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