Research With Human Subjects

In two linked papers, Haney et al. (1999a, 1999b) reported on intensive laboratory studies of the effects of oral and smoked THC administration on mood and behavior. In both instances, they reported that abstinence from THC was associated with increases in anxiety and irritability coupled with re- 

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Under US regulations, each institution conducting research with human subjects must have its own IRB. These perform the same functions as the Independent Ethics Committees in Europe, and should contain at least five members, one of which should be independent of the institution. There should be available a mixture of scientific and non-scientific expertise capable of assessing research proposals from legal, ethical and scientific perspectives. The IRB must grant written authorisation to the investigator before a study can commence. They are also responsible for on-going reviews of research, and must report to the FDA ... 

Clinical drug trials represent research with human subjects (Cato, 1988). All research involving human subjects that is supported by the federal government or... 

Over the years, scientific research with human subjects has provided valuable information to help characterize and control risks to public health, but its use has also raised particular ethical concerns for the welfare of the human participants in such research as well as scientific issues related to the role of such research in assessing risks. Society has responded to these concerns by defining general standards for conducting human research. As an example, studies carried out for the authorization of a medical product, have to be conducted in line with the World Medical Association s Declaration of Helsinki, which describes the general ethical principles for medical research involving human subjects (World Medical Association 2004). The Helsinki Declaration was first issued by the World Medical Association in 1964 and has been revised several times since then. 

Human research issues affect all programs in US-EPA. In its Office of Research and Development, US-EPA conducts research with human subjects to provide critical information on environmental risks, exposures, and effects in humans. This is referred to as first-party research. In both its Office of Research and Development and its program offices (including the Office of Air and Radiation, the Office of Water, the Office of Solid Waste and Emergency Response, and the Office of Prevention, Pesticides and Toxic Substances), US-EPA also supports research with human subjects conducted by others. This is referred to as second-party research. In aU this work US-EPA is committed to full compliance with the common rule. The US-EPA will continue to conduct and support such research, and to consider and rely on its results in US-EPA assessments and decisions. 

Much of the scientific information supporting US-EPA s actions is generated by researchers who are not part of or supported by a Eederal agency, including a significant portion of the research with human subjects submitted to the US-EPA or retrieved by the US-EPA from published sources. Such research is generally referred to as third-party research. ... 

For more than 50 years, scientists, physicians, bioethi-cists, and the media have focused on a variety of issues in research with human subjects, or clinical research. In 1948, in response to the atrocities perpetrated by Nazi experimentation, the Nuremberg Code was developed to set forth guidelines for the acceptable conduct of scientific research. In 1964 the World Medical Association adopted the Declaration of Helsinki, which specifically guides physicians in biomedical research. These documents specify basic moral guidelines ultimately founded on concerns for autonomy, beneficence, and justice. The guidelines require the following ... 

Some propose a duty to equitably share intellectual rights (UNDP 2001). The KFPE says, "Research results have intellectual worth and may also have a commercial value. All partners should share equally in the benefits of both" (SCRP/KFPE1998). Brazil says that research with human subjects "must ensure the research subjects the benefits resulting from the research project, in terms of social returns, access to procedures, products or research agents" (NBAC 2001 57). 

Papers presented earlier In this symposium described a number of approaches which were used to determine bloavalla-blllty of dietary zinc. Experiments with animal models and human subjects were reported. Most scientists agree that as much Information as possible should be first obtained from In vitro and laboratory animal experiments. However, since results of vitro and animal experiments do not always agree with results of human experiments, research with human subjects Is ultimately required to establish dietary requirements of humans and to determine bloavallabllty of nutrients to humans. 

Clinical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects... 

On the other hand, a topic such as the duty of honesty, although generally stated, holds a lot of interest for the philosopher for the particular manner in which the duty of honesty might appear in research using human subjects. The duty of honesty governs informed consent with regard to health risks, but it could also serve as a springboard to inform human subjects of the potential risks to privacy as well, even if those risks are not well understood. 

Although there are several ethical concerns with biobanks and other large-scale research repositories (Rothstein, 2002), the most important issue is informed consent. Participants in research involving human subjects must be advised of the intended research to be performed with their specimens. With biobanks, however, the future research uses of the samples are unknown at the time of collection. It would be infeasible to contact each of the donors to obtain consent every time a new research use is contemplated, yet IRBs are reluctant to approve the use of blanket consent for unspecified uses. One way to avoid this problem is for prospective sample donors to be given a menu of possible uses of their samples. Such a list might include research in mental health, HIV/AIDS, cancer, cardiovascular disease, or other areas. The donors would then have the opportunity to approve the use of their specimens for all or some of the listed uses. Other disclosures necessary to obtain informed consent include the financial interests of the biobank and researchers, whether individuals may elect to be notified of research findings, and whether it is possible for an individual to withdraw his or her sample from the bank (Rothstein, 2002). 

The Declaration of Geneva of the World Medical Association binds the physician with the words the health of my patient will be my first consideration, and the International Code of Medical Ethics declares that medical progress is based on research, which ultimately must rest in part on experimentation involving human subjects. In medical research on human subjects, considerations related to the well being of the human subject should take precedence over the interests of science and society. ... 

In the evaluation of human health risks, sound human data, whenever available, are preferred to animal data. Animal and in vitro studies provide support and are used mainly to supply evidence missing from human studies. It is mandatory that research on human subjects is conducted in full accord with ethical principles, including the provisions of the Helsinki Declaration (World Medical Association 2000). 

Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent. 

There are Limits to what animal studies can tell us about human behavior. There are also limits on what we can learn from laboratory experiments with human subjects. Because of financial constraints one may not be able to create high-stake situations in the laboratory/ unless one uses first-world research grants to study third-world subjects (Cameron 1995). Because of ethical constraints that were set up in the wake of Stanley Milgram s (1974) work, one cannot place subjects in situations that will induce strong negative emotions. Also, many of these studies rely on self-reports, which are a pretty fragile instrument. I believe, therefore, that to understand the subtler human emotions one has to turn to the last four sources, which is not to say that the first three have no value. 

Each study component has an ethical aspect. The ethical aspects of a clinical trial cannot be separated from the scientific objectives. Segregation of ethical issues from the full range of study design components demonstrates a flaw in understanding the fundamental nature of research involving human subjects. Compartmentalization of ethical issues is inconsistent with a well-run trial. Ethical and scientific considerations are intertwined (p. 4). 

NIH defines human clinical research as (1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes (a) mechanisms of human disease, (b) therapeutic interventions,... 

In addition, there is the added complexity of finding the optimal dose of neuroprotective and hypothermia treatment that will result in the optimal degree of neural protection. Because of the possibility of treatment interactions, significant preclinical testing will be necessary to identify the most clinically feasible and neurologically potent therapeutic regimen. This may be quite difficult, as the translation of preclinical research to human subjects is inexact. Added testing in phase I (safety) and phase II (dose escalation) human trials will be necessary, with a special emphasis on possible adverse interactions between the treatments. 

One essentially unexplored area for hair analysis is its application to the investigation of environmental toxin exposure. We received a research grant during 1979 from the National Institute of Occupational Safety and Health to explore the possibility of using hair analysis for monitoring exposure to polychlorinated biphenyl compounds (PCBs). Although the analytical chemical problems of this project were successfully solved, we were unable to mount successful field studies with human subjects. 

Research on Human Subjects—Pharmaceutical executives claim that the size of human clinical trials has increased dramatically over time. A rapid increase in trial sizes is consistent with an increase in the estimated cost of phase III clinical trials from 5.7 million (in 1990 dollars) for each new chemical entity (NCE) entering the phase in Hansen s study to 14.3 million (in 1990 dollars) in DiMasi s study. Part of the explanation... 

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