TABLE OF CONTENTS
Section I: Investigator Assurances
Section II: Funding
Section III: Summary Information
Section IV: Protocol Summary
Section V: hESC Scientific Protocol
Section VI: Protocol for Banking Stem Cells
Section VII: Investigational Drug Information Record
Section VIII: Investigational Device Information Record
Background
UCLA faculty, staff, and students who wish to conduct human pluripotent stem cell (hPSC) including human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC) research are required to comply with applicable Campus policies, including prospective Embryonic Stem Cell Research Oversight (ESCRO) Committee and when applicable Institutional Review Board (IRB) review to ensure that the research is conducted with consideration of all scientific, ethical, and social issues, and that the projects conform to applicable federal and state regulations, University of California policies, as well as National Academy of Science (NAS) guidelines.
California law permits hPSC research only “after full consideration of the ethical and medical implications of this research”.[1] State law requires and the NAS guidelines on hPSC research recommend scientific and ethical review as well as tracking of all hPSC research and cells. Additionally, California law and federal regulations require that all hPSC research undergo prospective Institutional Review Board (IRB) review when the research includes human subjects. Furthermore, regulations promulgated by the California Institute for Regenerative Medicine outline ESCRO Committee requirements, including the ESCRO Committee review of all stem cell research sponsored by the agency. Federal restrictions on hESC research require that the University track specific data in order to ensure appropriate accounting of expenditures in this area.
Contacts:
IRB Review: Office of the Human Research Protection Program: x55344
ESCRO Review: Steven Peckman, x54958 .
University of California, Los Angeles
APPLICATION FOR HUMAN PLURIPOTENT STEM CELL
HUMAN SUBJECTS RESEARCH
(IRB and Embryonic Stem Cell Research Oversight (ESCRO) Committee Review)
PROJECT TITLE:PRINCIPAL Name Degree(s) University Title Campus Phone No.
INVESTIGATOR:
Department Campus Mailing Address Campus Mail Code e-mail Address
CO-INVESTIGATOR Name Degree(s) University Title Campus Phone No.
or FACULTY SPONSOR: ______
Department Campus Mailing Address Campus Mail Code e-mail Address
______
PRIMARY CONTACT Name Campus Phone No. e-mail Address
PERSON:
APPLICATION STATUS: New Addendum Renewal Previous IRB number, if applicable: ______Previous ESCRO number:______
SECTION I: ASSURANCES
INVESTIGATOR'S ASSURANCE
I certify that the information provided in this application is complete and correct. I understand that as Principal Investigator, I have ultimate responsibility for the conduct of the study, the ethical performance of the project, the protection of the rights and welfare of human subjects, and strict adherence to any stipulations imposed by he Embryonic Stem Cell Research Oversight (ESCRO) Committee and when applicable the IRB.
I certify that the information provided in this application is complete and correct.
I agree to comply with all UCLA policies and procedures, as well as with all applicable federal, State, and local laws regarding hPSC and human subjects research, including, but not limited to, the following:
· performing the project by qualified personnel according to the approved protocol,
· implementing no changes in the approved protocol or informed consent form without prior ESCRO and when applicable IRB approval, except (where necessary to eliminate apparent immediate hazards to the human subjects or others),
· promptly reporting significant or untoward adverse effects to ESCRO and when applicable IRB in writing within 5 working days of occurrence,
· if I will be unavailable to direct this research personally, as when on sabbatical leave or vacation, I will arrange for an ESCRO and when applicable IRB approved co-investigator to assume direct responsibility in my absence,
· obtaining the legally effective informed consent from human subjects, and using only the currently ESCRO and when applicable IRB approved, stamped consent form with human subjects,
· ANY DISTRIBUTION OF CELLS OR DERIVATIVES TO INDIVIDUALS NOT NAMED IN THIS PROTOCOL REQUIRES PROSPECTIVE REVIEW AND APPROVAL OF BANKING AND DISTRIBUTION PROCEDURES BY THE ESCRO COMMITTEE AND WHEN APPICLABLE THE IRB.
______
Principal Investigator Date
FACULTY SPONSOR’S ASSURANCEBy my signature as sponsor on this research application, I certify that the student or guest investigator is knowledgeable about the regulations and policies governing research with human subjects and has sufficient training and experience to conduct this particular study in accord with the approved protocol. In addition,
· I agree to meet with the investigator on a regular basis to monitor study progress.
· Should problems arise during the course of the study, I agree to be available, personally, to supervise the investigator in solving them.
· I assure that the investigator will promptly report significant or untoward adverse effects to the IRB and ESCRO in writing within 5 working days of occurrence.
· If I will be unavailable, as when on sabbatical leave or vacation, I will arrange for an alternate faculty sponsor to assume responsibility during my absence, and I will advise the IRB and ESCRO by letter of such arrangements.
______
Faculty Sponsor * (if PI is a student or a fellow) Date
· The faculty sponsor must be a member of the UCLA faculty. The faculty member is considered the responsible party for legal and ethical performance of the project.
CO-INVESTIGATORS
1. [Name, degree]
[Department]
[Mailing address]
[Telephone]
[email]
Please list the research personnel and their training in stem cell science:
(Note: Please include the principal investigator’s information first. Please also attach curriculum vitae in NIH Biosketch form for each listed personnel. CIRMregulations and NAS guidelines requiredocumentation of sufficient hPSC training.)
Last name, First name, degree / Title / Training in Stem Cell Science(outline the experience, expertise or training in derivation or culture of stem cells)
1.
2.
3.
Research Location
Building Name / Room number(s)EX: Factor / 9-664
1.
2.
SECTION II – FUNDING
THIS SECTION MUST BE COMPLETED
1. Check all of the appropriate boxes for funding sources for this research, include pending funding source(s):
Extramural* UCLA Academic Senate Gift Other: _ _ ___
* P.I. of Contract or Grant: __ __
Funding Source: _.____
Contract or Grant No.: __ ___
Contract or Grant Title:
2. If using an IDENTICAL protocol for more than one extramural funding proposal, list all funding sources below. Attach an additional sheet if more space is needed.
a. P.I. of Contract or Grant: _____
Funding Source: __ ___
Contract or Grant No.: _____
Contract or Grant Title: _____
b. P.I. of Contract or Grant: _____
Funding Source: _____
Contract or Grant No.: _____
Contract or Grant Title: _____
3. STATEMENT OF FINANCIAL INTERESTS: Please attach the completed Form 700-U, “Statement of Economic Interests,” per the instructions at http://www.research.ucla.edu/researchpol/formIndex.htm .
SECTION III - SUMMARY INFORMATIONTHIS SECTION MUST BE COMPLETED
The review of human subjects and human pluripotent stem cells (hPSC) research is conducted by the Medical Institutional Review Board (MIRB) and the Embryonic Stem Cell Research Oversight (ESCRO) Committee. The MIRB and ESCRO are composed of members with research and biomedical expertise as well as non-scientists. To aid the MIRB and ESCRO in evaluating and tracking the protocol, please check all appropriate boxes in this section.
1. Will you perform medical procedures as part of this research proposal? Yes No
2. SUBJECT POPULATION: (Check all appropriate boxes.)
___Healthy adults ___UCLA students/staff
___Clinical human in vitro fertilization ___Cognitively or psychologically impaired
___Egg donors ___Elderly
___Somatic cell donors ___Institutional residents
___Fetuses (non-blastocyst) ___Children
___Pregnant women ___Exclusion of minorities
___Terminally ill ___Prisoners or parolees
___Non-English speaking ___Comatose
___Cancer patients
3. If the research involves any of the following, please check the appropriate boxes:
___Clinical studies ___Venipuncture (450cc)
___PI or Co-PI is the treating physician ___Interviews
___Study of human biological specimens ___Survey/questionnaire
___HIV/AIDS ___Behavioral observation
___Genetic research ___Waiver of informed consent
___Study of existing data ___Deception
___Radiation ___Controlled substances
___Microorganisms or recombinant DNA
___Banking of cells (if checked, complete Section VI)
___Potential development of commercial product from human biological materials
___Investigational devices (if checked, complete Section VII)
___Investigational drugs (if checked, complete Section VIII)
4. LOCATION(S) OF RESEARCH TO BE CONDUCTED AT:
UCLA campus _ ____ Santa Monica-UCLA Medical Center_ ____
Other locations, specify: _ ____
5. LAY LANGUAGE SUMMARY: (Please use non-technical language that is understood by nonscientific members to summarize the proposed research project. The information must include: (1) a brief statement of the problem and related theory supporting the intent of the study, and (2) a brief but specific description of the procedure(s) involving the human subjects. Attach an additional page as necessary. However, please do not exceed one single-spaced, type-written page.)
SECTION IV - PROTOCOL SUMMARYTHIS SECTION MUST BE COMPLETED
INSTRUCTIONS: In order to review your proposal, the ESCRO must have all of the following information. Please state “Not Applicable” for topics that are not applicable to your proposal. Address each topic independently in the sequence listed and do not rely on information covered under other subparts. Attaching sections of the grant application is not an acceptable substitute. Provide sufficient information for effective review by all members of the ESCRO, including non-specialists and community members. Define all abbreviations and terms not part of common language and use simple words and sentence structure as much as possible. Please number each page.
INFORMATION REGARDING RENEWAL APPLICATION (1)1. Renewal Application:
1.1. Please provide a summary of the research activities to date, including references to any publications resulting from the research.
1.2. What benefits to the participating subjects or to society have been derived?
1.3. How many subjects have been enrolled since the date of:
1.3.1. Last approval:
1.3.2. Initial approval:
1.4. Approximately how many more subjects/donors are required to complete the study?
1.5. Has there been any difficulty obtaining/retaining subjects or obtaining informed consent during the previous approval period?
1.5.1. Approximately how many potential subjects have refused participation?
1.5.2. How many subjects have voluntarily withdrawn participation at their own request?
1.5.3. How many subjects have withdrawn participation at the request of the PI?
1.5.4. How many subjects/donors requested withdrawal of their biological material from the research?
1.6. Have there been any unexpected reactions or complications since last scheduled review?
If you have submitted the Adverse Event Reports, please provide a list of reports with submission dates.
1.7. For iPSC Research, please describe the outcome of the reprogramming of the materials collected from donors.
1.7.1. Were you able to successfully reprogram the cells?
1.7.2. If not, please explain why you were not able to reprogram the cells and the steps you are taking to address the problem.
1.7.3. Number of iPSC lines created during the last approval period: ______
1.7.4. iPSC lines created since the initial approval:______
1.8. Please complete the Scientific Protocol Section V(D3) about animal research.
1.9. Please indicate the number of oocytes and embryos received and the number that were used during the past year. This allows audit of embryos received as well as those found to be unsuitable for research. Please give the name(s) of the center(s) supplying the material and provide the data for each supplying center separately. (If necessary, please continue on a separate sheet):
Dates: From:______To:______
Center Name:______
Total Number of embryos received / Total Number of Embryos Used / Total number of oocytes received / Total number of oocytes used / Total number of embryos createdSince the last approval:
Fresh:
Frozen:
Since the Initial Approval:
Fresh:
Frozen: / Since the last approval:
Fresh:
Frozen:
Since the Initial Approval:
Fresh:
Frozen: / Fresh:
Failed to fertilize:
Frozen / Fresh:
Failed to fertilize:
Frozen: / Since the last approval:
Total:
Total number of oocytes destroyed / Total number of embryos destroyed
PURPOSE OF THE STUDY, THE BACKGROUND AND THE LITERATURE REVIEW (2-3)
2. Purpose of the Study: What are the specific scientific objectives (aims) of the research?
CHARACTERISTICS OF THE SUBJECT POPULATION (4-6)3. Cells provided by another investigator or institution.
YES NO
Were the donated cells obtained under an IRB approval? If so, please attach the IRB approval and IRB approved informed consent document that was used to originally obtain the cells. Please use the hPSC informed consent form checklist and ensure that the IRB approved document includes the required elements for legally effective informed consent.
- If the IRB approved informed consent document does not include all of the applicable elements of informed consent as indicated on the checklist, please explain why.
4. Number of Subjects: What is the anticipated number of subjects/donors to be enrolled at UCLA and, in the case of multi-center research, the total number of subjects for the entire project? The number of subjects would include the donors of biological material either at UCLA or extra-mural.
[According to Federal regulations and California law previously stored embryos, gametes, and stem cells are not human subjects IF the material does not include identifiable private information that directly or indirectly links back to the donors. “Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects” (45 CFR 46.102(f)] Nevertheless, California law requires IRB review of all hPSC research].
Institution / Number of subjects/donors1. UCLA
2.
3.
5. Inclusion/Exclusion Criteria:
5.1. What are the criteria for inclusion and exclusion?
5.2. How will eligibility be determined, and by whom?
5.3 Are any inclusion or exclusion criteria based on age, gender, pregnancy or childbearing potential, or racial/ethnic origin? If so, explain and justify.
Note: Equitable inclusion of both men and women of all ages, and individuals from diverse racial/ethnic backgrounds, is important to assure that they receive an equal share of the potential benefits of research and that they do not bear a disproportionate share of its burdens. Participation of adult subjects of both genders and diverse racial/ethnic backgrounds should not be restricted without medical or scientific justification.
6. Vulnerable Subjects: Will any vulnerable subjects be included? If so, identify the subject groups and justify their involvement.