IRB’s Top Ten* What Every Investigator (and his/her research staff) Should Know about Conducting Human Research Activities Investigator Responsibilities *Based on David Lettermen’s Top Ten
PI Responsibility #1 • In designing the study, the investigator should take into consideration the three underlying ethical principles for conducting research with human subjects as delineated in theBelmont Report.
Belmont Report?What’s that?My research is ethical! • The Belmont Report outlines the ethical underpinnings of all of the federal regulations governing the use of human subjects.
Ethical Principles • Respect for Persons • Each person is autonomous • Respect for the person’s privacy when identifying him/her as a potential subject • Respect for the person’s autonomy includes obtaining consent for research procedures • Respect for the person’s willingness to share confidential information
Ethical Principles • Beneficience • The research will do no intentional harm • The research will provide opportunity for benefit, either to the individual, to the group which the individual represents, or to society • The risks associated with the research are minimized as much as possible
Ethical Principle • Justice • That the burdens (i.e., the risks) of the research will not be put upon any one particular group because of convenience, vulnerability, or lack of autonomy • The benefits of the research will not be exclusive to any one particular group but will be made available to anyone who might reap those benefits.
PI Responsibility #2 • Research investigators should acknowledge and accept their responsibility for protecting the rights and welfare of human research subjects and for complying with all applicable federal regulations dealing with protection of human subjects.
Federal Regulations?What regulations apply to my research?Which ones can I avoid? • Common Rule (Federal Policy for the Protection of Human Subjects • Effective August 19, 1991 • Adopted by 16 Federal Agencies • Based on Subpart A 45 CFR 46
Department of Health and Human Services • Core Requirements • (Subpart A) • Fetuses and Pregnant Women (Subpart B) • Prisoners (Subpart C) • Children (Subpart D) • Institutionalized Mentally Disabled (Proposed Subpart E)
Food and Drug Administration • Informed Consent 21 CFR 50 • Institutional Review Board 21 CFR 56
Are there ever times when I do not have to apply these regulations? • There are certain categories of research that are exempt from DHHS regulations. The regulations do not have to be applied when the only involvement of human subjects falls within one or more categories on the following list.
Exempt Categories • Research conducted in established or commonly accepted educational settings, involving normal educational practices. • Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior, unless: (1) Information obtained is recorded in such a manner that human subjects can be identified directly or through identifiers linked to the subjects; AND (2) any disclosure of the human subjects’ responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects financial standing, employability, or reputation.
Exempt Categories, cont. • Research not exempt under “2” may be exempt if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research thereafter (e.g., Department of Justice and National Center for Educational Statistics)
Exempt Categories, cont. • 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 investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to subjects. Please note: according to OHRP to quality for this exemption the data, documents, records, or specimens must be in existence before the project begins.
Exempt Categories, cont. • Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment of benefits or services under those programs.
Exempt Categories, cont. • Taste and food quality evaluation and consumer acceptance studies: (I) if wholesome food without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the FDA or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the US Department of Agriculture.
PI Responsibility #3 • Investigators are responsible for ensuring that all research involving human subjects is submitted to and approved by the appropriate Institutional Review Board (IRB).
So, what needs IRB review? *The IRB has purview over all research that involves human subjects. HUMAN SUBECT is defined as a living individual about whom an investigator conducting research obtains (1) data through intervention or interaction with the individual or (2) identifiable private information. [45CFR46.102(f)]
When is it research? “RESEARCH” Research is a systematic investigation designed to develop or contribute to generalizable knowledge [45CFR46.102(d)]
Does that mean I need IRB review for chart reviews? What about poster presentations?
The answer to both questions is “YES”!! • Chart reviews are the systematic collection of identifiable private information • If you are sharing your findings with anyone outside the research team, it is considered meeting the definition of “generalizable knowledge.
Applicability: FDA • Clinical Investigations • Regulated Products • Drugs • Devices • Biologics • Food/Color Additives
What is designated as a “clinical investigation”? • Involves use of a Test Article • One or more Human Subjects • Meets requirements for Prior Submission to FDA or • Results intended to be part of an Application for Research or Marketing Permit [21 CFR 56.102(c)]
PI Responsibility #4 • Investigators are responsible for complying with all applicable IRB policies, procedures, decisions, conditions, and requirements. • OKAY, OKAY – so I need IRB review. What do I do next and what does all that mean?
Complete an IRB Application http://www.research.usf.edu/cs/irb.htm
Mechanisms for Review • Expedited Review • Full Review • Expedited Review Criteria • No More Than “Minimal Risk” • Falls in One or More Federally Specified Categories • Minor Change in Previously Approved Research
Definition of Minimal Risk “Minimal Risk” mean that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves from those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 45 CFR 46.102(i)
What are the “federally specified categories” that qualify my research for expedited review? • Clinical studies that no not require an IDE or IND • Collection of blood samples • Noninvasive prospective collection of biological specimens • Noninvasive data collection used in clinical practice • Data, documents, records, specimens collected for non-research purposes • Voice, video, digital, or imaging recordings for research • Research on individual or group characteristics • Continuing Review (under certain conditions)
My research involves other kinds of procedures. Now what happens? • Full Review Requirements • Conducted at Convened Meeting • Quorum Present • Nonscientific Representative • 45 CFR 46.111 Satisfied • Approval by Majority • Conflict of Interest Abstain from Vote/Leave Room • PI Informed of Outcome In Writing
What Does it Take to Get My IRB Application Approved? Criteria for IRB Approval of Research [45 CFR 46.111] To approve research, an IRB should determine that all of the following conditions exist:
Risks to subjects are minimized;Risks are reasonable in relation to anticipated benefits, if any, to subjects and to the advancement of knowledge;Selection of subjects is equitable;Informed consent will be sought;Informed consent will be documented;Where appropriate, research plan makes adequate provision for monitoring the data collected to ensure safety of subjects;
There are adequate provisions to protect the privacy or subjects and to maintain the confidentiality of the data;Where any of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the study to protect subjects.In addition, local IRB policies and requirements apply.
Statement from Actual Informed Consent Document “…investigator may at his/her absolute discretion terminate the procedures and/or investigators at any time.”
And Yet Another Statement from an Actual Consent Form “…will be permanently able to perform sexual acts.”
And Finally….from an actual consent form… “We will insert three catheters, one in each arm.” • ARENA Newsletter, 1989
What has to go in my consent form to make sure it is approved? General Requirements 45 CFR Part 46.116 Basic Elements 45 CFR Part 46.116(a) Additional Elements 45 CFR Part 46.116(b) Alteration or Waiver 45 CFR Part 46.116(d) Documentation 45 CFR 46.117
Investigator Responsibilities #5 & #6 Unless otherwise authorized by the IRB, investigators are responsible for obtaining and documenting informed consent in accord with federal regulations (45 CFR Part 46.116 and .117 and 21 CFR Parts 50.25 and 50.27) and as approved by the IRB.
General Requirements • Obtained from the subject or the subject’s legally authorized representative • Language understandable to the subject/representative • Obtained under circumstances that provide subject w/opportunity to consider whether or not participate and that minimize coercive influences • Not include language through which the subject appears to waive his legal rights or which releases the investigator, sponsor, or institution from liability for negligence
Basic Elements • The study involves research! • Explanation of the purpose • Duration of subject’s participation • Description of procedures • Identification of experimental procedures • Description of risks or discomforts • Description of potential benefits to subject or others • Disclosure of alternatives available • Extent of confidentiality that can be made (FDA statement)
Basic Elements, cont. • If research is greater than minimal risk, explanation of compensation and availability of medical treatment • Whom to contact (3 contacts) Contact for questions about the research Contact for questions about subject rights Contact if research-related injury should occur • Statement that participation is voluntary, refusal to participate involves no penalty or loss of benefits, and that subject may discontinue at any time.
Additional Elements If required by the IRB, one or more of the following should be provided to the subject: • Statement that there may be unforeseen risks • Description of circumstances under which subject’s participation may be terminated • Additional costs to subject • Consequences of withdrawing from study • Statement that significant new findings which may related to the subject’s willingness to participate will be shared • Approximately number of subjects involved in the study
“Do I always have to obtain consent? My study is so low risk!!” An IRB may waive consent or alter the elements IF it finds and documents the following: • Research involves no more than minimal risk; • Rights and welfare of subjects will not be adversely affected; • Research could not be practicably carried out without waiver or alteration; and • If appropriate, subjects will be provided pertinent information after participation.
Documentation of Informed Consent • Informed consent will be documented using: • A written form approved by the IRB (in our case and appropriately stamped with the IRB approval period) • Signed by the subject or his legal representative; and • A copy of the form will be given to the person signing the form. (Be sure to document in the research/medical records that the form was given to the subject.)
“I can’t get written consent in a telephone survey. What do I do?” • IRB may waive documentation of informed consent if: • The only record linking the subject and the research is the informed consent document and the principle risk would be harm resulting from breach of confidentiality; each subject must be asked whether he/she wants documentation (not included in FDA regulations); or • The research presents no more than minimal risk and involves no procedures for which written consent is normally required.
“What’s the difference in requesting a waiver of documentation and a requesting a waiver of consent?” • Waiver of documentation will usually mean that the IRB requires that you provide the subject with written information but don’t obtain a signature. • Waiver of consent means that you meet the 4 criteria previously described and there is no consent process.
“What can I do to make sure subjects really do understand the research?” • Train individuals obtaining informed consent (they should be able to answer questions the subjects may have about the research) • Use technology or innovative approaches • Be sensitive to subjects’ needs • Make adjustments in the process, as necessary • Obtain IRB approval for substantive changes and a plan to re-consent, when necessary
“We were in a hurry; we just grabbed the only copy of the consent form we could find.” • It must be the most recently IRB approved form or it’s just not valid! • The subject or legally authorized representative must date and sign the form. • The subject must be given a copy of the form. • Maintain documentation!!!! If itisn’t documented, it didn’t happen.
Investigator Responsibility #7 The investigator is responsible for ensuring that the research is implemented as specified in the approved protocol and for promptly submitting to the IRB a modification to the previously approved protocol prior to initiating the change.
In lay terms… “I changed my mind - do I need to tell the IRB?” “The protocol says I will only enroll subjects with blue eyes but this subject has green eyes – can I enroll him?” Modifications – need to obtain prior IRB approval! Exceptions – need to obtain sponsor and IRB approval!!