1. IRB 101: IRB Review Criteria; Tips for Submission
Columbia University Medical Center IRB
July 14, 2005

2. Objectives Describe how submissions are routed for review;
Provide return criteria;
Explain the requirements for approval;
Demonstrate where in RASCAL information should be entered;
Provide tips for a complete and accurate submission.
Facilitate more timely review through a better understanding of the IRB review process and review criteria.

3. Submission Process: New Protocols
Protocol submitted to the IRB (“submitted”/Log-in queue);
Administrative review conducted by IRB staff:
Reviewer form guides review;
Performance standards provide timeline;
Review comments entered into Notes.

4. Submission process: New Protocol (2)
Protocol will be accepted (“logged in”/Chair queue) if complete.
PI submits protocol
“Submitted”
(Log-in queue) Staff review
“Logged in”
(Chair queue)

5. Submission process: New Protocol (3)
Return Criteria at log-in stage:
Cancer Center is not listed in Facilities section, and the research is cancer-related;
PI is not qualified;
Consent and/or Assent is not attached, and a waiver has not been requested;
Recruitment material is mentioned, but not attached;
Study instruments are described, but are not attached;
Sponsor’s protocol, IDB, or Package Insert is not attached;
Grant, contract, or other documentation of funding agreement is not attached;
There is insufficient information to make required determinations.

6. Submission process: New Protocol (4)
Protocol will
be returned (“returned”/
Investigator queue)
if one or more
return criteria
are met.
PI revises protocol
Correspondenc e from Chair to PI
PI submits protocol
Correspondenc e from team to Chair
“Submitted”
(Log-in queue) Staff review
Correspondenc e from logger to team
“Returned”
(Investigator queue)
PI receives protocol

7. Submission process: New Protocol (4)
Overview
PI revises protocol
Correspondenc e from Chair to PI
PI submits protocol
Correspondenc e from team to Chair
“Submitted”
(Log-in queue) Staff review
Correspondenc e from logger to team
“Logged in”
(Chair queue)
“Returned”
(Investigator queue)
PI receives protocol

8. RASCAL tip: Review IRB Submission Manual
Posted on Columbia University’s Office for Clinical Trials website:

9. RASCAL tip: Clarity
Describe clearly and accurately what will be done at this site or under the direction of a Columbia investigator;
Identify related procedures that will be or have been done elsewhere or previously;
Provide clear descriptions of relationships;
Accurately describe funding mechanisms;
Consistently and precisely describe data collection.

10. Submission Process: Renewals
Similar process, different form
Return criteria:
Clean copies of consent documents or study instruments not attached;
Enrollment information not provided;
Documents or fields not updated;
Conditions of previous approval not satisfied;
All required attachments not provided.

11. RASCAL tip: Review attachments
Archive superceded, reference, HIPAA documents;
Review content of attachments for currency, accuracy, outdated approval stamps, and inclusion of new requirements;
Review correspondence from previous approval.

12. Submission Process: Modifications
Similar process, summary of modification, assessment of revision in all applicable documents
Return criteria:
Clear explanation of changes not provided;
Description of modification does not match changes in documentation;
Changes are described but not incorporated;
Supporting documentation not attached.

13. Submission Process: Adverse Event Reports
Similar process, reconciliation of investigator assessment with AE policy
Return criteria:
All required documentation not attached;
Event does not meet criteria to be reported individually;
Investigator’s assessment does not comport with supporting information.

14. RASCAL tip: Name files logically

15. RASCAL tip: Include Correspondence
Cover letter with initial submission.
Correspondence or attached “response” with resubmissions.
Attached letter to IRB to explain unusual or complex collaborations, centers, affiliations, procedures, etc.

16. IRB Review
Low risk protocols may be eligible for exemption (6 categories)
Minimal risk protocols may be eligible for expedited review (9 categories)
Protocols that are not exempt or cannot be expedited require review by the full Board
Time required for review is dependent upon the type of review, complexity and risk level of procedures, and other factors
Chair schedule
IRB meeting schedule
Completeness of submission
Other required approvals
Recommendation:
Submit as soon as all protocol materials are available
Allow 60 days for renewal of full Board protocol

17. Review Process: Overview
“Logged in”
(Chair queue)
Chair reviews or distributes
“Distributed” then “Assigned to Meeting”
Exempt or expedited
Full Board
Approve
Approve
Return
Pending
Return
Defer
Disapprove

18. Criteria for IRB approval of research: 45 CFR 46.111 and 21 CFR 56.111
(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied:

19. Risks to subjects are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

20. New protocol considerations:
Research versus clinical care?
Design features?
Types of risk: physical, social, psychological, economic?
Risks reduced or managed to the extent possible?
Safeguards incorporated?
Potential for statistical validity demonstrated?
Investigators competent?
Inclusion and exclusion criteria clearly defined?
Renewal:
Is it the determination of the IRB, based on an evaluation of reported enrollment, adverse events, and unanticipated problems, that risks are still minimized?

21. RASCAL entry: Research Page

22. RASCAL entry: Study Description; attachments
1. Study Purpose and Rationale Study Design and Statistical Procedures Study Procedures Study Drugs or Devices Study Questionnaires Study Subjects Recruitment Confidentiality of Study Data Potential Risks Potential Benefits Alternatives

23. (2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

24. New protocol considerations:
Acceptable risk/benefit ratio?
Ethically acceptable to expose participants to risk of harm?
Available alternatives?
Renewals:
Is it the determination of the IRB that risks are still reasonable in relation to anticipated benefits?
Have any subjects been seriously harmed?
Should any new information be provided to subjects?

25. RASCAL entry: Study Description; attachments
1. Study Purpose and Rationale Study Design and Statistical Procedures Study Procedures Study Drugs or Devices Study Questionnaires Study Subjects Recruitment Confidentiality of Study Data Potential Risks Potential Benefits Alternatives

26. RASCAL tip: 11 Elements
Ensure that all 11 elements of a research protocol are addressed in the Study Description and/or attached protocol;
Study Description may be the “only” protocol or serve as an overview of a sponsor’s protocol;
Avoid “See attached protocol” as the Board members will receive the Study Description but not attached protocols.

27. (3) Selection of subjects is equitable
(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

28. New protocol considerations:
Easy availability, compromised position, or susceptibility to manipulation a factor?
If potential benefit, particularly for conditions with no effective treatment, are recruitment methods and enrollment criteria objective?
Are ethnic groups neither under- or over-represented?
Are women and children included where appropriate?
Renewals:
Has the actual selection/enrollment of subjects represented an equitable distribution of the benefits and burdens of the research (versus the anticipated study population)?

29. RASCAL entry: Subjects Page

30. RASCAL entry: Subjects Page

31. RASCAL tip: Subject Selection
Select “Special Populations” options thoughtfully
Understand why/when vulnerability exists
Justify inclusion of vulnerable groups
Consider and include additional protections, or exclude group, as appropriate
Select “Recruitment” options accurately
Text or documentation must be included in submission

32. (4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by 45 CFR or 21 CFR 50.

33. New protocol considerations:
Are procedures for an ongoing process described?
When and by whom will consent be obtained?
How will competency be addressed?
Is surrogate consent proposed, and if so, is it acceptable?
Is a waiver of consent* requested, and if so, is justification provided?
*Not permitted under most circumstances by FDA.
Renewals:
Has consent been obtained from enrolled subjects?
Is the consent process adequate or are changes required (to the process or the form/forms) before additional subjects may be enrolled?
Is there new information that should be, but has not yet been, conveyed to enrolled subjects so that they may make an informed choice about continuing their participation?

34. Basic elements of informed consent
(1) a statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;
(2) a description of any reasonably foreseeable risks or discomforts to the subject;
(3) a description of any benefits to the subject or to others which may reasonably be expected from the research;
(4) a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
(5) a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;

35. Basic elements of informed consent (2)
(6) for research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
(7) an explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and
(8) a statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

36. Additional elements of informed consent
(1) a statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
(2) anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
(3) any additional costs to the subject that may result from participation in the research;
(4) the consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
(5) A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and
(6) the approximate number of subjects involved in the study.

37. RASCAL entry: Consent Form Builder

38. RASCAL tip: Select Layout; Review Form

39. Waiver criteria: 45 CFR 46.116(d)
(1) the research involves no more than minimal risk to the subjects;
(2) the waiver or alteration will not adversely affect the rights and welfare of the subjects;
(3) the research 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.

40. Waiver criteria: 45 CFR 46.116(c)
(1) the research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and
(2) the research could not practicably be carried out without the waiver or alteration.

41. RASCAL entry: Subjects Page

42. (5) Informed consent will be appropriately documented, in accordance with, and to the extent required by 45 CFR or 21 CFR

43. New protocol considerations:
Is use of a written consent document proposed?
Does the consent document contain required elements, exclude exculpatory language, and include optional elements where appropriate?
Is waiver of written documentation of consent requested, and if so, is justification provided?
Will a copy of the form be provided to subjects?
If verbal consent will be obtained, are appropriate procedures proposed?
Renewals:
Has consent been appropriately documented for enrolled subjects?
Have subject complaints about the consent process been received?

44. Waiver of written documentation criteria: 45 CFR 46.117(c)
(1) The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or
(2) The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.

45. (6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

46. New protocol considerations:
Is a data and safety monitoring plan needed?
Are proposed data and safety monitoring procedures adequate?
Will the consent process be monitored?
Renewals:
Has the IRB been informed of any unforeseen problems or accidents that may have occurred?
Do reports of adverse events and monitoring bodies reflect that the data are being adequately monitored?
Should the IRB request that progress reports be submitted at regular intervals, more often than annually?

47. RASCAL entry: Study Description; attachments
1. Study Purpose and Rationale Study Design and Statistical Procedures Study Procedures Study Drugs or Devices Study Questionnaires Study Subjects Recruitment Confidentiality of Study Data Potential Risks Potential Benefits Alternatives

48. (7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

49. New protocol considerations:
In what manner will data be gathered and maintained (anonymously, de-identified, coded, identifiable)?
Are procedures for collecting and storing identifiable data adequate to reduce risk of breach of confidentiality?
If data will be transmitted to another site, are procedures appropriate?
Does the consent document adequately reflect data confidentiality issues and potential breaches?
Are research personnel trained in privacy practices?
Renewals:
Have there been complaints from subjects, or reports of unanticipated problems related to privacy and confidentiality?

50. RASCAL entry: Study Description
1. Study Purpose and Rationale Study Design and Statistical Procedures Study Procedures Study Drugs or Devices Study Questionnaires Study Subjects Recruitment Confidentiality of Study Data Potential Risks Potential Benefits Alternatives

51. (b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

52. New protocols considerations:
Is information included for the required determinations of Subparts B (pregnant women, fetuses), C (prisoners), and D (children and minors) to be made?
Do consent processes adequately address the needs of vulnerable subjects, e.g., translations, legally authorized representatives?
How will competency to provide consent be determined?
Are procedures in place to address loss of cognitive ability during the trial?
Renewals:
Are the determinations required by the Subparts still acceptable?
Should competency be reassessed?

53. Research with Children
When children or minors will be subjects, the IRB must determine and provide the basis for their determination of:
1. Category of research:
§ Research not involving greater than minimal risk.
§ Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects.
§ Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition.
§ Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.

54. Research with Children (2)
2. Requirements for parental permission:
One or both parents may provide permission for research in categories and
Both parents must provide permission for research in categories and
3. Whether assent should be obtained:
Considering age and maturity of the children
Evaluating whether effective alternatives are available
4. Whether wards will be involved:
An advocate must be provided for each ward that is enrolled

55. IRB Actions Defer Approve Require modifications
defer to Chair as “pending” or
defer to Board as “returned”
Defer
Suspend enrollment*
Suspend the study*
Terminate*
*Reportable to OHRP and/or FDA, as applicable, sponsor, subjects, institution

56. An IRB may also:
Impose additional precautions or reassess special requirements previously imposed
e.g., the IRB has the authority to observe or have a third party observe, the consent process as well as the research itself [45 CFR (e) and 21 CFR (f)]

57. Summary History Regulations IRB Review Criteria Tips for Submitting
RASCAL