Informed Consent Flashcards
8 basic elements of IC
1) Statement that the trial involves research, purpose of the research, duration, description of procedures and id procedures that are experimental.
2) reasonably foreseeable risks
3) reasonably foreseeable benefits
4) Alternative procedures or courses of treatment that may be available to the subject and their benefits/ risks
5) confidentiality: Records identify the subject will be kept confidential. If the results of the trial are published the subject’s identify will remain confidential
6) if more than min risk: explanation re compensation or med tx available
7) Contact information re research questions, pt rights, and for injury related to study.
8) Statement the study is voluntary (able to withdraw, no penalty or loss of benefits for refusal)
Additional Elements of IC
1) statement the study may involve unforeseeable risks
2) circumstance participation my be terminated by investigator regardless of consent
3) additional costs to the pt that may result from the research
4) consequences of withdraw and procedures for withdraw
5) statement that significant new findings that may relate to pt willingness to participate
6) number of pts involved
IC documentation
documented by written consent form approved by the IRB and signed by the subject with a copy given to the subject
⚫ Section 46.117 (45 CFR 46, Subpart A)
⚫ Section 50.27 (21 CFR 50)
🞆 FDA requires language that the FDA may inspect the records
🞆 ICH requires language that allows regulatory authorities, the sponsor and/or representatives and the IRB representatives to inspect the records
Waiver of written IC
HHS permit waiver by the IRB of documentation for purpose of confidentiality (45 CFR 46.117) under defined conditions.
🞆 An IRB may waive written IC requirement if it finds either:
(1) the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality; or
(2) the research presents no more than minimal risk of harm to subjects and involves no procedures that written consent is normally required outside of the research context.
Doc instead of written consent
The IRB may require that some document be provided to the participants about the research.
-Study information sheet: information, no signature
**The FDA does not permit waiver of documentation by the IRB.
Waiver of IC
IRB may approve a consent procedure that doesn’t include, or alters, the elements of IC, or waives the requirements to obtain informed consent if it finds and documents that:
(1) the research involves no more than minimal risk to the subjects;
(2) the waiver or alteration will not adversely affect the rights and welfare of the subjects;
(3) the research could not practicably be carried out without the waiver or alteration; and
(4) whenever appropriate, the subjects will be provided with additional pertinent information after participation.
EX: emergency research
Emergency Research
21CFR 50.24 Emergency Research Regulations
⚫ Human subjects are in a life-threatening situation, unable to provide consent, but research offers a potential benefit to improve outcome
⚫ Research must be approved by IRB, including waiver of written consent
⚫ Research could not practicably be conducted without the waiver
⚫ Community forum must be assembled to review and agree with the research having potential benefit for the community
⚫ Investigator still attempts to obtain consent from LAR within a specific time frame, and documents this attempted contact
IC requirements by CA
California Health and Safety Code, Section 27172: all persons requested to take part in a “medical experiment” must be given a copy of a specific bill of rights in a language in which the person is fluent.
-Health and Safety Code section 27176: civil and criminal sanctions for researchers who do not comply with section 27172.
CA Bill of Rights
a. what the study is trying to find out. b. what will happen in the study and whether any of the procedures, drugs or devices are different from what would be used in standard medical practice.
c. the risks, side effects or discomforts
d. if the subject can expect any benefit and what it is.
e. what other choices are available and how they may be better or worse than being in the study.
f. allowed to ask any questions before agreeing and during the study.
g. medical treatment available for complications
h. To refuse b/4 or during will not affect any right to receive the standard medical care.
i. Receive a signed and dated copy of the consent form and the Subject’s Bill of Rights.
j. allowed to decide to consent without any pressure.
CA witness signature
Signature of a witness on the informed consent document is required for all “medical experiments”
-Signature of a witness may be required by the IRB for any other study
1938: Federal Food, Drug & Cosmetics Act ⚫ Basic food and drug law of the U.S
🞆 Assures consumers that:
-Foods are pure and wholesome and safe to eat, sanitary conditions
-Drugs and devices are safe and effective for their intended use
-Cosmetics are safe and made from appropriate ingredients
-All labeling and packaging is truthful, informative and non- deceptive
DEPARTMENT OF HEALTH AND HUMAN SERVICES (HHS)
🞆 45CFR Part 46 “Common Rule”
Federal Policy for the Protection of Human Subjects
⚫ Subpart A: Basic HHS policy
⚫ Subpart B: Pregnant women, Fetuses and Neonates
⚫ Subpart C: Prisoners
⚫ Subpart D: Minors
Who enforces this regulation?
OHRP – Office for Human Research Protections
FDA 21CFR Parts 50 and 56
INDs- New Drugs/ Biologics (21CFR 312)
⚫ IDEs- New Devices (21CFR 812)
⚫ Emergency Use of Test Article
Who enforces this regulation?
FDA does their own enforcement
HHS AND FDA REGULATORY
DIFFERENCES
HHS and FDA do not have complete harmony between their regulations.
🞆 Some examples:
* HHS allows for waiver of written consent in minimal risk research; FDA does not recognize waiver of consent
* FDA clinical investigation = research; HHS definition of research is very detailed and specific
* Scope of responsibility
* FDA – all food, drug, biologic and device research
* HHS – research funded by Federal govt, or all research as per FWA
OFFICE OF GCP IN FDA-REGULATED CLINICAL TRIALS
🞆 Coordinates FDA policies
🞆 Provides leadership and direction through the administration of FDA’s Human Subject Protection/Good Clinical Practice Steering Committee
🞆 Coordinates FDA’s Bioresearch Monitoring program with respect to clinical trials, working together with FDA’s Office of Regulatory Affairs (ORA)
🞆 Contributes to international Good Clinical Practice harmonization activities
🞆 Plans and conducts training and outreach programs
🞆 Serves as a liaison with the HHS Office of Human Research Protection (OHRP) and other federal agencies and external stakeholders committed to the protection of human research participants.
STATE OF CALIFORNIA - CA HEALTH AND SAFETY CODE: 24170-24179.5
Protection of Human Subjects in Medical Experimentation Act
🞆 Requires “experimental subject’s bill of rights”
🞆 Defines Legally Authorized Representative 🞆 Section 24178 – surrogate consent for research
🞆 Consent for minors – if >7, assent required 🞆 Use of death records for research – requires IRB
ICH GUIDELINES
🞆 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) – first met in 1991
🞆 Joins efforts of Western Europe, U.S., Japan
🞆 Primary purpose is to coordinate the drug regulatory process to prevent redundancy in research
🞆 GCP Guidelines issued, based on Declaration of Helsinki, attempt to provide a unified standard for the protection of human subjects
DEFINITION OF GCP
🞆 Good clinical practice (GCP)
🞆 Good clinical practice (GCP): international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.
-provides public assurance that the rights, safety, and wellbeing of trial subjects are protected, consistent with Declaration of Helsinki,
-assures the clinical trial data are credible (ICH, 1996).
🞆 Be familiar with the E6 ICH document
ICH PRINCIPLES FOR GCP
-conducted in accordance with the ethical principles originating in the Declaration of Helsinki, and consistent with GCP and the applicable regulatory requirement(s).
-Before a trial is initiated, foreseeable risks and inconveniences weighed against anticipated benefits for the individual trial subject and society.
- anticipated benefits must justify the risks.
- The rights, safety, and well-being of the trial subjects are the most important - prevail over interests of science and society.
- The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
- trials should be scientifically sound, and described in a clear, detailed protocol.
-conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion.
-The medical care given to, and medical decisions made on behalf of, subjects are the responsibility of a qualified physician or, dentist.
- Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).
-Freely given informed consent obtained from every subject b/4 participation.
-All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.
-The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
-Investigational products should be
manufactured, handled, and stored in accordance with applicable good
manufacturing practice (GMP) and used in accordance with the approved protocol.
-Systems with procedures that assure the quality of every aspect of the trial should be implemented.
VULNERABLE POPULATIONS (45CFR46)
🞆 Pregnant women: (Subpart B)
🞆 Prisoners: (Subpart C)
🞆 Children: (Subpart D)
🞆 Handicapped or mentally disabled persons
45 CFR 46: SUBPART B:
PREGNANT WOMEN AND HUMAN FETUSES
Applies to all research involving pregnant women or human fetuses, and to research involving the in vitro fertilization of human ova
🞆 Allowable research if:
⚫ Previous research (pre-clinical, animal, non- pregnant women) has assessed potential risks for pregnant women and fetuses
⚫ Risk to fetus is minimal, or if greater than minimal also holds out prospect of direct benefit for the woman or the fetus
⚫ Risk is the least possible for achieving the objectives of the research
45 CFR 46: SUBPART B states
-woman’s consent has been obtained with usual provisions
🞆 The woman is fully informed of reasonably foreseeable impact of the research on the fetus
🞆 No inducements are offered to terminate the pregnancy
🞆 Researchers will have no involvement in termination of the pregnancy
🞆 Researchers will have no involvement in determination of viability of the fetus
45 CRF 46 sub B (d) and (e) consent
(d) Only the woman needs to consent- If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means
(e) the woman and father both need to consent- If the research holds out the prospect of direct benefit solely to the fetus
-EXCEPT father’s consent is not needed if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest
45 CFR 46: SUBPART C:
PRISONERS
🞆 Applicable to all biomedical and behavioral research involving prisoners as subjects
🞆 Additional safeguards are necessary since incarceration could affect their ability to make a truly voluntary and uncoerced decision about whether to participate as subjects in research
45 CFR 46 sub C IRB additional requirements
Research involving prisoners shall also meet additional specific requirements:
⚫ Majority of members will have no association with the prisons involved
⚫ At least one member of the review board will be a prisoner or prisoner representative with appropriate background and experience to serve in that capacity
45 crd 46 SUBPART C:Research may involve prisoners when:
⚫ Study of the possible causes, effects, and processes of incarceration, and of criminal behavior, or ⚫ Study of prisons as institutional structures or of prisoners as incarcerated persons,
*provided that the study presents no more than minimal risk and no more than inconvenience to the subjects.
⚫ Other types of research involving prisoners must have approval of the Secretary, DHHS
🞆 Advantages of participation in the research are not of such a magnitude that subject’s evaluation of risk/benefit is impaired
🞆 Risks involved are similar to risks accepted by non-prisoners
🞆 Subject selection within prison is fair
🞆 Parole boards will not take into account research participation in making parole decisions
🞆 Necessary follow-up has been provided
45 CFR 46: SUBPART D: CHILDREN
Applies to children (have not attained the legal age for consent to treatments or procedures) as subjects
🞆 No greater than minimal risk (category I)
⚫ Assent of child is necessary
⚫ Permission of parents or guardians is sought
⚫ Permission of one parent is adequate
45 CFR 46: SUBPART D: CHILDREN
> minimal risk; prospect of direct benefit (category II)
⚫ Risk is justified by anticipated benefit
⚫ Anticipated benefit/risk is comparable to available alternative approaches
⚫ Assent of child is necessary
⚫ Permission of parents or guardians is sought
⚫ Permission of one parent is adequate
> minimal risk; no prospect of direct benefit, but likely to yield generalizable knowledge about subject’s disorder or condition (category III)
Risk represents a minor increase over minimal risk
⚫ Intervention or procedures reasonably commensurate with those inherent actual or expected situations
⚫ Intervention or procedures are likely to yield generalizable knowledge that is of vital importance for understanding and/or ameliorating subject’s disorder or condition
⚫ Assent of child is necessary
⚫ Permission of parents or guardians is sought
⚫ Permission of both parents is required, except…
except when:
- One parent is deceased, unknown, incompetent, or not reasonably available, or
- One parent has legal responsibility for the care and custody of the child
RISK CATEGORY I FOR CHILDREN
🞆 Minimal risk
🞆 IRB Duties
-Confirm provisions for child assent
-Confirm provisions for parental consent
