IRB Refresher 2009IRB Refresher 2009

Helen PanageasAssociate Director

NYU School of MedicineNYU School of Medicine

INSTITUTIONAL REVIEW BOARDINSTITUTIONAL REVIEW BOARD

Kim DiccianniSenior Education Coordinator

www.med.nyu.edu/irb

Thank you for joining us. Thank you for joining us.

We hope to We hope to enhance your thinkingenhance your thinking as an as an IRB Member by refreshing your IRB Member by refreshing your

knowledge of Federal Regulations and knowledge of Federal Regulations and NYU SoM IRB Policies. NYU SoM IRB Policies.

GoalsGoals Conflict of Interest Conflict of Interest (presented by Office of Research Compliance)(presented by Office of Research Compliance)

International ResearchInternational Research Genetic ResearchGenetic Research GINA GINA Data and Tissue RepositoriesData and Tissue Repositories *NEW* Capacity to Consent Policy*NEW* Capacity to Consent Policy Informed Consent ProcessInformed Consent Process 111 Findings111 Findings

Policies on Conflicts of Interest, Policies on Conflicts of Interest, Consulting and CommitmentConsulting and Commitment

PART 2: RESEARCH CONFLICTS PART 2: RESEARCH CONFLICTS OF INTERESTOF INTEREST

IRB Training SessionsApril 30, 2009

Created by Monique Phillips

Part 2: Research Conflicts of InterestPart 2: Research Conflicts of Interest

Consists of two policies:

Policy on Conflicts of Interest in Research and Sponsored Programs - Replaces the Investigator Financial Interest Disclosure and Conflict of Interest Policy dated October 1, 1995

Policy on Institutional Conflicts of Interest in Human Subjects Research

Policy on Conflicts of Interest in Research Policy on Conflicts of Interest in Research and Sponsored Programsand Sponsored Programs

What’s the Purpose of the Policy?

To conduct research that is free of any appearance of impropriety or Conflict of Interest (research integrity)

To protect: Human and Non-Human Subjects Reputation of NYU Langone Medical Center and NYU SoM

What’s the General Policy?

All persons involved in a Sponsored Research Projectmust disclose their financial interest

If a financial interest exists, it must be evaluated, andmanaged or eliminated

Who Needs to Disclose Under this Policy?

All persons involved in the Sponsored Project must disclose theirfinancial interest:

Investigators Program Directors Key Personnel (e.g. study coordinator, outside collaborator)

When Do Disclosures Need to be Made?

Annually (Annual Disclosure Form) – except outside collaborators With each initial protocol submission When submitting annual protocol continuations Before obtaining a new financial interest

What Kinds of Things Need to Be Disclosed?

Outside Positions (Paid or Unpaid) Director, Trustee, Senior Executive, Officer or Employee

Ownership Interests (Any dollar amount) Stock or stock options

Consulting Compensation Consulting fee, honoraria/lecture fees, or other payment

Royalty Income

Intellectual Property Rights (Patent, license, or copyright)

Who Determines if a Financial Interest is Considered a

Conflict of Interest?

All financial interests related to a study (i.e. outside positions, consulting and other compensation, IP) should be disclosed

The CMU and/or RCOIC will determine if a conflict of interest exists

When is a Conflict of Interest Considered Manageable

vs. Unmanageable?

Financial Interests (not significant) Participation is generally permitted with a conflict management plan

issued by the CMU on behalf of the RCOIC

Significant Financial Interests Participation is not permitted unless the RCOIC determines that

“Compelling Circumstances” exist

A conflict management plan is implemented if participation is permitted

Appeals are made to the SVP and Vice Dean for Science

Review Thresholds: Human Subjects

Interest Type Financial Interest

Significant Financial Interest

Outside Position

Ownership Interest

Consulting Compensation (in 1 yr.)

$1-$10,000 $10,001+

Royalty Income $1-$10,000 $10,001+

Intellectual Property

Review Thresholds: Non-Human Subjects (Pre-Clinical)

Interest Type Financial Interest

Significant Financial Interest

Outside Position

Ownership Interest

Consulting Compensation (in 1 yr.)

$1-$10,000 $10,001+

Royalty Income $1-$10,000 $10,001+

Intellectual Property N/A

Review Thresholds: Non-Human Subjects

Interest Type Financial Interest

Significant Financial Interest

Outside Position

Ownership Interest

Publicly Traded

Privately-Held

$25,001+

Consulting Compensation (in 1 yr.)

$1-$25,000 $25,001+

Royalty Income $1-$25,000 $25,001+

Intellectual Property N/A

Policy on Institutional Conflicts of Interest in Policy on Institutional Conflicts of Interest in Human Subjects ResearchHuman Subjects Research

What’s the Purpose of this Policy? To remove the appearance of inappropriate influence over the

integrity of a research project and to ensure the safety and care of the human subjects enrolled in the study in cases where the Medical Center:

Receives or expects to receive royalty income from the sale of a product covered by a patent, license or copyright

Holds or proposes to hold any equity interests of any amount in the sponsor of the research study

What is the General Policy? The Medical Center will not participate in a human subject’s research

project when it has an institutional conflict of interest, unless the RCOIC determines Compelling Circumstances exist to warrant an exception

Appeals are made to the SVP and Vice Dean for Science

Individual vs. Institutional COIs: What is the RCOIC Process?

RCOIC Review & Evaluation – Individual Conflicts Review SFI matters to determine if “Compelling Circumstances”

exist to justify an Investigator’s participation

Propose and approve a conflicts management plan for those matters where an Investigator’s participation is permitted in the Sponsored Project

RCOIC Review & Evaluation – Institutional COIs Review of Institutional COI matters to determine if “Compelling

Circumstances exist to justify the Medical Center’s participation

Propose and approve a conflicts management plan for those matters where the Medical Center’s participation is permitted in a project

Compelling Circumstances TestFactors for Determining if “Compelling Circumstances”Exist:

Is the research appropriate and fundamental to the MedicalCenter?

Can the nature and amount of the financial interest significantly influence the outcome of the research?

Is this specific research essential to the continuity of the overall research?

Does the investigator have a unique expertise that is essential to the study?

Should there be any restrictions placed on publications or presentations related to this research?

Are there minimal risks to the subjects?

Compelling Circumstances Test (Cont’d.)

Factors for Determining if “Compelling Circumstances”

Exist:

For multicenter studies, is the %age of the total number of subjects so minimal as not to significantly impact the outcome of the study?

What are the proposed steps for oversight and management of the financial interests?

What role do the students/ trainees/ junior faculty and staff play? Are their roles free from exploitation and appropriate to the study?

For Institutional COIs: Is the Medical Center uniquely qualified to conduct the research (i.e. special facilities or equipment, unique patient population, qualifications of its investigators)

CMU Review & EvaluationWhat is the CMU’s role?

Disclosures with no financial interest

Sponsored Projects where a Financial Interest (not SFI) is disclosed The CMU makes a determination on behalf of the RCOIC

Initial evaluation of disclosures with a Significant Financial Interest The CMU passes these matters onto the RCOIC for final

determination

Sponsored Projects that have been previously, evaluated, and given a conflict management plan

RCOIC vs. the IRBRCOIC Reviews SFI matters and all other matters referred by the CMU

Review and evaluation must be completed by the RCOIC for all SFI matters before the IRB can give approval

Determines if Compelling Circumstances exist

Adopts management plans for matters where Compelling Circumstances exist

IRB Cannot approve protocols referred to the RCOIC without the

RCOIC’s approval recommendation (management plan)

May modify the RCOIC’s management plan to impose more stringent restrictions

Final approval for a study must come from the IRB

Changes from Existing PolicyChanges from Existing Policy Research Disclosure integrated w/Annual Disclosure

Investigator Disclosure Forms to be electronically submitted & searchable within the next 12 months

Increased requirements for Financial Interest Disclosure, especially NYU IP rights

CMU does initial review & in some cases issues a determination on behalf of RCOIC

Clearer instructions and mandates for RCOIC

Implementation of Compelling Circumstances Test for RCOIC members

Responsibilities of Vice Dean for Science more apparent

New Institutional COI Policy outlines policy & process

Dedicated website for further guidance and resources

Conflicts Management Unit (CMU) Conflicts Management Unit (CMU) WebsiteWebsite

Highlights Resource center for RCOIC Members

Agenda Meeting Schedule Meeting materials RCOIC Operating Guidelines

Full and abbreviated versions of Policies

Provides examples of conflicts in research, case studies and other useful tools for further guidance

CMU Website: http://cmu.med.nyu.edu

What is International What is International ResearchResearch

Research conducted by University investigators/faculty in foreign

countries

How should the IRB review How should the IRB review International Research…International Research…

As rigorously as if the project was being As rigorously as if the project was being completed at NYU SoM/Medical Center and its completed at NYU SoM/Medical Center and its affiliatesaffiliates

US rules prevail over US research being US rules prevail over US research being completed in another country.completed in another country.

Authorization required as per HIPAAAuthorization required as per HIPAA Informed Consent or Waiver requiredInformed Consent or Waiver required 111 findings must be made111 findings must be made Research study should have been or will be Research study should have been or will be

reviewed by the country’s research ethics review reviewed by the country’s research ethics review board or equivalent.board or equivalent.

Submission Materials In addition to all the usual IRB submission

materials, the Researchers should provide: Local review and documentation of the review and

approval If federal funding supports the research, the international

site is considered ‘engaged ‘in the research IRB approval from an institution with an FWA (in that country) is required

Provisions regarding how risks will be minimized for the subjects

Consent Process/Documentation Plan Illiteracy, native language consent forms, verbal consent

etc.

Consider the Research Methods to be used

What recruitment methods will be used? Do those methods violate cultural norms of

confidentiality?

Does the collection data or specimens involve sensitive, identifiable information?

How experienced is the PI in doing research in that country?

How about Informed Consent… Are there important historical or cultural

considerations?

Who will be doing the actual consent process?

Consent documentation: Translation – not just words, but culturally-

appropriate concepts – e.g., explaining randomization in terms of a lottery

Is a written form appropriate? Signature requirements

Do we have enough Knowledge of Local Research

Context? Ways for lead IRB to obtain knowledge

of local research context: knowledgeable IRB member consultants:

US faculty member foreign IRB member other individual

How Can an IRB Obtain Knowledge of Local Research Context?

Personal knowledge of an IRB memberPersonal knowledge of an IRB member Prior written review by a consultantPrior written review by a consultant Participation by a consultant at an IRB Participation by a consultant at an IRB

meeting (in person or by teleconference)meeting (in person or by teleconference) Systematic, reciprocal exchange:Systematic, reciprocal exchange:

Site visitsSite visits Interaction with consultantInteraction with consultant Interaction with institutional liaisonsInteraction with institutional liaisons Review of relevant written materialsReview of relevant written materials

Source: OHRP: IRB Knowledge of Local Research Context, July 21, 2000

Other IRB Considerations…Other IRB Considerations…

Consider the principles outlined in the Belmont Consider the principles outlined in the Belmont ReportReport

If there is no equivalent human subject protection If there is no equivalent human subject protection board board or group, or group,

investigators must rely on local experts or community investigators must rely on local experts or community leaders to provide approval. The IRB requires documentation leaders to provide approval. The IRB requires documentation of this "local approval" before it gives approval.of this "local approval" before it gives approval.

Hypothetical Survey: IRB Relationships

NYU SoMLead IRB

EnglandLocal IRB #1

PolandLocal IRB #2

BelarusCurrently has

no IRBestablished

Coordinating the Role of IRBs

Clarify the roles of the lead vs. local IRBs areas of responsibility? resolution of conflicts? initial vs. continuing review? Other?

Define working relationships – possible approaches: do joint reviews by primary reviewers foreign IRB member serve as consultant to US IRB

(and vice versa)

What about Belarus?

Options: Establish a new IRB in Belarus

Identify an existing IRB in a nearby country with appropriate knowledge of local research context – Polish IRB?

Rely on the NYU SoM IRB, if it can obtain knowledge of local research context

ResourcesReports and Articles Policy Issues in International Research: Clinical Trials in Developing

Countries

April 2001Report and Recommendations of the National Bioethics Advisory Commission (NBAC)

Ethics of Clinical Research in the Developing WorldMar. 2002Nature Reviews Immunology

International Ethical Guidelines for Biomedical Research Involving Human SubjectsOct. 2002by the Council for International Organizations of Medical Sciences

Report: The ethics of research related to healthcare in developing countries24 April 2002

International Compilation of Human Research Protections 2009 Edition Compiled By: Office for Human Research Protections, U.S. Department of Health and Human Services

Genetic Research

Genetic Research What is Genetics Research? Genetic research involves the analysis of any of

the following: DNA, RNA, chromosomes, proteins, or certain metabolites which might act as or identify markers associated with a known or suspected predisposition to disease or behavior. 

Usually genetic research involves the collection of human biological material such as blood, skin or other tissues, nail clippings or hair. 

Genetic research also may include the construction of pedigrees (maps of the distribution of a particular trait or condition among related individuals) or family medical histories. 

The potential power of genetic research is also the inherent risk such as: Patients and family members learn

of ominous mutations prior to disease symptoms.

Genetic information, not specifically solicited by the subject, could be the first warning sign of a troubled future.

Genetic Research

Mutations can be carried through subsequent generations, affecting as yet unborn descendants; and potential illness can be predicted even for family members, un-enrolled and unaffiliated with the research protocol. Un-validated results of genetic experiments can still cause actual psycho-social hardship even leading to financial loss.

What is considered genetic information?

Information about: A person’s genetic tests (defined in the NY State

Law as any laboratory test of human DNA, chromosomes, genes, or gene products to diagnose the presence of a genetic variation linked to a predisposition to a genetic disease or disability in the individual or individual's offspring; such term shall also include DNA profile analysis)

Genetic tests of a person’s family members

Disease or disorder in a family member

Participation of a person or family member inresearch that includes genetic testing,counseling, or education

What is considered genetic information?

Tests for BRCA1/BRCA2 (breast cancer) orHNPCC (colon cancer) mutations

Classifications of genetic properties of anexisting tumor to help determine therapy

Tests for Huntington disease mutations

Carrier screening for disorders, such as cystic fibrosis, sickle cell anemia, spinal muscular atrophy, and the fragile X syndrome

NOT Genetic Information:

Information about: Sex or age Routine tests such as complete blood

counts

(CBC, or blood panel), cholesterol tests, and liver-function tests Analysis, including DNA analysis, of

infectious agents such as bacteria, viruses,

and fungi, such as HIV.

How should the IRB review …. Consider the following 111

findings particularly: Risks Consent Process Privacy and Confidentiality

Genetic Research

Genetic Research and the 111 findings

Risks to Subjects are Minimized

Consider non physical risks including psychosocial risks. Examples of minimizing risks:

de-identification/anonymous samples or results; not disclosing results to subject or their

representatives; limiting the number of staff who have access to

identifiable results; not placing identifiable records such as signed

consent documents or results in the medical record; obtaining a certificate of confidentiality for

identifiable results; avoiding storage of specimens for future testing. Information should be included if genetic counseling

will be necessary and plan included on how this process is to be completed.

Genetic Research and the 111 findings

Reasonable Risk/Benefit RatioReasonable Risk/Benefit Ratio Possible BenefitsPossible Benefits

Subjects may be able to find ways to prevent the diseaseSubjects may be able to find ways to prevent the disease Generalizable knowledgeGeneralizable knowledge

Possible RisksPossible Risks Risks such as stigmatization, loss of insurance, employment Risks such as stigmatization, loss of insurance, employment

etc.. etc.. Learning about an ominous mutation prior to disease Learning about an ominous mutation prior to disease

symptoms. symptoms. Mutations can be carried through subsequent generations, Mutations can be carried through subsequent generations,

affecting as yet unborn descendants; and potential illness affecting as yet unborn descendants; and potential illness can be predicted even for family members, un-enrolled and can be predicted even for family members, un-enrolled and unaffiliated with the research protocol.unaffiliated with the research protocol.

Un-validated results of genetic experiments can still cause Un-validated results of genetic experiments can still cause actual psycho-social hardship even leading to financial loss.actual psycho-social hardship even leading to financial loss.

A subject may eventually suffer a serious loss of abilities A subject may eventually suffer a serious loss of abilities related to his/her career/every day life; related to his/her career/every day life;

incur higher then usual health care costs;incur higher then usual health care costs; statistically lower life expectancy; or,statistically lower life expectancy; or, ability to procreate and perform socially may become impaired. ability to procreate and perform socially may become impaired.

Informed Consent will be Informed Consent will be sought from each subjectsought from each subject

Consent document Consent document NY State has particular requirements. NY State has particular requirements.

Language is currently part of NYU SoM Language is currently part of NYU SoM standard templates.standard templates.

Consent process must be Consent process must be

described clearly.described clearly.

Protecting Privacy and maintaining Confidentiality

Description of all staff who may access identifiableDescription of all staff who may access identifiablesubject data. subject data.

Will results be provided to subjects or others. Will results be provided to subjects or others. What are the implications to others besides the What are the implications to others besides the

subjects including relatives of the participant and the subjects including relatives of the participant and the group the subject may be identified with such as group the subject may be identified with such as racial and/or ethnic.racial and/or ethnic.

Certificate of Confidentiality should be requested Certificate of Confidentiality should be requested when: socially sensitive conditions or traits are when: socially sensitive conditions or traits are studied; tests could have adverse consequences for studied; tests could have adverse consequences for the participant’s financial standing, insurability, or the participant’s financial standing, insurability, or employability should the results be disclosed outside employability should the results be disclosed outside the research team. the research team.

De-identification of samples and data before the De-identification of samples and data before the genetic testing or soon after can minimize risk to genetic testing or soon after can minimize risk to subjects and help protect confidentiality.subjects and help protect confidentiality.

Genetic ResearchGenetic ResearchUseful questions to consider:Useful questions to consider: Will test results be given?Will test results be given? Will disease risk be quantified, including the limits on Will disease risk be quantified, including the limits on

certainty of the testing?certainty of the testing? Will a change in a family relationship be disclosed, Will a change in a family relationship be disclosed,

such as mistaken paternity?such as mistaken paternity? Does the subject or family member have the option Does the subject or family member have the option

not to know the results? How will this decision be not to know the results? How will this decision be recorded?recorded?

Could other clinically relevant information be Could other clinically relevant information be uncovered by the study? How will disclosure of this uncovered by the study? How will disclosure of this added information occur?added information occur?

Do any practical limitations exist on the subject's right Do any practical limitations exist on the subject's right to withdraw from the research, withdraw data, and/or to withdraw from the research, withdraw data, and/or withdraw DNA?withdraw DNA?

Is the subject permitted to participate in the study Is the subject permitted to participate in the study while refusing to have genetic testing (such as in a while refusing to have genetic testing (such as in a treatment study with a genetic testing component)?treatment study with a genetic testing component)?

Genetic Research Virginia Commonwealth University (2000)Virginia Commonwealth University (2000)

Study involving twins, survey on the similar genetic Study involving twins, survey on the similar genetic structures. structures.

Survey intercepted by the parent of twins who Survey intercepted by the parent of twins who agreed to participate - Survey included question agreed to participate - Survey included question regarding parents and other relatives delving into regarding parents and other relatives delving into the family treethe family tree

Father complained to the federal authorities Father complained to the federal authorities Research into the genetics of health and psychology climbs through a Research into the genetics of health and psychology climbs through a

subject's family tree and across its branches to living family members, the subject's family tree and across its branches to living family members, the situation adds another ethical wrinkle for scientists trying to ensure privacy situation adds another ethical wrinkle for scientists trying to ensure privacy of information. of information.

As private citizens question the intrusiveness of research studies into lives As private citizens question the intrusiveness of research studies into lives beyond that of the person scribbling a signature on an informed consent beyond that of the person scribbling a signature on an informed consent form, IRBs at universities and medical centers may be forced to reevaluate form, IRBs at universities and medical centers may be forced to reevaluate how they secure informed consent.how they secure informed consent.

Genetic Information Nondiscrimination Act

(GINA) 2008 GINA is a Federal law that prohibits discrimination in health

coverage and employment based on genetic information.

GINA, together with already existing nondiscrimination provisions of the HIPAA, generally prohibits health insurers or health plan administrators from requesting or requiring genetic information of an individual or an individual's family members, or using such information for decisions regarding coverage, rates, or preexisting conditions.

GINA also prohibits employers from using genetic information for hiring, firing, or promotion decisions, and for any decisions regarding terms of employment.

The law take effect between May 22, 2009, and May 21, 2010, and those relating to employment (Title II) will take effect on November 21, 2009.(1)

What Does GINA Do?What Does GINA Do? For Health Insurers*

Prohibits group and individual health insurers from using a person’s genetic information in setting eligibility or premium or contribution amounts.

Prohibits health insurers from requesting or requiring that a person undergo a genetic test.

*Includes Medigap, but not Life, LTC, Disability

What Does GINA Do? For Employers

Prohibits employers from using a person’s genetic information in decisions such as hiring, firing, job assignments, and promotions.

Prohibits employers from requesting, requiring, or purchasing genetic information about an individual employee or family member.

GINA and Research Act includes a “research exception”

Allows health insurers or group health plans engaged in Allows health insurers or group health plans engaged in research to REQUEST, NOT REQUIRE, an individual to undergo a research to REQUEST, NOT REQUIRE, an individual to undergo a genetic test.genetic test.

IRBs should consider the provisions of GINA when IRBs should consider the provisions of GINA when assessing whether genetic research satisfies the assessing whether genetic research satisfies the criteria required for IRB approval of research:criteria required for IRB approval of research:

Test is voluntary and CANNOT be required. This information Test is voluntary and CANNOT be required. This information MUST be clear in the plan and consent informationMUST be clear in the plan and consent information

Research must comply to all elements of 45 CFR 46.111, Research must comply to all elements of 45 CFR 46.111, equivalent federal regulations and any applicable state or equivalent federal regulations and any applicable state or local laws for the protection of human research subjects , local laws for the protection of human research subjects ,

risks are minimized and reasonable in relation to anticipated risks are minimized and reasonable in relation to anticipated benefits benefits

there are adequate provisions in place to protect the privacy there are adequate provisions in place to protect the privacy of subjects and maintain the confidentiality of their data. of subjects and maintain the confidentiality of their data.

GINA and Informed Consent

OHRP recommends that for genetic research undergoing initial or continuing review reviews, IRBs consider whether consent processes and documents should include language regarding the protections provided by GINA especially risks and confidentiality protections.

What are Data and Tissue What are Data and Tissue RepositoriesRepositories

Data and Tissue Repositories are… Data and Tissue Repositories are… Databases, registries (data banks), and Databases, registries (data banks), and

repositories (tissue banks) all involve the repositories (tissue banks) all involve the collection and storage of information and/or collection and storage of information and/or biological specimens over time. biological specimens over time.

Some are created and maintained primarily Some are created and maintained primarily for diagnostic or clinical purposes. Others for diagnostic or clinical purposes. Others are created specifically for research. Many are created specifically for research. Many serve more than one purpose. serve more than one purpose.

All Data and Tissue Repositories used for research purposes

Database created for Research or being used for research

Registry

Repositories

What should the IRB review….

DatabaseDatabase

A database is collection of information elements (i.e., data) arranged for ease and speed of search and retrieval. Most databases are now maintained electronically, but the term can also be applied to paper record systems. Examples of databases include the following:

A set of observations (i.e., data) resulting from a research study

An electronic file of a medical provider’s patients

A collection of diagnosis, treatment, and follow-up information for a hospital’s oncology patients

A file of outcomes information compiled for quality assurance activities

A list of potential research subjects

A registry or “data bank” is a collection of information A registry or “data bank” is a collection of information elements or databases whose organizers; receive elements or databases whose organizers; receive information from multiple sources, maintain the information from multiple sources, maintain the information over time, control access to and use of information over time, control access to and use of the information by multiple individuals and/or for the information by multiple individuals and/or for multiple purposes, which may evolve over time multiple purposes, which may evolve over time

Registries often contain codes that link information Registries often contain codes that link information and specimens to their donor’s identify. Examples of a and specimens to their donor’s identify. Examples of a few well-known registries and data banks include: few well-known registries and data banks include:

Centers for Disease Control & Prevention (CDC) State Cancer Centers for Disease Control & Prevention (CDC) State Cancer Registries Registries

Familial Gastrointestinal Cancer Registry Familial Gastrointestinal Cancer Registry

National Registry of Myocardial Infarction (NRMI) National Registry of Myocardial Infarction (NRMI)

National Registry of Veterans with Amyotrophic Lateral SclerosisNational Registry of Veterans with Amyotrophic Lateral Sclerosis

RegistryRegistry

Repository: A repository or “tissue bank” is a collection of A repository or “tissue bank” is a collection of biological specimens whose organizers, rbiological specimens whose organizers, receive specimens eceive specimens from multiple sources, maintain the specimens over from multiple sources, maintain the specimens over time, control access to and use of specimens by time, control access to and use of specimens by multiple individuals and/or for multiple purposes, multiple individuals and/or for multiple purposes, which may evolve over time which may evolve over time

Repositories usually include demographic and/or medical Repositories usually include demographic and/or medical information about the individuals from whom the specimens were information about the individuals from whom the specimens were obtained. obtained.

Repositories often maintain codes that link the information and Repositories often maintain codes that link the information and specimens to their donor’s identify. Examples of a few well-known specimens to their donor’s identify. Examples of a few well-known repositories include: repositories include:

The National Human Radiobiology Tissue Repository The National Human Radiobiology Tissue Repository

The National Institute of General Medical Sciences (NIGMS) Human The National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository Genetic Cell Repository

The National Institute on Aging Cell RepositoryThe National Institute on Aging Cell Repository

RepositoryRepository

For DNA banking studies, several For DNA banking studies, several questions need to be addressed, questions need to be addressed, including:including:

will DNA be stored or shared? If shared, will DNA be stored or shared? If shared, will the subject's identity be known by will the subject's identity be known by the new recipient investigator?the new recipient investigator?

will the subject be contacted in the will the subject be contacted in the future by the investigator to obtain future by the investigator to obtain updated clinical information?updated clinical information?

how can the subject opt out of any how can the subject opt out of any distribution or subsequent use of distribution or subsequent use of his/her genetic material?his/her genetic material?

Data and Tissue Data and Tissue RepositoriesRepositories

Two possible submission types The project establishes the data or tissue

repository - would typically receive expedited review

A full board projects includes the collection of data and/or specimens for future use.

How should the IRB review How should the IRB review Data and Tissue RepositoriesData and Tissue Repositories

How should the IRB review How should the IRB review Data and Tissue RepositoriesData and Tissue Repositories

The IRB should: Review the protocol to determine what will be

collected, how will it be stored, who will store it, for how long will it be stored etc..

Evaluate the Informed Consent are subjects provided with information regarding the

purpose, description, risks, alternatives etc… for the future use of their data and/or specimens in the main consent?

Informed Consent

In this study we would like to use some of the tissue we collect for future research. Check below if you agree to allow us to use your tissue.

What is missing How long will the tissue be kept? Where will the tissue be kept? Who will have access to the tissue? Will identifiers be kept? Can the subject withdraw the tissue

if they change their mind? What will the tissue be used for? Will the subject know when the tissue

is being used and will they be able to consent to that use?

Capacity to Consent Policy Capacity to Consent Policy effective March 2009effective March 2009

What has changed in our capacity to consent policy?

In research involving subjects who lack capacity to consent NYU SoM IRB now allows a Health Care Proxy to consent on behalf of the subject The Health Care Proxy form does not state

the patient does not want to participate in research.

In the HC proxy form either the patient remains silent with regards to research or has positively affirmed their desire to participate in research.

What has NOT Changed…What has NOT Changed… A court-appointed legally authorized A court-appointed legally authorized

representative/guardian;representative/guardian;

   For an investigator to obtain surrogate For an investigator to obtain surrogate

consent utilizing a health care proxy, the IRB consent utilizing a health care proxy, the IRB must determine that the research provides must determine that the research provides potential therapeutic benefit to the subject. potential therapeutic benefit to the subject.

   For human subjects research conducted in For human subjects research conducted in

other states, requests for the use of other states, requests for the use of surrogate consent will be considered by the surrogate consent will be considered by the IRB in accordance with local state law.IRB in accordance with local state law.

The NYU SOM IRB PolicyThe NYU SOM IRB Policy

• Research involving persons with impaired decision-Research involving persons with impaired decision-making capability may only be approved when the making capability may only be approved when the following conditions apply:following conditions apply:

Only incompetent persons or persons with impaired Only incompetent persons or persons with impaired decision making capacity are suitable as research decision making capacity are suitable as research subjects. subjects.

There is a compelling reason to include There is a compelling reason to include incompetent individuals or persons with impaired incompetent individuals or persons with impaired decision-making capacity as subjects. Subjects decision-making capacity as subjects. Subjects should not be enrolled because they are readily should not be enrolled because they are readily available.available.

The proposed research entails no significant risks, The proposed research entails no significant risks, tangible or intangible. tangible or intangible.

The NYU SOM IRB PolicyThe NYU SOM IRB Policy

If the research presents some probability of If the research presents some probability of harm, the following evidence must be included:harm, the following evidence must be included:

A greater probability of direct benefit to the A greater probability of direct benefit to the participant. participant.

Incompetent people or persons with impaired Incompetent people or persons with impaired decision-making capacity are not to be decision-making capacity are not to be subjects of research that imposes a risk of subjects of research that imposes a risk of injury, unless that research is intended to injury, unless that research is intended to benefit that subject and the probability of benefit that subject and the probability of benefit is greater than the probability of harm.benefit is greater than the probability of harm.

Research in NYS and outside of NYSResearch in NYS and outside of NYS

For human subjects research For human subjects research conducted in New York State, NYU conducted in New York State, NYU SoM’s policy for surrogate consent and SoM’s policy for surrogate consent and its limits must be applied to the its limits must be applied to the researchresearch

For human subjects research For human subjects research conducted in other states, requests for conducted in other states, requests for the use of surrogate consent will be the use of surrogate consent will be considered by the IRB in accordance considered by the IRB in accordance with local state law.with local state law.

Additional Concerns…Additional Concerns… IRB Approval need to obtain consent from a IRB Approval need to obtain consent from a

representative of an adult subject rather than representative of an adult subject rather than directly from the subject (i.e., surrogate consent)directly from the subject (i.e., surrogate consent)

A subject previously determined to lack capacity to A subject previously determined to lack capacity to consent regains capacity during the study must be consent regains capacity during the study must be consented for the remaining part of the study. consented for the remaining part of the study. The consent process must disclose all research procedures The consent process must disclose all research procedures

performed to date and allow the individual an opportunity to performed to date and allow the individual an opportunity to continue in or withdraw from the study. continue in or withdraw from the study.

The subject must sign the IRB-approved consent document The subject must sign the IRB-approved consent document and the research record should document what research and the research record should document what research procedures were already performed or remain to be procedures were already performed or remain to be performed.performed.

What you need to know ….IRB must IRB must Approve any use of surrogate consent prospectively during Approve any use of surrogate consent prospectively during

review of the protocol or modification of the protocol. review of the protocol or modification of the protocol. Submission must include details of how the investigator will verify the Submission must include details of how the investigator will verify the

authority of the individual to serve as the legally authorized representative authority of the individual to serve as the legally authorized representative designated to provide surrogate consent. designated to provide surrogate consent.

Require investigators to conduct a competency assessment Require investigators to conduct a competency assessment whenever there is a possibility of either impaired mental whenever there is a possibility of either impaired mental status or decision-making capacity in prospective subjects. status or decision-making capacity in prospective subjects. Further, consultation with a psychiatrist or licensed Further, consultation with a psychiatrist or licensed psychologist must be obtained when the determination that psychologist must be obtained when the determination that the prospective research subject lacks decision-making the prospective research subject lacks decision-making capacity is based on a diagnosis of mental illness.capacity is based on a diagnosis of mental illness.

If feasible, the investigator must explain the proposed If feasible, the investigator must explain the proposed research to the prospective research subject even when the research to the prospective research subject even when the surrogate gives consent. Under no circumstances may a surrogate gives consent. Under no circumstances may a subject be forced or coerced to participate in a research study.subject be forced or coerced to participate in a research study.

Consent ProcessConsent Process

The Consent Process

Informed consent is not a single event or just a form to be signed -- rather, it is an educational process that takes place between the investigator and the prospective subject.

The basic elements of the consent process include:

full disclosure of the nature of the research and the subject's participation,

adequate comprehension on the part of the potential subjects, and

the subject's voluntary choice to participate.

Regulations require:Regulations require:

Informed consent will be sought from eachInformed consent will be sought from each

prospective subject or the subject's legally prospective subject or the subject's legally authorizedauthorized

representative, in accordance with, and to the extentrepresentative, in accordance with, and to the extent

required by 45 CFR 46.116 or 21 CFR 50.required by 45 CFR 46.116 or 21 CFR 50.

IRB findings:IRB findings:

If the research plan doesn’t tell how InformedIf the research plan doesn’t tell how Informed

Consent will be sought, can the IRB make Consent will be sought, can the IRB make

this finding?this finding?

Criteria for IRB approval of Criteria for IRB approval of researchresearch

What may happen if …

TAMPA - A lawsuit accusing USF doctors of experimenting on pregnant women without their consent is settled for $3.8 million…. The experiment wasn't considered risky and no adverse effects were documented, plaintiffs in the suit agree. However, the failure to inform … pregnant women of various experiments conducted between 1986 and 1990 has cost Tampa General Hospital, USF and the state $3.8 million.

Tampa Tribune 3/2000

Informed Consent ProcessInformed Consent Process Sample Protocol Language Sample Protocol Language

Each investigator will:Each investigator will:

Ensure that each patient is given full and adequate oral and Ensure that each patient is given full and adequate oral and written information about the nature, purpose, possible risk and written information about the nature, purpose, possible risk and benefit of the study.benefit of the study.

Ensure that the patients are notified that they are free to Ensure that the patients are notified that they are free to discontinue from the study at any timediscontinue from the study at any time

Ensure that the patients are given the opportunity to ask Ensure that the patients are given the opportunity to ask questions and are allowed time to consider the information questions and are allowed time to consider the information provided.provided.

Obtain and document each patient’s signed and dated informed Obtain and document each patient’s signed and dated informed consent before conducting any procedure specifically for the consent before conducting any procedure specifically for the study.study.

Ensure that the original, signed Informed Consent Form is Ensure that the original, signed Informed Consent Form is stored in a location where it may be immediately retrievable stored in a location where it may be immediately retrievable and available.and available.

Informed Consent ProcessInformed Consent Process Sample Protocol Language Sample Protocol Language

A properly executed, written, informed consent, in compliance with A properly executed, written, informed consent, in compliance with the Declaration of Helsinki, ICH GCP, US Code of Federal Regulations the Declaration of Helsinki, ICH GCP, US Code of Federal Regulations (CFR) for Protection of Human Subjects (21 CFR 50.25[a,b], CFR (CFR) for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), and local regulations, will be 50.27, and CFR Part 56, Subpart A), and local regulations, will be obtained from each patient prior to entering the patient into the trial. obtained from each patient prior to entering the patient into the trial. The investigator will prepare the informed consent form (ICF) and The investigator will prepare the informed consent form (ICF) and provide the documents to Sponsor for approval prior to submission to provide the documents to Sponsor for approval prior to submission to the IRB/IEC. Sponsor and the IRB/IEC must approve the documents the IRB/IEC. Sponsor and the IRB/IEC must approve the documents before they are implemented. The investigator will provide copies of before they are implemented. The investigator will provide copies of the signed ICF to each patient and caregiver (or the patient’s legal the signed ICF to each patient and caregiver (or the patient’s legal representative) and will maintain copies in the patient’s record file. representative) and will maintain copies in the patient’s record file. The investigator will obtain informed consent from subject and will The investigator will obtain informed consent from subject and will discuss the purpose of the research, a description of procedures, the discuss the purpose of the research, a description of procedures, the risks and any benefits, alternatives to participation, any costs, risks and any benefits, alternatives to participation, any costs, voluntary participation and a subject’s right to withdraw.voluntary participation and a subject’s right to withdraw.

Informed ConsentBasic Elements

Research Purpose/Duration Procedures Experimental

Risks Benefits Alternatives

Confidentiality Compensation for

Injury Whom to Contact Right to Refuse or

Withdraw

46.116(a)46.116(a)

Informed ConsentAdditional Elements

Currently Unforeseeable Risks Termination of Participation Additional Costs to Subjects Consequence of Withdrawal Informing of New Findings Number of Subjects

46.116(b)46.116(b)

Checklist for Consent Process

Investigator describes how it is done- Initial meeting

in person, over the phone, by mail or email? given time to digest information/ask questions Assessment of understanding Is the process coercive

Continued Consent Process Does the protocol include provisions for

continued IC process – If not, is that OK? Investigator includes: Who, What, Where and When

Are qualified personnel conducting the consent process?

What will be discussed with subject Physical Environment Timing

New protocol considerations:New protocol considerations: Are procedures for an ongoing process described?Are procedures for an ongoing process described? When and by whom will consent be obtained?When and by whom will consent be obtained? How will competency be addressed?How will competency be addressed? Is surrogate consent proposed, and if so, is it Is surrogate consent proposed, and if so, is it

acceptable?acceptable? Renewals:Renewals:

Has consent been obtained from enrolled Has consent been obtained from enrolled subjects?subjects?

Is the consent process adequate or are changes Is the consent process adequate or are changes required?required?

Is there new information that should be, but has Is there new information that should be, but has not yet been, conveyed to enrolled subjects?not yet been, conveyed to enrolled subjects?

Consent ProcessConsent Process

One last thing…

…Remember the 111 findings – these are the basis of what we do and why we do it

Risk to Subjects are minimizedRisk/Benefit Ratio is favorableSubject Selection is equitableInformed Consent is obtained and

documentedPrivacy is protectedConfidentiality is maintainedVulnerable Subjects are protected

Thank You