Risk management

Risk management

Section contributed by Dr. Paula Marioli (Renálida, Argentina [renalida.com])

Risk management is a fundamental pillar in the planning and execution of clinical trials, especially for naive research centers. Effective risk management, assisted by tools such as the risk matrix, is critical to ensuring participant safety, data integrity, and compliance with regulations.

The risk matrix for clinical trials

A risk matrix is a tool that helps categorize risks based on their likelihood of occurrence and the impact they would have on the project if they occurred. This allows trial management teams to prioritize risks and allocate resources to mitigate them effectively.

A simple three x three risk matrix assigns three levels of risk (low, medium, high) based on the likelihood and severity of a problem.


Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555299/

A practical example of how a research center might implement a risk matrix at the start of a clinical trial protocol is described below:

Clinical Trial Objective:

  • Clearly define the objective of the clinical trial. For example, “To evaluate the efficacy, safety, and tolerability of a new drug compared to the standard of care in chronic kidney disease (CKD) progression in participants with CKD and high blood pressure.”

Research Team Composition and delegate assignment:

  • Principal Investigator (PI): Responsible for the overall conduct of the trial, ensuring that protocols and ethical regulations are followed.
  • Study Coordinators: Manage the daily operations of the trial, from participant recruitment to data collection.
  • Nursing Staff: Responsible for administering treatments and collecting clinical data from participants.
  • Pharmacists: Oversee the handling, storage, and dispensing of study medications.
  • Project Administrators: Ensure that the project stays on schedule and within the established budget.

Stakeholder Identification:

  • Include in this phase the identification of all relevant stakeholders, such as sponsors, regulatory bodies, and the trial participants themselves. Understanding their expectations will help to better define the objectives and potential risks.

Review of Documentation and Protocols:

  • Before proceeding, the delegated team should review all relevant trial documentation, including the study protocol, informed consents, and any applicable regulation. This ensures that all team members have a clear understanding of the procedures and objectives.

Establishment of Communication Lines:

  • Define efficient communication channels and protocols among team members and with stakeholders. This is crucial for effective risk management, as it allows for a rapid response to any incidents.

Risk Management Training:

  • Provide initial risk management training to all team members, ensuring they understand how to identify, assess, and mitigate risks associated with the clinical trial.

The delegated team meets for brainstorming and uses their experience, data from previous trials, and relevant literature to identify potential risks.

Examples of identified risks:

  1. Insufficient Recruitment: Difficulty in reaching the target number of participants.
  2. Regulatory Approval Delay: Delays in obtaining approval from ethics committees and regulators.
  3. Loss of Follow-up: Participants who drop out of the study before its conclusion.
  4. Incomplete or Incorrect Data: Errors in data collection or entry.
  5. Unexpected Adverse Reactions: Occurrence of severe side effects not anticipated.

Using a spreadsheet or specialized software, the team creates the matrix and classifies each risk according to its likelihood of occurrence (low, medium, high) and its impact on the study (minor, moderate, critical). For example:

  • Insufficient Recruitment: High probability, Critical impact.
  • Regulatory Approval Delay: Medium probability, Moderate impact.
  • Loss of Follow-up: Medium probability, Critical impact.
  • Incomplete or Incorrect Data: High probability, Critical impact.
  • Unexpected Adverse Reactions: Low probability, Critical impact

For each risk identified as high priority, the team develops specific mitigation strategies:

  1. Insufficient Recruitment: Expand inclusion criteria, increase study sites, contact primary care physicians, and improve marketing and outreach strategies.
  2. Regulatory Approval Delay: Prepare center documentation and anticipate regulatory questions to speed up the review process.
  3. Loss of Follow-up: Implement a robust system of follow-up and reminders for participants. Review previous digital contacts.
  4. Incomplete or Incorrect Data: Extensive training for staff on data collection and conduct regular audits of the collected data.
  5. Unexpected Adverse Reactions: Establish a clear protocol for monitoring and immediate reporting of adverse effects and prepare a rapid response plan

The team commits to reviewing the risk matrix monthly, updating the likelihood and impact of each risk based on the study’s progress and the emergence of new risks. This review allows for the adjustment of mitigation strategies and maintains a focus on the prevention and management of risks throughout the trial.

How to use the risk matrix

1. Risk Identification

Begin by listing all potential risks that could affect the trial. This includes challenges in recruiting participants to possible regulatory delays. Comprehensive identification is the first critical step towards effective risk management.

2. Objective

For each identified risk, define a clear objective that describes what you aim to achieve to mitigate that risk. For example, the objective for “Insufficient Recruitment” might be to secure a specific number of participants before a certain date.

3. Start Date and End Date

Set a start date and an end date for each risk. This will aid in planning risk management within a specific timeframe, allowing for more effective allocation of resources and mitigation efforts.

4. Days

Use the difference between the start and end dates to calculate the duration of each risk. This calculation can be automated with Excel formulas to facilitate tracking and updating.

Examples of Risks and Mitigation Strategies

Insufficient Recruitment

  • Objective: Ensure the recruitment of 100 participants by June 30.
  • Mitigation Strategy: Expand recruitment channels and increase study promotion on social media and local communities.

Regulatory Approval Delay

  • Objective: Obtain regulatory approval before the planned study start date of August 1.
  • Mitigation Strategy: Prepare all necessary documentation in advance and schedule preliminary meetings with regulators.

Defining Impact

The impact of each risk in the Clinical Trials Risk Matrix is defined by considering the potential consequences of its materialization in the clinical trial. This evaluation is based on several factors, including but not limited to:

  • Participant Safety: How the risk could affect the safety and well-being of trial participants. For example, the impact of an unexpected adverse reaction would have a high priority on the impact scale due to its direct potential effect on participants.
  • Data Integrity: The influence of the risk on the quality and reliability of the trial data. Risks that could lead to incomplete or incorrect data are considered high impact, as they compromise the study’s conclusions.
  • Timeline Compliance: The extent to which a risk could delay critical trial activities and affect the overall project schedule. Delays in regulatory approval, for example, have a direct impact on the project timeline.
  • Project Costs: How the risk affects the trial budget, including unforeseen additional costs. Risks with a significant financial impact require careful management to avoid overruns.
  • Reputation and Trust: The potential effect of the risk on the perception and trust of the trial’s stakeholders, including participants, sponsors, and regulatory bodies.

For each identified risk, the team assigns an impact rating using a scale (e.g., minor, moderate, critical) based on these criteria. This rating helps prioritize the risks and guides the allocation of resources for mitigation strategies. It’s crucial that this process is collaborative, involving various team members to capture a broad range of perspectives and expertise.

Regular Review and Update

It is vital to regularly review and update the matrix, especially after significant changes in the trial environment or the emergence of new risks. This process ensures the matrix accurately reflects the current state of the project and allows for the adjustment of mitigation strategies as necessary.

Conclusion

The Risk Matrix for Clinical Trials is a dynamic and essential tool that supports informed decision-making and proactive risk management in clinical research. Its implementation and effective use require commitment and collaboration from the entire research team, thus ensuring the integrity of the study and the safety of the participants.

Steps to create a risk matrix in excel

1. Open Excel and Prepare the Sheet

  • Open a new Excel workbook.
  • Name the first sheet “Risk Matrix”.

2. Set Up the Header

  • In the first rows, add general information about the project, such as the study title, project leader, start date, site number, etc.

3. Create Table Headers

  • In row 5 (or wherever you prefer to start), create the following headers in columns A to H: “Risk ID”, “Risk Description”, “Probability”, “Impact”, “Severity (Probability x Impact)”, “Mitigation Strategies”, “Responsible”, “Status”.

4. Define Scales for Probability and Impact

  • Before starting to fill in the table, define a scale for “Probability” and “Impact”. For example, 1 for Low, 2 for Medium, and 3 for High.

5. Fill in the Matrix

  • Start filling in the matrix with the identified risks. For each risk, assign a unique ID, describe the risk, and rate the probability and impact using the defined scales. The “Severity” column can be automatically calculated by multiplying “Probability” by “Impact”. For this, you can use a simple formula like =C6*D6 in the “Severity” column (assuming C6 contains the probability and D6 the impact).

6. Add Mitigation Strategies

  • For each risk, detail the planned mitigation strategies in the “Mitigation Strategies” column.

7. Assign Responsible Parties

  • Identify who will be responsible for monitoring and mitigating each risk, noting it in the “Responsible” column.

8. Risk Status

  • Use the “Status” column to mark the progress in managing each risk (e.g., “Not Started”, “In Progress”, “Completed”).

9. Format for Better Visualization

  • Use colors to differentiate levels of severity. For example, you might use red for high-severity risks, yellow for medium severity, and green for low severity.
  • Adjust the width of the columns and apply cell formats to improve readability.

10. Save the Document

  • Make sure to save the document with a suitable name and in a secure place.

This matrix should be reviewed and updated regularly to reflect changes in risk assessment throughout the project. This tool becomes more useful when integrated into regular project team meetings and becomes part of the research center’s risk management culture.

Next

To ensure that your Excel risk matrix is easy to update month by month, you can implement some management and configuration practices in your spreadsheet that facilitate this process. Here’s how to do it:

1. Create a Clear and Consistent Structure

  • Ensure your matrix has a clear structure and well-defined columns so that updates are consistent and easy to perform.

2. Use Excel Tables

  • Convert your risk matrix into an Excel Table by selecting your data range and using the “Insert Table” functionality on the “Insert” tab. Tables offer facilities for adding data, filtering, and sorting, which is useful for managing and updating the matrix.

3. Automate Calculations

  • Use formulas to automatically calculate the risk severity (Probability x Impact) and other values requiring calculations. This reduces human error and streamlines updates.

4. Filter and Sort

  • Take advantage of Excel’s filtering and sorting functionalities to manage specific views, like seeing only high risks or those pending mitigation.

5. Incorporate a Change Tracking System

  • Add a “Last Updated Date” column for each risk. This will help you quickly identify when each risk was last reviewed or updated.
  • Consider using Excel’s “Comments” feature to add specific notes about what was updated or needs to be monitored.

6. Set Reminders

  • Use calendar functionalities of your email or project management tools (we use Trello, which is intuitive and excellent for organizing tasks, setting deadlines, and tracking project progress through boards and cards) to set monthly reminders that it’s time to update the risk matrix.

7. Scheduled Monthly Review

  • Schedule monthly meetings with the research team to review and update the risk matrix. This promotes accountability and ensures the matrix reflects the current state of the project.

8. Save Historical Versions

  • Consider saving a new version of the matrix each month to maintain a historical record of changes. You can do this manually or use a version control tool.

9. Training and Documentation

  • Ensure all team members understand how to use and update the matrix. Creating a short guide or documentation can be helpful.

Frequently asked questions (faq) about the risk matrix in clinical trials

1. What is a risk matrix and why is it crucial in nephrology and other clinical trials?

A risk matrix is a tool that classifies potential risks of a clinical trial based on their likelihood of occurrence and the impact they would have if they occurred. It is crucial for identifying and mitigating risks early, thus ensuring patient safety and trial integrity.

2. How can I determine the likelihood and impact of a specific risk?

Likelihood is evaluated based on how frequently the risk is expected to occur, while impact is measured by the severity of its consequences on the trial. Consider previous experience, historical data, and expert knowledge to rate each risk.

3. What should I do after identifying and classifying risks in the matrix?

Once identified and classified, you should develop mitigation strategies for each priority risk. These strategies may include changes in the protocol, additional training for the team, or the implementation of new monitoring tools.

4. How often should I review and update the risk matrix?

The matrix should be reviewed and updated regularly throughout the trial, especially after significant milestones, the discovery of new risks, or when mitigation strategies are implemented to assess their effectiveness.

5. How do I involve my team in the risk management process?

Conduct brainstorming sessions for risk identification and discuss mitigation strategies in regular meetings. Ensure that all team members understand their role in risk prevention and management.

6. How can I use the risk matrix to communicate risks to stakeholders?

Use the matrix as a communication tool to inform stakeholders about identified risks, their potential impacts, and the planned mitigation strategies. This can aid in informed decision-making and expectation adjustment.

7. Can I adapt the risk matrix to my specific trial in nephrology?

Yes, the matrix is highly adaptable. You can customize it to reflect the specific risks, regulatory requirements, and particular characteristics of your trial in nephrology.

8. Where can I find more resources or assistance to implement the risk matrix?

Consider consulting clinical practice guidelines, attending risk management workshops, and collaborating with risk management experts. Also, stay updated on the ISN-ACT Toolkit for additional resources.