Minimal risk and large-scale biobank and cohort research.

• Author: Caulfield, Timothy

Introduction

Minimal risk is a core concept in research ethics, but its proper role in the regulation of large-scale biobank and cohort research is unsettled. By framing a project as posing only minimal risk to research participants, researchers may be afforded a degree of latitude in the design and implementation of consent procedures. In the context of large-scale population biobank and cohort studies, whether and to what degree of specificity one is required to seek informed consent from study participants is a critical issue. (1)

Large-scale population biobank and cohort studies are best understood as research platforms rather than discrete research projects. They may involve very large numbers of research participants. The UK Biobank, for example, is aiming to recruit 500,000 participants and, as of December 2008, the project already has more than 200,000 individuals enrolled. (2) They may be designed to run for decades and encompass a great number of separate research projects over their lifespan.

While it is generally recognized that researchers have an obligation to seek the informed consent of research participants, the complexity of large-scale biobank and cohort studies poses a significant challenge to obtaining informed consent for each research project. As noted by the UN's ethics committee [UNESCO], "[a] system which required fresh consent would be extremely cumbersome and could seriously inhibit research." (3) In response, a variety of less onerous approaches to informed consent have been proposed and implemented. (4) The most common approach is a broad or blanket consent, which is a one-time consent covering all future research projects, including those not currently planned. (5)

While the legal, ethical and policy issues associated with these initiatives are complex, (6) it seems clear that blanket consent relies on a "less strict standard" of consent. (7) In other words, it is an alteration from what would normally be required. (8) As a result, from a regulatory standpoint, the use of a blanket consent approach would need to fulfill the requirements of a waiver of consent. In part, this would require that the research pose only "minimal risk" to participants. (9) It is commonly thought that large-scale biobank and cohort research often poses only minimal risk. For example, it has been suggested that studies involving low penetrance genes that have little clinical relevance should be regarded as posing only minimal risk. (10) Likewise, though most biobanks link genetic data to identifiable information, there are often strict privacy policies and procedures limiting the risk of inadvertent disclosure of private information. (11)

The Roles of Minimal Risk in the Tri-Council Policy Statement

The Tri-Council Policy Statement [TCPS] defines minimal risk as follows:

[I]f potential subjects can reasonably be expected to regard the probability and magnitude of possible harms implied by participation in the research to be no greater than those encountered by the subject in those aspects of his or her everyday life that relate to the research, then the research can be regarded as within the range of minimal risk.(12) To put it more simply, minimal risk refers to the risks of daily life. Minimal risk is used in three different ways in the TCPS. First, it is used to limit risk to vulnerable groups in research. Article 2.5 says that " ... individuals who are not legally competent shall only be asked to become research subjects when ... (c) the research does not expose them to more than minimal risks without the potential for direct benefits for them. (13) Clinical research often contains a mixture of therapeutic (e.g., drugs) and nontherapeutic procedures (additional tests for scientific purposes only). This standard limits the risks of nontherapeutic procedures to which children and incapable adults may be exposed to no more than minimal risk. (14)

Second, minimal risk is used to direct the scrutiny of research ethics boards [REBs] in initial and continuing review to riskier research. (15) Article 1.6 states that: "The REB should adopt a proportionate approach based on the general principle that the more invasive the research, the greater should be the care in assessing the research. (16) When research participation poses only minimal risk to subjects, full REB review may not be required. Institutional procedures may allow for expedited review by a subgroup of the REB when research poses no more than minimal risk. Also, for research in the humanities and social sciences, requirements for peer review of scholarly aspects of the research may be waived. (17) This, in turn, may speed approval of minimal risk studies.

Third, minimal risk is used to allow a waiver of consent in certain circumstances. Generally, researchers are required to obtain the free and informed consent of study participants. (18) Under certain circumstances, the REB may approve a consent procedure that modifies some elements of informed consent, or it may waive the requirement for informed consent. In either case, five conditions must be fulfilled:

1. The research involves no more than minimal risk to the subjects;

2. The waiver or alteration is unlikely to adversely affect the rights and welfare of the subjects;

3. The research could not practicably be carried out without the waiver or alteration;

4. Whenever possible and appropriate, the subjects will be provided with additional pertinent information after participation; and

5. The waivered or...