Basic↦Quality and Risk↦Risk-Based Approach to Quality↦Risk Control Measures
What is it? Why is it important?
Risk control-measures are proportionate and adaptive steps implemented to protect study defined Critical to Quality (CtoQ) factors from identified risks.
The aim is to reduce CtoQ related risks to an acceptable level needed to protect participant right and safety, ensure data quality, and prevent risk recurrence.
Upon risk evaluation & prioritisation, a decision is taken whether a risk should be:
- Accepted: no risk control-measures required
- Tolerated: allowed if impact and risk remain within predefined boundaries consistent with study objectives. Risk tolerance reflects an informed and deliberate risk acceptance
- Reduced: risk control-measures are tailored but remain adaptable throughout the study to respond to changes in risk behaviour
- Prevented: risk control-measures are proactively included in the design and conduct of the study to avoid risk occurrence
When assessing study risks, researchers should apply a “Quality-by-Design” (QbyD) approach to the study. The aim is to manage risks before they occur, thereby providing credible and useful study
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Example
In a blinded vaccine study, Placebo & Vaccine syringes look identical. Only vial coding distinguishes them as either placebo or vaccine.
Risk: Potential mix-up of placebo and vaccine syringes threatens participant safety and data integrity
Risk handling by the SP-INV:
- Identifies the vial mix-up as a risk able to threaten study defined CtoQ factors
- Evaluates and prioritises the risk (i.e. using a Risk Evaluation Matrix)
- Defines appropriate risk control-measures, such as:
- To physically separate placebo and vaccine syringes during storage (e.g. separate fridge compartments or separate fridges)
- Include double-check processes (4-eye principle) with documented verification to confirm that the match between vial coding and syringe content was correctly identified
- Train staff on risk control-measures
- Plan monitoring visits to ensure compliance with risk control-measures during study conduct
- Periodically review the effectiveness of risk control-measures and asses the need for improvement
What do I need to do?
As a SP-INV or Site-INV or HRO project-leader, envision an example from daily life (e.g. falling while walking on frozen pavement).
Train yourself in defining risk control measures:
- Risk acceptance: accept to walk on the frozen pavement
- Risk tolerance: accept to walk on frozen pavement considering that there is at least a certain amount of snow. Threshold is a “certain amount of snow”
- Risk reduction: such as to add salt or gravel on frozen pavement, wear crampons
- Risk avoidance: such as to take a public trasport instad of walking or remain inside
Effective risk control-measures target the root-cause threatening the integrity of CtoQ factors, while remaining:
- Dynamic and subject to continuous review and improvement as risk behaviour changes during study conduct
- Alert if risks deviate from predefined quality tolerance limits, triggering risk re-evaluation and corrective actions
- Integrated across all levels of study operations (e.g. study design, monitoring plan, delegated responsibilities, training, infrastructure)
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Based on the REM risk control measures:
- Are especially crucial for risks on the top right-hand corner of the diagram (e.g. high risk frequency with high impact)
- Are tested for robustness prior to study start to ensure efficacy during study conduct
- Can be implemented on several levels, such as
- Study design
- Extent and scope of study monitoring
- Delegation of roles & responsibilities
- Planned training of study staff
- Infrastructure adaptations
You can learn a lot about risks and how to manage them from lessons learned during previous studies. Thus, document implemented control measures and their efficacy in a risk management plan. The plan can be used as a basis for later studies.
Where can I get help?
Your local Research Support Centre↧ can assist you with experienced staff regarding this topic
Basel, Departement Klinische Forschung (DKF), dkf.unibas.ch
Lugano, Clinical Trials Unit (CTU-EOC), ctueoc.ch
Bern, Department of Clinical Research (DCR), dcr.unibe.ch
Geneva, Clinical Research Center (CRC), crc.hug.ch
Lausanne, Clinical Research Center (CRC), chuv.ch
St. Gallen, Clinical Trials Unit (CTU), h-och.ch
Zürich, Clinical Trials Center (CTC), usz.ch
References
ICH GCP E6(R3) – see in particular guidelines
- 3.10 Quality management
- 3.10.1.3 Risk control
ICH E8(R1) – see in particular
- 3.1 Quality by Design of clinical studies
- 3.2 Critical to Quality Factors
ISO 31000 (access liable to costs) – see in particular section
- Risk management: Principles and guidelines