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Government, Scientific Assessments of Oxygen Therapeutics, and Trauma
Alexander Charles Dukes
A Thesis for the Course of Honors Political Science at Tuskegee University
April 4, 2011
The following writing sample is an excerpt from the beginning of my 2011 thesis for the Senior “Honors” Political Science course at Tuskegee University.
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The purpose of this thesis is to examine the relationship between government, scientific assessments of oxygen therapeutics, and trauma. My central argument is that oxygen therapeutics do not provide a discernible benefit when used before, nor after a blood transfusion becomes available. Therefore, governmental regulatory bodies must seriously consider whether current FDA regulations are robust enough to protect patients from needless harm during the course of a drug’s clinical trials. I will explore the relationship between governmental regulatory bodies and corporations by utilizing the comparative method and case studies. The goal of these efforts will be to determine whether corporate entities or governmental regulatory bodies are at fault with regard to the continued approval of oxygen therapeutic research that is without benefit. The two central questions are these: Did governmental regulatory bodies improperly approve oxygen therapeutics for use in human experimentation during trauma settings? Did the corporations in question deceive the regulatory institutions? First, I will begin by examining the general subject of drug approval in the United States and internationally. This will be accomplished by comparing the FDA approval of a variety of drugs created by a variety of corporations; including, but not limited to oxygen therapeutics. Second, I will turn to a case study examination of oxygen therapeutics and examine the subject of their approval for use in human experimentation. Finally, I will render a series of policy proposals regarding the continued use of human experimentation in research studies.
STATEMENT OF THE PROBLEM
Oxygen Therapeutics are chemical formulas designed to deliver oxygen to the body’s cells as a temporary measure in place of human blood. These products are designed for use in traumatic situations in which are victims prone to losing large amounts of blood, such as a car crash or on the field of battle. The benefits of Oxygen Therapeutic formulas are threefold: First, their ability to be more portable than human blood, as human blood requires sensitive and bulky equipment to maintain usability. Second, oxygen therapeutics would be compatible across all blood types because they do not contain any cells. Finally, therapeutics are products borne from a sterile laboratory process- as opposed to transfusions from humans; thus, there is a very low risk of disease transmission from an oxygen therapeutic. Much of the experimental testing to determine the effectiveness of the various oxygen therapeutics has been conducted under the FDA's "Emergency Research Waiver" provision. This portion of FDA regulation removes the need to obtain informed consent from the test subject during the course of the experimentation, and transfers consent from the test subject to an Institutional Review Board. The little data that is made publicly available from corporations developing oxygen therapeutics suggests that the effects of the available oxygen therapeutics on humans are questionable at best, and possibly detrimental to public health. This evidence suggests that Institutional Review Boards have failed to prevent harmful experimentation on the public.
The Problem With the FDA:
Being the chief regulator of clinical trials in the United States, the Food and Drug
Oxygen Therapeutics 3 Administration is given the responsibility to protect Americans from experimentation that may harm them unnecessarily. However, it is also given the responsibility to review, and in some cases aid, the development of essential new drugs to cure ailments. The balancing of these two duties is one of the most difficult tasks presented to the FDA. To this end, the FDA must ensure that research for new products is carried out in a safe and ethical fashion. When one conducts any type of research with human beings, it is always ethically critical that the researcher obtains informed consent from the humans to be studied in the research. However, there are some cases where valuable research may be conducted but it would not be feasible to obtain consent from the subject of the test. In rare cases, the FDA has determined it ethically acceptable to waive the standard of informed consent. Such exceptions include research studies whose effects are of low risk to humans, and research that includes "legally authorized representatives" (LARs) who make decisions on behalf of persons that cannot communicate their approval or disapproval of any research conducted (Kipnis, King, Nelson). In addition to these exceptions, the regulations were modified to their current state in 1996 by the FDA to allow for research trials that take place during emergency situations. Such research falls under what the FDA calls its “Emergency Research Waiver” rules. Under these regulations, consent from the subject nor an LAR is required to implement the experiment. However, the subject and LAR of the experimentation must be informed of the experimentation as soon as possible ("Emergency Use of an Investigational Drug or Biologic - Information Sheet”). Examples of a situation where these rules would apply may be the scene of an automobile accident or the scene of a shooting. In such situations, the subject would possibly be unable to render a decision on whether or not they want to be subjected to experimentation. Due to the fact they are drugs whose primary purpose is to prevent death from blood loss at the scene of a trauma event, oxygen therapeutics must be tested under this FDA regulation. For research that takes place under the Emergency Research Waiver, the FDA requires that an Institutional Review Board (IRB) be established for each local community in which research will be conducted as part of a larger national trial. The FDA expects the members of IRBs to reflect the diverse nature of the community. Pursuant to this goal, the following rules exist regarding the membership of an IRB: Summary of FDA Rules Regarding IRB Membership: 1. IRBs are made up of at least five members. 2. Members are expected to hail from a diverse set of races, cultures, and social-economic backgrounds. 3. No IRB can consist entirely of men or women 4. No IRB can consist entirely persons whose “primary concern” is with science or people whose “primary concern” is non-scientific. ("Code of Federal Regulations Title 21 Sec. 56.107") IRBs are established to ensure that quality research is conducted and that ethical standards are adhered to. As part of this mission, IRBs are to make sure that those
Oxygen Therapeutics 4 conducting the research have properly informed the community of the fact that this research and experimentation is occurring on their citizens. The intent of the regulation is to ensure that no research is conducted that the community does not approve of. However, the FDA provides no specific instruction on what exactly constitutes effective communication (Holloway). In addition, some trials are simultaneously conducted under the FDA’s emergency research regulations and an FDA designation called a “Special Protocol Assessment” (SPA). Born of the 1997 FDA Modernization act, an SPA is meant to speed up the approval process for drugs the FDA considers potentially beneficial to certain high priority ailments. This designation sets the trial design for a drug into an inflexible agreement between the FDA and the trial's sponsor (typically the company developing the drug). SPA’s do not allow for modification of the trial at the point of community consultation because an agreement is already established between the FDA and the trial sponsor. This negates the affected community’s ability to negotiate with the sponsor for a change in the way the trial is conducted (Kipnis, King, Nelson). As a result of the SPA designation and the lack of a clear definition of what the FDA considers sufficient community consultation, it is possible for less than rigorous community consultation to occur. With such loopholes, an IRB may conduct experimental trials that the community would not approve of. Without the ability to lobby the IRB for a change in the conduct of an experiment within their community, the IRB and trial sponsor are able to remove the only form of consent the subjects of emergency trauma research have: the consent of their peers. Without community consultation, the final layer of protection the community has from profit driven drug corporations is the IRB that monitors the conduct of the trial. However, even in the event the IRB members properly exercise their oversight by consulting with the community properly, reviewing a study, and as a result voicing ethical concerns with the design of a study, the Principal Investigator (PI) may hinder the IRB’s ability to report the problem to the FDA. The principal investigator is responsible for the conduction of the study. He or she leads the research team conducting the trial and presides over IRB meetings. When a local IRB decides that it has a problem with a portion of a study under the Emergency Research Waiver, it must formally vote to express its disapproval. Because IRB’s are convened in local communities where individual portions of a larger national trial are being conducted, the FDA requires that the FDA and other IRBs conducting similar trials be informed when an IRB votes in disapproval ("Code of Federal Regulations Title 21 Sec. 50.24"). Depending on the nature of the disapproval, the FDA may shut down the trial nationwide. Alternatively, other IRBs may cancel the trial in their local communities once they learn of another IRB's disapproval of a trial. Neither of these outcomes would be in the trial sponsor’s interest, so the sponsor has a great incentive to prevent any expression of disapproval by the IRB. Such review board votes of no-confidence may be (and often are) suppressed by the sponsor through the principal investigator. Expressions of disapproval must be formally noted by the majority of IRB members present at a meeting. During the normal motions of amassing support among IRB members for the disapproval of a trial, it is likely that a PI and sponsor will discover that a vote of disapproval is coming. Since the PI has executive control over the study, the PI
Oxygen Therapeutics 5 may cancel the study before the IRB has a chance to formally disapprove of it (Kipnis, King, Nelson). The end result is that should a drug trial fail to yield favorable results for the sponsor, the IRB’s disapproval of the research is never revealed to the FDA or other IRB boards conducting trials on the same drug elsewhere. Essentially, the corporation sponsoring these trials may continue to test dangerous drugs on potentially unknowing communities even though one or multiple Institutional Review Boards have disapproved of the conduct of the trial in other parts of the nation.
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 Kipnis, Ken, Nancy King, and Robert Nelson. "Trials and Errors: Barriers to Oversight of Research Conducted under the Emergency Research Consent Waiver." IRB: ETHICS & HUMAN RESEARCH. 28.2 n. page. Print.  United States. Food and Drug Administration. Emergency Use of an Investigational Drug or Biologic - Information Sheet. 2011. Web. <http://www.fda.gov/RegulatoryInformation/Guidances/ucm126491.htm>.  Holloway, Karla. "Accidental Communities: Race, Emergency Medicine, and the Problem of PolyHeme." American Journal of Bioethics. 6.3 (2006): n. page. Print.  United States. Food and Drug Administration. Code of Federal Regulations Title 21. 1981. Print. <http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm? CFRPart=56&showFR=1>.  Natanson, Charles. "Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death." Journal of the American Medical Association. 299.19 (2008): 2304. Print.
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