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

particip

ate

in rese

arch

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 (wendy.lloyd@vanderbilt.edu)

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 70.70

75 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 tips

http://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/

(WebTableOfContents)/8AF759048966C29D86257731005ECD1F?OpenDocument

If you have additional comments or questions feel free to contact me

Wendy LloydWendy.lloyd@vanderbilt.edu

615-936-7106