Basic↦Quality and Risk↦Risk-Based Approach to Quality↦Risk Identification
What is it? Why is it important?
Risk identification addresses the question: What can go wrong in my study? In order to answer that question:
The first step is to identify:
The “Critical-to-Quality” (CtoQ) factors of the study, such as the:
- Right and safety of study participant (e.g. principles of ethics, study risk-benefit ratio)
- Scope, applicability and the quality of collected study data
- Complexity and applicability of the study design (e.g. blinded-, randomised studies)
- Ability to reach study endpoint/outcome
The second step is to identify:
Risks that threaten the integrity of the CtoQ factors. Risk identification occurs on many levels, such as:
- System level: infrastructure, partners, storage, facilities and material, freezer emergency plan
- Staff: qualification and training, availability, conflict of interest
- Study level: protocol complexity, informed consent procedures, selection of study design and study population, data collection, responsibility and oversight
- Scientific level: competitors, study relevance, conflict of interest
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By identifying risks threatening CtoQ factors, allows researchers to systematically plan and implement proportionate and adaptive risk control-measures
Examples of what can go wrong:
- Staff: untrained personnel, lack of staff back-up, inadequate time at disposal for study implementation
- Safety: unclear or missing procedures for identifying and reporting adverse events (assessment and reporting of IMP/IMD adverse events, SAE, or SUSAR)
- Data protection: participant data is accessible to staff not involved in the study
- Study Population: unclear communication of participant rights, inadequate information regarding study withdrawal
- Data quality: missing, incorrect, or inconsistent data not suitable for data analysis
- Analysis: use of inappropriate or invalid statistical methods, missing data lacking power for data interpretation and study conclusion
- Design: overly complex or unfeasible protocol leading to high participant burden, poor compliance, or low recruitment
- Documentation: insufficient and incomplete documentation of study related activities
- Biological material: lack of quality processes for sample retrieval, handling and storage (e.g. sample workflow)
- Regulatory compliance: missed deadlines for safety updates or required reporting to regulators
What do I need to do?
As a SP-INV:
- Actively engage in risk identification, by implementing a “Quality-by-Design” (QbyD) approach to your study. The aim is to manage risks before they occur, thereby providing credible and useful study results
- Identify risks that threaten Critical to Quality (CtoQ) factors early on during study planning, protocol development, and process mapping
- Ensure risk identification does not only take place during study planning but throughout the study life cycle (e.g. study planning, implementation, completion, and reporting)
- Evaluate and prioritize risks based on the likelihood of risk occurrence, detectability, and expected impact on CtoQ factors
- Define risk control-measures proportionate to risk significance
- Train staff and participating study sites on risk identification and mitigation
As a Site-INV, support the SP-INV in the identification of risks to CtoQ factors that are applicable to the settings of the participating study site.
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Consider critical circumstances and processes with inherent risks:
- Study design: such as randomised-, blinded- or cross-over design, required wash-out period
- Study population: vulnerable participants such as pregnant women or children, expected study compliance, drop-outs, lost to follow up
- Type of intervention: such as invasive or non-invasive procedures, carried out to improve, maintain or assess participant health
- Study inclusion and exclusion criteria: such as participant recruitment problems based on challenging criteria
- Methodological aspects: such as identification of treatment(s) and outcome used, statistical power used to test study hypothesis
- IC process: such as emergency situations, high recruitment numbers, non-native speakers
- Multi-centre studies: such as coordination and proficiency of participating sites
- Study partners: such as proficiency and ability to deliver requested services
- Informatics: such as access, data privacy protection, access to validated systems, data back-up
- Study staff: such as available resources, know-how, training, available time to dedicate to the study
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
- 3.10.1.1 Risk identification
ICH E8(R1) – see in particular guidelines
- 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