scire-lb.orgscire-lb.org/wp-content/uploads/2016/03/Guidelines-for-N… · Web viewExcept when the expedited review process is used, these actions will be taken by a vote of a majority

Department of Research and Development Veterans Affairs Long Beach He2althcare System

5901 East Seventh Street Long Beach, CA 90822

Guidelines for Investigators and Staff Conducting Human Research at the

Long Beach Veterans Affairs Healthcare SystemVersion 2: September 2016

Table of Contents: Institutional Review Board:

1. Investigator Responsibilities and Duties a. Becoming a VALBHS approved

PI b. General Responsibilities c. Investigator Responsibilities in

Using Investigational Drugs d. Investigator Responsibilities in

Using Investigational Devices 2. General Information and Regulations

a. Events Requiring Prompt Reporting

b. Non-Compliance/For-Cause Audits

c. Sponsor Audits, On-Site Evaluations, Reports

d. Flagging Medical Records for Research Subjects

e. Researcher Contact with Veterans

f. Vulnerable Populations g. Research Record Keeping h. Regulatory Binders i. Enrollment of Non-Veterans j. Clinical Trials.Gov k. Data Security and Privacy l. Coded vs De-Identified Data

m. Advertising n. Creating a Clinic in CPRS o. Dual Enrollment p. Impact Estimation Worksheets q. Data Safety Monitoring r. Study Monitor Processs. Categories of Action

3. Initial/Continuing/Closure Process a. Initial Process b. Continuing Review Processc. Study Closures d. Expiring Studies

4. Consent/HIPAA/Waiver a. Informed Consent b. HIPAA Authorization c. Waivers

5. Tissue Banking vs Long Term Storage a. Collection and Storing

Specimens or Future Research b. Collection and Storing

Specimens for a Single Research Protocol

c. VA-Approved Tissue Banks d. Exceptions

6. Research Pharmacy7. FAQ

Guidelines for Investigators and Staff Conducting Human Research at VALBHCS Page 1

Training and Credentialing: 1. VA Employee vs WOC 2. Requirements for completed HST&C 3. Study Monitor Requirements 4. Staff not located at the VHALON

Miscellaneous: 1. Acronyms2. Reference Information3. Definitions 4. Roles


Research Contact Information:

Dr. Christopher Reist: ACOS

Ext: 5801/Email: [email protected]

Dr. Edward DeMet: Research Compliance

Email: [email protected]

Alicia Del Villar: AO


Elizabeth Rundgren: HRPP Administrator


Tiffany Rose: IRB Coordinator


Stacey Paikoff: IRB Assistant

Ext: 4246/ Email: [email protected]

Valerie Viramontes: Program Assistant


Tamara Bon: R&D Coordinator


Sandy Graham: Budget Analyst

Ext: 4939/ Email: [email protected]

SCIRE Contact Information:

Jennifer Griffith: Director


Brian Noel: HR Manager


Lientra Lu: Accounting Assistant


Jasmine Williams: Purchasing

Ext: 8139 / [email protected]

Jennifer Nishikawa: Grants Manager

Ext: 2530/

Email: [email protected].

Rachel Heffner: Contract & Grants


Location:Building 11, Second Floor

Mail Code: 09-151Phone: 562-826-8000

Fax: 562-826-5675Website: www.scire-lb.org


http://www.scire-lb.org/

mailto:[email protected]








mailto:5801/Email:%[email protected]







History & Purpose: The Institutional Review Board (IRB) is a board established in accordance with and for the purposes expressed in the Common Rule (38 CFR §16.102(g)). As stipulated in the Belmont Report and based upon the principles of autonomy, beneficence and justice, the primary responsibility of the IRB is to ensure: (1) the sum of the benefits to the subject and the importance of the knowledge to be gained so outweigh the risks to the subjects as to warrant a decision to allow the subject to accept these risks (2) legally effective informed consent is obtained, unless the requirements for waiver of informed consent are met by adequate and appropriate methods in accordance with the provisions of applicable regulations, and (3) the selection of subjects is equitable and is representative of the group that will benefit from the research. The IRB will review all research at an interval appropriate to the degree of risk, but not less than once per year. Although designated as a subcommittee of the R&D Committee by VA regulations, the IRB functions independently, free of coercion and oversight of its decisions. The VALBHS IRB cannot serve as an IRB of record for any non-VA entity except DoD or VA nonprofit for research and education (at VALBHS this is the Veterans Biomedical Research Foundation (SCIRE)). On its FWA, SCIRE must have an IRB of record that is the VALBHS IRB. The IRB also serves as the Privacy and Confidentiality Review Committee and ensures compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The IRB has the authority to approve, require modifications to secure approval, and disapprove all research activities overseen and conducted by the organization. The IRB has the authority to suspend or terminate approval of research not being conducted in accordance with the IRB’s requirements or that had been associated with unexpected serious harm to participants. The IRB has the authority to observe, or have a third party observe, the consent process and the conduct of the research.

If you are interested in the history of the IRB, it is suggested to read some of the following items:

- The Nuremberg Code - The Wichita Jury Study - The Thalidomide Experience - The Declaration of Helsinki - The Tuskegee Syphilis Experiment - The Willowbrook Hepatitis Studies - The Milgram Studies of Obedience of Authority

The purpose of this manual is to assist in some of the common compliance issues Principal Investigators and Research Coordinators could run into. It is suggested to either contact the IRB Administration Office or reference the IRB Standard Operating Procedures for further information.


Section 1: Investigator Responsibilities and Duties In the conduct of human research, the investigator has obligations and duties to act in accordance with the policies of the IRB and to report to the IRB as required. The investigator must obtain written approval from the ACOS/R&D before initiating research. The IRB will investigate any allegations of research non-compliance, which affects a specific study protocol. It is strongly suggested to review the duties and responsibilities section of the IRB SOP prior to requesting approval from R&D for PI status.

A) Becoming a VALBHS Approved PI: Determining Eligibility. The R&D Committee will determine if applicants are eligible to supervise the conduct of research at VALBHS. Persons who are deemed eligible may become Principal Investigators (PI’s).

Who must be reviewed. Eligibility will be evaluated for all potential PI’s who: o Have never had a previously approved research project at VALBHS, OR o Have had a previously approved research project at VALBHS but who currently do not

have an approved project. This category includes investigators who have failed to submit closure documents within 90 days of a lapse of approval.

Criteria For Determination. In determining eligibility the R&D committee will consider: o If the applicant has adequate training and credentials to perform research. The R&D

Committee will review evidence that will include primary source verification of degrees, certifications, licenses, academic appointments or other experience. At a minimum, PI’s must have an M.D., D.O., Ph.D., (or equivalent) or an R.N. license, or Pharm.D. degree. PI’s must generally also have postgraduate training or experience in the area that is to be the focus of the research. The R&D Committee may waive the degree requirement if:

Applicant has demonstrated unusual competence and Applicant has adequate experience to function as a Principal Investigator.

o Applicants should generally have a paid position at VALBHS. Students, Fellows, Interns and other trainees are not eligible to be PI’s. Persons who are without compensation at VALBHS (WOC’s) must have their eligibility approved by the R&D Committee using the following criteria:

The proposed research must involve significant benefits to the patients that would not otherwise be available, and

The proposed research will not compete with research that is being performed by paid investigators at the VALBHS.

o Applicants must have a physical presence at VALBHS that is adequate to supervise research personnel, the conduct of research, and the retention of research records unless the medical program is not available at the VA Long Beach Healthcare System and the proposed research activity would not negatively impact VALBHS research activities.

o Applicants must adequately demonstrate that they are able to discharge non-research duties in an adequate manner. Persons who have failed to adequately discharge primary duties, are not eligible to conduct the extra duties associated with research. The R&D Committee will consult with the Chief of the applicant’s home healthcare group in making this determination.


o Applicants must affirm that they will be compliant with all procedures and regulations. If the applicant has a previous research history, then the R&D committee will consider any previous history of non-compliance. This may include, but is not limited to:

Previous suspensions or terminations of approved research. Failure to maintain adequate records. Failure to perform adequate supervision and/or training of staff. Failure to submit documentation in a timely manner. Aggressive or hostile actions against staff, or others. These may include oral or

physical threats, derogatory remarks, the taking of unauthorized photographs, following persons, surveillance (including the gathering of information about persons). Also included are the filing of excessive numbers of complaints and /or accusations where:

The outcome of such complaints and/or accusations is a failure to confirm, and

A reasonable person may consider the number to be excessive, and A reasonable person might infer that the applicant might be trying to

exert a pressure on the target of the complaint / accusation in order to influence an outcome, or

The target of the complaint / accusation has VA duties that involve either a recent or pending evaluation of the applicant’s performance.

Determination and Notification. Determinations of eligibility to supervise research may only be made by a convened meeting of the R&D Committee. The Committee will consider the preponderance of evidence and will vote to determine if the applicant is eligible. If the applicant is deemed ineligible, then the Chair of the R&D Committee and the ACOS R&D will notify the applicant in writing within 30 days. The notification will include the general reason(s) for the disapproval. The reasons should be adequately described so as to convey the basis for the decision. However, it should be noted that the decision is made on the basis of the overall evidence and not necessarily on the basis of specific criterion. The letter should also advise the applicant of his right to appeal the decision.

How do I obtain approval? You will need to submit a “letter of intent” and a copy of your current CV to the IRB. You can email these items to the Acting HRPPA. These items will be reviewed at the next convened R&D meeting. Your letter should include the following information:

An explanation that you have a sufficient presence at VALBHS to adequately conduct the planned research

A short summary of the planned research protocol If this is the first study you will have here at LBVAHS, it is suggested to mention who will

“mentor” you.

B) General Responsibilities: In addition to the requirements noted above, the investigator has numerous responsibilities in the conduct of human research. The investigator will:

Acknowledge and accept their responsibility for protecting the rights, safety, and welfare of human research subjects and for complying with all federal, state, VA and institutional regulations and the VALBHS FWA


Design research studies so that the research will likely develop or contribute to generalizable knowledge. When investigators do not design a research study, they should judge the research design to be sound enough to meet its objective before agreeing to enroll participants.

Design a research plan that is scientifically valid and sound Ensure that research is in compliance with all applicable local, VA and other Federal

requirements Personally conduct or supervise the investigation. Ensure that the investigation is conducted

according to the written, approved protocol, the sponsor agreement, and other applicable federal regulations and any conditions of approval imposed by the IRB and FDA.

Disclose relevant financial information and conflicts of interest Ensure that all associates, colleagues, and employees assisting in the conduct of the

investigation(s) are informed about their obligations in meeting Federal, state, local, and VALBHS requirements.

Ensure that the FDA, any reviewing IRB’s and all participating investigators are promptly informed of significant new information about an investigation.

Understand and comply with the reporting requirements of the organization. When appropriate, investigators should include additional reporting mechanisms in the research protocol beyond those described by local policies and procedures.

Ensure that he/she has the necessary resources to protect human subjects when conducting a research study.

Submit proposed research for review and approval (or exemption) for IRB review Acknowledge and accept their responsibility for all activities related to the conduct of their

research Submit to the IRB all requests for modifications to the protocol or the informed consent Make certain that a qualified clinician is responsible for all study-related healthcare decisions to

include, but not limited to:o Reviewing the data, adverse events, and new study findingso Making required decisions to protect the health of the subject (e.g., stopping the

participant’s involvement in the study or determining when to notify the subject or the subject’s health care provider of information that may affect the health of the subject.

Develop a research plan that minimizes risk to the subjects Take actions that minimize the risk of harm to the subjects Obtain legally effective informed consent of the subject or the subject's legally authorized

representative and legally effective authorization for the use and disclosure of the subject’s protected health information

Make certain that he/she, as well as all research personnel have appropriate qualifications, training, experience, and be credentialed to perform the research activities they will carry out

Make certain that neither the investigator nor the trial staff will attempt to coerce or unduly influence a subject to participate or to continue to participate in a trial

Place the original signed informed consent form and appropriate progress notes documenting the consent process in the subject's medical record

Document that subjects are informed in a timely manner if new information becomes available that may be relevant to the subject’s willingness to continue participation in the trial. The communication of this information should be documented Provide the IRB with all required data necessary for continuing review, especially serious or unexpected adverse events and modifications


Promptly report to the IRB any problems that require prompt reporting to the IRB as defined in IRB SOP Section QA 903.

Furnish required reports to the sponsor, including reports of adverse events, unanticipated problems involving risks to participants or others, and study completion

Keep copies of signed Informed Consent Forms readily accessible for review; Not seek to obtain research credit for, or use data from, patient interventions that constitute

the provision of emergency medical care without prior IRB approval. Such activities will not be counted as research nor the data used in support of research

Report any study suspension or termination by the sponsor Know the date of the continuing review and to be aware that the project becomes lapsed if

continuing review does not occur on schedule. Lapsed projects are not approved and no research is permitted except as may be required to protect the rights and welfare of the current participants.

Make provisions for retention of records at the institution if he/she leaves the VA facility Provide a plan for just, fair and equitable recruitment practices in research and avoid practices

that place participants at risk for coercion or undue influence Ensure appropriate telephone contact with subjects

o Initial Contact – During the recruitment process, ensuring the research team makes initial contact with the potential subject in person or by letter prior to initiating any telephone contact, unless there is written documentation that the subject is willing to be contacted by telephone about the study in question or a specific kind of research. The initial contact must provide a telephone number or other means that the potential subject can use to verify the study constitutes VA research.

o Later Contact – the research team begins telephone calls to the subject by referring to previous contacts and when applicable, the information provided in the informed consent form. The scope of telephone contacts with the subject is limited to topics outlined in IRB-approved protocols and informed consent forms.

Respond to subjects’ complaints or requests for information. Understand when activities are subject to the HRPP and when to seek guidance Seek approval by the IRB of all amendments to, or modification of, the research proposal

including the consent form prior to initiating the changes except when necessary to eliminate apparent immediate hazards to the subject.

If the investigator leaves the facility, the original research records must be retained at the institution.

Provide the IRB with sufficient information when requiring a waiver or alteration of the HIPAA Authorization for the IRB to find that such waiver or alteration is necessary.

Prepare and maintain adequate, current and complete case histories. The case history for each individual must document that informed consent was obtained prior to participation in the study.

Limit contact with Veterans to those clinically essential or as outlined in IRB approved protocols. Contacts must not solicit sensitive information (e.g., SSNs).

During the recruitment process, researchers must make initial contacts with Veterans in person and/or by letter prior to any telephone contact, and provide a telephone number or other means that Veterans can use to verify the validity of the study.

After recruitment and during follow-up phase, ensure that all staff begin calls by referring to previous contacts and the information provided on the informed consent document.


Comply with the requirements of the Controlled Substance Act Make every reasonable effort to provide the information brochure, “Volunteering in Research”

to potential subjects in settings where subjects may be recruited (e.g., clinical waiting areas), and to each prospective subject when that individual is approached to take part in a study.

Maintain written documentation on file that the protocol is being implemented as approved by the IRB and in accordance with other required approvals

o Copies of all IRB-Approved versions of the protocol and amendmentso Case report forms and supporting data, including, but not limited to, signed and dated

informed consent forms and HIPAA authorizationso Documentation on each subject including, but not limited to:

Informed Consent Interactions with subjects by telephone or in person Observations Interventions Other data relevant to the research study including but not limited to: progress

notes; research study forms; surveys and questionnaires; reports of adverse events; data analyses; reports including but not limited to, abstracts and other publications; all correspondence including but not limited to, that with the funding source or sponsor, and with applicable oversight entities including but not limited to, IRB, R&DC, ORO; and a master list of all subjects for whom informed consent has been obtained in the study.

o Documents must be maintained so that they may be audited by the facility RCO, or other entities according to applicable sponsor, local, VA or other Federal requirements, and

o Accounting of Disclosure must be maintained for each disclosure of information from the study to a non-VA entity. (The Privacy Officer can assist in providing this mechanism.

Maintain a Master List of All Subjects – The investigator must maintain a master list of all subjects from whom informed consent has been obtained whether or not IRB granted a waiver of documentation of informed consent:

o Investigators must not add a subject’s name to the master list of all subjects until after: Informed consent has been obtained from that subject, and When appropriate, informed consent has been documented using an IRB-

approved informed consent form. The IRB waives the requirement for the investigator to maintain a master list if

there is a waiver of documentation of informed consent. The IRB may also waiver this requirement at its own discretion in other circumstances but such waivers must be documented.

o The investigator must secure the master list appropriately in compliance with all VA confidentiality and information security requirements in the investigator’s file for each study.

Ensure Appropriate Laboratory Testing – The investigator must ensure that research laboratories not report laboratory results that are used for diagnosis, treatment, and prevention of disease in patients, unless the research laboratories are properly accredited and meet all requirements.


All VA Research publications, presentation information, media events and awards help to advance VA goals and distinguish the VA health care system as forward-looking, Veteran-centric and evidence based. As such, all ORD field investigators are required to upload notifications about upcoming publications, presentations, media interviews and other professional activities to PubTracker. The website URL is https://vaww.ord.portal.va.gov/sites/comm/PubTracker/Pages/default.aspx.

C) Investigator Responsibilities in using Investigational Drugs : The complete institutional policy for investigational drugs is described in a separate document, “Investigational Drug Policy”.

When investigational drugs are used in human research, the principal investigator is responsible for:

All of the responsibilities of the investigator that are described in sections B above. Establishing the research protocol for approval by the Research and Development Committee and

sharing the investigational drug related information with the Investigational Pharmacist and the nurse who will administer the drug to the patient.

The control of drugs under investigation. The PI will meet with (or otherwise consult) the Research Pharmacy in advance of application for

IRB approval, to ensure that adequate Pharmacy resources are available and that potential cost concerns have been addressed; The research pharmacy is responsible for the receipt, storage, and distribution of all investigational drugs.

The PI ensures that the Research Pharmacist receives:o Documentation of IRB and any other relevant approvalso A copy of VA Form 10-9012, Investigational Drug Information Record, when applicableo A copy of the current approved protocolo A copy of the Informed Consent Form for each participating subject with all appropriate

signatureso Documentation of the IRB continuing review approvalo Copies of sponsor-related correspondence specific to the drug(s) as appropriate; ando Copies of all correspondence addressed to the investigator from the FDA (and other

involved authorities) specific to the investigational drug(s) as appropriate. The PI will ensure compliance with all documentation requirements and make relevant records

accessible to the research pharmacist when requested. The PI will ensure compliance with all VALBHS pharmacy requirements regarding receiving,

dispensing, storing and record-keeping for investigational drugs. The PI shall administer the drug only to participants under the PI’s personal supervision or under

the supervision of a co-investigator responsible to the PI. The PI shall not supply the investigational drug to any person not authorized to receive it. The PI is required to maintain adequate records of the disposition of the drug, including dates,

quantity, and use by participants. If the investigation is terminated, suspended, or completed, the PI shall notify the Chief of

Pharmacy Service, the research pharmacist, and the IRB in writing and return the unused supplies of the drug to the Research Pharmacy.

PI’s are required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. Case histories include the case


https://vaww.ord.portal.va.gov/sites/comm/PubTracker/Pages/default.aspx

report forms, supporting data, and CPRS documentation in the medical record. CPRS documentation must include documentation of the consent process (see IRB SOP Section IC 701).

The PI shall retain case histories as required by the current Record Control Schedule. The PI shall furnish all reports to the sponsor of the drug who is responsible for collecting and

evaluating the results obtained. The sponsor is required to submit reports to the FDA on the progress of the clinical investigations.

All clinical investigators shall provide the sponsor with sufficient accurate financial information as may be required to support the sponsor’s application. This information shall be promptly updated if any relevant changes occur during the course of the investigation and for 1 year following the completion of the study.

If the investigational drug is subject to the Controlled Substances Act, the PI shall take adequate precautions, including assurance that the investigational drug is stored in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited, to prevent theft or diversion of the substance into illegal channels of distribution.

The PI shall upon request from any properly authorized officer or employee of the FDA, at reasonable times, permit such officer or employee to have access to, and copy and verify any records made by the investigator pursuant to 21 CFR 312.62 [21 CFR 312.68].

Including VA Form 10-9012 (IDIR) is included in the patient medical record (CPRS)

D) Investigator Responsibilities in using Investigational Devices : The complete institutional policy for investigational devices is described in a separate document, “VALBHS Policy on Use of Investigational Devices”. Also see IRB SOP Section IC 702.

When investigational devices are used in human research, the principal investigator is responsible for all of the more general requirements that are described in sections above. The principal investigator is also responsible for complying with the FDA regulations in 21 CFR 812. The following additional requirements are specific to investigational devices:

Obtain approval for use of the investigational device by preparing and submitting appropriate documents for review.

Ensure that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations.

Protect the rights, safety, and welfare of the participants under the investigator’s care. The control of device(s) under investigation. The PI shall administer the device only to

participants under the PI’s personal supervision or under the supervision of a co-investigator responsible to the PI. The PI shall ensure that the investigational device is not supplied to any person not authorized to receive it.

Ensure that the subject has read and signed the IRB approved patient informed consent. Properly documenting Informed Consent for the use of the investigational device and placing

original in the subject’s medical record. Storing the investigational devices in a locked, secure area. Ensure that all investigational devices are safe for human use, including electrical safety testing

by the Biomedical Engineering department. Ensure proper dispensing and utilization of the investigational device as outlined in the

approved protocol.


Supervise device use, permitting use of the device only with subjects under his/her supervision and not supplying an investigational device to any person not authorized under the IDE regulation to receive it.

Maintain records and tracking of all investigational devices which include: source of device, date device received, quantity received, IDE approval letter from the sponsor, prescription and patient receiving IDE and note about potential disposition of the device.

Disposal of used devices. Return to the sponsor any remaining supply of the device or disposing of the device as the

sponsor directs upon completion or termination of a clinical investigation or the investigator's part of the investigation or at the sponsor's request.

Removal and return of non-functioning implants, where appropriate. Following all reporting requirements described in the VALBHS Device Policy and in Subpart G of

the IDE regulation (21 CFR 812.140). Disclosing to the sponsor sufficient accurate financial information to allow the sponsor to meet

its financial reporting requirements, and promptly updating this information if any relevant changes occur during the course of the investigation and for 1 year following completion of the study.

For implanted devices, documenting the implantation and/or explanation of the device in the medical record.

Documenting use or implantation in the medical record. Return of equipment supplanted by the device, if any. If the investigator leaves the facility, making provisions for follow up of research subjects with

implanted devices. For implanted devices, permanently retaining appropriate emergency contact information. If

the investigator leaves the institution they must either designate another investigator to retain this information or provide the information to the research department.

Submitting complete, accurate, and timely reports of unanticipated adverse device effects to the IRB and the Sponsor.

Furnishing of all reports to the sponsor of the device who is responsible for collecting and evaluating the results obtained. The sponsor is required to submit reports to the FDA on the progress of the clinical investigations.

Complying with requests from any properly authorized officer or employee of the FDA, and at reasonable times, the permitting of such officer or employee to have access to, and copy and verify any records made by the investigator pursuant to 21 CFR 312.62 [21 CFR 312.68].

As part of the initial application, the investigator must provide a written plan for the device that adequately demonstrates his/her qualifications and how the above responsibilities will be met and documented.

Section 2: General Information and Regulations to follow:


The research and development committee (R&D) and the Institutional Review Board (IRB) must approve all research activities before the research may be initiated at the VA Long Beach (VALBHS). This includes research studies that recruit VALBHS subjects (staff, patients, volunteers, medical records), use VALBHS resources (funds, facilities, space, personnel), or wish to post advertisements for recruitment of subjects on VALBHS property.

a) Events Requiring Prompt Reporting to the IRB: Unanticipated problems involving risks to subjects or others, adverse events, protocol violations, breaches of confidentiality, subject complaints and other events meeting requirements for prompt reporting (please reference IRB SOP for any additional information) must be reported promptly to the IRB. The event should be reported within:

If a problem (1) involves or suggests risk to VA research subjects OR (2) the problem involves or suggests risk to anyone else in VA research (e.g., family members, researchers, others), the investigator must report the problem to the IRB within 5 days

If a local adverse event occurs and the adverse event is serious as defines by the FDA, meaning that the adverse event resulted in (or needed medical or surgical intervention to prevent) death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or jeopardy to any subject’s rights, safety or welfare, the investigator must report the problem to the IRB within 5 days

The IRB SOP Section QA903 has detailed description of any events requiring IRB reporting. Here is a timetable you can use for reference:

Action Maximum time permitted

Investigators must submit continuing approval materials prior to the expiration of IRB approval (i.e.,, the Continuing Review Deadline of the study, at least

60 days

Investigators must submit interim reports prior to the date required, at least 14 days

Investigators submit completion report after completion or termination of the study within

60 days

Members should receive materials prior to regularly scheduled meetings at least 3 working days

Reporting of fatal or immediately life-threatening events to the IRB after discovery no later than

3 working days

Other types of adverse events after awareness of the problem no later than 5 working days

Investigator notified in writing of the IRB’s decision after the meeting within 5 working days

Investigator must supply required modifications or appeal within 90 days

Investigator reports study modifications to eliminate hazards to subjects to IRB 5 working days


within

Investigator reports suspension or termination of study, IND, or IDE to IRB within 5 working days

Investigator notified in writing of results of IRB review of audit report within 3 working days

Deadline to submit relevant review documentation after emergency use of a test article outside of an approved study within

5 working days

Deadline to submit independent review after emergency use of a test article outside of an approved study within

5 working days

Complete Audit Report after completing the audit within 5 working days

The results of an IRB Review of an audit communicated in writing to the Investigator, after commencement of the review

5 working days

The investigator must respond to the notification of IRB review of an audit report within

30 days

Telephone notification of IRB Review finding of serious noncompliance 24 hours

Written notification of IRB Review finding of serious noncompliance 5 working days

Response by investigator after notification of serious noncompliance 10 working days

Appeal by investigator of IRB finding of noncompliance 90 days

Number of days prior to the Continuing Review Deadline during which IRB may re-approve research and still maintain the same date for the Continuing Review Deadline

30 days

b) Non-Compliance/For-Cause Audits: VA personnel, including WOC and IPA appointees, must ensure that the IRB is notified, in writing, within 5 business days after becoming aware of any apparent serious or continuing noncompliance with the IRB.

A “for cause” audit may be initiated in response to any of the following findings: an allegation of or evidence suggesting noncompliance with applicable regulations or

institutional policies non-compliance with policies of the IRB as outlined in this document ongoing research is identified which has not been approved by the IRB expressed concerns by the sponsor regarding the investigator’s work a complaint by a subject in a study about protocol or subject's rights violations a potential high risk to subjects, recruitment of vulnerable populations, studies that involve large numbers of subjects, investigators who are conducting multiple studies under IRB jurisdiction


research by an investigator outside of their specialty areas safety or effectiveness findings that are inconsistent with those of other investigators studying

the same test article too many subjects with a specific disease given the locale of the investigation are claimed laboratory results that are outside the range of expected biological variation studies selected at the discretion of the IRB an allegation of or evidence suggesting abuse of research subjects an allegation of or evidence suggesting scientific misconduct

c) Sponsor Audits, On-Site Evaluations, Reports to Sponsors or Federal Agencies: These events and/or reports should be reported simultaneously to the IRB. Please see section (s) for the process for handling Study/Sponsor monitor visits.

Any suspicions or concerns that are raised in the course of a monitor visit must be conveyed to the Investigator and the HRPPA, or designee(s), at an exit interview. These include any instances of non-compliance with the study protocol, IRB requirements, or applicable regulations or policies (e.g. failure to consent subjects who do not meet inclusion and exclusion criteria, failure to report promptly to the IRB the problems that require prompt reporting to the IRB as defined in IRB SOP Section QA 903. Problems will be evaluated and managed as described in section QA 903.

If a monitor records no findings or concerns, as listed above, then the study investigator or research coordinator must notify the research office in writing that there were no such findings identified by the monitor and must submit copies of any monitoring reports to the IRB.

d) Flagging of Medical Records for Research Subjects It is the PI’s responsibility to create a clinic in CPRS prior to enrolling any subjects. Please reference the section (n) for further instructions on setting up a research clinic in CPRS. The IRB may determine that the patient health records must be flagged to protect the subject’s safety by indicating the subject’s participation in the study. The IRB approval memo will state if you are “waived” from this requirement. If there is no statement regarding a “CPRS enrollment note waived,” it is understood that you will flag your subject’s medical records. The patient health record must be flagged if the subject’s participation in the study involves:

Any invasive research procedure (e.g., muscle biopsy or bronchoscopy) Interventions that will be used in the medical care of the subject, or that could interfere

with other care the subject is receiving or may receive (e.g., administration of a medication, treatment, or use of an investigational device.)

Clinical services that will be used in the medical care of the subject (e.g., orders for laboratory tests or x-rays orders as part of the study), or that could interfere with other care the subject is receiving or may receive

The use of a survey or questionnaire that may provoke undue stress or anxiety unless the IRB determines that mandatory flagging is not in the best interests of the subject (e.g., an interview study of victims of sexual assault.)

If the IRB determines that the patient health record must be electronically flagged in CPRS as participating in a research study, then the record must include:


Identify the investigator, as well as contact information for a member of the research team that would be available at all times.

Contain information on the research study or identify where this information is available.

e) Researcher Contact with Veterans During the recruitment process, the research team must make initial contact with the potential subject in person or by letter prior to initiating any telephone contact, unless there is written documentation that the subject is willing to be contacted by telephone about the study in question or a specific kind of research (e.g., if the potential subject has diabetes, the subject may indicate a desire to be notified of any diabetes-related research studies). The initial contact must provide a telephone number or other means that the potential subject can use to verify the study constitutes VA research.

NOTE: One source of information about clinical trials that can be shared with potential subjects is the NIH clinical trials Web site (http://www.clinicaltrials.gov) where VA clinical trials are listed.

f) Vulnerable Populations: The VHALON recognizes the following as vulnerable subjects:

Adults with cognitive impairments Mentally retarded/impaired People likely to need surrogate consent (incompetent, ventilator, etc) Persons with psychiatric disorders Non-English speaking people Economically disadvantaged Terminally ill patients Prisoners Employees Students/Trainees Homeless/Shelter Pregnant women/Fetuses/InVitro Fertilization

Staff will need to document any review of additional safeguards to protect the rights and welfare of subjects who are likely to be susceptible to coercion or undue influence. The IRB is here to protect human subjects from exploitation and harm and, at the same time, make it possible to conduct essential research on problems that are unique to persons who lack decision-making capacity (e.g., a study of treatment options for comatose persons can only be performed with persons who lack decision-making capacity). Persons who lack decision-making capacity are not to be subjects in research simply because they are readily available. Please reference the VHA Handbook 1200.05 for information regarding each specific population and their specific requirements.

g) Research Record Keeping: Investigators should always contact study sponsor prior to disposal of documentation. All records must be retained according to the requirements of the VA Records Retention Schedule or the study sponsor, whichever is longer. Disposal of records must be approved by, and arranged through, the Research office. Investigators are responsible for contacting and securing approval from study sponsors.


Once the study has been completed: When the sponsor has completed the final review, and the study staff has submitted the study for closure to the IRB, they will need to contact the Research Compliance Officer for a final audit. Once everything has been cleared by the sponsor, the IRB and the Research Compliance Officer, the staff can pack the research material into Iron Mountain boxes and contact SCIRE for a pick up time. Since this is an expensive process, and one that will cost to retrieve the boxes once shipped, please confirm everything is completed before sending to Iron Mountain.

All IRB records will be retained for the time prescribed by the National Archives and Record Administration as published in the VHA’s Records Control Schedule (RCS 10-1) (http://vaww.va.gov/vhapublications/rcs10/rcs10-1.pdf) These requirements include: IRB Protocol Files: IRB files related to the review and oversight of research protocols submitted by VA investigators for research conducted at the field facility. Records include, but are not limited to, the application to the VA Central IRB; research protocol and amendments; case report forms; reports of adverse events, complaints and deviations from the approved protocol; data and safety monitoring reports; research findings to date; and all relevant documents and related correspondence between the committee and the investigators in the review of an associated protocol.

Protocol files that are approved are retained 6 years after the cut-off (The end of the fiscal year after the research project has been completed or terminated)

Protocol files that are disapproved or withdrawn destroy in 3 years after cut-off (the end of the fiscal year after the research project has been disapproved or withdrawn)

The FDA has their own requirements to keeping records here at the VALBHS. These requirements are regarding the records you will store here at VALBHS. Once their specified time as passed, you will still need to store the data at Iron Mountain indefinitely.

For research involving drugs, the FDA requires the investigator to retain the records on site for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or if the application is not approved for such indication, until 2 years after the investigation is discontinued and the FDA is notified.

For investigational devices, the FDA requires retaining records for the latter of the following dates: The date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a premarket approval application or a notice of completion of a product development protocol.

Because of the difficulty in ascertaining these dates and varying sponsor requirements, the investigator is strongly advised to consult their research/funding source for any additional information.

h) Regulatory Binders: Most sponsors will provide the staff with regulatory binders. If you do not have a sponsor, it is still required for you to maintain a regulatory binder. Suggested contents: (depending on your study, you might not need all these options. The items in red are suggested be in every regulatory binder.) Note: As a reminder, any identifiable date must be stored in a locked cabinet, in a locked office, with only the study staff having access.

Study contact information (Sponsor/PI/Research Staff)


http://vaww.va.gov/vhapublications/rcs10/rcs10-1.pdf

Copies of approved protocols Copies of protocol amendments Copies of approved investigator brochures Sponsor visit log Delegation of authority Subject screening and enrollment forms FDA requirement forms IRB approved consent forms IRB approval Memos R&D approval memos IND Safety reports Adverse event reports/forms Laboratory ranges/certificates Protocol deviations Notes to File IVRS Site staff training records Financial disclosure forms Sponsor correspondence IRB correspondence Monitor correspondence Miscellaneous Recruitment materials HIPAA authorization documents (or documentation of waiver of HIPAA authorization) Any proposed amendments and the IRB action on each amendment Significant new findings. Statements of significant new findings provided to subjects Subject complaints Summaries of DMC findings

i) Enrollment of Non-Veterans: VA research needs to be relevant to Veterans or active duty military personnel. The investigator must justify including non-Veterans in a VA research protocol, and the IRB must review the justification for inclusion of non-Veterans and specifically approve entering non-Veterans into the study before any non-Veterans can be recruited. Non-Veterans may be entered into an approved VA research study when the investigator can present a compelling argument to the IRB for the inclusion of non-Veterans (e.g., insufficient number of Veterans; survey of VA employees; study of active duty military; study involving Veterans’ family members), and the research is relevant to the care of Veterans or active duty military personnel. Please see section (d) above (Flagging of Medical Records for Research Subjects) for information for Non-Vets CPRS notes.

j) Clinical Trials.gov: It is the investigator’s responsibility to register the research study with www.clinicaltrials.gov. The IRB will ask the investigator to confirm that he/she has confirmed the study has been registered. Most


http://www.clinicaltrials.gov/

sponsors will register the study; however investigator-initiated studies will need the investigator to register it.

k) Data Security and Privacy: Anyone performing duties for the VA including Principal Investigators, Research Coordinators, Research Assistants, students, contractors, WOCs and volunteers are required to complete the Privacy and Security Training. Please reference the “Requirements for completed HST&C” section in the “Training and Credentialing” section.

All identifiable data needs to be kept in a locked cabinet in a locked office with only the research staff listed on the application having access. Any electronic data needs to be saved onto the research “S” drive. You can contact the research office on information on how to access this drive.

To facilitate review of the protocol by the Information Security Officer (ISO), the investigator must either dedicate specific sections of the protocol to information security, or the investigator must develop an additional document that specifically addresses all information security issues in the protocol. This document becomes part of the IRB protocol file. The plan must clearly identify and include, but not limited to:

Whether or not individually identifiable information is to be collected or used How the data is to be collected or acquired Where the data (original and all copies) is to be stored and corresponding security systems How the data is to be transported or transmitted from one location to another Who is to have access to the data and how they are to access it (anyone who has access to the

data is responsible for its security) All entities or individuals outside VHA to whom the data is to be disclosed, and the justification

for such disclosure and the authority (e.g., the HIPAA authorization) Who is to have access and be responsible for the security of the information (e.g., the

Coordinating Center, the statistician, the PI who has ultimate responsibility) Mechanisms used to account for the information Security measures that must be in place to protect individually identifiable information if

collected or used A suspected or confirmed loss of VA information is to be reported to the ISO and AO, R&D as

soon as possible.

Any data (identifiable or coded or de-identifiable) may never leave the VA without approval from the IRB, the ISO and/or the PO. Please contact the research office on information on how to receive approval.

l) Coded vs De-Identified Data: De-identified data: refers to data that have been stripped of all subject identifiers, including all

18 HIPAA identifiers. This means that there can be no data points that are considered limited identifiers under HIPAA, i.e. geographic area smaller than a state, elements of dates (date of birth, date of death, dates of clinical service), and age over age 89. If the data set contains any limited identifiers, it is considered a limited data set under HIPAA. If the data includes an indirect link to subject identifiers (e.g. via coded ID numbers), then the data is considered by the IRB to be coded, not de-identified


http://hipaa.wisc.edu/ResearchGuide/limiteddatasets.html

http://hipaa.wisc.edu/ResearchGuide/limiteddatasets.html

Please note that data can be considered de-identified under the Common Rule but NOT the HIPAA Privacy Rule

Coded data: this refers to data that have been stripped of all direct subject identifiers, but in this case each record has its own study ID or code, which is linked to identifiable information such as name or medical record number. The linking file must be separate from the coded data set. This linking file may be held by someone on the study team (e.g. the PI) or it could be held by someone outside of the study team (e.g. researcher at another institution). A coded data set may include limited identifiers under HIPAA. Of note, the code itself may not contain identifiers such as subject initials or medical record number.

The 18 HIPAA Identifiers: 1. Names2. All geographical subdivisions smaller than a State, including street address, city, county, precinct, zip code, and their equivalent geocodes, except for the initial three digits of a zip code, if according to the current publicly available data from the Bureau of the Census: (1) The geographic unit formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and (2) The initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000.3. All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older;4. Phone numbers;5. Fax numbers;6. Electronic mail addresses;7. Social Security numbers;8. Medical record numbers;9. Health plan beneficiary numbers;10. Account numbers;11. Certificate/license numbers;12. Vehicle identifiers and serial numbers, including license plate numbers;13. Device identifiers and serial numbers;14. Web Universal Resource Locators (URLs);15. Internet Protocol (IP) address numbers;16. Biometric identifiers, including finger and voice prints;17. Full face photographic images and any comparable images; and18. Any other unique identifying number, characteristic, or code (note this does not mean the unique code assigned by the investigator to code the data)

m) Advertising :


All recruitment flyers or advertisements must be approved by the IRB. Unapproved postings could give Veterans or visitors the impression that it is VA approved research or is endorsed by the VA or that the VA will pay any research-related expenses that occur. General information can be posted advising patients who to contact for questions about research activities and/or listing the informational website: www.clinicaltrials.gov.

If you would like to post a VALBHS approved flyer, you will need to obtain approval from the department in which you would like to post it. Use of tape on hospital walls is not permitted. You will need to post your flyer on an approved space (usually a pin board or bulletin board). Flyers that are approved by the VALBHS IRB will have an IRB approval stamp on it or the study is a CSP study. If you see a research flyer that does not have an IRB approval stamp or is not a CSP study, please remove and bring the research office.

In situations where all of the research activities occur outside of the VA, the IRB must still be assured that the protocol and consent form from the other institution are adequate for these purposes; if not, it may request that the investigator process a modification through the IRB of the other institution. VA facilities may post/distribute recruiting documents, flyers, and advertising for research that is not VA research within or on the premises of a VA facility following review and approval by the IRB. In considering approval the IRB will determine if the activity is of benefit to VA patients, does not conflict with ongoing VA research and does not otherwise adversely affect the VA or VA investigators. General information can be posted advising patients who to contact for questions about research activities and/or listing the informational website: www.clinicaltrials.gov. Facebook or other social media may not be used to advertise non-VA studies. n) Creating a Clinic in CPRS: As soon as your study has been approved by the IRB, you can open a Clinic in CPRS. All medical notes regarding your study, should reference this clinic. You can find the “Clinic Request Form” on the SCIRE website. The study staff will need to complete the form, have the PI sign and then submit the research office. From there, the ACOS assistant will obtain the other required signatures then send it to Build-a-Clinic. This process will take a couple days, and once completed the ACOS assistant will contact you to inform you that the clinic has been opened.

As soon as you close your study, please submit the same form to the research office, but check the “Inactivation Request” option instead. It will be the responsibility of the research staff to keep their clinics up to date. The clinic will need to be set up prior to scheduling your first subject for your study. Please keep that in mind, as this process does take a couple days to complete.

The ACOS assistant will email the study staff with any clinic issues. These issues are mainly not completed CPRS notes. Please complete the requests as soon as possible.

If the procedure required will take more than one day to complete, a completion note will need to be completed in the subjects CPRS file.

o) Dual Enrollment




Simultaneous enrollment in more than one therapeutic research study is not permitted unless the IRB determines that such dual enrollment does not significantly increase the risks or discomfort to subjects and will have no conceivable medical or scientific impact on the studies involved. The IRB will only consider the granting of dual enrollment if:

The sponsors of all projects involved have given consent. The IRB has determined that one of the studies is of minimal risk and has no conceivable

medical or scientific impact on any other studyResearch subjects may be enrolled in multiple studies if the additional studies are non-therapeutical (e.g., registries, observational, single blood draw).

It is the responsibility of the PI to confirm with the subjects medical record that the subject is not enrolled in another study. It is suggested that the PI submit a memo to the IRB with the following information:

Brief description of both studies If any potential harm enrolling in both studies Confirmation that both PI’s are aware of the dual enrollment

p) Impact Estimation Worksheets: All 3 IEWs submitted at the initial review are reviewed by the department that is listed on the form. The 3 IEW submitted are:

Pharmacy Services Pathology & Laboratory Radiology

These forms inform the lab/pharmacy what tests/drugs will be neeed to be billed to the subject, which need to be billed to the sponsor and which is the responsibility of the VA. This needs to be approved BEFORE any tests are completed and/or any drugs dispensed. Every IEW is signed off by the Chief of the department. These signatures are obtained by the research office.

Please review the “Research Pharmacy” section below for information regarding any Pharmacy Services issues.

q) Data Safety Monitoring (DSM) Data Monitoring Committee (DMC), Data and Safety Monitoring Board (DSMB), or (Data and Safety Monitoring Committee (DSMC). A DMC, DSMB, or DSMC is a group of individuals with relevant expertise that reviews accumulating data from one or more ongoing research studies. The DMC, DSMB, or DSMC independently advises the sponsor or the principal investigator (PI) regarding the continuing safety of the research study’s subjects, as well as the continuing validity and scientific merit of the study. DMC, DSMC, and DSMC are considered synonymous for the purposes of this form.

After a DSM meeting, the sponsor should send the study staff the outcomes. This report will need to be submitted to the IRB. Most sponsors include all the DSMB information in the protocol.

Investigators are required to provide in the research plan adequate provisions to monitor the data to ensure the safety of participants including a description of the following information with the application for Initial Review:


Description of the data or events that will be captured under the monitoring plan including SAE’s.

Description of who will gather, evaluate and monitor the data. Provide evidence of a DSMB or DSMC if such is required. Provide a summary of the functions of

such a board or committee. Description of who will verify the accuracy of the data collected Description of the frequency of monitoring and how often the collected data are evaluated. Description of the triggers that will dictate when some specified action is required. Description of how interim reports will be disseminated if the study involves multiple sites. If there is no DSMB or DSMC, and if applicable, statistical tests may be required for analyzing the

safety data to determine if harm is occurring. Conditions that trigger an immediate suspension of the research, if applicable.

r) Study Monitor Process: Before the Visit: Before your study monitor visit, inform the research office of the visit along with the location of the monitoring (Bldg # and Rm #) via email. If the monitor requests to meet with the Research Pharmacist, please schedule a meeting prior to the day.

Day of the Visit: Please escort the monitor to (or meet them in) the research office. Confirm they complete the “External Site-Monitoring Visit Log” correctly and completely. Then escort the monitor to the police badge office (Bldg 162 Rm #) for a temporary badge.

After visit: Complete the “Site Monitoring Memo” form and submit to the IRB office.

If the monitor requests computer access or access to Patient Identifiable Data:The monitor will need to complete the required training BEFORE the visit. The monitor will need to submit copies of the completed certificates to the research office when they sign in. These certificates will be filed here in the research office and a copy should be in the regulatory binders as well.

Required Training: Privacy and HIPAA Training & VA Privacy and Information Security Awareness and Rules of Behavior. Both of these can be found on the TMS website: https://www.tms.va.gov/learning/user/login.jsp

s) Categories of Action: The IRB has the authority to take one of the actions outlined below after reviewing a research proposal. Except when the expedited review process is used, these actions will be taken by a vote of a majority of the voting members present (including qualified alternates), except for those members present but unable to vote in accordance with IRB's conflict of interest policies.

Approval: The protocol and accompanying documents are approved as submitted. The standard conditions of approval, as described in Section 602C will be clearly stated in the approval letter.

Conditionally Approved: At the time when the IRB reviews and approves a research study (or proposed changes to a previously approved research study), the IRB may require, as a condition of approval, that


https://www.tms.va.gov/learning/user/login.jsp

the investigator (a) make specified changes to the research protocol or informed consent document(s), (b) confirm specific assumptions or understandings on the part of the IRB regarding how the research will be conducted, or (c) submit additional documents, such that, based on the assumption that the conditions are satisfied, the IRB is able to make all of the determinations required for approval.

Table: If the IRB cannot make all of the determinations required for approval, the IRB must not approve the research project. This applies to both initial and continuing review of research, and review of proposed changes to previously approved research. Conditions to have the study be re-reviewed by the IRB will be sent to the PI.

Disapproved: When the convened IRB is unable to approve research because it cannot make the determinations required for approval, the IRB can either disapprove the project, or defer or table the project for further review at a future date.

Suspension or termination: The IRB has the authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's policies or that has been associated with concerns regarding the safety, rights, or welfare of human research subjects, investigators, research staff, or others.

Actions that may result in a suspension or termination include but are not limited to: Unanticipated problems that involve risks to subjects or others. Serious or Continuing Non-compliance Failure to Obtain appropriate Informed Consent Change in risks in relation to benefits

Section 3: Initial/Continuing/Closure Process:

a) Initial Process: New Investigators: Only individuals who are VALBHS employees or have a VALBHS appointment may serve as Principal Investigator. Investigators with part-time or WOC appointments may be required to document that they will have a sufficient presence at VALBHS to adequately conduct the planned research. Investigators without an appointment at VALBHS or an adequate on-site presence will be asked to submit the project with a Principal Investigator from the VALBHS. An investigator cannot submit a project unless it has been documented that the investigator has completed the HST&C. If the investigator fits this role, he/she will need to submit their resume to the research office and a memo requesting to be a Principal Investigator and explaining that he/she has “a sufficient presence at VALBHS to adequately conduct the planned research.” This will be reviewed at the next R&D meeting. It is strongly suggested to complete all of the Human Subjects Training and Credentialing before this time.

Here is some information regarding the required forms to submit a new human study at the VA Long Beach Healthcare System. Refer to the Initial Submission Checklist (item #1) for additional requirements. If you have any questions about the study submission, we will be happy to assist you. In addition to these documents, there are human subject training requirements that must be met by all individuals working on the study. Please contact Valerie Viramontes (ext. 5801) if you need guidance with training requirements.


Required Forms:1. Initial Submission Checklist2. RDIS3. Abstract (Emailed to IRB Assistant as well) 4. Prospectus5. Safety Survey6. Application for IRB Review7. Research Data Inventory Tool8. Impact Estimation Worksheets - (*Note: all must be filled out and signed even if not using

service)a. Radiology b. Pharmacyc. Pathology

All current versions of the IRB forms can always be found on the SCIRE website at:http://scire-lb.org/valbhs/research/clinical/forms.htm

Once you have submitted your new project to the IRB office, we will do a quick review. The main thing we look for at first is if all forms are signed and you have used all the current versions. Once we have done a quick review, we then make 3 copies of your submission. 3 different people then review your project. These people are: 1) An IRB Pre-Reviewer 2) The Information Security Officer and 3) The Privacy Officer.

The IRB Pre-Reviewer is looking for things that the IRB will have an issue with. They closely look at your submission to ensure that everything is consistent and filled out completely.

The Information Security Officer will review forms regarding to Veterans information security. How you store your data and where you are sending your results are very important to the ISO. Please explain each question fully and completely.

The Privacy Officer will be mainly looking at the Consent form and the HIPAA Autho. Please be consistent with your answers.

When all 3 of the “pre-reviewers” have reviewed your submission, they will email us. Once we have received all reviews, we will then combine all of their comments and send you one large email. While all of this is going on, your safety survey is being reviewed as well as your impact estimation worksheets. When you have re-submitted the changes to us, we will then contact the pre-reviewers, and ask them to re-review your submission. Once we have received the final approval by all reviewers, it will then be on the next available IRB agenda.

Departments that will review your submission: - Feasibility Phase

o Information Security Officer o Privacy Officer o IRB Pre-Reviewer o Pharmacy Chief of Staff


http://scire-lb.org/valbhs/research/clinical/forms.htm

o Radiology Chief of Staff o Pathology Chief of Staff o HRPP Administrator

- Full Committee Review: o IRB Committee o R&D Committee o Bio-Safety Committee

Due to the amount of entities that are required to review every study submitted to the IRB, please allow 4-6 weeks for the “feasibility phase” to be complete.

When all of the “pre-reviewers” have reviewed the submission, they will email the research office. Once all reviews are received, the IRB Assistant will then combine all of their comments and send the staff listed on the application one large email to the PI. While all of this is going on, the safety survey is being reviewed as well as the impact estimation worksheets. When the PI has re-submitted the changes to the research office, the pre-reviewers will be asked to re-review the submission. Once the IRB Assistant has received the final approval by all pre-reviewers, it will then be on the next IRB agenda.

b) Continuing Review Process: It is the PI’s responsibility to supply a list of patients to the Patient Business Office. Please contact that department for further instructions. All studies must be reviewed (at least) on an annual basis. Depending on the risk level, some studies will be reviewed more frequently. Continuing review materials must be submitted in a timely manner to provide IRB sufficient time for reviewing and approving the study before IRB approval expires. IRB approval automatically expires if the continuing review and approval does not occur by the expiration date of the current approval.

The staff listed on the study will be reviewed to ensure HST&C has been completed. If this requirement is not completed by the review time, the study may be put on hold until it is completed. Please contact the research office to check on staff.

The research office will contact the PI and study staff roughly 3 months prior to your expiration date requesting the continuing review submission. Once the submission is reviewed by the IRB, an approval memo will be produced and sent to the staff listed on the study.

c) Study Closure: Once the research has been completed, the PI will need to submit for study closure. It is suggested that this not be completed until the sponsor has completed their final review. When the closure forms are submitted, the staff will need to contact the RCO to schedule a final audit. Since none of the research material can be destroyed (please refer to section 1.8 above), the PI will need to contact SCIRE to coordinate an Iron Mountain pick. Please wait until the IRB and R&D has officially closed the study to before sending any data off site.

d) Expiring Studies: Lapse: A condition that exists when a study has failed to be re-approved within the time frame that was specified at the time of the previous approval. Unlike suspensions and terminations, a lapse results from a failure to act, by either the investigator or the IRB, rather than as a result of an IRB action. All


research activities must stop except for the continuation of follow-up activities necessary to protect the participants’ safety. Unlike suspended studies, lapsed studies are not approved. Unlike terminated studies, lapsed studies may be re-approved.

Studies that have lapsed in approval before Continuing Review by the IRB are unapproved until the IRB review has been conducted. The investigator will be promptly notified of the lapse in approval by the Research Office via a memorandum from the Chair of the IRB. The PI will be notified that enrollment for new subjects cannot occur and continuation of research interventions or interactions in already enrolled subjects should only continue when the IRB or IRB Chair, in consultation with the Chief of Staff finds that it is in the best interest of individual subjects to do so. Once notified of the suspension, the PI must immediately submit to the IRB Chair a list of research subjects for whom suspension of the research would cause harm. The IRB Chair, with appropriate consultation with the Chief of Staff, determines if the subject may continue in the research. If the study is FDA -regulated, the Chief of Staff and IRB Chair must follow FDA requirements in 21 CFR 56.108(b)(3) in making their decision. It is the responsibility of the Principal Investigator to notify the sponsor of the lapse in approval. The Research Office will notify ORD, ORO or other Federal agencies as appropriate. Once suspended, IRB review and re-approval must occur prior to the initiation of the research. The Chair will notify the ACOS/R&D and the RCO immediately of any such study expiration and the actions taken.

The expired study will be reviewed at the next convened IRB meeting. The investigator will be required to submit the required reports and to indicate whether any research activity occurred after the expiration of the study. If the study is not re-approved within 3 months then it must be resubmitted as a new study. The IRB will also make additional provisions for the care and protection of subjects as may be required, or require third party verification that the investigator has complied with its requests. The IRB may take any of the actions or sanctions against the investigator that are available to it, according to the procedures described in section QA 903. In all cases the IRB will solicit and review appropriate completion paperwork, make inquiries to assure that subjects have been protected and that research does not continue without approval.

Section 4: Consent/HIPAA/Waiver:Note: Every study will have a consent/HIPAA audit, completed by the RCO at the time of continuing review. The PI is required to submit signatures pages of the ICF, HIPAA Authorization and CPRS enrollment notes when the continuing review forms are submitted to the IRB.

a) Informed Consent General Information: An investigator may not involve a human being as a participant or subject in non-exempt research the VALBHS oversees unless the investigator or the investigator's designee obtains the informed consent of the person or the person's legally authorized representative, except when the requirement for obtaining such consent has been waived by the VALBHS IRB.

Circumstances Under Which Informed Consent May Be Sought: The Common Rule requires:

o The investigator to seek informed consent only under circumstances that: Provide the prospective subject or the subject’s LAR sufficient opportunity to

read the informed consent document when applicable


Provide the prospective subject, or the subject’s LAR, sufficient opportunity to consider whether or not to participate

Minimize the possibility of coercion or undue influenceo The information that is given to the subject or the subject’s LAR must be in language

understandable to the subject or the subject’s LARo No informed consent, whether oral or written, may include any exculpatory language

through which the subject or the subject’s LARo Is made to waive, or appear to waive, any of the subject's legal rightso Releases, or appears to release, the investigator, the sponsor, the institution, or its

agents from liability for negligence Designating Responsibility for Obtaining Informed Consent: If the PI does not personally obtain

informed consent, the investigator must formally and prospectively designate to another research team member in writing the protocol or the application for IRB approval the responsibility for obtaining informed consent, whether or not a waiver of documentation of informed consent has been approved by the IRB. This designee must be a member of the research team.

Documentation of Informed Consent: When documentation of informed consent is not waived by IRB, the investigator or designee must ensure the documentation is in accordance the Handbook and includes:

o The signature and date of the subject or the subject’s LARo The signature and date of the person obtaining the informed consento The signature of the witness and the date of the subject’s or LAR’s signature was

witnessed, when applicable.o Bears the “IRB Approval” stamp with an appropriate date.

Storage: The investigator must ensure all original signed and dated forms are in the investigator’s research files (here at VALBHS), readily retrievable, and secure.

LAR: An individual who is qualified to be a LAR for research purposes may not always qualify as a personal representative for purposes of consenting to use or disclose a living subject’s PHI (i.e., signing a HIPAA authorization). Therefore, in circumstances involving authorization for use or disclosure of a subject’s PHI, the investigator must ensure the LAR meets the requirements of a personal representative in HIPAA and the Privacy Act of 1974 (legal guardian or power of attorney) prior to the LAR’s signing a HIPAA authorization (see VHA Handbook 1605.1).

Investigator Responsibilities:It is the expectation of the VALBHS IRB that, when appropriate, investigators are responsible for:

Ensuring that informed consent is provided by a participant or a participant's legally authorized representative prior to conducting any research activities with the subject in accordance with the requirements of this standard operating procedure, as well as VA and other federal requirements. The only exceptions are if the VALBHS IRB determines the research is exempt or if a waiver of informed consent is approved by the VA Central I RB for the project or a portion of the project.

Creating an informed consent document containing all required basic elements, as well as any additional elements as applicable, for the participant populations that will be enrolled and describing the type of research that will be conducted. The investigator will obtain approval of this document from the VALBHS IRB prior to initiating any research activities or enrolling any participants.


Ensuring that such informed consent is appropriately documented using the most current version of the VALBHS IRB-approved consent form unless a waiver of documentation of informed consent has been approved by the VALBHS IRB.

Ensuring that all members of the investigator's project team who seek informed consent are appropriately qualified and trained to perform this function. The investigator must indicate on the VALBHS IRB Application a plan for training study team members who will be obtaining the informed consent and designate in writing those members of the study team who are authorized and qualified to obtain informed consent.

Maintaining documentation of informed consent in accordance with VA requirements, to include keeping a copy of the signed informed consent document in the research study file, as well as forwarding a copy for file in the subject's medical record if applicable.

Appropriately requesting a waiver (or partial waiver) or alteration of the informed consent process when needed or required by the study design.

Appropriately requesting a waiver of documentation of informed consent, when needed or required by the study design.

Ensuring the informed consent process clearly defines for the research participant which potential risks are related to the research and must be thoroughly discussed as part of the consent process versus those solely related to the usual care provided by the participant's health care provider. The investigator must ensure that the informed consent process contains language advising participants to review the risks of usual care with the participant's health care provider.

Ensuring that appropriate HIPAA authorization has been obtained, when required, by only those personnel designated in writing on the VALBHS IRB application as qualified to obtain informed consent. The investigator must ensure that the HIPAA authorization is consistent with the informed consent form, the protocol, and the VALBHS IRB

Requirements of all ICFs: The following are the required elements that must be in all informed consent forms submitted to the VALBHS IRB:

The name of the project, the name of the sponsoring organization, and the name of the Principal Investigator (Pl). For multisite studies that involve submission of Local Site Investigator Applications, both the name of the Pl and the LSI must be provided on the informed consent documents for a particular site.

A statement that the project involves research and an explanation of the purposes of the research

The expected duration of a participant's active participation, to include long-term follow-up, and the approximate number of participants to be involved in the project.

A description of the procedures to be followed, identifying any procedures which are going to be performed solely for research purposes and/or any procedures that are experimental.

A description of any reasonably foreseeable risks or discomforts to the participant to include but not limited to physical, social, legal, economic, psychological, and any privacy risks that may result from the research. Risks of usual care are not to be included and the participant must be advised to discuss these with the participant's health care provider.

A description of the potential benefits to the participant or to others that may reasonably be expected from the research.


A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the participant. If the only alternative is not to participate, this element does not need to be included in the consent form.

A statement describing the extent to which confidentiality of any records identifying the participant will be maintained. If appropriate, a statement that other federal agencies including but not limited to the VHA Office of Research Oversight (ORO), the Office for Human Research Protections (OHRP), and the Government Accountability Office (GAO) may have access to the records. If an FDA-regulated test article is involved, there must be an additional statement indicating the FDA may choose to inspect research records that include the participant's medical records.

For research involving more than minimal risk, an explanation as to whether any compensation and/or any medical treatments are available from the VA if injury occurs; what those treatments consist of; what the VA's authority is to provide such treatment; and where further information can be obtained.

An explanation of whom to contact with questions about the following: the research process; concerns, or complaints about the research; the research participant's rights in the event of a research-related injury; and to verify that the project in question is a valid VA project. The contact's name and phone number for questions about the participant's rights and whom to contact to verify that the project is a valid VA project, must be someone knowledgeable but not affiliated with the specific research project. The VALBHS IRB number will be included.

A statement that participation is voluntary and that refusal to participate will involve no penalty or loss of benefits to which the participant is otherwise entitled and that the participant may discontinue participation at any time without penalty or loss of benefits to which the participant is otherwise entitled.

A statement that a Veteran participant will not be required to pay for care received that is part of a VA research project. They will, however, be required to pay any co-payments they would ordinarily be required to pay for any non-research related VA medical care and/or services.

Note: For complete list of all ICF required elements & documentation & responsibilities (based on study design) please look at IRB SOP Section IC701.

b) HIPAA Authorization: The HIPAA Authorization is a stand-alone document (i.e., it may not be embedded within the Informed Consent Document). A written HIPAA authorization signed by the individual to whom the information or record pertains is required when VA health care facilities need to utilize individually-identifiable health information for a purpose other than treatment, payment, or health care operations.

Written authorization for the disclosure of information is required when: VA health care facilities need to utilize individually-identifiable health information for purposes

other than treatment, payment, and/or health care operations and other authority, as specifically noted by VHA Handbook 1605.1 does not exist.

VA health care facilities disclose information for any purpose where other legal authority does not exist

VA health care facilities conduct marketing except when communicated face-to-face to an individual


VALBHS investigators must obtain written authorization or a waiver of the authorization requirement from the IRB for using VHA individually-identifiable health information involving non-employee research subjects for research purposes. IRB does not approve a HIPAA authorization but ensures the protocol and informed consent form are consistent with the HIPAA authorization. When PHI must be reviewed or recorded prior to obtaining authorization from the subject, the IRB (Privacy Board) must have granted a waiver of authorization.

This form is reviewed by the Privacy Department at the initial submission. If any major changes are requested from the PI, the IRB will first request the PO to review the modifications. Once approved by the PO, the modification will then be reviewed by the IRB.

Authorization may be given by: The individual A court-appointed legal guardian. An individual who has written authorization to act on the individuals behalf (e.g. power of

attorney) The executor of Estate, next-of kin, or anyone with a significant personal relationship to the

individual (as defined by VHA 1605.1) if the individual is deceased.

As HIPAA is an extremely complex regulation, please refer to Handbook 1200.05, the IRB SOP, the Privacy Officer or the Research Office if you should have any concerns.

Required Elements: HIPAA Privacy rule authorization must be in plain language and must include:

The identity of the individual to whom the information pertainsO Investigators can obtain and use real Social Security numbers (SSNs) only when

real SSNs are required to meet the specific aims of the research protocol or to enter information into the subjects’ health records

O The collection and use of real SSNs must be approved by the IRB, and the investigators must follow all applicable VA and other Federal requirements for obtaining and using real SSNs.

A description of the information to be used or disclosed that identifies the information in a specific and meaningful fashion. If HIV, sickle cell anemia, drug and/or alcohol abuse treatment information is to be disclosed this information must be specifically identified in the discussion.

The name or other specific identification of the person(s), class of persons, or office designation(s) authorized to make the requested use or disclosure.

The name or other specific identification of the person(s), class of persons, or office designation(s) to whom the agency may make the requested use or disclosure.

A description of each purpose of the requested use or disclosure. The statement “at the request of the individual” is sufficient when an individual initiates the authorization and does not, or elects not to provide a statement and does not, or elects not to, provide a statement of the purpose.

An expiration date or event that relates to the individual or the purpose of the use or disclosure. Examples of appropriate expiration date language are as follows:


O The statement “end of the research study” or similar language is sufficient if the authorization is for use or disclosure of individually-identifiable health information for research.

O The statement “none” or similar language is sufficient if the authorization is for the agency to use or disclose individually-identifiable health information, including for the creation and maintenance of a research database or research repository.

The signature of the individual, or someone with the authority to act on behalf of the individual, and date signed.

A statement that the individual has the right to revoke the authorization in writing except to the extent that the VHA has already acted in reliance on it, and a description of how the individual may revoke the authorization (e.g., to whom the revocation is provided). For a use or disclosure of individually identifiable health information related to research the statement “end of the research study”, “none”, or similar language is sufficient.

A statement that VHA may not condition treatment, payment, enrollment, or eligibility for benefits based upon the individual completing an authorization.

A statement that individually identifiable health information disclosed pursuant to the authorization may no longer be protected by Federal laws or regulation and may be subject to re-disclosure by the recipient.

c) Waivers: HIPAA Waiver: A request from an investigator for the IRB to waive the HIPAA authorization must be accompanied by sufficient information to allow the IRB to make the required determination. This documentation must include, but is not limited to, all of the following:

The use or disclosure of the requested information involves no more than minimal risk to the privacy of individuals based on, at least, the presence of the following elements:

o An adequate plan to protect the identifiers from improper use and disclosureo An adequate plan to destroy the identifiers at the earliest opportunity consistent with

conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention is otherwise mandated by applicable VA or other Federal requirements

o Adequate written assurances that the requested information will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study, or for other research for which the use or disclosure of the requested information would be permitted by the Privacy Rule

The research could not practicably be conducted without the waiver The research could not practicably be conducted without access to and use of the requested

information A brief description of the PHI for which the IRB has determined use or disclosure to be necessary The specific findings on which the IRB based its decision to grant the waiver of HIPAA

authorization


Identification of the IRB review procedure used to approve the waiver of HIPAA authorization (either convened IRB review procedures (see par. 13 and 38 CFR 16.108(b)) or expedited review procedures (see par. 21 and 38 CFR 16.110)

Signature of Chair of the IRB, or qualified voting member of the IRB designated by the Chair, on the HIPAA authorization waiver document

Recruitment Waiver: All of the following conditions must be met and justified in order for the IRB to grant a waiver of authorization for the sole purpose of recruitment and screening. If you have any questions about the form or process, contact the IRB Office at (562) 826-5801. The IRB will make the final determination as to whether the conditions have been justified. If you wish to review CPRS records in order to determine appropriateness or eligibility for research, or if you will record PHI from respondents to advertisements with identifiers, without the written authorization of the patient you must request a waiver of authorization for recruitment and screening purposes. Answer N.A. if you do not require this or answer the following questions in order to obtain a waiver of authorization for this specific purpose.

Section 5: Tissue Banking vs Long Term Storage:A human biological specimen is any material derived from a human subject-such as blood, urine, tissues, organs, hair, nail clippings, or any other cells or fluids-whether collected for research purposes or as residual specimens from diagnostic, therapeutic, or surgical procedures. No patient identifiers can be sent off-site.

It is strongly advised to contact the Research Office prior to submission for guidance. Some of the forms that need to be completed need to be sent to Central Office. {Reference: http://www.research.va.gov/programs/tissue_banking/default.cfm}

Definitions: Tissue Banking: Samples are retained for future use in, as yet specified, research. Long Term Storage: Samples used for only the specific purposes as defined in the protocol and are destroyed either when the specific testing/use is completed or at the end of the protocol.

a) Collecting and Storing Specimens for Secondary or Future Research Guidance for collecting and storing human biological specimens for future research purposes that are beyond the scope of work described in the original protocol and informed consent or those collected under a protocol designed for banking of specimens are as follows:

A waiver is not needed if human biological specimens are banked at a VA site. A waiver should be obtained from the Office of Research and Development (ORD) before the

specimens are banked if human biological specimens are stored for secondary or future research uses at a non-profit or academic institution. Please contact the Research Office for assistance in obtaining waivers.

Human biological specimens should not be stored for future or secondary research uses at, or on behalf of, a for-profit institution.


http://www.research.va.gov/programs/tissue_banking/default.cfm

b) Collecting and Storing Specimens for a Single Research Protocol Guidance for collecting and storing human biological specimens that are collected under a VA-approved protocol only for use for the specific purposes defined in the protocol and that are destroyed either when the specific testing/use is completed or at the end of the protocol are as follows:

If the protocol is 5 years or longer and the specimens are stored off-site at a non-profit institution until the end of the protocol, then the investigator should obtain a waiver from ORD.

If the specimens are stored off-site at a for-profit institution for greater than 3 months, a waiver should be obtained from ORD. With a waiver the specimens may be stored for up to 1 year after the study completion date, to perform batch analyses or to repeat analyses that are described in the protocol and informed consent.

c) VA-Approved Tissue Banks In the past, if a tissue bank was designated VA-approved, human biological specimens could be stored there for any protocol. Currently, an off-site tissue bank waiver should be approved for each protocol. We maintain a list of academic and non-profit tissue banks that have been approved for multi-site protocols. If you are planning to participate in a multi-site study, check with the Research Office to determine whether the protocol is on the list.

d) Exceptions: As a result of a letter of understanding with the National Cancer Institute (NCI), many NCI-sponsored cooperative tissue banks are designated as VA-approved if they are used for one of their protocols (for example, the SWOG-supported tissue bank can be used for SWOG protocols without a waiver from ORD). Please contact the Research Office for assistance.

Section 6: Research Pharmacy:The Research Pharmacist reviews the Impact Estimation Worksheet when you submit it at the initial submission. This form will inform the pharmacy how many subjects you intend to give drugs to. This needs to be approved BEFORE any tests are completed. Every IEW is signed off by the Chief of Pharmacy and the Investigational Studies Pharmacist.

Whenever you plan to use an investigational drug in a study, you will need to complete an Investigational Drug Information Record (IDIR) form. The research pharmacist will review this form and might require further information from you. This form will inform the pharmacy regarding your drug, like how you intend to store the drugs, which will dispense them, the phase the drug is in, special precautions and instructions, etc.

As soon as you find out about your study, you should contact the research pharmacist (if the study has drugs). Some sponsors send the protocol early; it is helpful if you email this to Penny. She will be able to help you complete the IDIRs and IEWs.

The majority of the studies are handles via IVRS systems and the patient has to be in the clinic before medication can be dispensed. The IVRS system will assign the specific bottle/kit, etc to the patent so it cannot be done ahead of time. The study staff will send the prescription to Penny (this can be done via fax if the staff is off location). The order will then be filled and study staff is contacted when the medication is ready for pick-up.


If your sponsor would like to meet with the research pharmacist at any time, this needs to be scheduled well enough ahead of time.

Section 7: Frequently Asked Questions:What exactly does the IRB review during their meetings? The IRB will review whatever you submit. This does include any memos you attach, or IBs or Protocols. Anything you submit the office, gets passed to the board to review.

Can I come to an IRB meeting? We do allow guests to come. The typical IRB meeting lasts anywhere from 3-4 hours. Any guests need to be approved prior to, by the IRB chair, at least 1 week before the meeting. This can be done by contacting the IRB coordinator. Coming to meetings can be very beneficial to new coordinators. New coordinators can get a better grasp on how the IRB works and what they find important.

What is PHI? Protected health information (PHI) is any information in the medical record or designated record set that can be used to identify an individual and that was created, used, or disclosed in the course of providing a health care service such as diagnosis or treatment. HIPAA regulations allow researchers to access and use PHI when necessary to conduct research. However, HIPAA only affects research that uses, creates, or discloses PHI that will be entered in to the medical record or will be used for healthcare services, such as treatment, payment or operations.

For example, PHI is used in research studies involving review of existing medical records for research information, such as retrospective chart review. Also, studies that create new medical information because a health care service is being performed as part of research, such as diagnosing a health condition or a new drug or device for treating a health condition, create PHI that will be entered into the medical record. For example, sponsored clinical trails that submit data to the U.S. Food and Drug Administration involve PHI and are therefore subject to HIPAA regulations.

Who gets a copy of the ICF after the subject signs it? The subject will receive a copy of it You will need to walk a copy down the Medical Record (located in the basement)

o Be sure to include the Subjects SSN and date of birth on the first page of the ICF. If the study has drugs, you will send a copy to the Research Pharmacist. Reminder : ALWAYS keep original in your regulatory binders, located in a locked cabinet in a

locked office with only study staff having access.

Can I recruit subjects from UCI (or another Non-VA site)? Yes, however you will need to request approval from the IRB. Also, are the subjects you plan to recruit Non-Veteran subjects? That would also require IRB approval, as well as whether or not the Non-Veteran subjects would require CPRS notes. Contact the research office if you have any concerns.


What is the average time from submission to fully approved study? On average, the entire approval process could take up to 10-12 weeks. This obviously depends on the severity of the study, and how well the required documents are completed. Some tips for helping your study expedite through the approval process:

Have your Human Subjects Training & Credentialing completed prior to submitting to the IRB. Complete all the forms to the best of your ability. It is surprising how many submissions are

lacking answers, required forms or signatures. This snags the process. Have working knowledge of the protocol & all its components Confirm your answers are consistent throughout your submission. If you state in one section

that the study is not completing any lab tests, then don’t include the risks of blood draw in your ICF. It is these inconsistences that will table a study.

Grammar check the ICF. This might sound simple, but a mis-placed word (or entire paragraph) can table a study. Read and re-read and re-read your ICF, and give it to someone who is not on the study and ask them if it makes sense. Remember, your ICF should be in 8 th grade reading level.

Respond to any questions, concerns or requests from the IRB as soon as possible. The IRB staff usually finds out 1-2 weeks prior to the IRB meeting that your study is ready to be on the agenda. Which means if something is missing, they will need it ASAP.

Confirm all supplemental forms are completed and submitted with the packet. Are you using CPRS to recruit patients? Submit the waiver. Are you storing biological samples for more than 3 months? Submit the Supplement Application.. etc.

Why does my sponsor define “enrolled” differently than the VA? The VA considered a subject “enrolled” in a research study the minute that subject signs an ICF. Some sponsors define “enrolled” when the subject clears the screening phase, or when the subject is randomized. Different sponsors have different definitions. A good tip is to always follow the most conservative rule. When requesting enrollment amounts, consider your potential screen failure rate.

What is the difference between a “Personnel Change Form” and “Modification Form?” A modification is requesting to “modify the previously approved protocol.” To modify the previously approved protocol, the IRB Chair, or their designee, must sign the approval. A Personnel Change is to change the previously approval personnel staff for an approved study. The HRPPA can sign off on “minor” personnel changes.

I am brand new to research, where do I start? First, let me thank you for your interest in our research program.Were you hired by an active PI to be on a study? Discuss with your PI the required HST&C. Once you have completed the packet, contact Valerie Viramontes (ext: 5801) for further instructions.

Do you work in a different department, and would like to do research as a PI? Refer to the “PI Eligibility” section of this packet. Contact the IRB Office regarding PI requirements. If you meet these requirements, contact Valerie Viramontes (ext: 5801) to start your HST&C.

Do you not work for the VA? You will need to obtain a PI that has an appointment here at the VA. Once the PI agrees to be the Investigator for your study, you will need to start the WOC process with Valerie Viramontes (ext:5801).


What approvals do I need to have my study “fully approved”? The following approvals are required in order to start your study: (note: the IRB will facilitate these approvals)

IRB (via approval memo) R&D (via approval memo) Safety Committee (via approval memo) Pharmacy (via IEW) Radiology (via IEW) Pathology (via IEW) HST&C (via HRPPA approval) Information Security Officer (via signed check list) Privacy Officer (via signed check list)

Training and Credentialing Any research personnel who perform independent clinical activities (judgment based independent of the research protocol) as part of their research activities will be allowed to conduct such activities only if they are credentialed and privileged to provide those activities on patients by the standard credentialing and privileging process of the VALBHS (e.g., doctors, clinical psychologists). All other individuals involved in human studies research (whether a licensed Title 5 employee; and whether the individual receives VA compensation or is without compensation) will have their credentials confirmed, a scope of practice established and a record of such maintained for review.

A) VA Employee vs WOC: VA Employee: An employee who is “directly paid” through the Veterans Affairs Healthcare System WOC: Employee NOT paid through the VA.

b) Requirements for completing HST&C: Required On-Line Training: Required for ALL appointments (VA Employees & WOCs):

- VA Privacy Policy & Information Security Awareness and Rules of Behavior Training - VA Privacy & HIPAA

o Both can be completed on the TMS Website: https://www.tms.va.gov/learning/user/login.jsp

- CITI- VA Human Subject Protection o CITI Website: https://www.citiprogram.org/

Required forms to complete: The investigator should have packets ready for their potential new staff members. Once the packet is complete, staff will need to contact the research office to schedule an appointment. If you need additional copies of this information, please contact the research office.

New WOCs (Without Compensation): Required forms to complete:


https://www.citiprogram.org/


- Electronic Fingerprinting Memo - OF612-Application for Federal Employment (Please leave job description blank) - OF 306- Declaration for Federal Employment - SF85- Questionnaire for Non-Sensitive Positions - I-9- Tax form - VA form 5578 Applicant’s Statement of Selective Service Registration Status - Intellectual Property Agreement - Release of Information for Education Verification - WOC Appointment Request Form (HR requires this form to be filled out by the PI) - Employee Risk Assessment (Completed by the PI) - Scope of Practice (Completed by the PI & WOC)

o If you are the PI, please contact the research office for a different Scope of Practice. - Appointment Affidavit (Research Office will supply this form) - WOC Memo from Service to HR (Research Office will supply this) - Appointment Affidavit (Research will supply this form)

Additional Requirements: - TB Testing (or chest x-ray) (If you have done this already, bring proof. If not, HR will send you to

employee health) - A copy of your degree(s) - Copy of your medical license - Resume/CV signed & dated - Two forms of ID (see I-9 for instructions)

c) Study Monitor Requirements: If the monitor requests computer access or access to Patient Identifiable Data:The monitor will need to complete the required training BEFORE the visit. The monitor will need to submit copies of the completed certificates to the research office when they sign in. These certificates will be filed here in the research office and a copy should be in the regulatory binders as well.

Required Training: VA Privacy and HIPAA Training & VA Privacy and Information Security Awareness and Rules of Behavior. Both of these can be found on the TMS website: https://www.tms.va.gov/learning/user/login.jsp

d) Staff not located at the VHLON: Individuals outside VA (e.g., phlebotomists, x ray, and laboratory technicians) who are not VA employees (paid, WOC, or IPA), and whose work occurs exclusively outside the VA facility (e.g., at affiliated academic institution), must meet their own institutions’ requirements for training, but the local VA facility is not required to track such training.Note: All members of the research team for a VA research study must be VA employees (paid, WOC, or IPA). The only individuals outside VA who do not need a VA appointment or VA-specific training are those who perform a service for the research study in the course of their usual clinical duties.

Miscellaneous:



a) Acronyms: ACOS Associate Chief of Staff AE Adverse Event CFR Code of Federal Regulations COS Chief of Staff CPRS Computerized Patient Record System CRADO Chief Research and Development Officer FDA Food and Drug Administration GCP Good Clinical Practice HIPAA Health Insurance Portability and Accountability Act HIV Human Immunodeficiency Virus HRPPA Human Research Protection Program Administrator HRPP Human Research Protection Program HUD Humanitarian Use Device IB Investigator Brochure IRB Institutional Review Board ICF Informed Consent Form IDE Investigational Device Exemption IND Investigational New Drug NIH National institutes of Health OHRP Office for Human Research Protections ORD Office of Research and Development, VA Central Office ORO Office of Research Oversight PI Principal Investigator R&D Research & Development RCO Research Compliance Officer SAE Serious Adverse Event SCIRE On-site Non-Profit SOP Standard Operating Procedures UCI University of California, Irvine VA Veterans Administration VAMC VA Medical Center WOC Without Compensation

b) Reference Information: All of the information in this booklet was taken from one the following:

IRB SOP VHA Handbook 1200.05 VHA Handbook 1058.01 The Belmont Report Education Plan HRPP policy Reporting of Research Events R&D SOP Research Security SOP Use of Investigational Devices Policy


Use of Investigational Drugs Policy

c) Definitions: Note: Please reference IRB SOP for complete list of definitions:

Adverse Event (AE): Any untoward physical or psychological occurrence in a human subject participating in research. An AE can be any unfavorable and unintended event, including an abnormal laboratory finding, symptom, or disease associated with the research or the use of a medical investigational test article. An AE does not necessarily have to have a causal relationship with the research.

Apparent Serious or Continuing Noncompliance: VA personnel, including WOC and IPA appointees, must ensure that the IRB is notified, in writing, within 5 business days after becoming aware of any apparent serious or continuing noncompliance with IRB or other human research protection requirements. Blinded: A blinded study design is one comparing two or more interventions in which the research personnel, the subjects, or some combination thereof, do not know the treatment group assignments of individual subjects.

Caregivers: Caregivers are persons who assist in the personal care of other persons. Caregivers may be relatives or professional staff from dedicated facilities or organizations. Because of their close relationship to patients, caregivers are a valuable source of health information and are often called upon to provide their observations within a clinical setting. Since this information is about others, and not about themselves, the caregivers act as agents of the patients rather than as research participants. The IRB should consider if the subject's consent may be appropriate, e.g. where a formal arrangement is absent. Consent of the caregiver is not usually appropriate although the IRB may approve a form where the caregiver acknowledges their role. Care should be exercised that this form does not read like a contractual agreement or otherwise give the impression that the caregiver functions as a member of the research staff. Caregivers are distinguished from staff in that they serve a role that is independent of the research project as opposed to staff that have responsibilities that are determined solely by the research project. Caregivers provide information about patients, whereas staff gathers information from patients. Caregivers normally care for a single research participant whereas staff are responsible for all. Staff are trained and credentialed whereas caregivers are not.

Common Rule: Common Rule means the Federal Policy for the Protection of Human Subjects by Federal departments and agencies conducting or supporting human subject research. The Common Rule is codified for VA at Title 38 CFR Part 16.

Continuing Noncompliance: Continuing noncompliance is a persistent failure to adhere to the laws, regulations, or policies governing human subjects research.

Exempt Research: Research activities in which the only involvement of human subjects is in one or more of the categories listed in 38 CFR 16.101(b) and as described in Section 101. The exempt status must be determined by the Institutional Review Board (IRB) Chair or an IRB voting member designated by the Chair. Note: Such an exemption applies only to requirements found in 38 CFR Part 16. All other relevant VA and Federal requirements apply.


Expedited Review: is research initially reviewed and approved outside of a convened IRB meeting by the IRB Chair or by one or more experienced voting members of the IRB designated by the IRB Chair. The research must present no more than minimal risk to human subjects and involve only procedures in certain specific categories, as described in section 501. Minor changes to previously approved research during the period for which approval is authorized may also be approved through the expedited process (38 CFR 16.110(b)).

Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. (ICH 1.24)

HIPAA Authorization: The term HIPAA authorization means prior written permission for use and disclosure of protected health information (PHI) from the information’s source person, research subject, or legally authorized personal representative, as required under law, including HIPAA. The written authorization must include all elements of a compliant authorization (see VHA Handbook 1605.1) prior to any disclosure of information.

Human Biological Specimen: A human biological specimen is any material derived from human individuals, such as blood, urine, tissues, organs, hair, nail clippings, buccal swabs, or any other materials that are either collected specifically for research purposes or as residual specimens for diagnostic, therapeutic, or surgical procedures. Bacteria, fungi, or viruses obtained from human biological specimens are not considered human biological specimens, as long as the human material has been removed.

Human Research: Human research is research involving human subjects as defined in this SOP or one or more identifiable human biological specimens.

Human Research Protection Program (HRPP): A HRPP is a comprehensive system to ensure the protection of human subjects participating in research. The Human Research Protection Program (HRPP) consists of a variety of individuals and committees including:, the Medical Center Director, Associate Chief of Staff for Research and Development (ACOS/R&D), the Administrative Officer for Research and Development (AO/R&D), Human Research Protections Program Officer, Research Compliance Officer (RCO), the Research and Development Committee (R&DC), IRB, other committees or subcommittees addressing human subjects protection (e.g., Subcommittee on Research Safety (SRS), Institutional Biosafety Committee (IBC), Radiation Safety Committee), investigators, IRB staff, research staff, health and safety staff (e.g. Biosafety Officer, Radiation Safety Officer) and research pharmacy staff. The objective of this program is to assist the institution in meeting ethical principles and regulatory requirements for the protection of human subjects in research.

Human subject: This definition of human subject includes investigators, technicians, and others assisting investigators, when they serve in a “subject” role by being observed, manipulated, or sampled. Title 38 CFR Part 16 defines a human subject as a living individual about whom an investigator (whether professional or student) conducting research obtains either:

Data through intervention or interaction with the individual; interaction includes communication or interpersonal contract between the researchers and the subject; or


Identifiable private information (38 CFR 16.102 (f)).For research covered by Food and Drug Administration (FDA) regulations, human subjects means an individual who is or becomes a participant in a clinical investigation, either as a recipient of the test article or as a control. (21 CFR 50.3(g), 21 CFR 66.102(c)). For research covered by FDA device regulations, subject means a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease (21 CFR 812.3(p)).

Individually-Identifiable Information: Individually-identifiable information is any information, including health information maintained by the VHA, pertaining to an individual that also identifies the individual and, except for individually-identifiable health information, is retrieved by the individual’s name or other unique identifier. Individual-identifiable health information is covered regardless of whether or not the information is retrieved by name.

Individually-identifiable Health Information: Individually-identifiable healthinformation is a subset of health information, including demographic information collected from an individual, that is: (1) Created or received by a health care provider, health plan, or health care clearinghouse; (2) Relates to the past, present, or future condition of an individual and provision of or payment for health care; and (3) Identifies the individual or a reasonable basis exists to believe the information can be used to identify the individual.

Informed Consent: The process required under the human subject protection regulations (commonly known as the Common Rule) to obtain the legally effective informed consent of the subject or the subject’s legally authorized representative to participate in human subject research. The Common Rule is codified in VA at 38 C.F.R. Part 16. The general requirements for informed consent are set for at 38 C.F.R. 16.116. The written document approved by the Institutional Review Board (IRB) is sometimes referred to as the informed consent form and, when signed by a research subject, the written informed consent. When research involves creating biorepositories and/or data repositories, the informed consent document must expressly address and authorize this activity and must comply with HIPAA requirements. The informed consent document must also address ownership and commercialization of specimens. Discussion of commercialization and ownership must avoid the use of any exculpatory language. The informed consent is stamped with an approval date but does not expire. A newly approved Informed Consent document replaces all older versions.

International Research: VA international research is defined as any VA-approved research conducted at international sites (not within the U.S., its territories, or Commonwealths); any VA-approved research using either human biological specimens (identified, de-identified, or coded) or human data (identified, de-identified, or coded) originating from international sites; or any VA-approved research that entails sending such specimens or data out of the U.S. NOTE: This includes sending such specimens or data to individuals with VA appointments at international sites (e.g., a WOC appointment, a VA investigator on sabbatical at an international site). It also includes a VA’s serving as a coordinating center for an international research project.Investigational Device: As defined by the FDA, an investigational device is a device that is the object of an investigation (21 CFR 812.3(g)).


Investigational Device Exemption (IDE): An IDE is an application to FDA that allows an investigational significant risk device to be used in a clinical investigation to collect safety and effectiveness data. If the device is a non-significant risk device, it is considered to have an approved application for IDE after IRB approval is obtained. (see 21 CFR 812).

Investigational Drug: According to VHA Handbook 1108.04, an investigational drug is a chemical or biological drug that is used in a clinical investigation. An investigational drug can be: (1) A new chemical compound, which has not been released by the FDA for general use; or (2) An approved drug that is being studied for an approved or unapproved use, dose, dosage form, administration schedule, or under an Investigational New Drug (IND) application, in a controlled, randomized, or blinded study (see VHA Handbook 1108.04).NOTE: Concurrent medications, comparators, or rescue medications used in the investigational trial that are not the drug(s) being studied are not defined as investigational drugs unless they are not commercially approved or not available through commercial channels. Prescription drugs, over-the-counter drugs, nutritional supplements, herbal preparations, and legend items used for diagnosis or treatment and meeting the definition of “investigational drug” (see subpars. 3pp(1) and 3pp(2)) are considered investigational drugs.

Investigational New Drug (IND) Application. An IND is an application to the FDA that allows an investigational drug or biological product to be studied in humans. An IND must be in effect prior to shipment and administration of investigational drug or biological products (see 21 CFR 312).

Investigational Product: A pharmaceutical form of an active ingredient (21 CFR 312.3), device (21 CFR 812.3(g)) or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use (ICH 1.33). An investigational drug may also be an approved drug that is being studied for a previously unapproved use and/or efficacy.

An investigational drug can be a new chemical compound, which has not been released by the FDA for general use; or

An approved drug that is being studied for an approved or unapproved use, dose, dosage form, administration schedule, or under an Investigational New Drug (IND) application, in a controlled, randomized, or blinded study (see VHA Handbook 1108.04).

Note: Concurrent medications, comparators, or rescue medications used in the investigational trial that are not the drug(s) being studied are not defined as investigational drugs unless they are not commercially approved or not available through commercial channels. Prescription drugs, over-the-counter drugs, nutritional supplements, herbal preparations, and legend items used for diagnosis or treatment and meeting the definition of “investigational drug” are considered investigational drugs.

Investigator: An investigator is any individual who conducts research involving human subjects including but not limited to, the PI, sub-PI, and Local Site Investigator (LSI). The investigator must uphold professional and ethical standards and practices, adhere to all applicable Federal requirements and comply with applicable local policies and procedures. An investigator may be either compensated by VA, be appointed to work without compensation (WOC), or may be an employee assigned to VA


through the Intergovernmental Personnel Act of 1970. The FDA considers an investigator and a principal investigator to be synonymous.

VA Investigator: A VA investigator is any individual who conducts research approved by the VA R&DC while acting under a VA appointment on VA time, including full and part-time employees, WOC employees, and individuals appointed or detailed to VA under the Intergovernmental Personnel Act (IPA) of 1970. In addition, a VA investigator must comply with all applicable VA and VHA requirements, and comply with applicable Long Beach VA Healthcare System facility policies and procedures.

Principal Investigator (PI): The PI is a qualified person or persons designated by an applicant institution to direct a research project or program and who usually writes the grant application. The PI oversees scientific, technical, and day-to-day management of the research. In the event of an investigation conducted by a team of individuals, the PI is the responsible leader of that team. Note: FDA considers Investigator and PI to be synonymous.

Co-Investigator or Sub-Investigator: At VALBHS, Co-Investigator or Sub-Investigator is used interchangeably. A Co-Investigator assumes the responsibilities of the PI if the PI is unavailable.

Site Investigator or Local Site Investigator (LSI): The Site Investigator or LSI is an investigator at a site participating in a multi-site research project. The LSI oversees scientific, technical, and day-to-day management of the research at the local site.

IRB approval: The determination of the IRB that the human subjects research has been reviewed and may be conducted at an institution within the constraints set forth by the IRB and by other institutional and Federal requirements.

Lapse: A condition that exists when a study has failed to be re-approved within the time frame that was specified at the time of the previous approval. Unlike suspensions and terminations, a lapse results from a failure to act, by either the investigator or the IRB, rather than as a result of an IRB action. All research activities must stop except for the continuation of follow-up activities necessary to protect the participants’ safety. Unlike suspended studies, lapsed studies are not approved. Unlike terminated studies, lapsed studies may be re-approved.

Local AE: In the context of a multi-center study, internal or local SAE’s are those AEs experienced by subjects, research staff, or others at the reporting individual’s own VA facility or VA-approved research site.

Minimal risk: Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (38 CFR 56.102(i))

Research Involving Human Subjects: any activity that either meets the DHHS definition of “research” and involves “human subjects” as defined by DHHS; or meets the FDA definition of “research” and involves “human subjects” as defined by FDA.

Research Misconduct: Research misconduct is defined as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.


Research Records: Research records include, but are not limited to, IRB and R&D Committee records, records of all observations, other data relevant to the investigation, progress notes, research study forms, surveys, questionnaires, and other documentation regarding the study (VHA Handbook 1907.01).

IRB Records: IRB records include, but are not limited to: copies of all research proposals and amendments reviewed; scientific evaluations, if any, that accompany the proposals; approved informed consent documents; progress reports submitted by investigators; reports of injuries to subjects; reports of complaints from subjects; minutes of IRB meetings; reports of expedited review activities; records of continuing review activities; copies of all correspondence between IRB and the investigators; reports of deviations from IRB-approved protocol; a list of IRB members; written procedures for IRB in the same detail as described in 38 CFR 16.103(b)(4) and (5); and statements of significant new findings provided to subjects as required by 38 CFR 16.116(b)(5).

Investigators’ Research Records: Research records include the following when relevant to the study; copies of all IRB-approved versions of the protocol and amendments; case report forms and supporting data (including but not limited to signed and dated informed consent forms and HIPAA authorization forms); documentation on each subject including informed consent, interactions with subjects by telephone or in person, observations, interventions, and other data relevant to the research study; reports of adverse events; data analyses; codes and keys used to de-identify and re-identify subjects’ PHI; reports (including but not limited to abstracts and other publications); all correspondence (including but not limited to, that with the funding source or sponsor) and with applicable oversight entities (including but not limited to, IRB, R&D Committee, ORO, and FDA); and a master list of all subjects for whom informed consent has been obtained in the study.

Serious Adverse Event (SAE): An SAE is an AE in human research that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect. An AE is also considered serious when medical, surgical, behavioral, social, or other intervention is needed to prevent such an outcome.

Serious Noncompliance: A serious noncompliance is a failure to adhere to requirements for conducting human research that may reasonably be regarded as: (1presenting a genuine risk of substantive harm to the safety, rights or welfare of human research subjects, research personnel or others, including their rights to privacy and confidentiality of identifiable private information; or (2) Substantively compromising a facility’s human research protection or human research oversight programs.

Serious Problem: A serious problem is a problem in human research that may reasonably be regarded as: (1) Involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff, or others; or (2) Substantively compromising the effectiveness of a facility’s human research protection or human research oversight programs.

Suspension of IRB Approval: A suspension of IRB approval is a determination by the IRB Chair, a qualified IRB voting member designated by the IRB Chair, or the convened IRB to temporarily interrupt some or all previously-approved research activities. The suspended activities could include, but not be limited to, recruiting of new subjects for the research. Suspended studies remain open and require continuing review.


Termination of IRB Approval: A termination of IRB approval is a determination by the convened IRB to permanently halt some or all previously approved research activities including, but not limited to, enrollment of new subjects in research.

Unanticipated Adverse Event (UAE): An UAE is any AE that is new or greater than previously known, in terms of nature, severity, or frequency of occurrence, as documented in the protocol or other materials approved by the IRB. Such materials may include, but are not limited to: the informed consent form, clinical investigator’s brochure, and product labeling (see VHA Handbook 1058.01). Note: For the purposes of this SOP, “unanticipated” is the same as “unexpected.”

Usual Care: Usual care is medical or other treatment or services a research subject would receive if not participating in the research study (e.g., the chemotherapy an oncology patient would receive whether or not the patient was participating in a research study.).

d) Roles: - IRB Pre-Reviewer: This is a person who performs a preliminary review of all initial studies prior

to the IRB. Their comments are suggestions and attempts to help resolve issues prior to the IRB meeting, with the goal to get a study approved when reviewed by the IRB.

- IRB Reviewer: This person is a voting member of the IRB. They review studies prior to the IRB meeting and bring their concerns to the meeting. Their comments become stipulations to IRB approval.

- IRB Chair: The Chair will serve as the official representative of the IRB, and will chair all IRB meetings. Makes decisions in emergency situations to protect subjects and remain in compliance with regulations. Determines whether studies qualify for exemption from review. Determines whether studies qualify for expedited review (Section 501) Performs or delegates review of applications and revisions meeting expedited review criteria. Reviews all submitted investigator reports and determine if there is reason for full IRB review. Reviews policies, procedures and forms on an ongoing basis. Relate concerns of IRB staff and members to administration regarding issues in human research review. Acts as an advisor and educator in the institution's research community.

- IRB Administration: This is a group of people who maintain the human research study activities for all research that is conducted here at VALBHS.

- RCO: The RCO is an individual whose primary responsibility is to review research projects relative to requirements for the protection of human subjects, laboratory animal welfare, research safety, research laboratory security, research information protection, or other areas under the jurisdiction of ORO.

- Research Pharmacist: In studies using pharmaceutical products (particularly when an investigational product is involved), a pharmacist will review the Investigator’s Brochure and the IDIR and communicates any concerns or suggested modifications to the Committee. The pharmacist is also the one to dispense research medications.

- R&D Committee: The Research & Development Committee (R&D) reviews and approves all new and continuing projects. The Committee has oversight of the research program and all subcommittees. Therefore, new research must not be undertaken without the written approval of the R&D Committee. Project may not move forward to the R&D while there is a stipulation


or conditional approval. The R&D follows the guidelines and responsibilities of VHA Handbook 1200.01.

- Safety Committee: The Subcommittee on Research Safety (SRS) must review all research projects annually. The subcommittee adheres to regulations in VHA Handbook 1200.08 which contains the guidelines and policies for ensuring the safety of personnel engaged in research. The SRS members review the safety form and abstract and, if applicable, the chemical inventory list. All new or continuing projects must submit the Research Protocol Safety Survey, VAF 10-0398, with review documentation. The SRS meets monthly the week after the Research & Development Committee. After the meeting the R&D Coordinator will contact the clinical coordinator or the investigator if there is a meeting stipulation. The project must be approved before it can move forward to the Research & Development Committee. The SRS also acts as the Institutional Biosafety Committee (IBC) to review recombinant DNA research.
