The Impact of the Final Rule Changes Reilly Auditorium December 7 and 12, 2017

Effective January 19, 2018 Updates to the human subjects regulations (45 CFR 46 Subpart A) are effective January 19, 2018. Promoting individual autonomy Changing requirements of informed consent Reducing administrative burden and streamlining IRB processes Removing activities from the definition of research Expanding exempt research Updating and simplifying expedited review Eliminating certain continuing reviews Using single IRB review

Transition to revised Common Rule

What’s included in the final rule Revisions to the following sections: Definitions IRB Membership (in relation to vulnerable populations) Initial Application Criteria for Approval Informed Consent Continuing Review Expedited Review Processes Exempt Categories

What’s NOT included Subparts addressing additional protections for pregnant women, human fetuses, and neonates, children, and prisoners* FDA 21 CFRs Future efforts to harmonize HHS and FDA through 21st Century Cures law HIPAA *The Final Rule changes the pre-2018 rule to allow the exemptions to apply to Subpart C for research involving a broader subject population if the research only incidentally includes prisoners.

Update: Definition of Research The Final Rule removed the activities from the definition of research, including: Scholarly and journalistic activities that focus directly on the specific individuals from whom the information is collected. Public health surveillance activities that are necessary to allow a public health authority to "identify, monitor, assess, or investigate potential public health signals, onset of disease outbreaks, or conditions of public health importance." Collection and analysis of information or biospecimens required by or for a criminal justice agency for criminal justice purposes. Activities in support of intelligence, homeland security, defense, or other national security missions.

Update: Definitions The definition of “human subject” has been changed to include “identifiable biospecimens” as well as how data and/or biospecimens have been collected or will be used. Impact New criteria for approval and exempt categories related to biospecimens Require updates to policies, forms, reviewer sheets, initial application Human subject means a living individual about whom an investigator (whether professional or student) conducting research: (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens. Added the requirement for research that involves accessing or using private information or identifiable biospecimens that the research could not practicably be carried out without accessing or using such information or biospecimens in an identifiable format.

Tool: Decision Tree * Additional Explanation Review notes section for explanation of this slide. Additional Explanation Prior to the Final Rule, if researchers had not secured study-specific consent, the Common Rule contemplated only two alternatives for using identifiable data or biospecimens in a research study:  obtaining an IRB waiver of consent  or removing personal identifiers so that the research would not involve identifiable private information, therefore falling outside of the jurisdiction of the Common Rule.  Final Rule Framework for Broad Consent* (Broad consent may be implemented at a later date)   The Final Rule creates two new exemption categories under which research is excepted from compliance with the entire Common Rule if it satisfies certain abbreviated conditions, including obtaining the subject’s broad consent: (i) Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an institutional review board (IRB) conducts a limited IRB review and makes certain determinations.   (ii) Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if the following criteria are met:  a. Documentation of informed consent or waiver of documentation of consent was obtained;  b. An IRB conducts a limited IRB review and makes certain determinations; and  c. The investigator does not include returning individual research results to subjects as part of the study plan (although the investigator is not prevented from abiding by any legal requirements to return individual research results).  Exempt Category #4 - Secondary research for which consent is not required. Requirement: A waiver of inform consent document through IRB and HIPAA waiver requested through the Privacy Board. Broad Consent Exemption Categories (Broad consent may be implemented at a later date) Category #7 For storage or maintenance for secondary research for which broad consent is obtained. Requirements: Broad consent is obtained and documented. Category #8 For secondary research for which broad consent is obtained. Limited IRB review must determine that the research is within the scope of the broad consent. Investigator does not include returning individual research results to subjects as part of the study plan. Limited IRB review and broad consent (Requires broad consent approval through IRB and a HIPAA waiver requested through the Privacy Board) *

Update: Definitions Clinical Trials definition updated A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. Impact - Social behavioral researchers who conduct clinical trials are now subject to the same requirements as biomedical clinical trials. For example, GCP training required, registering clinical trials and reporting results. Clinical trial means a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. Social and behavioral researchers who conduct “clinical trials” are now subject to the same requirements as a biomedical clinical trial. GCP training required, registering clinical trials and reporting results

Tool: NIH Decision Tree Go to the NIH tool to determine if your study is considered an NIH clinical trial. Answer a few simple questions to help determine if your study is a clinical trial. https://grants.nih.gov/ct-decision/index.htm

Clinical Trials.gov New requirement to post to www.clinicaltrials.gov, a copy of an IRB-approved version of the consent form that was used for enrollment purposes for each clinical trial conducted or supported by a federal department or agency. One consent form for each study must be posted on the federal website after recruitment closes but not later than 60 days after the last study visit by any subject. Requirement for posting clinical trial consent forms on a publicly available Federal website(clinicaltrials.gov) as a repository for consent forms. One consent form for each study must be posted on the Federal website after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject.

Clinical Trials.gov Protocol registration and results system

Update: IRB Membership Final Rule no longer includes pregnant women or ‘‘handicapped’’ or physically disabled individuals as examples of populations that are potentially vulnerable to coercion or undue influence within 45 CFR 46 Subpart A. However, subpart B is unchanged. Revised for sensitivity Replaced cognitively impaired individuals with individuals with impaired decision making capacity clarified Added economically or educationally disadvantaged individuals new Impact: IRB member experience must cover new vulnerable population; special protections for new population Require updates to policies, forms, member roster and applications REMEMBER: Subpart B, additional protections for pregnant women, human fetuses, and neonates is not part of the Subpart A and the Final Rule. Vulnerability to impaired decision making The Educational Disadvantaged Persons may be vulnerable to impaired decision making if low education levels lead them to enroll in research without fully understanding study risks. Economically Disadvantaged Persons and Coercion Research may offer services or other goods so attractive that they impair decision making, causing the ED to irrationally disregard research risks, including economic harm (financial burden, higher cost, lost wages, etc.)

Update: Initial Application Funding Source: Elimination of grant congruency for IRB Study population: economically and educationally disadvantaged added; cognitively impaired individuals replaced with individuals with impaired decision making capacity.

Update: Initial Application Waiver or alteration of consent: Allowed in research involving public benefit and service programs conducted by or subject to the approval of state or local officials. Per the 21st Century Cures Act and FDA Guidance Waivers or Alteration of Informed Consent for Clinical Investigations Involving No more Than Minimal Risk to Human Subjects are allowed. Examples of research involving public benefit and services include (e.g., water or sewage treatment programs or pollution control programs, programs involving educational procedures, or programs involving emergency procedures related to extreme weather events, etc.) For this type of research, each Federal department or agency conducting or supporting the research and demonstration projects must establish, on a publicly accessible federal Web site or in such other manner as the department or agency head may prescribe, a list of the research and demonstration projects that the Federal department or agency conducts or supports under this provision. In regards to FDA waivers for minimal risk studies, the clinical investigation involves no more than minimal risk (as defined in 21 CFR 50.3(k) or 56.102(i)) to the subjects; 2. The waiver or alteration will not adversely affect the rights and welfare of the subjects; 3. The clinical investigation could not practicably be carried out without the waiver or alteration; and 4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Update: Initial Application Certificate of Confidentiality (CoC) NIH awardees no longer have to apply for a CoC. Effective October 1, 2017, all research that was commenced or ongoing on or after December 13, 2016 that is collecting or using identifiable, sensitive information in which subjects can be identified or has risk of being identified is automatically issued a CoC. Impact: If the research qualifies, it is automatically protected by a CoC from NIH In order for research qualify for a CoC the following apply: Research in which identifiable, sensitive information is collected or used, including research that Meets the definition of human subjects research, including exempt research in which subjects can be identified Is collecting or using human biospecimens that are identifiable or that have a risk of being identifiable Involves the generation of individual level human genomic data Involves any other information that might identify a person If your research meets any of the above criteria then your research data or information is automatically protected by a CoC from NIH.

Update: Criteria for Approval Privacy and Confidentiality Additional IRB approval criterion added for research that involves accessing or using private information or identifiable biospecimens. This new requirement is that the research could not practicably be carried out without accessing or using such information or biospecimens in an identifiable format. Non-identified information should be used whenever possible to respect subjects’ interests in protecting the confidentiality of their information and biospecimens.

Update: Consent Form New requirement states that the informed consent process must begin with “key information” (abstract) Impact: Key Information Consent Form template (IA) New basic and additional elements of consent form Impact: Revisions to the Informed Consent Form template (IB) Requires that subjects be provided with the information that a “reasonable person” would want to have. Reasonable person is undefined in the regulations. Responsibility remains for the investigator to: Provide more information when requested by subjects Make sufficient time and opportunity to discuss the research Answer questions to improve a subject’s understanding For certain types of research (such as, research for which there is reason to believe some subjects will find the research controversial or objectionable), a robust description of the research will be required to meet this reasonable person standard.

Update: Key Information Consent Part IA Adults

Update: Revised Informed consent IB (Adult) Minor IB will be forthcoming

Update: Continuing Review Rule eliminates the requirement for the traditional continuing review (CR) for many minimal risk studies unless the IRB determines otherwise. However, a transition to the new rule is required for all existing studies before the IRB institutes the “no CR rule” for eligible studies FDA CR requirement unchanged

Update: CR Application For pre-2018 approved research, once your continuing review is submitted, the IRB will devise a comprehensive transition plan for your study to encompass the new regulation requirements. If you are requesting to NOT have your study transition, you will be required to provide a justification.* The IRB will consider your justification and make the final determination. Research initially approved by an IRB, before 19 January 2018 (Grandfathered research), will be subject to the pre-2018 rule under transition. *A possible justification may include the following: The study is closed to enrollment or enrollment will close shorty (within x number of months) and consenting subjects with the new consent form would be burdensome and not add any additional safety and protections to subjects.

Update: Status Report A status report is required every three years for expedited studies and every five years for exempt studies if you are not submitting a continuing review report. Reminder to report major deviations, unanticipated problems (unexpected incident, unanticipated adverse device effects or unexpected adverse event), amendments and complaints as they occur.

Update: CR Existing Studies Exempt: After the rule is effective, we will expedite the continuing review in order to transition study to 2018 requirements. After transition, a status report is due every five years. If the study closes before the five year status report, please inform the IRB by submitting a closure report. Modification is required if the change alters the risk or there is a change in the scope of the project. Expedited: At the time of Continuing Review, the project will be reviewed and approved under the 2018 Requirements. Submit continuing review as usual. IRB will outline changes required for transition. After transition, a status report is due every three years. Annual update due each year. Does not apply to FDA regulated studies. 2, 3, 7, 8

Update: CR Existing Studies Full Board: At the time of Continuing Review, the project will be reviewed and approved under the 2018 Requirements. Submit continuing review as usual. IRB will outline changes required for transition. After transition, continuing review is still required annually. (no change) Transition Examples: Ongoing Full Board/Expedited/Exempt projects approved Prior to January 19, 2018 remains on the Pre-2018 Requirements until Continuing Review. 2, 3, 7, 8

Update: Exemptions Category 1 – Revised Category 2 – Revised Category 3 – Replaced* Category 4 - Revised Category 5 – Revised Category 6 – Unchanged Category 7 – New Category 8 – New Exempt categories added for secondary research on identifiable private information and identifiable biospecimens collected prior to and after the time of IRB review and approval. Exempt categories 2c, 3c, 7, & 8 added that require limited review. The limited review will be similar to an expedited review process. Further explanation of the exemption categories are on the next few slides.

Update: Exemptions Exemption 1 – Educational Exemption Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices Must consider “adverse affects” on student learning of required educational content or on assessment of educations Category 1 – Revised Category 2 – Revised Category 3 – Replaced* Category 4 - Revised Category 5 – Revised Category 6 – Unchanged Category 7 – New Category 8 – New Exempt categories added for secondary research on identifiable private information and identifiable biospecimens collected prior to and after the time of IRB review and approval. Exempt categories 2c, 3c, 7, & 8 added that require limited review. The limited review will be similar to an expedited review process.

Update: Exemptions What’s new? Exemption 2 – Surveys/Interviews/Educational Tests/Public Observation ONLY What’s new? Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) Projects collecting sensitive and identifiable data may be exempt after “limited IRB review” (for privacy/confidentiality protections) Clarifies that the exemption does not apply to projects involving: Interventions Collection of biospecimens Linking to additional personally-identifiable data Children (except for educational tests or some public observations) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;  (ii) Any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; or (iii) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by §__.111(a)(7).  “(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.” Exempt categories 2c, 3c, 7, & 8 added that require limited review. The limited review will be similar to an expedited review process.

Update: Exemptions Exemption 3 – Benign Behavioral Interventions What’s new? This exemption is completely new Limited to research with adults What is a benign behavioral intervention? Brief in duration Harmless and painless Not physically invasive Not likely to have a significant adverse impact on subjects Not offensive or embarrassing Solving puzzles under various noise conditions Playing an economic game Being exposed to stimuli such as color, light or sound (at safe levels) Performing cognitive tasks Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:  The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects; [or] Any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; or  The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by §__.111(a)(7).

Update: Exemptions Exemption 3 – Benign Behavioral Interventions Information is collected via Verbal or written responses (surveys/interviews) Data entry Observation of subject (including audiovisual recording) Does not permit data collection via physical procedures Physical sensors (e.g. blood pressure monitors, EEG, FitBits) Minimally invasive procedures (e.g. blood draw or saliva collection) Category 1 – Revised Category 2 – Revised Category 3 – Replaced* Category 4 - Revised Category 5 – Revised Category 6 – Unchanged Category 7 – New Category 8 – New Exempt categories added for secondary research on identifiable private information and identifiable biospecimens collected prior to and after the time of IRB review and approval. Exempt categories 2c, 3c, 7, & 8 added that require limited review. The limited review will be similar to an expedited review process.

Update: Exemptions Exemption 3 – Benign Behavioral Intervention Must obtain “prospective agreement to the intervention and information collection” No deception, except where the subject is told that they will be unaware or misled about the nature or purposes of the research and they agree Debriefing still encouraged Self-exemption permitted for projects that do not involve deception and where information collected is not identifiable or not sensitive “Limited IRB Review” required for projects collecting sensitive and identifiable data Category 1 – Revised Category 2 – Revised Category 3 – Replaced* Category 4 - Revised Category 5 – Revised Category 6 – Unchanged Category 7 – New Category 8 – New Exempt categories added for secondary research on identifiable private information and identifiable biospecimens collected prior to and after the time of IRB review and approval. Exempt categories 2c, 3c, 7, & 8 added that require limited review. The limited review will be similar to an expedited review process.

Update: Exemptions What’s new? Exemption 4 – Secondary Research Uses of Identifiable Private Information or Identifiable Biospecimens What’s new? No longer limited to retrospective data review Permits secondary use of identifiable protected health information (PHI) (with HIPAA privacy board review) New Policy defining mechanisms by which research involving the secondary use of identifiable private information and/or identifiable biospecimens may be permissible Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met: The identifiable private information or identifiable biospecimens are publicly available; (ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;  (iii) The research involves only information collection and analysis involving the investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164…. [HIPAA]

Update: Exemptions Exemption 5 – Federal Research and Demonstration Projects Research and demonstration projects that are conducted or supported by a Federal department or agency, … and that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs New requirement: Each agency must maintain a public list of these projects, to be published prior to conducting the research. Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met: The identifiable private information or identifiable biospecimens are publicly available; (ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;  (iii) The research involves only information collection and analysis involving the investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164…. [HIPAA]

Update: Exemptions Exemption 6 – Taste and food quality evaluation and consumer acceptance studies No changes Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met: The identifiable private information or identifiable biospecimens are publicly available; (ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;  (iii) The research involves only information collection and analysis involving the investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164…. [HIPAA]

Update: Exemptions Exemptions 7 & 8 – Storage and Secondary Use of Data/Biospecimens Exemption 7 covers the storage and maintenance of identifiable data and/or biospecimens for future research collected under broad consent (i.e. creation of a repository). More on broad consent later… “Limited IRB review” required to assess the terms of the broad consent Exemption 8 covers the use of data or biospecimens collected under broad consent “Limited IRB review” required to confirm that the proposed use is consistent with the broad consent and that privacy of subjects and confidentiality of data is appropriate Category 1 – Revised Category 2 – Revised Category 3 – Replaced* Category 4 - Revised Category 5 – Revised Category 6 – Unchanged Category 7 – New Category 8 – New Exempt categories added for secondary research on identifiable private information and identifiable biospecimens collected prior to and after the time of IRB review and approval. Exempt categories 2c, 3c, 7, & 8 added that require limited review. The limited review will be similar to an expedited review process.

Update: Exempt Research The Final Rule allow the exemptions to apply to prisoners (Subpart C) for research involving a broader subject population if the research only incidentally includes prisoners.

Making a Determination of Non-Exempt Human Subjects Research

Cooperative Research Streamlining IRB review is accomplished in part by a mandate for the use of a single IRB for cooperative research conducted in the US. Revisions to cooperative research and the use of single Institutional Review Boards (sIRBs) will take effect January 20, 2020. The National Institutes of Health (NIH) policy on “Use of a Single Institutional Review Board for Multi-Site Research” goes into effect January 25, 2018 for NIH-funded multi-site research. The Pennington IRB is a member of SMART IRB for online reliance agreements and IRB Choice. Membership significantly furthers our efforts to successfully comply with NIH requirements for single IRB (sIRB) and the upcoming 2020 sIRB Final Rule requirements. Cooperative research studies involve more than one institution.  The SMART IRB authorization agreement serves as a model to help investigators adhere to the NIH’s policy on single IRB use for multisite studies. This policy was designed to improve IRB efficiencies while ensuring the protection of research participants so that research can proceed expeditiously.

Smart IRB

IRB Choice