Ethics in Research

Nazi Medical Experiments

From 1933 to 1945, the Third Reich in Europe implemented atrocious, unethical activities (Steinfels & Levine, 1976). The programs of the Nazi regime consisted of sterilization, euthanasia, and numerous medical experiments to produce a population of racially pure Germans, or Aryans, who the Nazis maintained were destined to rule the world. The Nazis encouraged population growth among the Aryans (“good Nazis”) and sterilized people they regarded as racial enemies, such as the Jews. They also practiced what they called “euthanasia,” which involved killing various groups of people whom they considered racially impure, such as the insane, deformed, and senile. In addition, numerous medical experiments were conducted on prisoners of war, as well as racially “valueless” persons who had been confined to concentration camps.

The medical experiments involved exposing subjects to high altitudes, freezing temperatures, malaria, poisons, spotted fever (typhus), and untested drugs and operations, usually without any anesthesia (Steinfels & Levine, 1976). For example, in the hypothermia studies, subjects were immersed in bath temperatures ranging from 2° to 12° C. The researchers noted that “immersion in water 5° C is tolerated by clothed men for 40 to 60 minutes, whereas raising the water temperature to 15° C increases the period of tolerance to four to five hours” (Berger, 1990, p. 1436). These medical experiments were conducted to generate knowledge about human beings but the end result often was to destroy certain groups of people. Extensive examination of the records from some of these studies showed that they were poorly designed and conducted. Thus, they generated little if any useful scientific knowledge.

The Nazi experiments violated numerous rights of human research subjects. The selection of subjects was racially based, demonstrating an unfair selection process. The subjects also had no opportunity to refuse participation; they were prisoners who were coerced or forced to participate. Subjects were frequently killed during the experiments or sustained permanent physical, mental, and social damage as a result (Levine, 1986; Steinfels & Levine, 1976). These studies were not conducted by a few isolated scientists and physicians; they were “the product of coordinated policymaking and planning at high governmental, military, and Nazi Party levels, conducted as an integral part of the total war effort” (Nuremberg Code, 1986, p. 425).

Nuremberg Code

The people involved in the Nazi experiments were brought to trial before the Nuremberg Tribunals, which publicized these unethical activities. The mistreatment of human subjects in these studies led to the development of the Nuremberg Code in 1949. This code contains guidelines for (1) subjects’ voluntary consent to participate in research; (2) the right of subjects to withdraw from studies; (3) protection of subjects from physical and mental suffering, injury, disability, and death during studies; and (4) the balance of benefits and risks in a study (Table 9-1). The Nuremberg Code was formulated mainly to direct the conduct of biomedical research; however, the rules it contains are essential to research in other sciences, such as nursing, psychology, and sociology. This code was developed to promote the ethical conduct of research in all countries and can be reviewed online at http://ohsr.od.nih.gov/guidelines/nuremberg.html.

Declaration of Helsinki

The Nuremberg Code provided the basis for the development of the Declaration of Helsinki, which was adopted in 1964 and amended in 1975, 1983, 1989, 1996, 2000, and 2002 by the World Medical Association; it can be viewed online at www.rotrf.org/information/Helsinki_declaration.pdf. The Declaration of Helsinki differentiated therapeutic research from nontherapeutic research. Therapeutic research gives the patient an opportunity to receive an experimental treatment that might have beneficial results. Nontherapeutic research is conducted to generate knowledge for a discipline, and the results from the study might benefit future patients but will probably not benefit those acting as research subjects.

The Declaration of Helsinki requires that (1) greater care be exercised to protect subjects from harm in nontherapeutic research; (2) there be a strong, independent justification for exposing a healthy volunteer to risk of harm just to gain new scientific information; (3) investigators must protect the life, health, privacy, and dignity of research subjects; and (4) extreme care must be taken in making use of placebo-controlled trial and used only in the absence of existing proven therapy (World Medical Association General Assembly, 2002). Thus, this legal document provides an ethical basis for the clinical trials and other research conducted today in the United States and internationally. Clinical trials must focus on improving diagnostic, therapeutic, and prophylactic procedures for patients with selected diseases without exposing subjects to any additional risk of serious or irreversible harm. Most institutions worldwide in which clinical research is conducted have adopted the Declaration of Helsinki. However, neither this document nor the Nuremberg Code has prevented some investigators from conducting unethical research (Beecher, 1966; Nelson-Marten & Rich, 1999; ORI, 2004).

Tuskegee Syphilis Study

In 1932, the U.S. Public Health Service (U.S. PHS) initiated a study of syphilis in black men in the small, rural town of Tuskegee, Alabama (Brandt, 1978; Rothman, 1982). The study, which continued for 40 years, was conducted to determine the natural course of syphilis in the adult black male. The research subjects were organized into two groups: one group consisted of 400 men who had untreated syphilis and the other consisted of a control group of 200 men without syphilis. Many of the subjects who consented to participate in the study were not informed about the purpose and procedures of the research. Some individuals were unaware that they were subjects in a study.

By 1936, it was apparent that the men with syphilis developed more complications than the control group. Ten years later, the death rate of the group with syphilis was twice as high as that for the control group. The subjects were examined periodically but were not treated for syphilis, even after penicillin was determined to be an effective treatment for the disease in the 1940s (Levine, 1986). Information about an effective treatment for syphilis was withheld from the subjects, and deliberate steps were taken to keep them from receiving treatment (Brandt, 1978).

Published reports of the Tuskegee Syphilis Study first started appearing in 1936, and additional papers were published every 4 to 6 years. No effort was made to stop the study; in fact, in 1969, the U.S. Centers for Disease Control (CDC) decided that it should continue. Numerous individuals were involved in conducting this study, including

In 1972, an account of the study published in the Washington Star sparked public outrage. Only then did the U.S. Department of Health, Education, and Welfare (DHEW) stop the study. The Tuskegee Syphilis Study was investigated and found to be ethically unjustified, but its racial implications were never addressed (Brandt, 1978). There are still many unanswered questions about this study, such as where were the checks and balances in the government and health care systems that should have prevented this unethical study from continuing for 40 years and why was public outrage the only effective means of halting the study?

Willowbrook Study

From the mid-1950s to the early 1970s, Dr. Krugman at Willowbrook, an institution for the mentally retarded, conducted research on hepatitis (Rothman, 1982). The subjects, all children, were “deliberately infected with the hepatitis virus; early subjects were fed extracts of stool from infected individuals and later subjects received injections of more purified virus preparations” (Levine, 1986, p. 70). During the 20-year study, Willowbrook closed its doors to new inmates because of overcrowded conditions. However, the research ward continued to admit new inmates. To gain their child’s admission to the institution, the parents were forced to give permission for the child to be a subject in the study.

From the late 1950s to early 1970s, Krugman’s research team published several articles describing the study protocol and findings. Beecher (1966) cited the Willowbrook study as an example of unethical research. The investigators defended injecting the children with the virus by citing their own belief that most of the children would have acquired the infection after admission to the institution. The investigators also stressed the benefits the subjects received, which were a cleaner environment, better supervision, and a higher nurse-patient ratio on the research ward (Rothman, 1982). Despite the controversy, this unethical study continued until the early 1970s.

Jewish Chronic Disease Hospital Study

Another highly publicized example of unethical research was a study conducted at the Jewish Chronic Disease Hospital in the 1960s. Its purpose was to determine the patients’ rejection responses to live cancer cells. Twenty-two patients were injected with a suspension containing live cancer cells that had been generated from human cancer tissue (Hershey & Miller, 1976; Levine, 1986).

The patients were not informed that they were taking part in research or that the injections they received were live cancer cells. In addition, the Jewish Chronic Disease Hospital Institutional Review Board never reviewed the study; even the physicians caring for the patients were unaware that the study was being conducted. The physician directing the research was an employee of the Sloan-Kettering Institute for Cancer Research, and there was no indication that this institution had reviewed the research project (Hershey & Miller, 1976). The research project had the potential to cause the human subjects serious or irreversible harm and possibly death.

Other Unethical Studies

In 1966, Henry Beecher published a now classic article describing 22 of the 50 examples of unethical or questionably ethical studies that he had identified in the published literature. The examples, which included the Willowbrook and Jewish Chronic Disease Hospital studies, indicated a variety of ethical problems that were relatively widespread. Consent was mentioned in only 2 of the 50 studies, and many of the investigators had unnecessarily risked the health and lives of their subjects. Beecher (1966, p. 1356) believed that many of the abuses in the research were due to “thoughtlessness and carelessness, not a willful disregard of patients’ rights.” These studies reinforce the importance of conscientious institutional review and ethical researcher conduct.

U.S. Department of Health, Education, and Welfare Regulations

The continued conduct of harmful, unethical research made additional controls necessary. In 1973, the DHEW published its first set of regulations intended to protect human subjects. By May 1974, clinical researchers were presented with strict regulations for research involving humans, with additional regulations to protect persons having limited capacities to consent, such as the ill, mentally impaired, and dying (Levine, 1986).

In the 1970s, researchers went from a few vague regulations to almost overwhelming guidelines. All research involving human subjects had to undergo full institutional review, even nursing studies that involved minimal or no risks to the human subjects. Institutional review improved the protection of human subjects; however, reviewing all studies, without regard for the degree of risk involved, overwhelmed the review process and greatly prolonged the time required for a study to be approved (Levine, 1986).

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Because the DHEW regulations far from resolved the issue of protecting human subjects in research, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1978) was formed. This commission was established by the National Research Act (Public Law 93-348) passed in 1974. The goals of the commission were (1) to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and (2) to develop guidelines based on these principles.

The commission developed The Belmont Report, which identified three ethical principles as relevant to research involving human subjects: the principles of respect for persons, beneficence, and justice. The principle of respect for persons holds that persons have the right to self-determination and the freedom to participate or not participate in research. The principle of beneficence requires the researcher to do good and “above all, do no harm.” The principle of justice holds that human subjects should be treated fairly. The ethical principles in this report continue to influence the conduct of ethical research in the United States and internationally. This commission developed ethical research guidelines based on these three principles, made recommendations to the U.S. Department of Health and Human Services (U.S. DHHS), and was dissolved in 1978 (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1978).

In response to the commission’s recommendations, in 1981 the U.S. DHHS developed a set of federal regulations to protect human research subjects, and these regulations were revised over the years (U.S. DHHS, 1981, 1983, 1991, 2001, 2005). The most current 2005 regulations are part of the Code of Federal Regulations (CFR), Title 45, Part 46, Protection of Human Subjects. These regulations are interpreted by the Office for Human Research Protection (OHRP), an agency within U.S. DHHS, whose functions are described online at www.hhs.gov/ohrp. These regulations provide direction for (1) the protection of human subjects in research, with additional protection for pregnant women, human fetuses, neonates, children, and prisoners; (2) the documentation of informed consent; and (3) the implementation of the institutional review board process (U.S. DHHS, 2005). These regulations apply to all research involving human subjects in the following areas: (1) studies conducted, supported, or otherwise subject to regulations by any federal department or agency; (2) research conducted in educational settings; (3) research involving the use of educational tests, survey procedures, interview procedures, or observation; and (4) research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens.

Most of the biomedical and behavioral research conducted in the United States is governed by the U.S. DHHS Protection of Human Subjects Regulations (U.S. DHHS, 2005) or the U.S. Food and Drug Administration (FDA) (see www.fda.gov/oc/gcp). The FDA, within the U.S. DHHS, manages the CFR Title 21, Food and Drugs, Part 50, Protection of Human Subjects, and Part 56, Institutional Review Boards. The FDA has additional human subject protection regulations that apply to clinical investigations involving products regulated by the FDA under the Federal Food, Drug, and Cosmetic Act and research that supports applications for research or marketing permits for these products. Thus, these regulations apply to studies of drugs for humans, medical devices for human use, biological products for human use, human dietary supplements, and electronic products and can be viewed online at www.fda.gov/oc/gcp/regulations.html. The physician and nurse researchers conducting clinical trials to generate new drugs and refine existing drug treatments must comply with these FDA regulations. These regulations focus on the protection of human subjects’ rights, informed consent (FDA, 2006b), and institutional review boards (FDA, 2006b), with content that is consistent with Title 45, Public Welfare, Part 46, Protection of Human Subjects (U.S. DHHS, 2005).

The U.S. DHHS and FDA regulations provide guidelines to protect subjects in federally and privately funded research by ensuring that their privacy and the confidentiality of the information obtained through research. However, with the advent of electronic access and transfer, the public has become concerned about the potential abuses of the health information of individuals in all circumstances, including research projects. Thus, Public Law 104-191, the Health Insurance Portability and Accountability Act (HIPAA), was enacted in 1996 and implemented in 2003 to protect an individual’s health information. The U.S. DHHS developed regulations titled the Standards for Privacy of Individually Identifiable Health Information, and compliance with these regulations is known as the Privacy Rule (U.S. DHHS, 2002, 45 CFR Parts 160 and 164). The HIPAA Privacy Rule established the category of protected health information (PHI), which allows covered entities, such as health plans, health care clearinghouses, and health care providers that transmit health information, to use or disclose PHI to others only in certain situations. These situations are discussed later in this chapter.

The HIPAA Privacy Rule affects not only the health care environment but also the research conducted in this environment. An individual must provide his or her signed permission, or authorization, before his or her PHI can be used or disclosed for research purposes. Researchers must modify their current studies and develop their new research projects to comply with the HIPAA Privacy Rule. The U.S. DHHS developed a website, “HIPAA Privacy Rule: Information for Researchers,” to address the impact of this rule on the informed consent and institutional review board processes in research and to answer common questions about the HIPAA (see http://privacyruleandresearch.nih.gov). The full impact of the privacy rule on the protection of individuals’ privacy and on the conduct of research is yet to be determined (Conner, Smaldone, Bratts, & Stone, 2003; Olsen, 2003); however, you can view the privacy rule enforcement highlights online at www.hhs.gov/ocr/privacy/enforcement.

In summary, Table 9-2 was developed to clarify the overall objectives and applicability of the HIPAA Privacy Rule, U.S. DHHS Protection of Human Subjects Regulations Title 45 CFR Part 46, and FDA Protection of Human Subjects Regulations Title 21 CFR Parts 50 and 56 (U.S. DHHS, 2007, February 2, b). The specifics of these regulations are discussed later in this chapter in the sections on protecting human rights, obtaining informed consent, and institutional review.

Right to Self-Determination

The right to self-determination is based on the ethical principle of respect for persons. This principle holds that because humans are capable of self-determination, or controlling their own destiny, they should be treated as autonomous agents who have the freedom to conduct their lives as they choose without external controls. As a researcher, you treat prospective subjects as autonomous agents by informing them about a proposed study and allowing them to voluntarily choose to participate or not. In addition, subjects have the right to withdraw from a study at any time without a penalty (Levine, 1986). Conducting research ethically requires that research subjects’ right to self-determination not be violated and that persons with diminished autonomy have additional protection during the conduct of studies.

Right to Privacy

Privacy is an individual’s right to determine the time, extent, and general circumstances under which personal information will be shared with or withheld from others. This information consists of one’s attitudes, beliefs, behaviors, opinions, and records. An individual’s privacy was initially protected by the Privacy Act of 1974. As a result of this act, data collection methods were to be scrutinized to protect subjects’ privacy, and data cannot be gathered from subjects without their knowledge. Individuals also have the right to access their records and to prevent access by others (U.S. DHHS, 2002, 2005). The intent of this act was to prevent the invasion of privacy that occurs when private information is shared without an individual’s knowledge or against his or her will. Invading an individual’s privacy might cause loss of dignity, friendships, or employment or create feelings of anxiety, guilt, embarrassment, or shame.

The HIPAA Privacy Rule expanded the protection of an individual’s privacy, specifically his or her protected individually identifiable health information, and described the ways in which covered entities can use or disclose this information. Covered entities are the individual’s health care provider, health plan, employer, and health care clearinghouse (public or private entity that processes or facilitates the processing of health information). Individually identifiable health information (IIHI)

According to the HIPAA Privacy Rule, the IIHI is protected health information (PHI) that is transmitted by electronic media, maintained in electronic media, or transmitted or maintained in any other form or medium. Thus, the HIPAA privacy regulations affect nursing research in the following ways: (1) accessing data from a covered entity, such as reviewing a patient’s medical record in clinics or hospitals; (2) developing health information, such as the data developed when an intervention is implemented in a study to improve a subject’s health; and (3) disclosing data from a study to a colleague in another institution, such as sharing data from a study to facilitate development of an instrument or scale (Olsen, 2003).

The U.S. DHHS developed guidelines to help researchers, health care organizations, and health care providers determine when they can use and disclose IIHI. IIHI can be used or disclosed to a researcher in the following situations:

The first two items are discussed in this section of the text. The authorization process is discussed in the section on obtaining informed consent, and the waiver or alteration of authorization requirement is covered in the section on understanding institutional review.

Right to Autonomy and Confidentiality

On the basis of the right to privacy, the research subject has the right to anonymity and the right to assume that the data collected will be kept confidential. Anonymity exists if the subject’s identity cannot be linked, even by the researcher, with his or her individual responses (ANA, 2001; Sasson & Nelson, 1971). For studies that use de-identified health information or data from a limited data set, the subjects will be anonymous to the researcher. You will be unable to contact these subjects for additional information.

In most studies, researchers desire to know the identity of their subjects and promise that their identity will be kept anonymous from others. However, in these situations, you must receive authorization from the potential subject to use his or her health information, or you must have a waiver or an alteration of the authorization requirement from the IRB (see section on institutional review later in this chapter). Confidentiality is the researcher’s management of private information shared by a subject that must not be shared with others without the authorization of the subject. Confidentiality is grounded in the following premises:

Right to Fair Treatment

The right to fair treatment is based on the ethical principle of justice. This principle holds that each person should be treated fairly and should receive what he or she is due or owed. In research, the selection of subjects and their treatment during the course of a study should be fair.

Right to Protection from Discomfort and Harm

The right to protection from discomfort and harm is based on the ethical principle of beneficence, which holds that one should do good and, above all, do no harm. According to this principle, members of society should take an active role in preventing discomfort and harm and promoting good in the world around them (Frankena, 1973). Therefore, researchers should conduct their studies to protect subjects from discomfort and harm and try to bring about the greatest possible balance of benefits in comparison with harm.

Discomfort and harm can be physiological, emotional, social, and economic in nature. Reynolds (1979) identified the following five categories of studies, which are based on levels of discomfort and harm: (1) no anticipated effects, (2) temporary discomfort, (3) unusual levels of temporary discomfort, (4) risk of permanent damage, and (5) certainty of permanent damage. Each level is defined in the following discussion.

Assessment of Benefits

The probability and magnitude of a study’s potential benefits must be assessed.

In most proposals, the research benefits are described for the individual subjects, subjects’ families, and society. Some optimistic researchers overestimate these benefits.

The type of research conducted, whether therapeutic or nontherapeutic, affects the potential benefits for the subjects. In therapeutic nursing research, the individual subject has the potential to benefit from the procedures, such as skin care, range of motion, touch, and other nursing interventions, that are implemented in the study. The benefits might include improvement in the subject’s physical condition, which could facilitate emotional and social benefits. In addition, the knowledge generated from the research might expand the subjects’ and their families’ understanding of health. The conduct of nontherapeutic nursing research does not benefit the subject directly but is important to generate and refine nursing knowledge for practice. By participating in research, subjects have the potential to increase their understanding of the research process and an opportunity to know the findings from a particular study.

Assessment of Risks

You must assess the type, severity, and number of risks that subjects will experience or might experience by participating in your study. The risks involved depend on the purpose of the study and the procedures used to conduct it. Research risks can be physical, emotional, social, and economic in nature and can range from no risk or mere inconvenience to the risk of permanent damage (Levine, 1986; Reynolds, 1979). Studies can have actual (known) risks and potential risks for subjects. In a study of the effects of prolonged bed rest, for example, an actual risk would be muscle weakness and the potential risk would be a DVT. Some studies have actual or potential risks for the subjects’ families and society. You must determine the likelihood of the risks and take precautions to protect the rights of subjects when implementing your study.

Benefit-Risk Ratio

The benefit-risk ratio is determined on the basis of the maximized benefits and the minimized risks. The researcher attempts to maximize the benefits and minimize the risks by making changes in the study purpose or procedures or both. If the risks entailed by your study cannot be eliminated or further minimized, you need to justify their existence. If the risks outweigh the benefits, you should revise the study or develop a new study. If the benefits equal or outweigh the risks, you can justify conducting the study, and an institutional review board (IRB) will probably approve it (see Figure 9-1).

Say, for example, that you want to balance the benefits and risks of a study that would examine the effect of an exercise and diet program on the participants’ serum lipid values (serum cholesterol, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) and cardiovascular (CV) risk level. The benefits to the participants are instruction about exercise and diet and information about their serum lipid values and CV risk level at the start of the program and 1 year later. The potential benefits are improved serum lipid values, lowered CV risk level, and better exercise and dietary habits. The risks consist of the discomfort of having blood specimens drawn twice for serum lipid measurements and the time spent participating in the study (Bruce & Grove, 1994). These discomforts are temporary, are no more than what the subject would experience in his or her daily life, and would cease with the termination of the study. The subjects’ time participating in the study can be minimized through organization and precise scheduling of research activities. When you examine the ratio of benefits to risks, you find that (1) the benefits are greater in number and importance than the risks and (2) the risks are temporary and can be minimized. Thus, you could justify conducting this study, and it would probably receive approval from the IRB.

The obligation to balance the benefits and risks of studies is the responsibility of the researcher, health professionals, and society. The researcher must balance the benefits and risks of a particular study and protect the subjects from harm during it. Health professionals participate on IRBs to ensure the conduct of ethical research. Society must be concerned with the benefits and risks of the entire enterprise of research and with the protection of all human research subjects from harm.

The voluntary consent of the human subject is absolutely essential…. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. (Nuremberg Code,1986, p. 425)

Information Essential for Consent

Informed consent requires the researcher to disclose specific information to each prospective subject. The following information has been identified as essential content for informed consent in research by CFR 45 Section 46.116 (U.S. DHHS, 2005) and CFR 21 Part 50 (FDA, 2006b).

Comprehension of Consent Information

Informed consent implies not only the imparting of information by the researcher but also the comprehension of that information by the subject. Studies performed to determine subjects’ levels of comprehension after they received the essential information for consent have found the comprehension to be low (Levine, 1986). The amount of information to be taught depends on the subjects’ knowledge of research and the specific research project proposed. However, the purpose, benefits, and risks of the study must be presented clearly in the consent form. Subjects need to have a clear understanding of the therapeutic potential of participating in a study. They need to know if the research treatment is going to be nontherapeutic for them but has a potential to benefit future patients.

Federal regulations require that the information given to subjects or their representatives must be in a language they can understand (FDA, 2006b; U.S. DHHS, 2005). Thus, the consent information must be written and verbalized in lay terminology, not professional jargon, and must be presented without the use of loaded or biased terms that might coerce a subject into participating in a study. Meade (1999) identified the following tips for promoting the comprehension of a consent document by potential research subjects:

Meade (1999) used these tips to simplify a paragraph from an example consent form, as shown in Table 9-5. Once you have developed the consent document, pilot-test it with patients who are comparable to the proposed subjects for the study. These patients can give feedback on the ease of reading, clarity, and understandability of the consent document. You can then revise the document as needed on the basis of the feedback. These guidelines will help you to develop a high-quality consent document that your study subjects can comprehend.

In qualitative research, the participants might comprehend their participation in a study at the beginning, but unexpected events or consequences might occur during the study to obscure that understanding. These events might precipitate a change in the focus of the research and the type of participation by the participants. For example, the topics of an interview might change with an increased need for information from the participants to address these topics. Thus, informed consent is an ongoing, evolving process in qualitative research. The researcher must renegotiate the participants’ consent and determine their comprehension of that consent as changes occur in the study. By continually informing and determining the comprehension, of participants, you will establish trust with them and promote ethical, high-quality study outcomes (Munhall, 2001a).

Competency to Give Consent

Autonomous individuals, who are capable of understanding and weighing the benefits and risks of a proposed study, are competent to give consent. The competence of the subject is often determined by the researcher (Douglas & Larson, 1986). Persons with diminished autonomy resulting from legal or mental incompetence, terminal illness, or confinement to an institution might not be legally competent to consent to participate in research (see the earlier discussion of the right to self-determination). However, the researcher makes every effort to present the consent information at a level potential subjects can understand, so that they can assent to the research. In addition, the researcher presents the essential information for consent to the legally authorized representative, such as the parents or guardian, of the prospective subject (U.S. DHHS, 2005).

Voluntary Consent

Voluntary consent means that the prospective subject has decided to take part in a study of his or her own volition without coercion or any undue influence. Voluntary consent is obtained after the prospective subject has been given essential information about the study and has shown comprehension of this information (FDA, 2006b; U.S. DHHS, 2005). Some researchers, because of their authority, expertise, or power, have the potential to coerce subjects into participating in research. Researchers must make sure that their persuasion of prospective subjects does not become coercion. Thus, the rewards offered in a study ought to be congruent with the risks taken by the subjects.

Documentation of Informed Consent

The documentation of informed consent depends on (1) the level of risk involved in the study and (2) the discretion of the researcher and those reviewing the study for institutional approval. Most studies require a written consent form, although in some studies, the consent form is waived.

Authorization for Research Uses and Disclosure

The HIPAA Privacy Rule provides individuals the right, as research subjects, to authorize covered entities (health care provider, health plan, and health care clearinghouse) to use or disclose their private health information (PHI) for research purposes. This authorization is regulated by the HIPAA and is in addition to the informed consent that is regulated by the U.S. DHHS (2005, CFR 45 Part 46) and the FDA (2006b, CFR 21 Part 50). The authorization focuses on the privacy risks and states how, why, and to whom the PHI will be shared. The authorization form must include the following information:

The authorization information can be included as part of the consent form, but it is probably best to have two separate forms (Olsen, 2003). U.S. DHHS (2004) developed a sample authorization form that is presented in Figure 9-3.

Levels of Reviews Conducted by Institutional Review Boards

The functions and operations of an IRB involve the review of research at three different levels: (1) exempt from review, (2) expedited review, and (3) complete review. The level of the review required for each study is decided by the IRB chairperson or committee, but not by the researcher. Studies are usually exempt from review if they pose no apparent risks for the research subjects. The studies that are usually considered exempt from IRB review by the federal regulations are identified in Table 9-6. For example, studies by nurses and other health professionals that have no foreseeable risks or are a mere inconvenience for subjects might be identified as exempt from review by the chairperson of the IRB committee.

Studies that have some risks, which are viewed as minimal, are expedited in the review process. Minimal risk means “that the risks of harm anticipated in the proposed research are not greater, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests” (U.S. DHHS, 2005, 45 CFR Section 46.102). Expedited review procedures can also be used to review minor changes in previously approved research. Under expedited IRB review procedures, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except disapproval of the research. A research activity may be disapproved only after a complete review of the IRB (FDA, 2006b; U.S. DHHS, 2005). Table 9-7 identifies research that usually qualifies for expedited review.

A study that has greater than minimal risks must receive a complete IRB review. To obtain IRB approval, researchers must ensure that

Amdur (2003) provided a detailed discussion of the role of the IRB in health care research, and this information is a good resource for health care agencies and researchers. The process of seeking approval from a research review committee to conduct a study is described in Chapter 28.

Published studies often indicate that an IRB has approved the research project. For example, Bindler, Massey, Shultz, Mills, and Short (2007) conducted their study to examine metabolic syndrome in a multiethnic sample of schoolchildren. They described the following consent and IRB approval process for their study.

The subjects in this study were parents and school-age children from different ethnic backgrounds (English and Spanish) who were invited to participate in the study by a flyer sent to all affiliated with the selected school. The parents and children received information about the study in their appropriate language. Then the parents signed consent forms and the children signed assent forms documenting the informed consent process. The two versions of the consent forms (Spanish and English) probably increased the subjects’ ability to comprehend the consent form and the purpose of the study. IRB approvals were obtained from both the university and the school district where the study was conducted. Thus, the consent process and IRB approvals were clearly documented in this study

Influence of HIPAA Privacy Rule on Institutional Review Boards

Under the 2003 HIPAA Privacy Rule, IRBs or an institutionally established privacy board can act on requests for a waiver or an alteration of the authorization requirement for a research project. If an IRB and a privacy board both exist in an agency, the approval of only one board is required, and it will probably be the IRB for research projects. Researchers can choose to obtain a signed authorization form from potential subjects or can ask for a waiver or an alteration of the authorization requirement. An altered authorization requirement occurs when an IRB approves a request that some but not all of the required 18 elements be removed from health information that is to be used in research. The researcher can also request a partial or complete waiver of the authorization requirement from the IRB. For a partial waiver, discussed earlier, the researcher obtains PHI to contact and recruit potential subjects for a study. An IRB can give a researcher a complete waiver of authorization in studies where the informed consent requirements might also be waived. Thus, a waiver or alteration of the authorization requirement might occur when the following criteria have been met:

The covered entity (health care provider, health plan, or health care clearinghouse) cannot release the PHI to the researcher until the following documentation has been received: (1) the identity of the approving IRB, (2) the date the waiver or alteration was approved, (3) IRB documentation that the criteria for waiver or alteration have been met, (4) a brief description of the PHI to which the researcher has been granted access or use, (5) a statement as to whether the waiver was approved under normal or expedited review procedures, and (6) the signature of the IRB chair or the chair’s designee.

The HIPAA Privacy Rule does not change the IRB membership and functions that are designated under the U.S. DHHS and FDA Regulations. For clarification, the responsibilities of the IRB/privacy board for HIPAA (U.S. DHHS, 2007, February 2, a) and the responsibilities of the IRB under the U.S. DHHS (2005) and FDA (2006a) are outlined in Table 9-8.

Role of the Office of Research Integrity in Promoting the Conduct of Ethical Research

Currently, ORI promotes the integrity of biomedical and behavioral research in approximately 4000 institutions worldwide (ORI, 2007, September 10). ORI applies federal policies and regulations to protect the integrity of the U.S. PHS’s extramural and intramural research programs. The extramural program provides funding to research institutions, and the intramural program provides funding for research conducted within the federal government. The ORI carries out its responsibilities by doing the following:

Since the mid-1990s, ORI has had a major role in the investigation of allegations of misconduct in research within several institutions. “Research misconduct means fabrication, falsification, or plagiarism in processing, performing, or reviewing research, or in reporting research results. It does not include honest error or differences in opinion” (ORI, 2005, 42 CFR Section 93.103). Fabrication in research is the making up of results and recording or reporting them. Falsification of research is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record. Plagiarism is the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit, including those obtained through confidential review of others’ research proposals and manuscripts.

The ORI classifies research misconduct as (1) an act that involves a significant departure from the acceptable practice of the scientific community for maintaining the integrity of the research record; (2) an act that was committed intentionally; and (3) an allegation that can be proved by a preponderance of evidence. ORI has a section on their website titled “Handling Misconduct” that includes a summary of the allegations and investigations managed by its office from 1992 to 2001 (ORI, 2004). The most common sites for the investigations were medical schools (68%), hospitals (11%), and research institutes (10%). The individuals charged with misconduct were primarily males holding a PhD or medical degree (MD) and were mostly associate professors, professors, and postdoctoral fellows. When research misconduct was documented, the actions taken against the researchers or agencies might have included debarment from receiving federal funding for periods ranging from 18 months to 8 years; prohibition from U.S. PHS advisory service; and other actions requiring supervised research, certification of data, certification of sources, and correction or retraction of articles. The regulations governing ORI and the current investigations and activities of ORI can be viewed online at http://ori.dhhs.gov.

Role of Journal Editors and Researchers in Preventing Scientific Misconduct

Editors of journals also have a major role in monitoring and preventing research misconduct in the published literature. Friedman (1990, p. 1416) identified criteria for classifying a publication as fraudulent, questionable, or valid and indicated research articles were “fraudulent if there was documentation or testimony from coauthors that the publication did not reflect what had actually been done.” Articles were considered questionable if no coauthor could produce the original data or if no coauthor had personally observed or performed each phase of the research or participated in the research publication. A research article was considered valid “if some coauthor had personally performed or participated in each aspect of the research and publication” (Friedman, 1990, p. 1416).

Preventing the publication of fraudulent research requires the efforts of authors, coauthors, reviewers, and editors (Hansen & Hansen, 1995; Hawley & Jeffers, 1992; Relman, 1990). Authors who are primary investigators for research projects must be responsible in their conduct, reporting, and publication of research. Coauthors and coworkers should question and, if necessary, challenge the integrity of a researcher’s claims. Sometimes, well-known scientists have been added to a research publication as coauthors to give it credibility. Individuals should not be listed as coauthors unless they were actively involved in the conduct and publication of the research.

Peer reviewers have a key role in determining the quality and publishability of a manuscript. They are considered experts in the field, and their role is to examine research for inconsistencies and inaccuracies. Editors must monitor the peer review process and be cautious about publishing manuscripts that are at all questionable. Editors also need procedures for responding to allegations of research misconduct. They must decide what actions to take if the journal contains an article that has proven to be fraudulent. Usually, fraudulent publications require retraction notations and are not to be cited by authors in future publications (ORI, 2005). However, Pfeifer and Snodgrass (1990) studied the continued citation of retracted, invalid scientific literature and found that articles commonly continued to cite retracted articles in U.S. publications and even more so in the literature of other countries.

The publication of fraudulent research is a major concern in medicine and a growing concern in nursing (Rankin & Esteves, 1997). The smaller pool of funds available for research and the greater emphasis on research publications could lead to a higher incidence of fraudulent publications. However, ORI (2007, June 20) has made major advances in addressing scientific misconduct since the regulations were enacted by doing the following:

Each researcher is responsible for monitoring the integrity of his or her research protocols, results, and publications. In addition, nursing professionals must foster a spirit of intellectual inquiry, mentor prospective scientists regarding the norms for good science, and stress quality, not quantity, in publications (Wocial, 1995).

• The ethical conduct of research starts with the identification of the study topic and continues through the publication of the study if quality research evidence is going to be developed for practice.

• The debate about ethics and research continues, probably because of (1) the complexity of human rights issues; (2) the focus of research in new, challenging arenas of technology and genetics; (3) the complex ethical codes and regulations governing research; and (4) the variety of interpretations of these codes and regulations.

• Two historical documents that have had a strong impact on the conduct of research are the Nuremberg Code and the Declaration of Helsinki. More recently, the U.S. Department of Health and Human Services (U.S. DHHS, 2005) and the Food and Drug Administration (FDA, 2006a, 2006b) have promulgated regulations that direct the ethical conduct of research. These regulations include (1) general requirements for informed consent, (2) documentation of informed consent, (3) institutional review board (IRB) review of research, (4) exempt and expedited review procedures for certain kinds of research, and (5) criteria for IRB approval of research.

• The Council for International Organizations of Medical Sciences revises and updates ethical guidelines for biomedical research conducted internationally. The Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada (Tri-Council) (2005) developed a policy statement to promote the ethical conduct of research in this country.

• A relatively new federal regulation, Public Law 104-191, the Health Insurance Portability and Accountability Act (HIPAA), was enacted in 1996 and implemented in 2003. HIPAA includes privacy rules to protect an individual’s protected health information.

• Conducting research ethically requires protection of the human rights of subjects. Human rights are claims and demands that have been justified in the eyes of an individual or by the consensus of a group of individuals. The human rights that require protection in research are (1) self-determination, (2) privacy, (3) anonymity and confidentiality, (4) fair treatment, and (5) protection from discomfort and harm.

• The rights of research subjects can be protected by balancing benefits and risks of a study, securing informed consent, and submitting the research for institutional review.

• To balance the benefits and risks of a study, the type, level, and number of risks are examined, and the potential benefits are identified. If possible, the risks must be minimized and the benefits maximized to achieve the best possible benefit-risk ratio.

• Informed consent involves the transmission of essential information, comprehension of that information, competency to give consent, and voluntary consent of the prospective subject.

• In institutional review, a study is examined for ethical concerns by a committee of peers called an institutional review board (IRB). The IRB conducts three levels of review: exempt, expedited, and complete. The process for accessing protected health information according to the HIPAA Privacy Rule is also detailed.

• Research misconduct includes fabrication, falsification, and plagiarism during the conduct, reporting, or publication of research. The Office of Research Integrity (ORI) was developed to investigate and manage incidents of scientific misconduct so as to protect the integrity of research in all disciplines.

• Another current ethical concern in research is the use of animals as subjects. Two important questions are addressed: Should animals be used as research subjects, and if animals are used in research, what mechanisms ensure that they are treated humanely? The U.S. Public Health Service Policy on Humane Care and Use of Laboratory Animals provides direction for the conduct of research with animals as subjects.

Amdur, R. Institutional review board: Member handbook. Sudbury, MA: Jones & Bartlett, 2003.

American Nurses Association (ANA). Code of ethics for nurses with interpretive statements. Washington, DC: American Nurses Association, 2001.

American Psychological Association (APA). Ethical principles of psychologists and code of conduct. Washington, DC: American Psychological Association, 2002.

Arras, J.D. Noncompliance in AIDS research. Hastings Center Report. 1990;20(5):24–32.

Beecher, H.K. Ethics and clinical research. New England Journal of Medicine. 1966;274(24):1354–1360.

Berger, R.L. Nazi science: The Dachau hypothermia experiments. New England Journal of Medicine. 1990;322(20):1435–1440.

Bindler, R.C.M., Massey, L.K., Shultz, J.A., Mills, P.E., Short, R. Metabolic syndrome in a multiethnic sample of school children: Implications for the pediatric nurse. Journal of Pediatric Nursing. 2007;22(1):43–58.

Brandt, A.M. Racism and research: The case of the Tuskegee Syphilis Study. Hastings Center Report. 1978;8(6):21–29.

Broome, M.E. Consent (assent) for research with pediatric patients. Seminars in Oncology Nursing. 1999;15(2):96–103.

Broome, M.E., Stieglitz, K.A. The consent process and children. Research in Nursing & Health. 1992;15(2):147–152.

Bruce, S.L., Grove, S.K. The effect of a coronary artery risk evaluation program on serum lipid values and cardiovascular risk levels. Applied Nursing Research. 1994;7(2):67–74.

Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada Tri-Council Policy Statement: Ethical conduct of research involving humans, 2005. Retrieved October 2, 2002, from http://pre.ethics.gc.ca/english/policystatement/policystatement.cfm.

Carico, J.M., Harrison, E.R. Ethical considerations for nurses in biomedical research. Journal of Neuroscience Nursing. 1990;22(3):160–163.

Conner, J.A., Smaldone, A.M., Bratts, T., Stone, P.W. HIPAA in 2003 and its meaning for nurse researchers. Applied Nursing Research. 2003;16(4):291–293.

Council for International Organizations of Medical Sciences (CIOMS) International ethical guidelines for biomedical research involving human subjects, 2002. Retrieved October 2, 2007, from www.cioms.ch/guidelines_nov_2002_blurb.htm.

Damrosch, S.P. Ensuring anonymity by use of subject-generated identification codes. Research in Nursing & Health. 1986;9(1):61–63.

Douglas, S., Larson, E. There’s more to informed consent than information. Focus on Critical Care. 1986;13(2):43–47.

Floyd, J. Research and informed consent: The dilemma of the cognitively impaired client. Journal of Psychosocial Nursing and Mental Health Services. 1988;26(3):13–21.

Food and Drug Administration (FDA), Institutional review boards. Code of Federal Regulations, 2006, April 1. Title 21, Part 56. Retrieved October 1, 2007, from www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=56.

Food and Drug Administration (FDA), Protection of human subjects (informed consent). Code of Federal Regulations, 2006, April 1. Title 21, Part 50. Retrieved October 1, 2007, from www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=50.

Ford, J.S., Reutter, L.I. Ethical dilemmas associated with small samples. Journal of Advanced Nursing. 1990;15(2):187–191.

Frankena, W.K. Ethics, (2nd ed.). Englewood Cliffs, NJ: Prentice-Hall, 1973.

Friedman, P.J. Correcting the literature following fraudulent publication. JAMA. 1990;263(10):1416–1419.

Garfield, E., Welljams-Dorof, A. The impact of fraudulent research on the scientific literature: The Stephen E. Breuning case. JAMA. 1990;263(10):1424–1426.

Goodwin, F.K., Morrison, A.R. Science and self-doubt. Reason. 2000;32(5):22–28.

Grbich, C. Qualitative research in health: An introduction. London: Sage, 1999.

Hansen, B.C., Hansen, K.D. Academic and scientific misconduct: Issues for nursing educators. Journal of Professional Nursing. 1995;11(1):31–39.

Happ, M.B., Swigart, V.A., Tate, J.A., Arnold, R.M., Sereika, S.M., Hoffman, L.A. Family presence and surveillance during weaning from prolonged mechanical ventilation. Heart & Lung. 2007;36(1):47–57.

Hawley, D.J., Jeffers, J.M. Scientific misconduct as a dilemma for nursing. Image: Journal of Nursing Scholarship. 1992;24(1):51–55.

Henderson, J., When scientists fake it. American Way. 1990:56–101.

Hershey, N., Miller, R.D. Human experimentation and the law. Germantown, MD: Aspen, 1976.

Hinds, P.S., Burghen, E.A., Pritchard, M. Conducting end-of-life studies in pediatric oncology. Western Journal of Nursing Research. 2007;29(4):448–465.

Holaday, B., Gonzales, O., Mills, D. Assent of school-age bilingual children. Western Journal of Nursing Research. 2007;29(4):466–485.

Holditch-Davis, D., Brandon, D.H., Schwartz, T. Development of behaviors in preterm infants: Relation to sleeping and waking. Nursing Research. 2003;52(5):307–317.

Kelman, H.C. Human use of human subjects: The problem of deception in social psychological experiments. Psychological Bulletin. 1967;67(1):1–11.

Levine, R.J. Ethics and regulation of clinical research, (2nd ed.). Baltimore–Munich: Urban & Schwarzenberg, 1986.

Lin, C., Lu, M., Chiang, H, Chung, C., Lin, T., Yin, T.J., Yang, C. Using a citizen consensus conference to revise the code of ethics for nurses in Taiwan. Journal of Nursing Scholarship. 2007;39(1):95–101.

McClain, N., Laughon, K., Steeves, R., Parker, B. Balancing the needs of scientist and the subject in trauma research. Western Journal of Nursing Research. 2007;29(1):121–128.

Meade, C.D. Improving understanding of the informed consent process and document. Seminars in Oncology Nursing. 1999;15(2):124–137.

Milgram, S. Behavioral study of obedience. Journal of Abnormal and Social Psychology. 1963;67(4):371–378.

Munhall, P.L. Ethical considerations in qualitative research. In: Munhall P.L., ed. Nursing research: A qualitative perspective. 3rd ed. Sudbury, MA: Jones & Bartlett; 2001:537–549.

Munhall, P.L., Munhall, P.L. Institutional review of qualitative research proposals: A task of no small consequence. In Nursing research: A qualitative perspective, 3rd ed., Sudbury, MA: Jones & Bartlett; 2001:551–563.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Belmont report: Ethical principles and guidelines for research involving human subjects. Washington, DC: U.S. Government Printing Office, 1978. [(DHEW Publication No. [05] 78-0012)].

Nelson-Marten, P., Rich, B.A. A historical perspective of informed consent in clinical practice and research. Seminars in Oncology Nursing. 1999;15(2):81–88.

Nuremberg Code. Levine R.J., ed. Ethics and regulation of clinical research, (2nd ed.). Baltimore–Munich: Urban & Schwarzenberg, 1986:425–426.

Office of Laboratory Animal Welfare (OLAW) Public Health Service policy on humane care and use of laboratory animals, 2007. Retrieved October 1, 2007, from http://grants.nih.gov/grants/olaw/olaw.htm.

Office of Research Integrity (ORI) Scientific misconduct investigations: 1992–2001, 2004. Retrieved October 1, 2007, from http://www.ori.dhhs.gov/misconduct/documents/NewInstitutionalResearchMisconductActivity.pdf.

Office of Research Integrity (ORI), Public Health Service Policies on Research Misconduct. Code of Federal Regulations, 2005, May 17. Title 42, Part 50 and 93, Policies of General Applicability. Retrieved October 1, 2007, from http://ori.dhhs.gov/documents/FR_Doc_05-9643.shtml.

Office of Research Integrity (ORI), Handling misconduct. Office of Research Integrity, 2007, June 20. Retrieved October 1, 2007, from http://ori.dhhs.gov/misconduct.

Office of Research Integrity (ORI), About ORI – History. Office of Research Integrity, 2007, September 10. Retrieved October 1, 2007, from http://ori.dhhs.gov/about/history.shtml.

Olsen, D.P. Methods: HIPAA privacy regulations and nursing research. Nursing Research. 2003;52(5):344–348.

Orb, A., Eisenhauer, L., Wynaden, D. Ethics in qualitative research. Journal of Nursing Scholarship. 2001;33(1):93–96.

Pardes, H., West, A., Pincus, H.A. Physicians and the animal-rights movement. New England Journal of Medicine. 1991;324(23):1640–1643.

Pfeifer, M.P., Snodgrass, G.L. The continued use of retracted, invalid scientific literature. JAMA. 1990;263(10):1420–1423.

Ramos, M.C. Some ethical implications of qualitative research. Research in Nursing & Health. 1989;12(1):57–63.

Rankin, M., Esteves, M.D. Perceptions of scientific misconduct in nursing. Nursing Research. 1997;46(5):270–275.

Relman, A.S. Publishing biomedical research: Roles and responsibilities. Hastings Center Report. 1990;20(5):23–27.

Reynolds, P.D. Ethical dilemmas and social science research. San Francisco: Jossey-Bass, 1979.

Rothman, D.J. Were Tuskegee and Willowbrook “studies in nature”? Hastings Center Report. 1982;12(2):5–7.

Sasson, R., Nelson, T.M. The human experimental subject in context. In: Jung J., ed. The experimenter’s dilemma. New York: Harper & Row; 1971:265–296.

Silva, M.C. Comprehension of information for informed consent by spouses of surgical patients. Research in Nursing & Health. 1985;8(2):117–124.

Steinfels, P., Levine, C. Biomedical ethics and the shadow of Naziism. Hastings Center Report. 1976;6(4):1–20.

Thompson, P.J. Protection of the rights of children as subjects for research. Journal of Pediatric Nursing. 1987;2(6):392–399.

U.S. Department of Health and Human Services (U.S. DHHS), Final regulations amending basic HHS policy for the protection of human research subjects. Code of Federal Regulations, 1981, January 26. [Title 45, Part 46].

U.S. Department of Health and Human Services (U.S. DHHS), Protection of human subjects. Code of Federal Regulations, 1983, March 8. [Title 45, Part 46].

U.S. Department of Health and Human Services (U.S. DHHS), Protection of human subjects. Code of Federal Regulations, 1991, June 18. [Title 45, Part 46].

U.S. Department of Health and Human Services (U.S. DHHS), Protection of human subjects. Code of Federal Regulations, 2001, November 23. [Title 45, Part 46].

U.S. Department of Health and Human Services (U.S. DHHS), Standards for privacy of individually identifiable health information: Final rule. Code of Federal Regulations, 2002, August 14. Title 45, Public Welfare, Parts 160 and 164. Retrieved October 1, 2007, from www.hhs.gov/ocr/hipaa/privrulepd.pdf.

U.S. Department of Health and Human Services (U.S. DHHS), Institutional review boards and the HIPAA Privacy Rule. HIPAA Privacy Rule: Information for researchers, 2003, September 25. Retrieved October 1, 2007, from http://privacyruleandresearch.nih.gov/irbandprivacyrule.asp.

U.S. Department of Health and Human Services (U.S. DHHS), HIPAA authorizations for research. HIPAA Privacy Rule: Information for researchers, 2004, April. Retrieved October 1, 2007, from http://privacyruleandresearch.nih.gov/authorization.asp.

U.S. Department of Health and Human Services (U.S. DHHS), Protection of human subjects. Code of Federal Regulations, 2005, June 23. Title 45, Part 46. Retrieved October 1, 2007, from www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

U.S. Department of Health and Human Services (U.S. DHHS). How can covered entities use and disclose protected health information for research and comply with the Privacy Rule? HIPAA Privacy Rule: Information for researchers. February 2, a Retrieved October 1, 2007, from http://privacyruleandresearch.nih.gov/pr_08.asp, 2007.

U.S. Department of Health and Human Services (U.S. DHHS), How do other privacy protections interact with the privacy rule?. HIPAA Privacy Rule: Information for researchers, 2007. February 2, b Retrieved October 1, 2007, from http://privacyruleandresearch.nih.gov/pr_05.asp.

Watson, A.B. Informed consent of special subjects. Nursing Research. 1982;31(1):43–47.

Williams, A.M. Issues of consent and data collection in vulnerable populations. Journal of Neuroscience Nursing. 2002;34(4):211–218.

Wocial, L.D. The role of mentors in promoting integrity and preventing scientific misconduct in nursing research. Journal of Professional Nursing. 1995;11(5):276–280.

World Medical Association (WMA) General Assembly World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. Washington, DC: WMA General Assembly, 2002. Retrieved October 1, 1007, from www.rotrf.org/information/Helsinki_declaration.pdf.