Since ICH-GCP (or officially, ICH E6 R1) was first drafted more than 20 years ago, the complexity of clinical trials has increased, with the design of trials, technology use, and data quality and collection changing to the evolving face of research.
The first update to ICH-GCP (r2) was published in 2016 and focused on a risk-based approach to clinical trials and their design and conduct. However, since the publication of this update, clinical trials have continued to evolve with new designs and technological innovations. The upcoming update of ICH GCP (Good Clinical Practice), the E6(R3), will be designed to advance the concept of risk-based approach further and encourage relevant parties to utilize it.
In Part 1 of this series, we will talk about the overall changes expected in ICH-GCP R3, and in Part 2, we will explore the changes to the annexes.
ICH-GCP R3
In 2024, the latest version of ICH-GCP guidelines is expected to be published. R3 will see the guidelines split into three parts:
- Principles
- Annex I
- Annex II
This restructure has been developed with the intention that the GCP guidelines, in addition to drug research (Annex I), will also apply to other types of clinical research (Annex II) and focuses more on the most essential principles and objectives (the principles). Novel trial methods and technological innovations are also included.
This update will strengthen the current approach to clinical trials in medicines to support regulatory and healthcare decision-making. But what changes have been made to the guideline since R2, and what will each part cover? Let us look.
Introduction
We see a few amendments with the introduction, the most noticeable being “conduct.” This is an umbrella term to cover an expanded overview of the guidance. We also see changes in the administration of ICH membership and outlining the structure of the new guidelines.
The guideline still has a core focus on clinical trials, supporting application to regulators, but clarifies how the guideline applies to trials that are not for medicinal products, and local requirements.
Principles
The principles of ICH GCP still place importance on clinical trials, and their place in answering the questions that are raised in drug development, and how poorly designed and conducted trials may provide unreliable information, waste resources and be unsustainable, or not be conducted ethically.
The primary focus of this guidance is to safeguard the rights, safety, and well-being of trial participants while ensuring the reliability of trial results. Achieving this objective entails meticulously considering risk mitigation and the various processes influencing these critical factors. To accomplish this, a quality-by-design and risk-based approach will be implemented, ensuring that the level of protection is proportional to the potential risks involved. The guidance builds upon the addendum and underscores the importance of tailoring its application to each specific trial, thereby ensuring a balanced and appropriate implementation.
The principles themselves have been extensively expanded, incorporating existing guidance with minor change.
Examples of changes:
- Four current principles (2.1(trials to be conducted in alignment with the Declaration of Helsinki, 2.2 (foreseeable risks and inconveniences should be weighed against the anticipated benefit ) , 2.3 (rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society) and 2.7 (medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist) ) have been incorporated into the new principle 1. This includes also new expectations for review of safety information periodically and the delivery of medical care and decisions that concern patients can be undertaken by other qualified healthcare professionals (current guidance only includes physicians and dentists), opening the pathways for decentralized clinical trials, amongst other innovative clinical trial design.
- Periodic or new information review during trial conduct is strongly advocated in the new R3 principles, determining whether modifications are needed to the trials and for risk assessment.
- An interesting change is that the current principle 2.13 (Systems with procedures that assure the quality of every aspect of the trial should be implemented) has not been included, and a whole new set of principles are set out in section 6, 7 and 9. The main focus of these principles involves identifying crucial factors that are essential for qualification and ensuring a well-executed trial that facilitates informed decision-making. The emphasis lies on areas that go beyond standard medical care. It is important to ensure that processes, data capture, and management are aligned with the trial’s objectives, feasible to implement, free from unnecessary complications, and appropriate in safeguarding the safety, rights, and well-being of participants while ensuring the reliability of the trial outcomes.
- Principle 2.1 has been revised to include efficiency in record management and data integrity, ensuring that records are retained and available to regulators
- Transparency in clinical trials is also emphasized, with public registration of trials and publication of results encouraged. (For example, aligning with the EU CTR)
- A new principle covers the role of sponsors and investigators and their responsibilities.
The changes are comprehensive, and expand on the changing needs of clinical trials, especially in alliance with the rising profile of decentralized clinical trials.
Summary Part 1
As you can see, the upcoming changes to ICH-GCP in R3 are quite comprehensive, adding much more clarification to the design and conduct of clinical trials, in alignment with the evolution of clinical trials. More clarity has been given to the conduct of decentralized clinical trials, and a broader definition given to the professionals who can make medical decisions and provide care to trial participants.
Part 2 of this series will see us explore the changes to the annexes, and how this will impact clinical trials from their adoption.
If you would like to explore the changes proposed in R3, you can click the link to the official website here.
If you are in need of ICH-GCP training, explore the range of training options offered by GCP Central here. As updates are made to the guideline, you’ll be able to keep up to date with the changes via our learning system and stay compliant on the go.
