# NHGRI Human Subjects Research Protocol Template 

# 

Project title:

Principal Investigator:

Title/Section/Branch/Institute:

Associate Investigators \[include name, institution, and city\]:

Study type (check all that apply):

Archived biological specimens/medical information

Natural history; definition of phenotype, genotype/phenotype correlation

Prospective linkage/gene identification, NOT providing information to
participants

Prospective linkage/gene identification, providing information provided
to participants

Social science; assessments of knowledge, attitudes and behavior

Genetic counseling

Drugs or devices

Gene transfer

Other interventions

Key Words:

•Disease(s) •Population (i.e., pediatric, specific gender, race, etc).

•Other (Drugs, interventions)

Results routinely communicated to subjects?

No

Yes CLIA Certification

Research participants to be seen at:

> NIH only\*

Off-site only

Both NIH\* and off-site

> *\*Includes participants who physically come to the NIH Clinical
> Center and/or for whom specimens/data are analyzed by Clinical Center
> departments. If participants will be seen at NIH, a Medical Advisory
> Investigator must be indicated on the 1195 form, unless this is a
> social science project with no clinical interventions.*

Collaborative Project:

• FWA for each
Institution:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

*see <http://ohrp.cit.nih.gov/search/asearch.asp#ASUR> for assurance #s*

Instructions: Insert your responses for each section. Be sure to address
each point in all sections that are relevant. (It is not necessary to
itemize each point or to specify "not applicable.")

Please use a readable font, like Times 12-point type, to facilitate
legibility. We encourage investigators to limit the overall length of
protocols to 20 single-spaced pages or fewer, not including appendices
and other attachments.

1.  **Precis:** *(In 400 words or fewer, describe the study objectives,
    population, design, and outcome measures*)

2.  **Objectives and specific aims.** *(List the objectives concisely;
    whenever possible state objectives as hypotheses.)*

3.  **Brief Rationale and Background**: *Write a **[brief]{.underline}**
    \[**no more than 5 pages in length**\]* *summary of the clinical
    background, limits of current knowledge, and significance of this
    protocol. For background on drugs and devices, cite animal studies,
    prior experience in humans, and discuss potential toxicities.
    Include **up to 20** key references.*

4.  **Description of study design** *(Brief description of what study
    design has been selected)*

5.  **Description of procedures:** *(what will be done, when will it be
    done, where will it be done, duration of participant involvement;
    **[Please include a flow-sheet or chart]{.underline}).***

    1.  Medical information *(what information will be collected, any
        sensitive information, how long will it be stored, are there
        future anticipated uses?)*

    2.  Diagnostic studies *(include use of radiation or sedation.)*

    3.  Biological Specimens *(How much will be collected, what disease
        categories will be studied, will cell lines be created, how long
        will sampled be stored, are there future anticipated uses?)*

    4.  Approved Drugs *(Include dosage in study and range approved for
        clinical use.)*

    5.  Unapproved Drugs/Devices *(indicate if approved for other use,
        include dosages in study, and [IND or IDE number]{.underline},
        if applicable.)*

    6.  Specific results that will be given to participants or their
        health care providers *(Is laboratory CLIA certified?)*

    7.  Describe questionnaires or other psychological instruments and
        estimate how long they will take to complete, and whether they
        address sensitive topics *([Enclose copies.]{.underline})*

    8.  Genetic counseling *(By whom, would counseling happen in person,
        will understanding be assessed?)*

    9.  Description of criteria for withdrawal from study.

6.  **Description of Study Population:**

    1.  Estimated number of participants, enrollment ceiling, and
        anticipated enrollment by year.

    2.  Description and justification of clinical inclusion/exclusion
        criteria. *(affected individuals, family members, controls?
        Define clinical criteria: Will this determination be made by
        review of prior records or will a screening evaluation be
        performed? Justify population choice in regards to age, gender,
        ethnicity, prisoners, pregnant women, fetuses, people with
        impaired decision-making ability, healthy volunteers, lab
        personnel)*

    3.  Location of study *(specify NIH Clinical Center facilities
        and/or other off-site locations).*

    4.  Description of recruitment strategies *(How participants will be
        identified; note efforts to include under-represented
        minorities; [include copies of recruitment advertisements and
        letters]{.underline}.)*

    5.  For existing sample/data sets, note whether samples were
        originally collected for research or clinical practice. If
        obtained for research, include a description of the original
        purpose of study and prior plans for sample storage. Was consent
        obtained that would be applicable to this study? (*[Include copy
        of original consent forms.]{.underline}*)

    6.  Description of any financial compensation. If participant
        withdraws early, describe how compensation will be modified.

7.  **Description of study statistical considerations and/or analytic
    plan:** *Write a **[brief]{.underline}** \[**no more than 3 pages in
    length**\]* *description of how data will be used to answer
    hypotheses, sample size and power calculations, methods of analysis,
    criteria for significance, as applies to this protocol.)*

8.  **Description of potential benefits of study:**

    1.  Direct benefits to participants *(Include only those physical or
        psychosocial benefits that derive directly from an intervention
        being studied)*

    2.  Collateral benefit to participants *(medical or genetic
        counseling care and other benefits associated with being a
        research subject at the NIH that are not directly related to the
        specific study intervention. Do not include financial
        compensation as a direct or collateral benefit.)*

    3.  Benefits to society

9.  **Description of likelihood and seriousness of harms and how safety
    will be maximized:** *(Include potential physical and psychosocial
    harm from both research-related and medically-indicated procedures,
    alternative interventions that might be advantageous to
    participants, and provisions for medical or other professional
    interventions in the event of adverse events.)*

    1.  Therapeutic interventions *(drugs/devices/gene transfer)*

    2.  Diagnostic interventions *(blood draws/imaging/biopsies)*

    3.  Radiation *([Provide documentation from Radiation Safety
        Committee.]{.underline})*

    4.  Sedation

    5.  Psychological harms *(misunderstanding, anxiety, self esteem,
        depression)*

    6.  Risks to family relationships *(related to determination of
        genetic/disease status, parentage, adoption)*

    7.  Discrimination *(insurance, employment)*

10. **Description of how privacy and confidentiality of medical
    information/biological specimens will be maximized**

10.1 Will participant identifiers be attached to data, or will
samples/data be coded or unlinked*? (Even if names are removed, how
likely is potential identification?)*

10.2 Description of any clinical/demographic information that will be
included. (*age, ethnicity, sex, diagnosis, stage, treatment*)

10.3 How might this information make specific individuals or families
identifiable?

10.4 If research data will be coded, how will access to the "key" for
the code be limited? Include description of security measures
(*password-protected database, locked drawer, other*). List names or
positions of persons with access to the key.

10.5 Will pedigrees be published? Include description of measures to
minimize the chance of identifying specific families.

10.6 Will any results be provided to participants or their health care
providers? Explain.

10.7 Will personally identifiable information be released to third
parties?

10.8 Under what circumstances will data/samples be shared with other
researchers?

10.9 Describe any additional features to protect confidentiality.

11. **Assessment of Risk/Benefit Ratio** *(Reasonableness of risks to
    participants in relation to the anticipated benefits of the study
    and in relation to the importance of the knowledge that may
    reasonably be expected to result.)*

12. **Collection, monitoring, analysis and reporting of adverse events**

    1.  Describe all potential adverse events that can be anticipated
        and monitored for this protocol. If this is either a natural
        history or limited encounter protocol, explain this to the IRB
        and specify the occurrences that will be excluded from adverse
        event reporting. *(For natural history protocols, describe range
        of medical events [independent of any protocol
        encounter]{.underline} that are known to occur in subjects who
        qualify for study enrollment. Natural history protocols will
        monitor, but not consider as reportable, occurrences that are
        purely a consequence of an underlying genetic or medical
        condition under study in a protocol. Furthermore, adverse events
        need not be ascertained in limited encounter protocols such as
        linkage studies or tissue array studies, in which NHGRI
        investigators are not providers of medical services.)*

    2.  Describe plan to monitor and report adverse events as defined
        above for this protocol (*anticipated and unanticipated, serious
        and non-serious*), in accordance with NIH and NHGRI regulations.
        Note that all serious adverse events as defined for this
        protocol must be reported in writing by mandated deadlines to
        the NHGRI Clinical Director, NHGRI IRB, and other agencies, if
        pertinent.

    3.  Describe whether a Data Safety and Monitoring Board (DSMB) will
        be used.

13. **Description of alternatives to participation** *(Other clinical or
    research interventions, if any, that participants should consider.)*

14. **Description of Consent Process**

    1.  Who will obtain consent *(PI, study coordinator, and primary
        physician)?* If collaborators who are not designated as
        co-investigators will be obtaining consent, the consent form
        should be signed by *both* the PI and the collaborator who is
        obtaining consent.

    2.  Setting where consent will be obtained *(location of in-person
        discussion, phone, mail).*

    3.  What information will be provided to participants? *([Include
        consent and/or assent forms]{.underline}, printed or web-based
        materials, phone scripts and any other related material.).*

    4.  Protections for participants who may be vulnerable to coercion
        or undue influences *(pregnant women, fetuses, children, people
        with impaired decision-making ability).*

    5.  Are there special circumstances regarding obtaining *consent?
        (Waived consent, opt-out, verbal consent, consent with speakers
        of other languages and translation of materials into other
        languages.)*

(version 8/5/07)