- Conflicts of Interest
- Compliance Training and Education
- Quality Assurance / Quality Improvement Projects
- Preparatory to Research Projects
- Human Subjects Research Projects (Working with the IRB)
- Registration of Clinical Trials
- UPMC Research Fiscal Review
Conflicts of Interest
Conflicts of interest (COIs) can threaten the integrity of an institution’s scholarship, research, instruction, evaluation, and administration. Because these are serious issues, the University must disclose conflicts to federal funding agencies and provide assurances that potential conflicts are being managed. Therefore, all faculty and certain staff members are required to complete conflict of interest disclosure forms upon appointment, annually thereafter on or before April 15, and at any time their outside interests change. Individual researchers may also be required to complete an online training module concerning conflicts of interest that covers the following information: various types of COI; underlying ethical principles associated with COI; risks of unmanaged COI; management tools, including special regulations for human and animal subject research; University and federal COI policies; requirements to disclose outside interests; and sanctions for violation of COI policies. Without question, a current COI form must be on file with the University of Pittsburgh Conflict of Interest Office before a research study involving human subjects can begin. Note, however, that in the event of conflicts of interest, the University’s COI Office is willing to work with investigators to develop a management plan that satisfies all parties so the research can continue.
Compliance Training and Education
In order to proceed with a human subject research study and submit a protocol to the University of Pittsburgh Institutional Review Board (IRB), the principal investigator, key research personnel, and research coordinator(s) must have completed the following online training modules: Research Integrity and either Human Subject Research in Biomedical Science or Human Subject Research in Social and Behavioral Sciences offered through Pitt’s Internet-based Studies in Education and Research (ISER) Program. The IRB’s online submission process known as OSIRIS (Online Submission for Institutional Reviews) is linked to the ISER database and will not permit the inclusion of any co-investigator or research coordinator who has not completed the required modules. All principal investigators, listed co-investigators, and study coordinators are also required to complete the Good Clinical Practice training module if the study will be regulated by the U.S. Food and Drug Administration (FDA).
Quality Assurance / Quality Improvement Projects
A quality assurance (QA) project, sometimes known as a quality improvement (QI) project, is typically one that focuses primarily on improving patient care within a particular hospital or health care organization; as such, the outcome of the project may not be applicable to other patient care environments. QA projects do not require IRB review and approval unless they involve human subjects research as defined by federal guidelines. However, local QA projects are still subject to oversight. Projects involving UPMC facilities are reviewed by the UPMC Total Quality Council (412-454-7940); for studies at Children’s Hospital of Pittsburgh of UPMC, review is conducted by the CHP Quality Improvement Committee (412-692-5780). For guidance in distinguishing QA projects from research, see “Quality Assurance Projects versus Research” from the preface of the IRB Reference Manual.
Preparatory to Research Projects
For some projects, you may need to review or collect protected health information (PHI) to design your study or assess its feasibility. If the information will be identifiable (include patient names or other identifiers, for instance), a HIPAA Research Agreement: PHI Usage for Reviews Preparatory to Research must be filed with the IRB. The protected health information is limited in use and must meet specific standards as outlined in the agreement. If the PHI has been de-identified, no approval is required to use the information.
Human Subjects Research Projects
(Working with the IRB)
The purpose of the Institutional Review Board (IRB) at the University of Pittsburgh or any other research institution is to protect the rights and welfare of human subjects, including patients, recruited to participate in research activities.
The fundamental issue in determining whether a project is subject to IRB review and approval is whether it is a human subjects research project—as opposed to a quality assurance project or a preparatory to research project. Federal regulations (45 CFR 46.102) define research as “a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.”
According to the Belmont Report, a 1979 document developed by The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, “the term ‘research’ designates an activity designed to test a hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships).” The Belmont Report further states that “three basic principles, among those generally accepted in our cultural tradition, are particularly relevant to the ethics of research involving human subjects: the principles of respect of persons, beneficence, and justice.”
For information about informed consent, assessment of risks and benefits, and selection of subjects, see Ethical Considerations for Clinical Research.
For research projects subject to IRB review, following is information about protocol application, OSIRIS submission, as well as the initial screening and full screening of studies.
- Protocol Application—Once you have established that your project is defined as human subjects research, you must file a protocol application with the IRB office for review and approval. The protocol will outline the design of the project; define the subject pool (which should be as diverse as possible in terms of sex, age, and race); delineate measures to ensure the safety of those involved and their privacy in conformance with the Health Insurance Portability and Accountability Act (HIPAA); and spell out procedures for adverse event reporting.
- OSIRIS Submission—All IRB applications must be submitted electronically through OSIRIS (Online Submission for Institutional Reviews). This system enables you to check on your application’s status and identify who is currently reviewing or has completed reviewing it. Materials can be submitted through OSIRIS at any time, but projects requiring full board review may not appear before a committee for up to three weeks from the time of submission. If your study also requires UPMC Research Fiscal Review, you must submit the forms through OSIRIS along with your IRB application.
- Initial Screening—An IRB application is initially screened by the protocol processing coordinator to ensure that it is complete and to determine whether it should be forwarded to the exempt/expedited team for review or to the full board. Submissions requiring full board review are assigned to a committee as they are received and are reviewed based on the full board calendar.
- Full Screening—If your protocol requires full board review, you’ll receive notification of any questions posed by the committee shortly after the board meeting. You’ll have up to six weeks to respond. The committee will then review your responses and indicate whether further clarifications are required or whether the protocol has been approved.
- Additional IRB Information—The preface of the University of Pittsburgh IRB manual spells out the jurisdiction, structure, and responsibilities of the Institutional Review Board. In addition, the IRB maintains a detailed Web site with information on all stages of the IRB process. Individuals can sign up for the Pitt IRB mailing list by clicking on the link found on the right side of the home page. The IRB also conducts periodic seminars called, “Ask the IRB.” The schedule of these seminars can be found on the IRB calendar.
Registration of Clinical Trials
On September 27, 2007, the federal government enacted Section 801 of Public Law 110-85, which amends the Public Health Service Act to mandate registration and results reporting of all “applicable clinical trials” in the ClinicalTrials.gov registry and outlines penalties for noncompliance. If an applicable clinical trial is funded in whole or in part by a grant from any agency of the Department of Health and Human Services, any grant or progress report must include a certification that all required submissions have been made to ClinicalTrials.gov. For more information, click here.
Principal investigators (PIs) are responsible for determining whether they are obliged to register their trials in accordance with the law.
The NIH has encouraged registration of all clinical trials, even if registration is not required by law. If PIs are unsure if a trial is an “applicable clinical trial,” they are encouraged to register it. Trials must be registered in full prior to enrollment of the first subject. In addition, many journals require trial registration as a condition for consideration for publication.
Under the statute, “applicable clinical trials” generally include (1) clinical trials of drugs or biologics that are clinical investigations (other than Phase 1 investigations) of a product subject to FDA regulation and (2) clinical trials of devices that are controlled clinical trials with health outcomes (other than small feasibility studies) and all pediatric post-marketing surveillance.
In addition to the registration requirement, there are requirements for publication of applicable clinical trial results.
To initiate the clinical trial registration process, a PI must establish an account with the ClinicalTrials.gov Protocol Registration System (PRS) by sending an e-mail message to the University’s PRS administrator, Laurel Yasko, at lyasko@pitt.edu. The subject line must state “Protocol Registration,” and the body of the message should contain the PI’s name, phone number, and e-mail address. After being notified that an account has been created, the PI can complete the registration process on the ClinicalTrials.gov Protocol Registration System Web site. A unique identifier, called an NCT number, will be generated during the registration process. This number should be used for NIH reporting purposes and for manuscript submissions.
Note that trials may be registered prior to receiving IRB approval. However, before the first patient is randomized into the trial, IRB approval must be obtained, and the ClinicalTrials.gov record for the clinical trial must be updated by the PI. In addition to including the IRB approval number in the update, the “approval status” field should be set to “approved,” the “overall status” field should be set to “recruiting,” and the recruiting status should be updated for each location (as applicable).
More information about registration of clinical trials is available online from the Office of Clinical Research. Questions may be addressed to Laurel Yasko: lyasko@pitt.edu or 412-648-9756.
UPMC Research Fiscal Review
In addition to applicable IRB certifications, all clinical research studies or clinical trials that involve UPMC patient care services must undergo UPMC research fiscal review to ensure that UPMC and the investigators avoid billing compliance risks associated with clinical research.
To determine whether your study requires UPMC fiscal review, ask yourself these two questions:
1) Will research subjects undergo diagnostic testing, physical or mental exams, medical procedures or therapies, or receive any other health care services?
2) Will any of the above services be performed at a UPMC facility?
If both answers are “yes,” the study requires UPMC fiscal review. (For additional information, call the Research Fiscal Review Office at 412-647-4446.)
Once you’ve determined that a study requires research fiscal review, you must submit documentation to the UPMC Research Fiscal Review Office. For new studies being submitted through OSIRIS, you must provide the proposed informed consent document, a completed Research Fiscal Review Form, and a Research Fiscal Review Approval Form (with only the top two sections completed). Additional required forms will vary depending on whether the study involves a medical device, is being conducted through the UPMC Clinical Trials Office, or uses a Clinical and Translational Research Center. Details about specific documents needed for particular kinds of studies can be found in the Instructions and Information document provided by the UPMC Research Fiscal Review Office, which has compiled a list of helpful hints to aid in navigating the review process.
For industry-sponsored and -initiated trials, which are monitored by the UPMC Clinical Trials Office (CTO), you do not need to file fiscal review forms; CTO will take care of this process for you.
