Attachment A: Recommended Guidance on Minimal Risk Research and Informed Consent

A. Statement of Issue

Introduction

The Federal Policy for the Protection of Human Subjects in Research (56 FR 28003), enacted in 1991 and codified by 18 Federal Departments or agencies, sets out the core protections of organizational assurances of compliance, institutional review board review and informed consent for federally funded research involving human subjects. The regulations delineate General Requirements for Informed Consent in 45 CFR Part 46.116. The responsibility for obtaining legally effective informed consent is specifically assigned to investigators (46.116), while responsibility for approving the consent form is delegated to IRBs (46.117). Improving understanding and the decision-making capacity of subjects is a paramount responsibility of investigators, and the process by which consent is obtained must be designed to contribute to that end. SACHRP recognizes that in the context of minimal risk research, there is a general consensus among regulators, ethicists, researchers, IRBs, sponsors and subjects that there has been too much focus on the consent form.

Statement of the Problem

Over the years, consent documents have been steadily growing in length and complexity, even for research deemed minimal risk. Consent forms too often include confusing and difficult wording that obscures the information that is necessary to assure adequate disclosure, comprehension and voluntariness, detracting from the ability of a prospective subject to focus on the important information. Previous SACHRP recommendations have attempted to address the problem of lengthy and incomprehensible consent forms, but the problem persists.[1]

The tendency of sponsors, institutions, researchers and IRBs to include more information than necessary in consent forms is due to the form often being the only document viewed by a research participant. Additions to the consent form include information not required by the regulations; and, information that is intended to protect an institution or a sponsor or ensure research integrity and investigator compliance. Institutions have turned to IRBs to serve as the primary gatekeeper for all information related in any way to research, with the consent document serving as the vehicle for communication. Examples of this include HIPAA requirements, GINA, and clinicaltrials.gov.

The regulations themselves provide flexibility in adapting a consent document to a specific research project and yet it is clear that the research community has not been willing to take advantage of the regulatory flexibility. Several of the elements of informed consent, outlined in both the basic and additional sections of 45 CFR Part 116, are only necessary if the research involves greater than minimal risk research; if there are “any” issues relating to certain elements identified in the regulations; and, in other cases only “if appropriate.” In addition, IRBs are empowered to “approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent.” (45 CFR 46.116(d)) And, IRBs “may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if … the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.” (45 CFR 46.117(c)(2)) It should be noted that under the current regulations there are some elements of informed consent that can only be waived or altered if the criteria at §46.116(d) are met. The criterion at §46.116(d)(3) may be problematic, as it will be difficult to demonstrate that the research would not be practicable without the waiver of selected elements based on an IRB’s determination that a given element is not necessary for the potential subject’s decision to participate in research. SACHRP recommends that OHRP permit IRBs to waive elements of consent without meeting this criterion for research that is determined to represent minimal risk.

It has thus become clear that informed consent documents have become: (1) a repository for any information to be provided to a research subject; (2) a “one-size fits all” template that contains all elements, regardless of whether they are all necessary for minimal risk research; and, (3) unacceptably long and complicated because information that is not required by the regulations is nonetheless expected to be included. All of this is perpetuated because of the reticence of IRBs and their institutions to invoke the flexibility permitted by the regulations. The net result of this is that research subjects receive an exorbitant amount of information that does not add value to the decision-making process, thereby undermining the informed consent process.

Informed Consent Processes in the Context of Minimal Risk Research

While the issues above regarding informed consent are well-known in clinical research, they have also manifested themselves in minimal risk research settings: both biomedical and social and behavioral.

The regulations state that “minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (45 CFR 46.102(i)) It is acknowledged that understanding of this definition and its objective application to research has been problematic, leading to inconsistencies across IRBs reviewing similar protocols. SACHRP previously approved recommendations on the interpretation of minimal risk.[2]

SACHRP therefore recommends that OHRP and FDA encourage sponsors, investigators, institutions and IRBs to embrace a simplified informed consent process for minimal risk research. When reviewing a minimal risk project IRBs should, at the outset, consider whether an oral consent process is appropriate given the nature of the research and institute documentation through written forms only when necessary. (45 CFR Part 46.117(c)(2)) Much of the research that is minimal risk involves no procedures for which written consent is required outside the research context. Additional documents such as information sheets or brochures can be useful companions to a robust oral informed consent process.

The regulations describe documentation of informed consent as the obtaining of a subject’s signature on either a written consent form (45 CFR 46.117(a)) or a short form (45 CFR 46.117(b)). This type of written documentation is one way of recording that consent was obtained, but there are other methods of recording that consent was obtained. Two examples of this is are a signed and dated attestation by an investigator affirming that consent was obtained, or a data field on an internet survey indicating that a subject scrolled through the information about the survey and clicked on a button affirming their intent to participate before being allowed to start the survey. Use of alternative models to record consent requires the IRB to approve a waiver of documentation. Although such alternative methods for recording that consent was obtained are not required by the regulations and do not satisfy the regulatory requirements for documentation, IRBs should be willing to consider them as effective mechanisms for capturing the outcome of the consent process.

SACHRP recognizes that, given the wide range of research activities included in the minimal risk category, there will not be a single consent model that will apply. Therefore, IRBs should refocus on the consent process to determine what is most appropriate, and not automatically require consent documentation. Rather than relying solely on consent forms, investigators, institutions and IRBs should create other techniques/mechanisms for ensuring compliance and facilitating auditing functions. When an IRB determines that a written form is appropriate, IRBs and researchers should strive for simplicity.

B. Guiding Principles for Minimal Risk Research

SACHRP proposes the following guiding principles for informed consent for minimal risk research:

The consent process for minimal risk research, whether solely oral or including written materials, should be concise and include only the information about the research that a reasonable person would want to know. (45 CFR 46.116) It is the responsibility of the investigator to provide more information when requested by subjects or to improve a particular subject’s understanding.
Investigators and IRBs should use the existing flexibility provided in the regulations to match the informed consent process, and supplemental materials, if any, to the specific circumstances of the research under consideration
An oral consent process when appropriate under 46.117(c)(2) should be used when it will enhance the quality of the consent process. In its deliberations and discussions with investigators the IRB should consider how the consent process will be implemented, what information will be communicated, and whether supporting materials will be given to the subjects.
Consent materials for studies should be written in language understandable to the study population. Simplification/reading comprehension should take precedence over shortening the length of the document. That is, simple language and formatting for ease of reading may increase the length of a document, but the end result can be a more understandable and useful document.
Where an oral consent process is not an option, the next consideration should involve use of simplified written consent materials, as demonstrated in models that will be developed.
Where relevant, separate supplemental documents should be used to convey information that is not directly relevant to a decision to participate in the research.
Risks or burdens that are immaterial or obvious to potential participants need not be explicitly addressed in the consent form or dialogue. For example, participants need not be told that needle sticks can cause minor pain or that surveys can be boring. There is also no need to specifically state the absence of risk where none exists.
With regard to confidentiality, it is not necessary to describe all of the mechanisms to protect research data; a simple statement regarding confidentiality and its limitations will be sufficient.

[1] SACHRP has approved multiple recommendations related to informed consent, including Guidance on Applying the Regulatory Requirements for Research Consent Forms: What Should and Should Not be Included?

[2] SACHRP letter to HHS Secretary dated January 31, 2008.