ICH E6(R3), a significant development on the regulatory horizon, is a revision to the International Council for Harmonization’s guidelines for Good Clinical Practice and is slated for release in August 2023.

As the healthcare industry continues to evolve, it’s important for researchers and clinicians alike to stay informed on regulatory changes that could impact their work.

In this blog, we have highlighted what you need to know about these new standards and how you can prepare yourself and your team for success in the era of modern clinical research.

What is the ICH, and Why Does it Matter?

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is a critical organization that helps ensure the safety, efficacy, and quality of pharmaceuticals on a global scale. By promoting consistency and reducing duplication in the development and registration of medicines, the ICH plays a key role in facilitating access to safe and effective drugs for patients worldwide.

With the pharmaceutical industry expanding rapidly and operating in an increasingly interconnected global marketplace, the work done by the ICH has never been more important. By bringing together regulatory authorities and the pharmaceutical industry in a collaborative effort to develop harmonized guidelines, the ICH ensures that pharmaceuticals are developed, tested, and registered in a consistent and efficient manner, regardless of the geographical region.

This ultimately leads to faster patient access to lifesaving and life-improving treatments, making the ICH a vital part of the modern healthcare ecosystem.

What is ICH E6?

The ICH E6(R2) Good Clinical Practice (GCP) Guideline, as released in 1996, serves to provide guidance on how to conduct clinical trials safely, effectively, and in compliance with regulatory requirements. This guideline sets clear expectations and responsibilities for all stakeholders involved in a clinical trial – Investigators, Monitors, Sponsors and Institutional Review Boards (IRBs). It covers essential aspects such as monitoring, reporting and archiving practices and also includes addenda related to essential documents and investigator’s brochures.

Now let’s discuss the new changes in ICH E6(R3). While a lot has been reorganized, rewritten, and expanded upon more thoroughly than the previous revision, there are four principles, in particular, we want to take a closer look at.

Principle 7: Integrating Quality into Clinical Trials

“Quality should be built into the scientific and operational design and conduct of clinical trials.”

While the last revision mentioned quality, it did not have the same level of emphasis as the latest edition. ICH E6(R2) states, “Systems with procedures that assure the quality of every aspect of the trial should be implemented.” However, the updated guideline stresses that quality should not be an afterthought but rather a central aspect of both trial design and conduct.

The drafted revision includes sub-points under this principle.

• Quality is defined as being “fit for purpose,” meaning that the information generated during a trial should be sufficient to support good decision-making.
• Critical factors that are essential for protecting participants ensuring the reliability and interpretability of the trial results, and informing decisions based on those results should be identified and prioritized.
• The guideline encourages organizations to adopt a Quality by Design (QbD) approach throughout the clinical trial and supporting processes.

By incorporating quality principles into every aspect of the trial, organizations can improve the reliability and interpretability of trial results, protect participants, and make more informed decisions based on those results.

 

Principle 8: Proportional Approach to Clinical Trials

“Clinical trial processes, measures, and approaches should be proportionate to the risks to participants and to the reliability of trial results.”

This new principle is aimed at “working smarter, not harder” in clinical trial processes and keeping with the theme of risk management.

One of the guideline’s sub-points focuses on the need to prioritize risk-based approaches throughout the trial design, identifying risks to participant rights, safety, well-being, and the reliability of trial results. By prioritizing critical data at the outset, it will allow trials to run more efficiently while still maintaining an emphasis on safety. The document also notes that risks beyond those of standard medical care should be the focus of considerations and offers guidance on managing risks that impact critical quality factors.

Overall, it offers a useful framework for ensuring that clinical trial processes are proportional to participant risks and the importance of collected information.

Principle 10: Reliable Results in Clinical Trials

“Clinical trials should generate reliable results.”

Immediately your first thought is probably, “Isn’t this something we already do?” While this is true, this principle and its sub-points expand past the focus from the closest, existing principle, “Ensure all data is recorded and can be verified,” to focusing on reliable results.

The first two sub-points in this principle state that “The quality and amount of the information generated in a clinical trial should be sufficient to provide confidence in the trial’s results and support good decision making” and “Systems and processes that help ensure the quality of the information generated from the clinical trial should be implemented in a way that is proportionate to the risks to participants and the reliability of trial results.”

This new principle of generating reliable results complements the other updates. Unlike the previous ICH E6 standards, the new revision no longer requires monitors to review all data. Instead, researchers must prioritize collecting and monitoring the data necessary for regulatory agencies to make scientifically sound decisions.

Principle 11: Who Does What in Clinical Trials

“Roles, tasks and responsibilities in clinical trials should be clear and documented appropriately.”

“Again, we do this.” And again, you’re not wrong, as ICH E6(R2) states that individuals running the trials are fully qualified to perform the tasks they’re in charge of. However, ICH E6 (R2) only talks about physicians and dentists, while R3 includes “physicians, scientists, ethicists, technology experts, and statisticians.”

While doctors are still a vital and necessary component of clinical trials, this inclusion within R3 allows for even better avenues for trials, especially decentralized or hybrid trials that rely on continually evolving technology. This will ensure that those at physician offices understand what their roles are versus the research site staff.

How to Prepare for the Future

The implementation of ICH E6(R3) principles represents a significant change in the clinical trial industry, as it calls for a more proactive and strategic approach to trial design and management.

To meet these new standards, organizations must adapt by identifying critical quality factors related to patient safety and the validity of trial results. This requires a shift from a reactive approach to monitoring trial quality to one in which quality is built into the design of the trial from the outset.

One key tool for achieving this is Quality by Design (QbD), which has become the new gold standard in trial design. QbD approaches should be applied to both the clinical trial itself and supporting processes, ensuring that quality is ingrained throughout the entire lifecycle of the trial.

Organizations should also employ risk-based approaches to trial management and monitoring, which will help to expedite the process whilst maintaining patient safety and the validity of results.

Data integrity remains a crucial component of any clinical trial, and ICH E6(R3) emphasizes the importance of taking a more holistic approach in examining how reliable the results of trials are on a larger scale. As such, organizations must ensure that roles, tasks, and responsibilities are clearly defined for all stakeholders in the trial and that they are equipped with the necessary tools and training needed to fulfill their respective duties effectively.

Ultimately, mastering ICH E6(R3) principles requires a strategic mindset and a great deal of preparation when addressing the design and conduct of trials. However, by taking a proactive and strategic approach towards trial design and management, organizations can ensure that they are fully compliant with the new standards while improving quality, efficiency, and patient safety across their clinical trial programs.

Author: Katherine Blount, Quality and Compliance Services

Our experienced and knowledgeable team can help assess and get you in compliance with these changes that are just around the corner. Email info@mmsholdings.com to be connected to a quality and compliance expert.