THE COMMITTEE ON HUMAN RESEARCH

UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES

EXEMPT CERTIFICATION AND NON-HUMAN SUBJECT RESEARCH APPLICATION (Effective 02-19-04, Revised: October 2004, June 2007, August 2007, March 2008 )

•  General Instructions
•  Filling Out the Exempt Certification Forms
•  Submission Requirements
•  Review Turnaround
•  Approval Period
•  Exempt Categories 1, 2, and 3
•  Exempt Category 4
• Determining Whether Human Subjects are Involved in Research When Obtaining Private Information (data) or Biological Specimens
• Additional Discussion: Prospective versus Retrospective Collection of Information or Specimens
• Useful Links and References

General Instructions

Exempt certification - exempt categories of research are defined by the Department of Health and Human Services (DHHS) regulations for protection of human subjects in 45 CFR 46.101. If an investigator believes his or her study qualifies as exempt from Institutional Review Board (IRB) review, then the exempt certification form must be completed and submitted to the CHR office for review and approval. Funding agencies do not allow investigators to make this determination on their own, nor does the University.

There are two Exempt applications. The Exempt Certification Application: Category 4 is for all pre-existing data or biological specimens. The Exempt Certification Application: Category 1, 2, 3 is for research that is being conducted in educational settings, some interviews, surveys, and observations of public behavior. See Exempt Categories below for additional explanation of what may be submitted as exempt at UCSF.

There are hyperlinks throughout the application form to provide quick and easy access to definitions, brief instructions and explanations, other web pages and other forms.

Research that is NOT human subject research: Under limited circumstances, research involving only unidentifiable or coded private information or specimens is not human subjects research. This is determined and certified by the Principal Investigator based on the diagram ‘Determining Whether Human Subjects are Involved in Research When Obtaining Private Information (data) or Biological Specimens’. PIs may use the self-certification form for funding purposes.

Filling Out the Exempt Certification Forms

Submission Requirements

Submit three copies of the completed and signed form to the CHR. Mail copies to the CHR office at Box 0962 (San Francisco, CA 94143), or deliver them to the CHR Office located at the Laurel Heights Campus, in the Office of Research at 3333 California St., Suite 315, or fax three copies to 502-1347

If attachments are included in your application, include a complete set with each copy of the application.

Review Turnaround

Applications are reviewed in the CHR and approved by a member of the IRB. Review turnaround time is typically two weeks from the date of receipt in the office. However, review may be handled more expeditiously upon request for the occasional emergency.

Evidence of certification is the original submission form itself signed and certified as exempt by the CHR; no separate approval numbers are assigned nor are approval letters issued.

Important note: If it is determined that the application does not qualify for Exempt it will be returned to the investigator to be submitted for Expedited or Full Committee Review.

Approval Period

Unlike expedited and full committee applications which must be renewed on a yearly basis, the period for which the certification of an exempt study is valid is three years. At the end of three years the study will have to be terminated or renewed. A renewal notice will be sent to you approximately 60 days before this certification expires. If the CHR does not receive a re-certification at the time of expiration you will be sent an expiration notice.

Important Note: The CHR sends the renewal notices as a courtesy, it is the PI’s responsibility to keep track of their expiration dates.

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For re-certification, fill out and submit the same Exempt Certification Form as completed previously and modify/update any sections as needed by highlighting the changes. Please mark in the Application Type section of Administrative Requirements that this is a re-certification.

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If the investigator plans any modifications of the procedures which will affect the information given on a previously approved Exempt Certification Form, a new form, with changes highlighted, should be submitted for reconsideration. Please mark in the Application Type section of Administrative Requirements that this is a Modification / Update. At this time the study will be re-certified for 3 years.

Important Details About the Exempt Certification Procedure

Exempt Review Categories 1, 2, and 3

As described and numbered in DHHS regulations (45CFR46.101(b)), research activities in which the only involvement of human subjects will be in one or more of the following categories may qualify as exempt if:

#1: The research is conducted in established or commonly accepted educational settings, involving normal education practices, such as research on regular and special education instructional strategies, or research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

#2: The research involves the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observations of public behavior, except where any of the following conditions exist:

#3: The research involves the use of educational tests, survey or interview procedures, or observations of public behavior when the human subjects are elected or appointed public officials or candidates for public office.

For survey and interview research that is exempt, UCSF requires that the request for exemption describe how subjects’ consent will be obtained with or without out collecting identifiers. The application should include a consent form, information sheet, or script that will be used to obtain consent. Items addressed in the consent process should include but are not limited to:

• purpose of the study and that the activity involves research,
• name and contact information for who is conducting the study,
• why or how the subjects were selected,
• that participation is voluntary,
• types of questions that will be asked,
• how long the subjects participation will take, and
• how confidentiality of the research data will be maintained.

Exempt Review Category 4

#4: The research involves 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.

*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 in research and non-research activities.

**Publicly available means available to the general public. Note: Medical records are not considered publicly available.

Example: Extra vials of identifiable specimens exist (are “on the shelf”) at the time the research is proposed. This may include specimens from Pathology or Laboratory Medicine. If the researcher obtains these specimens and removes the identifiers, prior to the research, an Exempt Certification is required because the PI had access to identifiable information.

Example: A researcher studies publicly available data sets that include identifiers, i.e., NCI SEER, (Surveillance Epidemiology and End Results), NHANES, DMV records.

Determining Whether Human Subjects are Involved in Research When Obtaining Private Information (Data) or Biological Specimens

Research that is NOT human subject research: Under limited circumstances, research involving only unidentifiable or coded private information or specimens is not human subjects research. Therefore, HRPP review is not required. The determination is made and certified by the Principal Investigator. To Guide PIs in making this determination the HRPP published the diagram ‘Determining Whether Human Subjects are Involved in Research When Obtaining Private Information (data) or Biological Specimens’. PIs may use the self-certification form for funding purposes.

Important note: This is a change (as of 2007) from UCSF’s previous requirements for Exempt Certifications for Category 4.

Self-Certification Form

• Use the Determining Whether Human Subjects are Involved in Research When Obtaining Private Information (Data) or Biological Specimens decision tree to make the determination whether human subjects are involved in your proposed research study.
• Fill out the Self-Certification Form and keep this for your records or submit to Contracts and Grants for your funding agency. The CHR will not keep a record of the Self-Certifications.

Example: Coded private information and biological specimens obtained from IRB approved repositories that do not include any of the 18 Protected Health Identifiers . (e.g. Cancer Center Tissue Core, UCSF AIDS Specimen Bank, Neurosurgery Tissue Bank) are not human subjects. This is not human subjects research because the IRB approved procedures the repository has but in place to provide specimens without identifiers. Example: Research with live tissue, i.e., surgical tissue that has been resected for clinical purposes and will otherwise be discarded is not considered human subjects if and only if an agreement exists between both parties that the individual providing the specimen will never provide the recipient with identifiable information. Example: A UCSF researcher provides a collaborator with coded data or biological specimens and there is a written agreement between the UCSF researcher and the collaborator that the key or access to the identifying information will never be shared. Example: Proposed research with extra vials of identifiable or coded specimens from Pathology or Laboratory Medicine. The provider of the samples must remove the identifiable information prior to turning the samples over to the researcher. Example: Aggregate data that has been de-identified from its source and is provided to the PI, i.e. STOR provides PI with and aggregate data set or secondary data sets that do not contain any identifiers. Important Notes: 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.

Additional Discussion: Prospective versus Retrospective Collection of Information or Specimens:

• If the private information or specimens are “pre-existing” when the research is first proposed, the study may require
  • No exemption certification or CHR application, if the researcher never obtains identifiers or codes, or there are agreements to prevent sharing identities; or
  • Exempt certification (category 4), if the researcher obtains identifiers but does not record them in research records; or
  • At least an Expedited CHR application if the researcher records identifiers.
• If the private information or specimens are gathered after the research is first proposed (for example, if medical information is entered into a database after the research is proposed), the gathering is considered “prospective” collection.
  • Exemption category 4 above cannot apply, because information or specimens are not pre-existing.
  • No exemption certification or CHR application is required if the researcher never obtains identifiers or codes, or there are agreements to prevent sharing identities.
  • At least an Expedited CHR application must be submitted if the researcher obtains or records identifiers or codes without agreements to prevent sharing identities.
• If the researcher never obtains identifiers and the research is not considered “human research,” it does not matter whether or not the information or specimens existed or are collected before the study is proposed. For example, the research may use de-identified specimens that will be collected by a tissue bank after the research begins—as long as the researcher never obtains identifiers or keys to codes.
• Prospective collection of identifiable private information of specimens—collecting information or specimens after a study is being proposed—always requires at least an expedited application to the CHR.

Useful Links and References:

• OHRP Guidance on Research Involving Coded Private Information or Biological Specimens
• OHRP Human Subjects Regulations Decision Charts
• NIH Decision Tree for Research Involving Private Information or Biological Specimens
• NIH PHS 398: Part II – Exemption 4 Guidance and Information