The history of clinical research is filled with examples of serious ethical violations and research that failed to protect human subjects.
Through these tragic examples, however, researchers also developed many guidelines that form the basis of what we consider to be Good Clinical Practice today. One of the essential medical research guiding statements is the Declaration of Helsinki.
Read on to learn more about its origins and revisions, its principles, and how it influences clinical research practices today.
What Is The Declaration of Helsinki?
The Declaration of Helsinki was initially adopted by the 18th Assembly of the World Medical Association in Helsinki, Finland, on June 1964, detailing the ethical principles for clinical research involving human subjects.
The Declaration was developed from the ten principles first stated in the Nuremberg Code in 1947, which followed horrific experiments Nazi scientists conducted on Jewish concentration camp prisoners during World War II. It also incorporated elements from the Declaration of Geneva, made in 1948 as a statement comprising physicians' ethical duties. Before the Nuremberg Code of 1947, there was no generally accepted code of conduct that governed the ethics of research involving human subjects.
The Declaration of Helsinki's General Guiding Principles
The Declaration of Helsinki provides several guiding principles that enable a firm foundation for ethical standards during clinical research. Notable guiding principles include:
Protection of patients' health
Medical researchers are expected to act in a manner that promotes and protects the health and well-being of all human subjects involved in research. The Declaration of Helsinki expounds on the importance of designing research to reduce the risks of potential harm while ensuring anticipated benefits are achieved. This principle is in line with the Hippocratic Oath that states, "First, do no harm.” It also emphasizes the Declaration of Geneva that states, "The health of my patient will be my first consideration."
The pursuit of knowledge can never supersede the rights of patients
Medical research typically aims to find insights into the causes and development of a disease. It also seeks to enhance diagnostics and treatment efforts. The Declaration of Helsinki states that "the purpose of medical research can never take precedence over the rights and interests of individual research subjects."
The Declaration expects researchers to protect the life, dignity, health, integrity, privacy, right to self-determination, and confidentiality of all research subjects.
To achieve the principles outlined in the Declaration, there are additional considerations that must be made.
First, all medical research that involves humans as subjects must be conducted by individuals with the requisite scientific and ethical education and training. Qualified health care professionals or physicians should also supervise the research. Additionally, during the research, the physician-scientists should ensure minimal potential harm to the environment. If the patient suffers harm, they should receive appropriate treatment and compensation if applicable.
The physician's scientist is also expected to consider their specific local regulatory norms and standards for research that involve human subjects. These requirements should not compromise or reduce the protections outlined in the Declaration of Helsinki. Where the local regulatory norms provide additional protection, physicians should incorporate them.
How Does The Declaration of Helsinki Influence Clinical Research Today?
Currently, there are ten specific sections addressed within the Declaration of Helsinki. These areas guide physicians and other participants in medical research that involve human subjects.
Let's look at these areas and how they influence best practices for clinical research today.
1. The risks and burdens vs. benefits
The Declaration of Helsinki states that medical research should only be conducted if its findings outweigh the subjects' risks and burdens. The physician-scientists need to determine the impact that the research will have on participating persons and the potential benefits to them and other people affected by the disease. They must also monitor and mitigate any risks during clinical research. Should these risks outweigh the potential benefits, the researchers should immediately modify their techniques or stop the research altogether.
2. Protection of vulnerable groups and persons
Professionals undertaking research should ensure vulnerable groups and individuals receive special protection. Vulnerable groups and individuals are participating subjects who are more likely to be wronged or incur harm owing to their special status. Such groups and persons can include minor children, people with disabilities, the imprisoned, and racial or ethnic minorities.
3. The need for sound scientific inquiry
The principles of medical research must meet specific requirements and research protocols. Researchers should be well acquainted with all the knowledge of existing scientific literature and other crucial sources of information. They should also have a thorough knowledge of accepted techniques of experimentation. The study design should be explicitly described and justified in the research protocol.
Researchers are also required to provide critical information on:
- Compensation for harm
- Incentives for the subjects
- Potential conflicts of interest
- Institutional affiliations
4. Review of research protocols by research ethics committees
Before starting a study, researchers should submit their protocol for review by the Research Ethics Committee. The Research Ethics Committee is an assigned institutional review board made up of qualified experts. They provide objective comments, guidance, and the approval of research. Researchers need to seek the knowledge and approval of the committee before they amend the protocol. Once the study is finished, researchers are also expected to submit final reports that comprise their findings and conclusions to the committee.
5. Privacy and confidentiality
The Declaration of Helsinki also underscores the need for researchers to keep the personal information of the subjects confidential. The privacy and identity of the participating subjects should also be kept protected.
6. Obtaining informed consents
The Declaration of Helsinki states that medical research subjects should never be forced, bribed, or coerced to participate in clinical research. Their decision to participate should be purely voluntary. The researchers must obtain informed consent in writing from those willing to participate. When obtaining consent, the following information must be provided
- Study aims
- Methods of study
- The sources of funding
- Conflicts of interest
- Anticipated benefits
- Post-study provisions
- Study outcomes
- Institutional affiliations
A research subject also has a right to withdraw consent at any time during the study. Additionally, researchers must consider potential subjects incapable of giving informed consent due to their physical or mental incapacity. In these scenarios, researchers should obtain consent from a legally authorized representative, according to the Declaration of Helsinki.
7. Use of placebo
In general, researchers should test new interventions against existing accepted standards that relate to the best-proven interventions. In some cases, the new interventions can be compared to a placebo. This often happens where there is no proven intervention or when there is a need to assess the efficacy and safety of the intervention that is believed to present no additional risks to abstaining from treatment.
8. Post-trial provisions
Where intervention is deemed to be beneficial within a trial, researchers are required to offer a provision for post-trial access for all participating subjects.
9. Research registration and publication of results
The Declaration of Helsinki requires clinical researchers to register all studies involving human subjects in a publicly accessible database. Additionally, once the trial is complete, researchers have an ethical duty to disseminate the results. They are required to provide complete and accurate results. They should also disclose all the negative and inconclusive results alongside their positive findings
10. Use of the unproven intervention in clinical proactive
In the absence of a proven intervention, a physician-scientist can use an unproven intervention. However, this should only be done once appropriate consideration incorporating professional judgments, expert advice, and the committee's oversight is done.
Questions About the Declaration of Helsinki
When was the Declaration of Helsinki last updated?
The Declaration of Helsinki has been amended several times by the nine General Assemblies of the association. The first version of the Declaration was adopted in 1964 and has since been updated seven times. The latest update was made at the General Assembly meeting in 2013. Here is a closer look at its updates:
- 1975 — This was one of the largest revisions to the original document. It clarified the interests of the individual must always take precedence over those of society at large or scientific inquiry. This revision also introduced the concept that an independent committee should provide oversight for any medical research.
- 1983 — The text was updated to include seeking the consent of minors whenever possible.
- 1989 — Another minor update, this one refined the structure and function recommended for the independent oversight committee.
- 1996 — The fourth update was relatively minor, but did include some controversial language that restricted the use of placebo-controlled trials.
- 2000 — This was another major revision, and met with some controversy. It expanded the introductory section to include scientific researchers as well as physicians. Once again, debate over whether placebo-controlled trials are ethical slowed consensus on the changes. Physicians in developing countries were also concerned that the new document called for each patient to be given the best health care methods identified in the study. This would make it difficult for physicians in those countries to comply with, given their relatively limited resources. Because of the restrictions on placebo trials, the U.S. Food and Drug administration replaced the Declaration of Helsinki with the Good Clinical Practice guidelines.
- 2008 — In keeping with the core value of the rights of the individual, this minor update added language to include protection of the privacy rights of research subjects.
- 2013 — The most recent revision of the Declaration states that research subjects should be compensated for any harm they may experience during the study and guaranteed access to the best treatments discovered during the study.
It’s important to note the current updated version is the only official piece that replaced the other preceding versions. The old versions should not be used or cited unless for historical purposes.
Is the Declaration of Helsinki legally binding?
The Declaration of Helsinki is not legally binding. However, it has a substantial impact on national legislation on rules and principles related to medical research that involve humans as subjects. A critical fundamental principle of the Declaration is that the individuals participating in clinical research must always take precedence over science and society's interests.
Despite the fact that the United States and some other countries have adopted other internationally recognized guidelines in response to restrictions on the use of placebo during testing, the Declaration of Helsinki remains the official source of medical ethics in many countries around the world. As a living declaration, it continues to evolve, and the worldwide medical community continues to provide input. Because of the weight of the World Medical Association, the Declaration of Helsinki and the discussions it provokes as it evolves continue to shape the way medical researchers view emerging ethical concerns, regardless of whether their country of origin embraces the declaration.
Because there were no other international guidelines for a long time after the Declaration of Helsinki was created, it remains a foundational part of the laws even in countries that no longer embrace it as an official set of principles. Its two sets of core principles can be found in the practices of research labs worldwide.
At IMARC, we are committed to ensuring clinical research complies with all applicable legal and regulatory guidelines and the ethical considerations established throughout history. We offer a full range of services to support trials at every stage, from planning to closeout.
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