Title: Institutional Review Boards IRBs and Human Subjects Research Protection Programs HRPP A short course
1Institutional Review Boards (IRBs) and Human
Subjects Research Protection Programs (HRPP)A
short course
2Course Content
- Part 1 Brief Description of the IRB and
Research at Lifespan - Part 2 IRB Support Staff Function
- Part 3 Researcher Responsibilities
- Part 4 How to submit items for
review by the IRB - Part 5 Brief discussion about
Informed Consent
3Part 1
- Brief overview of the IRB and Research at Lifespan
4What is an IRB?
- IRB Institutional Review Board
- at least 5 members
- at least 1 must have a scientific background
- at least 1 must be a non-scientist (this member
must attend a meeting to achieve quorum) - at least 1 non-affiliated member (not affiliated
with the institution) - Members should have expertise in the research
that will be reviewed.
5IRBs are regulated by State and Federal
Regulations
- Federal
- FDA (Food and Drug Administration, Title 21 CFR )
and - OHRP (Office for Human Research Protection, Title
45 CFR Part 46) - State of Rhode Island
- Section 16, Rules and Regulations for Licensing
Hospitals.
6Why is research so heavily regulated?
- The history of Research has not always been one
of ethics and regulations Nazi war crimes
Tuskegee syphilis study Yale Milgram experiments
(obedience to authority, 1961-62) tea room
experiments (homosexual behavior in public
restroom mid 60s)
7The Modern IRB is Born
- 1974- National Research Act mandated specific
requirements for institutional review committees
which became known as Institutional Review Boards
(IRBs) - 1979- The Belmont Report provided guidance as to
how the new rules should be applied. The Belmont
Report defined the three philosophical principles
relevant to research - Respect to persons must provide adequate
information and obtain voluntary consent - Beneficence Minimize harm maximize benefits
- Justice Selection of subjects must be fair and
justified
8- The Primary Concern of the IRB is the Rights and
Welfare of the Research Participants
9The Main Purpose of IRB Review
- To assess the risk/benefit ratio.
- To ensure that informed consent is obtained in an
appropriate manner - To verify that the recruitment methods/materials
are not misleading or coercive - To ensure that the selection of subject is
equitable and justified
10Research at Lifespan
- Lifespan has three IRBs (2 at RIH and 1 at TMH)
- Researchers at Lifespan may submit to any of the
3 IRBs. The exception is prison protocols which
must be submitted to TMH IRB. - The Lifespan Research Program is considered to
be of medium size when compared across the
country. - Currently we have
- 1,250 active protocols
- TMH has 335 and the RIH IRBs have 915
11Lifespans HRPP hierarchy
- Dr. Arthur Klein, Sr.VP Institutional Official
- oversight responsibilities for the HRPP,
delegated to Dr. Klein through the Presidents at
each Lifespan Affiliate - Peg McGill -Director
- Lifespan Office of Research Administration
- Pat Houser- Manager
- Research Review Committees
12Who are the members of Lifespans IRBs?
- Lifespans IRBs are made up of physicians, PhDs,
pharmacists, nurses, clergy, retirees, and
community members who VOLUNTEER their time to
review human subject research proposals. - Members typically spend 2 hours per month
reviewing protocols and 2 hours at the IRB
meeting. Chairpersons spend considerably more
time in service to the IRB.
13Accreditation of the Human Research Protection
Program
- Lifespan is seeking accreditation of our human
research protection program - This accreditation seeks to accredit the entire
human research protection program for all of
Lifespan not just the IRBs. That means were all
in this together.
14Part 2
- Research Review Committee Office
15Who Are We?
- The Research Review Committee Office is made up
of the following - IRB Manager-
- Responsible for the management of research
activity and IRB support staff involved in the
daily activities of processing research. - Assures regulatory compliance of IRBs as well as
researchers and protocols - Assists the research community with information
needed to ensure compliance - Committee Assistants-
- Provide administrative support to the IRB,
researchers and coordinators. - Process, maintain, and update the database,
paperwork and files of all research projects. - Committee Coordinators-
- Review initial IRB applications, continuing
review, adverse events and amendments - Act as a communication liaison between the
committees and the Investigator - Review all submissions to the IRB for appropriate
documentation - Transcribes the IRB meeting minutes and follows
up with the investigator with IRB requests for
approval.
16What Do We Do?
- Review all submissions for completeness and
accuracy - Make a preliminary determination of whether the
submission qualifies for exempt, expedited, or
full board review - Process new applications, revisions to current
protocols, adverse events, continuing reviews,
and protocol deviations/exception reports - Prepare the agenda and distribute review
materials to IRB members - Prepare meeting minutes and communicate with
researchers as to what the IRB requires - Serve as resource to the research community
- Maintain the database
17Part 3
- Researcher Responsibilities
18Responsibility of the PI
- Is to know and understand the regulations and
policies prior to initiating any human research. - Acknowledge and accept their role to protect the
rights and welfare of the research subjects by
complying with all of the regulations.
19GCP and the PI
- When a principal investigator receives an
approval letter from the Lifespan IRB, they are
notified that this institution and the
investigator complies with ICH GCP guidelines as
they correspond to the FDA/DHHS regulations. - Good Clinical Practice (GCP) is an international
ethical and scientific quality standard for
designing, conduction, recording and reporting
trials that involve the participation of human
subjects. - Compliance with GCP standards provides public
assurance that the rights, safety and well being
of trial subjects are being protected and that
clinical trial data is credible.
20GCP and the PI
- The investigators responsibility according to
ICH GCP guidelines - 4.1 Investigator qualifications and agreements
- 4.2 Adequate resources
- 4.3 Medical care of trial subjects
- 4.4 Communication with IRB
- 4.5 Compliance with the protocol
- 4.6 Investigational product
- 4.7 Randomization procedures and unblinding
- 4.8 Informed consent of trial subjects
- 4.9 Records and reports
- 4.10 Progress reports
- 4.11 Safety reporting
- 4.12 Premature termination or suspension of a
trial - 4.13 Final report by the investigator
21So what are some of the other PI requirements?
- Ensure that research activities are carried out
according to the IRB approved protocol - Protect subject confidentiality by storing
electronic research data on password protected
computers, and paper data in locked cabinets
within locked offices - Follow HIPAA regulations when the research
involves the use or disclosure of PHI -obtain
authorization from prospective subjects. - Ensure that only IRB approved recruitment
materials and research authorizations are used - Provide signed copies of consent and
authorization forms to research subjects and keep
the originals in secured research files - When appropriate, place copy of the consent form
and authorization in the subjects medical record.
22So what are some of the other requirements for
PIs?
- Human Subject Protection (HSP) Training is
required for all research personnel who interact
with human subjects or their identifiable data.
Re-certification is required every 3 years. - Each PI must also sign a HIPAA Security Assurance
annually. - HIPAA for Research training is an annual
requirement. Each department in Lifespan must
provide this training to their employees. - HSP and HIPAA training can be done on-line at
http//www.citiprogram.org
23Part 4
- Process for Submission to the IRB
24Process for Submission to the IRB
- This section will cover
- New Applications
- Continuing Review (progress reports)
- Requests for Revision to Protocol
- Adverse Events/Unanticipated Problems
25IRB forms and Instructions are posted at
www.lifespan.org/research/
26IRB forms and Instructions are posted at
www.lifespan.org/research/irb/irb.asp
- From the ORA web page, select Human Subject
Research
27IRB forms and Instructions are posted at
http//www.lifespan.org/research/irb/irbformslist.
htm
- From the IRB web page, select Human Subject
Committee forms
28IRB forms and Instructions are posted at
http//www.lifespan.org/research/irb/irbformslist.
htm
- Each of the forms are available as hyperlinks on
the forms list. - The new application form includes a checklist
that details each of the IRB forms that are
required for your new application. - Form specific instructions are also available for
download by clicking on the LINK in the third
column
29When in doubt- read the instructions
- Instructions and helpful tools are available for
download. - From the IRB forms page, select the first item on
the list, - How do I submit an IRB application and other
guidance
30How to submit an application to the IRB
- Develop a research plan/grant application or
obtain a study protocol from the sponsor - Obtain required forms for IRB review from the ORA
website http//www.lifespan.org/research/ refer
to IRB application checklist and instructions for
further information - Determine when the application is due
- Deadlines are posted on the IRB web page and are
labeled Deadline/Meeting dates - In most cases, any of the three Lifespan IRBs
can review an application for use at a Lifespan
affiliate. - Special circumstances for research to be
conducted at Bradley or Newport, and research
involving prisoners
31How to submit an application to the IRB
- Do you need Full Board, Expedited, or Exempt
review? Reminder Expedited/exempt projects do
not have a deadline and only require 2 complete
copies. - Financial Considerations before you submit your
application - provide Dept cost center if internally funded,
- submit business forms to Grants and Contracts
Office if externally funded - Submit the completed application, with the
required number of copies, to Review Committee
staff by the due date. -
-
32What happens Next?
- Research Review Committee staff review the
submitted application for completeness. After
the application is accepted, it is processed for
review. - Expedited/Exempt projects Research Review
Committee staff will contact the PI when the item
comes back from the reviewer - Full Board Review -Applications that are accepted
for full board review are placed on the agenda
for the next committee meeting. Principal
Investigators, or their representatives, are
required to appear before the committee to
address any questions or concerns raised by the
reviewers.
33What happens Next?
- 3. After the IRB meeting, Review Committee staff
prepare the minutes from the meeting and send a
summary of the application discussion and
comments to the investigator. - Investigators make the committee required changes
and return any requested information/clarification
s to Review Committee staff. - Review Committee staff verify that the requested
corrections have been made and process approval
as appropriate.
34What happens Next?
- 6. If the study is funded by an external source
(grant/contract), then the approval letter will
specify that the project is approved but not
activated and that no activity is allowed until
the activation is in place. When the
grant/contract has been finalized, an activation
notice with the new cost center will be sent to
the investigator from the Grants and Contracts
Office. If the project will use Dept. funds,
and a cost center has been provided, then the
IRB approval letter will also include an
activation notice. - Investigators cannot begin any project involving
human subjects until IRB approval and financial
activation have been received.
35Congratulations, Your Study Has Been Approved!
Now What?
- Projects are approved for a period up to 12
months. The IRB may require more frequent review
depending on the level of risk. - Before IRB approval expires, Review Committee
will send a progress report to be completed by
the PI. It is ultimately the PIs responsibility
to submit the continuing review report in a
timely fashion to ensure a lapse in IRB approval
does not occur.
36Congratulations, Your Study Has Been Approved!
Now What?
- Be sure to answer all questions. Follow the
checklist at the back of the progress report to
ensure that all required documents have been
included. - Progress reports are processed and reviewed in
the same manner as new applications. - Please note the following
- Continuation of the project beyond the
anniversary date is contingent upon submission of
this report. If the progress report is not
received by the due date, approval will expire
and no work will be allowed until the report is
submitted, reviewed, and approved.
37Steps to submitting a Request for Revision to
Protocol for review by the IRB
- 1. Determine which aspects of the project will
be revised (e.g. protocol, consent forms,
advertisements, personnel, etc) - Obtain required form for IRB review from the ORA
website and submit with all required attachments - www.lifespan.org/research/irb/irbformslist.asp
38Steps to submitting a Request for Revision to
Protocol for review by the IRB
- If the revision includes information that must
be communicated to currently enrolled subjects
(such as altered schedules, revised compensation,
newly identified side effects), then you must
describe the plan for notifying enrolled
subjects and attach any documentation that will
be used for this purpose.
39Steps to submitting a Request for Revision to
Protocol for review by the IRB
- Most minor revisions can be processed for
expedited review. - Changes which substantially alter the protocol,
or change the RiskBenefit ratio require review
by the convened IRB (full board review). Contact
the IRB Coordinator/Manager for guidance. - Please Note The IRB Chairperson has the
authority to refer any item to the full board for
review.
40Reporting Unanticipated Problems
- The principal investigator must report to the IRB
those unanticipated problem/adverse events
occurring locally or at another site, that are - specific to a study approved by a Lifespan IRB,
and that - involve risk to human subjects or others (i.e.
subject family members, research staff) and are - Unanticipated, serious, and related to the
research activity Or, are - Expected but occurring at greater frequency or
severity than anticipated. Or, - The AE indicates an increase in the risk to
participants, regardless of severity
41Reporting Unanticipated Problems
- The principal investigator must also report to
the IRB - any deviations from the protocol or an
accidental or unintentional change to the
protocol taken without prior IRB approval to
eliminate apparent immediate hazard to a research
participant (submit a deviation report for this
event as well) - a breech in confidentiality that may involve
risk to that individual or others - a complaint of or from a participant that
indicates an unanticipated risk or which cannot
be resolved by the research staff.
42Reporting Unanticipated Problems
- Adverse Event and Deviation Reporting forms are
posted on the IRB webpage at - www.lifespan.org/research/irb/irbformslist.asp
43Part 5
- Informed Consent
- Its a Process not a form
44Historical Background
- The requirement that researchers obtain informed
consent from research subjects originates with
Principal 1 of the Belmont Report Respect for
Persons
45Respect for Persons
- Individuals are treated as autonomous agents.
This means that the subjects are not controlled
by others and are able to make independent
decisions - Persons with diminished autonomy are given
protection (e.g. vulnerable subjects such as
children, prisoners, mentally disabled) - Consent to participate in research is voluntary
and informed
46Informed Consent - Process
- Informed consent is a process that begins when
you first approach the potential research subject
and continues throughout the course of the study.
47Informed Consent- Process
- The first contact with research subjects may be
through any of the following - direct advertising
- medical record review to screen for eligible
subjects - physician referral
48Informed Consent - Process
- Obtaining Informed Consent involves
- Providing information to the subject in a
language that is understandable to the subject or
their representative - Ensuring that the subject understands what they
are being asked to do - Answering any questions that the subject may have
- Allowing enough time for the person to think
about the research before consenting to
participate - Obtaining voluntary agreement of the subject to
participate in the study -
49Informed Consent - Process
- The consent process continues each time that an
investigator has contact with a research
subject. -
- The consent dialogue is renewed every time that
the study is revised, or if new information
becomes available that would impact upon a
subjects decision to participate, -
50Informed Consent - Elements
- Elements of informed consent
- Information that the study involves research
- Risks or discomforts
- Benefits
- Alternatives
- Confidentiality
- Compensation/treatment offered
- Contact for additional information
- Contact information for research subject rights
- Statement that participation is voluntary
-
51Informed Consent - Waivers
- Federal regulations allow for some types of
research to be conducted without obtaining
written informed consent from research subjects. - Typically, waivers are only granted for studies
that present no greater than minimal risk. The
most frequent types of studies that are eligible
for waivers are chart reviews and surveys. -
52Want to learn more about research and the IRB?
- The Office of Research Administration has an
online Human Subjects Protection course through
the CITI program. www.citiprogram.org - This site also offers
- A good clinical practice course (GCP)
- A Recombinant DNA course
- For information and instructions go
tohttp//www.lifespan.org/research/irb/mandatory
edguidance.asp
53Contacts for IRB Questions
- If you have any questions you can contact
- Patricia Houser, Manager Research Review
Committees and Communication at
phouser_at_lifespan.org 444-2099 - Adrienne McParlin, Coordinator Research Review
Committees at amcparlin_at_lifespan.org 444-3527 - Jacqui Poore, Coordinator Review Committees and
Compliance at jpoore_at_lifespan.org 444-2093 - Dawn Roux, Coordinator Research Review Committees
at droux_at_lifespan.org 444-7547 - Deb Temple, Manager Compliance and Training at
DTemple_at_lifespan.org 444-5843