Human Research Protection Program Training Preparing an Exempt or Expedited Application Lisa Voss, MPH, CIP Assistant Director, HRPP Quality Improvement

Human Research Protection Program Training

Preparing an Exempt or Expedited Application

Lisa Voss, MPH, CIPAssistant Director, HRPPQuality Improvement [email protected]

February 20, 2009

mailto:[email protected]

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Human Research Protection Program

HRPP Training: Upcoming Sessions

• The Study Coordinator's Role in Investigator-originated StudiesDate and Time: Tuesday, March 10, 2009, 10 a.m.-noon Location: Parnassus campus, N-225 Speaker: Diane Davies RN, Manager, Clinical Research Unit, Helen Diller Family Comprehensive Cancer Center

• Preparing Consent and Assent FormsDate and Time: Thursday, April 30, 2009, 10 a.m.-noon Location: Parnassus campus, N-225 Speaker: Richard Wagner, Associate Director

Introduction

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Outline for Today

• Demystifying the CHR review process

• The Exempt Application

• The Expedited Application

• Top Tips for Speeding Up CHR Approval

• Getting Answers After this Class

• Open Questions and Answers

Introduction

Demystifying the CHR Review Process

Committee AssistantsAdministrative Assistant IIs

Meri Figueroa Brian HertzogDenisha OtisMario Velez

--------------------------TEP for Data Entry

TEP for Filing

HRPP Director John Heldens

Manager Assessment Unit

(Pre-CHR Review Activities) Vacant

Analyst V Supervisor

HRPP Associate DirectorCHR Review UnitRichard Wagner


HRPP Assistant Director Quality Improvement Unit

(Post CHR Approval Activities)Lisa Voss


Committee CoordinatorsMt. Zion

Michael Thomas -- IVNicole Ketroser -- II

Committee CoordinatorsParnassus

Annette Bugatto -- IVWendy Stephens -- II

Committee CoordinatorsSFGH

Elizabeth Mendelsohn -- IVTerry Colbert -- II

QIU GroupBeth Shields -- Analyst IV

Susie Corl – Analyst IVJill Magee – Analyst II

Education & Assessment UnitAnita Katona – Analyst IV

Joanne Mickalian– Analyst IVMegan Sullivan – Analyst II - Supervisor

Fred Hendrickson – Analyst II

HRPP Business Analyst Judy Der - Analyst II

Cancer Ctr. Asst. CoordinatorSusanne Henderson -II

Committee CoordinatorsLaurel Heights

Karen Chao - IVKate Nolan - Analyst II

HRPP Organization – January 2009

Education CoordinatorMelanie Mace - Analyst IV

HRPP – Human Research Protection Program CHR – Committee on Human Research QIU – Quality Improvement Unit

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First Step:

Determining

“Is the project human subject research?”


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Definition of Research

• A systematic investigation, including

– Research development, testing and evaluation

– Designed to develop or contribute to generalizable knowledge

45 CFR 46.102


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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 45 CFR 46.102


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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:

– 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.


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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

Data and/or specimens are de-identified*

Human subjects

Not human subjects

See the conditions that must be met.

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

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.

Do the PI or Co-Investigators on the study have access to the

“key” to link back to the identifiers*?

Examples1. Commercially available specimens

2. Adult cells lines with no identifiers, NOT stem cells

3. Cadaveric tissue with no identifiers

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Human subjects

Expedited Review or Full Committee 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.

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.

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Second step:

Determining the Level of Review/Type of Application to Submit


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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 regulations

• “Minimal risk” 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 examinations or tests

45 CFR 46.102


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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


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Expedited Review Categories

1. Research with approved drugs or devices

2. Blood sampling (small amounts)

3. Noninvasive specimen collection

4. Noninvasive clinical procedure

5. Use of data or specimens collected for nonresearch purposes

Demystifying the CHR Approval Process

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Expedited Review Categories

6. Research recordings: voice, video, digital, or image recordings

7. Low risk behavioral research

8. Renewal of inactive research protocols or protocols that are essentially complete

9. Renewal of other minimal risk research protocols


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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


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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

The Expedited Review Application

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• PI, Co-PI, Contact Person

• Study sites

• Funding

• Scientific Merit

• Key Personnel

• Financial Interests

• PI Signature

Part 1: Administrative Requirements


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• Synopsis vs. Design vs. Procedures

• Hypotheses

• Specific Aims

• Background vs. Preliminary Studies

• Design

• Statistical Analysis

• Sample Size

Part 2: Study Design


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Expedited Review Application

• 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

Part 3: Procedures


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• Provide a discussion of the alternatives to participation

• Many times includes not participating!

Part 4: Alternatives


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• 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

Part 5: Risks and Discomforts


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• HIPAA section

• Identify source and personal health information that will be collected

• How will it be maintained and protected

• Disclosures

• Benefits – Overall risk/benefit analysis

• Explanation of why the benefit outweighs the risk of loss of confidentiality

Part 5: Risks and Discomforts


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• CHR Supplements?

• Inclusion & Exclusion Criteria

• Be specific

• Determining eligibility

• Non-regulated vulnerable populations

• HIV

Part 6: Subject Information


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• 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

Part 7: Recruitment


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• How, where, when and by whom informed consent will be obtained

• Ensuring understanding

• Consent

• Signed consent

• Waiver of signed consent

• Waiver of consent

Part 8: Informed Consent


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• 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?

Part 9: Financial Considerations


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• Bibliography

• Provide a comprehensive list of references as it pertains to your application

• Attachments

• Sponsor’s protocol

• Survey instruments

• Recruitments and advertisement materials

• Consent forms

Part 10: BibliographyPart 11: Attachments


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CHR Application Supplements

• 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 Investigator’s Financial Conflict of Interest

• IRB Approval Certification for UCSF Researchers Involving Non-UCSF Affiliated Sites

• More on HRPP website


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Expedited Review Application: No Subject Contact

• Procedure section (Part 3)

• Biological specimen or data analysis involving identifiers

• Identify source and how collected

• Consent section (Part 6)

• Waiver of consent/authorization

• Does not include

• Alternatives, recruitment, payment and cost sections

Differences from other applications


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Fourth step: Exempt Certification

Filling out the Exempt Certification Application

The Exempt Application

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Exempt Certification Application

• PI, Co-PI, Contact Person

• Study sites

• Funding

• Key Personnel

• Financial Interests

• PI Signature

Part 1: Administrative Requirements


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• Study purpose and design

• Describe human research subject population

• How human research subjects will be contacted

• Study instruments (surveys, questionnaires)

• How to 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

Part 2: Study Specific Information for Category 1, 2, 3


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• 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 cannot be identified, directly or through identifiers linked to the subjects.

• DOES NOT APPLY to research with medical records

Part 2: Study Specific Information for Category 4


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Fifth step: Consent

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

waiver of consent

The Expedited and Exempt Application

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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


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Sixth step: Review Process


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Review Process

• Expedited and Exempt Applications

– Assessment/screening

– Review by IRB member(s) or Chair

– Post-review correspondence

Approval


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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

The Expedited and Exempt Applications

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Top Tips for Speeding Up Your CHR Approval

• Make sure science is sound. Study should be reviewed by scientific merit, preferably by a group of peers, before submitting to the CHR

• Determine appropriate level of review, or if review is required.

Top Tips for Speeding Up CHR Approval

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

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


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• 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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• 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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• Write a cover letter to:

• Explain and highlight any particularly difficult or sensitive issues to show that you have thought them though ahead of time, or ask for CHR input, or

• Inform the CHR is you have special time constraints i.e., if study is being sent in “just in time” for NIH funding or 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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• 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.


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• 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.


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Ask Questions

• Ask your PI or Mentor

• Call or email the CHR and ask for the Analyst of the Day

• Main CHR Line: 415-476-1814

• Main CHR Email: [email protected]

• www.research.ucsf.edu/chr/


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Getting Answers After this Class

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Topics from Survey Request

• Pre existing data and how to get it published

• What to look for when preparing an application for International work

• Research with other sites

• Collaborative studies that only involve laboratory analysis

• How long does it take to get an approval?

• Documentation for Exempt applications

Getting Answers After This Class

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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

Getting Answers After This Class

Documents

Human Research Protection Program Training Preparing an Exempt or Expedited Application Lisa Voss, MPH, CIP Assistant Director, HRPP Quality Improvement