Human Research Protection Program Training CHR Introductory Training: Protecting Human Research...

Human Research Protection Program

Training

CHR Introductory Training: Protecting Human Research Subjects

Melanie Mace, MAEducation Coordinator, [email protected]

May 22, 2009

mailto:[email protected]

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Overview of Human Research Protection Review

• Why does the CHR exist?

• Why do researchers need CHR review and what needs review?

• What does the CHR look for during the review process?

• Where to go from here?

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Committee on Human Research (CHR)

= UCSF Institutional

Review Board (IRB)

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Why Do IRBs Exist? • Ensure the ethical and equitable treatment of

human research subjects

• Driving Ethical Principles – Belmont Report

– Beneficence

• Favorable risk/benefit ratio

– Respect for Persons

• Voluntary participation

• Informed consent

– Justice

• Sharing of risks and benefits

• Fair selection of subjects

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Human Research Governed by Multiple Regulations

• 45 CFR Part 46 (OHRP)

• 21 CFR Parts 50 and 56 (FDA)

• HIPAA Privacy Rule

• Additional state and federal laws

• University policies

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What’s at stake for the PI and Institution?

• Release of funding

• Release of investigational drugs/devices

• Ability to treat patients on research protocols

• Ability to publish research results

• An extra layer of subject and PI protection

• Reputation and academic standing

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Make-up of an IRB Panel

• 4 equal panels, each meeting twice a month

• Members are appointed by Institutional Official

• Most members are MDs, RNs or PharmDs

• At least one unaffiliated member (usually a lawyer or subject advocate)

• At least one non-scientist

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Mandate of the CHR

• Review and make decisions on all research involving human subjects performed by UCSF faculty, staff and students regardless of funding and location.

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First Step:

Determining

“Is the project human subject research?”

Demystifying the CHR Review Process

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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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Not Human Subjects Research

Research involving private information or specimens does not involve human subjects and does not require CHR review if:

• The researcher never obtains identifiers or codes.

• Includes pre-existing or prospectively collected data or samples that were not collected specifically for the current research project.

• Consult guidance chart and confirm using the Self-Certification Form.

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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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Second step:

Determining the Level of Review Required and Submitting to the CHR


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Who can serve as PI on aCHR Application?

• PI – must be a UCSF faculty member who meets the eligibility requirements for PI status on grant applications

• UCSF Postdoctoral Fellow – only with eligible Co-PI

• Others can request PI status – requires Department and Dean sign-off

• Reminder: PIs, Co-PIs and Key Personnel must complete human subjects training (CITI)

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Determining Level of Review/Type of Application to Submit

• The level of risk to the subject determines the level of review required and the type of application

• The risk level is compared to “minimal risk”

• “Minimal risk” = 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

• 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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Exempt Certification

• This type of research involves human subjects, but the level of risk is low enough so that CHR approval is not required.

• However, the CHR must review the application and certify that the project qualifies for the exemption.

• Research must fit into one of four federal categories.

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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 AND disclosure of individuals’ identities does not put them at risk

– DOES NOT APPLY to research with UCSF patients, children (minors), and prisoners

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Exempt Review Categories

3. Interviews or surveys with public officials

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: Does not apply to medical record review.

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Expedited Review

Expedited Review Application for research which presents no more than minimal risk to the subjects and fits into one of the 9 federal expedited review categories:

1. Research with approved drugs or devices

2. Blood sampling (small amounts)

3. Non-invasive specimen collection

4. Non-invasive clinical procedure

5. Use of data or specimens collected for non-research purposes

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Expedited Review Categories (con’t)

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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Full Committee

Full Committee Application: for studies which may present greater than minimal risk to subjects; examples include

• Phase I, II, III, and IV studies

• Studies using investigational agents

• Studies using x-rays (but not ultrasounds or dopplers)

• Compassionate use protocols

• Behavioral studies involving vulnerable populations

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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

– Allowed in limited circumstances in which confidentiality is main risk or signed consent is not usually required

• Waiver of all consent

– Only if the research is minimal risk, the waiver will not adversely affect subjects, it’s impracticable to obtain consent, and subjects will be provided with additional pertinent information after participation (when applicable).

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Review Process

• Full, Expedited, and Exempt Applications

– Assessment/screening

– Review by Committee, CHR member(s) or Chair

– Post-review correspondence

Approval

This process takes time, so plan accordingly!

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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) and the importance of the knowledge that may result

• Selection of subjects is equitable

– Inclusion/exclusion criteria are adequate

– Research purpose and setting is appropriate

– Recruitment process is fair

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Remember! IRB Review is required before initiating, modifying or extending any research project that uses human subjects

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Step 3:

• Items to submit after initial approval

– Modifications

– Renewals

– Post-Approval Event Reporting

– Study Close Out Reports

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ModificationsMinor vs. Administrative

• Minor– Very minimal or no increased risk to subject

– Examples: changing minor procedures, reducing or adding minor risks, adding or changing an advertisement, and changing information in study documents (beyond fixing the errors listed below).

• Administrative – Changes that do not affect participants

– Examples: fixing typographical, grammatical, formatting or spelling errors; changes in shipping methods

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ModificationsMajor

• Major– More than a minimal increase in risk

– Anything that requires reevaluation of the risk/benefit ratio

– Examples: adding new procedures, changing study design, changing or adding investigational drugs or devices, and adding a vulnerable population

• Must undergo full Committee review

• Submit as a renewal

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Renewals

• Maximum approval is 364 days, per Federal Regulations

– Exempt certification valid for 3 years

• Work CANNOT continue on an expired study unless it is for subject safety – notify the CHR before any such research activities are done

• Renewals and modifications can be combined

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Adverse Events, Incidents, Violations

• Follow CHR guidance to report unanticipated problems involving risk to participants or others, or serious or continuous noncompliance:

http://www.research.ucsf.edu/CHR/Apply/Post-Approval_Reporting.pdf

• If you are audited and there are significant findings, let the CHR know.

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Tip #1: Be Consistent

All documents and sections of the application should be internally consistent:

• Check the purpose, significance, procedures, benefits and alternatives in both the protocol and consent form.

• Always define groups with clear labels and use this throughout the application and consent, i.e. focus group, interview group, and key stakeholders

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Tip #2 – CHR Application

• Provide a thorough discussion of the background and goal of study

• Clearly spell out the procedures in a way they can be reproduced

• Address all sections – don’t overlook providing a discussion of risk, privacy and confidentiality even if just doing interviews

• What is experimental versus standard of care?

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Tip #3: Recruitment and Consent Process

• Thoroughly discuss the processes for each subject group

• Provide all of the recruitment and consent materials for each group

• What happens to subjects who decline to be in the study?

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Tip #4: Explain What Is Different or Sensitive• Carefully address and discuss any issues that

may raise ethical concerns for the members or may be uncomfortable for the subjects

• Explain these in

– The application

– The consent form

– A cover letter

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Tip #5: 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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HRPP Training: Upcoming Sessions

• Submitting Modifications and Renewals

– Thursday, July 16, 1:30 p.m.-3 p.m., N-225

– Michael Thomas, Manager, HRPP Assessment Unit

• Post-Approval Event Reporting

– Tuesday, August 11, 10-11:30 a.m., N-225

– Lisa Voss, Assistant Director, HRPP Quality Improvement Unit

Human Research Protection Program Training CHR Introductory Training: Protecting Human Research...

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