Clinical trials are the cornerstone of medical advancements, enabling the development of new treatments and therapies. However, as global scientific knowledge and ethical standards evolve, so too are the regulations governing these trials. In 2024 and 2025, significant changes have been or will be made to several key regulatory frameworks that shape clinical research. These updates, including among others the Declaration of Helsinki, the WHO best practices for clinical trials, ICH E6 GC, FDA Guidance documents, EMA GCP Questions & Answers, and Swiss regulations, highlight the increasing complexity of clinical trial governance.
Pharmaceutical and biotech companies, especially those involved in global trials, must stay informed and compliant with these updates, summarized below.
Declaration of Helsinki – Amended version October 2024
The Declaration of Helsinki, a foundational document that sets ethical principles for medical research involving human subjects, has undergone significant revision in October 2024. These updates, driven by the World Medical Association, emphasize the importance of safeguarding vulnerable populations in clinical trials and ensuring that their participation is voluntary and informed.
The 2024 revision introduces more detailed guidelines for ensuring the informed consent of participants, especially in regions where literacy or language barriers could complicate the process. Additionally, it strengthens requirements for post-trial access, mandating that trial participants, especially in low- and middle-income countries, have access to the treatment being studied if it proves beneficial.
This revision aims to address growing concerns about inequities in global clinical trials and ensure that research is conducted with the highest ethical standards, irrespective of the geographical region.
WHO Best Practices for Clinical Trials: September 2024
In September 2024, the World Health Organization (WHO) released updated guidance on best practices for clinical trials to improve the design, conduct and oversight of clinical trials in countries of all income levels.
The WHO's 2024 update places particular emphasis on the use of digital technologies in clinical trials. From electronic informed consent (eConsent) to remote monitoring, these guidelines recognize the increasing role of technology in making trials more efficient and accessible. There is also a focus on diversity and inclusion in trial populations, encouraging sponsors to design trials that reflect the diversity of the real-world populations likely to use the therapies being studied.
Another major theme in the updated guidance is the importance of data sharing and transparency, particularly in the context of public health emergencies like the COVID-19 pandemic. The new guidelines will push for faster sharing of trial data to ensure that the global research community can act quickly in response to emerging health crises.
ICH GCP E6 (R3) Update: A Major Revision in the Making
The most significant upcoming regulatory change is the long-anticipated update to the ICH GCP E6 (R3) guidelines, expected in 2025. Good Clinical Practice (GCP) is a set of internationally recognized ethical and scientific quality standards for the design, conduct, and recording of clinical trials. The E6 (R3) revision will be the most comprehensive update to GCP since its initial adoption and will fundamentally reshape how trials are conducted globally.
One of the most notable changes in this revision is the adoption of a risk-based approach to trial monitoring, which allows for more flexibility in how sponsors monitor trial sites. This shift acknowledges that a "one-size-fits-all" approach is no longer feasible, particularly in large, multinational trials. Instead, monitoring strategies will be tailored to the risk profile of each trial, with an emphasis on protecting participant safety and ensuring data integrity.
The integration of digital tools into the trial process is also a central theme of the E6 (R3) revision. This includes more robust standards for electronic records and data management, ensuring that new technologies like artificial intelligence (AI) and blockchain can be integrated into trial design while maintaining regulatory compliance.
Finally, the revision will enhance the role of patient-centric approaches in trial design, recognizing that involving patients more actively in the process can improve both trial participation and the relevance of study results.
FDA Guidance on Conducting Clinical Trials With Decentralized Elements, September 2024
The guidance offers detailed recommendations for incorporating decentralized elements into clinical trials. These trials involve conducting certain trial activities outside traditional clinical sites, utilizing tools like telehealth, in-home visits, and digital health technologies (DHTs). The aim is to enhance participant accessibility, improve diversity, and streamline trial operations by allowing patients to participate from their homes or local settings.
Key highlights of the guidance include:
- Sponsor Responsibilities: Sponsors are accountable for ensuring trial quality, data integrity, and compliance, even when trial activities are decentralized. This includes managing remote interactions, monitoring the use of investigational products, and ensuring accurate data collection.
- Risk Management: The FDA emphasizes the need for risk-based monitoring (RBM) and centralized monitoring systems to ensure consistency and safety in remote trial operations. These tools help identify data discrepancies and manage patient safety remotely, especially in cases where adverse events may occur away from traditional sites.
- Digital Health Technologies: The guidance advocates for the use of validated and accessible DHTs, such as wearables, to enhance data collection. Sponsors are advised to ensure all participants have the necessary technology and support to engage fully in the trial.
- Patient-Centric Focus: The FDA encourages a patient-centric approach, where trials are designed to reduce the burden on participants, making it easier for them to engage and comply, while still maintaining the necessary regulatory and safety standards.
FDA Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers, October 2024.
Key points include:
- Trustworthiness and Reliability: The guidance emphasizes that electronic records and signatures must be considered trustworthy, reliable, and equivalent to paper records and handwritten signatures. This is critical for maintaining data integrity in clinical trials.
- Compliance: It outlines the regulatory requirements and best practices for ensuring electronic systems used in clinical trials comply with FDA standards, including aspects such as system validation, audit trails, and data security.
- Electronic Signatures: The FDA provides clarity on the use of electronic signatures, reinforcing that they should meet the requirements of 21 CFR Part 11 to ensure their validity in legal and regulatory contexts.
EMA GCP Question & Answer # 19, January 2024: What are the expectations for distribution of Updated Investigator’s Brochures (IBs) and updated Informed Consent Forms (ICFs) to clinical sites / Investigators?
The Q&A emphasizes that updated Investigator's Brochures (IB) with substantial changes must be promptly distributed to clinical sites and investigators after receiving approval from the competent authority and a favorable ethics committee opinion, where required. It's not acceptable to delay distribution until approvals are obtained in all EU Member States or for all trials.
Sponsors must consult separate guidelines for the start of the use of new Reference Safety Information (RSI) based on the applicable legal framework, but this shouldn't delay IB distribution. Delays in submitting substantial amendments, including updated RSIs, to all Member States simultaneously are discouraged, as they prolong the distribution of critical safety information.
Similarly, revised Informed Consent Forms (ICF) should be distributed immediately after receiving the necessary approvals. Delays in distributing updated ICFs are considered non-compliant with Good Clinical Practice (GCP), as they risk participants not being adequately informed.
Upcoming Changes in Swiss Clinical Trial Regulations
In line with ongoing international efforts to modernize clinical trial regulations, the Swiss government will introduce two key updates to its clinical trial regulations in November 2024 and March 2025.
The November 2024 update will streamline the clinical trial approval process, with a particular focus on enhancing patient safety and data transparency. This includes stricter requirements for adverse event reporting and an increased emphasis on risk-based monitoring. Swissmedic, Switzerland's regulatory authority, is also expected to enhance its digital infrastructure, allowing for faster submission and review of trial data.
The March 2025 update will align Swiss regulations more closely with the EU Clinical Trials Regulation (EU-CTR) to further facilitate cross-border research collaboration. This alignment is particularly important for Swiss pharma and biotech companies conducting trials across the EU. Changes will include harmonized timelines for ethical committee reviews and mandatory public disclosure of trial results in a transparent and timely manner.
How can you ensure compliance of your clinical trials in this changing regulatory landscape?
The ongoing and upcoming regulatory changes underscore the increasing complexity of the clinical trial landscape. Staying compliant with these new standards is critical for pharma and biotech companies and should include:
- Continuous Monitoring: Have a process to stay updated on evolving regulations.
- Gap Analysis: Perform periodic gap analyses to identify whether your processes are compliant.
- Regular Training: Conduct frequent training sessions to ensure all employees are aware of new regulations and their implications.
- Document Control: Ensure robust document management systems are in place for timely updates of SOPs and protocols.
- Audits and Mock Inspections: Regular audits/Mock inspections ensure ongoing compliance, identifying potential issues before they escalate.
This is where ObelysQ may come in. As a Swiss quality assurance consulting firm with a deep understanding of both local and international regulations, and their impact, ObelysQ is ideally positioned to help pharmaceutical and biotech companies navigate these changes.
We offer tailored services to ensure that your clinical trials are fully compliant with the latest regulations and guidelines, while also helping you optimize your processes for efficiency and risk management. For further information please do not hesitate to contact us.
