COTTAGE HEALTH SYSTEM POLICY

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SUBJECT:

IRB REVIEW OF RESEARCH

IRB Review

 

DEPT: IRB POLICY #: 8012.06

 

GOAL:
To establish departmental policies regarding IRB review of research that are in compliance with federal regulations.

 

POLICY:

Initial and continuing reviews of research must be conducted by the IRB in accordance with HHS regulations.  These regulations are codified in the Code of Federal Regulations, Title 45, Part 46 (also known as the Common Rule) at 45CFR46.108-111.

PROCEDURES:

I.   Office of Research Applications to Conduct Research
Office of Research Applications to Conduct Research Institutional Review Board applications for initial review of a new study are contained  within the Application to Conduct Research, provided by the Office of Research.  Upon submission of an Application to Conduct Research, the Office of Research staff will determine what reviews the application will receive.  All studies conducted at a Cottage Health System (CHS) facility will receive operational/financial, and budget/contractual review.  Once all the necessary approvals have been obtained, the Office of Research issues a Ready to Accrue letter to the PI.  Studies may not be initiated until the Ready to Accrue letter has been issued.  Approvals generally take one month from the date of submission  Incomplete applications will be returned without review.

 

A completed Application to Conduct Research shall consist of the following items:

  • Application cover page
  • Two copies of the protocol
  • The study contract with budget (for on-site studies)
  • A copy of the form FDA 1572 (for drug studies) or the Sponsor's Investigator Agreement (for device studies)
  • Investigational Device Exemption (IDE) approval letter, if applicable (for device studies)
  • A CV for each investigator involved in the study
  • IRB fee
  • One original and 15 copies of the following items:
    • IRB cover page
    • Written responses to the 10 items
    • Investigator's Financial Disclosure Statement
    • Study budget
    • Informed Consent document including the Experimental Subject's Bill of Rights
    • Recruitment methods / Sample advertisements
    • If the research is sponsored by NIH, include a copy of the Supplemental Report on the Inclusion of Women and Minorities in Clinical Research.

 

II. Criteria for IRB Approval of Research.

In order to approve research in accordance with federal regulations, the IRB determines that all of the following requirements are satisfied:

  1. Risks to subjects are minimized:
    • By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
    • Whenever appropriate, by using procedures already being performed on the subject for diagnostic or treatment purposes.
  2. Risks to subjects are reasonable in relation to anticipated benefits, if any, and to the importance of the knowledge that may be expected to result. In evaluating risks and benefits, the IRB will consider only those risks and benefits that may result from the research (as distinguished from risks and benefits from therapies that subjects would receive even if not participating in the research). The IRB will 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.
  3. Selection of subjects is equitable. In making this assessment the IRB will take into account the purposes of the research and the setting in which the research will be conducted and shall be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, handicapped, mentally disabled persons, or economically or educationally disadvantaged persons.
  4. Informed consent will be sought from each prospective subject or the subject's legally authorized representative  (see policy 8012.07).
  5. Informed consent will be appropriately documented (see policy 8012.13).
  6. The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
  7. There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
  8. The research protocol is compatible with Cottage Health System's Mission and Value Statement.

When some or all of the subjects (children, pregnant women, handicapped, mentally disabled persons, or economically or educationally disadvantaged persons) are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the study to protect the rights and welfare of these subjects. See IRB Policy 8012.27: IRB Guidelines for Enrolling Vulnerable Subjects in Research.

The CHS IRB does not review protocols that plan for the inclusion of prisoners as research subjects. Please refer to IRB Policy 8012.28: Prisoners as Research Subjects for exceptions.

 

III.   Full Board Protocol Review Process

Review of research that does not qualify for expedited review or exempt status must be conducted by the IRB at convened meetings at which a majority of the members of the IRB (also known as the Committee) are present, including at least one member whose primary concerns are in nonscientific areas (i.e., a quorum).  Approval of research is by a majority vote of this quorum.  Should the quorum fail during a meeting (eg, loss of a majority through recusal of members with conflicting interests or early departures, or absence of a nonscientist member), the IRB may not take further actions or votes unless the quorum can be restored.  Currently, there are 11 members serving the Cottage Health System IRB Committee and the presence of six members at a meeting represents a quorum.

 

For initial review of a new study undergoing full board review, all members receive:

  • IRB cover page
  • Written responses to the 10 items
  • Investigator's Financial Disclosure Statement
  • Study budget
  • Informed Consent document including the Experimental Subject's Bill of Rights
  • Recruitment methods / Sample advertisements
  • If the research is sponsored by NIH, a copy of the Supplemental Report on the Inclusion of Women and Minorities in Clinical Research.
For applications undergoing full board review, the principal investigator is required to attend the meeting at a specified time to make a summary presentation of the project to the members of the IRB and to respond to any questions.   With permission, the co-investigator may present the study in place of the primary investigator.  After the presentation, the Principal Investigator and any member with a conflict of interest with the research under review are excused from the room. The Committee, a quorum being present, then discusses the application prior to voting.  A simple majority vote is required for approval.  Votes are conducted by hand and recorded by the IRB Administrator.

Only members are to be in the room during discussion and voting procedures, unless a confidentiality waiver is signed by any non-member.

The Principal Investigator is notified in writing of the outcome of the IRB review.  The research study may not be conducted if the application has been disapproved.  If modifications are requested, the study may not begin until those concerns are satisfactorily addressed.  The principal investigator must respond to the comments of the committee in writing, which the committee or designee will then consider.  This process continues until the protocol is approved, withdrawn, or denied.

Under certain circumstances the IRB may wish to provide a shorter approval period.  Such situations include:  
  • Perceived increased risk to subjects;
  • First time investigators;
  • New devices; and/or
  • Potentially harmful treatments.

 

IV. Conditional Approvals

Convened IRBs often set conditions under which a protocol can be approved.  OHRP recommends the following guidelines in such cases:

  • When the convened IRB requests substantive clarifications or modifications regarding the protocol or informed consent documents that are directly relevant to the determinations required by the IRB under HHS regulations at 45 CFR 46.111, IRB approval of the proposed research shall be deferred, pending subsequent review by the convened IRB of responsive material.
  • When the convened IRB stipulates specific revisions requiring simple concurrence by the investigator, the IRB Chair (or another IRB member designated by the Chair) may subsequently approve the revised research protocol on behalf of the IRB under an expedited review procedure.

The IRB approval period for research protocols may be no longer than one year from the time of initial review.  Therefore, if an investigator does not fulfill the IRB’s contingency requests for changes to the study for one or more months following the study’s initial review, the study’s expiration date is one year from the time of initial review, NOT one year from the final approval date.  Similarly, if the investigator does not fulfill the IRB’s contingency requests within one year of the request, the investigator’s study will be closed by the IRB and the investigator will be notified of this action in writing.

 

V. Expedited Review Procedures

For certain kinds of research involving no more than minimal risk, and for minor changes in approved research, the IRB refers to the current list of categories of research that may be reviewed by the IRB through an expedited review procedure published under HHS regulations at 45 CFR 46.110(b)(1) for the categories of research listed in the Federal Register of November 9, 1998 (63 FR 60364-60367) (See Attachment A: Expedited Review Procedures in Word document).

 

The IRB may use the expedited review procedure to review either or both of the following:

  1)   Some or all of the research appearing on the list and found by the reviewer(s) to involve no more than minimal risk;

Minimal risk is defined as :
The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.  This notion of minimal risk does not imply that the risks associated with the research will be considered exclusively in relation to those experienced in the daily life of a healthy person – when relevant, the clinical circumstances and experiences of the subject as an ill person will be considered in making this determination.

 

In the context of research involving medical records, surveys, and genetic research on tissue samples, “risk” may be considered psychosocial in nature, related primarily to the potential consequences of breaches of privacy and confidentiality; however, an important general rule applicable to this kind of research is that the expedited process may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

  2)   Minor changes in previously approved research during the period (of 1 year or less) for which approval is authorized. Under an expedited review procedure the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the IRB chairperson from among the members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the full board review procedure.  Minor changes include:
 
  • Non-significant protocol and/or consent form changes (changes which do not increase the risk to participants);
  • Advertisements and proposed recruitment methods;
  • Adverse Event Reports;
  • Closure to enrollment notices;
  • Study closures;
  • Miscellaneous handouts / written materials to participants, such as "Dear Patient..." letters from the sponsor;
  • Other sponsor updates and correspondences that do not significantly impact the protocol or participants' risk to benefit ratio.

The IRB provides a monthly Expedited Activities Report as a method for keeping all members advised of research submissions that have been approved under the procedure.

 

VI. Research Exempt From IRB Review

The Common Rule specifies, in section 45CFR46.101(b) that certain research activities are exempt from the requirements of the Rule, and may be conducted without continuing IRB review, following initial expedited review (see Attachment B: Review Exemptions in Word document).

 

All human subject research that is exempt under Section 101(b)(1-6) or 101(i) will be conducted in accordance with:

  • The Belmont Report;
  • The IRB's administrative procedures to ensure valid claims of exemption;
  • Orderly accounting for such activities.
The request will be reviewed by the IRB Administrator, and occasionally the IRB Chairperson, with a final determination issued by the former on behalf of the Committee. The specific category justifying exemption will be documented in the approval letter and in the Expedited Activities Report distributed to the Committee.

 

An investigator may not initiate research, which s/he believes is exempt until s/he has received formal concurrence of this determination from the IRB department.

 

 

Research involving certain subject populations (i.e. vulnerable subjects) is not eligible for exemption: children, prisoners, pregnant women, and subjects with impaired decision-making capacity. In addition, research or surveys concerning "sensitive" aspects of individuals' behavior, attitudes or beliefs, posing a risk of psychosocial harm, is also not eligible for exempt status. Research using human biological material may be eligible for exemption under specific circumstances.

 

VII. Continuing Review of Approved Studies .

If the study is not complete at the end of the approval period, the Principal Investigator may apply for a renewal of the approval.  Requests for renewal follow the same procedures as the initial review.  This process of Continuing Review is mandated by the Common Rule (Section 46.109(e)).

 

Approval by the IRB is for a specified period of time appropriate to the degree of risk, but in no case is approval given for more than one year from the last review.  Continuing review of IRB-approved research addresses the entire study, not just changes in it.

 

A reminder letter and Progress Report form are sent to the Principal Investigator approximately two months before the expiration of the approval, or they may be requested from the IRB Office. The Progress Report contains sections in which the investigator lists new information or unanticipated risks that were discovered during the research since the last IRB review.  Also included in the Progress Report are the number of subjects enrolled and whether or not the study has closed to enrollment.

 

The investigator must submit any reports received during the year, such as interim reports from the sponsor and reports from the Data and Safety Monitoring Board (DSMB). It is the investigator’s obligation to continuously monitor the overall risk-benefit ratio associated with participation in the study, thus promoting the safety and interest of the subjects under his/her care.  Any published material or other information that supports the continuation of the study may be included with the continuing review application.

 

It is the responsibility of the Principal Investigator to place requests for renewal sufficiently in advance so that the research study can be placed on the agenda for the IRB before the approval period expires.  Continuation of research after expiration of IRB approval is not allowed.  Research activities should stop, except for activity deemed appropriate to ensure the safety of currently enrolled subjects, and no new subjects may be entered into the study.  Additionally, an investigator (or the off-site institution he/she represents) may not open a new study until the investigator has resolved the expiration.  This may be done either by submitting the Progress Report requesting to close the study or by submitting a continuing review application requesting the study to be reopened.

 

The application for continuing review of an existing study should contain:

  • The IRB cover page
  • Responses to the 10 items, updated if necessary
  • The Progress Report
  • DSMB Report / Interim Report from the sponsor, if available
  • The consent document currently in use*
  • 1 copy of the current version of the protocol*
    *(Once a study has been closed to patient enrollment, submission of the consent document and study protocol is no longer required.)

Studies for which continuing review is sought that have had no protocol or consent form changes since the last review may be submitted for IRB review at a convened meeting without the investigator present.  However, investigators may be asked to attend the convened IRB meeting at which their active study is undergoing continuing review if there are any issues or questions.  If questions arise during the full board’s evaluation of the study and the investigator is not present t respond to the questions, the investigator’s responses must be received by the IRB prior to the study’s expiration date in order to prevent expiration of the study.

 

Studies subject to continuing review which were previously reviewed by the IRB at a full board meeting, but with zero enrollment or in which all patients are in follow-up (protocol-specified treatments/interventions have been completed), can be re-approved by expedited review, so long as they are received by the deadline for the meeting one month prior to their required IRB renewal date (one month prior to their expiration date).  Review of studies one month in advance is essential to allow a window of opportunity for studies to receive full board review in the event of a participant enrolling prior to completion of the expedited review.  (Once a participant has enrolled, the study is no longer eligible for expedited review – therefore it must be submitted in time to receive continuing review by the full board prior to the expiration of the studies’ continuing review date).

 

If no patients have been enrolled after 2 years of original approval of the study the IRB will reassess the value of continuing the study with the primary investigator.

 

VIII.   Review of Proposed Changes.

In accordance with HHS regulations review of proposed protocol changes must be conducted by the IRB at convened meetings at which a majority of the members are present, including at least one member whose primary concerns are in nonscientific areas, except where expedited review is appropriate under HHS regulations at 45 CFR 46.110(b)(2).

 

Changes in the design or consent procedure for a research study must be approved by the IRB before they are initiated.  The material should be presented with notation made as to the elements that have changes.

 

The required application documents for a proposed change are:  

  • The IRB cover page
  • A memo explaining the change.
  • The sponsor's letter outlining each change, the reason for the change, where it is found in the consent/protocol; and the exact wording changes.
  • An edited copy of the previously IRB-approved version of the consent form or protocol with a list of itemized changes and the changes marked using highlighting for new text and strike-through for deleted text
  • A clean copy of the new consent or protocol
Revisions qualifying for expedited review require the submission of one original copy of each of the items listed above.  For Full Board revisions, the original copy of each of the items is required, plus 15 copies of the original packet and one copy of the revised protocol.
    
    OHRP recommends that each revision to a research protocol be incorporated into the written protocol. This practice ensures that there is only one complete protocol with the revision dates noted on each revised page and the first page of the protocol itself.  This procedure is consistent with the procedure used for revised and approved informed consent documents which then supersede the previous one.

 

IX.   Authorized Signers

Except for exemption letters (which are signed off by the IRB Administrator), the IRB Chair is authorized and shall sign all official IRB approval letters, unless so designated by the Chair to authorize another individual.  This includes full board and expedited review of studies undergoing initial and continuing reviews, and all reportable changes to studies.  Although any IRB member may be designated, the Vice-Chair is most frequently selected to sign approval letters in the absence of the IRB Chair, or when the IRB Chair has a conflict of interest (e.g. he is the investigator of the study).
    
The name of the individual who has been given authority to sign the approval letter shall be on the approval letter.  The CHS IRB does not allow an individual to sign the name of another individual with or without his/her initials.
    
In certain situations, and when the IRB Chair is unavailable, minor revisions may be reviewed and approved by the IRB Administrator or the IRB Coordinator.  These include:
  • FYI reports from the sponsor or investigator's office
  • Cooperative group protocol approval forms
  • Minor revisions to the consent and/or protocol that are merely administrative and editorial, and do not include scientific changes (when the Chair is unavailable).

These minor submissions, requiring only a notice of receipt, will be stamped and copied by a member of the IRB department staff.  The original stamped document will be returned to the investigator and a copy will be placed in the study's IRB file.

 

X.    Telephone Conferencing

oth OHRP and the FDA allow full board IRB meetings to take place via telephone conferences when no other alternative is available.  In order to fulfill the requirements of an acceptable telephone conference, all IRB members must have in their possession a copy of the meeting materials, including copies of the applications of all of the studies to be reviewed.  The members must be able to speak and hear each other clearly, and the phone must be in a private location where non-IRB members are not able to hear the deliberations.
    
All of the requirements set forth in the regulations regarding IRB meetings apply, including:
  • A quorum must be met and maintained throughout the phone conference
  • Detailed minutes of the meeting must be recorded
  • Each study must be reviewed and voted upon separately
  • All of the materials provided to members for full board meetings must be received in advance enough to be reviewed prior to the phone conference

Cottage Health System uses the AT&T Teleconferencing Services. (Attachment C provides full details and instructions).

 

> Attachment A: Expedited Review Procedures  

> Attachment B: Review Exemptions

2/13

 

 

COTTAGE HEALTH SYSTEM POLICY

RECOMMENDED BY: Leilani Price DATE: 8/02

ORIGINAL POLICY EFFECTIVE DATE: 12/02

APPROVED BY: .. DATE:

DATE REVISED: 1/08; 4/10; 3/11, 7/12
DATE REVIEWED: 4/06; 1/08; 1/09