**Title**

**Investigators:**

**Funding Source:**

**TITLE:**

**INVESTIGATORS:**

**A. SPECIFIC AIMS**

**B. BACKGROUND AND SIGNIFICANCE**

# C. PRELIMINARY STUDIES

**D. RESEARCH DESIGN AND METHODS**

**E. BIOSTATISTICS**

*List power calculations and explain how data will be analyzed.*

**F. JUSTIFICATION FOR USE OF GENERAL CLINICAL RESEARCH CENTER**

**G. FUNDING**

######## **H. HUMAN SUBJECTS RESEARCH PROTECTION FROM RISK** 

1)  **Risk to Subjects**

**Characteristics:** *Describe the characteristics of the subject
population, including their anticipated number, age range, and health
status. Identify the criteria for inclusion or exclusion of any
subpopulation. Explain the rationale for the involvement of special
classes of subjects, such as fetuses, pregnant women, children,
prisoners, or others who may be considered vulnerable populations.*

**Sources of Materials:** *Identify the sources of research material
obtained from individually identifiable living human subjects in the
form of specimens, records, or data. Indicate whether the material or
data will be obtained specifically for research purposes or whether use
will be made of existing specimens, records, or data*

**Potential Risks:** *Describe the potential risks (physical,
psychological, social, legal, or other) and assess their likelihood and
seriousness to the subjects Where appropriate, describe alternative
treatments and procedures, including the risks and benefits of the
alternative treatments and procedures to participants in the proposed
research.*

**Physical**:

**Psychological:**

**Social:**

**Economic:**

2)  **Adequacy of Protection Against Risks**

**Protection Against Risk:** *Describe plans for the recruitment of
subjects and the process for obtaining informed consent. Include a
description of the [circumstances]{.underline} under which consent will
be sought and obtained, [who]{.underline} will seek it, the nature of
the [information to be provided]{.underline} to prospective subjects,
and the [method documenting]{.underline} consent. State if the CPHS has
authorized a modification or waiver to the elements of consent or the
requirement for documentation of consent.*

3)  **Potential Benefits of the Proposed Research to the Subjects and
    Others**

*Discuss the potential benefits of the research to the subjects and
others. Discuss why the risks to subjects are reasonable in relation to
the anticipated benefits to subjects and others.*

**4) Importance of the Knowledge to be Gained**

*Discuss the importance of the knowledge gained or to be gained as a
result of the proposed research. Discuss why the risks to subjects are
reasonable in relation to the importance of the knowledge that
reasonable may be expected to result.*

# I. DATA SAFETY MONITORING PLAN

1.  **Study Description:**

    a.  **Purpose:**

> Therapeutic Investigator initiated clinical trial
>
> Diagnostic Studies using drugs/devices
>
> Physiologic Studies using drugs for other than
>
> indicated use
>
> Genetic Epidemiologic
>
> **b. Design:**
>
> Interventional Observational
>
> **c.** **Study Phase:**
>
> I II III IV Pilot
>
> Not Applicable

d.  **Blinded:**

> Yes No
>
> Single blind

Double Blind

e.  **Randomized:**

> Yes No

f.  **Placebo arm:**

> Yes No

g.  **Multi-center:**

> Yes No

h.  **Number of Participants: [     ]{.underline}**

i.  **Study Length: [     ]{.underline}**

j.  **Procedures: check all that apply**

> Drugs Devices
>
> Questionnaires Educational
>
> Surgery Prevention **(**Vaccines)
>
> Exercise Diet
>
> IV Arterial Line
>
> Gene Therapy Blood/Urine collection
>
> Fasting Feeding
>
> Ultrasound Imaging Procedure **[     ]{.underline}**
>
> Radioisotopes Use of existing specimens or data

Other **[     ]{.underline}**

k.  **Will this research involve the use of an investigational new
    drug?**

> Yes No
>
> IND \#**[     ]{.underline}**

l.  **Will this research involve the use of an investigational device?**

> Yes No
>
> IDE \#**[     ]{.underline}**
>
> significant risk device

nonsignificant risk device

m.  **Will blood or tissue specimens be stored?**

Yes No

n.  **Study Population:**

> **Healthy volunteers** Yes No
>
> **Vulnerable subjects** Yes, indicate below No

Children Prisoners

> Pregnant women Mentally disabled
>
> Clinically vulnerable Economically vulnerable
>
> Elderly subjects Substance Abusers

o.  **Study Risk Determination:**

> Minimal Moderate High

2.  What potential risks are inherent in the study? *This should
    correspond with the risks that are described in the protocol and
    consent form.*

> **     **

3\. How will risks be minimized? *Describe* *the procedures that will be
used to minimize risk to the subject. List the specific tests,
evaluations, examinations, observations, questionnaires, etc., that will
be used, and their frequency to assess subject safety, to monitor for
toxicity, or to detect adverse events. The frequency and intensity of
monitoring described must be appropriate for the level of risk
identified. If there is a table (Schedule of Events) in the Master
protocol, it should be reproduced here or if not possible to reproduce,
referenced clearly.*

     

4\. Individual who will be performing the safety monitoring:

Investigator Data Safety Monitoring Board

(DSMB) attach charter

Institutional colleague Confirmation that IRB and GCRC

will receive all DSMB meeting

Outside colleague minutes and safety reports

Other [     ]{.underline}

5\. How often will the data be monitored?

Weekly Yearly

Monthly After [     ]{.underline} subjects enrolled

Quarterly Other **[     ]{.underline}**

Semi-annually

**6. How will adverse events be classified/graded?**

> utilizing the mild, moderate, severe criteria**d**

-   Mild: Awareness of sign, symptom, or event, but easily tolerated

-   Moderate: Discomfort enough to cause interference with usual

> activity and may warrant investigation.

-   Severe: Incapacitating with inability to do usual activities or
    significantly affect clinical status, and warrants intervention

-   Life-threatening: immediate risk of death.

World Health Organization Toxicity Criteria

Common Toxicity Criteria

> *This may be viewed at http://ctep.cancer.gov/. Once at this website,
> click on Reporting Guidelines, next click on Common Toxicity Criteria,
> then click on Common Toxicity Criteria Document (PDF) for the actual
> CTC table.*

**7**. **Identify the AE attribution scale to be used in the study**

> The PI will determine the relationship of adverse events to the test
> procedure/drug/device using the following scale

Definite: AE is clearly related to the procedure/drug/device

Probable: AE is likely related

Possible: AE may be related

Unlikely: AE is doubtfully related

Unrelated: AE is clearly not related

> PI will use an alternative scale (*specify)*

**8. Describe criteria for stopping or modifying treatment or early
termination of the study in relation to the adverse event grading
scale?**

9\. By checking the box below, you are confirming that you have read and
will comply with the Adverse Event reporting policies of Stony Brook
University's Committee on Research Involving Human Subjects. See CORIHS
policy at

[**http://www.research.sunysb.edu/research/HSG/HSGsec16.html**](http://www.research.sunysb.edu/research/HSG/HSGsec16.html)

> **This will also confirm that the GCRC Research Subject Advocacy
> Office will get a copy of the AE reports.**

**AE reporting confirmation**

# 

**J. LITERATURE CITED**

**Appendix I: QAC**

**Appendix II RDRC**

**Appendix I**

**Quality Assurance**

**[Personnel]{.underline}**

**List all personnel and responsibility on protocol:**

**[Quality Assurance Procedures]{.underline}**

Ensure all scientific processes (such as isotope preparation, machine
calibration, tissue culture work, etc) related to the protocol
adequately performed and controlled so as to support the risk factors
listed in protocol:

(Please check all that apply)

 Protocol in Procedures Manual

 QA testing procedures in Procedures Manual

 Calibration procedures in Procedures Manual

**APPENDIX 1**

**RADIONUCLIDE**

**A.** **Radionuclide**

1\. **Species:** Radionuclide or labeled compound, e.g., ^24^NaCl or
1-^14^C-glucose.

2\. **Physical Characteristics:**

a\. physical half-life

b\. type of decay

c\. energy, and relative frequency of major emissions

d\. average energy, if known

3\. **Source:** (Reactor, cyclotron, hot lab, commercial supplier)

4\. **Preparation:** (Target material, quantity, special problems,
location)

Give details of preparation if this is not a previously approved
radiopharmaceutical. Use separate pages to describe synthetic scheme,
narrative description of synthesis.

5.  **Composition:** List how are the following determined:

    a.  chemical purity,

    b.  radiochemical purity,

    c.  pH,

    d.  dosage,

    e.  sterility and pyrogen-free status

6\. **Specific Activity and Isotopic Purity of Administered Material:**

a.  List the minimum and maximum amount of activity of each radiotracer
    to be administered.

b.  Calculate the maximum total mass injected of each radiotracer.

c\. Supply documentation that this amount will not cause clinically
detectable pharmacological effects.

# 7. Outside Materials:

If any radioactive material is brought into BNL from an outside source
such as a commercial supplier or other radioisotope production facility,
a certificate of analysis must be supplied.

8\. **Instruments or devices used to measure the radioactivity after
administration to the subject:** (e.g., tomograph)

9\. **Radioassay and Calibration Procedures:** (Include validation to be
performed at BNL prior to use)

10\. **Route of Administration and Vehicle:**

11\. **Procedures for Controlling Sterility and Pyrogenicity:**

Note if the commercial isotopes used are certified as ready for
administration to humans.

12\. **Pertinent Side Effects:**

Describe any pharmacological or toxic actions of the parent compound or
vehicle. Provide current literature reference for pharmacological
effects in humans.

**B.** **Radiological Health Aspects**

1\. **Hazards to Other Subjects and to Personnel From External or
Internal Radiation:** (e.g., mr/hr. at 1 meter at the time of
radioisotope injection)

2\. **Personnel Monitoring Procedures, If Necessary:**

3\. **Special Procedures for Handling Waste Products, Excreta, and
Biological Samples:**

4\. **Supply a** **Plan for Isotope Accountability:**

**C.** **Radiation Dosage**

1\. **Biological Half-Life or Physical Half Live:** State whether the
physical half-life of the radioisotope us shorter than the biological
half-life, and by how much.

2\. **Dosimetry:**

Supply a dosimetry table for the maximum amount of radioactivity to be
injected. The table should include contributions from all radioactivity
administered. **List minimum and maximum injected activity to be
administered.**

+-------------+--------------+---------------+--------------+--------+
| Organ       | Dose to      | Dose to Organ | Dose to      | Total  |
|             | Organ        |               | Organ        |        |
|             |              | Cmpd.2 dose = |              | Dose   |
|             | Cmpd.1 dose  | mCi           | Cmpd.3 dose  | to     |
|             | = mCi        |               | = mCi        | organ  |
+-------------+--------------+---------------+--------------+--------+
|             |              |               |              |        |
+-------------+--------------+---------------+--------------+--------+
|             |              |               |              |        |
+-------------+--------------+---------------+--------------+--------+
|             |              |               |              |        |
+-------------+--------------+---------------+--------------+--------+

The maximum allowable dose for a single injection is 3000 mR to the
whole body, active blood-forming organs, lens of the eye and gonads. The
dose to any other organ cannot exceed 5000 mR.

The maximum allowable dose for one year is 5000 mR to the whole body,
active blood-forming organs, lens of the eye and gonads. The dose to any
other organ cannot exceed 15000 mR.

3\. **Organ, Cellular, or Subcellular Localization:** If any
non-radioactive agent is being administered, will that agent alter the
distribution of the radioactivity? If so, briefly describe what effect
the non-radioactive agent will have upon that distribution

a\. **Critical or \"Target\" Organ(s)**

b\. **Gonadal Exposure**

4\. **Give a Literature Reference for the Dosimetry. If none is
available, then give sample calculations:** If standard software
packages (such as MIRDose 3) are being used, give the residence time in
the organ. Dosage should be calculated for the whole body and for
\"target\" or other separate organs, where indicated. Prototype
equations are desired; not extensive calculations. Where applicable, the
Medical Internal Radiation Dose (MIRD) Committee\'s recommended methods
(J. Nuclear Medicine Supplements) should be used. Otherwise, standard
dosage equations from references such as Hine and Brownell\'s *Radiation
Dosimetry,* and the *National Bureau of Standards Handbook 69*, should
be given and the reference cited. The relationship to the administered
dose should be clarified.

**D. Maintenance of records of radionuclide administration and subject
response:**

List how records are maintained and indicate their location.

**E. External Subject Irradiation:**

1**. List radiation source**

2\. **List whole-body dose to the subject**

3\. **List organ or area where the radiation is concentrated and give
dose**

4\. **Describe how radiation dose to the subject is verified**

5\. **Describe how the radiation source is calibrated**

6\. **Describe how possible leakage from the external radiation source
is monitored**