Research Compliance What’s the Buzz?

Research Compliance The Buzz Publicized research participant deaths since 1999 Changing federal authorities Increasing federal audits, fines, and enforcements IRB members named in civil suite Qui Tam (Whistleblower) Statute applying to federally funded grants Increased public interest in funded bioterrorism research

Consequences of Non-Compliance Fines and Penalties Shutdown of projects - Loss of research funding Institution considered “exceptional” by funding agency Loss of “expanded authorities” under FDP” Additional oversight/monitoring by the government Potential reduction in funding Professional integrity compromised Reputational risk

INSTITUTIONS FAILING TO MANAGE ETHICAL AND REGULATORY ISSUES InstitutionAccusation University of MinnesotaMisuse federal grants Thomas Jefferson University Research Fraud University of OklahomaClinical Trial Shutdown Duke UniversityShutdown for Clinical Trials University of PennsylvaniaHuman Gene Therapy Trials Mount Carmel HealthShutdown for Clinical Trials GOVERNMENT DEMAND IMPROVED CONTROL

What, Who, When, Why, How?

What is research? Research is a systematic investigation (including development, testing, and evaluation) designed to discover or contribute to a body of generalizable knowledge.

Who is the research participant? The human participant is a living individual about whom a researcher obtains either 1.data through intervention or interaction with the individual or 2.indentifiable private information

When does research at CMU require Compliance review? If research involves humans animals recombinant DNA

Why protect research participants and researchers? Institutions have a fundamental responsibility to safeguard the right and welfare of the people participating in research activities. Allows research to advance and continue by insuring research is done safely, properly, and ethically. Government regulations requires it of CMU. IT IS THE RIGHT THING TO DO

How do we protect the research participants? Institutional Review Board (IRB) Institutional Animal Use and Care Committee (IACUC) Institutional Biosafety Committee (IBC) Laboratory, Health and Safety

What is an Institutional Review Board? (IRB) A Committee whose primary mandate is to protect the rights and welfare of humans who participate in research

IRB Membership At least five members of varying backgrounds –Sufficiently qualified –Not solely of one profession –Gender diversity At least one non-scientist At least one non-affiliated member Expertise on “vulnerable populations” Outside consultants

IRB Responsibilities Review and approve, require modifications, or disapprove all covered research Require that informed consent is in accordance with regulations Require documentation of informed consent or may waive documentation in accordance with regulations Notify investigators in writing of decisions Conduct continuing review of research no less than once per year

Criteria for IRB Approval Risks to subjects are minimized Risks are reasonable in relation to anticipated benefits Selection of subjects is equitable Informed consent is sought from each subject Informed consent is appropriately documented

The Nuremberg Code (1947) Rules for “Permissible Medical Experiments”. These rules include: –Voluntary consent –Benefits outweigh risks –Ability of the subject to terminate participation

Nuremberg Code (1947) fundamental ethical principles for the conduct of research Declaration of Helsink (1964) ethical standards in medical research Belmont Report (1974) ethical principles and Federal regulations for the protection of research participants based upon respect for person, beneficence, and justice

Belmont Report Basic Ethical Principles: Respect for Persons –Individual autonomy –Protection of individuals with reduced autonomy Beneficence –Maximize benefits and minimize harms Justice –Equal and just distribution of research burden

Types of IRB Review Exempt Expedited Full Board

Exempted Review The following are the six exempt categories as listed in 45 CFR (b): 1.Research conducted in established or commonly accepted educational settings, involving normal educational practices 2. Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior, unless: a. Participants can be identified, directly or through identifiers linked to them. b. Any disclosure of the human participant’s responses outside the research could reasonably place the participant at risk of criminal or civil liability or be damaging to the participant’s financial standing, employability, or reputation.

Exempted Review 3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (2) of this section, if: a. The participants are elected or appointed public officials or candidates for public office. b. Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information be maintained throughout the research and thereafter.

Exempted Review 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 researcher in such a manner that participants cannot be identified, directly or through identifiers linked to them 5. Research and demonstration projects conducted by or subject to the approval of Federal department or agency heads and designed to study, evaluate, or otherwise examine public health benefit or service programs 6. Taste and food-quality evaluation and consumer acceptance studies

Expedited Review For certain kinds of research involving no more than minimal risk, and for minor changes in approved research, the IRB Chair or a designated voting member or group of voting members review the proposed research rather than the entire IRB. It cannot be assumed that research poses minimal risk because it involves only interview or survey data collection. Sensitive questions may lead to distress that exposes participants to greater than minimal risk. Loss of confidentiality can cause harm to participants, their relatives, and others.

Full Board Review Research involving greater than minimal risk must be reviewed by the full IRB board. When full board review is necessary, the research proposal is presented and discussed at a meeting at which a quorum of IRB members is present. For the research to be approved, it must receive the approval of a majority of those voting members present. (Note that, in effect, an abstention counts as a negative vote.)

Submitting Applications Get application Complete application Get signatures Send Application Take Training

Submitting Applications Get application –Instructions –Cover page –HIPPA forms – if PHI is being accessed –Consent form checklist

Purpose and Definition of Informed Consent Informed consent is a primary ethical principle governing human participant research; it assures that prospective human subjects will understand the nature of the research and can knowledgeably and voluntarily decide whether or not to participate.

Elements of Informed Consent Scope of research and identity of researchers Risk/Benefit disclosure to participants Participation is voluntary and no penalty for early withdrawal Description of research procedures How confidentiality is protected Disclosure of conflicts of interest What’s the compensation Who to contact for questions Signatures

Submitting Applications Get application Complete application –Cover page –Protocol –Consent forms or Request for Waiver of Consent –Recruitment documents –Surveys, Questionnaires –Documentation of IRB Training

Submitting Applications Get application Complete application Get signatures –Principal Investigator Individual who have ultimate responsibility for research –Other researchers Collaborators, graduate students, other students

Submitting Applications Get application Complete application Get signatures Send Application – –Fax : –Campus Mail: Regulatory Compliance Administration UTDC Building, Room 312 (Secure Building) Drop Off/Pickup Times: 8:00am-12:00pm and 1:00pm-5:00pm –Regular Mail: Carnegie Mellon University Regulatory Compliance Administration. UTDC Building, Room Forbes Avenue Pittsburgh, PA 15213

Submitting Applications Get application Complete application Get signatures Send Application Take Training –

Questions? Call or !Who? Regulatory Compliance Administration John Chinn, Compliance Officer (84727) voice fax Website: