A Quick Reference to, and Brief Summary of Ethical Resources:
The Beecher Article, “Ethics and clinical research” (Henry K. Beecher)
https://www.nejm.org/doi/full/10.1056/NEJMms1603756
A brief summary of how unethical research and research conducted without any oversight eventually became to fall under regulative oversight with ethical guidelines.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632196/
A summary of important documents in the field of research ethics.
Nuremberg Code
This is a set of research ethics principles for human experimentation set as a result of the subsequent Nuremberg trials at the end of the Second World War.
Basically, in the 1920s German politics tried to make a “master race” by exterminating all those considered to be inferior (they targeted Jewish people). Nazi members held a large portion of the population of German physicians and were all in for these experiments. There were several arguments against this practice, primarily that it had no therapeutic purpose, there was no informed consent, it lacked beneficence and appeared maleficent instead.
The US led what became as the Nuremberg Trial. The trial resulted in the creation of 10 points that currently make up the “Nuremberg Code”.
The Nuremberg Code covers principles of informed consent, absence of coercion, scientific research validity, beneficence and other important aspects of ethical human subject research.
**Interesting Point** Because the Code was based off extreme acts that seemed almost barbaric, many physicians felt that following the code didn’t apply to them as they didn’t see their research as relevant nor their practices as anything but ethical. Regardless, the Code is considered to be one of the most important and influential documents in regards to human subject research ethics and highlights the importance of global human rights.Because of that the Nuremberg Code and Declaration of Helsinki are basis for the Code of Federal Regulations (CFR 45 Part 46) and what the Department of Health and Human Services and IRBs refer to.
Declaration of Helsinki while the trials were being held, six points defining legitimate medical research were submitted to the Counsel for War Crimes. Three judges, in response to expert medical advisers for the prosecution, adopted these points and added four additional points. The 10 points constituted the “Nuremberg Code,” which includes such principles as informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants. (has undergone 7 revisions since initially published)
“The Declaration is morally binding on physicians, and that obligation overrides any national or local laws or regulations, if the Declaration provides for a higher standard of protection of humans than the latter. Investigators still have to abide by local legislation but will be held to the higher standard.”
The Declaration originally adopted the 10 principles in the Nuremberg Code, combined them with the Declaration of Geneva, and introduced the concept of requiring an independent committee (e.g., the IRB, which came into effect in the US in 1981). The requirement to disclose conflicts of interest wasn’t addressed until the 5th revision in 2000. By 2013, the 7th revision was published and required dissemination of research (even if it was inconclusive) and included the requirement for compensation for research related injuries. However, the US FDA rejected all versions after the 3rd and developed the Good Clinical Practices as its replacement.
https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
https://history.nih.gov/research/downloads/helsinki.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884510/
Good Clinical Practices (GCP)
Different from the Nuremberg Code and the Declaration of Helsinki, the GCP is not so much focused on morals but more on procedures. In summary, international clinical trials varied based on inconsistent guidelines and standards which led to investigators having to repeat their studies so in the 1990’s Japan, the U.S., and the European Union came together to establish the ICH (International Conference on Harmonization) with the intention of harmonizing the technical guidelines and requirements for drug marketing which resulted in the GCP (ICH E6 Good Clinical Practices). The GCP is now the international standard for the design, conduct, monitoring, and reporting of clinical research of investigational drugs. This has since been revised to now be called the ICF E6(R2) GCP.
The U.S. FDA has opted out of adopting these as law, however, and only uses them as guidance. Of note, it is said that the ICH guidances and FDA regulations do not contradict each other, rather, the ICH guidances tend to go beyond the regulations. Sponsors generally prefer to abide by these “guidances” though, as it assures their studies are in compliance with the regulations at an international level.
The National Research Act:
in response to the growing concern over research ethics, specifically the prisoner studies, Willowbrook study, and the PHS Syphilis Study, congress passed the National Research Act in 1974 which resulted in the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research which now mandate the requirement for IRBs to oversee any PHS-funded study. Ethical Principles and Guidelines for the Protection of Human Subjects of Research” was thus developed for the regulation of human subject research and is now commonly known as The Belmont Report.
The Belmont Report covers three main principles: Respect for Persons, Justice, and Beneficence.