Transcript irb.wayne.edu
Wayne State University Detroit, MI
The Human Subjects’ Protection Regulations and You: What Everyone Should Know October 25, 2010
Elyse I. Summers, J.D.
Director Division of Education and Development
Outline History/Background Ethical Principles Overview of OHRP Investigator Responsibilities Activities Update
Philosophical Basis Immanuel Kant (1724 - 1804): “For all rational beings come under the law that each of them must treat itself and all others never merely as means, but in every case at the same time as ends in themselves.”
Pre WWII Edward Jenner (1789)
Smallpox Vaccine
Claude Bernard (1865)
Ethical Maxims
Louis Pasteur (1885)
Rabies Vaccine
Walter Reed (1900)
Yellow Fever
Nuremberg During the Nuremberg War Crimes Trials, 23 German doctors were charged with crimes against humanity for “performing medical experiments upon concentration camp inmates and other living human subjects, without their consent, in the course of which experiments the defendants committed the murders, brutalities, cruelties, tortures, atrocities, and other inhuman acts.”
The Nuremberg Code (1947)
As part of the verdict, the Court enumerated some rules for "Permissible Medical Experiments", now known as the “Nuremberg Code”. These rules include:
voluntary consent benefits outweigh risks ability of the subject to terminate participation
Declaration of Helsinki
Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects
“Concern for the interests of the subject must always prevail over the interests of science and society.”
Beecher Article “Ethics and clinical research” Henry K. Beecher New Engl J Med 274 (1966):1354-60 22 published medical studies presenting risk to subjects without their knowledge or approval Published in some of the most prestigious journals and conducted at some of the most prestigious institutions
Public Health Service Policy NIH Director and Surgeon General requested that the National Advisory Health Council review human subject protections Council recommended prior institutional review for PHS supported research to: – Protect the rights and welfare of the subjects – Assure appropriate methods of informed consent – Determine acceptable balance of risks and benefits Adopted as Public Health Service policy in 1966 Beginnings of the Institutional Review Board (IRB)
Tuskegee Syphilis Study American medical research project conducted by the U.S. Public Health Service from 1932 to 1972, examined the natural course of untreated syphilis in black American men. The subjects, all impoverished sharecroppers from Macon county, Alabama, were unknowing participants in the study; they were not told that they had syphilis, nor were they offered effective treatment.
National Research Act 1973 Kennedy Hearings “Quality of Health Care - Human Experimentation” 1974 National Research Act – Established the “National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research” – Required IRBs at institutions receiving HEW support for human subjects research
The Belmont Report
Ethical Principles and Guidelines for the Protection of Human Subjects of Research The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research April 18, 1979
The Belmont Report Basic Ethical Principles: Respect for Persons – Individual autonomy – Protection of individuals with reduced autonomy Beneficence – Maximize benefits and minimize harms Justice – Equitable distribution of research costs and benefits
Office for Human Research Protections (OHRP) (Formerly Office for Protection from Research Risks)
OHRP Oversight All research involving human subjects conducted or supported by the Department of Health and Human Services (HHS) -- 45 CFR Part 46
“Top 10” Investigator Responsibilities
Protecting Human Subjects is a Shared Responsibility Institution Investigator IRB Sponsor Subjects Advocates Government Public Research Team Family
Investigator Responsibility #1
Recognize when the regulations apply to planned activities
Determining Applicability Does activity involve
research
? Does research involve
human subjects
?
Is the human subject research
exempt
?
Human Subject Regulations Decision Chart: http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.
htm
Examples of Investigator Activities Obtaining information about living individuals by intervening or interacting with them Obtaining identifiable private information about living individuals Obtaining informed consent Interacting with subjects Studying, interpreting, or analyzing identifiable private information or data
Investigator Responsibility #2
Comply with relevant Federal regulations
Regulations for Protection of Human Subjects 45 CFR part 46 • Subpart A – basic HHS Policy - “The Common Rule” or Federal Policy - Other federal departments & agencies have adopted
Subpart B
- Pregnant Women, Human Fetuses, and Neonates
Subpart C
- Prisoners
Subpart D
- Children 6
Investigator Responsibility #3
Initial Review
Materials Submitted to the IRB Protocol, grant proposal, informed consent(s) Recruitment materials and plan Any IRB mandated or other related documents
Considerations for IRB Review and Approval Understand IRB expectations and policies Provide sufficient information and materials – Criteria for 46.111 determinations – Provides safeguards for vulnerable subjects – Creates legally effective informed consent, assent, and permission materials – Consider characteristics of local research Recognize and manage conflicts of interest – (e.g., disclose, reduce, eliminate) Comply with IRB decisions and requirements Respond to IRB requests in a timely fashion
Investigator Responsibility #4
Prospective IRB review of proposed changes to research
No Changes to Research Without IRB Review and Approval Prompt reporting to the IRB of proposed changes in a research activity Changes in approved research may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to the subject §46.103(b)(4)(iii)
Investigator Responsibility #5
Continuing Review
Continuing Review Status Report Number of subjects accrued Unanticipated problems (or adverse events) Withdrawal of subjects Complaints about the research Summary of any recent literature, findings, or other relevant information, especially information about risks associated with the research Copy of the current informed consent document Amendments or modifications
Lapse in Continuing Review ALL ACTIVITIES MUST STOP!
No enrollment of new subjects IRB will determine if currently enrolled subjects can continue study related interventions/activities Data analysis activities with private identifiable information
Investigator Responsibility #6
Obtain and document legally effective informed consent, assent, and parental permission in accord with §46.116 and applicable subpart(s) and as approved by the IRB.
Informed Consent Informed consent will be sought from each prospective subject or the subject’s legally authorized representative, in accordance with, and to the extent required by §46.116 [46.111(a)(4)] – required unless IRB finds and documents that the criteria for a waiver or alteration of informed consent are satisfied – IRB may require written statement be provided to subjects
The Consent Process Use currently approved informed consent document “Re-consent” as appropriate Provide copy to subject or LAR Subpart D – – Child Assent – Parental or guardian permission
Investigator Responsibility #7
Realize your role when reporting certain incidents
OHRP Reporting Requirements Institutions MUST report: Unanticipated Problems Involving Risks to Subjects or Others Serious or Continuing Noncompliance with the Regulations or IRB Requirements Any suspension or termination of IRB approval
What is an Unanticipated Problem?
Incident, experience, or outcome that is: Unexpected (nature, severity, frequency) Related or possibly related to research, AND Suggests greater risk of harm than previously known or recognized
YES Algorithm for Determining Whether an Adverse Event is an Unanticipated Problem An adverse event occurs in one or more subjects.
1. Is the adverse event unexpected in nature, severity, or frequency?
YES 2. Is the adverse event related or possibly related to participation in the research?
YES 3. Does the adverse event suggest that the research places subjects or others at a greater risk of physical or psychological harm than was previously known or recognized? NO NO NO Report the adverse event as an unanticipated problem under 45 CFR part 46 The adverse event is not an unanticipated problem and need not be reported under 45 CFR part 46
Only Report Unanticipated Problem to OHRP
Reporting Process INVESTIGATOR RESPONSIBILITIES: Describe incident Suggestive Corrective Actions & Possible Modifications
Reporting Process, cont’d IRB RESPONSIBILITIES: Reviewing of incident and report by PI Confirm that corrective actions are sufficient Report to OHRP: – Project title, PI name, HHS or other federal support – Details of UP(s), serious or continuing noncompliance, or reason for suspension or termination of IRB approval – Description of any corrective action or modification to the research required by IRB or institution
Investigator Responsibility #8
Record Retention
Record Retention Maintaining records per IRB requirements 3 years after the study is completed – At least three years past completion of the research activity – Accessible for inspection and copying – In accord with institutional policies & other regulations
Investigator Responsibility #9
Fulfill responsibilities when study is completed
When is Study Completed?
When all following completed: Interactions & intervention Data collection Analysis of identifiable private information Note that institutions/IRBs/funding entities may have additional requirements
Study Completion Responsibilities Notify IRB that study has closed Retain signed consent documents and other IRB records Store study data consistent with IRB plan Honor commitments
Investigator Responsibility # 10
Compliance with the IRB determinations
Compliance Definition of non-compliance: anything that is done outside of IRB approval except to avoid apparent or immediate hazard What is serious and continuing?
Investigator Responsibility # 11
Know your institution’s policies and procedures
Summary Investigator Responsibilities Follow Belmont Report, Federal regulations, IRB & institutional procedures and policies Promptly report changes to the IRB Obtain, document, and retain legally effective informed consent Ensure ongoing protections Understand role when reporting incidents to OHRP
What’s Going On?
OHRP Organizational Chart International Program Office of The Director SACHRP Division of Education and Development (5 staff) Division of Policy and Assurances (10 staff) Division of Compliance Oversight (4 staff )
Update on Education Activities International Program Office of The Director SACHRP Division of Education and Development Division of Policy and Assurances Division of Compliance Oversight
Upcoming OHRP Research Community Fora (RCFs)
Houston, TX (MD Anderson Cancer Center) – January 24, 2011
Boston, MA (Dana Farber Cancer Institute, Harvard) – June 21, 2011
St. Louis, MO (Washington University) – September 26, 2011
Educational Videos
Online Educational Videos Now Showing
Research use of human biological specimens and other private information.
Reviewing and reporting unanticipated problems and adverse events
General informed consent requirements
IRB membership Available on HHS YouTube channel and, for the first two, in RealPlayer format hosted on NIH website (see: http://www.hhs.gov/ohrp/education/index.html# materials )
Online Educational Videos: Coming Soon
IRB recordkeeping
Vulnerable populations
Update on Policy Activities International Program Office of The Director SACHRP Division of Education and Development Division of Policy and Assurances Division of Compliance Oversight
Hot Off the Press: New Final Guidance Document
Guidance on Withdrawal of Subjects from Research: Data Retention and Other Related Issues Clarifies that when a subject chooses to withdraw from an ongoing research study, or when an investigator terminates a subject’s participation, investigator may retain and analyze already collected data relating to that subject, even if that data includes identifiable private information about the subject. Issued: September 21, 2010
Draft Guidance Documents Posted for Public Comment - Status
Draft Guidance on IRB Continuing Review of Research commented).
(posted November 6, 2009; 8 individuals and 10 organizations
Draft Guidance on IRB Approval of Research with Conditions (posted November 6, 2009; 5 individuals and 7 organizations commented).
Request for Information and Comments (ANPRM) on IRB Accountability
March 5, 2009 notice in Federal Register solicited comments on whether HHS should pursue a notice of proposed rulemaking.
The contemplated new rule would allow OHRP to hold IRBs, and the institutions or organizations operating them, directly accountable for meeting certain requirements of 45 CFR part 46.
Goal is to encourage institutions to be more willing to rely on external IRBs and reduce administrative burden without diminishing human subjects protections.
Recently Issued Final Guidance Documents -- FAQs
Frequently asked questions (FAQs) regarding quality improvement activities (posted December 30, 2008; http://www.hhs.gov/ohrp/qualityfaq.html).
FAQs regarding exempt research determinations (posted October 15, 2009; http://www.hhs.gov/ohrp/policy/exempt_res_ det.html).
Revised FAQs regarding the IRB registration process (posted March 29, 2010; http://www.hhs.gov/ohrp/IRBfaq.html).
Posting Documents for Public Comment
Establish dockets at www.regulations.gov
Update on Assurance Activities International Program Office of The Director SACHRP Division of Education and Development Division of Policy and Assurances Division of Compliance Oversight
Federalwide Assurance (FWA) Statistics (as of 8/19/10) Total number of FWAs approved since 2000: 16,079
Total number of currently active FWAs: 10,612
–
Domestic: 8220 (77%)
–
International: 2392 (23%)
Number of domestic FWAs “checking the box” to extend applicability:
–
Extend subpart A (HHS promulgation of the Common Rule): 2596 (31%)
–
Extend subparts A, B, C, and D: 2857 (35%)
–
No extension: 2777 (34%)
IRB Registration Statistics (as of 8/19/10) Total number of IRBs registered since 2000: 7618
Total number of currently active IRB registrations: 5516
–
Domestic: 3553 (64%)
–
International: 1963 (36%)
Total number of institutions/organizations with registered IRBs: 4698
–
Domestic: 2912 (62%)
–
International: 1786 (38%)
Update on Compliance Oversight Activities International Program Office of The Director SACHRP Division of Education and Development Division of Policy and Assurances Division of Compliance Oversight
Updated Compliance Oversight Procedures
Posted October 14, 2009; see http://www.hhs.gov/ohrp/compliance/oh rpcomp.pdf
“For-cause evaluations occur, at OHRP’s discretion , in response to OHRP’s receipt of substantive written allegations or indications of non-compliance with the HHS regulations.” [emphasis added]
OHRP Compliance Oversight Activities New For-Cause Cases Initiated – 1990-2010 100 # of New For Cause Cases 80 60 40 20 0 90 93 96 99 Year O2 O5 O8
OHRP Compliance Oversight Activities New Not-For-Cause Evaluations – 1990-2010 5 # of New Not For-Cause Evaluations 4 3 2 1 0 O2 O3 O4 O5 O6 O7 O8 O9 10 Year
OHRP Compliance Oversight Activities Site Visits – 1990-2010 6 5 4 3 2 1 0 90 93 96 99 Year O2 O5 O8
OHRP Compliance Oversight Activities Suspend/Restrict Assurance – 1990 2010 8 6 # 4 Suspend Assurance Restrict Assurance 2 0 90 93 96 99 O2 O5 O8 Year
Sources of Additional Information and Guidance
OHRP listserv: for instructions on signing up, see http://www.hhs.gov/ohrp/news/distributionlist.ht
ml
OHRP website: www.hhs.gov/ohrp
OHRP telephone (toll free): 1-866-447-4777
OHRP e-mail: [email protected]
OHRP staff telephone numbers/emails: http://www.hhs.gov/ohrp/about/staff.html