# Department of

# Veterans Affairs

Date: February 15, 2006

From: Chief Officer, Office of Research Oversight (ORO) (10R)

Subj: ORO Quality Assurance Project: Evaluation of Institutional Review
Board (IRB) Minutes

To: Institutional Officials at VA Facilities with Federalwide Human
Subject Assurances (FWAs)

1.  As part of its ongoing program of quality assurance in compliance
    with human subject protection requirements under 38 CFR Part 16 and
    VHA Handbook 1200.5, ORO evaluated fundamental IRB procedural and
    documentation practices, as reflected in the minutes of 371 VA IRB
    meetings and 406 affiliate IRB meetings conducted from December 2003
    through April 2004 (see attached report).

2.  The minutes of VA and affiliate IRB meetings reflected substantial
    compliance with fundamental IRB procedural and documentation
    requirements. Over 90% of the minutes for both VA and affiliate IRBs
    reflected compliance with the requirements related to:

    a.  IRB composition and membership.

    b.  The presence of a majority of members for each vote.

    c.  The presence of a nonscientist member for each vote.

    d.  Full documentation of separate votes for each initial and
        continuing project review.

    e.  Application of regulations specifying that informed consent
        requirements may not be waived or altered in research regulated
        by the Food and Drug Administration (FDA).

3.  Results suggested that greater attention to the following
    requirements was warranted at some facilities:

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a.  Full documentation of nonparticipation by members in IRB
    deliberations and votes on research for which they have conflicting
    interests \[38 CFR 16.107(e) and VHA Handbook 1200.5, §7.i.(2)(g)\].

b.  Full documentation of findings required for waiver or alteration of
    informed consent requirements under VA regulations \[38 CFR
    16.116(d) and VHA Handbook 1200.5, §7.i.(2)(e).\]

4\. ORO Regional Offices conducted followup where warranted, and many
facilities have undertaken quality improvement activities since the time
sampled.

![](media/image1.png){width="2.1222222222222222in"
height="0.5597222222222222in"}

David A. Weber, PhD, FACNP

Attachment

cc: Under Secretary for Health (10)

Principal Deputy Under Secretary for Health (10A)

Deputy Under Secretary for Health for Operations and Management (10N)

Chief Research and Development Officer (12)

Network Directors

ACOSs/R&D or Research Coordinators

Office of Research Oversight

Quality Assurance Project:

Review of Institutional Review Board (IRB) Minutes

From VA and Affiliate IRBs

February 15, 2006

> *Summary: The Office of Research Oversight (ORO) evaluated fundamental
> Institutional Review Board (IRB) procedural and documentation
> requirements as reflected in the minutes of 371 Veterans Health
> Administration (VHA) IRB meetings and 406 affiliate IRB meetings
> conducted from December 2003 through April 2004.* *These minutes
> demonstrated substantial compliance with IRB requirements under 38 CFR
> Part 16 and VHA Handbook 1200.5 in the fundamental areas reviewed.
> However, increased attention was warranted at some facilities to the
> requirements for full documentation in the minutes that (i) IRB
> members are not present during IRB deliberations and votes on research
> for which they have conflicting interests; and (ii) the IRB makes the
> required findings justifying waivers or alterations of informed
> consent requirements.*
>
> The VHA Office of Research Oversight (ORO) advises the Under Secretary
> for Health (USH) on all matters of compliance and assurance related to
> the protection of human research subjects, laboratory animal welfare,
> research safety and security, and research misconduct.
>
> As part of its ongoing program of quality assurance, ORO periodically
> collects baseline and trend-line data to monitor system-wide
> compliance with VHA requirements relevant to its areas of
> responsibility. Such data also provide information for optimizing the
> relevance and timeliness of ORO's Routine On-Site Reviews of
> individual VHA research facilities.
>
> To examine baseline compliance with fundamental human subject
> protection requirements under 38 CFR Part 16 and VHA Handbook 1200.5,
> ORO reviewed the minutes of meetings conducted by the VA-designated
> IRBs of record at VHA research facilities and their affiliate
> institutions from December 2003 through April 2004.
>
> **Method**
>
> ORO staff developed a questionnaire of descriptive characteristics and
> a checklist of fundamental procedural and documentation requirements
> that should be reflected in the minutes of IRB meetings under the
> human subject protection requirements in VA
>
> regulations at 38 CFR Part 16 and VHA Handbook 1200.5. Tables 1 and 2
> contain selected items from the questionnaire and the checklist,
> respectively.
>
> To conduct its review, ORO requested the following documents from each
> VA facility holding a Federalwide Assurance (FWA) for the protection
> of human subjects, and thus authorized to conduct human subject
> research:

-   For facilities using VA IRBs as their IRB(s) of record, a copy of
    the minutes (including appendices) of all IRB meetings occurring
    from December 2003 through April 2004.

-   For facilities using the IRB(s) of an affiliate institution as their
    IRB(s) of record, a copy of the minutes (including appendices) of
    all meetings occurring from December 2003 through April 2004 for (up
    to) two affiliate IRBs most frequently reviewing the VA facility's
    human subject research.

-   A roster for each IRB reflecting as accurately as possible its
    membership from December 2003 through April 2004.

> ORO Regional Office (RO) staff reviewed the meeting minutes from the
> IRBs in their respective regions relative to each item on the
> checklist. Common review criteria were developed across ROs for any
> items that were open to differing interpretations. RO staff forwarded
> their review data to ORO Central Office (CO) staff to be compiled.
>
> **Results**
>
> As Table 1 (Item 1a) indicates, 120 VA facilities held FWAs at the
> time of ORO's review. These facilities used one or more IRBs operated
> by their own facility, by another VA facility, or by an affiliate
> institution. Seventy-five of the 120 FWAs listed IRBs operated by 58
> VHA facilities, and 45 of the 120 FWAs listed IRBs operated by 33
> affiliate institutions \[Table 1, Item 1b\].
>
> ORO reviewed the minutes of 371 VA IRB meetings and 406 affiliate IRB
> meetings conducted from December 2003 through April 2004 \[Table 1,
> Item 1c\]. These minutes reflected the deliberations of 63 IRBs from
> the 58 VA facilities operating IRBs, and 52 VA-designated IRBs from
> the 33 affiliate institutions \[some entities operated more than one
> IRB; Table 1, Item 1d\].
>
> Table 2 presents the results for checklist items related to
> fundamental procedural or documentation requirements that should be
> reflected in the minutes of IRB meetings. All results were based only
> on minutes containing information that was relevant and applicable to
> the individual item. Consequently, the number of meetings referenced
> in Table 2 varies across items.
>
> Overall, the minutes of VA and affiliate IRB meetings demonstrated
> substantial compliance with the fundamental IRB procedural and
> documentation requirements examined in this project. Over 90% of the
> minutes for both VA and affiliate IRB meetings reflected compliance
> with the requirements for:

-   IRB composition and membership \[38 CFR 16.107(c); Table 2, Item
    1\].

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-   The presence of a majority of members for each vote \[38 CFR
    16.108(b); Table 2, Item 2\].

-   The presence of a nonscientist member for each vote \[38 CFR
    16.108(b); Table 2, Item 3\].

-   Documentation of votes \[38 CFR 16.115(a)(2); Table 2, Item 4\].

-   Separate voting on each continuing review \[38 CFR 16.115(a)(2);
    Table 2, Item 5\].

-   Adherence to the regulation that prohibits waiver or alternation of
    informed consent for FDA-regulated research \[21 CFR 50.23 & 50.24;
    Table 2, Item 9\].

> Results suggested that greater attention to compliance with
> fundamental IRB procedural and documentation requirements was needed
> by some facilities in the following areas:

-   [Participation of IRB Members with Conflicting
    Interests]{.underline}. Minutes of meetings for both VA and
    affiliate IRBs sometimes failed to document fully the
    nonparticipation of members in deliberations and votes on research
    for which they appeared to have conflicting interests, as required
    under VA regulations at 38 CFR 16.017(e) and VHA Handbook 1200.5,
    Subparagraph 7.i.(2)(g) \[Table 2, Items 7a and 7c\].

-   [Waiver or Alteration of Informed Consent Requirements]{.underline}.
    Minutes of meetings for both VA and affiliate IRBs sometimes failed
    to document fully the findings required for waiver or alternation of
    informed consent requirements under VA regulations at 38 CFR
    16.116(d) and VHA Handbook 1200.5 Subparagraph 7.i.(2)(e) \[Table 2,
    Item 8b\].

> **Discussion**
>
> These findings suggest that VA and affiliate IRBs substantially
> complied with the most fundamental VA requirements for IRB review and
> documentation of IRB review under 38 CFR Part 16 and VHA Handbook
> 1200.5.
>
> Additional efforts may be needed to make VA and affiliate IRBs aware
> of the requirements to document that (i) IRB members are not present
> during IRB deliberations and voting on research for which they have
> conflicting interests; and (ii) the IRB makes the required findings
> justifying waivers or alterations of informed consent requirements.
>
> These findings were based on the minutes of IRB meetings conducted
> from December 2003 through April 2004. ORO ROs conducted followup
> where warranted, and many facilities have undertaken quality
> improvement activities since the time sampled. Future ORO projects
> should not only include the fundamental review and documentation
> procedures examined in this project, but should also address more
> qualitative aspects of IRB review and oversight.

+------------------+----------------+----------------+----------------+
| **Item**         | **VA IRBs**    | **Affiliate    | **All IRBs**   |
|                  |                | IRBs**         |                |
+==================+================+================+================+
| **1.a. Number of | 75             | 45             | 120            |
| VA FWAs**        |                |                |                |
+------------------+----------------+----------------+----------------+
| **b. Number of   | 58             | 33             | 91             |
| Facilities**     |                |                |                |
|                  |                |                |                |
| **Operating      |                |                |                |
| IRBs**           |                |                |                |
+------------------+----------------+----------------+----------------+
| **c. Number of   | 371            | 406            | 777            |
| Meetings,**      |                |                |                |
|                  | 63             | 52             | 115            |
| **i.e., Sets of  |                |                |                |
| Minutes**        |                |                |                |
|                  |                |                |                |
| **d. Number of   |                |                |                |
| IRBs**           |                |                |                |
+------------------+----------------+----------------+----------------+
| **2. Average     | (Based on 371  | (Based on 406  | (Based on 777  |
| Full Board**     | Meetings)      | Meetings)      | Meetings)      |
|                  |                |                |                |
| **Reviews Per    | 3.1            | 8.8            | 6.0            |
| Meeting**        |                |                |                |
|                  |                |                |                |
| **a. Initial     |                |                |                |
| Review**         |                |                |                |
+------------------+----------------+----------------+----------------+
| **b. Continuing  | 5.6            | 13.2           | 9.6            |
| Review**         |                |                |                |
+------------------+----------------+----------------+----------------+
| **c. Amends /    | 3.6            | 12.0           | 8.0            |
| Revisions**      |                |                |                |
+------------------+----------------+----------------+----------------+
| **3. Average     |                |                |                |
| Expedited**      |                |                |                |
|                  |                |                |                |
| **Reviews Listed |                |                |                |
| Per**            |                |                |                |
|                  |                |                |                |
| **Meeting**      |                |                |                |
+------------------+----------------+----------------+----------------+
| **a. Initial     | 0.7            | 4.9            | 2.9            |
| Review**         |                |                |                |
+------------------+----------------+----------------+----------------+
| **b. Continuing  | 1.2            | 8.3            | 4.9            |
| Review**         |                |                |                |
+------------------+----------------+----------------+----------------+
| **c. Amends /    | 4.7            | 13.4           | 9.2            |
| Revisions**      |                |                |                |
+------------------+----------------+----------------+----------------+
| **\              | (Based on 371  | (Based on 406  | (Based on 777  |
| 4. Average       | Meetings)      | Meetings)      | Meetings)      |
| Exemptions**     |                |                |                |
|                  | 0.3            | 2.7            | 1.5            |
| **Listed Per     |                |                |                |
| Meeting**        |                |                |                |
+------------------+----------------+----------------+----------------+
| **5. Average     | 2.0            | 3.7            | 2.9            |
| Study**          |                |                |                |
|                  |                |                |                |
| **Closures       |                |                |                |
| Listed**         |                |                |                |
|                  |                |                |                |
| **Per Meeting**  |                |                |                |
+------------------+----------------+----------------+----------------+
| **6. Average     | (Based on 342  | (Based on 278  | (Based on 620  |
| Length of**      | Meetings)      | Meetings)      | Meetings)      |
|                  |                |                |                |
| **Meeting**      | 2.3 hours      | 2.2 hours      | 2.3 hours      |
|                  |                |                |                |
| **(where         |                |                |                |
| specified)**     |                |                |                |
+------------------+----------------+----------------+----------------+

+-----------------+----------------+----------------+----------------+
| **Item**        | **VA IRBs**    | **Affiliate    | **All IRBs**   |
|                 |                | IRBs**         |                |
+=================+================+================+================+
| **1. IRB        | (Based on 362  | (Based on 377  | (Based on 739  |
| Complies with** | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **VA            | Yes = 362      | Yes = 342      | Yes = 704      |
| Membership**    | (100%)         | (90.7%)        | (95.3%)        |
|                 |                |                |                |
| *               | No = 0 (0%)    | No = 35 (9.3%) | No = 35 (4.7%) |
| *Requirements** |                |                |                |
+-----------------+----------------+----------------+----------------+
| **2. Majority   | (Based on 366  | (Based on 404  | (Based on 770  |
| of IRB**        | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **Members       | Yes = 362      | Yes = 404      | Yes = 766      |
| Present for**   | (98.9%)        | (100%)         | (99.5%)        |
|                 |                |                |                |
| **Each Vote**   | No = 4 (1.1%)  | No = 0 (0%)    | No = 4 (0.5%)  |
+-----------------+----------------+----------------+----------------+
| **3.            | (Based on 352  | (Based on 367  | (Based on 719  |
| Non-Scientist   | Meetings)      | Meetings)      | Meetings)      |
| Member**        |                |                |                |
|                 | Yes = 351      | Yes = 363      | Yes = 714      |
| **Present for   | (99.7%)        | (98.9%)        | (99.3%)        |
| Each Vote**     |                |                |                |
|                 | No = 1 (0.3%)  | No = 4 (1.1%)  | No = 5 (0.7%)  |
+-----------------+----------------+----------------+----------------+
| **4. Votes      | (Based on 366  | (Based on 406  | (Based on 772  |
| Recorded as**   | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **For / Against | Yes = 360      | Yes = 373      | Yes = 733      |
| / Abstain**     | (98.4%)        | (91.9%)        | (94.9%)        |
|                 |                |                |                |
|                 | No = 6 (1.6%)  | No = 33 (8.1%) | No = 39 (5.1%) |
+-----------------+----------------+----------------+----------------+
| **5. Separate   | (Based on 344  | (Based on 377  | (Based on 721  |
| Votes on**      | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **Continuing    | Yes = 343      | Yes = 372      | Yes = 715      |
| Reviews**       | (99.7%)        | (98.7%)        | (99.2%)        |
|                 |                |                |                |
|                 | No = 1 (0.3%)  | No = 5 (1.3%)  | No = 6 (0.8%)  |
+-----------------+----------------+----------------+----------------+
| **6. Minutes    | (Based on 371  | (Based on 388  | (Based on 759  |
| Document**      | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **Review of     | Yes = 330      | Yes = 269      | Yes = 599      |
| Prior IRB**     | (88.9%)        | (69.3%)        | (78.9%)        |
|                 |                |                |                |
| **Meeting       | No = 41        | No = 119       | No = 160       |
| minutes**       | (11.1%)        | (30.7%)        | (21.1%)        |
+-----------------+----------------+----------------+----------------+

\* NOTE: All results were based only on minutes containing information
that was relevant and applicable to the individual item. Consequently,
the number of meetings referenced in Table 2 varies across items.

+-----------------+----------------+----------------+----------------+
| **Item**        | **VA IRBs**    | **Affiliate    | **All IRBs**   |
|                 |                | IRBs**         |                |
+=================+================+================+================+
| **7.a. Minutes  | (Based on 238  | (Based on 165  | (Based on 403  |
| Document**      | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **N             | Yes = 230      | Yes = 116      | Yes = 346      |
| onparticipation | (96.6%)        | (70.3%)        | (85.9%)        |
| of**            |                |                |                |
|                 | No = 8 (3.4%)  | No = 49        | No = 57        |
| **Apparently    |                | (29.7%)        | (14.1%)        |
| Conflicted**    |                |                |                |
|                 |                |                |                |
| **Member(s)**   |                |                |                |
+-----------------+----------------+----------------+----------------+
| **b. If         | (Based on 230  | (Based on 116  | Based on 346   |
| N               | Meetings)      | Meetings)      | Meetings)      |
| onparticipation |                |                |                |
| is**            | Yes = 229      | Yes = 108      | Yes = 337      |
|                 | (99.6%)        | (93.1%)        | (97.4%)        |
| **Documented,   |                |                |                |
| Minutes**       | No = 1 (0.4%)  | No = 8 (6.9%)  | No = 9 (2.6%)  |
|                 |                |                |                |
| **Identify      |                |                |                |
| Conflicted**    |                |                |                |
|                 |                |                |                |
| **Member(s)**   |                |                |                |
+-----------------+----------------+----------------+----------------+
| **c. If         | (Based on 230  | (Based on 116  | Based on 346   |
| N               | Meetings)      | Meetings)      | Meetings)      |
| onparticipation |                |                |                |
| is**            | Yes = 130      | Yes = 108      | Yes = 238      |
|                 | (56.5%)        | (93.1%)        | (68.8%)        |
| **Documented,   |                |                |                |
| Minutes**       | No = 100       | No = 8 (6.9%)  | No = 108       |
|                 | (43.5%)        |                | (31.2%)        |
| **Note          |                |                |                |
| Whether**       |                |                |                |
|                 |                |                |                |
| **Conflicted    |                |                |                |
| Member**        |                |                |                |
|                 |                |                |                |
| **Was Present   |                |                |                |
| for**           |                |                |                |
|                 |                |                |                |
| **Deliberations |                |                |                |
| / Vote**        |                |                |                |
+-----------------+----------------+----------------+----------------+
| **8.a. Average  | (Based on 371  | (Based on 406  | (Based on 777  |
| Informed**      | Meetings and   | Meetings and   | Meetings and   |
|                 | 215 Waivers /  | 256 Waivers /  | 471 Waivers /  |
| **Consent       | Alts)          | Alts)          | Alts)          |
| Waivers or**    |                |                |                |
|                 | 0.6            | 0.6            | 0.6            |
| **Alterations   |                |                |                |
| Per**           |                |                |                |
|                 |                |                |                |
| **Meeting**     |                |                |                |
+-----------------+----------------+----------------+----------------+
| **b. Minutes    | (Based on 101  | (Based on 78   | (Based on 179  |
| Reference**     | Meetings       | Meetings       | Meetings       |
|                 | Listing        | Listing        | Listing        |
| **All Four      | Waivers /      | Waivers /      | Waivers /      |
| §116(d)**       | Alts)          | Alts)          | Alts)          |
|                 |                |                |                |
| **Criteria**    | Always = 39    | Always = 63    | Always = 102   |
|                 | (38.6%)        | (80.8%)        | (57.0%)        |
|                 |                |                |                |
|                 | Sometimes = 13 | Sometimes = 4  | Sometimes = 17 |
|                 | (12.9%)        | (5.1%)         | (9.5%)         |
|                 |                |                |                |
|                 | Never = 49     | Never = 11     | Never = 60     |
|                 | (48.5%)        | (14.1%)        | (33.5%)        |
+-----------------+----------------+----------------+----------------+
| **9. Minutes    | (Based on 101  | (Based on 78   | (Based on 179  |
| Include**       | Meetings       | Meetings       | Meetings       |
|                 | Listing        | Listing        | Listing        |
| **Inappropriate | Waivers /      | Waivers /      | Waivers /      |
| Consent**       | Alts)          | Alts)          | Alts)          |
|                 |                |                |                |
| **Waiver or     | Yes = 2 (2.0%) | Yes = 4 (5.1%) | Yes = 6 (3.4%) |
| Alteration**    |                |                |                |
|                 |                |                |                |
| **for           |                |                |                |
| FDA-Regulated** |                |                |                |
|                 |                |                |                |
| **Research**    |                |                |                |
+-----------------+----------------+----------------+----------------+

+-----------------+----------------+----------------+----------------+
| **Item**        | **VA IRBs**    | **Affiliate    | **All IRBs**   |
|                 |                | IRBs**         |                |
+=================+================+================+================+
| **10.a. AEs and | (Based on 367  | (Based on 395  | (Based on 762  |
| SAEs**          | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **Included in   | Yes = 290      | Yes = 195      | Yes = 485      |
| Minutes**       | (79.0%)        | (49.4%)        | (63.6%)        |
|                 |                |                |                |
| **or            | No = 77        | No = 200       | No = 277       |
| Supplement**    | (21.0%)        | (50.6%)        | (36.4%)        |
+-----------------+----------------+----------------+----------------+
| **b. Minutes    | Yes = 220      | Yes = 83       | Yes = 303      |
| Include**       | (59.9%)        | (21.0%)        | (39.8%)        |
|                 |                |                |                |
| **Off-Site AEs  | Yes = 238      | Yes = 146      | Yes = 384      |
| / SAEs:**       | (64.9%)        | (37.0%)        | (50.4%)        |
|                 |                |                |                |
| **c. Minutes    |                |                |                |
| Include**       |                |                |                |
|                 |                |                |                |
| **On-Site AEs / |                |                |                |
| SAEs:**         |                |                |                |
+-----------------+----------------+----------------+----------------+
| **11.a. One or  | (Based on 367  | Based on 367   | (Based on 762  |
| More AEs or**   | Meetings)      | Meetings)      | Meetings)      |
|                 |                |                |                |
| **SAEs in       | Yes = 30       | Yes = 55       | Yes = 85       |
| Minutes**       | (8.2%)         | (13.9%)        | (11.2%)        |
|                 |                |                |                |
| **Resulted in   |                |                |                |
| Modified**      |                |                |                |
|                 |                |                |                |
| **Consent,**    |                |                |                |
|                 |                |                |                |
| **Notification  |                |                |                |
| of**            |                |                |                |
|                 |                |                |                |
| **Subjects,     |                |                |                |
| or**            |                |                |                |
|                 |                |                |                |
| **Suspension    |                |                |                |
| /**             |                |                |                |
|                 |                |                |                |
| **Termination** |                |                |                |
+-----------------+----------------+----------------+----------------+
| **b. Average**  | (Based on 371  | (Based on 406  | (Based on 777  |
|                 | Meetings)      | Meetings)      | Meetings)      |
| **Suspensions   |                |                |                |
| or**            | 0.0            | 0.2            | 0.1            |
|                 |                |                |                |
| **Terminations  |                |                |                |
| of**            |                |                |                |
|                 |                |                |                |
| **Projects Per  |                |                |                |
| Meeting**       |                |                |                |
+-----------------+----------------+----------------+----------------+