53 Risk & Issue Management
53.1 Purpose
Risk and issue management is the primary mechanism by which project management maintains control over trial execution.
The goal is not to eliminate problems, but to: - anticipate them, - detect them early, - mitigate their impact, - and escalate appropriately.
53.2 Risk vs Issue vs Deviation
These terms are often confused but represent different concepts:
| Concept | Meaning |
|---|---|
| Risk | A potential future problem |
| Issue | A current active problem |
| Deviation | A compliance failure |
Examples:
- Risk: Sites may fail to enroll on time
- Issue: Site A missed enrollment target
- Deviation: Site A violated protocol inclusion criteria
Each requires a different response.
53.3 The Risk Register
A risk register is a structured list of:
- identified risks
- probability of occurrence
- potential impact
- mitigation strategies
- current status
Typical risk categories:
- Operational (enrollment, monitoring)
- Regulatory (IRB delays)
- Safety (late SAE reporting)
- Data quality (high query rates)
- Vendor performance
53.4 Risk Assessment Dimensions
Risks are assessed using two primary dimensions:
| Dimension | Question |
|---|---|
| Probability | How likely is this to occur? |
| Impact | How severe would the effect be? |
High-probability, high-impact risks receive highest priority.
53.5 Issues and Escalation
An issue represents a risk that has materialized.
Issues require: - immediate attention, - root cause analysis, - and often escalation.
Common escalation triggers: - missed critical milestones - repeated protocol deviations - systemic safety reporting failures - data integrity concerns
53.6 Escalation Pathways
Escalation typically flows:
CRA → CTM → CPM / Trial Lead → Sponsor → Steering Committee
Escalation is not failure. It is a control mechanism.
53.7 Relationship to CAPA
Issues that represent: - systemic failures, - repeated deviations, - or quality breakdowns
often require Corrective and Preventive Actions (CAPA).
Risk management identifies problems.
CAPA resolves root causes.
53.8 Risk Management as a Living Process
Risk management is not a one-time activity.
It evolves throughout the trial: - new risks emerge, - priorities shift, - mitigations change.
The risk register should be reviewed: - at every study team meeting, - before major milestones, - and during inspection preparation.
Vaccine trials frequently require accelerated decision-making cycles due to enrollment speed and public health timelines. Governance structures must support rapid escalation and response.