Jesse is a teenager with an inherited liver disease. He is invited to participate in a gene therapy experiment to help determine whether an injection of genes might correct the problem. Before he agrees to participate, he and his father ask about the risks and possible side effects. Should he go forward with the experiment? How can he know the information he’s being given by researchers is complete and accurate? How will his safety be protected during the experimental procedure?
The advances in medicine that we take for granted today—dialysis, organ transplantation, the artificial heart, amniocentesis—are only available because someone was the first patient to use the experimental treatment. Without experimentation and research on humans, medical technology could not improve.
At the same time, it is essential that the patients’ rights to confidentiality and privacy be observed and that their informed consent be obtained before experimentation begins. Unfortunately, in the past some of that experimentation was forced on patients who either were unable to say no or did not know that they were being used as research subjects.
During World War II, Nazi doctors used concentration camp prisoners as research subjects. At the Dachau concentration camp, doctors were experimenting on the best way to treat persons who had been severely chilled or frozen. Doctors put prisoners in tanks of ice water for hours at a time or put naked prisoners outside in temperatures below freezing. At the Ravensbrück concentration camp, wounds were inflicted on prisoners so that the doctors could infect the wounds with bacteria. The goal was to create wounds similar to those found in the battlefield and then figure out how to better treat German soldiers. At the Buchenwald concentration camp, doctors secretly put poisons into the prisoners’ food. The prisoners would be studied as they died, or they would be immediately put to death so that Nazi doctors could do autopsies.
THE NUREMBERG CODE SETS STANDARDS
The Nuremberg Code continues to set guidelines for research on humans. The following paraphrases it:
When the war ended, three United States judges presided over the “Doctors’ Trial” at Nuremberg. Twenty-three Nazi doctors were found guilty of war crimes and crimes against humanity, and seven were executed. The Nuremberg War Crimes Court devised the Nuremberg Code, which sets ethical standards for appropriate experimentation on humans.
Americans were quick to condemn the Nazi doctors for their actions. Yet many Americans, for decades after World War II ended, were subjected to medical experiments without their knowledge. In the Tuskegee Syphilis Study, hundreds of low-income African American men in the South were denied treatment for syphilis so that the “natural history” of the disease could be studied. The study went on for 40 years. There were other instances of experimentation without consent as well.
Congress enacted the National Research Act in 1974 to protect the public when taking part in medical research and experiments. The Act does not mean that doctors cannot experiment on you. Rather, the National Research Act set up standards for research on humans that must be followed if the researchers want to receive federal funds for their programs. These standards require the following:
•You must give informed consent to take part in experimental treatment. This means the doctors must tell you about the procedure and about the risks, side effects, and benefits associated with it. They must also tell you about any alternative procedures available to you.
•You must volunteer to take part in the research. Your doctor cannot force you or pressure you into being part of an experiment.
The National Research Act required that Institutional Review Boards (IRBs) be established at every program conducting research funded by the U.S. Department of Health and Human Services or carried out on products regulated by the Food and Drug Administration (FDA). Because the federal government is a major source of research funds, IRBs have been set up at virtually all medical schools, universities, and hospitals where research on humans is conducted.
The IRBs review the research plans or experiments that are requested and either approve or deny the request. They review the plans to make certain that they provide subjects with adequate opportunity to provide informed consent and do not expose them to unreasonable risks. After the research is approved, they provide continuing oversight to ensure that protections remain in force.
WHO CAN BE ON AN IRB?
An IRB must have at least five members (but may have dozens) of
The IRB must make seven findings in order to approve a research program:
Informed consent is a legal doctrine governed by the laws of each state. While each state may require something a little different, the basic concept for human research remains the same: you must be given sufficient opportunity to decide whether you want to be part of the research. When the research is explained to you, the researchers must use language that you understand. If they do not, your consent is not informed because you do not have all the information necessary to make your decision.
Your informed consent to be a research subject will most likely be in written form and include eight parts:
You have the right to leave the research program at any time. If you do so, your doctor or hospital cannot refuse to treat you simply because you left the program. You are still entitled to receive treatment from your doctor as would any other patient who did not take part in the research.
Many persons battling illness wish to get into clinical trial programs in the hope of benefiting from drugs or procedures not generally available. This predisposes many of them to trust their hopes and not their fears and to give consent to some possibly dangerous experiments. In addition, a presidential advisory committee reported in 1996 that as many as a third of research studies had problems with informed consent, including consent forms that are overly optimistic about the benefits of research, that inadequately explain the impact of the treatment, and that are difficult for laypeople to understand.
Some celebrated experiments gone wrong have also raised widespread public concern. This chapter began with a paragraph about a teenager contemplating entering a research study. In real life, that story had an unhappy ending. Eighteen-year-old Jesse Gelsinger died four days after being injected with genes at a University of Pennsylvania Hospital. Gelsinger’s father later testified before a Senate subcommittee, saying that they were not told that a monkey had died in a similar experiment and that another patient had serious side effects. The university later announced that its gene therapy institute would no longer perform research on humans and announced a systemwide review of its policies and procedures regarding research on humans.
The federal government has also become more active in monitoring research. Federal investigators greatly increased their number of site visits in the late 1990s. They suspended some programs because of lax safety oversight, including almost all government-funded research involving humans at Duke University Medical Center.
In addition, the Inspector General of the Department of Health and Human Services issued several reports analyzing the Institutional Review Board system and making recommendations for improvements.
What does all this mean to you if you’re contemplating entering a research program? Problems haven’t been found at most programs, and problems are probably taken a good deal more seriously at other programs. Still, you are your own best defense. Make sure you investigate any possible research study as carefully as you can. Ask questions until you are sure you fully understand the consent form and your concerns have been addressed.
In that situation you may be able to sue your doctor for medical malpractice. You might be required to demonstrate the extent of any injury you suffered during the procedure. Malpractice is discussed in the previous chapter.
Whether a health plan should cover experimental treatment is a common cause of disputes between patients and their insurance companies. Expensive new treatments and technologies can drive up medical costs, which in turn drive up insurance costs for you and everyone else. Insurance companies review these experimental treatments on a case-by-case basis. While laws give insurance companies great leeway in denying coverage for experimental treatment, courts tend to be sympathetic toward the patient, particularly if the patient’s life is at stake. A court can force an insurance company to pay for the treatment if the court reviews the policy and determines that the policy does not clearly state that it won’t pay for that treatment.
One of the factors the court will consider is whether the treatment is widely accepted within the medical and scientific community. If it is widely accepted, you stand a better chance of having your insurance company pay for the treatment. If it is not widely accepted, your chances are fifty-fifty. In contrast, the current majority of states do not require insurance companies to cover infertility treatments, in part because infertility is not a life-threatening illness. Rather, it is considered an elective procedure.
In the past, the answer was generally no. Medicare typically did not pay for treatment that was experimental, looking instead to whether the treatment is safe, effective, cost-effective, appropriate, and accepted by the medical and scientific community. However, in June 2000, President Bill Clinton directed the government to begin paying for “routine patient care” of Medicare recipients who volunteer for experimental medical treatments. The change was made to bring more older people into clinical trials, especially those dealing with conditions most common in the elderly.
There is a catch-22 when it comes to finding new medical treatments for children and the elderly. Research must be done to better understand diseases that affect those groups in particular, such as cystic fibrosis and Alzheimer’s disease. That means research must be done on children and the elderly, which are two of the most vulnerable groups in society. Neither a child nor an elderly person suffering from a mental illness such as Alzheimer’s has the legal capacity to consent to being part of a research study. So how can researchers study people who cannot consent to being studied?
Researchers must get consent from the parents or guardians of the people they wish to study in order to proceed with the research. The goal is to allow researchers to study children and the elderly while at the same time protecting them from abuse and mistreatment.
Using prisoners for medical testing is highly controversial and generally not allowed. One school of thought holds that an inmate may not be a true “volunteer.” Consider this: The prisoner is told when to wake up, when to eat, when to work, when to go to bed. Because he is confined in a prison, he can easily be forced into “volunteering” in exchange for privileges not given to other inmates. There is an inherent inequality between his position as inmate and that of the people running the prison. The inmate cannot be expected to make a decision about being a test subject without feeling some pressure. Thus, his consent is not voluntary, and he cannot be a research subject.
The counterargument is that experimentation is permissible if prisoners volunteer and provide informed consent. Prisoners retain some rights of self-determination and autonomy. Moreover, participating in such experiments might be a legitimate way for them to help society. Those making this argument caution, however, that prisoners should never receive a reduction in sentence for participating.
One of the biggest controversies in human research is the use of fetuses (either still in the uterus or aborted) and embryos. Research is allowed on fetuses within the uterus as long as the risk is minimized and the mother gives her consent. This is only done in situations where the fetus needs the medical treatment or procedure to continue developing until birth.
Federal regulations severely limit the research that may be done on aborted fetuses. For those who oppose abortion, the regulations do not limit the research enough. Others believe that the regulations should allow more testing on aborted fetuses so that other fetuses can benefit from the research, which would possibly lead to fewer miscarriages, stillbirths, and severe birth defects. In general, research on aborted fetuses is allowed only when needed to develop important biomedical knowledge that cannot be obtained in any other possible way. In addition, the mother must consent to the research.
Most research on embryos is aimed at increasing the rate of pregnancy in women seeking in vitro fertilization or other means of assisted reproduction. Other research focuses on gene therapy or on understanding how embryos develop. Couples who undergo fertility treatment and do not want to have the embryos transferred sometimes donate the embryos for research. This type of research brings religious and political controversy. Current federal law prohibits research on embryos, as well as the creation of embryos for the sole purpose of research. At present embryos are not legally considered “life,” but embryos do get special respect in the law because of their potential for human life.
The issue of research using tissue from embryos and fetuses took on heightened importance in December 1998, when two groups of scientists announced that they had successfully isolated and cultured human pluripotent stem cells. According to an article by Susan Lee (Journal of Law, Medicine & Ethics 28, no. 1: 81-83),
This news was greeted with both tremendous enthusiasm and concern. Because these cells can develop into most types of cells or tissues in the human body, they hold great promise for scientific research and medical advances. For example, stem cells can potentially be used to:
At the same time, the advent of laboratory-ready human pluripotent stem cells provokes pressing legal and ethical concerns. The derivation of stem cells from human embryos and fetal tissue raises legal issues in light of the federal ban on human embryo research and federal regulations on fetal tissue research. There is also considerable ethical disagreement on the appropriate level of respect for human embryos and fetal tissue as sources of stem cells. Finally, some fear that stem cell research sits at the brink of a slippery slope that may lead to human cloning practices (p.81).
Lee goes on to note that the National Institutes for Health (NIH) has come up with guidelines to apply to publicly funded research involving pluripotent stem cells. Attempting to walk a fine line, the guidelines require scientific investigators to show that stem cells originating from human embryos must come from excess embryos created for the purposes of infertility treatment, not expressly for research. If stem cells originate from fetal tissue, the research must be in compliance with all laws and regulations governing human fetal tissue research and the fetal tissue transplantation research statute. Excess embryos and fetal tissue must be obtained with the donor’s informed consent.