Transcript Slide 1

Human Research Protection Program Training:

Preparing an Expedited or Exempt Application

December 12, 2007 Lisa Voss, MPH, CIP Policy Analyst Human Research Protection Program [email protected]

514-2152 Joanne Mickalian, MS Assessment Team Human Research Protection Program [email protected]

476-1744

Outline for Today

    Intro to HRPP (CHR and QIU) organization, applications, and review process Preparing Expedited and Exempt Applications Common errors and Tips Q&A 12/12/07

HRPP Director

Sharon Friend

HRPP Policy Analyst

Lisa Voss

HRPP Operations Manager

Stephen Dorsey

Front Desk Support Group

Jessica Loomis Meri Figueroa Mario Velez Denisha Otis Keith Martin Brian Hertzog

Screeners Group

TBD Joanne Mickalian Fred Hendrickson Megan Sullivan

HRPP Associate Director

Richard Wagner

HRPP Associate Director

John Heldens

Committee Coordinators

Laurel Heights

Karen Chao Kate Nolan

Committee Coordinators

Mt. Zion

Michael Thomas Annette Bugatto

Committee Coordinators

Parnassus

Liz Tioupine Wendy Stephens

Committee Coordinators

SFGH

Elizabeth Mendelsohn Terry Colbert

QIU Director

Carroll Child

QIU Group

Patti Tosta Maria Bahn TBA

First step:

Determining – “ Is the project human subject research?”

Definition of Research

 A systematic investigation , including  research development, testing and evaluation  designed to develop or contribute to

generalizable knowledge

.

(45 CFR 46.102) 12/12/07

Definition of Human Subject

 A living individual about whom an investigator (whether professional or student) conducting research obtains   data through intervention or interaction with the individual, or identifiable private information . (DHHS 45CFR46.102) 12/12/07

When is it NOT a Human Subject

 If the Investigator obtains coded data or biological samples under the following conditions: The coded private information or specimens cannot be collected specifically for the current proposed research project, and one or more of the following apply: 12/12/07

Conditions

 The key to decipher the code is destroyed before the researcher begins, or  The PI and holder of the key enter into an agreement prohibiting the release of the key under any circumstance (The CHR recommends a written agreement be secured between the recipient and the provider of the specimens or data. The CHR will not require review of these agreements.), or  There are IRB-approved written policies for the repository or data management that prohibit the release of the key. 12/12/07

Determining Whether Human Subjects are Involved in Research When Obtaining § Private Information (data) and/or Biological Specimens – October 2007 CAUTION: This diagram does not apply to 1) initial collection of tissue, 2) human stem cell research , 3) FDA regulated research, and 4) research involving prisoners. All of these must be reviewed by Full Committee or Expedited Review. Data and/or specimens have identifiers Data and/or specimens are coded and identifiers* are kept separately Do the PI or Co-Investigators on the study have access to the “key” to link back to the identifiers*?

Human subjects Yes No

Not

human subjects

See the conditions that must be met.

Data and/or specimens are de-identified* Examples 1. Commercially available specimens 2. Adult cells lines with no identifiers, NOT stem cells 3. Cadaveric tissue with no identifiers

Definitions:

§

Obtaining

- is defined as receiving or accessing data or biological specimens.

* Identifiers

– Any of the 18 Protected Health Identifiers and other type of personal identifiers. IMPORTANT NOTE: The data or biological specimens may include a limited set of data including all elements of dates and geographical codes (zip codes) as long as the individuals identity cannot be ascertained.

Conditions:

The coded data and/or specimens were not collected specifically for the current proposed research project, and one or more of the following apply: 1. The key to decipher the code is destroyed before researcher begins, or 2. PI and holder of the key enter into an agreement prohibiting the release of the key under any circumstances, or 3. There are IRB-approved written policies for the repository or data management that prohibit the release of the key. Important Note: If these are not applicable then the coded data or specimens are considered human subjects. Please see the PI Self-Certification Form for Sponsors

Human subjects The data and/or specimens are pre-existing+,

and

the information is recorded in a manner that subjects cannot be identified directly or through identifiers* linked to the subject.

Expedited Review or Full Committee No Ye s Exempt Certification

Definitions:

§

Obtaining

- is defined as receiving or accessing data or biological specimens.

* Identifiers

– Any of the 18 Protected Health Identifiers and other type of personal identifiers. IMPORTANT NOTE: The data or biological specimens may include a limited set of data including all elements of dates and geographical codes (zip codes) as long as the individuals identity cannot be ascertained.

+ Pre-existing

- means collected (i.e., on the shelf) prior to the research for a purpose other than the proposed research. It includes data or specimens collected during research and/or non-research activities.

Second step:

Determining the Level of Review/Type of Application to Submit

Review Level Based on Risk to the Subject

  The level of risk to the subject determines the level of review required and therefore the type of application.

The risk level is compared to “minimal risk” as defined by federal regulation.

 “Minimal risk” (45CFR46.102).

means 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 examination or tests” 12/12/07

CHR Levels of Review/Applications

   Greater than minimal risk:  Full Committee Less than minimal risk:  Expedited Review (Category 1-4, 6,7)   Expedited Review: No Subject Contact (Category 5) Exempt (Category 1, 2, 3)  Exempt (Category 4) Not Human Subjects  Self-Certification Form 12/12/07

Expedited Review Categories

1. Research with approved drugs/devices 2. Blood sampling (small amounts) 3. Noninvasive specimen collection 4. Noninvasive clinical procedure 5. Use of data or specimens collected for nonresearch purposes 12/12/07

Expedited Review Categories

6. Research recordings (voice, video, 7. Low risk behavioral research 8. digital, or image recordings) Renewal or protocols that are essentially complete of inactive research protocols 9. Renewal protocols of other minimal risk research 12/12/07

Exempt Review Categories

1. Research conducted in established or commonly accepted educational settings. 2. Research involving the use of educational tests, survey procedures, interview procedures, or observations of public behavior if they are anonymous or disclosure of individuals identity does not put them at risk.

DOES NOT APPLY

to research with UCSF patients, children (minors), and prisoners 3. Interviews or surveys with public officials 12/12/07

Exempt Review Categories

4. Research involving the collection or study of

existing

data, documents, records, pathological specimens, or diagnostic specimens, if these sources are

publicly available

or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects. Important Note: Exempt Categories involve human subjects.

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Third step: Expedited Review

Filling out the Expedited Review Application and Supplements

Expedited Review Application

Part 1: Administrative Requirements        PI, Co-PI, Contact Person Study sites Funding Scientific Merit Key Personnel Financial Interests PI Signature 12/12/07

Expedited Review Application

Part 2: Study Design        Synopsis vs. Design vs. Procedures Hypotheses Specific Aims Background vs. Preliminary Studies Design Statistical Analysis Sample Size 12/12/07

Expedited Review Application

Part 3: Procedures   Clear description of research procedures.  What is the subject being asked to do for the purpose of the research study   How does this compare or what is the subject being asked to do in addition to their normal standard of care Written in a way that can be replicated and understood by someone not in your field Tables, charts, or flow-diagrams may help explain the process and timeline 12/12/07

Expedited Review Application

Part 4: Alternatives  Provide a discussion of the alternatives to participation.

 Many times includes not participating!

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Expedited Review Application

Part 5: Risks and Benefits  Risks and Discomforts  Description of risks  Physical risk of blood draw to emotional risk of asking questions    Steps to minimize risks  Providing an opportunity for questions, follow recommended recruitment guidelines Maintaining confidentiality - data Maintaining privacy - individuals 12/12/07

Expedited Review Application

Part 5: Risks and Benefits   HIPAA section    Identify source and personal health information that will be collected How maintained and protected Disclosures Benefits – Overall risk/benefit analysis  Explanation of why the benefit outweighs the risk of loss of confidentiality 12/12/07

Expedited Review Application

Part 6: Subject Information    CHR Supplements?

Inclusion & Exclusion Criteria  Be Specific  Determining eligibility Non-regulated vulnerable populations 12/12/07

Expedited Review Application

Part 7: Recruitment  How, when, where and by whom are potential subjects approached     Respect for privacy Lack of pressure Unbiased presentation Who conducts initial contact? Written so that it can be understood by a reviewer that is not in your scientific field or works in your Department 12/12/07

Expedited Review Application

Part 8: Informed Consent  How, where, when and by whom 

informed will be obtained

 Ensuring Understanding Consent    Signed consent Waiver of signed consent Waiver of consent 12/12/07

Expedited Review Application

Part 9: Financial Considerations   Will there be reimbursement for subjects?   How will they be paid, check, cash, gift card?

Is the amount coercive?

Will subjects have to pay for any costs associated with the study? 12/12/07

Expedited Review Application

Part 10: Bibliography Part 11: Attachments   Bibliography  Provide a comprehensive list of references as it pertains to your application Attachments     Sponsors protocol Survey instruments Recruitments and advertisement materials Consent forms 12/12/07

CHR Application Supplements:

Full Committee and Expedited Only       Inclusion of Children and Minors Human Biologic Specimen Collecting and/or Banking for Future Research Waiver of Informed Consent/Authorization for Minimal Risk Research or Screening Disclosure of Investigators’ Financial Conflict of Interest IRB Approval Certification for UCSF Researchers Involving Non-UCSF Affiliated Sites More on HRPP website 12/12/07

Expedited Review Application: No Subject Contact

Differences form main applications    Procedure section (Part 3)  Biological specimen or data analysis (involves identifiers)  Identify source and how collected Consent section (Part 6)  Waiver of consent/authorization Does not include  Alternatives, recruitment, payment and cost sections 12/12/07

Third step: Exempt Certification

Filling out the Exempt Certification Application

Exempt Certification Application

Part 1: Administrative Requirements       PI, Co-PI, Contact Person Study sites Funding Key Personnel Financial Interests PI Signature 12/12/07

Exempt Certification Application (Category 1, 2, 3) Part 2: Study Specific Information        Study purpose and design Describe

human research subject

How

human research subjects

population will be contacted Study instruments (surveys, questionnaires) How inform subjects of research study– consent regulations do not apply to Exempt research but UCSF requires some form of information sheet. See Exempt Guidance on HRPP website.

How information obtained will be recorded and maintained PI Signature 12/12/07

Exempt Certification Application (Category 4) Part 2: Study Specific Information  Briefly describe study activities  Identify source of biological specimens and/or data  Must be pre-existing at time of proposed research  Can have access to identifiers if information is publicly available or information is recorded in a way that the biological specimen or data can be identified, directly or through identifiers linked to the subjects.

DOES NOT APPLY

to research medical records 12/12/07

Fourth step: Consent

Preparing a consent form, assent form, information sheet, or requesting waiver of consent

Three types of consent

   Signed consent  consent forms, parental consent forms, assent forms Waiver of signed consent  Information sheet or verbal script Waiver of consent  Waiver of Informed Consent/Authorization for Minimal Risk Research or Screening Supplement 12/12/07

Fifth step: Review Process

Review Process

Expedited and Exempt Applications

  

Assessment/screening

 

Review by IRB member(s) or Chair

  

Post review correspondence

Approval

 12/12/07 

What do CHR members consider when reviewing a new study?

   Risks to subjects are minimized   Procedures are consistent with sound research design and do not unnecessarily expose subjects to risk.

Study utilizes procedures already performed for diagnosis/treatment Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result Selection of subjects is equitable    Inclusion/exclusion criteria are adequate Research purpose and setting is appropriate Recruitment process is fair 12/12/07

Top Tips and Additional Discussion Points

Top Tips for Speeding Up Your CHR Approval

 Make sure science is sound. Study should be reviewed for

scientific merit

, preferably by a group of peers, before submitting to the CHR.

 Determine

appropriate level of review ,

or if review is required.

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Top Tips for Speeding Up Your CHR Approval

  Download and follow the most current CHR Application Forms and Consent Templates from HRPP website. Click on links in application for help.

Check the HRPP website to see which Application Supplements are needed for your particular study.

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Top Tips for Speeding Up Your CHR Approval

 Consider the audience when writing application and consent documents:  Avoid acronyms if possible; if needed, spell out before first use.   Write application with understanding that not all members are scientists, and few if any are experts in your field.

Consent documents should be written in lay language at a grammatical level appropriate for the prospective subjects. Avoid jargon, legalese, long complex sentences, and use of passive voice.

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Top Tips for Speeding Up Your CHR Approval

 Strive for consistency within and among the various parts of the submission:  Assure that all sections within the CHR Application are consistent with each other, i.e., the purpose, benefits and alternatives.

   Assure that all sections within the consent form are consistent (see above). Assure that the protocol and consent form are consistent. Use the same name for the subject groups throughout the application and consent documents.

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Top Tips for Speeding Up Your CHR Approval

 Provide a detailed discussion of the recruitment and consent process. Include the who, what, when, where and how of each. Submit copies of all recruitment materials and consent documents, including scripts.

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Top Tips for Speeding Up Your CHR Approval

 Write a cover letter to  explain and highlight any particularly difficult or sensitive issues to show that you have thought them through ahead of time, or ask for CHR input, or  inform the CHR if you have special time constraints, i.e., if study is being sent in “just in time” for NIH funding, you have a patient waiting.

 Explain how many consent forms are being used if there are several – this is particularly important for research involving minors.

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Top Tips for Speeding Up Your CHR Approval

Proofread Your Work!!!!!

Do a final review of CHR Application and study documents. If you are preparing the application and are not the study PI, make sure the study PI has read the application. This is critical if the PI is your mentor.

12/12/07

Top Tips for Speeding Up Your CHR Approval

  If you have any questions about the process, call the CHR office at 476-1814 and ask to speak to the Analyst of the Day or e-mail [email protected]. Calls and e-mails will be returned within 24 hours.

Bonus Tip: Get a separate CHR approval for each discrete study. Do not group related studies into a complicated application 12/12/07

Ask Questions

   Ask your PI or Mentor Call or email the CHR and ask for Analyst of the Day Main Line: 415-476-1814  http://www.research.ucsf.edu/chr/ 12/12/07

Topics from Survey Request

      Modifications and Renewals Certificates of Confidentiality Research vs. Quality Improvement Writing Consent Forms and Informed Consent Process HIPAA AE’s, Violations and Incidents 12/12/07

HRPP Training: Upcoming sessions

 

Preparing Consent and Assent Forms

  February 2008 Richard Wagner, HRPP Associate Director

After CHR Approval: Post Approval Event Reporting

  April 2008 HRPP QIU Program 12/12/07

More Resources

  CTSI: Clinical and Translational Science Institute

http://ctsi.ucsf.edu/

RKS: Regulatory Knowledge and Support 

http://ctsi.ucsf.edu/rks/request/

 Marlene Berro [email protected]

, 476-3426 BREAD: Biostatistics, Research Ethics And Design Program  [email protected]

, 502-7893 12/12/07

www.research.ucsf.edu/chr