Session 1
Session 1
What makes clinical research ethical?
Many national and international codes and guidelines exist to promote the ethical conduct of clinical research. These contain a mixture of ethical principles and procedural prescriptions.
In this session we will survey U.S. and selected international guidelines for the conduct of human subjects research, and explore common themes and principles.
Objectives
To review the evolution of the Nuremberg Code, Declaration of Helsinki, Council for International Organization of Medical Sciences' guidelines for biomedical human subjects research, and the International Conference of Harmonisation's guidelines for Good Clinical Practice.
To review 45CFR46 (informally known as the Common Rule), that section of the Code of Federal Regulations, applicable to research performed with federal funds; the FDA's regulations; and the Belmont Report.
To review universal requirements for the ethical conduct of clinical research : social and scientific value; scientific validity; fair subject selection; a favorable harm-benefit balance; independent review; informed consent; and respect for prospective and enrolled subjects.
Required Reading for this session
Emanuel E, et al. What makes clinical research ethical? JAMA, 2000; 283:2701-2711.
Case Discussion (Credit : Onlineethics.org)
Fan Chen, a new post-graduate researcher in Dr. Thomas's laboratory, is studying the genetics of a neurological disorder. Fan is still learning English and adjusting to a new culture and research environment. Mark Adams, a graduate student in Thomas's laboratory, is studying the genetics of breast cancer. Thomas and Mark have worked very hard to get IRB approval to collect human DNA samples from breast cancer patients and their family members. Through this process, Mark has learned a great deal about human subject research. According to the IRB-approved protocol, blood will be drawn, DNA extracted and samples coded by clinical laboratory technicians with no connection to the Thomas laboratory. The linking identifiers for each sample will be locked in a file cabinet, and only two clinicians, who are not involved in the research study, will have access to the files. This arrangement is intended to maintain the donors' confidentiality and is outlined in the consent form. Thomas's laboratory receives only the vials of donor DNA number-coded with highly visible red tags attached to each tube.
One morning, as Mark enters the laboratory, he walks past Fan's bench and greets him. Something catches Mark's eye. Mark notices the red-tagged tubes in a bucket of ice sitting on Fan's bench. Mark knows that Fan is not working on the breast cancer study. At first, Mark believes there has just been a mistake or a misunderstanding. He explains to Fan that the red-tagged tubes contain DNA samples collected for use in the breast cancer study. Fan replies that Thomas authorized the use of a small amount of the breast cancer DNA as a control in the neurology study and shows Mark a handwritten note from Thomas that confirms Fan's account.
Mark feels uneasy about this use of the breast cancer DNA. He returns to his desk to review an unsigned consent form he has on file, which is just like the one that every donor signs before participating in the study. He notes that the consent form does not state that the DNA will be used in other studies; however, Mark also notices that the consent form does not directly indicate that the samples will not be used in other studies, either. Mark keeps coming back to the introductory statement of the consent form, which contains the following wording: "...you are being asked to participate in a breast cancer study to test for..." He can't seem to dismiss this statement.
Questions
Which ethical principles (explicated in the Belmont Report) are relevant to Mark's concerns in this scenario?
Which of the (seven) requirements for the ethical conduct of clinical research are relevant?
What should Mark do?
What is Fan's responsibility?
What considerations apply to the Investigator's design and the IRB's review of this research?
Additional Resources
The Nuremberg Code from Trials of War Criminals before the Nuremberg Military Tribunals, October 1946 - April 1949.
The Declaration of Helsinki, revised most recently in September 2004.
The Council For International Organization of Medical Sciences' guidelines for biomedical research involving human subjects.
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines for Good Clinical Practice. This is applicable to pharmaceutical clinical trials, is "endorsed" by the FDA, and is applicable to trials conducted internationally, the results of which may be proffered in support of a marketing application.
The Belmont Report, from The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, April 1979.
The Canadian Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans
