OBJECTIVES Identify consent process requirements Distinguish between IRB, PI/Designee
consent process responsibilities Identify with what went wrong? Summarize tips to avoid deficiencies
"A word is not a crystal, transparent and unchanged; it is the skin of a living thought and may vary greatly in color and content according to the circumstances and the time in which it is used" — Oliver Wendell Holmes Jr.
REGULATIONS/GUIDANCE REGARDING CONSENT DOCUMENTS: DHHS – 45 CFR Part 46.116
Common Rule FDA 21 CFR 50.25
Part 50 (Informed Consent)
Part 56 (IRB) ICH GCP E-6 Section 4.8.10
45 CFR 46.116 “No investigator may involve a human being as a
subject in research… unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative
An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that
minimize the possibility of coercion or undue influence.
The information that is given to the subject or the representative shall be in language understandable to the subject or the representative”
45 CFR 46.11
WHAT IS THE CONSENT DOCUMENT?
A document that provides a summary of the research and explains the subjects rights as a participant
It is designed to outline and be a reference regarding what is expected of the participant
WHAT IS INFORMED CONSENT?
information exchange including subject recruitment materials, verbal instructions, written materials, questions and answer
sessions and signature documenting
consent with date.
Protecting study volunteers in research Cynthia McGuire Dunn, MD & Gary Chadwick, PHARM.D, mph 1999.
VALID INFORMED CONSENT REQUIRES: Disclosure of relevant information to
prospective subjects about the research; their comprehension of the information, and their voluntary agreement, free of coercion
and undue influence, to research participation.
http://ohsr.od.nih.gov/info/sheet6.html
IRB POLICY: PROCEDURE FOR OBTAINING LEGALLY EFFECTIVE AND PROSPECTIVE INFORMED CONSENT.
Detailed description of the method for obtaining informed consent WhoWhere
The process submitted for IRB approval Changes in the process are submitted as
amendments PI assures the informed consent process in
research is an ongoing exchange of information throughout the course of the research and it is documented
TYPES OF CONSENTING PROCESS’:
E consent
Oral
Telephonic
VideoFacsimile
WHO CAN CONSENT SUBJECTS?The person must be trained regarding informed consent process and be knowledgeable about study
FDA Requirements: IRB must know who will conduct consent process FDA does not require the that the PI personally
conduct the consent process.
ECOG Requirements: “Legally, it is the physician’s responsibility to discuss
the study with the patient and obtain the written consent.”
“After an initial discussion it may be the physician, nurse, or CRA who provides further details to the patient.”
7.2.6 “Presenting the Consent Form to the Patient,” ECOG Protocol Management
WHO TYPICALLY CONSENTS SUBJECTS? 41% Study nurse 21% PI 19% No one 12% Family member 8% Other
Source: 2002 Center Watch Survey of 1,561 Study Volunteers
HHS (45 CFR 46) SPECIAL PROTECTIONS FOR VULNERABLE POPULATIONS Fetuses, Pregnant Women, and
Human In Vitro Fertilization Prisoners Children Elderly Cognitively Impaired Minorities Etc.
BARRIERS TO UNDERSTANDING INFORMED CONSENT.
Cognition/capacity Level of education Social/cultural values Language Age Environment Anxiety/fear Pain Influence of medications Quality of disclosed information Readability of informed consent
THERAPEUTIC MISCONCEPTION:
The subject believes that his medical needs will determine his assignment to a treatment group or the PI will modify the protocol to serve his own medical need.
The subject has unreasonable expectations about the likelihood of benefit from study participation. In this example the subject believes the PI will not administer treatment that might harm them, but rather, will provide interventions that only help them.
“the belief that the purpose of a clinical trial is to benefit the individual patient rather than to gather data for the purpose of contributing to scientific knowledge”
WHEN IS THE INFORMED CONSENT PROCESS FINISHED? When the study is closed and final reports
are issued At each interaction, the investigator must
reassureVoluntary participation continuesNew information is given to the subject
ARE ALL THE RULES THE SAME?
FDA MandatesFDA has no regulations concerning delegation of consenting although it is discussed in the FDA Information Sheets
FDA only requires that a copy of consent be provided to subject
If consent is obtained the same day that the subject's involvement in the study begins, the subject's medical records/case report form should document that consent was obtained prior to participation
ICH/GCP 4.8 suggests
ICH allows the delegation of the informed consent process to a designee
ICH recommends the person conducting the informed consent process sign and date the consent form
ICH recommends that the subject receive a signed and dated copy of the consent form
research“FDA Consent information sheet”
MORE DIFFERENCE IN FDA VS ICH-GCPFDA and ICH BOTH require the IRB to review:
The informed consent, process, protocol, advertisements, and the Investigator's Brochure
ICH/GCP 3.1 also recommends IRB review of:Subject recruitment proceduresWritten information provided to subjects Information about subject compensation Investigator's current CV and/or other
documents evidencing qualifications
DHHS
OHRP
IRB Policy
IRB Policy
State Law
Institution Policy
Other Federal
Agencies (NIH, CDC and CMS
FDA
HOW DO WE KNOW WHAT RULES TO FOLLOW?
Department Policy
Research Team SOP’sStudy Protocol/ Contract
Depending on funding and/or Dept policy
ICH/GCP
IS THERE A TIME WHEN THE PROCESS CAN BE WAIVED OR ALTERED? Emergency, life threatening situation
that requires intervention
Minimal risk study with IRB approval
WHAT ARE THE RESPONSIBILITI
ES OF THE PI/DESIGNEE?
INVESTIGATOR RESPONSIBILITIES IN INVOLVING SUBJECTS IN RESEARCH
Ultimate protector of the subject’s rights and safety
Be personally certain that each subject is adequately informed and freely consents to participate in the investigator’s research
Assure that every reasonable precaution is taken to reduce risk to a minimum for the subject
The investigator is responsible for whom he delegates authority
Follow the protocol and IRB approved study documents
WHAT IS THE PI/DESIGNEE’S ROLE IN THE CONSENT PROCESS? Obtain consent before initiating ANY study-
specific procedures Provide a quiet, comfortable, and private
setting Explain the consent procedures and
process to the subject Ensure sufficient time to consider all
options Access the subject's reading abilities,
cognitive status now and throughout study
Access subjects understanding
WHAT IS THE PI/DESIGNEE’S ROLE IN THE CONSENT PROCESS? Ensure the subject is the one who wants to
participate, free from coercion or other undue influence
Consistent with IRB approved process Provide additional safeguards as required Provide new information promptly Provide a copy of the consent document and
each revised consent document to the subject During the interview be aware of the things
you might be saying that would affect voluntariness or be coercive “free drug” “free treatment” “I think this is
best for you” “do this for me” Document process and response from patient
WAYS TO BEGIN THE CONSENT PROCESS?
Know the protocol Introduce yourself and
state who referred you Do not depend on subject
enrolling You are not a salesman Provided consent
document for review Methods of conveying
information differs Check list Read consent to subject Read highlights /review
calendar Video Electronic Web-based resources
WAYS TO FACILITATE THE TWO WAY CONVERSATION AND ENHANCE UNDERSTANDING.
Establish a relationship with the subject Provide privacy Assess views on research vs. standard of care Keep the subject in the center of the process Be an active listener Ask open-ended questions (test back) Be aware of non-verbal messages Empathize with the subject’s concerns Be a teacher by educating the subject and
verifying his understanding of the research study
Assure withdrawal is possible at ANY time Inform other options are available Be available anytime for any question Do not rush the process or the subject
Informed Consent Worksheet Date of Consent:__________________ Name of Study:_____________________________ IRB Study Number:__________________________ Patient Name:_____________________ Patient MRN:_________________ _Study ID#:__________ The following has been explained to the potential study subject, and the subject has been offered the
opportunity to ask questions regarding the study: TOPIC COMMENTS Purpose of the study _________________________________ Qualifications to participate _________________________________ Location and participants _________________________________ What will happen during the study _________________________________ Risk and benefits _________________________________ Study related injury or illness _________________________________ Alternative treatments _________________________________ Confidentiality _________________________________ Study costs _________________________________ Compensation _________________________________ Who to contact with questions _________________________________ Voluntary participation _________________________________ Termination of participation _________________________________ Questions or comments: __________________________________________________________________ __________________________________________________________________ Does the patient state an understanding of the study and procedures and agree to
participate? ___yes ___no _____________________________________ __________________________ Person administering consent Date / Time Signed copy given to patient? ___yes ___no Copy in patients chart? ___yes ___no
CONTINUING THE STUDY AND THE CONSENT PROCESS. Ask if problems arose since
last visit (A/E’s) Provide new information if
applicable Encourage questions each
visit Talk about what comes next Re-assess subjects desire
to continue each visit Assess compliance (diary,
meds etc)
WHEN DO WE RE-CONSENT? If subject regains cognitive ability New information becomes available Significant protocol changes New surrogate is identified IRB instructs you to re-consent Investigator has the option to re-consent
for longitudinal data collection time points
WHAT HAPPENS WHEN RESEARCH IS CONDUCTED WITHOUT FULLY INFORMED CONSENT?
Non compliance The trust based physician-patient relationship may be damaged
Complaints to the IRB, the institution, the OHRP or the FDA
Subjects
no longer
willing to
participate
in research
Word of mouth about experienceSubjects placed in
vulnerable situationStudy yield unusable data due
to non adherence
Longer drug
approval
times
CONSENT PROCESS TIPS: Ongoing Interactive process Different for every subject Different for every study Essential for study success IRB approved Providing clear definition between where standard of care leaves off and research begins Allows re-education Requires re assessment of subject
understanding with each visit
WHAT ARE THE RESPONSIBILITI
ES OF THE INSTITUTIONAL
REVIEW BOARD?
WHAT DOES THE IRB LOOK FOR REGARDING THE INFORMED CONSENT PROCESS? Method of presentation appropriate
for type of study and population Voluntary participation Environment Length of time devoted to the process Adequate time offered to ask
questions How subject demonstrates
understand of the study and desire to participate
Promptness of reporting new information
Auditing/Compliance Reviews
WHAT DO MONITORS/AUDI
TORS LOOK FOR?
WHAT DO AUDITORS/MONITORS LOOK FOR ? If SOP’s exist are they followed Confirm consent process IRB approved Change implemented only after IRB
approval Consent signed prior to ANY procedures Consenting person has appropriate training Consenting person listed as KSP
OBSERVE THE CONSENT PROCESS
You know you want to: Volunteer to have your consenting
process observed
Contact Wendy Lloyd by phone (936-7106) or by email ([email protected])
in advance or just prior to consenting
COMPLIANCE FINDINGS OF THE INFORMED CONSENT PROCESS. Signatures of subject and consenting person on different
dates Consent and study procedures on same date Consent was performed by an untrained or unqualified care
provider Person consenting is not listed as KSP Unable to locate consent for subject on study Subjects not re-consented with revised consent as instructed Multiple consent documents for same patient with no
explanation why Person consenting did not state the purpose or procedures of
the study Consent document left on clip board for subjects to complete
and return to nurse if interested Person consenting the subject did not sign the form
HOW CAN YOUR DEPARTMENT AVOID DEFICIENCIES? Only use approved consent process Confirm all personnel consenting subjects are
KSP Document training and qualifications of all KSP Confirm person consenting knows the protocol Conduct random audits of the consent process
documentation ( if form created, confirm use) Review the FDA Warning Letters and FDA IRB
Information Sheets –“A Guide to Informed Consent”
Become familiar with the Regulations, state law, institutional and IRB Policies
Call the VHRPP
HOW CAN YOU AVOID NEGATIVE FINDINGS? Know the protocol Only do what you are trained to do Volunteer for consent observation Ask subjects if they felt fully informed Seek education Stay organized If you find something don’t hide it Network Become certified If you don’t know ask
WE ARE ALL RESPONSIBLE. Although the regulations
place the burden of responsibility on the PI, the protection of human research subjects is a shared responsibility among all research professionals involved in the conduct of the study
Members of a research team
have a moral obligation to uphold the ethical and regulatory standards by which human subjects research is conducted
I challenge you not to accrue, accrue, accrue but to inform, inform, inform
HOW ARE WE DOING?
PROSPECTIVE EVALUATION OF PATIENT COMPREHENSION OF INFORMED CONSENT
Measure the immediate level of patient comprehension at the time surgical consent is obtained and the effect of time on this level of understanding.
In addition, the effect of sex (no difference), education level (college scored better), and age (<50 scored higher) on comprehension.
http://www.ncbi.nlm.nih.gov/pubmed/22005875 2011 study Crepeau AE, McKinney
100 subjects consented
When test administered
Percent of Correct answers
98 Preoperatively 70.7075 1st Post op (no more
than 2 weeks)59.50
39 1st Post op (no more than 2 weeks)
60.8
THE TRAGIC CASE OF JESSE GELSINGER
18 year old with partial ornithine transcarbamylase deficiency
Usually fatal in infancy
The first person to die from gene therapy
REACTIONS FDA suspended all gene therapy
trials and other experiments Hearings on quality of oversight
and safety President Clinton demanded
improvements in consent and access to information about gene therapy research
LITIGATION Gelsinger v. Univ. of Penn. (C.P.
Phila. Co., 2000) 18 year old boy died during a gene
transfer experiment for ornithine transcarba – mylase deficiency.
PI founded company that sponsored trial – owned 30% of stock
University of Pennsylvania owned 5% of stock
University’s Conflicts of Interest Committee was aware of the potential conflict of interest between the parties – allowed study to proceed
Gelsinger v. Univ. of Penn. One of the many counts Intentional Assault and
Battery Informed consent process did not disclose
Monkey deaths Previous adverse events Relationship between PI and sponsor True efficacy results
Confidential settlement Sued University trustees, PI, sponsor and hospital
LITIGATION
PERSONAL BEST Each interaction is different because
every subjects, circumstance, question, communication style is different.
It is up to each one of us to take the consent process serious and fully inform each subject
WE WILL ALL BENEFIT FROM A MORE EFFECTIVE ICD PROCESS: By possibly increasing
subject recruitment and retention on a wide scale
Playing a substantial role in shaping public perceptions of the value of clinical research
REFERENCE PAGEFor federal guidance on obtaining informed consent of human researchsubjects, see the following websites:
General requirements for informed consenthttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?
fr=50.20http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?
fr=50.23http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?
fr=50.24http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?
fr=50.25Documentation of informed consent
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.27
Research involving pregnant women, fetuses or neonateshttp://www.hhs.gov/ohrp/humansubjects/guidance/
45cfr46.htm#46.204http://www.hhs.gov/ohrp/humansubjects/guidance/
45cfr46.htm#46.205http://www.hhs.gov/ohrp/humansubjects/guidance/
45cfr46.htm#46.206http://www.hhs.gov/ohrp/humansubjects/guidance/
45cfr46.htm#46.207
REFERENCE PAGEResearch involving children (also found in 21 CFR 50.50-56)
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.404http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.405http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.406http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.407http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.408http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.409
Pediatric research “assent”decision matrixhttp://www.hhs.gov/ohrp/panels/407-01pnl/riskcat.htm
Office for Human Research Protections (OHRP) informed consent tipshttp://www.hhs.gov/ohrp/policy/index.html
OHRP informed consent FAQhttp://answers.hhs.gov/ohrp/categories/1566
Vanderbilt IRB Policyhttp://mcapps01.mc.vanderbilt.edu/IRB/policy&procedures.nsf/
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If you have additional comments or questions feel free to contact me
Wendy [email protected]
615-936-7106