Risk Management in the Clinical Study

With ICH E6(r3) in draft, I think it is important to look at the current state of risk management expectations in a clinical study.

Risk management is an essential part of any clinical study, and is a critical component of the ICH E6 and E8 guidelines for Good Clinical Practice (GCP). These guidelines provide a framework for ensuring the safety and well-being of study participants, as well as the integrity and reliability of the study data. By following the principles outlined in these guidelines, researchers can help to ensure that their study results are reliable and can be used to inform clinical practice.

Through risk management we ensure the four main goals of the GCPs are obtained.

The ICH E6 guideline provides recommendations for the conduct of clinical trials, emphasizing the importance of risk management, specifying that a risk management plan should be developed and implemented for each study. The guideline also provides recommendations for the content of the risk management plan, including the identification of potential risks, the assessment of their likelihood and potential impact, and the development of strategies for managing or mitigating those risks.

Risk management is a key enabler and result of the quality management system.

The ICH E8 guideline, which focuses on the conduct of clinical trials also emphasizes the importance of risk management. It specifies that the risk management plan should include a comprehensive evaluation of the risks associated with the study interventions, as well as a plan for managing or mitigating those risks. The guideline also recommends that the risk management plan be regularly reviewed and updated as needed, to ensure that it continues to effectively address the risks facing the study.

When planning a clinical study, sponsors must carefully consider the potential risks involved and take steps to minimize them. Sources of the risk assessment include performing a thorough literature review to identify any known risks associated with the study interventions, as well as conducting pre-study assessments to identify potential risks specific to the study population. E8 also state sthe importance of a wide variety of stakeholders, including the patient population.

Once the study is underway, it’s important to closely monitor for potential risks and have a plan in place for managing them.

In addition to protecting the safety of study participants, effective risk management is also essential for maintaining the integrity of the data being collected. Risks to the study data might include things like errors in data entry or missing data, which can compromise the validity of the study results. To address these risks, sponsors must have robust quality control measures in place, such as regular data audits and checks for missing or inconsistent data.

Overall, the role of risk management in a clinical study is to ensure the safety and well-being of study participants, while also protecting the integrity of the data being collected. By carefully considering and managing potential risks, researchers can help to ensure that their study results are reliable and can be used to inform clinical practice.

Risk Based Monitoring

Risk-based monitoring is a approach to monitoring the quality of a clinical study that focuses on identifying and addressing potential risks to the study. This approach involves regularly assessing the risks associated with a study and implementing strategies to manage or mitigate those risks.

In a risk-based monitoring approach, the study team typically uses a risk register to identify and assess potential risks to the study, such as the potential for errors in data collection or analysis, or the potential for adverse events in study participants. The team then develops a plan for addressing these risks, which might involve implementing additional quality control measures or training for study staff.

During the study, the team regularly monitors for potential risks and takes action to address them as needed. This might involve conducting regular audits or reviews of the study data to identify potential errors, or monitoring the health and well-being of study participants to identify and address any adverse events.

Overall, the goal of risk-based monitoring is to ensure the quality and integrity of a clinical study by proactively identifying and addressing potential risks. By using a risk-based approach, the study team can help to ensure that the study results are reliable and can be used to inform clinical practice.

Risk Register

A risk register is a document that is used to identify, assess, and track potential risks in a clinical study. It typically includes a list of identified risks, along with information about their likelihood and potential impact, as well as the actions that are being taken to manage or mitigate the risks.

In a clinical study, a risk register might include risks such as the potential for errors in data collection or analysis, the potential for adverse events in study participants, or the potential for the study to be impacted by external factors, such as changes in regulatory requirements.

The purpose of a risk register in a clinical study is to help the study team identify and prioritize potential risks, and to develop strategies for addressing them. By having a clear and comprehensive overview of the risks that a study is facing, the team can take proactive steps to manage or mitigate those risks, and can monitor their progress over time.

Overall, a risk register is an essential tool for managing risks in a clinical study. By providing a clear and comprehensive overview of potential risks, it helps the study team identify and address risks in a proactive and effective way.

Identifying potential risks: The first step in implementing a clinical risk management program is to identify potential risks to the study, such as the potential for errors in data collection or analysis, or the potential for adverse events in study participants. This might involve reviewing the study protocol and data collection tools, consulting with the study team and other stakeholders, and conducting a thorough assessment of the study environment.
Assessing risks: Once potential risks have been identified, the next step is to assess their likelihood and potential impact. This will help to prioritize the risks and determine the appropriate level of response. For example, a risk with a high likelihood and a high potential impact might require more immediate action, while a risk with a low likelihood and a low potential impact might not require as much attention.
Developing strategies for managing risks: Based on the assessment of risks, the next step is to develop strategies for managing or mitigating those risks. This might involve implementing additional quality control measures, providing training to study staff, or conducting regular audits or reviews of the study data. The goal is to develop a comprehensive and effective plan for addressing the identified risks.
Monitoring for potential risks: Once the risk management plan is in place, it’s important to regularly monitor for potential risks and take action to address them as needed. This might involve conducting regular audits or reviews of the study data, or monitoring the health and well-being of study participants. By proactively monitoring for potential risks, the study team can help to ensure the safety and well-being of study participants, as well as the integrity and reliability of the study data.
Follow-up and corrective action: If potential risks are identified during the study, it’s important to take prompt action to address them. This might involve implementing corrective action plans, such as retraining study staff or revising the study protocol. It’s also important to track the progress of these plans and ensure that they are effective in addressing the identified risks. By taking timely and effective action to address potential risks, the study team can help to ensure the safety and well-being of study participants, as well as the integrity and reliability of the study data.

Risk Management in the Clinical Study Process

To summarize, each clinical study should:

Identify Risks

Before the study begins, the sponsor should perform a thorough review of the study protocol, data collection tools, and other study-related documents to identify potential risks to the study.
The cross-functional study team, CROs and other relevant stakeholders, such as the sponsor and regulatory authorities, to identify additional potential risks.
All identified risks should be documented in the study’s risk register.

2. Assess Risks

For each identified risk, assess its likelihood and potential impact on the study.
The risks should be prioritized based on their likelihood and potential impact, with a focus on the highest-priority risks.

3. Manage Risks

For each identified risk, the sponsor should develop a plan for managing or mitigating the risk. This plan should be documented in the study’s risk register.
The plan for managing or mitigating each risk should include specific actions to be taken, as well as the individuals or groups responsible for implementing those actions.

4. Monitor Risks

Regularly monitor key risk indicators and the study for success of the study risk plan and to identify new potential risks and take action to address them as needed. This might involve conducting regular audits or reviews of the study data, or monitoring the health and well-being of study participants.
Any significant risks that arise during the study should be reported to the sponsor and relevant regulatory authorities.

AI Can Create Value, but Only If You Bring Employees Along

Great article in HBR by Behnam Tabrizi and Babak Pahlavan “Companies That Replace People with AI Will Get Left Behind” that makes excellent points about how companies should be looking for AI to free up employees to create new value, and not to replace employees.

Automation has been a truism throughout my career. Organizations that leveraged that automation to create value were superior to the ones which used that automation as an excuse to cut jobs.

The Challenges Ahead for Quality

As we move oh so quickly to dealing with the impact of hyper-automation on our organizations it is important to have a vision and a strategy. Apply quality principles, and remember to drive out fear through the strategic execution.

Quality vs Quality

The word quality is a loaded word in organizations, and I’m sure most of my readers have been in a least one major discussion that has felt like an Abbott and Costello routine.

The difference between “quality” and the “Quality department” is that “quality” refers to the overall level of excellence or excellence in a product, service, or process, while the “Quality department” is part of an organization that is responsible for ensuring that the organization’s products, services, or processes meet certain quality standards.

In other words, “quality” is a general concept that refers to the level of excellence or excellence in something, while the “Quality department” is a specific part of an organization that is responsible for managing and improving the quality of that organization’s products, services, or processes.

The Quality department typically plays a key role in ensuring that an organization’s products, services, or processes meet the required quality standards. This might involve activities such as conducting quality assurance audits, implementing quality control measures, or providing training and support to help employees understand and comply with quality standards.

Overall, the difference between “quality” and the “Quality department” is that “quality” is a broad concept that refers to the overall level of excellence or excellence in something, while the “Quality department” is the specific part of an organization that is responsible for managing and improving the quality of that organization’s products, services, or processes.

In FDA-regulated industries, this continues to be a stressful point. We have some regulations that specifically call out the Quality Unit or Quality Control (a different point of fun), while others provide quality expectations that may or may not be the responsibility of the Quality Unit, depending on the way your organization is built.

Add to this that quality is a culturally sensitive term. It gets to the heart of what people consider integral to themselves. That they have quality in their work. And there can be gaps between people’s perceptions and the reality of the organization. The whole concept of what quality is in an organization gets to three central aspects:

Role Conception: what people think their jobs are and how they have been trained to perform them
Role Expectation: what others in the organization think another person’s job is and how it should be carried out
Role Behavior: what people actually do in carrying out their job

So we have quality as a set of habits and practices and Quality as a concept of a role within an organization. And the boundaries between the two can be contentious. Add in the quality control layer (and how quality control does not require a department called quality control) and we can have a whole fun set of arguments.

This post was brought to you by me being in a meeting where someone referenced a version of the golden triangle and I instantly wondered what work someone else was trying to foist off onto me.

4th GxP Cloud Compliance Summit – September 5-7

I am looking forward to speaking at the GxP Cloud Compliance Summit in Boston in September on Implementing a Lifecycle Risk Management Approach to the Cloud. I’ll be discussing some of my favorite topics:

Best practices to harness a life cycle risk management approach to protect product quality and patient data
What does a living risk assessment look like when key parts of your IT infrastructure is maintained by cloud service providers
How does Q9 R1 impact functional and usage assessments around cloud applications

I am looking forward to meeting and discussing some of the critical questions in our heady embrace of the cloud.

Cloud based GxP systems have shifted in the last few years from “Something I guess we should figure out” to “Well guess we have it now” to “Well that is all I seem to have now.” And where 5 years ago it seemed we were obsessed about the fine details of Open vs Closed systems and what cloud-based applications are, we are now looking at much more mature questions around a risk based strategy that evaluates and ensures appropriate controls around Data Integrity, Privacy, and Security. Through a risk-based approach, we drive activities such as auditing, change control, qualification/validation, and oversight.

I am looking forward to having this discussion with my peers and sharing best practices and experiences. It is only though this type of event that we can grow as a professional.

I hope to see you there.

Build Your Knowledge Base

Engaging with knowledge and Knowledge Management are critical parts of development. The ability to navigate the flood of available data to find accurate information is tied directly to individuals’ existing knowledge and their skills at distinguishing credible information from misleading content.

There is ample evidence that many individuals lack the ability to accurately judge their understanding or the quality and accuracy of their performance (i.e., calibration). To truly develop our knowledge, we need to be engaged in deliberative practice. But to truly calibrate requires feedback, guidance, and coaching that you may not have access to within our organizations. This requires effort and deliberate building of a system and processes.

Information can be found with little mental effort but without critical analysis of its legitimacy or validity, the ease of information can actually work against the development of deeper-processing strategies. It is really easy to go-online and get an answer, but unless learners put themselves in positions to struggle cognitively with an issue, and unless they have occasions to transform or reframe problems, their likelihood of progressing into competence is jeopardized.

Creative teams

The more learners forge principled knowledge in a professional domain, the greater their reported interest in and identity with that field. Therefore, without the active pursuit of knowledge, these individuals’ interest in professional development may wane and their progress toward expertise may stall. This is why I find professional societies so critical, and why I am always pushing people to step up.

My constant goal as a mentor is to help people do the following:

Refuse to be lulled into accepting a role as passive consumers of information, striving instead to be active producers of knowledge
Probe and critically analyze the information they encounter, rather
than accepting quick, simple answers
Forge a meaningful interest in the profession and personal connections to members
of professional communities, instead of relying on moment-by-moment stimulation and superficial relationships

Competence

If we are going to step up to the challenges ahead of us, to address the skill gaps we are seeing, we each need to be deliberate in how we develop and deliberate in how we build our organizations to support development.