How Changes To The Declaration Of Helsinki Impact Clinical Trials

By Jessica Cordes, senior consultant, Clinical Excellence GmbH

The World Medical Association (WMA) formulated the Declaration of Helsinki to outline ethical principles for conducting medical research involving human participants, including studies utilizing identifiable human material or data. This Declaration is designed to be read comprehensively, with each paragraph considered in the context of all other relevant sections. Although primarily adopted by physicians, the WMA maintains that these principles should be adhered to by all individuals, teams, and organizations engaged in medical research, as they are essential for ensuring respect and protection for all research participants, encompassing both patients and healthy volunteers.

The latest version, issued in 2024, builds upon the previous version from 2013 with notable updates and revisions.

5 Areas Of Change In The 2024 Update Of The Declaration Of Helsinki

Informed Consent

The 2013 Declaration emphasizes informed consent, requiring researchers to provide detailed clinical trial information, including its purpose, methods, risks, and benefits. Participants must be aware of their rights, including the right to withdraw at any time. Ensuring participants understand this information may involve using simple language and confirming comprehension. Special measures are suggested for vulnerable populations to ensure proper informed consent.

The 2024 version of the Declaration places a greater emphasis on ensuring that participants receive comprehensive and understandable information. This involves several key elements:

• Researchers must provide detailed explanations of the clinical trial's purpose, methods, potential risks, and benefits.
• Information must be communicated in plain language that is easily understood by participants, avoiding technical jargon.
• Researchers are required to verify that participants fully comprehend the provided information, which may involve interactive discussions and assessments of understanding.
• Participants must be informed of their rights, including the right to withdraw from the clinical trial at any time without penalty.

The 2024 version also introduces specific measures to protect vulnerable populations, ensuring that their consent process is handled with extra care:

• Vulnerable individuals, such as those with limited understanding or those in dependent relationships, must receive additional support to fully understand the research and their role in it.
• Consent must be sought by a qualified individual who is independent of any relationship that could influence the participant's decision.
• For those incapable of giving informed consent, such as unconscious patients, consent must be obtained from legally authorized representatives, and research involving these individuals can only proceed if it directly addresses their health needs or if no alternatives exist.
• Special attention is required to ensure that vulnerable participants are included in research only when it serves their best interests and provides them with the potential for personal benefit or entails minimal risk and burden.

Ethical Review

The 2013 version of the Declaration highlights the need for a structured and transparent process within institutions to oversee the ethical aspects of research. Key aspects include:

• Independence: The ethical review committee must function independently of the researchers, sponsors, and any other influence to maintain objectivity and integrity in its evaluations.
• Transparency: The committee's processes and decisions should be transparent to ensure accountability and trust among all stakeholders.
• Qualification: Members of the committee must possess appropriate qualifications and training to competently assess the ethical implications of research proposals.
• Monitoring: The committee has the right to monitor ongoing studies and must receive regular updates, especially regarding any serious adverse events, to ensure continuous protection of research subjects.
• Compliance: The committee must consider national and international ethical, legal, and regulatory standards, ensuring that no requirement diminishes the protections for research subjects outlined in the Declaration.

The 2024 Declaration requires ethical review board members to have relevant qualifications and training to evaluate research proposals ethically. This includes a requirement for:

• Education: Members must have relevant academic credentials or equivalent professional experience.
• Training: Members must participate in ongoing training programs to stay updated on ethical guidelines, legal standards, and scientific advancements.
• Diversity: Members must represent a range of expertise, including medical, ethical, legal, and lay perspectives, to ensure a well-rounded review process.

These requirements ensure the board can effectively evaluate medical research involving humans and emphasize transparency and accountability in the ethical review process.

Key aspects include:

• Independence: The review committee must operate independently from researchers and sponsors to avoid conflicts of interest.
• Transparency: The processes and decisions of the committee must be clear and accessible to all stakeholders, fostering trust and accountability.
• Monitoring: The committee has the right to monitor ongoing studies and must receive regular updates, especially regarding any serious adverse events, ensuring continuous protection of research subjects.
• Compliance: Adherence to national and international ethical, legal, and regulatory standards is crucial, and the committee must ensure that these standards do not diminish the protections for research subjects as outlined in the Declaration.

The enhancements in the 2024 version aim to fortify the integrity and efficacy of ethical reviews, ensuring that medical research is conducted with the highest ethical standards.

Risk-Benefit Assessment

The 2013 Declaration outlines several fundamental principles for conducting medical research involving human subjects, with a strong focus on the thorough assessment of risks and benefits:

• Medical research involving human subjects requires a thorough evaluation of risks and burdens against potential benefits for those involved and others affected by the condition under clinical trial.
• Research should only proceed if its importance justifies the risks and burdens to participants. Researchers must ensure that potential benefits outweigh the risks.
• To minimize risks, appropriate measures should be implemented. The researcher must continuously monitor, assess, and document the risks throughout the clinical trial.
• Physicians can only engage in research if they are sure risks are well-assessed and managed. If risks outweigh benefits or when positive outcomes are seen, they must decide whether to continue, modify, or stop the clinical trial.

These principles ensure that medical research prioritizes the safety and well-being of participants while maintaining a balance where the potential benefits of the research significantly surpass the associated risks.

The 2024 Declaration tightens risk assessment standards for human medical research, enhancing protection for participants and ethical rigor.

The revised Declaration includes detailed guidelines for the thorough evaluation of long-term risks associated with medical research. These guidelines mandate researchers to:

• Conduct comprehensive assessments of long-term risks before initiating research projects.
• Identify potential long-term adverse effects on participants and plan for their management.
• Regularly review and update risk assessments throughout the research.

To further enhance participant safety, the 2024 Declaration requires the implementation of robust risk mitigation strategies, including:

• Developing and enforcing protocols to minimize identified risks.
• Maintaining continuous monitoring and documentation of risks by researchers.
• Ensuring that mitigation measures are adaptive and responsive to new information and emerging risks during the research.

The updated guidelines underscore the responsibility of physicians and other researchers to:

• Ensure that risks are adequately assessed and managed before involving participants.
• Make informed decisions about continuing, modifying, or halting research based on ongoing risk evaluations.
• Prioritize participant safety and well-being throughout the clinical trial.

The 2024 Declaration emphasizes ethical oversight in medical research by introducing strict guidelines for risk assessment and mitigation, ensuring participant protection and research integrity.

Post-Clinical Trial Provisions

The 2013 version of the Declaration establishes a comprehensive framework to ensure the safety and well-being of research participants.

The Declaration requires a thorough risk assessment before starting any medical research involving humans. Researchers must continuously monitor and document these risks, adjusting or stopping the clinical trial as needed based on new evidence.

The Declaration states that research must prioritize the importance of the objective over the risks to participants, considering both immediate and long-term effects on their health and well-being.

The framework highlights the need for effective risk mitigation. Researchers must minimize harm through careful planning and adaptive strategies, including ongoing risk evaluations to adjust measures as needed.

Ethics committees play a crucial role in overseeing risk assessments. Research protocols require review and approval by a qualified ethics committee, which monitors studies to ensure adequate risk management.

The 2024 Declaration significantly advances the ethical guidelines for medical research, especially regarding post-clinical trial obligations. It emphasizes participant welfare even after clinical trials end, detailing plans for post-clinical trial access and care.

The updated Declaration also mandates that researchers and sponsors ensure participants have access to beneficial clinical trial interventions, fostering trust and ethical integrity in research.

Researchers must inform participants about post-clinical trial provisions during the consent process. This ensures participants know what care they will receive after the trial and for how long.

A qualified ethics committee must review and approve post-clinical trial access plans, ensuring they are feasible, well-resourced, and ethical. The committee can also monitor their implementation and ensure compliance.

Sponsors and researchers must arrange post-clinical trial provisions, collaborating with healthcare systems or governments to ensure participants have access to beneficial treatments identified during the clinical trial.

Data Transparency

The 2013 Declaration stresses that researchers, authors, sponsors, editors, and publishers must share data and publish research results as an ethical duty. Researchers must publicly share their clinical trial outcomes, ensuring accurate and complete reports, including negative, inconclusive, and positive results.

However, the 2013 Declaration lacks specific mandates for data sharing. It does not include detailed protocols or mandatory registration requirements for clinical trials in public databases. While it promotes transparency and accountability in research, it leaves implementation to researchers' discretion without concrete guidelines or enforceable measures.

The updated 2024 Declaration imposes stricter requirements for data sharing within the research community. Researchers are now required to develop and adhere to comprehensive data-sharing protocols. These protocols ensure that data from clinical trials are made accessible to other researchers and the public, thus promoting transparency and accountability.

One of the major enhancements in the 2024 Declaration is the mandate that all clinical trials must be registered in publicly accessible databases before the recruitment of the first participant. This requirement ensures that information about clinical trials is available to the public, facilitating scrutiny and fostering trust in the research process.

The newest version of the Declaration underscores the ethical obligation of researchers, authors, sponsors, editors, and publishers to make the results of their studies publicly accessible. It emphasizes the importance of timely, complete, and accurate reporting of research findings, including negative and inconclusive results.

Implications For The 2024 Declaration Of Helsinki Updates

The 2024 revision of the Declaration implements substantial updates designed to advance the ethical conduct of medical research. It represents a comprehensive update that enhances the ethical framework for medical research involving human participants. By introducing stricter data-sharing protocols, mandatory clinical trial registration, detailed ethical obligations, robust post-clinical trial provisions, and considerations for environmental sustainability, the 2024 Declaration addresses contemporary ethical challenges more effectively. These updates reaffirm the WMA’s commitment to protecting research participants and promoting transparency and accountability in clinical research globally. As medical research continues to evolve, these principles will serve as a crucial guide, ensuring that the dignity, rights, and well-being of research participants remain at the forefront of scientific advancement.

About The Expert:

Jessica Cordes started her clinical operations career in 2009, working at various companies including Big Pharma and several small to midsize biotech companies. She gained extensive experience on different levels from country study management to global study management, and, since 2018, leadership in clinical operations. During her time at Medigene and Immatics, she structured the clinical operations department, built cohesive global teams, and implemented GCP and ATMP-compliant processes. For more than 12 years, she has been working in oncology clinical trials (including hemato-oncology as well as solid tumors) and with ATMPs since 2018. Since 2023, she has been working as an independent consultant and trainer, supporting small companies in building their clinical operations group and setting up their clinical trials for success. She provides a GCP refresher course via her Clinical Excellence Training Academy.