Frederic C. Bartter
General Clinical Research Center (GCRC)

Level of Risk Review Form

Title of Project
Principal Investigator(s)
IRB #
Reviewer(s)
Date of Review

                               I. Level of Risk Evaluation

	LEVEL 1	LEVEL 2	LEVEL 3	LEVEL 4
	minimal	low	moderate	high
Evaluated by GAC (check one →)

Risk of Study

                     The Code of Federal Regulations (45 CFR 46.102, 46.111, & 46.406) defines risk as:

Minimal Risk- The probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical and psychological examinations or tests. 

Low Risk- Involves a minor increase over minimal risk- the intervention or procedure presents experiences that are reasonably commensurate with those inherent in actual or expected medical, dental, physiological, social or educational situations.

Moderate Risk- Risks are reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result.

High Risk- Involves greater than minimal risk with no prospect of direct benefit to individual subjects, but is likely to yield generalized knowledge about the subject’s disorder or condition. Studies that are of high levels of risk may result in permanent physical and/or mental changes, hospitalization, and/or death.

Minimal, low and moderate risk protocols will be reviewed annually by the GAC unless there are specific factors which suggest the need for more frequent review.  High risk protocols may be reviewed more frequently as designated by the GAC. The examples cited after each level of risk category is to be used as a general guide.  Other factors influence the risk assignment and must be taken into consideration including: potentials for invasion of privacy/breach of confidentiality, the psychological impact of protocol, social implications, experience of research team, potential for conflicts of interest, etc.  Vulnerable populations such as children, pregnant women, elderly, psychologically or neurologically impaired, and prisoners will be assessed for participation by the level of risk and not solely on their specific vulnerable category.

According to the November 18, 2002 memorandum from NCRR, any “protocol that places participants at significant risk”, “the constitution and membership of an independent data and safety monitoring board must be described”. 

                    Level 1: The study is a minimal risk clinical project with no serious adverse events anticipated.

·        Study poses no more risk than expected in daily life (blood draw, physical exam, routine psychological testing)

·        Behavioral Studies

·        Nutrition studies

·        Observation Studies

·        Survey/Questionnaire Studies

·        Venipuncture

·        intravenous catheter insertion

·        oral glucose tolerance tests

·        intravenous glucose tolerance tests

·        DEXA scans

·        MRI scans

·        special diets

·        exercise testing

·        EKGs

·        anthropomorphic evaluations

·        Category I radiation risk (H_E (mrem) < 500 mrem and organ limit of H_T < 150/W_T)

These pose little risk to human subjects. Any serious adverse events will be promptly reported by the PI, to the IRB and GCRC Research Subject Advocate (RSA). In addition, all changes in protocol procedures will be submitted for review and approval of the IRB and, when approved, will be promptly implemented on the GCRC.

Level 2:  The study has a low level of risk.

 ·       Studies which might meet requirements for minimal review, but include special populations or
      invasive procedures

·        Studies of normal volunteers using well-described research procedures such as an intravenous infusion, euglycemic clamp, indirect calorimetry

·        Post marketing study- phase IV drug study or device (as defined by FDA)

·        Category I radiation risk (H_E (mrem) < 500 mrem and organ limit of H_T < 150/W_T)

Level 3:  The study has a moderate level of risk associated with:

·        Involves subjects with HIV/AIDS, hepatitis, or cancer on a treatment study

·        Subjects treated with a placebo for a recognized disease

·        Substantial risk (>5%) of a Serious Adverse Event originating from the underlying condition of the enrolled subject

·        Phase I or II study with  available safety data in humans

·        Industry sponsored phase III clinical trial

·        research associated procedures (specify):___________________; ___________________; _______________

·        study drugs (specify): ____________________________, _________________, _______________________

·        Category II radiation risk (H_E (mrem) 500 < H_E < 5000 mrem or organ limit of 150/ W_T  <  H_T < 750/W_T)

·        PET scans

All serious adverse events (SAEs) will be reported by the PI, to the IRB and the GCRC Research Subject Advocate (RSA). In addition, all changes in protocol procedures will be submitted for review and approval of the IRB and, when approved, will be promptly implemented on the GCRC.

 

Level 4: The study has the potential for high (significant), levels of risk which may result in permanent physical
                and/or mental changes, hospitalization, and/or death.

·        An investigator-initiated IND trial

·        Involves an intervention or invasive procedure with substantial risk

·        Implantation of device with an IDE

·        Involves the use of a new chemical or drug for which there is little or no toxicology data in humans

·        A gene therapy study or research involving recombinant DNA molecules (gene transfer)

·        An investigator initiated multi-center trial

·        Investigator initiated phase III clinical trial

·        Involves the manufacturing of agents on campus

·        Study has provisions to waive consent in emergency circumstances

·        Blinded Phase I and II trials

·        is a gene transfer study

·        involves higher risk procedures (specify): ________________; ________________; ________________

·        study drugs (specify): ________________________, ______________________, _____________________

·         Category III radiation risk (H_E (mrem) > 5000 mrem or organ limit of H_T > 750/W_T)

·        Phase I or II studies with no available safety data in humans

There is a formally established external Data Safety Monitoring Board (DSMB) that has specific oversight of the safety monitoring of the study (such as company-sponsored).  In the event an external DSMB is not established, an internal DSMB is needed. All correspondence from the Data Safety Monitoring Board will be submitted to the IRB and to the GCRC Research Subject Advocate. All serious adverse events will be promptly reported by the PI to the IRB, the DSMB, and the GCRC Research Subject Advocate, and the study sponsor. In addition, all changes in protocol procedures will be submitted for approval to the IRB and when approved will be promptly implemented on the GCRC.

 

            II. Conflict of Interest

 

	Yes	No
Does the PI disclose any potential conflicts of interest?
Is the GAC aware of any potential conflicts that are not disclosed?

 

            III. Stipulations (if different from study review form):

 

 

 

 

---

Name of Reviewer:

 

Signature of Reviewer:

 

Date:

 

---

        Overview of the requirements for a Data and Safety Monitoring Plan (DSMP)

        Level of Risk Review Form (PDF)

        Quality Management (QM) and the Data and Safety Monitoring Plan (DSMP)

        Data and Safety Monitoring Plan Guidelines

        Data and Safety Monitoring Plan document   PDF   Word

        VA Policies related to the GCRC DSMP

        Joint Commission 2004 Hospital Accreditation Standards Applicable to the GCRC DSMP

        RSA responsibility with Quality Management (QM) and Data and Safety Monitoring (DSM)

Return to GCRC home page

                     Email: GCRC webmaster

                        Date page last modified:  08/08/05 03:05 PM