1. Everything you Need to Know About the Common Rule Changes
Susan Kornetsky
Matt Stafford
Yvette Marts

2. It’s Been in the Works for Some Time
ANPRM
7/2011
NPRM
9/2015
Final Rule
1/2017
1/2018 but implementation delayed until 1/2019
1/2020 ( Federally funded cooperative research single IRB)
All Federally Funded Research

3. Major Changes For PIs
New categories of exempt research/not human subject research
Removes the requirement to conduct continuing review of some minimal risk research
Informed Consent Changes
Format
Elements
Posting Requirements for Clinical Trials
Requirement for a single IRB for U.S.-based institutions engaged in cooperative research

4. This is Not Research: No Submission
Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship)
Public health surveillance activities (note there are other forms of public health research)
Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or investigative purposes
Authorized operational activities in support of intelligence, homeland security, defense, or other national security missions

5. Exemption Reminder
Activities that ARE considered human subject research BUT…
They do not need to follow all of the other human subject rules (for example obtain consent, waive consent, satisfy all the criteria for approval).

6. Exemptions New RESTRICTED Normal Education Setting
The research must not adversely impact the student’s opportunity to learn required educational content or the assessment of educators who provide the instruction.
Educational Tests, Surveys, Interviews, Public Observation
Can be identified and sensitive if IRB determines there are adequate privacy and confidentiality protections in the study. Children not allowed for surveys .
Benign Behavioral Intervention (adults only)
Brief in duration, intervention must be harmless, painless, and not physically invasive, not be likely to have significant adverse lasting impact on subjects, not offensive or embarrassing
Secondary Research of Identifiable Information or Specimens Collected for Other Purpose for which Consent Not Required
RESTRICTED
EXPANDED
New
EXPANDED

7. Exemptions
Research conducted supported by Federal Agency Taste & Food Quality Storage or Maintenance for Which Broad Consent Is Required Secondary research for which Broad Consent Required
EXPANDED
No Change
New
Will Not Use
We will continue to have IRB reviewed protocols and consents contain provisions for broad research use of data and specimens . Will not use categories 7 & 8.

8. Exemption 4 Change
Secondary research for which consent is not required: use of identifiable private information or identifiable biospecimens if at least one of the following is met: o Information or biospecimens are publicly available
Recorded information cannot be readily identified (directly or indirectly) and investigator does not attempt to contact subjects and will not reidentify subjects
Information collection and analysis involving identifiable health information when use is regulated by HIPAA*
Research by or behalf of Federal dept/agency using government generated or collected information; compliant with relevant privacy policies
*HIPAA covers data not specimens but most PIs use specimens with data

9. Primary vs. Secondary Use of Biospecimens and Data
Introduce concept secondary use instead of “existing” specimens/data
Re-using information or biospecimens that are collected for some other “primary” or “initial” activity.
Examples: chart review study, using leftover biospecimens from routine clinical care
Private information and biospecimens no longer have to be in existence prior to the start of the research to be considered exempt

10. Options Under the Pre-2018 Requirements
Nonidentifiable biospecimens, nonidentifiable private information?
Not human subjects research under 45 CFR part 46
Identifiable biospecimens or identifiable private information?
Human subjects research under 45 CFR part 46
Research may be exempt if:
If research is non-exempt, IRB review required. Options:
Already existing publicly available information or specimens or
Seek a waiver of informed consent from the IRB + IRB approval or
Already existing information or specimens recorded by the investigator in nonidentifiable form OR
Seek informed consent for this new activity from subjects + IRB approval
Certain research and demonstrations conducted by or subject to the approval of department or agency heads
Thanks to Marianna Bledsoe, Elizabeth Buchanan, Lauren Hartsmith

11. Secondary Research Options Under the 2018 Requirements
Nonidentifiable biospecimens, nonidentifiable private information?
Identifiable biospecimens or identifiable private information?
Not human subjects research under 45 CFR part 46
Human subjects research under 45 CFR part 46
Research may be exempt if:
If research is non-exempt, IRB review required. Options:
Publicly available information or
Seek a waiver of informed consent from the IRB + IRB approval or
Information (including information about biospecimens) recorded by the investigator in nonidentifiable form or
Seek informed consent for this new activity from subjects + IRB approval
If activities covered by HIPAA-regulated or
HIPPA authorization and waivers still required
Certain activities by or on behalf of the federal government or
Certain research or demonstration projects conducted or supported by the federal government, or otherwise subject to the approval of department or agency heads
Thanks to Marianna Bledsoe, Elizabeth Buchanan, Lauren Hartsmith

12. How Exempt Changes Implemented
CHeRP Exemption form has been changed to address new categories and requirements
There are some pediatric limitations
Any research limited to secondary use of specimens/data will still need to be submitted on limited research form - staff will determine
Not human subjects
Exempt
Review (expedited or full)

13. Continuing Review Changes
No regulatory required continuing review when
The study qualifies for expedited review as specified on list of categories in the regulations.
The study has research that has reached the state of involving only the analysis of data or accessing follow-up clinical data from procedures that the subjects would undergo as part of clinical care (even with identifiers).
BUT BCH will substitute Administrative Update
Notification in CHeRP
Simplified form
Consent approval and expiration dates will still be updated
CR form revised
No longer completion report in CHeRP it will be included in CR form
CR has new category to determine if can move to an administrative update

14. How Continuing Review Implemented
CR form changed to collect information to allow us to close out or change protocol to administrative reviews.
New administrative review form and notification in CHeRP.
You will be sent appropriate forms in CHeRP.

15. Continuing Reviews One Last Point
On 1/21/2019 the continuing review form will change
If one was started, completed or submitted BUT NOT approved by 1/21/2019 you will need modify and complete new questions
Therefore
WE WILL SHUT DOWN ability to create or submit CR SUBMISSIONS AS OF midnight January 15, 2019
There will special IRB meeting for CRs only January 18, 2019.
CHeRP opens January 21, 2018 and some CRs will be sent back for updating if required

16. Informed Consent Changes
New concept of “concise summary”
New basic and additional elements to disclose
Public posting of consent documents
Changes to waivers of consent

17. Informed Consent Changes
The intent of these changes is:
To facilitate the subjects' understanding of the proposed research
AND
Ensure that the subject understands how their data and biospecimens may be used
Emphasis is on the subject’s comprehension

18. General Requirements for Informed Consent
Following remains unchanged:
Obtain legally effective Informed Consent
Under circumstances that:
Provide opportunity to discuss and consider participation
Minimize possibility of coercion or undue influence
In a language understandable to the subject
No exculpatory language
language understandable: English or other language (Spanish, sign language), but also reading level and terminology used

19. General Requirements for Informed Consent
Newly added: Must provide information that a reasonable person would want to have in order to make an informed decision about participation.
REASONABLE PERSON STANDARD
Rule

20. General Requirements for Informed Consent
Newly added:
Informed consent must begin with a concise and focused presentation of key information
Assist in understanding the reasons why one might or might not want to participate.
Must be organized in a way that facilitates comprehension.
Informed consent as a whole must:
Present information in sufficient detail related to the research.
Organized and presented in a way that does NOT merely provide lists of facts.
Facilitates understanding of reasons why one might or might not want to participate.
IC as a whole -> not limited to Consent Form itself, but the entire consent process
This is not “new” -> but now that it is defined in the regulations it allows auditors to ding researchers during audits

21. Concise Summary
Is a summary of information that is most crucial to making a decision whether or not to participate.
Is presented first rather than being dispersed in the document.
Is an opportunity for the PI to consider or seek input on the key pros and cons that a prospective participant would need to weigh, in making a decision.
Type of information is not defined in rule – depends on the nature of the study.
Length is not defined – BCH -> keep it to 2 pages or less.
Does not need to include all 9 Basic and/or 9 Additional Elements.
Does not limit pros and cons to just risks and benefits.
Does not have to look exactly like it is presented in the template.
Pros/cons: risk/benefit but also burden/inconvenience (# or size of oral pill vs weekly infusion, time commitment, visit frequency/length)
Source: UK IRB website

22. BCH template “Summary of Important Information”
Concise Summary is included in the revised Informed Consent Template available on the IRB website.
There are 3 examples available on the IRB website.
Clinical trial randomized study
Minimal risk study
Biorepository

24. BCH template “Summary of Important Information”
Remember:
Concise Summary is only one part of the consent document and the informed consent process.
It is NOT acceptable to only review the Summary to obtain informed consent.

25. Basic Elements of Informed Consent
Newly added:
Future use:
Research collecting identifiable private information and/or identifiable biospecimen must include one of two statements about future use.
Note: Nearly all studies collect identifiable private information
Survey studies

26. Basic Elements of Informed Consent
Newly added (cont):
Collecting identifiable private data or biospecimen then must include one of the following statements:
- That identifiers might be removed from identifiable private information or identifiable biospecimen and - That, after such removal, it can be used for future research studies without obtaining additional Informed Consent. OR
That the subject’s information or biospecimen collected as part of the research, even if identifiers are removed, will NOT be used or distributed for future research studies.
Survey studies

27. Additional Elements of Informed Consent
Newly added:
Commercial profit:
Statement that subject’s biospecimen may be used for commercial profit
and
Specify whether the subject will or will not share in the profit.
Clinically relevant research results:
Statement regarding clinically relevant research results, including individual results, will be disclosed to subjects,
And if so, under what conditions.

28. Additional Elements of Informed Consent
Newly added:
Whole Genome Sequencing:
For biospecimen, specify whether the research will or might include whole genome sequencing
Note: Be realistic about future use, sharing and the possibility of using the biospecimen for whole genome sequencing

29. Informed Consent Document
Summary of Important Information
Detailed Consent
Signature Page
Required Concise
Summary first
Main Body
Updated Informed Consent Template/Document
Source: UK IRB website

30. Posting requirements for clinical trials
One IRB approved consent form used to enroll subjects must be posted on a publically available Federal Website.
Applies only to clinical trials that are Federally funded.
The purpose of this requirement is to be more transparent about the consent forms being used and, over time, improve the quality of consent forms.

31. Posting requirements for clinical trials
Currently identified publically available Federal Website:
Clinicaltrials.gov
Regulations.gov
More may follow in the future
BCH will require posting on Clinicaltrials.gov

32. Posting requirements for clinical trials
The informed consent document must be posted after the trial is closed to recruitment and no later than 60 days after the last study visit by any subject, as required by the protocol
60 days after last visit
any subject*
Database lock – data analysis
Study and data analysis complete
Start trial
Enrollment first subject
Enrollment last subject
Trial closed to
recruitment
Last visit any subject
Ideally enrollment last subject = study closed to recruitment. Sometimes enrollment target is not reached and study will close to enrollment prematurely, so there may be a gap.
timeline
Period in which 1 consent must be posted
Note: Last visit by ANY subject is not by default the last enrolled subject,
but of the last ‘ACTIVE’ subject in the trial

33. Posting requirements for clinical trials
60 days after
last visit
any subject*
Trial closed to
recruitment
Period in which the consent must be posted
PI responsibility:
Keep track of when this window opens and closed.
Posting 1 consent form used for enrollment during this window.

34. Posting requirements for clinical trials
Only 1 consent document posting would be required for each multi-institution study.
Things to consider at the beginning of the multi-site trial:
Who will be responsible for posting the IC?
How will this site/person keep track of overall enrollment closure and last study visit by last active subject across all sites?
What kind of tracking/reporting structure needs to be in place?
Responsibility of the coordinating center? What if there is no coordinating center?

35. Posting requirements for clinical trials
If Federal department or agency determines that certain information should not be made publically available (e.g. confidential commercial information, they may permit redactions on the information posted.

36. General Implementation
Applies to all research with approval dates as of January 21, 2019 going forward.
Protocols previously approved will not change - with exception of transitioning over existing protocols in data analysis only at time of continuing review.

37. Transition: On 1/21/2019 Protocols in Preparation
New Protocols ( any type) in
Draft
Scientific review
Department review
Analyst review
Assigned to meeting or expedited review (IRB Chair)
New Rule will APPLY
May need to revise/include
consent changes
possibly answer some new questions
post consent if clinical trial and federally funded

38. Transition: On 1/21/2019 Full Review
If protocol underwent full IRB - but no final approval
Conditional Approval
This is because approval date will be before 1/21/2019 , activation afterwards
Deferrals
Will need to revise/include
consent changes
possibly answer some new questions
post consent if clinical trial and federally funded
OLD

39. Transition: On 1/21/2019 Expedited
Undergoing expedited review
If IRB final approval has been released.
If in process or questions
May need to revise/include
consent changes
possibly answer some new questions
post consent if clinical trial and federally funded
OLD

40. Now What About FDA Regulated?
FDA has not revised regulations: Many changes will not apply to research with
Drugs
Devices ( significant risk and non significant risk)
Biologics
Mobile medical apps
Continuing review still required
Since consent changes are not inconsistent with current FDA regulations - BCH will implement consent changes for FDA regulated research unless sponsors object

41. What About Other Funding Sources?
Will apply most changes on a voluntary basis to assist in consistency
Will help reduce regulatory burden
Will implement consent changes for FDA regulated research unless sponsors object
Will not implement posting of consents for clinical trials

42. Common Rule Implementation at BCH smaller no
New Exemptions
Eliminate Continuing
Reviews
Change Consent Format and Elements
Post Consents on CT.gov
Required Single IRB
NIH
Federal
Voluntary until Jan 2020
FDA NA
Still requires CR review
Do not need to post clinical trials
Voluntary at present
Other
With exceptions

43. Other IRB Changes 1/21/2019 Single patient expanded access form
Now includes emergency use and single patient expanded access outside clinical trial
New requirement for annual update if therapy is continuing ( you will get CHeRP notification)
New updated genetics questions on all protocols
Separated incidental findings for genetics from other types of testing
CheRP will throw an error and you will need to complete new questions for
Any protocol in process of review that has genetics questions answered
Before you submit an amendment if protocol has existing genetic questions answered

44. In Conclusion
We have tried to make as many changes transparent in the forms and CHeRP notifications – but this means new forms and notifications.
Plan ahead – the fewer protocols, amendments, continuing reviews in process on Jan 21, 2019 the better. Either finish up now or wait to start.
The requirement for key information in consent forms will likely be the biggest burden for PIs/research teams.
Help us figure out what “key information” is for consent. You are the experts.
Start using new template now.
We need you to do your part to minimize delays in approval.
Things may change as we receive more guidance from the regulators . We have had to implement the changes in CHeRP with no regulatory guidance.
Expect some bumps: Let us know when things do not work or seem odd. Changing CHeRP is complex but we will course correct !
Lastly please be patient with the IRB staff and committee- this is as new to us as it is to you; we will do our best!

45. Thank you this takes teamwork!
Questions ?