Federal Agencies Issues Proposed Rule on Policy for Protection of Human Subjects
Federal Policy for the Protection of Human Subjects
Publication Date:
Agencies:
Dates: To be assured consideration, comments must be received at one of
Entry Type: Proposed Rule
Action: Notice of proposed rulemaking.
Document Citation: 80 FR 53931
Page: 53931 -54061 (131 pages)
CFR: 10 CFR 745
14 CFR 1230
15 CFR 27
20 CFR 431
22 CFR 225
28 CFR 46
29 CFR 21
32 CFR 219
34 CFR 97
38 CFR 16
40 CFR 26
45 CFR 46
45 CFR 690
49 CFR 11
6 CFR 46
7 CFR 1
RIN: 0937-AA02
Document Number: 2015-21756
Shorter URL: https://federalregister.gov/a/2015-21756
Action
Notice Of Proposed Rulemaking.
Summary
The departments and agencies listed in this document propose revisions to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule in 1991. This NPRM seeks comment on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. This proposed rule is an effort to modernize, simplify, and enhance the current system of oversight. The participating departments and agencies propose these revisions to the human subjects regulations because they believe these changes would strengthen protections for research subjects while facilitating important research.
DATES:
To be assured consideration, comments must be received at one of the addresses provided below, no later than
ADDRESSES:
You may submit comments, identified by docket ID number HHS-OPHS-2015-0008, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov. Enter the above docket ID number in the "Enter Keyword or ID" field and click on "Search." On the next Web page, click on "Submit a Comment" action and follow the instructions.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM submissions] to:
Comments received, including any personal information, will be posted without change to http://www.regulations.gov.
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
Executive Summary
Purpose of the Regulatory Action
Individuals who are the subjects of research may be asked to contribute their time and assume risk to advance the research enterprise, which benefits society at large. U.S. federal regulations governing the protection of human subjects in research have been in existence for more than three decades. The
Since the Common Rule was promulgated, the volume and landscape of research involving human subjects have changed considerably. Research with human subjects has grown in scale and become more diverse. Examples of developments include: An expansion in the number and type of clinical trials, as well as observational studies and cohort studies; a diversification of the types of social and behavioral research being used in human subjects research; increased use of sophisticated analytic techniques for use with human biospecimens; and the growing use of electronic health data and other digital records to enable very large data sets to be analyzed and combined in novel ways. Yet these developments have not been accompanied by major change in the human subjects research oversight system, which has remained largely unchanged over the last two decades.
The regulations are codified in each department or agency's title or chapter of the Code of Federal Regulations (CFR). The Common Rule was based on HHS' regulations, 45 CFR part 46, subpart A, and includes identical language in the separate regulations of each department and agency.
Although they have not issued the Common Rule in regulations, three departments and agencies currently comply with all subparts of the HHS protection of human subjects regulations at 45 CFR part 46. These are the
Pursuant to Executive Order 12333 of
DHS, created after issuance of the Common Rule, is required by statute (Pub. L. 108-458, title VIII, section 8306) to comply with 45 CFR part 46, or with equivalent regulations promulgated by the Secretary of Homeland Security or his designee. This proposed rulemaking initiates the process of promulgating equivalent regulations, consistent with statute. Once DHS executes a final rule, DHS will comply with the DHS regulations as the requirements will be equivalent to compliance with HHS regulations at 45 CFR part 46, subpart A.
SSA was separated from HHS in 1995 and, pursuant to the transition rules provided in Section 106 of title 1 of Public Law 103-296, must apply all regulations that applied to SSA before the separation, absent action by the Commissioner. Once the final rule is codified in SSA regulations, SSA will follow the SSA regulations instead of HHS regulations at 45 CFR part 46, subpart A. See Public Law 103-296 section 106(b), 108 Stat. 1464, 1476.
Another department is joining this proposed rulemaking.
Finally, note that there are two current Common Rule agencies that are not listed as part of this proposed rulemaking.
On
Since the publication of the ANPRM, science has continued to advance, as has the dialogue regarding the changing nature of research and the preferred balance of protections for research participants among the principles of respect for persons, beneficence, and justice. Important elements of that debate have centered on the appropriate level of transparency in government and medicine and how patient and research participant expectations should be incorporated into government policies. These factors have helped shape the development of the regulatory actions proposed in this NPRM.
The proposal also benefits from public comments submitted in response to more recent policy proposals regarding specific topics such as informed consent through the
Finally, the NPRM more thoroughly addresses behavioral and social science research perspectives and the broader types of research conducted or otherwise supported by the other Common Rule agencies. Similarly, the proposal benefits from continuing efforts at HHS to harmonize human subjects policies, particularly between OHRP and the
Summary of the Major Provisions of the Proposed Regulatory Action
The goals of the NPRM are to increase human subjects' ability and opportunity to make informed decisions; reduce potential for harm and increase justice by increasing the uniformity of human subject protections in areas such as information disclosure risk, coverage of clinical trials, and coverage of IRBs; and facilitate current and evolving types of research that offer promising approaches to treating and preventing medical and societal problems through reduced ambiguity in interpretation of the regulations, increased efficiencies in the performance of the review system, and reduced burdens on researchers that do not appear to provide commensurate protections to human subjects. It is hoped that these changes will also build public trust in the research system.
An example of some major changes being proposed that will better protect research subjects and help build public trust are the rules relating to informed consent. With regard to informed consent in general (such as consent to participating in clinical trials), the rules would be significantly tightened to make sure that the process becomes more meaningful. Consent forms would no longer be able to be unduly long documents, with the most important information often buried and hard to find. They would need to give appropriate details about the research that is most relevant to a person's decision to participate in the study, such as information a reasonable person would want to know, and present that information in a way that highlights the key information. In addition, to assure that these rules do indeed change current practices, there will be a one-time posting requirement for the consent forms for clinical trials, so that anyone drafting a consent form will do so knowing that it will eventually be subject to public scrutiny.
In addition, informed consent would generally be required for secondary research with a biospecimen (for example, part of a blood sample that is left over after being drawn for clinical purposes), even if the investigator is not being given information that would enable him or her to identify whose biospecimen it is. Such consent would not need to be obtained for each specific research use of the biospecimen, but rather could be obtained using a "broad" consent form in which a person would give consent to future unspecified research uses.
The NPRM also attempts to strengthen the effectiveness and efficiency of the oversight system by making the level of review more proportional to the seriousness of the harm or danger to be avoided. Research that poses greater risk to subjects should receive more oversight and deliberation than less risky research. The NPRM seeks to avoid requirements that do not enhance protection and impose burden, which can decrease efficiency, waste resources, erode trust, and obscure the true ethical challenges that require careful deliberation and stakeholder input. Cumbersome and outdated regulatory standards overwhelm and distract institutions, IRBs, and investigators in ways that stymie efforts to appropriately address the real risks and benefits of research.
The result of these types of changes, as the NPRM proposes to implement them, is that some studies that currently require IRB review would now become exempt. Some that are currently exempt would specifically be declared as outside the scope of the regulations ("excluded"), and thus would not require any administrative or IRB review. Further, in terms of determining when a study is exempt, a web-based "decision tool" will be created. That decision tool will provide a determination of whether or not a study is exempt. That result, so long as the tool was provided with accurate information, will be presumed by the Common Rule agencies to be an appropriate determination of exempt status. Thus, it is expected that in many instances the tool would be used by the investigators themselves, thus obviating both the need for further review and the concern that the institution might be subjecting itself to future liability by allowing investigators to use the tool. For all of the excluded and exempt research activities, this NPRM also affirms the importance of applying the ethical principle of respect for persons, in addition to the importance of abiding by this principle in fully regulated non-exempt research involving human subjects.
The following list encompasses the most significant changes to the Common Rule proposed in the NPRM:
(1) Improve informed consent by increasing transparency and by imposing stricter new requirements regarding the information that must be given to prospective subjects, and the manner in which it is given to them, to better assure that subjects are appropriately informed before they decide to enroll in a research study.
(2) Generally require informed consent for the use of stored biospecimens in secondary research (for example, part of a blood sample that is left over after being drawn for clinical purposes), even if the investigator is not being given information that would enable him or her to identify whose biospecimen it is. That consent would generally be obtained by means of broad consent (i.e., consent for future, unspecified research studies) to the storage and eventual research use of biospecimens.
(3) Exclude from coverage under the Common Rule certain categories of activities that should be deemed not to be research, are inherently low risk, or where protections similar to those usually provided by IRB review are separately mandated.
(4) Add additional categories of exempt research to accommodate changes in the scientific landscape and to better calibrate the level of review to the level of risk involved in the research. A new process would allow studies to be determined to be exempt without requiring any administrative or IRB review. Certain exempt and all non-exempt research would be required to provide privacy safeguards for biospecimens and identifiable private information. New categories include:
a. certain research involving benign interventions with adult subjects;
b. research involving educational tests, surveys, interviews or observations of public behavior when sensitive information may be collected, provided that data security and information privacy protections policies are followed;
c. secondary research use of identifiable private information originally collected as part of a non-research activity, where notice of such possible use was given;
d. storing or maintaining biospecimens and identifiable private information for future, unspecified secondary research studies, or conducting such studies, when a broad consent template to be promulgated by the Secretary of HHS is used, information and biospecimen privacy safeguards are followed, and limited IRB approval of the consent process used is obtained.
(5) Change the conditions and requirements for waiver or alteration of consent such that waiver of consent for research involving biospecimens (regardless of identifiability) will occur only in very rare circumstances.
(6) Mandate that U.S. institutions engaged in cooperative research rely on a single IRB for that portion of the research that takes place within
(7) Eliminate the continuing review requirement for studies that undergo expedited review and for studies that have completed study interventions and are merely analyzing data or involve only observational follow-up in conjunction with standard clinical care.
(8) Extend the scope of the policy to cover all clinical trials, regardless of funding source, conducted at a U.S. institution that receives federal funding for non-exempt human subjects research.
In sum, the proposed modifications described above are designed to continue to uphold the ethical principles upon which the Common Rule is based, as applied to the current social, cultural, and technological environment.
The legal authority for the departments and agencies that are signatories to this action is as follows:
Estimated Costs and Benefits
Table 1 summarizes the quantified and non-quantified benefits and costs of all proposed changes to the Common Rule. Over the 2016-2025 period, present value benefits of
Table 1--Accounting Table of Benefits and Costs of All Proposed Changes
Benefits ..... Present value of 10 years by discount rate (millions of 2013 dollars) ..... Annualized value over 10 years by discount rate (millions of 2013 dollars)
3 Percent ..... 7 Percent ..... 3 Percent ..... 7 Percent
Quantified Benefits ..... 2,629 ..... 2,047 ..... 308 ..... 291
Non-quantified Benefits ..... ..... ..... .....
Improved human subjects protections in clinical trials and biospecimen research not currently subject to oversight; enhanced oversight in research reviewed by unaffiliated IRBs; increased uniformity in regulatory requirements among Common Rule agencies; ethical benefit of respecting an individual's wishes in how his or her biospecimens are used in future research; standardization of human subjects protections when variation among review IRBs is not warranted; improved informed consent forms and processes; improved protection of biospecimens and individually identifiable private information; better ensuring availability of biospecimens for future research activities; and increased transparency of Common Rule-supported clinical trials to inform the development of new consent forms. ..... ..... ..... .....
Costs ..... 3 Percent ..... 7 Percent ..... 3 Percent ..... 7 Percent
Quantified Costs ..... 13,342 ..... 9,605 ..... 1,564 ..... 1,367
Non-quantified Costs ..... ..... ..... .....
Time for consultation among Common Rule agencies before federal guidance is issued; time for investigators to obtain consent for secondary use of biospecimens or identifiable private information. ..... ..... ..... .....
I. The Rationale for Modernizing the Common Rule
A. The Changing Nature of Research
In the last two decades there has been a paradigm shift in how research is conducted. Evolving technologies, including imaging, mobile technologies, and the growth in computing power have changed the scale of information collected in many disciplines. Computer scientists, engineers, and social scientists are developing techniques to integrate different types of data so they can be combined, mined, analyzed, and shared. Research has also increased, evolved, and diversified in other areas, such as national security, crime and crime prevention, economics, education, and the environment, using a wide array of methodologies in the social sciences and multidisciplinary fields. The advent of sophisticated computer software programs, the internet, and mobile technology has created new areas of research activity, particularly within the social and behavioral sciences. In biomedical science, the
Research settings are also shifting. While much biomedical research continues to be conducted in academic medical centers, more research is being conducted in clinical care settings, thus combining research and medical data. Biospecimen repositories and large databases have made it easier to do research on existing biospecimens and data. Clinical research networks connected through electronic health records (EHRs) have developed methods for extracting clinical data for research purposes and are working toward integration of research data into EHRs in a meaningful way. The overall volume of research has increased across the board, with growing reliance on research networks and multi-site studies. Large cohort studies number well into the hundreds in
At the same time, the level of public engagement in the research enterprise has changed; more people want to play an active role in research, particularly related to health, and they have different expectations than when the Common Rule was first established. A more participatory research model is emerging in social, behavioral, and biomedical research, one in which potential research subjects and communities express their views about the value and acceptability of research studies. This participatory model has emerged alongside a broader trend in American society, facilitated by the widespread use of social media, in which Americans are increasingly sharing identifiable personal information and expect to be involved in decisions about how to further share the personal information, including health-related information that they have voluntarily chosen to provide. In many ways, these changes are extensions of the fact that over the past half-century, rather than being passive recipients of health advice and treatment, patients have gradually become more active in decisions about their health and health care. The shift from a paternalistic research environment to one where participants are active partners in biomedical and behavioral research is a critical development in human subjects research.
As technology evolves, so does the nature of the risks and benefits of participating in certain types of research. Many studies do not involve interaction with research subjects, but instead involve, for example, analyzing information obtained from medical records, administrative claims data, education records, criminal justice records, research data shared through data repositories, and existing biospecimens stored in repositories. Risks related to these types of research studies are largely informational, not physical; that is, harms could result primarily from the inappropriate release of information and not from the research interventions themselves. Nonetheless, those harms can be significant.
New methods, more powerful computers, and easy access to large administrative datasets produced by local, state, and federal governments have meant that some types of data that formerly were treated as non-identified can now be re-identified through combining large amounts of information from multiple sources. In 2013, scientists demonstrated that the identity of individual research subjects could be ascertained by collating and analyzing certain types of genomic data, including genomic data from publicly available information sources. [4] Thus, the possibility of fully identifying biospecimens and some types of data from which direct identifiers had been stripped or did not originally include direct identifiers has grown, requiring vigilance to ensure that such research be subject to appropriate oversight. Most importantly, people want to be asked for their permission. A growing body of survey data show that many prospective participants want to be asked for their consent before their biospecimens are used in research. 5 6 7 8
Because of these shifts in science, technology, and public engagement expectations, a wide range of stakeholders have raised concerns about the limitations of the existing framework, arguing for a re-evaluation of how the fundamental principles that underlie the Common Rule --respect for persons, beneficence, and justice--are applied in practice to the myriad new contexts in which U.S. research is conducted in the 21st century. 9 10 Dialogue focuses around whether the current system:
Is sufficiently supportive of a participant-centered research model that adequately respects participants as partners;
is not sufficiently risk-based, resulting in both over- and under-regulation of research activities; 11 12 13
is sufficiently tailored to new and emerging areas of research, including social and behavioral research and research involving the collection and use of genetic information; 14 15 16 17 18 19
effectively informs subjects of psychological, informational, or privacy risks; 20 21 22
adequately accounts for the needs of a "learning" healthcare system for continual quality improvement; 23 24 25
provides sufficient mechanisms to ensure the consistency, quality, and accountability of IRB decision-making. 26 27 28 29
B. Public Comments, Expert Advice, Stakeholder Dialogue
The revisions to the Common Rule proposed here are based upon a variety of sources of public, stakeholder, and expert comments and advice. First, the NPRM more thoroughly addresses social science and behavioral research perspectives, benefiting from guidance provided by a
Second, since the publication of the ANPRM, HHS has continued to solicit public comment on a variety of human subjects related issues, including consent, the use of a single IRB for multi-site studies, and sharing of genomic data. Although these policies were more specific than the issues raised in the ANPRM, the responses received from public comments provide insight for refining the proposals initially put forward in the ANPRM. Of particular interest:
NIH's proposal that it expects the use of a single IRB for all multi-site research studies funded or conducted by the NIH. [31] Under that proposal, all domestic sites of a multi-site study would be expected, as a condition of NIH funding, to use a single IRB of record. In response to this proposal, NIH received 165 comments from a range of stakeholders, including investigators, IRB members, and members of the public. The majority of respondents were supportive; however concerns were raised that it would be expensive and time-consuming to identify a single IRB for each new multi-site study.
OHRP's draft guidance discussing the required content of consent language for research done within the standard of care. [32] In August of 2013, prior to the publication of the draft guidance document, HHS held a public meeting to hear from the community on issues raised during the debate surrounding the SUPPORT study. [33] The public meeting and the draft guidance document spurred a significant public discussion about the nature of the information included in informed consent forms, specifically how investigators should communicate the risks of research studies done within the standard of care. A total of 93 comments were received from bioethicists, investigators and research institutions, hospitals and physicians, IRB members, patient advocates, and industry.
To enhance human subject protections and reduce regulatory burden, OHRP and
NIH's proposal to promote sharing of large-scale human genomic data generated from studies funded or conducted by NIH. [34] The policy lays out an expectation that investigators generating genomic data get consent for future research use of those data. The NIH received 107 comments on the policy, including many that addressed the concept of broad consent for unspecified future research use.
There have also been developments on the legislative front that have informed the discussions leading up to this NPRM. In December of 2014, the Newborn Screening Saves Lives Reauthorization Act of 2014 (Pub. L. 113-240), was signed into law. The new law makes a number of changes relevant to the HHS regulations for protecting research subjects, including declaring that research with newborn dried blood spots that is federally funded pursuant to the Public Health Service Act is to be considered research with human subjects, and the provisions allowing IRBs to waive consent will not apply. These changes will be effective until updates to the Common Rule are promulgated. In addition, in April of 2015, the Medicare Access and CHIP Reauthorization Act of 2015 (Pub. L. 114-10) was passed. That law requires HHS to issue a clarification or modification of the Common Rule with regard to how they apply to activities involving clinical data registries.
Most recently, with the launch of the President's Precision Medicine Initiative (PMI), 35 36 the Federal Government is proposing a new research cohort based on a model that puts participants at the center. [37] To understand participant preferences the
C. Guiding Principles for Proposed Changes
In 1979, the Belmont Report [38] was predicated on three principles that were felt to be central to shaping an ethical framework for the conduct of research with human subjects. The three ethical principles are respect for persons, beneficence, and justice. Interpretation of, and balancing among, these three principles played a major role in shaping what became the development the federal regulations that have become known as the Common Rule. The preamble to the proposal considers whether and how the interpretation of these fundamental principles might be updated within the context of the current technological, social, cultural, and ethical environment. That consideration involves explicitly identifying the interplay among the principles. The Common Rule provides a framework for how researchers and IRBs weigh the often conflicting implications of these three principles.
Beneficence: Individuals who participate in research contribute their time and may assume significant risks to advance the research enterprise. Their valuable contributions produce knowledge that benefits society at large. The Belmont Report describes the principle of beneficence as the goal of maximizing possible benefits of research and minimizing possible harms. This principle has been interpreted to, in part, emphasize the benefit associated with the knowledge that might be generated by a research study. Evaluating beneficence requires examining the likelihood that knowledge would be generated, and how important or useful that knowledge might be to the population. When more weight is given to research that has the potential to generate a great deal of knowledge, particularly knowledge that could be very useful to society (such as how to treat serious diseases that are currently untreatable), policies would lean in favor of encouraging and facilitating more of that type of research.
A distinct aspect of the principle of beneficence concerns the benefits and risks to the specific persons who would be participating in a particular research study. In the example of a randomized clinical trial comparing two treatments for a disease, the benefits and risks to the subjects in the trial are distinct from the possible benefits to society as a whole from learning which of the two treatments is better. This aspect of beneficence assumes that there are limits on the risks to which people should be subject, even if they are willing to undergo those risks.
Society is in an information age. In all facets of one's life information about that person is generated, stored, shared, analyzed, and often provides tremendous societal value. People share information about themselves with large numbers of people with the click of a button, and this trend of rapid and widespread sharing is only likely to grow. The increase in concern about unauthorized and inadvertent information disclosure, in combination with newer research techniques that increase the volume and nature of identifiable data suggest the need for the Common Rule to more explicitly address data security and privacy protection.
Of particular interest for this proposal is addressing risks from inappropriate disclosure of information generated from biospecimens. One way to protect subjects from such risks is to bring under oversight research for which risks are greater of subjects being identified and information being inappropriately disclosed. Although it may be difficult to identify individuals from their non-identified biospecimens at present, and most investigators would have no need to do so unless they were seeking additional associated phenotypic information, certain technologies and methods can be used to generate data that are unique to the individual who provides the biospecimen, and those data can sometimes be combined with other data sources to identify the individual. In the future, technologies will facilitate the use and analysis of greater variety and volumes of information, and there is a possibility that it will be increasingly difficult, if not impossible, to make biospecimens fully non-identified. In fact, a number of reports have already demonstrated the ability to re-identify individuals from biospecimens or data that lack direct identifiers. 39 40 As analytic techniques become more sophisticated and large datasets become more accessible, it will not be possible to guarantee that an individual could never be identified from a biospecimen or combination or data sources, particularly if whole genome sequencing is conducted.
Respect for Persons: The Belmont Report describes this concept as the notion of treating people as autonomous agents, and allowing them to make choices based on their own judgments and opinions. Inherent in the principle of autonomy is the concept of transparency--clearly providing the information necessary for the research participant to make such judgments. Transparency requires a clear articulation of risks, potential benefits, and alternatives to participating in a research study, as well as the purpose of the research. The principle of autonomy encompasses the value ascribed to an individual's right to know how one's data is being used and who will have access to it. As such autonomy also covers the paired concept of protecting those persons who lack the capability to make such decisions. There are a variety of different ways of demonstrating respect for persons.
Obtaining informed consent from human subjects for the collection and analysis of information about them is one means of implementation of respect for persons in the research context. Informed consent is designed to ensure that each individual approached to participate in a research study fully understands the risks and potential benefits of the study so that they have sufficient information to make an individualized calculation as to whether or not the tradeoffs inherent in participation are worth it for them to agree to participate. Both the potential harms and benefits tend to be greater in the context of a clinical trial where subjects are randomized to one or another of two possible treatments with significantly different suspected risks than in situations where subjects are simply asked to provide, for instance, a urine sample.
Notice, in which individuals are informed about how data will be used, but explicit consent is not obtained, is another means of facilitating transparency. Notice is sometimes used in the context of informing people about how data collected for non-research purposes (e.g., when providing information in the context of applying for public benefits) might be used for either general or specific research purposes. Another method for showing respect for persons with regard to using data about them for research could be providing them with a right to opt out of such research, by, for example, filing a form stating such a wish with the holder of the data.
Related, implicit consent might be obtained when a research subject completes a questionnaire. If they did not wish to provide the information, presumably they would not be answering the questions. The NPRM contains a number of provisions that are designed to further promote respect for participants through increases in both transparency and opportunities for consent.
Justice: The Belmont Report describes this principle as being about fairness in terms of who receives the benefits from research and who bears its burdens. One of the most direct applications of the principle of justice to the Common Rule relates to determining who is studied and how subjects are selected. This principle also is relevant to protection of vulnerable populations. In addition, the idea of justice is relevant to one of core goals of this NPRM: Clarifying important aspects of the Common Rule where there has been ambiguity in interpretation. To the extent that IRBs and others interpret the regulations in significantly different ways, the result is that participants in research can end up being treated in very different ways, even when they are participating in the same study. Thus this idea is embedded in all of the NPRM's attempts to make sure that these rules are applied in a more uniform and consistent manner.
The three ethical principles of the Belmont Report often cannot all be fulfilled at the same time. In many cases, it will be necessary to choose which of those principles will deserve the greatest adherence. This NPRM, at its heart, represents an attempt to evaluate the weights to be applied to each of these three core principles in a variety of specific contexts. Giving greater weight to one of the principles will frequently mean a decreased ability to fulfill one of the other principles. By necessity, value judgments, influenced by the social norms of the time, drive the implementation of the broad principles underlying the Belmont Report. The efficacy of the oversight system also requires proportionality in weighing the application of these three principles. This is reflected in the analysis that follows, in terms of evaluating the specific aspects of beneficence, respect for persons, and justice that relate to a particular issue, and weighing those aspects against one another. Research that poses greater risk should receive more attention and deliberation than less risky research, and the degree and type of oversight should be commensurate with the level of risk. In addition, requirements that do not enhance protection but that impose burden can increase inefficiency, waste resources, erode trust, and obscure the ethical challenges that require careful deliberation and stakeholder input. Cumbersome and outdated regulatory standards overwhelm and distract oversight bodies and other stakeholders from appropriately addressing the real risks and benefits of research.
There is tremendous support for research in this country. American society values advances in knowledge and has reaped the reward of many key insights that have led to increases in quality of life and a doubling of our life expectancy in the last century. There would not have been such strides in medical and behavioral research without the willingness of individuals to join research studies. Participants are told that they are not likely to benefit directly from any given study, yet they choose to participate for the greater good. Beneficence is a powerful driver. On the other hand, members of the public deserve, and indeed now expect, to know how publicly-funded research is being conducted and overseen, and need to have confidence that the interests of research participants are adequately protected. Transparency is key for developing trust, especially between investigators, funders, regulators, and the public.
Our reassessment of these ethical principles in the context of current technology and social norms suggests the need for changes to the Common Rule that: (1) Increase subject autonomy by increasing human subjects' ability and opportunity to make informed decisions; (2) reduce potential for harm and increase justice by increasing the uniformity of human subject protections in areas such as information disclosure risk, coverage of clinical trials, and coverage of IRBs; and (3) increase beneficence by facilitating current and evolving types of research that offer promising approaches to treating and preventing medical and societal problems though reduced ambiguity in interpretation of the regulations, increased efficiencies in the performance of the review system, and reduced burdens on researchers that do not appear to provide commensurate protections to human subjects. If a reasonable balance is struck between protecting human research subjects, minimizing the administrative burden of the system, and engendering public trust, this should maximize beneficence and raise all ships.
Public comment is sought not only on the provisions outlined below, but on whether the proposals strike a reasonable balance among the core ethical principles. A better balance among the core principles should increase the strength of the partnership between the research enterprise and the public, and even greater scientific understanding and innovation will be fostered.
Finally, it is important to note that, to the extent appropriate, the intent is to eventually amend the other subparts of the HHS human subjects protection regulations in 45 CFR part 46 (subparts B, C, D, and E), and consider the need for updates to
1. Question for Public Comment
1. Public comment is sought on whether the proposed changes will achieve the objectives of (i) decreasing administrative burden, delay and ambiguity for investigators, institutions, and IRBs, and (ii) strengthening, modernizing, and making the regulations more effective in protecting research subjects.
D.
Section II of the NPRM, which immediately follows, describes in detail the major proposals for revisions to the Common Rule. In general, the changes that are likely to be of greatest significance are discussed in the earlier parts of section II of this preamble. Section II.A is devoted to changes that affect which activities are subject to the Common Rule. Following that section are discussions devoted to changes relating to informed consent (section II.B), changes relating to privacy safeguards for the research use of information and biospecimens (section II.C), and a proposal to encourage greater harmonization of guidance across the agencies that adhere to the Common Rule (section II.D). Discussions of changes relating to how IRBs operate, including a proposal to reduce the number of reviews by different IRBs that take place for multi-site studies, are in the several sections that follow (sections II.E, F and G). The final section (section II.H) collects a variety of other changes, including expanding the scope of the rule to cover clinical trials that are not federally funded but are conducted at institutions that received some federal funding for research with human subjects.
The three sections that follow then discuss various administrative review requirements: Regulatory Impact Analyses (section III), Environmental Impact (section IV), and Paperwork Reduction Act (section V). The final section of the document (section VII) provides the full regulatory text of the proposed changes to the Common Rule. Section VI provides a comprehensive summary of responses received to the 2011 Common Rule ANPRM.
II. Major Proposals To Modernize the Common Rule
A. Proposed Changes to the Scope and Applicability of the Regulations
1. Expanding the Definition of Human Subject to
This section focuses on the ethical principles associated with the secondary research use of biospecimens. These biospecimens may have been originally collected from either research or non-research settings (e.g., leftover portion of tissue from a clinical biopsy).
a. NPRM Goals
One of the goals of this NPRM is facilitating cutting edge research in genomics and other `omics' such as the transcriptome and the microbiome, which generate a wealth of data from biospecimens designed to inform the development of treatments and preventative measures for chronic diseases such as cancer. Facilitating such research, however, requires navigating complex ethical issues. The key question is, under what circumstances should the Common Rule govern what research investigators are able to do with biospecimens that have been collected for some other (e.g., clinical) purpose? (Note that if a researcher interacted with an individual to actually collect a biospecimen for research purposes--for example, obtaining a saliva sample--that "primary" research activity is already covered under the current regulations, and is not the focus of the change discussed in this section.) In this case, maximizing the societal value of research would mean reducing barriers to the secondary use of biospecimens to the extent possible.
However, there is a growing recognition that many people want to have some degree of control over the circumstances in which an investigator can derive information about them, above and apart from their interest in whether or not that information might be inappropriately disclosed. More specifically, a growing body of literature shows that in general people prefer to have the opportunity to consent (or refuse to consent) to research involving their own biological materials. [41] Furthermore, in 2012, the
In assigning weights to the principles of beneficence and respect for persons in the context of research with biospecimens, strong consideration was given to the fact that failure to acknowledge and give appropriate weight to this distinct autonomy interest in research using biospecimens could, in the end, diminish public support for such research, and ultimately jeopardize our ability to be able to conduct the appropriate amount of future research with biospecimens. To that end, the proposals given below are designed to meet the goals of increasing transparency in when and how biospecimens collected in a variety of circumstances will be used for research purposes and increasing opportunities for consent. Various ways in which these goals might be achieved are the subject of alternative proposals discussed below.
b. Current Rule
The application of the current regulations to secondary research use of a biospecimen is tied to the identifiability of the biospecimen in the hands of the researcher. In particular, the definition of human subject in the current Common Rule at section __.102(f) states that a human subject is a living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual, or identifiable private information. Private information is described as information that is individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.
Consistent with historical interpretation of identifiable private information under the Common Rule, the terms "non-identified" or "non-identifiable" are used throughout this NPRM to signify biospecimens or data that have been stripped of identifiers such that an investigator cannot readily ascertain a human subject's identity. Re-identification of non-identified or non-identifiable biospecimens or information may be possible, depending on the circumstances. The term "de-identified" is distinct; it is only used in this proposal to refer specifically to the HIPAA standard of non-identifiability.
Thus, where there is no intervention or interaction with an individual, central to determining whether human subjects are involved in a research activity covered by the current Common Rule is determining the meaning of "identifiable." Under the current Rule, provided the biospecimens and data were collected for purposes other than the currently proposed research, it is permissible for investigators to conduct research on biospecimens and data that have been stripped of all identifiers without obtaining consent because the non-identified biospecimens and data do not meet the regulatory definition of human subject.
It is, however, worth noting that although informed consent is not strictly required by the current regulations when research takes place using non-identified biospecimens, some IRBs have indicated that they are requiring that investigators explicitly obtain consent for future analysis of biospecimens collected in the research setting, and some are refusing to waive consent for use of biospecimens collected in non-research contexts.
Under Secretary for Science and Technology, DHS.
Under Secretary for Research, Education, and Economics,
Deputy Secretary of Energy.
Chief Health and Medical Officer.
Chief of Staff,
Acting Commissioner of
Senior Deputy Assistant Administrator for Global Health,
Deputy Attorney General.
Deputy Secretary of Labor.
OSD Federal Register Liaison, Officer,
Secretary of Education.
Chief of Staff,
Acting Deputy Administrator.
Secretary, HHS.
General Counsel.
Secretary of Transportation.
Editor's note: For the full-text of this document, click this link or copy it into your browser: https://www.federalregister.gov/articles/2015/09/08/2015-21756/federal-policy-for-the-protection-of-human-subjects.
-1225473
QBE North America Appoints Kathleen O. Zortman President, Standard Lines – Property & Casualty
Advisor News
Annuity News
Health/Employee Benefits News
Life Insurance News