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THE COMMITTEE ON HUMAN RESEARCH

UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES

Working with Other Institutions – Collaborating with Researchers at Academic Medical Centers, Hospitals, Clinics and Practices within the United States and at International Locations (February 2005, Revised March 2008, Revised December 2008)

• Brief Overview
• Research Activities: What Defines Engagement in Human Subjects Research
• Types of Collaborations: Working With -
  • UCSF-Affiliated Institutions
  • San Francisco Bay Area Hospitals and Academic Institutions
  • Other US-based Academic Institutions
  • US-based Non-academic Hospitals, Clinics, and Practices
  • International Entities
• Federalwide Assurance (FWA) of Compliance
• When the CHR Can Serve as the IRB of Record and When It Cannot
  • Federally Funded Research
  • Research that is Not Federally Funded

Brief Overview

The purpose of this guidance is to help UCSF investigators meet the regulatory requirements involved with conducting human subject research with other institutions such as academic medical centers, hospitals, clinics, and private medical practices, located within the United States, as well as entities located outside US territories. UCSF investigators who work with other institutions must fulfill requirements that may vary depending on:

• The role the collaborating organization plays;



• The type of regulatory infrastructure in place, namely whether the institution has a governing Institutional Review Board (IRB) or Independent Ethics Committee (IEC); and



• The source of funding for the research.
  
  With these issues in mind, some general principles to be aware of when seeking approval to conduct human research with other institutions include the following:



• Research at other institutions, domestic and foreign, requires review by the IRB at UCSF, the Committee on Human Research (CHR), and review from the IRB/IEC at other location(s).



• UCSF Researchers who function as the lead investigator, prime grant holder or serve as a coordinating center for a multi-center study are responsible for :
  
  
  • Obtaining CHR review for the overall project,
  • Ensuring that other sites receive IRB review at their respective institutions, and
  • Ensuring that relevent safety information is apporpriateley recorded and shared between engaged sites.


• Each institution where research activities satisfy the federal definition of engagement in human subjects research must have its own IRB review.



• For federally funded studies, each institution that must have IRB review also must have assurance under the Federalwide Assurance program (FWA)

  IMPORTANT NOTE: CHR policies and procedures for working with other institutions are consistent with guidance set forth by the Office of Human Research Protection (OHRP) and encompass ethical principles accepted internationally.

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Research Activities: What Defines Engagement in Human Subjects Research

For the purpose of human research oversight, current guidance from the Office of Human Research Protection (OHRP) defines engagement in human research by the type of research activities the institution conducts. For federally funded studies engaged institutions must obtain Federalwide Assurance (FWA) of compliance.

IMPORTANT NOTE: The Committee on Human Research (CHR) requires review at UCSF, and review from the IRB/IEC at other location(s) regardless of funding.

A. Institutions Engaged in Human Subjects Research

In general, institutions are considered engaged in an HHS-conducted or -supported non-exempt human subjects research project (and, therefore, would need to hold or obtain OHRP-approved FWAs and certify IRB review and approval to HHS) when the involvement of their employees or agents in that project includes any of the following:

(1) Institutions that receive an award through a grant, contract, or cooperative agreement directly from HHS for the non-exempt human subjects research (i.e. awardee institutions), even where all activities involving human subjects are carried out by employees or agents of another institution.

(2) Institutions whose employees or agents intervene for research purposes with any human subjects of the research by performing invasive or noninvasive procedures.

Examples of invasive or noninvasive procedures include drawing blood; collecting buccal mucosa cells using a cotton swab; administering individual or group counseling or psychotherapy; administering drugs or other treatments; surgically implanting medical devices; utilizing physical sensors; and utilizing other measurement procedures.

[See scenarios B.(1), B.(2), and B.(3) below for limited exceptions.]

(3) Institutions whose employees or agents intervene for research purposes with any human subject of the research by manipulating the environment.

Examples of manipulating the environment include controlling environmental light, sound, or temperature; presenting sensory stimuli; and orchestrating environmental events or social interactions.

[See scenarios B.(1) and B.(3) below for limited exceptions.]

(4) Institutions whose employees or agents interact for research purposes with any human subject of the research.

Examples of interacting include engaging in protocol dictated communication or interpersonal contact; asking someone to provide a specimen by voiding or spitting into a specimen container; and conducting research interviews or administering questionnaires.

[See scenarios B.(1), B.(2), B.(3), and B.(4) below for limited exceptions.]

(5) Institutions whose employees or agents obtain the informed consent of human subjects for the research.

(6) Institutions whose employees or agents obtain for research purposes identifiable private information or identifiable biological specimens from any source for the research. It is important to note that, in general, institutions whose employees or agents obtain identifiable private information or identifiable specimens for non-exempt human subjects research are considered engaged in the research, even if the institution’s employees or agents do not directly interact or intervene with human subjects. In general, obtaining identifiable private information or identifiable specimens includes, but is not limited to:

(a) observing or recording private behavior;
(b) using, studying, or analyzing for research purposes identifiable private information or identifiable specimens provided by another institution; and
(c) using, studying, or analyzing for research purposes identifiable private information or identifiable specimens already in the possession of the investigators.

In general, OHRP considers private information or specimens to be individually identifiable as defined in 45 CFR 46.102(f) when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems.

[See scenarios B.(1), B.(2), B.(3), B.(7), B.(8), B.(9), and B.(10) below for limited exceptions.]

B. Institutions Not Engaged in Human Subjects Research

Institutions would be considered not engaged in an HHS-conducted or -supported non-exempt human subjects research project (and, therefore, would not need to hold an OHRP-approved FWA or certify IRB review and approval to HHS) if the involvement of their employees or agents in that project is limited to one or more of the following. The following are scenarios describing the types of institutional involvement that would make an institution not engaged in human subjects research; there may be additional such scenarios:

(1) Institutions whose employees or agents perform commercial or other services for investigators provided that all of the following conditions also are met:

(a) the services performed do not merit professional recognition or publication privileges;
(b) the services performed are typically performed by those institutions for non-research purposes; and
(c) the institution’s employees or agents do not administer any study intervention being tested or evaluated under the protocol.

The following are some examples, assuming the services described would not merit professional recognition or publication privileges: an appropriately qualified laboratory whose employees perform routine serum chemistry analyses of blood samples for investigators as a commercial service. a transcription company whose employees transcribes research study interviews as a commercial service. a hospital whose employees obtain blood through a blood draw or collect urine and provide such specimens to investigators as a service. a radiology clinic whose employees perform chest x-rays and send the results to investigators as a service.

(2) Institutions (including private practices) not selected as a research site whose employees or agents provide clinical trial-related medical services that are dictated by the protocol and would typically be performed as part of routine clinical monitoring and/or follow-up of subjects enrolled at a study site by clinical trial investigators (e.g., medical history, physical examination, assessment of adverse events, blood test, chest X-ray, or CT scan) provided that all of the following conditions also are met:

(a) the institution’s employees or agents do not administer the study interventions being tested or evaluated under the protocol;
(b) the clinical trial-related medical services are typically provided by the institution for clinical purposes;
(c) the institution’s employees or agents do not enroll subjects or obtain the informed consent of any subject for participation in the research; and
(d) when appropriate, investigators from an institution engaged in the research retain responsibility for:

(i) overseeing protocol-related activities; and
(ii) ensuring appropriate arrangements are made for reporting protocol-related data to investigators at an engaged institution, including the reporting of safety monitoring data and adverse events as required under the IRB-approved protocol.

Note: Institutions (including private practices) not initially selected as research sites whose employees or agents administer the interventions being tested or evaluated in the study—such as administering either of two chemotherapy regimens as part of an oncology clinical trial evaluating the safety and effectiveness of the two regimens—generally would be engaged in human subjects research (see scenario B.(3) below for a limited exception). If such an institution does not have an FWA, its employees or agents may be covered by the FWA of another institution that is engaged in the research through an Individual Investigator Agreement.

(3) Institutions (including private practices) not initially selected as a research site whose employees or agents administer the study interventions being tested or evaluated under the protocol limited to a one-time or short-term basis (e.g., an oncologist at the institution administers chemotherapy to a research subject as part of a clinical trial because the subject unexpectedly goes out of town, or is unexpectedly hospitalized), provided that all of the following conditions also are met:

(a) an investigator from an institution engaged in the research determines that it would be in the subject’s best interest to receive the study interventions being tested or evaluated under the protocol;
(b) the institution’s employees or agents do not enroll subjects or obtain the informed consent of any subject for participation in the research;
(c) investigators from the institution engaged in the research retain responsibility for:

(i) overseeing protocol-related activities;
(ii) ensuring the study interventions are administered in accordance with the IRB-approved protocol; and
(iii) ensuring appropriate arrangements are made for reporting protocol-related data to investigators at the engaged institution, including the reporting of safety monitoring data and adverse events as required under the IRB-approved protocol;

and (d) an IRB designated on the engaged institution’s FWA is informed that study interventions being tested or evaluated under the protocol have been administered at an institution not selected as a research site.

(4) Institutions whose employees or agents:

(a) inform prospective subjects about the availability of the research;
(b) provide prospective subjects with information about the research (which may include a copy of the relevant informed consent document and other IRB approved materials) but do not obtain subjects’ consent for the research or act as representatives of the investigators;
(c) provide prospective subjects with information about contacting investigators for information or enrollment; and/or
(d) seek or obtain the prospective subjects’ permission for investigators to contact them.

An example of this would be a clinician who provides patients with literature about a research study at another institution, including a copy of the informed consent document, and obtains permission from the patient to provide the patient’s name and telephone number to investigators.

(5) Institutions (e.g., schools, nursing homes, businesses) that permit use of their facilities for intervention or interaction with subjects by investigators from another institution.

Important Note: The UCSF investigator must provide a letter of support from the institution to the CHR.

Examples would be a school that permits investigators from another institution to conduct or distribute a research survey in the classroom; or a business that permits investigators from another institution to recruit research subjects or to draw a blood sample at the work site for research purposes.

(6) Institutions whose employees or agents release to investigators at another institution identifiable private information or identifiable biological specimens pertaining to the subjects of the research.

Note that in some cases the institution releasing identifiable private information or identifiable biological specimens may have institutional requirements that would need to be satisfied before the information or specimens may be released, and/or may need to comply with other applicable regulations or laws. In addition, if the identifiable private information or identifiable biological specimens to be released were collected for another research study covered by 45 CFR part 46, then the institution releasing such information or specimens should:

(a) ensure that the release would not violate the informed consent provided by the subjects to whom the information or biological specimens pertain (under 45 CFR 46.116), or
(b) if informed consent was waived by the IRB, ensure that the release would be consistent with the IRB’s determinations that permitted a waiver of informed consent under 45 CFR 46.116 (c) or (d).

Examples of institutions that might release identifiable private information or identifiable biological specimens to investigators at another institution include: (a) schools that release identifiable student test scores; (b) an HHS agency that releases identifiable records about its beneficiaries; and (c) medical centers that release identifiable human biological specimens.

Note that, in general, the institutions whose employees or agents obtain the identifiable private information or identifiable biological specimens from the releasing institution would be engaged in human subjects research. [See scenario A.(6) above.

(7) Institutions whose employees or agents:

(a) obtain coded private information or human biological specimens from another institution involved in the research that retains a link to individually identifying information (such as name or social security number); and
(b) are unable to readily ascertain the identity of the subjects to whom the coded information or specimens pertain because, for example:

• the institution’s employees or agents and the holder of the key enter into an agreement prohibiting the release of the key to the those employees or agents under any circumstances;
• the releasing institution has IRB-approved written policies and operating procedures applicable to the research project that prohibit the release of the key to the institution’s employees or agents under any circumstances; or
• there are other legal requirements prohibiting the release of the key to the institution’s employees or agents.

For purposes of this guidance, coded means that:

(a) identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, and/or combination thereof (i.e., the code); and
(b) a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

(8) Institutions whose employees or agents access or utilize individually identifiable private information only while visiting an institution that is engaged in the research, provided their research activities are overseen by the IRB of the institution that is engaged in the research.

(9) Institutions whose employees or agents access or review identifiable private information for purposes of study auditing (e.g. a government agency or private company will have access to individually identifiable study data for auditing purposes).

(10) Institutions whose employees or agents receive identifiable private information for purposes of satisfying U.S. Food and Drug Administration reporting requirements.

(11) Institutions whose employees or agents author a paper, journal article, or presentation describing a human subjects research study.

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Types of Collaborations

USCF researchers participate in a broad range of collaborative relationships including those with:

• UCSF-affiliated institutions;



• Other US-based academic institutions;



• US-based, non-academic hospitals, clinics, and practices;



• International entities

Although these collaborations may vary widely in scope and complexity, all human research studies must be reviewed and approved by the Committee on Human Research (CHR), the Institutional Review Board at UCSF. In most cases, approval by the collaborator’s IRB or by the Independent Ethics Committee (IEC) in the host country is also required.

In addition, UCSF must be sure that collaborative research at other institutions meets the requirements of the Federalwide Assurance (FWA) Program. Through the FWA program Institutional Review Boards and Independent Ethics Committees (IRB/IEC) charged with reviewing and approving human research are registered and the respective institution receives approval from the Office of Human Research Protection indicating assurance of compliance with federal regulations (45 CFR 46.103) for the protection of human subjects.

• Working with UCSF-Affiliated Institutions: Many UCSF investigators collaborate with researchers at UCSF-affiliated units. UCSF’s Committee on Human Research (CHR) serves as the IRB of record for the organizations listed below. Links to each organization’s homepage and their respective FWA numbers are provided.
  

IMPORTANT NOTE: Although UCSF is the IRB of record for these UCSF-affiliated institutions, each may have local submission requirements that must be met prior to beginning the human subjects research (e.g. SFGH and SFVAMC).

• Working with San Francisco Bay Area Hospitals and Academic Institutions: UCSF investigators interact with many hospitals and other academic institutions in the San Francisco Bay Area. The CHR provides a list of organizations including IRB contact information.



• Working with other US-Based Academic Institutions: Most, if not all, academic institutions within the US, if they receive federal funding will have already obtained assurance of compliance through the FWA program. Investigators need to ensure that they or their collaborators meet the respective IRB-review requirements.



• Working with US-Based Non-Academic Hospitals, Clinics, and Practices: Hospitals, clinics, and practices that are not affiliated with academic medical centers may not already have in place the IRB and FWA programs necessary for federally-funded research to take place. If investigators are committed to working in these settings, they may be faced with finding a local IRB to review the study and with guiding the organization’s pursuit of assurance of compliance through the FWA program. More information can be found in the section Federalwide Assurance of Compliance.
  
  
  
  • For information on IRB requirements and on determining whether the CHR can serve as the IRB of record, refer to the section When the CHR Can Serve as the IRB of Record and When It Cannot



• Working with International Entities: Researchers who wish to conduct human subjects research in countries outside the United States or its territories must obtain approval from the host country’s ethics committee and from the Committee on Human Research at UCSF.
  
  
  
  • The CHR expects the standards for human subjects protection are no less than those that apply to US-based research.
  
  
  
  • The appropriate Institutional Review Board (IRB) or Independent Ethics Committee (IEC) must be in place and all federally funded studies must have Federalwide Assurance (FWA) before the study can begin.
  
  
  
  • Refer to the Office of Human Research Protection website for:
    
    
    • Lists of the international sites that have approved assurances.
    
    
    
  • Additional topics to consider when conducting international research:
    
    
    
    • Cultural differences that influence study design and the consent process.
    
    
    
    • The rationale for conducting the study with an international population.
    
    
    
    • A description of the host country’s ethics review and oversight mechanism for participant protection.

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Federalwide Assurance (FWA) of Compliance

If an institution is engaged in human subjects research that is conducted or supported by any agency of the U.S. Department of Health and Human Services (HHS), the institution must have assurance of compliance with the HHS regulations (45 CFR 46.103) for the protection of human subjects. Assurance of compliance and federal oversight are managed by the Office for Human Research Protections (OHRP) under the provisions of the Federalwide Assurance (FWA) program. Links to additional information are provided below:

• Obtaining an approved assurance from OHRP: Obtaining assurance is a two-step process:
  
  
  1. The IRB(s) designated under the Assurance must be registered with OHRP. If not, submit the registration.
  
  
  
  2. Complete the Assurance application.

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When the CHR Can Serve as the IRB of Record and When It Cannot

The Committee on Human Research (CHR) is the Institutional Review Board (IRB) at UCSF and, as described elsewhere, serves as the IRB for many UCSF-affiliated organizations. In general, UCSF cannot be considered the IRB of record for non-affiliated institutions or investigators. However, there are a few exceptions and the conditions wherein the CHR can and cannot serve as the IRB for institutions not affiliated with the University are presented below.

Federally Funded Research: The CHR will agree to be the IRB of record if and only if the scope of human subject research at the collaborating site is considered minimal risk and discussed in the CHR Application.The UCSF PI must also complete and submit the IRB Approval Certification Supplement with their CHR Application.

IMPORTANT NOTE: If the risk is greater than minimal, the site engaged in human subject research must obtain its own FWA and designate a registered IRB, or register its own IRB. Refer to the FWA section for details.


• Non-Affiliated Institutions: For the CHR to be the IRB of record, the following must occur:


• The institution must designate the UCSF registered Institutional Review Boards on its Federalwide Assurance application.


• Once this has been signed and posted on the OHRP website, the institutions must complete an IRB Authorization Agreement. The IRB Authorization Agreement must designate whether the IRB review is for all research or specific to one study.


• The research may begin only after the Institutional Officials at the respective organization have signed the IRB Authorization Agreement.
  
  


• Non-Affiliated Individual Investigators: For the CHR to be the IRB of record, the following must occur:


• The individual investigator signs an Individual Investigator Agreement.


• This document requires various assurances of the individual investigator as well as the signature of the FWA Institutional Official.
  
  IMPORTANT NOTE: The Individual Investigator Agreements are rarely approved.

Research that is NOT Federally Funded: There is no formal mechanism for the CHR to be the IRB of record for non-affiliated institutions when federal funds are not involved. However, the CHR may agree to be the IRB of record if and only if the scope of human subject research at the collaborating site is considered minimal risk and discussed in the CHR Application. Because this type of research is handled on a case-by-case basis, contact the CHR to discuss the details of the proposed study. The UCSF PI must also complete and submit the IRB Approval Certification Supplement with their CHR Application.

IMPORTANT NOTE: If the risk is greater than minimal, the site engaged in human subject research must contract with a private IRB.