH E8(R1), ACRP CCRA Exam Content Outline.