Unfulfilled Promise: How the Belmont Report Can Amend the Code (Research Involving Human Participants V2)
The power of the Belmont Report to amend the Code of Federal Regulations Title 45 Part 46 has never been realized. This paper will indicate why and how an incorporation of the content and spirit of Belmont into the body of the Federal Regulations can rectify major problems in the Regulations, strengthen the protection of human subjects, and accent the inescapable roles of moral judgments for assessing when research involving human participants is permissible.
Signed into law on 12 July 1974, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (hereafter called the National Commission or Commission) was charged by the U.S. Congress to identify the basic ethical principles that should underlie the conduct of...research involving human subjects.1 In response to this charge, the National Commission published the Belmont Report2 in the Federal Register on 18 April 1979. Belmont was then adopted in its entirety as a policy statement by U.S. Department of Health, Education, and Welfare (DHEW) - now called the Department for Health and Human Services (DHHS). Its principles of respect for persons, beneficence, and justice are regarded as the three quintessential requirements for the ethical conduct of research involving human subjects by the National Institutes of Healths (NIH) Office for Protection from Research Risks (OPRR).3
I. The Federal Regulations and the Belmont Report: Shared Purposes and Different Approaches
The Federal Regulationsand the Belmont Report share the overarching purposes of promoting research and protecting human subjects.4 The Federal Regulationsassume that extensive research conducted within or sponsored by 14 federal agencies should be approved according to the conditions set forth in the Regulations. In the Belmont Report, the promotion of research serves as a pervasive, but de facto purpose. Belmont 1) begins with the sentence, Scientific research has produced substantial social benefits, 2) views research as a moral obligation in several places,5 and 3) justifies a number of research activities and practices in order to accomplish the goals of research.6 As indicated by their subtitles, the explicit purpose of both the Federal Regulations and the Belmont Report is the protection of the human subjects of research. These documents, however, adopt different approaches to this protection.
The protection of research subjects in the Federal Regulations includes rules about how subjects should be protected by risk/probability of benefit determinations [46.111 (a) (1) and (2)], by an equitable selection of subjects [46.111 (a) (3)], by informed consent [41.111 (a) (4) and 46.116], and by adding additional safeguards for vulnerable populations of prospective subjects [46.111 (b)].
Notably, the Regulations also protect human subjects by giving detailed attention to organizational and enforcement mechanisms - the oversight of federal agencies such as OPRR, rules pertaining to the necessity and structure of IRBs, the documentation of IRB deliberations and informed consent, record keeping, and so on. This is as it should be in an effective regulatory system. The fact that some of the greatest abuses and harms in history perpetrated on human beings in research experiments occurred in Germany after its Minister of Interior in 1931 promulgated laudable and visionary ethical guidelines for conducting research involving humans underscores the necessity of institutionalizing ethics through organizational and enforcement mechanisms.7 In contrast to the Regulations, the Belmont Report proposes to protect human subjects through its ethical principles and guidelines. The Report asserts that its principles will enable investigators and Institutional Review Boards (IRBs) to resolve ethical problems arising from research, and will enable researchers, reviewers, human subjects, and interested citizens to understand the ethical issues inherent in research.8 The Regulations are either silent or virtually silent about the protective value of ethics. This paper will show that the ethical purposes and content of Belmont should serve as a basis for amending the Federal Regulations in order to strengthen its subject protections.
The purposes of protecting human subjects and enhancing the benefits of biomedical and behavioral research are fully justifiable, although their balance should be critically and periodically
reassessed. It is a mistake to assume that the relationships between these purposes have to be a zero sum game, whereby increased protections for subjects subtracts from the conducting of research. Over the last 25 years, efforts to protect human subjects have enhanced, not just curtailed, research initiatives. Ethical ferment and regulatory protections have eased the publics anxiety and increased the publics trust, the effects of which are greater public participation in and advocacy for new and expanding levels and types of research.9
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II. Promise: The Belmont Report as a Critical Source for Rectifying Major Problems in the Regulations with Respect to Human Subject Protections
The four explicit purposes of the Belmont Report are set forth in its entangled second and third paragraphs. The report 1) identifies ethical principles that will 2) provide a foundation for formulating, criticizing, and interpreting the regulatory rules of research found in codes of research ethics such as the Nuremberg Code, the Declaration of Helsinki, and existing codes of Federal Regulation, and 3) enable scientists, research subjects, IRBs, and interested citizens to understand the ethical issues that are inherent in research involving human subjects. At the end of these paragraphs Belmont then says that its objective is 4) to provide an analytical framework that will guide the resolution of ethical problems arising from research involving human subjects. This analytical framework includes the reports principles and their applications.10 Belmont focuses on the first and fourth of the above purposes, and its contents display that the third is inescapably true. Notably, however, the report does not discuss the second purpose just listed. This paper will focus on this unaddressed and unfulfilled purpose articulated in the report itself.
The ethical content of Belmont consists of principles and guidelines that are organized according to the following schema, or, to use the reports terminology, analytical framework:11
| The Principle of: |
Guidelines/Applications/Requirements for: |
| Respect for Persons |
Informed Consent
- Information
- Comprehension
- Voluntariness
|
| Beneficence |
Risk/Benefit Assessment |
| Justice |
Selection of Subjects |
The term guidelines in this schema is drawn from Belmonts subtitle and is accented in the introductory letter composed by the members of the National Commission when the Belmont Report was delivered to the secretary of DHEW.12 The guidelines are entitled applications in the body of the report. These applications consist of requirements (a term used several times) or moral requirements regarding informed consent, risk/benefit analysis, and the selection of subjects of research.
Taken together, the purposes and schematized content of the Belmont Report rest on the assumption that ethical principles, reasoning, and guidelines should serve as an essential basis for protecting human subjects of research. This includes formulating, criticizing, and interpreting codified regulations, including the U.S. Code of Federal Regulations. Yet for over 20 years the Belmont Report has not been systematically used as a source of additional and essential protections in the Federal Regulations. Instead, the report has been by and large marginalized to the status of encouragement and oratory. Belmont has been and is being preached about, rather than plowed into the fabric of human subject protections.
From the vantage point of Belmont, the present Federal Regulations (Common Rule) contain a number of major problems, all of which can be rectified by using the Report to amend the Regulations. The Regulations problems include:
- A negligible emphasis on ethics,
- A disorganized set of rules that easily confuse and confound researchers and IRB members as they seek to discover what the Regulations require them to do,
- An irresponsible view of the sources that define and discuss research ethics,
- A seriously flawed understanding of the ethics of research,
- Blind spots with respect to important protections accented in Belmont,
- A preoccupation with rule stating and rule following that convey the message that the Common Rule is a bureaucratic document without a soul,
- A distortion of the elements of informed consent found in the Belmont Report.
All of these problems will be further identified and discussed in section IV of this paper. Section IV will also propose clear and concise ways to amend the Code of Federal Regulations.
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III. The Belmont Report: Treasures in an Earthen Vessel
A. Principles
The meaning of Belmonts principles is often misunderstood. Robert J. Levine, for example, claims that the report mandates a form of ethical reasoning, in which abstract principles are taken to be an ultimate foundation for second-order rules or norms. Levine contrasts this type of reasoning with the views of certain philosophers who argue that the traditional and received norms of society are logically prior to basic ethical principles.13 This view easily lends itself to a principle-based approach to bioethics (often called principalism and viewed with suspicion) that begins with a-theoretical, top-down, ad hoc constructions that are unconnected to one another.14
The nature and functions of the principles articulated in the Belmont Report should be identified by the text of the report, by the thinking of its primary author, Tom L. Beauchamp,15 and by the recollections of its Commissioners. The following four points describe how the principles in Belmont should be understood in relation to ethical reflection, judgments, and action.
First, Belmonts principles are condensations or constitutive elements of morality related to research and derived from culture. Belmont itself says that its principles were chosen because they are particularly relevant to research and are generally accepted in our cultural tradition.16 In other words, rather than serving as abstract norms, they reflect the fabric of morality and morally sensitive cultures to such an extent that no responsible research investigator could conduct research without reference to them.17 Principles are the common coin of moral discourse.18
When the Belmont Report was composed, principles were used by ethicists and bioethicists to identify the basic and comprehensive elements of morality - akin to identifying the basic elements of nature in the periodic table.19 Principles summarized the right-making and wrong-making elements of human interaction that could serve as an easily grasped set of moral standards for persons with diverse backgrounds and training.20 Consider the first principle articulated by Belmont - respect for persons. Commissioner Jonsen could understand this principle as an action guide drawn from ethical theory. 21Commissioner Lebacqz could regard it as crediting all human beings and communities with measures of dignity and worth. Lawyers could identify it with the U.S. Constitutions rights of self-determination and privacy, theologians with the sacredness of human life and human dignity endowed by God, and philosophers with respect for the autonomy of the will from Immanual Kant and liberty of choice from John Stuart Mill. Belmont says that its comprehensive principles are stated at a level of generalization that should assist scientists, subjects, reviewers and interested citizens to understand the ethical issues inherent in research involving human subjects. The reports principles were suited to diverse professional groups within the pluralism of American culture.22
Second, the report does not explicitly ground its principles in ethical theory, but this does not mean that theory is superfluous and, consequently, that its principles are the ultimate foundation of moral reasoning. The Belmont Reportdoes not purport to offer a canonical understanding of philosophical ethics. Its purposes are practical and specific. Why, then, is Belmont silent about ethical theories? It is silent primarily because the Commissioners could not agree upon the theoretical justifications of the principles, even though they had no difficulty in agreeing on the principles themselves.23
Nevertheless, even though the Belmont Report does not display its indebtedness to ethical theory, that theory lurks behind both its principles and applications - the theories of Mill and the deontological ethics of Kant within the principle of respect of person, ethical consequentialism behind the principle and applications of beneficence, and so on. Beauchamp and others ultimately relented to Commissioners requests that the bolder philosophical defenses of theories and theorists in earlier drafts of Belmont should be stripped away from the final report.24
Third, the text of Belmont shows that its principles are advanced as free standing moral norms that are not linked together or prioritized by one or more overarching theories. How these principles are understood in Belmont is subject to two interpretations. First, they are sometimes regarded as equally and absolutely required: they all must be satisfied before research is ethically acceptable.25 Second, they are widely construed as non-absolute, prima facie ethical duties that are always morally binding unless they come into conflict.26 When prima facie principles conflict in particular situations, decision makers must determine how these principles ought to be balanced with one another or whether one of the principles appears to be overriding and, therefore, binding. The Belmont Reportdoes not choose between these very different moral perspectives.27
And fourth, this discussion about the nature of Belmonts principles partially defines what the report is promulgating. To say that according to Belmont, the purpose of a regulatory system is to promulgate ethical principles in order to protect human subjects and enhance science28 skims the surface of Belmonts intent. Belmont promotes the ethics of research for the sake of protecting human subjects 1) through general principles that reflect basic, readily understood, and commonly shared moral values found in and advanced by philosophical ethics, law, and religious traditions and 2) through particular moral requirements and guidelines that resonate with these principles. This presses us to explore the protections provided by Belmont.
B. Protections
To apprehend the protections of human research subjects Belmont provides, its principles must be morally related to its applications. The language of the report says that its principles lead to find expression in, and serve as a basic justification for...particular ethical prescriptions (presumably its applications). These phrases and the word applications itself imply that Belmonts applications are deduced from its principles.29
This should not, however, be taken to mean that its applications are morally secondary or inferior to its principles in terms of their ethical weight. Belmonts principles represent moral requirements, obligations, and imperatives found in its applications. As such, its applications require actions and consist of obligations. Informed consent requires conditions free of coercion and undue influence; and the assessment of risks and benefits requires a careful arrayal of relevant data. The protections provided the Belmont Report are rooted in the moral requirements of both its principles and applications, which in the reports subtitle are referred to as ethical guidelines.
While Belmonts text primarily connotes that its applications are derived from its principles, the contents of the report display a reciprocal interplay between its principles and applications. Members of the National Commission did not merely discover and affirm a set of ethical principles from which they deduced all the applications of the report. By the time Belmont was published, the Commissioners had produced a series of reports on various aspects of biomedical and behavioral research that either focused upon or were filled with the applications found in Belmont. These included reports on research involving prisoners (1976), children (1977), disclosure of research information (1977), and IRBs (1978).30 The Commissions extensive work enabled it to recognize which set of ethical principles (among other moral principles in the ethics literature)31 were relevant or particularly relevant to research.32
The equally strong moral requirements of its principles and applications and the interplay between them directly relates to the protections provided by Belmont.33
The most noteworthy feature about the protections promulgated by Belmont is that at critical points its protections are far greater in the applications section of the report than in its basic ethical principles section. The crucial place in which this occurs entails protections pertaining to respect for persons. According to Belmont, the principle of respect for persons requires that persons should be treated as autonomous agents, which involves giving weight to the opinions and choices of individuals who are capable of deliberating about and acting in accord with their personal goals. Respect also requires refraining from heavy-handed disrespect, such as repudiating the considered judgments of prospective subjects or denying their freedom to act on these judgments. To give weight to a research subjects opinions and choices, however, implies that the authority to weigh and judge resides with someone other than the subject. This phrase undercuts the ethical and legal understandings of respect for autonomy, namely that individuals are free and self-determining agents who have the final authority to decide what should happen to them.34
But what the principle (as stated in Belmont) denies, the applications supply. All prospective participants 1) must be granted the opportunity to choose what shall or shall not happen to them; 2) must be given all the information (much of it detailed in the report) that reasonable volunteer[s] would need to know to decide whether they wish to participate; 3) must comprehend this information (which involves the way the information is organized, the time needed to understand and ask questions, and communication suited to subjects language and levels of intelligence, maturity, rationality); and 4) must be situated in conditions free of coercion, undue influence (due to excessive or improper rewards, overtures, or inducements), and unjustifiable pressures from persons in positions of authority or commanding influence over either the prospective subject or through the controlling influence of a close relative. These applications show that the subjects choice should be free and final.
The principle of respect for persons in Belmont also includes the requirement to protect those with diminished autonomy, which may involve excluding some groups of subjects from research depending upon the risk of harm and the likelihood of benefit to these subjects. Belmonts applications are far more explicit than this dimension of the principle of respect.35
The principle of beneficence encompasses the obligation to reduce social harms and increase social benefits through research - an obligation that can be viewed as nonprotective, if not outright threatening to human subjects of research. This obligation, however, is restrained by the other obligations included within the principle of beneficence, namely, the imperatives of protecting [subjects] from harm and making efforts to secure their well-being by maximizing possible benefits and minimizing possible harms. The applications of this principle offer further restraints. For example, they require a careful arrayal of relevant data, including, in some cases, alternative ways of obtaining the benefits sought in the research, and they embrace a broad range of risks and foreseeable benefits - physical, psychological, social, legal, and economic.36
Belmonts principle of justice charts the different ways justice is defined, but primarily focuses on injustice as occurring when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly. Within its discussion of justice as a principle, the report catalogues historical examples of excessively burdened and exploited patients and begins to deal with how justice and injustice apply to past policies of selecting subjects due to their easy availability, compromised position, or manipulability. The report extends this analysis in its applications section.37
Importantly, the principles of beneficence and its applications and the principle of justice and its applications serve as gate keeper functions. They are the ethical criteria which IRBs must use to determine which research projects and protocols are acceptable enough to move to the stage of subject enrollment. They serve, therefore, as essential, but nevertheless initial moral screens prior to the ethical bedrock of Belmonts human subject protection - the vital protections surrounding informed consent.
The Belmont Reports great reliance upon informed consent accords with the fundamental moral values of a free and democratic society. This requires a high bar for informed consent, which Belmont strongly upholds as its bedrock basis for subject protection. Without this bar, permissible research would have to reflect strict and delimited research risks.38 Without the protections inherent to informed consent, the resulting stricter controls of risks and benefits would have the effect of transmogrifying the relationships between subject protections and the research enterprise into a zero-sum game.
These points enable us to complete the description (begun at the end of section A above) of what the Belmont Report is promulgating for the purpose of protecting human subjects. Belmont promulgates the ethics of research through general principles 1) that reflect basic, readily understood, and commonly shared moral values found in and advanced by philosophical ethics, law, and religious traditions, and 2) that are strengthened and expanded by the ethical requirements and guidelines specified in its applications.
C. Flaws
In spite of its manifest strengths, the Belmont Report bears the flaws and cracks of an earthen vessel. First, in spite of its clear, schematized outline, it is not easily understood or fathomed. It contains the multilayered features of a document comprised by a committee with many agendas.39
Second, Belmonts silence about how its three principles are related to each other has given rise to confusions and conflicting interpretations about their relationships. This is regrettable, because relating, prioritizing, or balancing Belmonts principles is inevitable for the assessment of many protocols. Some level of guidance is needed for the sake of encouraging moral reflection and more responsible decision making by IRBs.40
Third, Belmont is conceptually flawed. By linking its principle of respect for persons with autonomy, the report exposes itself to cogent criticisms by bioethicists who argue that its principle of autonomy is anemic, if not wrong headed.41 Belmonts principle of autonomy does not square with its applications. Bioethicists also point out that this principle should be distinguished from the principle of protecting persons from harm, which pertains to beneficence.42 But unless the Commissioners were hopelessly confused, which, given all the philosophical papers they heard and read, we have no pressing reasons to believe, Commissioner Lebacqzs interpretation of what Belmont was meant to convey under its respect for persons principle is probably correct. The majority of Commissioners wanted the rather open-ended phrase respect for persons to denote respect for autonomy, respect of persons with diminished autonomy, respect of fetuses and infants, and possibly respect for communities of persons.43 A sentence or two could have clarified some of the confusion.
Fourth, the Belmont Report mentions (which has often gone unnoticed),44 but does not accent or expand upon the ways distributive justice or fairness requires extending the benefits of research to underserved populations of patients.45 The report also does not mention issues related to compensatory justice - the imperative of compensating at least some subjects in some circumstances for the injuries sustained in research.46
Fifth, Belmont focuses on the protection of individuals to the neglect of communities. Had the report discussed probable benefits and harms to communities, its protections could have been extended to other areas of research, including stem cell, xenotransplantation, and genetics research.47
And sixth, the report does not offer direct guidance or examples regarding one of its explicit purposes - the purpose of formulating, criticizing, and interpreting codified regulations. Belmonts silence in this regard has likely contributed to its marginalization and neglect, as well as to its not yet being used as a basis for critical revisions of the Code of Federal Regulations.
D. Power
Do Belmonts flaws undermine its power to effect changes in the Federal Regulations in order to enhance subject protections? No. The treasures of the Belmont Report are found in its legal, historic, and revered status, and its great intrinsic worth. Its intrinsic value encompasses:
- The strong protections provided in Belmonts applications of informed consent, which correct the flawed definition of autonomy in its principles section and which several of the reports bioethics critics seem to have overlooked,
- How the reports sections on justice and injustice serve as strong protections for vulnerable populations of research subjects,
- The many ways Belmont insightfully and specifically links its principles and applications to the realities of biomedical research,
- The degrees to which Belmont puts the language of ethics into commonly used and easily grasped categories suitable to diverse professional groups and reflective of common morality,
- The ways in which the Belmont Report proves that research involving human subjects inherently includes ethical issues and raises moral problems,
- And the way Belmont forges a confluence between serious ethical reflection, empirical study, and legal and policy analysis at a national level.48
Belmonts flaws limit its ability to enlighten and resolve day-to-day decision making by IRBs and researchers, but they do not keep Belmont from serving as a powerful basis for
correcting serious problems in the Federal Regulations.
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IV. Changes in the Code of Federal Regulations Mandated by Belmont
This section has a clear and specific goal. It will show how coherent and systematic linkages between the Belmont Report and the Federal Regulations will rectify the serious problems in the Regulations identified in section II above. These changes will also make the Regulations clearer, better focused, easier to use, and less bureaucratic.
The subsections that follow are arranged in a problem-solution format. Each will first describe a major problem in the Federal Regulations , then suggest how the relevant
section(s) of the Regulations should be reformed and reorganized.
A. Corrections of the Federal Regulations Disregard of Ethics
Unfortunately, the accent on the importance and roles of ethics in the Belmont Report is virtually absent from the Federal Regulations . Any mention of ethical standard or ethical principles appears only in later Subparts that deal with special populations of patients/subjects. Subpart B (Protections of Fetuses and Pregnant Women) 46.202 says that the activities under review should conform to appropriate ethical standards. And subpart D (Protections for Children) 46 (b) (1) (ii) states that the research will be conducted in accordance with sound ethical principles. Furthermore, the term ethics is mentioned only once in the main body of the regulations - in 46.103 (b) (1) in connection with a statement of principles that should be adopted by institutions that are applying for assurance of compliance agreements with a federal department or agency.49 Specific recommendations for correcting this disregard are given in the sections that follow.
B. Rectification of the Regulations Irresponsible Standards Pertaining to the Sources that Define and Articulate Research Ethics
The one place where ethics is mentioned in the main body of the Federal Regulations reflects an irresponsible approach to the ethics of research. Section 46.103 (b)(1) says that a statement of principles for the purpose of protecting the rights and welfare of human subjects of research is required in an assurance of compliance agreement. But the actual content of such a statement is not taken seriously, and its uses are not addressed.
Here is the wording about the statement that is required of institutions: This [statement] may include an appropriate existing code, declaration, or statement of ethical principles, or a statement formulated by the institution itself.50 So stated, a document that deals with the ethical principles of research is 1) viewed as an option on equal par with some existing code (The Nuremberg Code?), or declaration (The Declaration of Helsinki?), or some statement formulated by an institution itself. This falsely assumes 2) that all of the above options will serve to protect the rights and welfare of human subjects. 3) This wording also apparently assumes that the statement that is submitted in an assurance of compliance application will inform IRB deliberations at the institution making the application. But how or when the statement is to be used is not mentioned. And 4) this directive conflicts with explicit statements in the first paragraphs of the Belmont Report that the often inadequate and conflicting codified rules in Nuremberg, Helsinki, and the U.S. Federal Regulations of 1974 need to be expanded, criticized, and interpreted by utilizing ethical principles.
Section 46.103 (b) (1) should be revised to convey the following [in which changes and additions are underlined]:
Assurances applicable to federally supported or conducted research shall at a minimum include:
(1) A statement of ethical principles and rules governing the institution in the discharge of its responsibilities for protecting the rights and welfare of human subjects of research conducted at or sponsored by the institution, regardless of whether the research is subject to Federal regulations. This statement of ethical principles should include, at minimum, the tenets of the Belmont Report. The statement should serve as an ongoing basis for training programs and protocol evaluation by the institutions IRB members and investigators.
C. Correction of the Flawed Understanding of the Ethics of Research in the Federal Regulations
Regrettably and surprisingly, the Federal Regulations themselves incorporate a seriously flawed understanding of research ethics. This is found in the body of the Regulations 46.107 (a) under the heading of IRB membership. The third sentence of 46.107 (a) says:
In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas.51
In this directive the critical task of ascertaining the acceptability of proposed research 1) rests on the vague, unspecific category of institutional commitments and regulations, 2) does not even mention ethics or sound ethical reasoning, and 3) falsely assumes that standards of professional conduct and practice (presumably, professional codes of ethics) directly relate to the ethics of research. The import of this last and false assumption is highlighted in the discussions and recommendations of the Final Report of the Advisory Committee on Human Radiation Experiments. Recommendation 9 of this Final Report includes the following:
The historical record and the results of our contemporary projects indicate that the distinction between the ethics of research and the ethics of clinical medicine was, and is, unclear. It is possible that many of the problems of the past and some of the issues identified in the present stem from this failure to distinguish between the two.
The Committee suggests...the following:Incorporating of research ethics, and the differences between the ethics of research involving human subjects and the ethics of clinical medical care, into curricula for medical student, house staff, and fellows.52
To correct this flawed understanding of research ethics in the body of the Federal Regulations , the wording quoted above from part 46.107 (a) should be revised to convey the following [in which the word changes are underlined]:
In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of sound ethical reasoning that distinguishes the ethics of research from the ethics of clinical care, applicable law, and each institutions statement of ethical principles and rules specified under 46.103 (b) (1).
D. Clarification of Organizational Confusions in the Regulations
To make the Regulations clearer, better focused, and easier to use, the criteria investigators and IRB members are to follow and utilize as they develop, approve, or disapprove of research protocols should be reorganized. The places where the Regulations require researchers and members of IRBs to make judgments or determinations regarding research protocols are separated from each other and are interspersed between IRB house keeping rules and enforcement powers. This results in an array of directives that obscures, rather than highlights, what investigators and IRBs are supposed to do.
The primary organizational confusion of the Regulations occurs between sections 46.111 (Criteria for IRB approval of research) and section 46.116 (General requirements for informed consent). Between these sections there are several others that deal with the powers and limits of non-IRB institutional officials (46.112), the power of IRBs to suspend or terminate research (46.113), the roles of IRBs respecting cooperative research projects (46.114), and management-and-federal-oversight concerns regarding IRB records (46.115). In short, the types of judgments that researchers and IRBs are to make are imbedded in lists of rules pertaining to management and enforcement.
In order to bring these judgments into focus and highlight their importance, the Federal Regulations should be reordered in a logical progression and, on occasion, display different titles. A cursory review of the items that follow indicates how they are scrambled and disorganized in the Common Rule. [Note: Changes in ordering, numbering, and wording are underlined in the suggested reorganization that follows, and the numbering of the Regulations as they now exist are placed in brackets.]
- 46.109 IRB review of research.
- 46 .110[46.111] Criteria for IRB approval of research.
- 46 .111 [46.116] Criteria for informed consent.
- 46 .112 [46.117] Requirements for the Process and Documentation of informed consent.
- 46 .113 [46.110] Expedited review procedures for certain kinds of research.
- 46 .114 [46.113] Suspension or termination of IRB approval of research.
- 46 .115[46.114] Cooperative research.
- 46 .116 [46.115] IRB records.
- 46 .117 [46.112] Additional review by institutional officials.
- 46.118 Applications and proposals lacking definite plans for involvement of human subjects.
E. Emendations of Sections in the Federal Regulations that Deal with Criteria for IRB Determinations and Investigator Compliance
The rules and requirements IRBs should utilize to review and approve of research involving human subjects (other than special populations) and that investigators should follow are in sections 46.111 and 46.116 of the Regulations - reordered as sections 46.110 and 46.111 above.
These sections of the Regulations display four main problems:
- First, at points the Regulations are incomplete. They do not capture a number of the important points and themes in the Belmont Report that increase and ensure the protection of human subjects.
- Second, the Regulations are preoccupied with protecting human subjects via rule-stating and IRB and investigator rule-following. This contrasts with the Belmont Reports explicit statements about the inadequacy of codified rules and how a simple listing of rules fails to identify the standards that should be used to judge how these rules are interpreted and applied.53
- Third, the Regulations are not organized according to the Belmont Reports conceptual categories and moral guidelines, which can make the duties of IRB members and researchers more intelligible, add necessary provisions, and highlight the importance of moral reasoning and judgment making. These conceptual categories and moral guidelines do not need to mention the first two ethical principles articulated in Belmont. Instead, they should draw upon the readily understood wording and categories in the application sections of the report. Some of the application sections offer greater protections than the principles, and they clearly indicate how ethical principles relate to the conduct and review of research - risk/benefit assessment, justice, ethical reasoning, comprehension, voluntarism, and so on.
Section 46.111 is more or less clear and well outlined, but can be and should be improved.54 Section 46.116 is far more problematic both in terms of its outline and content.55
- Fourth, section 46.116 distorts major themes in the Belmont Report that pertain to subject protections. This section begins with a paragraph that conveys some of what Belmont says about the three elements of consent - information, comprehension, and voluntarism. But then the Regulations identify the Basic Elements of informed consent with only one of Belmonts categories - information that should be provided to each subject [46.16 (a)].56 While all of the items in this section are important, their being called basic elements of informed consent directly encourage investigators and IRBs to equate informed consent with rules about the information subjects should receive in consent forms. This undermines the content of the first paragraph in 46.116 and distorts the analysis and essential features of informed consent in the Belmont Report.
Taken together, these four problems show that the Federal Regulations do not embody the purposes and power of the Belmont Report - its insistence on critical and organized reasoning, and a number of its recommendations regarding the protection of research subjects.
These serious problems should be corrected. The purposes, concepts, and language of the Belmont Report readily serve as a foundation for this correction.
The corrections/revisions suggested for 46.111 (Criteria for IRB approval of research) are given in Appendix A of this paper. The suggested corrections/revisions of 46.116 (General requirements for informed consent) and 46.117 (Documentation of informed consent) are given in Appendix B. The emendations suggested for 46.116 and 46.117 reflect the applications of informed consent in the Belmont Report, as well as the discussion in section III. B of this paper concerning the bedrock protective value of informed consent in a democratic society.
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V. Putting Ethics into Practice: What are Researchers and IRB Members Supposed to Be Doing?
To be effective, protections of human subjects of research should be suited to the everyday concerns and practices of researchers and the reviewers of human subject research. This can be done by stepping into the shoes of investigators and IRB members who, upon wrestling with research regulations and working with regulatory bodies, regularly ask, What are we supposed to be doing? This question serves as a simple, straightforward test for what an effective regulatory system ought to be communicating through its codified regulations and the ethical principles and requirements upon which these regulations rest. This pragmatic test means that those who compose and/or amend and alter the Code of Federal Regulations should ask themselves, Are we clearly communicating what those on the front lines of human subject protection need to be doing to protect human subjects?
The foregoing sections of this paper show that at the present time the Federal Regulations tell investigators and regulators what they should be doing in a considerably disorganized, incomplete, confusing, and follow-the-rules fashion. For example, IRB members are told that risks to subjects should be minimized and reasonable in relation to anticipated benefits [46.111 (a) (1) and (2)] without being told how this can and should be done by means of a systematic assessment of risks and probable benefits. IRBs are also told that informed consent will be sought...in accordance with, and to the extent required by 46.116. Four sections later in the Regulations, 46.116 does not mention IRB oversight. In its initial paragraph, 46.116 tells investigators that they should seek to secure the consent of subjects or their representatives only under circumstances...that minimize the possibility of coercion or undue influence, and through giving information in language understandable to the subject or the representative. This paragraph is a prelude to the clearly outlined and listed basic elements of informed consent [46.116 (a)], the wording, outline, and contents of which clearly convey what investigators and IRB members should be doing to protect human subjects: They should make sure that consent forms contain all the information listed in the Regulations, and they should refine or tweak consent forms that cannot be understood or that lack any of the required information.57
The emendations advanced in this study retain the contents of above requirements, but they link these requirements together, outline what should be done more clearly, fill in blind spots, correct misunderstandings, and make them more thought provoking. These emendations give the following answers to the question, What are researchers and IRB members supposed to be doing to protect human beings enrolled in research?
- Make thoughtful decisions based on your institutions training program regarding the ethics and regulation of research.
- Do a systematic and rational evaluation of the risks and benefits pertaining to each research protocol in order to make sure that its risks and probable benefits are morally justifiable.
- Take steps to assure that the selection of subjects reflects a just and equitable sharing of both the burdens and benefits of research.
- Make sure that the consent form is part of a consent process that will enable all subjects or their representatives 1) to freely choose whether or not to become enrolled, 2) to comprehend what is being told to them, and 3) to understand essential information about what the research entails, what their options are, and so on.
- And see that prospective subjects and researchers engage in mutual communication that will assure that the above three essential elements of consent are adequately fulfilled.
The thesis of this paper is that the above actions and practices are necessary for the protection of human subjects. Each directly reflects the ethics of research promulgated in the Belmont Report. Each and all of these moral imperatives should, therefore, be clearly and adequately communicated through the Federal Regulations and suited to concerns and practices of researchers and IRB members.
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Conclusions and Recommendations
This paper has explored the shared purposes and different approaches of the Belmont Report and the Code of Federal Regulations with respect to protecting human subjects of research. It has identified a number of major problems in the current Code of Federal Regulations, and has shown that the purposes and content of the Belmont Report can and should be used to rectify these problems. The presence of these problems prove that the protections of human subjects of research advanced within Belmont have not yet been adequately incorporated within the Federal Regulations . This paper also describes clear and specific ways to revise the actual wording and organization of the Regulations. And it argues that truly effective guarantees of subject protection must give clear and adequate answers to the practical concerns of and questions asked by investigators and reviewers of research protocols.
Predicated upon this study, the author makes two recommendations to the members of the National Bioethics Advisory Commission:
- First, seize the present opportunity to call for an expert task force that will utilize the Belmont Report and this commissioned paper to make ethically imperative recommendations for changes in the Federal Regulations.
- Second, strongly consider the need to call for a revision of the Belmont Report itself - Belmont II - for the sake of articulating a clearer and more comprehensive understanding of the ethics of research. The members of a task force that would be able effectively to revise the Belmont Report should either be students or willing students of the reports text, meaning, manifest strengths, weaknesses, and historic contributions. They should be or should have a passion for becoming thoroughly acquainted with the research enterprise as it now exists and as it is likely to exist in the foreseeable future. They should value clarity of communication. They should be deeply committed to the dynamics of a free society and to the two overarching purposes of a regulatory system: protection of the rights and welfare of human beings who become involved in research and the promotion of beneficial research.
Note: I thank my colleagues Ronald A. Carson, Cheryl M. Chanaud, and William J. Winslade for their critical comments and suggestions.
Appendix A
- Note: The word changes below are underlined. Deletions from the present Regulations are indicated by removing the bold typescript and the numbering of the items have been changed, with the numbering as it now exists placed in brackets.
- 46.111 Criteria for IRB approval of research.
- [a] In order to approve research covered by this policy the IRB shall determine that all of the following requirements pertaining to the welfare and rights of human research subjects are satisfied.
- a) A systematic and rational assessment of the risks and probable benefits which shows
- (1) Risks to subjects are minimized: (i) by using procedures which are consistent with sound research design, (ii) by considering physical, psychological, and social risks, and (iii) [ii] whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
- (2) Risks to subjects are reasonably balanced in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result from the research.
- (i) by giving special weight to subjects risks over the probable social benefits of research, (ii) by considering only those risks and probable benefits that may result from the research (as distinguished from comparing these to the risks and probable benefits of therapies prospective subjects would receive as patients not participating in the research), and (iii) by giving particular consideration to the voluntariness and comprehension of subjects of research that offers fewer, if any, benefits and greater risks to the subjects, but significant benefits to society. The IRB should not consider possible long-range effects of applying knowledge gained in research (for example, the possible effects of the research on public policy) as among the research risks that fall within the purview of its responsibility.
- b) [3] Just and equitable procedures are used in the selection and recruitment of prospective subjects. IRBs should be particularly cognizant of the ethical problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons. They should also be cognizant of justly including women, ethnic minorities, and all age groups in research that will likely contribute to their health and well being.
- [Keep the present wording of sections 46.111 (4) through (7), but renumber them as (c) through (f).]
- [b] When some or all of the subjects are likely to be vulnerable to coercion or undue influences, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantage persons, (i) the appropriateness of involving them should be demonstrated, and (ii) additional safeguards have been included in the study to protect the rights and welfare of these subjects.
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Appendix B
- Note: The word changes below are underlined. Deletions from the present Regulations are indicated by removing the bold typescript. The numbering of the items has been changed, with the numbering as it now exists placed in brackets.
- 46.116 Criteria for informed consent.
- Except as provided elsewhere in this policy, no investigator may involve a human being as a subject in research covered in this policy and IRBs may not approve of such research unless the investigator obtains the legally effective and ethically justifiable informed consent of the subject or the subjects legally authorized representative. The consent process has the following three basic elements: (a) Voluntariness-An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative the opportunity to freely choose whether or not to participate and that minimize the possibility of coercion, undue overtures, rewards, or inducements, and unjustifiable pressure from researchers or through relatives. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subjects legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence.
- (b) Comprehension. The information that is given to the subject or the representative shall be organized and presented in language understandable to the subject or the representative. The subjects comprehension of information and explanations should be assured through mutual communication and practical methods of comprehension assessment. Subjects or the representative should be given sufficient time to make an informed choice.
- (c) [a] Understanding. Except as provided in paragraph (e) [c] and (f) [d] of this section, in seeking and evaluating informed consent, the following information shall be provided to each subject:
- (1) An explanation that the study involves research . . .
- (5) An explanation describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; . . .
- (8) An explanation that participation is a voluntary choice the subject is free to make, that refusal to participate will involve no penalty or loss of benefits to which the subject is entitled and aware of, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is entitled and aware of.
- [b] Additional elements of informed consent . . .
- (1) An explanation that the particular treatment or procedure . . .
- (5) An explanation that significant new findings . . .
- 46.117 Requirements for the Process and Documentation of informed consent. . .
- (b) Except as provided in paragraph (c) of this section, the consent form may be either of the following:
- (1) A written consent document that embodies the basic elements of informed consent required by 46.116. This form may be read to the prospective subject or the subjects legally authorized representative, but in any event, the investigator shall give either the subject or the representative adequate opportunity to read, discuss, ask questions, and comprehend it before it is signed.
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Footnotes