An otherwise healthy young woman agrees to take part in a clinical research study (“Study”) and dies after inhaling an experimental compound of the drug hexamethonium.  She was the third subject in the Study.  The Office of Human Research Protections (“OHRP”) faulted Dr. Togias, the researcher in this case, for: (1) inadequately researching the potential risks of this drug; (2) not consulting the FDA since hexamethonium was not FDA approved; and (3) not alerting the Institutional Review Board (“IRB”) when the first research subject developed a cough and shortness of breath after inhaling hexamethonium.   The OHRP cited the IRB for failing to properly protect research subjects when it approved the Study. This commentary will focus on whether Dr. Togias was negligent in his role as principal investigator in the Study and/or whether the IRB was negligent in approving the Study.

Negligence is basically defined as engaging in conduct that is culpable because it does not rise to the level of what a reasonable person would do to protect others from unreasonable risks of harm.   In order to find negligence, a court of law would have to weigh the evidence at hand and the judge or jury, as the case may be, would have to decide if Dr. Togias’ conduct and/or the IRB’s conduct was culpable because it did not rise to the level of what a reasonable person would do to protect a research subject from unreasonable risks of the Study.

Evidence in this case suggests that Dr. Togias missed some research which indicated that hexamethonium might damage the lungs.  Through testimony, it would need to be determined if it is reasonable to expect Dr. Togias to have found such research and whether Dr. Togias should have stated the risks of hexamethonium in the protocol and informed consent consistent with such research.  Second, FDA regulations state that under certain circumstances, the FDA needs to be consulted before the investigator conducts a study on investigational drugs.[1]  If it is determined that Dr. Togias failed to consult the FDA in violation of the law, Dr. Togias may be found negligent.  Third, Dr. Togias failed to report to the IRB that the first research subject in the Study suffered from adverse symptoms after inhaling hexamethonium.  To find negligence, it would need to be determined if the symptoms rose to the level of an adverse event which should have been reported to the IRB.  

The IRB obtains its authority for the review, approval and monitoring of research from federal regulations.  Title 45 of the Code of Federal Regulations contains regulations promulgated by the United States Department of Health & Human Services (“HHS”) for the protection of human subjects.[2]  Similarly, Title 21 of the Code of Federal Regulations contains regulations promulgated by the Food and Drug Administration (“FDA”) for various aspects of clinical research[3].  One of the requirements the IRB must comply with is to ensure that risks to human subjects are minimized.  Furthermore, the HHS regulations set forth the procedures the IRB must follow in reviewing protocols, including discussing the protocols at convened meetings where a majority of the IRB members are present.[4]  In order to make an informed decision about the research study and comply with its requirements to protect human subjects, the IRB needs to review the research protocols and related documents (including the informed consent) and obtain sufficient detail of the information presented to it.