Human Research Protection Program

The regulations define research as "a systematic investigation, including development, testing and evaluation, designed to develop or contribute to generalizable knowledge" (§46.102, Section d).

The regulations define human subjects as “a living individual about whom an investigator (whether professional or student) conducting research obtains:

1. Data through intervention or interaction with the individual, or

2. Identifiable private information (§46.102, Section f).

• Can research questions be answered without human subjects research?

In its discussion of the systematic assessment of risks and benefits, the Belmont Report discusses the necessity of using human subjects to answer the research question(s): "The assessment of risks and benefits requires a careful arrayal of relevant data, including in some cases, alternative ways of obtaining the benefits sought in the research. Assessment of the justifiability of research should reflect at least the following considerations … (ii) Risks should be reduced to those necessary to achieve the research objective. It should be determined whether it is in fact necessary to use human subjects at all" (Part C, Section 2).

In its discussion of the assessment of risks and benefits, the Belmont Report adds to the question of appropriateness of the use of human subjects, the question of the appropriateness of the study's design: "… For the investigator, it is a means to examine whether the proposed research is properly designed. … Risk can perhaps never be entirely eliminated, but it can often be reduced by careful attention to alternative procedures" (Part C, Section 2).

In addition, the regulations discuss how risks to subjects be minimized "by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk" (§46.111, Section a1).

While the Nuremberg Code lists the investigator's qualifications as a requirement for ethical research (#8: "The experiment should be conducted only by scientifically qualified persons"), the Belmont Report and the regulations are quiet on the subject. However, as the principal investigator is responsible for ensuring the safety of the research subjects, an assessment of their qualifications is often considered as an aspect of the risk-benefit analysis (including whether they have the knowledge and experience to determine the most appropriate study design), and the Brandeis University IRB has traditionally included this in its review.

• Is a certain group being targeted without justification?

• Is (are) the research question(s) relevant to the group(s) included in the research?

• Do enrollment procedures support equitable selection?

• Is a vulnerable population being used? If yes:

  • Is the justification for the use of the vulnerable population sufficient?
    • Is the use of the vulnerable population vital to answer the research question(s)?
  • Is protection of the vulnerable population's rights and welfare appropriate?

The regulations list seven general criteria to the review of research, including the equitable selection of subjects: "In making this assessment, the institutional review board should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons or economically or educationally disadvantaged persons" (§46.111, Section a3).

The regulations continue … "When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects" (§46.111, Section b).

In addition, the selection of subjects is central to the principle of justice, and is discussed extensively in the Belmont Report: "Just as the principle of respect for persons finds expression in the requirements for consent, and the principle of beneficence in risk/benefit assessment, the principle of justice gives rise to moral requirements that there be fair procedures and outcomes in the selection of research subjects. …" (Part C, Section 3).

• Is there a danger of prospective subjects feeling coerced?

• Is equitable selection of subjects supported in recruitment materials and procedures?

  • Does the language/style of the materials target specific populations such that they may be overrepresented in the research?

  • Are materials distributed only in locations most often frequented by specific populations such that they may be overrepresented in the research?

• Is there the potential for the invasion of prospective subjects' privacy in recruitment procedures?

• Is the research and subjects' participation accurately portrayed in the recruitment materials?

While neither the regulations nor the Belmont Report reference recruitment materials specifically, there are a number of issues surrounding recruitment that require consideration.

The issue of undue influence and coercion, and its threat to the principle of respect for persons is discussed in the Belmont Report: The "element of informed consent requires conditions free of coercion and undue influence. … Unjustifiable pressures usually occur when persons in positions of authority or commanding influence — especially where possible sanctions are involved — urge a course of action for a subject" (Part C, Section 1).

The Belmont Report goes on to discuss the importance of the equitable selection of subjects and its significance to the principle of justice: "Social justice requires that distinction be drawn between classes of subjects that ought, and ought not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens and on the appropriateness of placing further burdens on already burdened persons. … Injustice may appear in the selection of subjects, even if individual subjects are selected fairly by investigators and treated fairly in the course of research. Thus, injustice arises from social, racial, sexual and cultural biases institutionalized in society. Thus, even if individual researchers are treating their research subjects fairly, and even if IRBs are taking care to assure that subjects are selected fairly within a particular institution, unjust social patterns may nevertheless appear in the overall distribution of the burdens and benefits of research" (Part C, Section 3).

In addition, the regulations require both the equitable selection of subjects and the protection of privacy: "In making this assessment [of the selection of equitable subjects] the IRB should take into account the purposes of the research and the setting in which the research will be conducted (§46.111, Section a3). … When appropriate, there are adequate provisions to protect the privacy of subjects" (§46.111, Section a7).

• Are the risks and benefits adequately discussed?

• Is it anticipated that subjects will be exposed to greater than minimal risk?

• Are anticipated risks minimized to the extent possible?

• Are anticipated risks justified based on the possible benefits of the research?

• Are provisions for managing anticipated risks adequate?

The regulations require that risks to subjects be "reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result" (§46.111, Section a2).

In addition, the Belmont Report includes a lengthy discussion of the assessment of risks and benefits in human subjects research: "The term 'risk' refers to a possibility that harm may occur. However, when expressions such as 'small risk' or 'high risk' are used, they usually refer (often ambiguously) both to the chance (probability) of experiencing a harm and the severity (magnitude) of the envisioned harm… so-called risk/benefit assessments are concerned with the probabilities and magnitudes of possible harm and anticipated benefits. Many kinds of possible harms and benefits need to be taken into account. There are, for example, risks of psychological harm, physical harm, legal harm, social harm and economic harm and the corresponding benefits. … The idea of systematic, nonarbitrary analysis of risks and benefits should be emulated insofar as possible. This ideal requires those making decisions about the justifiability of research to be thorough in the accumulation and assessment of information about all aspects of the research, and to consider alternatives systematically. … The method of ascertaining risks should be explicit. …" (Part C, Section 2).

While neither the regulations nor the Belmont Report discuss specifically the appropriateness of the data being collected, the Brandeis University IRB has traditionally considered it in relation to subjects' privacy, the protection of which is specified in the regulations: "When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data" (§46.111, Section a7).

• Will the data compiled be anonymous?

• Will the data compiled be confidential?

The regulations require that "when appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data" (§46.111, Section a7).

In addition, the importance of maintaining subjects' privacy is inherent in the Belmont Report's principle of respect for persons and a person's choice with whom to share private information: "An autonomous person is an individual capable of deliberation about personal goals and of acting under the direction of such deliberation. To respect autonomy is to give weight to autonomous persons' considered opinions and choices. ... To show lack of respect for an autonomous agent is to repudiate that person's considered judgments, to deny an individual the freedom to act on those considered judgments" (Part B, Section 1).

• Where and in what form will data be stored?

• Will subject identifiers be stored separately from research data?

• Is the data disposal plan appropriate and timely?

The regulations require that "when appropriate, there are adequate provisions for monitoring the data collected to ensure the safety of subjects" (§46.111, Section 6).

In addition, the data management plan is central to the protection of subjects' privacy.

Note that we are currently developing data management plan requirements for human subjects research. Our current default is for electronic data to be uploaded to box.com or
files.brandeis.edu, hard copies of data should be stored in a locked cabinet (and disposed of when finished with), and consent forms and master codes/pseudonyms must be stored in a separate locked cabinet. Variations/deviations are sometimes required and should be assessed on a case-by-case basis.

If yes:

• Is the justification for the use of deception sufficient?

  • Is the deception vital to answer the research question(s)?
• Is the debriefing adequate?

• Is the debriefing conducted at the earliest time feasible?

• Is a waiver of debriefing being requested? If yes:

  • Is the waiver appropriate and justified?
    • Would the debriefing increase the risks to subjects?
    • Would the debriefing cause more harm than the deception itself?

The regulations detail the elements of informed consent, and while the use of deception is not specifically discussed, the necessity of a debriefing is included in the requirements for a waiver or alteration of informed consent (a necessity in cases where deception is used): "An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent … or waive the requirement to obtain informed consent provided the IRB finds and documents that. … Whenever appropriate, the subjects will be provided with additional pertinent information after participation" (l§46.116, Section d4).

The Belmont Report, on the other hand, specifies the lack of informed consent in cases of deception: "A special problem of consent arises where informing subjects of some pertinent aspect of the research is likely to impair the validity of the research. In many cases, it is sufficient to indicate to subjects that they are being invited to participate in research of which some features will not be revealed until the research is concluded. In all cases of research involving incomplete disclosure, such research is justified only if it is clear that (1) incomplete disclosure is truly necessary to accomplish the goals of the research, (2) there are no undisclosed risks to subjects that are more than minimal and (3) there is an adequate plan for debriefing subjects, when appropriate, and for dissemination of research results to them. Information about risks should never be withheld for the purpose of eliciting the cooperation of subjects, and truthful answers should always be given to direct questions about the research. Care should be taken to distinguish cases in which disclosure would destroy or invalidate the research from cases in which disclosure would simply inconvenience the investigator" (Part C, Section 1).

If yes:

• Is compensation equitable and reasonable?

The regulations do not discuss specifically the role of compensation to research subjects; they do, however, list voluntariness as one of the basic elements of informed consent: "A statement that participation is voluntary" (§46.116, Section a8).

The importance of voluntariness is then outlined in the Belmont Report: "An agreement to participate in research constitutes a valid consent only if voluntarily given. This element of informed consent requires conditions free of coercion and undue influence. Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance. Undue influence, by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance. Also, inducements that would ordinarily be acceptable may become undue influences if the subject is especially vulnerable" (Part C, Section 1).