APPENDIX IV: Institutional Review Board (IRB) Forms

A. IRB Online Forms

## Research Informed Consent Document (VA Form 10-1086)

> The VA Research Informed Consent Document is Available at
>
> <http://vaww.va.gov/resdev/fr/forms.cfm>.
>
> VA policy states that the form 10-1086 must be used by all designated
> IRB\'s performing review for VA. All the elements required by VA must
> be on the form. Headings may differ, but the form must be easy for the
> research participant to understand.

**Investigational Drug Information Record** (VA Form 10-9012)

> The VA Investigational Drug Information Record is available at
>
> <http://vaww.va.gov/resdev/fr/forms.cfm>.

B. Systematizing the Institutional Review Board (IRB) Review: Developing
Reviewer's Checklists

Institutional Review Board (IRB) members must keep a multitude of
factors in mind when carrying out their reviews. Many IRBs adopt local
formats or checklists for IRB members to use to ensure that all the
regulatory and other relevant review points have been considered. The
suggested contents of these lists are not exhaustive and should be
tailored to meet needs of the local research program portfolio. The
following reviewer checklists are outlined in this section for:

1.  Initial Review

2.  Evaluating an Informed Consent Document (VA Form 10-1086)

3.  Studies Involving Persons Not Competent to Consent

4.  Waiver or Alteration of Consent in Minimal Risk Research

5.  Waiver of Documentation of Informed Consent

6.  Determining Eligibility for Expedited Review

7.  Determining Eligibility for Exempt Status

8.  Evaluating Reports of Serious or Unexpected Adverse Events (SAEs,
    UAEs, and AEs)

9.  Reviewing Research Involving Prisoners

> **1. Initial Review.**

a.  Are the aims and methods of this protocol consistent with the
    mission of the institution?

b.  Are the risks greater than \"minimal risk\"?

c.  Are the risks minimized?

d.  Are the risks reasonable in relation to benefits?

e.  Is the subject selection equitable (e.g., do inclusion/exclusion
    criteria favor one group or another; will gender, racial and ethnic
    groups be recruited equitably; is there a risk of coercion for some
    groups?)

f.  Is the process for obtaining informed consent adequate?

g.  Is informed consent appropriately documented?

h.  Does the informed consent document itself entail any additional
    risks to the patient?

i.  Does the proposal request any waiver or variation on full documented
    consent (i.e., short form consent)? If YES, does the protocol meet
    the criteria for granting a variation or waiver of informed
    consent?  Of documentation of informed consent?

j.  Is there adequate provision for monitoring the data collection to
    insure safety of subjects?

k.  Are the provisions for protecting privacy and maintaining
    confidentiality adequate?

l.  Will any of the following vulnerable groups be recruited? Does the
    study meet criteria for enrolling these vulnerable subjects?

    -   Minors

    -   Prisoners

    -   Persons not competent to consent to research

    -   Employees

    -   Students

    -   Pregnant women or fetuses

m.  If children or incompetent persons will be involved, is there a
    possibility of direct benefit to the participant?

n.  Have additional safeguards been included if subjects might be
    vulnerable to coercion or undue influence?

o.  If subjects will be compensated, is the level and timing of payment
    appropriate to avoid potential coercion?

p.  If an investigational device will be used, is it a significant risk
    device or a non-significant risk device? Is there an IND/IDE number
    if appropriate?

q.  Are there appropriate provisions for both permission by a parent or
    representative and assent by the subject for persons not competent
    to consent to research?

r.  Does the research staff have sufficient expertise to perform this
    study?

s.  Is the sample size appropriate?

t.  Does the research setting provide adequate safeguards for protecting
    subjects?

u.  Does the protocol include sub-studies in which the risks and/or
    benefits are substantially different?

v.  If approved, what review period do you recommend?

> **2. Evaluating an Informed Consent Document. (VA Form 10-1086)**

a.  Does the document accurately reflect the information found in the
    protocol and the investigator's brochure?

b.  Is the language used appropriate to the population to be studied?

c.  Will a translated consent be necessary for non-English speaking
    participants? Has one been provided?

d.  Is the format of the document easily readable? Is it on the 10-1086?

e.  Is there exculpatory language through which the subject is made to
    waive or appear to waive any of his/her legal rights, or releases or
    appears to release the investigator, the sponsor, the institution,
    or its agents from liability for negligence?

f.  Will consent be obtained under circumstances that provide the
    subject with an opportunity to consider whether or not to
    participate, and that minimize coercive influences?

g.  Are the following required elements all addressed?

    -   A statement that the study involves research and clearly
        delineates the difference between procedures intended as
        treatment and procedures intended as research

    -   An explanation of the purposes of the research

    -   The expected duration of the subject\'s participation

    -   A description of procedures to be followed

    -   Identification of any procedures which are experimental

    -   A description of the expected risks or discomforts to the
        subject

    -   A description of benefits to the subject or to others

    -   A disclosure of alternative procedures, if appropriate

    -   A description of the extent to which confidentiality will be
        maintained

    -   For FDA-regulated research, a statement that the FDA may inspect
        the records, and a global statement about what other regulators
        have access, for example ORCA, OHRP, other Federal and state
        authorities.

    -   For research involving more than minimal risk, an explanation as
        to whether compensation and medical treatments are available if
        injury occurs

    -   An explanation of whom to contact if questions arise about

    -   The research

    -   The subjects\' rights, or whom to contact if a research-related
        injury occurs (in language specific to the VA).

    -   A statement that participation is voluntary, that refusal to
        participate involves no penalty or loss of benefits, and that
        the subject may discontinue at any time.

h.  Should the informed consent document also include any of these
    elements?

    -   A statement that a procedure may involve unforeseeable risks.

    -   A description of circumstances under which the subject\'s
        participation may be terminated by the investigator without the
        subject\'s consent.

    -   Additional costs to the subject resulting from participation in
        the research.

    -   The consequences of the subject\'s decision to withdraw from the
        research.

    -   A statement that significant new findings developed during the
        research which may relate to the subject\'s willingness to
        continue will be provided to subject.

    -   The approximate number of subjects involved in the study.

    -   Instructions or restrictions concerning potential risks to
        fetuses or offspring if pregnancy occurs during research
        participation.

> **3. Studies Involving Persons Not Competent To Consent.**
>
> [VA Requirements]{.underline}:
>
> a\. Criteria for IRB Approval:
>
> 1\) Are only incompetent patients suitable for the research?
>
> 2\) Is there a favorable risk/benefit ratio? The proposed research
> entails no significant risks, [or]{.underline} if the research
> presents some probability of harm, there must be at least a greater
> probability of direct benefit to the participant.
>
> 3\) Is participation voluntary? Incompetent patients may resist
> participating in a research protocol. No subjects may be forced or
> coerced to participate against their will.
>
> 4\) Are the representatives giving surrogate consent (permission) well
> informed regarding their roles and obligations to protect incompetent
> subjects?
>
> b\. Criteria for surrogate consent:
>
> 1\) Will surrogate consent be sought only from appropriate
> representatives as defined by VA policy or (when applicable) State
> law?
>
> 2\) Will surrogate consent be obtained only after the prospective
> research participant has been determined to be incompetent two VA
> physicians, after appropriate medical evaluation, and they have judged
> that there is little or no likelihood that the patient will regain
> competence within a reasonable period of time, [or]{.underline} the
> prospective research participant has been determined to be incompetent
> as established by a legal determination.
>
> c\. Other considerations:
>
> 1\) Does the IRB include member(s) or non-voting ad hoc consultants
> with expertise with this type of vulnerable subject?
>
> 2\) Does the protocol include a methodology for determining lack of
> decision-making capacity? Will results of this evaluation be
> documented?
>
> 3\) Must the subject be present during the informed consent procedure
> and will he/she be asked for assent whenever possible?
>
> 4\) Will the relationship of surrogate to subject and the presence of
> subject be documented on the informed consent document?
>
> 5\) Does the informed consent procedure clearly delineate the
> difference between procedures intended as treatment and those intended
> for research?
>
> **4. Waiver or Alteration of Consent in Minimal Risk Research**
>
> All four criteria must apply:

a.  Does the research involve no more than minimal risk to the subjects?

b.  Will the waiver or alteration adversely affect the rights and
    welfare of the subjects?

c.  Can the research practicably be carried out without the waiver or
    alteration?

d.  Whenever appropriate, will the subjects be provided with additional
    pertinent information after participation?

> **5. Waiver of Documentation of Informed Consent**
>
> a\. When identification of subjects poses a risk:

-   Is the informed consent document the only record linking the
    research with the subject?

> [and]{.underline}

-   Is the principal risk a potential harm resulting from a breach of
    confidentiality?

> Will each subject be asked whether he/she wants documentation linking
> him/her with the research? (The subject\'s wishes will govern.)
>
> b\. For minimal risk research using routine procedures:

-   Does the research present no more than minimal risk of harm to
    subjects?

> [and]{.underline}

-   Involve no procedures for which written consent is normally required
    outside of the research context?

> If the documentation requirement is waived, do you recommend that the
> IRB require the investigator to provide subjects with a written
> statement regarding the research?
>
> **6. Determining Eligibility for Expedited Review**
>
> a\. For Initial Review of a new protocol:

-   Is this a minimal risk study?

> [and]{.underline}

-   Does it fall into one of these categories?

> 1\) Clinical studies of drugs when an investigational new drug
> application (IND) is not required. (However: Research on marketed
> drugs that significantly increases the risks or decreases the
> acceptability of the risks associated with the use of the product is
> not eligible for expedited review.), or
>
> Research on medical devices for which (a) an investigational device
> exemption application (IDE) is not required; or (b) the medical device
> is cleared/approved for marketing and the medical device is being used
> in accordance with its cleared/approved labeling.
>
> 2\) Collection of blood samples: (a) From healthy, non-pregnant adults
> who weigh at least 110 pounds: No more than 550 ml in an 8 week
> period, and no more frequently than 2 times per week; [or]{.underline}
> (b) from other adults and children, the lesser of 50 ml or 3 ml per kg
> in an 8 week period and no more frequently than 2 times per week.
>
> 3\) Prospective collection of biological specimens for research
> purposes by noninvasive means.
>
> [Examples]{.underline}:
>
> a\) Hair and nail clippings in a non-disfiguring manner
>
> b\) Deciduous teeth at time of exfoliation or if routine care
> indicates a need for extraction
>
> c\) Permanent teeth if routine patient care indicates a need for
> extraction
>
> d\) Excreta and external secretions (including sweat)
>
> e\) Uncannulated saliva collected either in an unstimulated fashion or
> stimulated by chewing gum base or wax or by applying a dilute citric
> solution to the tongue
>
> f\) Placenta removed at delivery
>
> g\) Amniotic fluid obtained at the time of rupture of the membrane
> prior to or during labor
>
> h\) Supra- and subgingival dental plaque and calculus, provided the
> collection procedure is not more invasive than routine prophylatic
> scaling of the teeth and the process is accomplished in accordance
> with accepted prophylactic techniques
>
> i\) Mucosal and skin cells collected by buccal scraping or swab, skin
> swab, or mouth washings
>
> j\) Sputum collected after saline mist nebulization
>
> 4\) Collection of data through noninvasive procedures routinely
> employed in clinical practice, excluding procedures involving x-rays
> or microwaves. Where medical devices are employed, they must be
> cleared/approved for marketing.
>
> [Examples]{.underline}:
>
> a\) Physical sensors that are applied either to the surface of the
> body or at a distance and do not involve input of significant amounts
> of energy into the subject or an invasion of the subject\'s privacy
>
> b\) Weighing or testing sensory acuity
>
> c\) Magnetic resonance imaging
>
> d\) Electrocardiography, electroencephalography, thermography,
> detection of naturally occurring radioactivity, electroretinography,
> ultrasound, diagnostic infrared imaging, Doppler blood flow, and
> echocardiography;
>
> e\) Moderate exercise, muscular strength testing, body composition
> assessment, and flexibility testing where appropriate given the age,
> weight, and health of the individual.
>
> 5\) Research involving materials (data, documents, records, or
> specimens) that have been collected or will be collected solely for
> non-research purposes (such as medical treatment or diagnosis).
>
> 6\) Collection of data from voice, video, digital, or image recordings
> made for research purposes.
>
> 7\) Research on individual or group characteristics or behavior or
> research employing survey, interview, oral history, focus group,
> program evaluation, human factors evaluation, or quality assurance
> methodologies.
>
> b\. For Continuing Review:

-   Is this a minimal risk study?

> [and]{.underline}

-   Do the following apply?

> 1\) For a study originally approved by expedited review: Are the
> design, apparent risks and consent procedure unchanged?
>
> 2\) For a study originally approved by full review, does it meet one
> of the following criteria?
>
> a\) No subjects were enrolled, and no additional risks were identified
> in the past year.
>
> b\) The research is permanently closed to the enrollment of new
> subjects; **and** all subjects have completed all research-related
> interventions; **and** the research remains active only for long-term
> follow-up of subjects.
>
> c\) The remaining research activities are limited to data analysis
> only.
>
> d\) Continuing review of research, not conducted under an
> investigational new drug application or investigational device
> exemption where categories above do not apply but the IRB has
> determined and documented [at a convened meeting]{.underline} that the
> research involves no greater than minimal risk and no additional risks
> have been identified.
>
> c\. For Amendments/Revisions:
>
> 1\) Is this a minor change in previously approved research? A minor
> change makes no substantial alteration in:
>
> a\) The level of risks to subjects;
>
> b\) The research design or methodology;
>
> c\) The number of subjects enrolled in the research;
>
> d\) The qualifications of the research team;
>
> e\) The facilities available to support safe conduct of the research;
> or
>
> f\) Any other factor that would warrant review of the proposed changes
> by the convened IRB.

## [or]{.underline}

> 2\) Is the research minimal risk and does it fall within the
> categories of expeditable research listed above?
>
> **7. Determining Eligibility for Exempt Status**
>
> Does the research fall into one of these categories?
>
> a\. Research conducted in established or commonly accepted educational
> setting, involving normal educational practices, such as (1) research
> on regular and special education instructional strategies **or** (2)
> research on the effectiveness of or the comparison among instructional
> techniques, curricula, or classroom management methods.
>
> b\. Research involving the use of educational tests (cognitive,
> diagnostic, aptitude, achievement), survey procedures, interview
> procedures or observation of public behavior, unless: (1) information
> obtained is recorded in such a manner that human subjects can be
> identified, directly or through identifiers linked to the subjects;
> **and** (2) any disclosure of the human subjects\' responses outside
> the research could reasonably place the subjects at risk of criminal
> or civil liability or be damaging to the subjects\' financial
> standing, employability, or reputation.
>
> c\. Research involving the use of educational tests (cognitive,
> diagnostic, aptitude, achievement), survey procedures, interview
> procedures, or observation public behavior that is not exempt under
> paragraph (2)(b) of this section, if: (1) the human subjects are
> elected or appointed public officials or candidates for public office;
> **or** (2) Federal statute(s) require(s) without exception that the
> confidentiality of the personally identifiable information will be
> maintained throughout the research and thereafter.
>
> d\. Research involving the collection or study of existing data,
> documents, records, pathological specimens, or diagnostic specimens,
> if these sources are publicly available or if the information is
> recorded by the investigator in such a manner that subjects cannot be
> identified, directly or through identifiers linked to the subjects.
>
> e\. Research and demonstration projects which are conducted by or
> subject to the approval of Department or Agency heads, and which are
> designed to study, evaluate, or otherwise examine: (1) Public benefit
> or service programs; (2) procedures for obtaining benefits or services
> under those programs; (3) possible changes in or alternatives to those
> programs or procedures; or (4) possible changes in methods or levels
> of payment for benefits or services under those programs.
>
> f\. Taste and food quality evaluation and consumer acceptance studies,
> (1) if wholesome foods without additives are consumed or (2) if a food
> is consumed that contains a food ingredient at or environmental
> contaminant at or below the level found to be safe, by the Food and
> Drug Administration or approved by the Environmental Protection Agency
> or the Food Safety and Inspection service of the U.S. Department of
> Agriculture.
>
> g\. Will prisoners be recruited or is the research primarily focused
> on pregnant women or fetuses? (No research of these types may be
> exempted.)

-   Will children be recruited for a study that falls in category b?
    Will researchers directly interact with the children? (If there will
    be direct interaction, e.g., an interview or a questionnaire, the
    study may not be exempted)

-   Does the data already exist for a study that falls into category d?
    If the data is not now in existence (e.g., it is yet to be
    collected), the study may not be exempted under exemption d.

> **8. Evaluating Reports of Serious or Unexpected Adverse Events (AEs,
> SAEs, and UAEs)**
>
> a\. Was this a serious event?
>
> How severe do you judge this event to be?
>
> b\. Was this event related to the research?
>
> Can you rule out the drug, device, or procedure as directly related to
> or as a probable cause of this event?
>
> c\. Was this event unexpected?

-   Is the possibility of this event described in the consent form,
    protocol, and investigator brochure for this study?

-   Was the severity of this event greater than described in the consent
    form, protocol, and investigator brochure for this study?

-   Have similar events previously been reported for this study?

> d\. Based on this event, would you recommend additional monitoring of
> other patients in the study to detect similar problems early?
>
> e\. Do you recommend revision of the consent procedure to include
> information about events like this, or precautions that patients
> should take because of the possibility of events like this?
>
> f\. Is the seriousness and likelihood of this event great enough that
> patients already enrolled in the study should be informed about it?
>
> g\. What action do you recommend?
>
> 1\) That the IRB accept the report without further action; or
>
> 2\) That the IRB take a specific action *when the event raises new
> questions about risks to participants*. Such actions may include:

-   Request for further clarification from the investigator

-   Changes in the protocol

-   Changes the consent form

-   Requirement to inform already enrolled subjects about the risk of
    this adverse event

-   A change in the continuing review period

-   Additional monitoring by the IRB

-   Further inquiry to other protocols utilizing the particular
    drug/device in question

-   Notification of regulatory agencies

-   Suspension or termination of the study

> **9. RESEARCH INVOLVING PRISONERS**
>
> a\. Is at least one member of the IRB a prisoner, or a prisoner
> representative with appropriate background and experience to serve in
> that capacity?
>
> b\. The seven findings described below should be made and documented
> in the IRB minutes. For research funded by DHHS, the institution must
> certify to the Secretary, DHHS, by way of OHRP, that the IRB has made
> these findings.
>
> 1\) Does the research under review fall into one of these categories
> of research?

-   Minimal risk research to

> a\) Study of the possible causes, effects, and processes of
> incarceration, and of criminal behavior, provided that the study
> presents no more than minimal risk and no more than inconvenience to
> the subjects.
>
> [or]{.underline}
>
> b\) study of prisons as institutional structures or of prisoners as
> incarcerated persons, provided that the study presents no more than
> minimal risk and no more than inconvenience to the subjects.

-   Research on conditions particularly affecting prisoners as a class
    (for example, vaccine trials and other research on hepatitis which
    is much more prevalent in prisons than elsewhere; and research on
    social and psychological problems such as alcoholism, drug addition,
    and sexual assaults). DHHS funded research in this category may
    proceed only after the Secretary has consulted with appropriate
    experts including experts in penology, medicine, and ethics, and
    published notice, in the **Federal** **Register**, of his intent to
    approve such research;

-   Research on practices, both innovative and accepted, which have the
    intent and reasonable probability of improving the health or
    well-being of the subject. If control groups of prisoners will be
    used who will not benefit from the research, and if the research is
    DHHS-funded, the study may proceed only after the Secretary has
    consulted with appropriate experts, including experts in penology,
    medicine, and ethics, and published notice, in the **Federal
    Register**, of the intent to approve such research.

> 2\) Are the advantages offered to prisoners for participation (e.g.,
> in general living conditions, medical care, quality of food, amenities
> and opportunity for earnings in the prison) so great as to be
> coercive?
>
> 3\) Are the risks involved in the research commensurate with risks
> that would be accepted by non-prisoner volunteers?
>
> 4\) Are the procedures for the selection of subjects within the prison
> fair to all prisoners and immune from arbitrary intervention by prison
> authorities or prisoners? Will control subjects be selected randomly
> from the group of available prisoners who meet the characteristics
> needed for the research project? If not, what is the justification?
>
> 5\) Is the information about the research presented in language, which
> is understandable to the subject population?
>
> 6\) Is there adequate assurance that a parole board will not take into
> account a prisoner's participation in the research in making decisions
> regarding parole? Is each prisoner clearly informed in advance that
> participation in the research will have no effect on his or her
> parole?
>
> 7\) If there is a need for follow-up examination or care of
> participants after the end of their participation, has adequate
> provision been made for this, taking into account the varying lengths
> of individual prisoners' sentences? Will participants be informed this
> fact?

C. What Every IRB Needs to Know: Obtaining Information from
Investigators through Forms or Questionnaires

> In the material to follow are suggestions about the kinds of
> information an IRB might need from investigators for each of their key
> interactions with the IRB. It is organized by type of review or
> action. The IRB may elicit information by providing investigators with
> detailed instructions about what their applications, protocols or
> reports should contain, or may obtain it by using standard local
> forms. Many institutions use forms that investigators complete when
> there is a decision or other action necessary by the IRB.
>
> This information should be customized to reflect the local situation
> and the type of research proposed. Many of the questions provided in
> this document are important for reviewing a high-risk biomedical
> research protocol. If the IRB at your VAMC is reviewing a low-risk
> project, for example, a health services research project with no
> privacy issues, many of the questions herein are not pertinent. For
> some of the items designed to elicit descriptions, sample language is
> also provided to show the level of detail, which may be desired.
>
> Additional models of IRB forms and instructions for various purposes
> can be obtained by going to the ORCA website at
> <http://www.va.gov/orca/> or to
> <http://www.mcwirb.org/WebCatalog.cgi?m2=References+m1=graphics+cwd=/documents+>

-   **[Initial Review]{.underline}.** Most Institutional Review Boards
    (IRBs) develop a protocol submission application, which has thought
    provoking questions for the Principal Investigator and is organized
    in a way that makes protocol review easier for the IRB. It is
    advisable to match the format of the submission application with the
    screens of the database used by your VA Medical Center (VAMC). Data
    entry is more easily accomplished when the fields in the database
    and the headings on the forms are in the same order and named the
    same.

> As described in Chapter 9b, "Initial Review by the Convened IRB," the
> IRB's first evaluation of a proposed study is based on a description
> of the research that includes information relevant to human research
> protections, such as information about subject recruitment and
> selection, the research plan, risks and benefits, privacy and
> confidentiality protections, safety monitoring, informed consent
> procedures, protections for vulnerable subjects, and any other
> information relevant to the approval criteria described in the
> regulations, such as recruitment materials or questionnaires.
>
> The following list identifies attachments that an IRB may want to
> receive at the time of protocol submission to assist the members in
> conducting a thorough review. The items with an "\*" identifies the
> material that is federally mandated to be IRB reviewed and available
> to the IRB.
>
> a\. \*Protocol submission application
>
> b\. \*Copy of grant (normally sent to the granting agency)
>
> c\. \*Detailed protocol
>
> d\. \*Proposed consent form
>
> e\. \*Proposed advertisement(s) to be used to recruit subjects
>
> f\. \*Surveys/questionnaires including standard measures,
> psychological tests, interview forms, scripts, etc.
>
> g\. \*Clinical investigational brochure from the sponsor, if
> applicable
>
> h\. Case report forms, if available
>
> i\. Bio-sketch or curriculum vitae to evaluate training and
> qualifications
>
> j\. Certificate of Completion of education in the protection of human
> research subjects (where applicable)
>
> k\. IRB Approval letters from other facilities, if multi-center

# 

# The following questions may be used in a Protocol Submission Application or in instructions for inclusion in a protocol:

# 

# a. Responsible investigator contact information

> b\. Name
>
> c\. PI personal identifier
>
> d\. PI department
>
> e\. PI VA title
>
> f\. Percentage of effort
>
> g\. PI university title
>
> h\. Percentage of effort
>
> i\. PI phone number
>
> j\. PI mailing address
>
> k\. Number of ongoing projects
>
> l\. Years of research experience
>
> m\. Human subjects training
>
> n\. Copy of CV or bio-sketch to evaluate qualifications

# Study staff information. Study staff could be those who may perform procedures involving the research subjects for the purposes of recruiting, consenting, administration of surveys, or conducting the actual clinical interventions).

a.  Name

b.  Title

c.  Phone number

d.  Mailing address

e.  Years of research experience

f.  Human subjects training

g.  Copy of CV or biosketch to evaluate qualifications

h.  Level of participation in this project

# 2. Basic Protocol information.

a.  Title of Project.

b.  Brief background of the projects with reference to pertinent medical
    literature and describing the results of previous related research.

c.  Purpose of the Project.

d.  What is the clinical significance of the trial and the impact to
    society?

e.  Is the request for full review, expedited review or exemption from
    review from the IRB. For expedited research requests, check under
    which criteria you believe this research falls. \[Insert current
    list of expedited categories.\] For Exempt research requests, check
    under which criteria you believe this research falls. \[Insert
    current list of expedited categories.\]

f.  Performance site(s).

g.  Is this protocol part of an active or pending externally funded
    project? List grant support or commercial support for the project.

h.  Estimated duration of total project.

# 3. Special Considerations.

a.  Do any members of the research team have a conflict of interest
    (financial or otherwise)? Is there a current conflict of interest
    form for each investigator on file?

b.  Does this involve the use of bio-hazardous materials, recombinant
    DNA, infectious agents and/or gene therapy? If yes, Institutional
    Bio-safety Committee (IBC) approval must be obtained.

c.  Does this project involve the use of radioisotopes, radiation
    exposure and/or radiation-producing devices regardless of whether
    the use of incidental to the project? If yes, Radiation Safety
    Committee approval must be obtained.

d.  Does this project involve the use of an investigational drug? If
    yes, list phase of investigations and IND #. Is this an off-label
    use of an approved drug?

e.  Does this project involve the use of an investigational device? If
    yes, list name and manufacturer of the device. Is this device a
    non-significant (NSR) or significant risk (SR) device? If an SR,
    provide the IDE \# if it has been secured. Is this a new use of the
    device?

f.  Does this project involve the use of obtaining or storing biological
    materials (i.e. tissue, urine or blood samples, serum etc.)? Does
    the sample contain identifiers? If yes, there are additional
    confidentiality issues to consider. How will sample be stored? Is
    there use of fetal tissue? Is there DNA analysis/genetic testing?

g.  Does this project meet ORD policy requirements with respect to
    tissue banks/repositories?

# 4. Plan for Recruitment of subjects.

a.  What is the total number of subjects to be enrolled at this
    institution?

b.  If multi-center, how many subjects will be enrolled from all
    institutions?

c.  How will subjects be identified for recruitment (i.e., name of
    clinics, patient records, advertisements, etc)? If through
    advertisements, indicate the method of recruitment, (i.e., posted
    flyer, internet radio, newspaper, etc.) Investigators using patient
    records should also indicate how they plan to obtain the data.

d.  Describe how informed consent will be sought from subjects or from
    the subjects' legally authorized representative. If children are
    subjects, discuss whether their assent will be sought and how the
    permission of their parents will be obtained. If persons incompetent
    to consent are subjects, discuss how the consent of appropriate
    representatives will be obtained and if assent will be sought from
    the subject.

e.  Is a copy of the advertisement included with the submission?

# 5. Selection of subjects and the Informed Consent.

# a. Is the research designed to include or likely to include human subjects from the following special populations:

-   Children

-   Prisoners

-   Pregnant Women

-   Cognitively impaired or mentally disabled subjects

-   Economically or educationally disadvantaged subjects,

-   Elderly

-   Non-English speaking

> b\. What additional safeguards will be in place to protect these
> populations from coercion or undue influence to participate?
>
> c\. What are the procedures to determine incapacity to consent?
>
> Identify the inclusiveness of the sample including the sex, race and
> age range of the subjects.
>
> d\. Justify the exclusiveness of the sample.
>
> e\. Describe the informed consent process for this study.
>
> f\. Describe the procedures for documentation of informed consent,
> including any procedures for obtaining consent (permission) from
> surrogates, assent from minors, using witnesses, translators, and
> document access and storage.
>
> g\. Identify the proposed method of obtaining informed consent: For
> example, written informed consent, if recruiting children, provision
> of assent of minor, translated consent, emergency waiver of consent
> provisions, short form consent, oral consent, waived consent. If
> applying for a waiver or alteration of consent in minimal risk
> research, provide responses to the following questions:

-   Does the research involve no more than minimal risk to the subjects?

-   Will the waiver or alteration adversely affect the rights and
    welfare of the subjects?

-   Can the research practicably be carried out without the waiver or
    alteration?

-   Whenever appropriate, will the subjects be provided with additional
    pertinent information after participation?

-   Note: all four criteria must apply to receive a waiver or alteration
    of consent in minimal risk research.

> h\. If applying for waiver of documentation of informed consent,
> provide responses to one of the following:

-   When identification of subjects poses a risk is the informed consent
    document the only record linking the research with the subject? Is
    the principal risk a potential harm resulting from a breach of
    confidentiality?

-   Will each subject be asked whether he/she wants documentation
    linking him/her with the research? (The subject\'s wishes will
    govern.)

-   For minimal risk research using routine procedures does the research
    present no more than minimal risk of harm to subjects? Does the
    research involve no procedures for which written consent is normally
    required outside of the research context?

-   Are subjects provided with a written statement regarding the
    research?

> i\. If children are involved in the study, has the required waiver
> from ORD been obtained?
>
> j\. Will there be screening for participation in other studies?

# 6. Study Plan.

a.  Describe plan of study

b.  State hypothesis or research question to be answered

c.  Describe the research design and procedures (including standard
    survey instruments or procedures) to be used in the research

d.  Specifically identify any experimental procedures

e.  Identify the duration of participation

f.  Provide statistical justification for the number of subjects to be
    studied and the degree of change expected (i.e. power analysis).

g.  Describe any special equipment or unusual procedures to be used for
    this research project.

h.  Will the subjects be:

-   In-Patient

-   Out-Patient

-   Non-Va

-   Students/Staff

# 7. Risk Identification and Consideration.

a.  What are the risks to subjects?

b.  What are the precautions to be taken to minimize or eliminate these
    risks? Note that risks can include physical, psychological, social
    or economic harms.

c.  Justify the need for a placebo control group, if one is included in
    this study.

d.  Where appropriate, describe the data monitoring procedures that will
    be employed to ensure the safety of subjects.

e.  Are there procedures to notify or counsel subjects if immediate
    risks to their health or well-being are identified?

# 

# 8. Surveys and Questionnaires.

a.  Will there be use of patient identifiers?

b.  Address the psychological and social implications to sensitive
    questions or topic matter.

c.  Include any follow-up PI will take if sensitive information is
    discovered (i.e. notifying authorities, notifying other family
    members, notification to primary physician, referral for psychiatric
    assistance, etc.) This must be spelled out to the subject in the
    consent form.

# 9. Benefits. Is there a direct benefit to the subjects? If children or incompetent patients will be used as research subjects, specifically address whether there will be any direct benefit to the subject.

# 10. Alternative Procedures. List the alternative drugs/devices/procedures, if any, available to subjects.

# 

# 11. Compensation for participation. 

# If subjects will be compensated, how much in cash or kind.

a.  Describe a plan for prorating payments if a subject withdraws from
    the study early or provide justification as to why prorated payments
    are not being offered.

# 12. Costs.

a.  Will there be any extra costs to subjects for their participation in
    the study? Are the costs spelled out in the consent form?

b.  Will there be any extra costs to this VAMC or to third party payers
    because of subject's participation?

> **13. Privacy and Confidentiality of Data and Records.**

a.  Will identifiable, private, or sensitive information be obtained
    about target subjects or other living individuals?

b.  Whether or not such information is obtained, describe the provisions
    to protect the privacy of subjects and to maintain the
    confidentiality of data.

c.  Who will be looking at the data?

d.  Is the information secured in a locked cabinet?

e.  Is the information coded?

f.  Is the information only reported in aggregate?

g.  Non-descriptive answers such as "standard methods" are unacceptable.

h.  Will the information be stored in electronic form? How is that
    secured?

# 14. Signature of PI. Signature/certification of PI and date.

# 15. Signature of Department Chairman. A statement of certification may also be included. For example: I have reviewed the above protocol and approve its submission to the IRB. 

-   [Continuing Review (Progress Report)]{.underline}. IRB procedures
    for continuing review are detailed in Chapter 9c, "Continuing Review
    by the Convened IRB," and 9g., "Expedited Initial and Continuing
    Review: Permitted Categories."

> Guidance from the Office for Human Research Protections (OHRP) states:
> "Continuing IRB review of research must be substantive and meaningful.
> In conducting continuing review of research not eligible for expedited
> review, all IRB members should at least receive and review a protocol
> summary and a status report on the progress of the research, including
> (a) the number of subjects accrued; (b) a description of any adverse
> events or unanticipated problems involving risks to subjects or others
> and of any withdrawal of subjects from the research or complaints
> about the research; (c) a summary of any recent literature, findings
> obtained thus far, amendments or modifications to the research since
> the last review, reports on multi-center trials and any other relevant
> information, especially information about risks associated with the
> research; and (d) a copy of the current informed consent document.
> Primary reviewer systems may be employed, so long as the full IRB
> receives the above information. Primary reviewers should also receive
> a copy of the complete protocol including any modifications previously
> approved by the IRB." (OHRP Compliance Activities: Common Findings and
> Guidance - 9/1/2000)
>
> When notifying the investigator that a progress report is due, some
> institutions also send study related information generated from the
> IRB database for the PI to verify (i.e. protocol title, protocol
> number, co-investigators/participants, last review date, etc.), along
> with a form or instructions for making the report. The following
> questions may be used in a progress report form or instructions for
> the PI:
>
> a\. Has the staff involved in the conduct of this study changed? All
> personnel involved in the design or conduct of the study must be
> listed and new staff must have successfully completed a VA-accepted
> human subjects education program.
>
> b\. Has study changed since last continuing review? All changes must
> be submitted to and approved by the IRB prior to initiation.
>
> c\. Have there been any changes regarding use of vulnerable
> populations?
>
> d\. Has the understanding of the risks/benefits changed?
>
> e\. Have any investigators on this protocol disclosed significant
> financial interest or other conflict of interest relating to this
> research? Please make sure that all conflict of interest statements
> are submitted.

# 1. Recruitment.

> a\. Are advertisements used to recruit subjects? Provide a copy of the
> advertisement used to recruit subjects. All advertisements must be
> submitted to and approved by the IRB prior to initiation.
>
> b\. How many subjects were approached regarding this study and
> declined to participate? Specify the reasons.

# 2. Enrollment and Retention.

> a\. What is the total number of subjects enrolled to date at all
> facilities (cooperative or multi-center trials)?
>
> b\. What is the total number of subjects enrolled to date at this
> facility?
>
> c\. How many subjects were enrolled at this facility in this reporting
> period?
>
> d\. Has recruitment been at the rate projected?
>
> e\. What is the total number of subjects who were enrolled but later
> withdrew? Specify the reasons.
>
> f\. Please provide the racial, ethnic, and gender breakdown of the
> subjects that have been enrolled.
>
> g\. Indicate which of the following populations have been or will be
> included in the research *(mark all that apply)*:
>
> Children
>
> Intellectually or emotionally impaired
>
> Patients
>
> Pregnant subjects or fetuses
>
> Prisoners, parolees, incarcerated subjects
>
> Students or trainees
>
> Employees of study sites
>
> Subjects whose 1^st^ language is not English
>
> Normal Volunteers
>
> Employees or subordinates of investigators
>
> h\. Did you experience any unanticipated difficulties in recruiting or
> retaining subjects for this study?
>
> i\. Did you receive any complaints from subjects about the study?
>
> j\. Was surrogate consent (permission) obtained from any subjects?
>
> k\. How long will enrollments continue?
>
> l\. Are subjects being seen for follow-up?
>
> m\. How long will subjects be followed?
>
> n\. If you have not yet enrolled any subjects into this study, provide
> justification for keeping the study open.

# 3. Adverse Events/Serious Adverse Events/Unexpected Adverse Events (AEs/SAEs/UAEs).

> a\. To date, how many AEs/SAEs/UAEs have occurred in this study?
>
> b\. How many of these adverse events were from this facility?
>
> c\. Has any subject suffered an adverse event within the last
> reporting period at this facility?
>
> d\. If yes, was the adverse event related to the study? All serious or
> unanticipated AEs/SAEs must be reported to the IRB on the within
> \[specified\] days of occurrence.

# 4. Informed Consent.

> a\. Informed consent is obtained by what means:

-   Oral

-   Written

-   Waiver of documentation of informed consent

-   Waiver of consent

-   Surrogate

-   Short Form

-   Assent for children or incompetent subjects

> b\. Provide a copy of all current informed consent documents in use
> (e.g. English and/or translated version and/or statement to the
> subject).

# 5. Additional Information.

> a\. Is this drug/device still considered investigational? If no, give
> date of FDA approval .
>
> b\. Brief description of the preliminary results of the project, if
> any. This summary must include any new information, recent literature,
> new findings or other relevant information, especially information
> about adverse events, risks or benefits to the subjects or associated
> with the research.
>
> c\. Have there been any monitoring visits by the sponsor, coordinating
> center or the FDA? If yes, please attach a copy of the final or on
> site report.
>
> d\. Have there been any publications or presentations as a result of
> this study? If yes, please attach a copy of the publication.
>
> e\. What is the planned study completion date?
>
> f\. PI signature and date to confirm accuracy of information.
>
> **6. Final Report.** When a study is terminated the PI should be asked
> to give a final report. An IRB may include a section in its regular
> Progress Report form to facilitate filing a final report.
>
> a\. Reason for protocol termination

-   Protocol reached accrual goals

-   Never received funding

-   PI/major participant left institution

-   Not enough subject for project to be completed

-   Closed due to adverse reaction(s)

-   PI lost interest

-   Procedure or drug/device now approved

-   Lost funding

-   Study drug/device had minimal treatment effect

> b\. If deception was involved in the study design, note that all
> subjects must be debriefed.
>
> c\. Will participants received a copy of the study summary results?
>
> d\. Is there a mechanism for follow-up or referral for subjects?
>
> e\. PI Certification including Signature and date.

-   **[Questions to Obtain Information on Adverse Event (AE)
    Reports]{.underline}.** IRB review of adverse events is described in
    Chapter 9i, "Review of Reports of Unanticipated Problems or Adverse
    Events," 9j, "Review of Adverse Event or Safety Reports in Sponsored
    or Cooperative Group (Multi-center) projects," and 9k. "Review of
    Data and Safety Monitoring Board (DSMB) Reports." Adverse event (AE)
    reports may arise from a number of sources such as sponsors, copies
    of AE reports that have been sent to sponsors about on-site events,
    reports filed with the FDA Medwatch System, reports from Data Safety
    Monitoring Boards (DSMBs) or ad hoc reports generated about events
    in studies for which there is no standard report form. To handle the
    different sources and kinds of information received, some IRBs
    tailor their forms or instructions to the source of the report. Many
    use a locally-developed form, for those events which occur on-site.

> The FDA states that: "IRB continuing review responsibilities include
> reviewing reports of adverse reactions and unexpected events involving
> risks to subjects or others. The IRB should establish a procedure for
> receiving and reviewing these reports. The level and promptness of
> review may depend upon factors such as the seriousness of the event,
> whether the event is described in the study protocol and consent and
> whether the event occurred at a location for which the IRB is the IRB
> of record. The written procedures may include a brief form to be
> completed by the principal investigator when an adverse event occurs,
> asking for his/her opinion as to whether the event was related to the
> study and other information to aid the IRB in an appropriate and
> efficient review of the event.

Researchers should be made aware of the IRB\'s policies and procedures
concerning reporting and continuing review requirements. This can be
accomplished by notifying the investigator, in the IRB\'s letter of
approval, of the requirement to report changes and unanticipated
problems in research activities. The IRB\'s written procedures
pertaining to continuing review and reporting requirements should be
distributed to ensure that all individuals involved in research
activities understand their obligations." (IRB Information Sheets, 1998,
page 3).

> **1. Questions that may be used when a standard report exists.** If
> the AE was detailed on a Medwatch or Case Report Form or by other
> means, the IRB may choose to request a copy of the AE details and
> responses to the following information in a cover letter:
>
> a\. Date/time of onset of AE
>
> b\. Was the event/problem from this facility, or another participating
> site if multi-center sponsor or study?
>
> c\. Was the event/problem deemed mild, moderate, severe, or fatal?
> Need date of death including a copy of the death certificate and
> autopsy report.
>
> d\. Was the event/problem expected or unexpected?
>
> e\. Was the event/problem related to the research intervention?
>
> It helps to specify with descriptives such as:

-   [Causative]{.underline}: probable, inconclusive, and unlikely.

-   [Study related]{.underline}: definitely, probably, possibly,
    probably not related to the study.

> f\. What was the outcome? Is it resolved, ongoing, or did subject die?
>
> g\. Based on this event, will additional monitoring of other patients
> be done in the study to detect similar problems early? If yes, please
> describe.
>
> h\. Is the possibility, severity and specificity of this event
> described in the consent form, protocol, and investigator brochure for
> this study?
>
> i\. Will the consent procedures be revised as a result of this event?
> If yes, attach the new version of the consent form.
>
> j\. Will patients already enrolled in the study be informed about the
> possibility of this adverse event? If yes, how?
>
> k\. Name and date of individual submitting the report.
>
> **2. Questions which may be used when a Medwatch Form, Case Report
> Form, or other standard form does not exist** to detail the AE
> information, the VAMC may want to create a form, which could include
> questions like the following:
>
> a\. Title of protocol
>
> b\. IRB protocol \#
>
> c\. Name of drug/device/procedure
>
> d\. IND/IDE number
>
> e\. Name of study sponsor
>
> f\. Manufacturer's control number
>
> g\. Dosage from (tab, cap, etc.)
>
> h\. Total daily dose
>
> i\. Route of administration (po, im, iv, etc.)
>
> j\. Duration of therapy
>
> k\. Dates of Administration
>
> l\. Use as described in application to the IRB
>
> m\. Date/time of onset of AE (admission and discharge dates if
> applicable)
>
> n\. Description of symptoms and signs (from medical history and
> physical exam)
>
> o\. Lab tests or other tests performed to diagnose AE (date and test
> results)
>
> p\. Medications or other treatments for AE (include start and stop
> dates)
>
> q\. Outcome of the AE
>
> r\. If death occurred (SAE), cause of death (attach copy of death
> certificate and autopsy report)
>
> s\. Has this type of AE (SAE, UAE) been reported before?
>
> t\. Could this type of SAE occur again?
>
> u\. The SAE occurred:

-   Within 30 days of treatment.

-   More than 30 days after treatment began.

-   More than 30 days after treatment was stopped.

> v\. To what extent was this SAE an expected event, based on the
> information in the protocol, investigator brochure and informed
> consent document? Provide a scale such as: Unexpected (0) -- Expected
> (10)
>
> w\. To what extent is the investigational drug/device to be the cause
> of this event? Very Unlikely (0) -- Very Likely (10)
>
> x\. How severe is this event?
>
> Not Severe (0) -- Very Severe (10)
>
> y\. Based on this event, will additional monitoring of other patients
> in the study be done to detect similar problems early? If yes, please
> describe.
>
> z\. Is the possibility, severity and specificity of this event
> described in the consent form, protocol, and investigator brochure for
> this study?
>
> aa. Will consent procedures be revised as a result of this event? If
> yes, attach the new version of the consent form.
>
> ab. Will patients already enrolled in the study be informed about the
> possibility of this adverse event? If yes, how?
>
> ac. Name, signature and date of individual submitting the report.

-   **[Questions to Obtain Information on a Request for
    Amendment]{.underline}.** IRB review of planned changes in a
    protocol is part of its continuing review process. Some IRBs use a
    form for requesting approval of amendments to ensure receiving all
    information necessary for review. These questions may be used in a
    request for approval of an amendment:

> a\. Is a revised protocol necessary as the result of this amendment?
>
> If yes, attach a revised protocol to this amendment.
>
> b\. Is a revised consent form necessary as a result of this amendment?
>
> If yes, attach a revised consent form to the amendment.
>
> c\. Is a revised advertisement necessary as a result of this
> amendment? If yes, attach a revised advertisement to this amendment.
>
> d\. Please list the specific changes to the previously approved
> protocol and provide sufficient rationale for each a change to allow
> the committee to make a decision. For example:

-   PI or co-investigator

-   Participant

-   Contact

-   Treatment procedure

-   Other protocol-related procedure

-   Drug/device

-   Advertisement

-   Survey instrument

-   Risks/benefits

-   Study population

-   Number of subjects

-   Inclusion/exclusion criteria

-   Editorial corrections

-   Investigator's brochure

-   Funding

-   Performance site

-   Other

> e\. Name and Signature of Principal Investigator and Date

-   [Questions to Obtain Information on Reporting Emergency Use of a
    Test Article]{.underline}. As described in Chapter 8j,
    "Documentation of Exceptions from Informed Consent Requirements for
    Emergency Use of a Test Article," and 8k, "Documentation of
    Exemptions from IRB Review Requirements for Emergency Use of a Test
    Article," a physician may, under some circumstances, use an
    investigational article in an emergency situation without prior IRB
    approval, and in some extreme cases without the informed consent of
    the patient or the patient's representative. These uses must be
    reported to the IRB within 5 days. A form or instructions may be
    used to elicit a description of the use, its justification under
    applicable policies, and any required independent verification, if
    informed consent was not obtained. Somewhere in the form there
    should be a reminder that one-time use only is permitted, and
    additional use will require submission of a protocol to IRB.
    *([Note]{.underline}: Data collected in this type of event is not
    usable for research purposes.)*

> Questions which may be used to report emergency use:
>
> a\. Description of use

-   Identification of patient (i.e., Initials, medical record number)

-   Name of drug/device

-   Provider of drug/device

## *IND/IDE number*

-   Date of administration

-   Nature of ailment/disease

-   Expected duration of use

-   How did the patient respond to the use of the test article?

> b\. Rationale/justification for use in this subject
>
> c\. Physician verification that these conditions were met for use of
> the article without prior IRB review:

-   A life-threatening situation

-   In which no standard acceptable treatment was available, and

-   In which there was not sufficient time to obtain IRB approval.

> d\. Was informed consent obtained? If yes, attach a copy of the
> consent form used. If not, verification by independent physician that
> these conditions were met for use of a test article without consent as
> required by regulation.
>
> e\. Name and signature of treating physician and date.