Part 2 of 3 part series: Informed consent: The Process
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Transcript of Part 2 of 3 part series: Informed consent: The Process
PART 2 OF 3 PART SERIES:
INFORMED CONSENT: THE
PROCESSWendy Lloyd
BA, LPN, CIP,CCRPRegulatory Affairs and Compliance Specialist
OBJECTIVES Identify consent process requirements Distinguish between IRB, PI/Designee
consent process responsibilities Identify with what went wrong? Audit
results, FDA Warning Letters and OHRP Determination Letters
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 REGARDING CONSENT DOCUMENTS: DHHS – 45 CFR Part 46 FDA 21 CFR
Part 50 (Informed Consent)Part 56 (IRB)
45 CFR 46.116 (21 CFR 50.20) No investigator may involve a
human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative
The information that is given to the subject or the representative shall be in language understandable to the subject or the representative and include the elements of consent
21 CFR 55.109 (B) An IRB shall require that information
given to subjects as part of informed consent is in accordance with 50.25.
The IRB may require that information, in addition to that specifically mentioned in 50.25, be given to the subjects when in the IRB's judgment the information would meaningfully add to the protection of the rights and welfare of subjects.
IRB POLICY: PROCEDURE FOR OBTAINING LEGALLY EFFECTIVE AND PROSPECTIVE INFORMED CONSENT Detailed description of the method for obtaining
informed consent All informed consent documents submitted for IRB
approval Changes in ICD’s are submitted as amendments Consent must contain all required elements Consent is documented in writing through the use of
a current IRB-approved ICD, unless waived PI assures the informed consent process in research
is an ongoing exchange of information throughout the course of the research and it is documented
DHHS (45 CFR 46) SPECIAL PROTECTIONS FOR VULNERABLE POPULATION. Fetuses, Pregnant Women, and
Human In Vitro Fertilization Prisoners Children Elderly Cognitively Impaired Minorities Etc.
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 in the
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 submission 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
ICH/GCP
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
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
FROM THE MOUTH OF BABES -WHAT DO SUBJECTS WANT IN CONSENT?
Simplicity Summary QOL How many adverse events? How many visits? Know how many subjects are on study?
This dose
Different dose
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”
FACTORS THAT CONTRIBUTE TO THE LACK OF SUBJECT PARTICIPATION IN CLINICAL TRIALS.
Harris Interactive Online Studies of 2031 and 2261 adults Only a minority of the public is confident that clinical
trials subjects
However 83 % believe it is essential and very important all new
pharmaceutical products be tested on humans before they are approved for general use
www.harrisinteractive.com/news/allnewbydate.asp?NewsID=213www.harrisinteractive.com/news/allnewbydate.asp?NewsID=941
2002 2005are not treated like guinea pigs 24% 54%do not suffer more pain or side effects than with standard of care treatment 13% 53%receive high quality care 32% 48%receive honest accurate information 25%
STRONGLY AGREED THE PROCESS WAS EXPLAINED TO YOU WHEN YOU AGREED TO BE PART OF THE CLINICAL RESEARCH STUDY.2,261 US adults over 18 surveyed online April 2005 2004 2005
% %I understood that participation was voluntary. 90 84I understood that I was agreeing to participate in a clinical research study. 89 83I fully understood what was required of me (number of visits, how long the study lasted, etc.). 81 78I knew I could stop participating in the study at any time. 79 75I felt comfortable asking additional questions regarding the study. 79 75I was assured confidentiality of all personal information that I provided, with the exception of those allowed by federal law.
73 73
I felt secure that my confidentiality was protected throughout the study. 71 69I was made aware of the benefits involved in participating in the clinical research study. 74 68I was made aware of the risks involved in participating in the clinical research study. 74 65I understood that I could choose other treatment options, including no treatment at all. 66 63The informed consent document was easy to read and understand. 60 61
www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941
OVERVIEW OF INFORMED CONSENT PROCESS.2,261 US adults over 18 surveyed online April 2005
%
Said purpose of the study was "clear" after reading the informed consent
85
Agreed their questions were answered by the study team regarding the informed consent process
80
Said the study coordinator conducted the informed consent process.
54
Read the informed consent by themselves 48
www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941
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
PROTECTING HUMAN SUBJECTS IS A SHARED RESPONSIBILITY ME NIH Sponsor Investigator Research Team Compliance OfficerInstitutional Official Educators Government Auditors Public IRB Chair and Members COG Family Translator Advocates Press / Media FDA DOD Pharmacist YOU OHRP
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
THE CONSENT PROCESS IS: 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
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
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
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 to
Follow the protocol
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 Requires accessing 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
Document process and response from patient
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 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
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
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
INFORMED CONSENT & RECONSENT PRESENTATION CHECKLISTClinical Research Trial: ________________________________ Version Date:________________Physician discussed diagnosis and treatment options (standard of care, no treatment)Physician discussed clinical research trial including the following:• Description of the clinical research trial, its goals, and medications involved• Voluntary participation• Anticipated duration of participation• All known risks: reported side effects and management of known side effects and…• Possibility of unknown side effects• Potential and reasonable expected benefits• Treatment groups and randomization (if applicable)• Required study procedures• Follow-up after completion of study treatment• Rights and responsibilities of research participants (including contraception if applicable)• Confidentiality• Compensation / Additional CostsConsent presented to patient / legal representative / legal guardianTime allowed for patient / legal representative / legal guardian to read consent and ask questions prior tosigning consentPatient / legal representative / legal guardian acknowledged understanding of the clinical trial andindicated questions were answered to their satisfactionPatient / legal representative / legal guardian signed informed consentPatient / legal representative / legal guardian received a copy of each signed research consent formStudy specific procedures were not done prior to consent being signedContact information provided to patient / legal representative / legal guardian for study related concernsPerformance Status today (per protocol): Karnofsky / __________ Lansky ECOG / Zubrod / WHO ___________Consent document(s) signed on: / / Amount of time explaining the consent:________________Time consent signed:_______ AM/PM **Translation Services: Translated document(s) and / or interpreter provided as needed:q NO (translation services not needed) _____ YES List language provided:______________________Any additional comments regarding translation:____________________________________________Physician’s Signature (print name):____________________________________Physician (sign): Date:________________________
Full size document in back
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 TO 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 ARE THE RESPONSIBILITI
ES OF THE INSTITUTIONAL
REVIEW BOARD?
WHAT DOES THE IRB LOOK FOR REGARDING THE INFORMED CONSENT PROCESS? Method of presentation Voluntary participation Environment Complete explanations Length of time devoted to the process Simple explanations Adequate time offered to ask
questions How subject demonstrates
understand of the study and desire to participate
Promptness of reporting new information
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
WHAT DO MONITORS/AUDI
TORS LOOK FOR?
WHAT DO AUDITORS/MONITORS LOOK FOR ? If SOP’s exist are they followed? Confirm consent process documentation Implementation of changes only after IRB
approval Correct version non expired consent used All options completed by subject Consent signed and dated by all parties Consent signed prior to ANY procedures Consented by trained individuals
PROBLEMS OBSERVED IN 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 Check boxes within the consent incomplete Crossed out sections or white out used in the IRB approved consent Unable to locate consent for subject on study Subjects not re-consented with revised consent as instructed Ineligible subjects enrolled 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? Confirm all personnel consenting subjects are
KSP Document training and qualifications of all KSP Establish one place to retrieve ONLY the latest
IRB approved consent Conduct random audits of the consent
documentation 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
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
WHO ELSE KNOWS?
FDA WARNING LETTER 2010RELATED TO INFORMED CONSENT
January 19 – PI failed to obtain ICD for subjects (? Number), During response PI gave ICD to FDA not IRB approved
January 28 – PI failed to obtain consent with complete study info, conducted lab tests for two subjects without consent
February 18- PI failed to consent 1 subject (hand writing not subjects), enrolled 4 ineligible subjects
February 24 – PI failed to obtain legally authorized ICD: child was enrolled with 1 parent signature, child was in DHS custody
February 25 – PI failed to obtain legally authorized consent; implemented changes in the investigational plan without approval
March 2 – 7 of 25 subjects met EXCLUSION criteria, failed to properly consent 3 subjects, 1 was told would receive investigational device but received control device
FDA WARNING LETTER 2010RELATED TO INFORMED CONSENT March 18 – PI failed proper monitoring of the
investigational study March 10 – PI failed to notify subjects following
study participation regarding safety events March 21- PI failed to consent 2 subjects, 4
ineligible subjects enrolled March 24- IRB approved protocol allowing
consent following study procedures instead of before
April 1- PI failed to consent 1 subject, response letter found consent but it was visibly altered and the PI did not alter it.
June 28 – PI failed to consent with updated consent for 7 subjects, enrolled 7 subjects who were ineligible.
OHRP DETERMINATION LETTERS 2010 RELATED TO INFORMED CONSENT
January 28 – IRB did not document specific criteria when approving waiver or alteration of consent
January 29 – IRB did not waive consent for subjects, PHI was obtained from family members and the approved consent did not contain the appropriate risk language
April 8 – PI retain PHI on subject for a study without approval or consent. PI also implemented study changes (a 3rd intervention) without IRB approval
June 3 – PI decided not to inform subjects of new drug information since they had completed the study and PI did not conduct all follow-up visits (although subject was in the office) per protocol requirements
Nov 24 – IRB approved research involving pregnant woman/fetus that held the prospect of direct benefit to the fetus. Only one signature line was on the consent instead of the required two. IRB also approved telephone and electronic consents for studies however did not properly waive documentation or alteration of consent.
May 10- subject complained he was encouraged to continue a study he did not wish to continue in
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