Effective Risk Management Planning

Biweekly Post 2 of the weekly newsletter:

Risk management is about recognizing the unique characteristics of each clinical trial and embracing consistent documentation, stakeholder ownership, best practices informed from experience, and best practices.

It is clear that clinical studies, which are already challenging, are becoming more difficult in terms of patient recruitment and regulatory compliance.?-- and also longer and more complicated.?Instead of being burned by this fire, organizations that are forged in it strive to run high quality studies, be vigilant in risk management and implement processes that prevent data loss or adverse events from affecting the entire study.

Risk management is at the core of all this effort. It involves anticipating study risks and devising mitigation strategies to try to reduce, eliminate or accept those risks.?Risk management encompasses the entire life cycle of clinical trials.?It requires stakeholders to identify and calculate the risk associated with critical study processes.

The industry and individual studies are constantly changing their risk management plans.?Some things that are currently part of every organization's risk management plan may not be considered all the time (e.g. pandemics), and some items previously considered to be risks are sometimes phased out.

Risk management and risk-based surveillance, which are often confused as one and the same, can be distinct activities.?While risk-based monitoring includes some elements of risk management, it is focused more on the monitoring of your clinical trial.

REVISE AS SOON AS APPROPRIATE

Prior to trying to prioritize and identify the risks that you want to avoid, it is important to identify key stakeholders.?Based on the purpose of the project, able project managers have already identified their key stakeholders. Who will have an impact on the clinical research??This is an important tenet in basic risk management.

The task of the project manager is to gather all major voices (medical monitors, data managers, clinical supply staff, safety personnel, and so on) in the room.?Not only is the primary role to gather the necessary voices (medical monitor, data manager, clinical supply staff, safety personnel, etc.), but also additional roles (clinical quality assurance and monitors, representatives of sites that might be involved in the research) -- people who may not be present throughout the project's life cycle but whose perspectives and risk assessments should still be taken into consideration.?The logistical challenges associated with this effort shouldn't be significant. Each member of the clinical trial team must communicate regularly to ensure the trial runs smoothly.

Because of the current pandemic, and the reality of the operations being conducted practically simultaneously, not everyone has to be in the same room or communicate simultaneously.?Are there any team members who missed whiteboard discussions about critical data points, critical process, or clinical supply??You can send the information to those individuals and ask for detailed feedback.?Many organizations have established procedures for recording and capturing input from team members.

Each step of the risk management or risk monitoring process must adhere to the life sciences adage "If it's not documented, it didn’t happen." This is true from the beginning of the clinical study process. It must be reviewed and updated throughout.

Instilling the notion that everyone in a well-conducted study takes responsibility for quality control and risk management is crucial.?Every step should be documented and accompanied with questions (e.g. What is the risk??This is a risk that we should add to our risk list??This ownership increases compliance documentation by showing regulators that you have thought through all possible outcomes and prepared contingencies and mitigations when necessary.

At the beginning of any study, the greatest risk management problem is the temptation to rush.?Be patient and don't rush.?The study team will be prepared for all possible risks by meticulously planning and executing a risk-management plan from the beginning.

Some executives might want to move at a speed that is too fast, which can lead to system breakdown or hindering its effectiveness. However, most C-suite executives understand the overall risk and the impact it has on quality and cost.?A study that fails to have a comprehensive risk management plan can often be rescinded.

It is a good idea to begin with the relevant regulations and guidance documents from ICH , FDA E6 EMA, MHRA -- all these document discuss risk management.?Notably,?FDA, EMA?and?MHRA?all issued updated guidance documents pertaining to clinical trial risk management in the COVID-19 pandemic.

STUDY RISKS AND LEARNING OUT OF EXPERIENCE

Prioritizing risks should be done according to the golden standard for likelihood, impact, detectability, and detectability.?This method is well-known for assessing and scoring standard risk areas such as protocol deviations, subject retention, data entry timelines, and data entry times.

You don't want every risk to be included in your initial risk management plan.?You should limit your risks to the most important concerns.?It may be difficult for you to follow the entire plan if there are too many risks.?This central list is kept up-to-date in the trial master (TMF) by reviewing the risks regularly throughout the clinical study.

Study size and composition are key factors in determining the extent of initial risks and frequency of updates.?How many people are involved and what characteristics define the population, for example??Are you a Phase 1 or Phase 5 study? If so, monthly updates may be necessary. However, quarterly updates could be sufficient.

The COVID-19 pandemic is a prime example of this.?Although the pandemic was impossible to predict, a flexible risk management plan would allow for new challenges.?Studies have had to adapt to unexpected adverse events such as pandemics and protocol deviations.?There are many scenarios that could be addressed by risk management measures such as the planning for shipping medication to patients or alternate locations.

When the COVID-19 pandemic broke out, organizations with strong risk management plans had a framework and a platform from which to quickly implement mitigations.

A periodic risk review is a way to prioritize risks that are not relevant to your study. For example, an enrollment criterion which presents a risk must be removed once enrollment has been completed.?Recalling the COVID-19 example of a pandemic, organizations might discover different severity levels and risk factors associated with the virus' impact and likelihood.

TransCelerate Risk Assessment Categorization Tool, MCC Risk Assessment & Mitigation Tool (RAMMT), as well as similar tools, allow study team members to identify, document, and measure the risk associated with a study protocol as well as create a risk-monitoring program.?This plan includes critical processes, critical data and source data review strategies. It also contains key risk indicators.

These tools can be used to build a solid foundation for a company's risk management program. Organizations can also modify these tools (e.g. how they capture information) to suit their needs and match their processes.?While there are no regulations governing the use of these tools they do meet regulatory expectations.

A company might start risk management by looking at key data and processes.?All aspects of the scan are critical if the study involves an imaging agent.?All risks related to blood draws (e.g., bleeding or bruising), must be considered.?This analysis generates a list listing all possible risks. Then, the risk is reduced by likelihood, impact and detectability. Will risk X have an impact on a specific end point or cause a minor protocol deviation?

An organization can build a risk library to benefit from the combination of all these activities. This allows stakeholders to record their experiences and make it easier to manage risk as they grow.?Although a risk library contains common risks, you can add more as you identify and assess how they may affect your study.?It is a starting point for teams, but it should not be considered exhaustive. Each study is unique, so teams need to remain alert in assessing each study's risks.

CONCLUSIONS

Like the clinical studies it successfully executes, risk management has become more complex and dependent on new technologies and job roles.?As important as detailed execution is an early start and the consistent application of sound principles through the entire life cycle of a clinical study. Risk management that is applied retroactively rarely, or ever, results in positive outcomes.?A team that is focused on the most important concerns and a commitment to quality are the keys to successful risk management initiatives.