Posted: June 24, 2002
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PART III
Several oxygen therapeutic products currently are in late-stage clinical trials. In preparation for the emergence of this totally new class of oxygen delivery agents, AABB held its first Oxygen Therapeutics and Transfusion Alternatives Conference from May 30 to 31. The following is the third and final part in a series providing highlights from conference presentations and discussions.
Risks vs. Benefits
"Known risks should always outweigh perceived benefits when deciding whether or not to administer any medical procedure", said Richard K. Spence, MD, director of surgical education at Baptist Health Systems in Birmingham, Ala. "The risk vs. benefit ratio for oxygen therapeutic products must be weighed against those for red blood cell transfusion." Risk/benefit considerations for transfusion include transfusion-transmissible diseases (TTDs) and non-infectious serious hazards of transfusion (NISHOTS), while risk/benefit considerations for oxygen therapeutics should include vasoactivity, potentiation, sepsis, RES blockade, and iron overload (not applicable to PFCs), according to Christopher P. Stowell, PhD, director of the Blood Transfusion Service at Massachusetts General Hospital in Boston.
Ethical Issues
It is well known in the field of transfusion medicine that some patients do not believe in receiving blood transfusions. For example, Jehovah's Witnesses, whose religious strictures forbid the acceptance of allogeneic blood, typically refuse this type of treatment. However, health care providers have not always been as respectful of patient rights as they should be, according to Kenneth Kipnis, PhD, from the Department of Philosophy at the University of Hawaii in Manoa.
"Patients who refuse transfusion historically have been considered heretics in the cathedrals of medicine", said Kipnis. "This paternalistic attitude, which, unfortunately has been common in the medical community, disregards patient autonomy"," Kipnis said it is absolutely imperative that health care providers secure the informed consent of "decisionally capacitated" adults prior to treatment. A patient can be considered decisionally capacitated if he or she is able to: Understand his or her medical condition; Understand the medical alternatives (including no treatment); Understand the risks and benefits associated with each alternative; and Express a choice.
Kipnis recommends health care providers say to patients who have refused treatment "Please help me understand why you are refusing this treatment." If the patient tells a "story" in which his or her decision makes sense in relation to a history of stable personal values, the patient's refusal of treatment must be considered an informed decision and respected as such.
Bloodless medicine can play an important role in the treatment of patients who refuse transfusion, and such patients can aid the medical community as a whole by providing motivation for exploring transfusion alternatives, according to Kipnis. "The progress medicine makes toward the respectful treatment of those who abstain from blood has the potential to benefit all patients," he said.
Cost, Oversight, and Implementation
Many administrative issues will need to be addressed by facilities adding oxygen therapeutics to their catalog of transfusion alternatives Where should the products be stored? Which products should be kept in stock? How much will they cost? And perhaps most importantly Who should be in charge of making decisions about oxygen therapeutics?
When determining who should oversee the administration of oxygen therapeutics, Stowell recommended facilities ask themselves two questions "Who are the stakeholders? And who are the experts?" Stakeholders might include surgeons, anesthesiologists, blood bankers, pharmacists, nurses, clinical lab workers, administrators, and most of all patients.
The experts referred to by Stowell are hospital staff members who best understand the physiology of oxygen transport and delivery, including anesthesiologists, hematologists, surgeons, pharmacists, and critical care physicians. "It remains to be seen where blood bankers will fit into this picture," Stowell said.
"Their expertise in these areas will be their biggest advantage." Paul Ness, MD, director of transfusion medicine at Johns Hopkins Hospital in Baltimore, Md., and co-moderator of the conference, suggested that a hospital transfusion practices committee (TPC) could take on many of the responsibilities associated with the administration of these products.
"The TPC may need to function in a manner similar to the Pharmacy Oversight Committee," he said. "As a result, membership requirements [for the TPC] may change." Once it is clear who will oversee the implementation of oxygen therapeutics, facilities can more clearly identify which component of their existing infrastructure is best equipped to handle storing and issuing these products. Two possible alternatives are the hospital pharmacy and its transfusion service. According to Stowell, a pharmacy has the main advantage of precedent, as other plasma derivatives like albumin, IVIG, and Factor VIII often are stored here. However, the permissive storage requirements and universal compatibility of oxygen therapeutics mean these products potentially can be stored anywhere.
A hospital transfusion service has storing precedents similar to those of the pharmacy, and has the additional advantage of unit tracking capabilities. The expertise and STAT capability of the transfusion service do not necessarily recommend it as the only ideal administrator of oxygen therapeutics, according to Stowell, because these capabilities also can be found in other hospital departments, such as in the operating room.
The cost of oxygen therapeutics will be affected by many variables, said Stowell. Factors that could raise costs for these products include Increased per unit acquisition costs; Adverse event costs; and Increased costs for laboratory testing.
Factors that could lower costs for oxygen therapeutics include Ability to store at room temperature; Unmonitored storage; Minimal outdating; Lack of compatibility testing requirements; Lack of infectious risks; and Fewer NISHOTS (Non-Infectious Serious Hazards Of Transfusion).
Government Perspectives
"The United States government has a legitimate public health interest in the development of blood substitutes", said Stephen D. Nightingale, MD, executive secretary of the Advisory Committee for Blood Safety and Availability, Department of Health and Human Services. Nightingale pointed out that oxygen carriers will be used to Supplement peacetime blood supplies; Supplement wartime and disaster blood supplies; Supplement the orphan drug armamentarium; and Act as novel therapeutic agents.
Nightingale said he considers the last two on this list to be the most important. "There is a market out there for orphan drugs and a public health interest in fostering the development of orphan drugs. The transfusion medicine community can do us all a favor by continuing to develop orphan drugs", he said.
The federal government should become involved in the individual and collective uses for oxygen therapeutics, as well as overseeing the regulation of these products, according to Nightingale. He sees the Department of Defense in the role of consumer advocate on blood-related issues, because military personnel are more aware than civilians that they may some day need a blood transfusion. "The military is a very important stakeholder in the issue of blood substitutes", Nightingale said.
Nightingale envisions the Food and Drug Administration (FDA) as the "gate-keeper" of oxygen therapeutics. However, many questions about the regulation of these products remain to be answered, he said. "Who is responsible for off-label use and for the unintended consequences of off-label use? Is cost a regulatory concern, a public health concern, or a legislative concern?" Nightingale asked. The answers to these questions must be worked out to the satisfaction of FDA and the transfusion medicine community.
Toby Silverman, MD, chief of the Clinical Review Branch of the Center for Biologics Evaluation and Research (CBER) at FDA, agreed that there are many issues regarding oxygen therapeutics that will need to be resolved. Silverman said the agency believes more studies need to be done on the uses of oxygen carriers in both trauma situations and elective surgery in order to better understand the benefits and risks associated with these products.
Furthermore, dosing requirement guidelines must be developed for the use of oxygen therapeutics at the bedside, she said. Silverman indicated that a draft guidance on the many issues associated with these products would be forthcoming, but she did not specify when such guidance could be expected.
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