A deeper look at Institutional Review Board (IRB) history and - - PowerPoint PPT Presentation

A deeper look at Institutional Review Board (IRB) history and implications for participants and researchers in today’s social landscape

CoPPiR Council Meeting , 9.20.17 Presented by Deborah Barnard, MS Director, Clinical Research Administration Clinical Research Support Center Anschutz Medical Campus

 Researchers and ethicists have long considered

these issues

 Ist Century writer, perhaps physician – recorded his

beliefs that prisoners should be used for medical experimentation as it gave them a chance to give back to society (paraphrased)

 Walter Reed, physician and soldier, conducted research

• n yellow fever in the early 1900s. He had consent forms

in English and Spanish and paid subjects – regardless of whether or not they survived the study.

 The Prussians were known to have had laws about

informed consent and research with children prior to the 1930s.

 Nazi experiments during WWII  Willowbrook study – purposefully infected

children with hepatitis in an attempt to learn how to control it

 Jewish Chronic Disease Hospital – inpatients

were infected with live cancer cells in order to study cancer

 Public Health Syphilis study that went on until

1972 even though there was treatment for the disease

 A number of issues arose over the years that

led to the National Research Act of 1974

 Beecher Articles  Various studies that were of questionable ethics  The PHS Syphilis Study aka the Tuskegee Syphilis

Study The end result was the Belmont Report and then the federal regulations governing human research

 The IRB is responsible for finding and

documenting that a study meets the criteria for approval.

 A close look at these criteria reveal a

foundation in the Belmont Report.

 Respect for Persons protecting the autonomy of all people

and treating them with courtesy and respect and allowing for informed consent.

 Beneficence the philosophy of "Do no harm"  Justice ensuring reasonable, non-exploitative, and well-considered procedures are administered fairly — the fair distribution of costs and potential benefits to research participants — and equally.

 Research is risky, but the regulations allow the

IRB to approve research provided:



Risks to subjects are minimized:

 By using procedures which are consistent with

sound research design and which do not unnecessarily expose subjects to risk, and

 whenever appropriate, by using procedures already

being performed on the subjects for diagnostic or treatment purposes.

 In evaluating risks and benefits IRBs need to

consider whether or not the risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.

 Note: research doesn’t have to be risk free and

research is not required to provide direct or immediate benefit

 Selection of subjects is equitable

 History has shown us that it was not uncommon for

researchers to use individuals who were reasonably accessible – regardless of the long term impact of the research on that population

 The Belmont Report and the subsequent regulations

guide us toward a population that is reasonable, ethical and is the population most likely impacted by the issues outlined in the research question

 Informed consent will be sought from each

prospective subject or the subject's legally authorized representative

 Informed consent will be appropriately

documented (unless waived by the IRB )

 Federal definition  an institutional review board established in accord

with and for the purposes expressed in this policy. (This Policy = 45 CFR 46)

 Made up of at least 5 members  sufficiently qualified through the experience and

expertise of its members,

 diversity of the members, including consideration

• f race, gender, and cultural backgrounds

 Sensitivity to such issues as community attitudes,

to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects

 If an IRB regularly reviews research that

involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of

• ne or more individuals who are

knowledgeable about and experienced in working with these subjects.

 Every nondiscriminatory effort will be made to

ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB

• n the basis of gender. No IRB may consist

entirely of members of one profession.



At least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.



At least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.



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, except to provide information requested by the IRB.



An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB

 Voluntary service  Questions to ask

 What kind of training will I receive?  What is expected of IRB meetings one must attend?  Is there a specific number of meetings?  Is there ongoing training?  How is the IRB perceived?

 Often misunderstood

 When appropriate, there are adequate provisions to

protect the privacy of subjects and to maintain the confidentiality of data.

 Note:

 When appropriate  Provisions are adequate  This is not the same as privacy as discussed in the

HIPAA regulations – PHI is not the same as private information – PHI (HIPAA) data are generated by and for medical care and then used for research

 Privacy

 the state or condition of being free from being

• bserved or disturbed by other people.

 Confidentiality

 the state of keeping or being kept secret or private.

 When some or all of the subjects are likely to be

vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, 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 subjects.

 After World War II, the US was the only

country that experimented on her prisoners

 By 1972, the FDA estimated that 90% of all

investigational drugs were conducted using prisoners

 Today, inclusion of prisoners must be very

specific criteria found in 45 CFR 46.301-306 aka Subpart C

 Concerns over the impact of the unborn led the

regulators to severely restrict research in pregnant women

 The criteria for approving such research is very

strict and clearly laid out

 Note:

 The research can often be approved but the rationale in

support of such approval must be carefully documented

 The regulations provide very careful criteria

under which research involving children can be approved

 For example:

 IRB considers whether or not research poses “a minor

increase over minimal risk”

 IRB considers whether or not “ Assent from children

should be considered”

 IRB considers parents permission as part of the

research consent process

 Situational?

 Just received a terrible diagnosis

 Fleeting?

 Got into a car accident, getting a divorce, can’t really

focus right now

 Temporary?

 anesthesia

 Change over time?

 Progressive and degenerative cognitive disorder

 Have we created so many safeguards that we

have limited our ability to answer research questions with some populations?

 Coercion –

 intimidation

 Undue influence –

 quid pro quo or money or other gifts in excess

 Exculpatory language –

 giving up one’s legal right – more on this in a

moment

 Language understandable –

 language, reading level, dialect

 A statement that the study involves research,  an explanation of the purposes of the research and the

expected duration of the subject's participation,

 a description of the procedures to be followed, and

identification of any procedures which are experimental;



A description of any reasonably foreseeable risks or discomforts to the subject;



A description of any benefits to the subject or to others which may reasonably be expected from the research;



A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;



A statement describing the extent, if any, to which confidentiality

• f records identifying the subject will be maintained;



For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be

• btained;



An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and



A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is

• therwise entitled, and the subject may discontinue participation

at any time without penalty or loss of benefits to which the subject is otherwise entitled.

 Unless the requirement is waived by the IRB,

informed consent shall be documented by the use of a written consent form approved by the IRB and signed by the subject or the subject's legally authorized representative.

 A copy shall be given to the person signing the

form.

 Institutions and IRBs add their own additional

requirements.

 For example, requiring the researcher or

Principle Investigator to sign the consent form

 Requiring the person obtaining consent to sign

the consent form

 Requiring the subject to initial and date each

page of the consent form

 An ongoing activity  An opportunity to continue to discuss and

engage the subject in the research

 An opportunity to review and confirm interest

and participation

 Henrietta Lacks

 Immortal cell lines

 Moore v Reagents of California

 Immortal cell lines and suit for ownership

 Catalono and Wash U. St. Louis

 Biobank with thousands of samples wanting to move

to another university

 Does a signature = an informed decision

 References: OHRP guidance  45 CFR 46  COMIRB policies page

Deborah Barnard, MS Director, Clinical Research Administration Clinical Research Support Center Building 500, GW109 Anschutz Medical Campus 303-724-7628