New Member Orientation
Our primary responsibility as IRB reviewers is to work to safeguard the rights and welfare of research participants.
I. Regulatory and Ethical Basis
- 45CFR46 (the Common Rule and Subparts B-D)
- OHRP and FDA Regulations are viewed as the the floor
- Federal-wide assurances (FWAs)
- Reporting obligations and oversight
II. Structure-Activity Relationships
- The convened IRB is the vested authority
- IRB staff vs. members roles are distinct
- Members, alternates, and quorum obligations
• Confidentiality of review protects the integrity of the review process
• We are obligated to respect an investigator’s protocol as proprietary information/intellectual property
B. Conflict of interest
• The IRB should be perceived as and, more importantly, be fair and impartial. The Board must be immune from pressure by the institution's administration as well as from the investigators whose protocols are brought before it. (OHRP guidebook)
• No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest (e.g., Co-Investigator role, obtaining consent), except to provide information requested by the IRB (45CFR46.107)
Levels of IRB Review
• Full-board review is the default process for more than minimal risk studies or studies involving particularly vulnerable populations. More than minimal risk studies involve an intervention defined in the regulations as both physical procedures by which data are gathered and manipulations of the participant or participant's environment that are performed for research purposes.
• Only Minimal Risk research that falls within predefined categories and minor changes to approved research can be expedited. Expedited review means the review may be conducted by the IRB Chair or his/her designate.
• Federal rules Exempt some research, but this is not an option at NYSPI because we are subject to NY State Office of Mental Health regulations which currently do not recognize exempt categories.
Steps in Review
• Level of review is assigned (minimal or more than minimal risk)
• Protocol Management
• Chair or member review
• Subcommittee Review
– Primary and secondary reviewers
– Grant, Sponsor Materials
– Communication with PI's
• Full Board Review
• The idea of "Simple Concurrence"
• Final approval
• Changes to approved research
• Continuing Review
• Unanticipated problems, Adverse events, monitoring data, and protocol violations
– Communication with Chair
The regulations: 45CFR46: Definitions
• Research - a systematic investigation designed to develop or contribute to generalizable knowledge.
• Human Subject - a living individual about whom an investigator conducting research obtains
– data through intervention or interaction with the individual, or
– identifiable private information
§46.116 General requirements for informed consent.
....no investigator may involve a human being as a participant in research covered by this policy unless the investigator has obtained the legally effective informed consent of the participant or the participant's legally authorized representative.
....if the study is defined as research
....and it involves human subjects,
....then IRB review and informed consent are required.
• Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research [as experienced by the participants of the study] are not greater in and of themselves than those ordinarily encountered in daily life [for an average person] or during the performance of routine physical or psychological examinations or tests.
(b) An IRB may use the expedited review procedure to review either or both of the following:
(1) some or all of the research appearing on the list and found by the reviewer(s) to involve no more than minimal risk (see 45CFR46.110(b)(1)(f) for a list of categories),
(2) minor changes in previously approved research during the period (of one year or less) for which approval is authorized.
Criteria for IRB approval
(1) Risks to subjects are minimized:
(i) by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
(ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
• Consider the nature of the disorder and inherent risks
• Consider the phase of illness under study
• Carefully consider co-morbidities and contraindications
• Consider duration of delay to treatment
• Consider permitted/restricted treatments
• Consider the setting
• Examine inclusion criteria
• Examine exclusion criteria
• Examine frequency and nature of assessments
• Consider qualifications of staff
• Require operationalized clinical drop-out criteria to permit otherwise un-approvable research
• Request feedback and research monitoring
• Require (suggest?) end of study care/referral
(2) Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result.
(3) Selection of participants is equitable.
The IRB should be particularly cognizant of the special problems of research involving vulnerable populations...
Protections in the risk-benefit analysis
• Weighing autonomy vs. protectionism
• Tensions between risk reduction and scientific aims.
• Defining unacceptable risk.
• What is the precedent?
....Consider the scientific benefits and the risks introduced by the research:
are the risks only those necessary to answer the proposed scientific question?
Some persons are in need of extensive protection, even to the point of excluding them from activities which may harm them;
other persons require little protection beyond making sure they undertake activities freely and with awareness of possible adverse consequence.
Implications and Applications
• Vulnerability is multi-dimensional, and occurs along a spectrum--not simply as present or absent.
• Protections are proportional to the degree of vulnerability.
• Protections are proportional to the degree of risk and benefit.
Protections in subject selection, and recruitment
• Study the least vulnerable population that will serve the project's scientific aims.
• Study less vulnerable groups first.
• Address stigma and burden.
• Protection begins in approaches to advertising, screening, and recruitment.
• Carefully consider compensation.
• IRB review and informed consent represent two fundamental protections.
• The protections provided by consent do not relieve the IRB of its obligation to determine what is approvable, what is "reasonable."
• Yet, these are not wholly independent considerations
(4) Informed consent will be sought from each prospective participant or the participant's legally authorized representative
(5) Informed consent will be appropriately documented
(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of participants.
(7) When appropriate, there are adequate provisions to protect the privacy of partcipants and to maintain the confidentiality of data.
(8) When some or all of the participants are likely to be vulnerable to coercion or undue influence, such as children, prisoners, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these participants.
Risk/Benefit Thresholds: Adults vs. Children
From Subpart A, criteria for study approval
• Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result.
Versus, from Subpart D (Children)
• The risk is justified by the anticipated benefits to the participants, and
• The relation of the anticipated benefit to the risk presented by the study is at least as favorable to the participants as that provided by available alternative approaches.
Types of Research
Not greater than minimal risk
Greater than minimal risk and prospect of direct benefit
Greater than minimal risk and NO prospect of direct benefit
Any other research
(1) Assent of child and permission of at least one parent
(1) Assent of child and permission of at least one parent
(2) Anticipated benefit justifies the risk
(3) Benefit/risk ratio is at least as favorable as that of alternative approaches
(1) Assent of child and permission of at least one parent
(2) Only a minor increase over minimal risk
(3) Likely to yield generalizable knowledge about the child's disorder or condition that is of vital importance for the understanding or the amelioration of the disorder or condition
(4) The intervention or procedure presents experiences to the child that are reasonably commensurate with those in the child's actual or expected medical, dental, psychological, social, or educational situations.
(2) IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children
• Assent of child and permission of both parents
(3) The HHS Secretary approves, after consultation with a panel of experts in pertinent disciplines (e.g., science, medicine, education, ethics, law) and following publication in the Federal Register and public comment
Protections, consent and capacity to consent
• Informed, Understanding, Voluntary
• Investigators are responsible for ascertaining that the participant has comprehended the information
• When the risks are more serious, that obligation increases.
The nature of decisional "vulnerability"
• Situational vs. disorder-related impairment
(e.g. emergency room, "institutions" vs. stroke)
• Global vs. specific impairment
(e.g. sedative overdose vs. paranoid psychosis)
• Static vs. progressive vs. episodic vs. time limited impairment
(e.g. severe mental retardation vs. Alzheimer's disease vs. manic depressive disorder vs. TBI)
• Acute vs. persistent impairment
(e.g. hypoxia secondary to asthma or acute pain vs. MR, autism)
• The research procedure
• The purpose of the study
• The risk of harm or discomfort
• The anticipated benefits
• The alternatives to study participation
• The opportunity to ask questions
• Statement about study withdrawal
Capacity is task specific
IRB Waiver of Consent
The IRB may approve a waiver of some or all of the consent requirements provided that:
• The research involves no more than minimal risk to participants;
• The waiver will not adversely affect the rights and welfare of participants;
• The research could not practicably be carried out without the waiver; and
• Whenever, appropriate, the participants will be debriefed.
Waiver of documentation of Consent
The IRB may waive the requirement for documentation of consent in cases where:
• The principle risks are those associated with a breach of confidentiality concerning the participant's participation in the research; and the consent document is the only record linking the participant with the research;
• The research presents no more than minimal risk; and involves procedures that do not require written consent when performed outside of a research setting.
• Identification (the mere fact of linking them to involvement in the study) of participants and/or their responses could place them at risk of criminal or civil liability or be damaging to the participants' financial standing, employability, insurability, reputation, or be stigmatizing
• There is no researcher-patient "privilege"
• Our obligations and the quid pro quo
Resources and references
• Belmont Report
• The Regs (OHRP 45CFR46 and FDA GCP 21 CFR Part 11, 54, 312, 314, 807, 812, 814, 820, 510K and Post-Market Approval
• IRB Member Handbook
• LW Roberts (2 papers)
• Workshops, conferences
- You are covered