This is a ready-to-use validation protocol for the study-specific configuration of an Interactive Response Technology / Randomization and Trial Supply Management (IRT/RTSM) system. It assumes the base platform was separately qualified by the vendor; this protocol tests the randomization, dispensing, and accountability logic your study team configured on top of it. Replace every <<FILL: ...>> placeholder, scale the test depth to your documented risk assessment, and route it through your normal validation review and approval before first-subject-first-visit. A filled specimen test set follows. Verify each cited regulation against the current source before you rely on it. This content is general educational reference, not legal or regulatory advice.
1. Approval page
| Role | Name | Signature | Date |
|---|---|---|---|
| Author (Validation / Clinical Operations) | <<FILL>> | ||
| Clinical Operations lead | <<FILL>> | ||
| Clinical QA | <<FILL>> | ||
| Biostatistics representative | <<FILL>> | ||
| Study pharmacist / supply chain lead | <<FILL>> | ||
| System owner (IRT platform) | <<FILL>> |
| Field | Entry |
|---|---|
| Protocol number | <<FILL: VAL-IRT-###>> |
| Study / protocol number | <<FILL>> |
| IRT/RTSM platform / version | <<FILL: vendor product and release>> |
| Protocol version / date | <<FILL>> |
2. Objective
Provide documented evidence that the study-specific IRT/RTSM configuration performs as intended: randomization, stratification, dispensing logic, drug accountability tracking, resupply and expiry alerting, and emergency unblinding all function per the approved specification and preserve subject safety and data integrity, in line with GCP, 21 CFR Part 11, and EU GMP/GCP Annex 11 and Annex 13 expectations.
3. Scope
In scope: the study-specific build layered on the qualified base platform for <<FILL: study / protocol number>>, covering the randomization algorithm and every stratification factor the protocol defines, dispensing rules across visit types and dose levels, drug accountability and expiry/low-stock alerting, the emergency unblinding workflow, user roles, audit trail, and the interface to EDC. Out of scope: base platform qualification (covered by the vendor/platform qualification record <<FILL: reference>>), and the EDC study build, validated separately and referenced only at the interface test in section 7.
4. System description
<<FILL: hosting model, randomization method (fixed block, minimization, adaptive), number of treatment arms, stratification factors, dispensing model (site stock vs. direct-to-patient), depot/supply chain integration, EDC interface, user roles (site coordinator, unblinded pharmacist, blinded investigator, drug supply manager, monitor)>>
5. Prerequisites
- Approved User Requirements Specification (URS) and risk assessment on file; see User Requirements and Traceability and CSV Risk Assessment Methodology.
- Base platform qualification record referenced and current.
- Randomization specification approved by biostatistics, including the algorithm, block size handling, and every stratification factor and combination.
- Dispensing and accountability specification approved, covering every dose level, visit type, and resupply/expiry threshold.
- Test environment representative of production, with the same configuration version deployed and a large enough test randomization list to exercise every stratum.
- Test accounts provisioned for every role in scope, including an unblinded pharmacist role and a blinded investigator role, for negative testing of blind-preservation controls.
6. Roles and acceptance
Each test case is executed by <<FILL: tester role, e.g. Clinical Operations>> and independently reviewed by <<FILL: QA or biostatistics>>. A case passes when the actual result equals the expected result with objective, dated evidence attached (system output, randomization list extract, or audit trail excerpt). Randomization, stratification, dispensing, and unblinding are high-risk functions: any deviation in these areas is resolved and retested, never risk-accepted, before the summary is signed.
7. Test cases
Record for each: actual result, pass/fail, tester, date, evidence reference.
| ID | Requirement | Test step | Expected result |
|---|---|---|---|
| TC-01 | Randomization list generation | Generate the study randomization list per the approved algorithm and seed | List matches the pre-specified algorithm, block structure, and allocation ratio; list is stored securely with access restricted to unblinded roles |
| TC-02 | Single-factor stratification | Randomize test subjects across each level of one stratification factor in isolation | Each stratum draws from its own list; allocation ratio holds within each stratum |
| TC-03 | Combined stratification | Randomize test subjects across every combination of two or more stratification factors | Each combined stratum cell balances independently; no cross-contamination between strata |
| TC-04 | Block integrity | Randomize a full block within one stratum | Block completes with the specified arm balance before the next block opens |
| TC-05 | Missing stratification value | Attempt to randomize a subject with a required stratification field left blank | System blocks randomization or routes to the protocol-defined default; no silent mis-assignment |
| TC-06 | Dispensing logic: standard visit | Dispense at a standard scheduled visit for each dose level | Correct kit/dose assigned per the dispensing algorithm and treatment assignment |
| TC-07 | Dispensing logic: dose modification | Process a dose reduction and a subsequent re-escalation | System reflects the current approved dose at each dispensing event; history of prior levels retained |
| TC-08 | Drug accountability tracking | Dispense several kits and verify running inventory | Quantity on hand decrements correctly; accountability record matches dispensing events |
| TC-09 | Low-stock alert | Reduce site or depot stock below the configured threshold | Alert fires to the configured recipients at the configured threshold |
| TC-10 | Expiry alert | Load a kit with a near-term expiry date | Alert fires within the configured lead time; expired kit is blocked from dispensing |
| TC-11 | Emergency unblinding | Execute an emergency unblinding as an authorized unblinded user | Correct treatment assignment revealed only to the authorized user; event captured in the audit trail with user, timestamp, and reason |
| TC-12 | Blind preservation | Attempt to access unblinding information as a blinded investigator or site role | Access denied; no treatment-arm information exposed anywhere in that role’s view, including reports and exports |
| TC-13 | EDC interface | Trigger a randomization or dispensing call from the EDC integration | Correct assignment/kit data returned and recorded in both systems with no duplicate or dropped calls |
| TC-14 | Audit trail | Perform a randomization, a dispensing event, and an unblinding event | Trail records user, timestamp, and action for each, and cannot be disabled by a non-privileged user |
| TC-15 | Role-based access | Log in as each defined role | Each role sees only the functions and data appropriate to it; a revoked account cannot authenticate |
| TC-16 | Paper backup fallback (if applicable) | Simulate an IRT outage and execute the documented manual randomization fallback | Fallback follows the approved procedure, preserves attributability, and reconciles back into IRT with a documented, audit-trailed entry once the system is restored |
8. Deviation handling
Log each deviation with description, impact, root cause, and resolution. A failure in randomization, stratification, dispensing, accountability, or unblinding must be resolved and re-tested, and biostatistics must confirm the fix does not require re-generating or re-validating the randomization list, before the summary is signed.
| Dev # | Test case | Description | Disposition |
|---|---|---|---|
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
9. Acceptance criteria (protocol level)
- The randomization algorithm produces the pre-specified allocation ratio and block behavior in every stratum and combination tested, with no stratum left untested.
- Dispensing logic assigns the correct product across every dose level and visit type tested, including dose modifications.
- Drug accountability tracking, low-stock alerting, and expiry alerting all fire at the configured thresholds with no missed or duplicate alerts.
- Emergency unblinding reveals treatment assignment only to authorized roles, is fully audit-trailed, and blind preservation holds for every other role tested.
- The EDC interface reconciles completely, with no duplicate or dropped randomization or dispensing records.
- Every URS requirement traces to at least one executed test case with no orphans; see the Requirements/Test Traceability Matrix.
10. Summary and conclusion
<<FILL: statement that the study-specific IRT/RTSM configuration is validated for its intended use, or the conditions/restrictions on release; signed by Clinical Operations, Biostatistics, and QA>>
11. Attachments
- Requirements traceability matrix (URS to test case).
- Executed test evidence (system outputs, randomization list extracts, audit-trail excerpts).
- Deviation records and resolutions.
- Randomization specification and dispensing specification (referenced, not reproduced).
Filled specimen: stratified block randomization test set
A two-arm trial, 1:1 allocation, permuted blocks of 4, stratified by prior therapy (yes/no) and region (A/B). Details are illustrative.
| Stratum | Prior therapy | Region | Test subjects randomized | Expected arm split | Observed | Block integrity | Result |
|---|---|---|---|---|---|---|---|
| S1 | Yes | A | 8 | 4 / 4 | 4 / 4 | Each block of 4 balanced | Pass |
| S2 | Yes | B | 8 | 4 / 4 | 4 / 4 | Each block of 4 balanced | Pass |
| S3 | No | A | 8 | 4 / 4 | 4 / 4 | Each block of 4 balanced | Pass |
| S4 | No | B | 8 | 4 / 4 | 4 / 4 | Each block of 4 balanced | Pass |
| Missing-stratum case | n/a | n/a | 1 (deliberate blank prior-therapy field) | Randomization blocked, routed to data manager per protocol | Randomization blocked as expected | n/a | Pass |
Because the interaction between strata, not either factor alone, is the usual failure mode, the test deck enumerates every combination rather than testing each factor in isolation. The deliberate missing-value case is included because a silent default assignment here would be a randomization integrity failure that could go undetected until an unblinding review.
Common inspection findings this protocol prevents
- Randomization tested for overall allocation ratio but never for balance within each individual stratum, missing an interaction-driven imbalance.
- A missing or malformed stratification value silently defaulted to one arm instead of being blocked or routed per protocol.
- Emergency unblinding tested for the “happy path” only, with no negative test proving a blinded role genuinely cannot see treatment assignment anywhere, including in a report or export.
- Dispensing logic validated at build time but never re-tested after a mid-study dose-modification amendment.
- A paper backup randomization procedure that exists on paper but was never actually tested for reconciliation back into IRT.
How to adapt this protocol
- Scale test depth to your risk assessment; randomization, stratification, dispensing, and unblinding get full scripted testing regardless of program size.
- Enumerate every stratification factor combination your protocol defines, not just each factor in isolation.
- If the protocol allows dose modifications or has an adaptive design element, add test cases for every modification path.
- If the study amends mid-conduct in a way that changes stratification, dosing, or the randomization list, re-run the affected test cases under change control with biostatistics sign-off.
- Confirm every cited regulation against the current source before execution.