How Quality by Design Can Help Pave the Path Forward for Clinical Trials in a Post-COVID World

One of the major barriers facing clinical trials is poor trial design, which can lead to incomplete data sets, an expensive trial process, and ultimately contribute to a trial’s failure.

This is why drug developers and CROs are focusing on risk-based monitoring, utilizing the quality by design principles as outlined in ICH E6 R2, a 2016 update to the Good Clinical Practice Guidelines.

ICH E6 R2 Quality by Design Principles

The revisions in the amendment mainly affect sponsors, stipulating a more proactive approach to study design, risk management and study monitoring. Currently sponsors conduct multi-site international clinical trials, but repeating trials in different markets to comply with different regulations is inefficient and leads to delays in delivering new drugs to patients.

By “baking” quality into the process, trials can be continually monitored to achieve optimization; this standardization leads to greater efficiency.

We’ve all seen just how much the world has changed over the last six months. The pandemic has upended our way of life and many trials have been cancelled or delayed. The benefits of improving trial design cannot be overstated!

First things first, let’s look at the main reasons for low quality trials:

• Inadequate staff training
• Lack of protocol clarity leading to poor understanding of what is required
• Lack of management supervision or quality control of required tasks during the study
• Reduced quality control over collection and recording of study data
• Problems with patient recruitment, enrollment and retention

Enter Quality by Design

Clinical trial quality relies on having an investigational plan with solid objectives and outcome measures. Quality by Design (QbD) emphasizes building quality into the process from the beginning.

Initially introduced in the early 1990s, the approach focuses on identifying Critical to Quality (CTQ) key data and trial processes. By understanding the factors that are CTQ, risks can be managed effectively.

QbD allows for risk and knowledge-based decisions and continuous improvement. It is a systematic approach to development that starts with predefined objectives and emphasizes product and process understanding and control, based on sound science and quality risk management.

Risk-based thinking can be broken down into two main aspects:

1. Defining what is critical to success. What matters most? Patient safety and data reliability are crucial.
2. Managing the elements of the clinical trial. It is vital to continually evaluate, control, communicate, review and report risks.

So, how can we ensure success when combining these two concepts?

• Study set-up is key. Setting the team up for success begins with identifying what is critical to succeed along with processes that have an impact on patient safety and data reliability. This requires a rigorous review of the protocol by cross-functional teams. In addition, it's vital that key critical to quality indicators are developed with the appropriate thresholds identified as early as possible. De-risking the protocol incorporates the quality by design philosophy and ensures risk is managed proactively.

• Continuously review the study. Once the risks have been identified and CTQ indicators with thresholds have been established, the process needs to be managed. Utilizing the QbD approach requires a continuous review of the study throughout the study lifecycle.

PDCA Cycle Method

One method of doing this is by using the four-step management method used in business – PLAN, DO, CHECK, ACT – or PDCA cycle method. PDCA is an iterative four-stage approach to improve processes, products and services in order to resolve problems. It was originally developed by renowned management consultant Dr. William Edwards Deming in the 1950s.

His focus was on identifying what caused products to fail to meet customer expectations and predicting the results of an improvement effort, by constantly comparing results to revise the theory. This very practical approach is used today to help businesses develop hypotheses about what needs to change and test them in a continuous feedback loop.

Let’s take a closer look at how the PDCA cycle can be used to improve QbD in clinical trials:

Risk Management: Everyone’s Responsibility

This risk management process requires that every department and individual must be responsible for the delivery of the product – in this case the clinical trial. Here are a few ideas on how to do this:

• Manage customer’s expectations early. This involves asking the right questions, such as what does success look like? Understanding this will enable the team to create a systematic process to build in quality that will enable the task to be more achievable. If quality is ignored, this result will be much more costly than evaluating on an ongoing basis.
• Utilize best practices and lessons learned to avoid similar issues throughout the study. These reviews highlight issues that have occurred, the root causes of these issues, and the actions that were implemented to resolve the issue. Why not draw upon these experiences to avoid the same?
• Risk management throughout the study is vital. This willensure that the pre-identified risks are monitored and managed with expediency. Also, this is a continual process, and the risks can change during the study. Quality needs to be managed at a micro-level and early detection is priority.
• Communicate clearly and often. Transparency allows for issues to be addressed thoughtfully and thoroughly. This way, clinical teams can avoid miscommunication and delayed resolutions to tackle issues.

Trial Quality in a Post-COVID World

In the wake of the pandemic, trial quality is going to be of utmost importance to help clinical trials get back on track. We have seen considerable improvement when it comes to the uptake of new technologies in order to manage trials during the pandemic, solutions which can help expedite risk-based management processes.

But it’s important not to get complacent because there is still a long way to go. Despite the introduction of the ICH E6 R2 amendment in 2016, just 18% of new studies applied a risk-based approach to monitoring that very same year. Although this improved by 2018, jumping to 61%, industry-wide adoption has been slow to date. And even though clinical trials are modernizing due to the restrictions ushered in by the pandemic, old habits die hard.

However, I remain optimistic. I believe the years ahead will see a rush to implement Quality by Design into clinical trials because COVID-19 has been a wake-up call for the industry. We can no longer ignore the pressing need to build quality into the clinical trials process.

Andrea Parish

Quality Assurance Leader

Guest

Andrea is an accomplished leader with 22 years of comprehensive experience in the clinical research industry. A conscientious planner and manager of all aspects of customer expectations, she has a proven ability to lead teams to achieve focused results and creative solutions.