Development↦Quality and Risk↦Quality and Risk Management↦Procedures
What is it? Why is it important?
To ensure the scientific value of research results, the SP-INV implements study quality and risk procedures, which include to:
- Maintain a Quality by Design (QbyD) approach during study planning, development, conduct and completion
- Identify the Critical to Quality (CtoQ) factors of the study
- Identify risks to CtoQ factors from planning until completion
- Evaluate and prioritise risks based on the probability of occurrence and their impact on CtoQ factors
- Define risk control-measures
- Implement risk surveillance throughout the study life cycle, from planning until completion (i.e. assessment of risk efficacy and the emergence of new risks)
When writing the study protocol, an estimation of potential study risks and the required risk control-measures are defined.
During study conduct the management and adaptation of risk control-measures may become necessary. Consequently, risk identification and handling are continuous processes, starting at the time of protocol writing and only ending upon study completion.
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Examples of study risks or what can go wrong:
- Safety: non-compliant processes in the assessment and documentation of adverse events
- Data protection: participant data becomes accessible to non-study staff
- Participant right: study participants are not properly informed regarding their right to withdraw, at any time, from the study
- Data quality: data collection is incomplete, unusable for data analysis and reporting
- Analysis: not applicable statistical method(s) are used to analyse the data
- Design: highly complex with questionable feasibility resulting in poor compliance and incomplete dataset
- Biological material: lack of standardised processes for sample collection, processing, storage, and analysis (e.g. sample workflow)
- IMP/IMD: lack of optimal storage conditions and regulated access control
Newly identified risks during study set-up, development and conduct might potentially necessitate a protocol amendment.
What do I need to do?
As a SP-INV, you are responsible for the risk management of your study.
Identify study risks by asking:
- What are the CtoQ factors of my study?
- What are risks that could threaten CtoQ integrity?
- What is the level of detectability and expected risk occurrence, including the impact on CtoQ factors (e.g. risk evaluation/prioritisation)?
- What are applicable risk control-measures?
Additional procedures include to:
- Access the feasibility questionnaire providing information on potential study risks
- Access lessons-learned providing information on risk handing in previous studies
- Implement a QbyD approach, and plan the implantation of a risk-based Quality Management System
As a SP-INV and Site-INV:
- Document the identification and handling of study risks in a Risk Assessment Form (RAF)
- Train study staff on required risk control-measures and risk responsibilities (e.g. delegation-log)
- Define processes for regular risk reviews in order to assess effectiveness of risk-control measures during study conduct, including emerging of new risks
- Update the RAF during study conduct
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Risk control-measures can be a single measure or a combination of different measures, with the involvement of different staff members, (e.g. surgery, study nurse, laboratory, data manager, statistician).
Note: Excessive risk control activities beyond requirements can overburden staff, extend study milestones and timelines, increase the budget, and the occurrence of risks. Align quality activities proportionally to trial complexity and defined CtoQ factors.
Examples of risk control-measures:
- Study protocol: use appropriate study design avoid unnecessary complexity which increases risk occurrence. Avoid unnecessary data collection that challenges available resources (e.g. study staff, infrastructure, budget)
- Study Documents: provide clear guidelines for study relevant procedures such as data collection, participant informed consent, handling of IMP/IMD (e.g. SOPs, WIs)
- Staff trainings: ensure study staff is trained on the risk management of your study, including ongoing adaptations
- QbyD approach: ensure the implementation of a risk-based quality management system throughout your study. Consider quality assurance and quality control aspects
- Infrastructure & functionality: optimize eCRF usability, provide analytical materials, ensure appropriate premises are available
Example of risk identification and control
In a blinded vaccine study, placebo & vaccine vials are identical only distinguishable through an 8-digit identifier placed on the vial.
Risk: mix-up of placebo and vaccine vials could threaten study outcome/endpoint, and endanger participant safety (e.g. unwanted side effects are falsely attributed to the treatment intervention)
Risk Control-Measures: the study SP-INV recognises the risk and proposes measures to mitigate risk occurrence.
- Store placebo and vaccine vials in separate sections of the fridge or in 2 separate fridges
- Use a 4-eye/double-check process to confirm vial identity against an identifier list
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 Risk Management
- 3.10.1.1 Risk Identification
- 3.10.1.2 Risk Evaluation
- 3.10.1.3 Risk Control
- 6.2 Factors critical to quality
- 7.3 Management of CtoQ factors
ICH E8(R1) – see in particular guideline
- Art. 3.2 Critical to Quality Factors
ISO 31000 (access liable to costs) – see in particular section
- Risk management: Principles and guidelines