Rules of Human Rules of Human ExperimentationExperimentation

Elaine LarsonElaine LarsonCUMC IRB ChairCUMC IRB Chair

Associate Dean for Research, Associate Dean for Research, School of NursingSchool of Nursing

Professor of Epidemiology, Professor of Epidemiology, Mailman School of Public HealthMailman School of Public Health

Oversight for Human ResearchOversight for Human Research

•• Office of Human Research Protection Office of Human Research Protection (OHRP)(OHRP)•• http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htmhttp://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

•• FDAFDA–– http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearchttp://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfmh.cfm

•• New York StateNew York State–– http://http://caselaw.lp.findlaw.com/scripts/getcode.pl?framecaselaw.lp.findlaw.com/scripts/getcode.pl?frame=right2&code==right2&code=NY&lsNY&ls==claws&lawclaws&law=91&art=94=91&art=94

OHRPOHRP

•• Reviews institutional compliance with Reviews institutional compliance with federal regulations governing the federal regulations governing the protection of human subjects in HHSprotection of human subjects in HHS--sponsored research (~30,000 protocols)sponsored research (~30,000 protocols)

•• Evaluates all written substantive Evaluates all written substantive allegations or indications of allegations or indications of noncompliance with the HHS noncompliance with the HHS regulationsregulations

IRB MembersIRB Members

•• At least five members, with varying At least five members, with varying backgrounds backgrounds

•• Sufficiently qualified through the Sufficiently qualified through the experience, expertise and diversity of experience, expertise and diversity of its membersits members

•• At least one member whose primary At least one member whose primary concerns are in scientific areas, whose concerns are in scientific areas, whose primary concerns are in nonscientific primary concerns are in nonscientific areas, unaffiliated with institution areas, unaffiliated with institution

Criteria for ApprovalCriteria for Approval

•• Risks to subjects are minimized Risks to subjects are minimized •• Risks to subjects are reasonable in Risks to subjects are reasonable in

relation to anticipated benefits relation to anticipated benefits •• Selection of subjects is equitable Selection of subjects is equitable •• Informed consent is sought and Informed consent is sought and

documenteddocumented•• Adequate provision for monitoring data Adequate provision for monitoring data

and protecting privacy/confidentiality and protecting privacy/confidentiality

Required Elements of Informed Required Elements of Informed ConsentConsent

•• Statement that the study involves Statement that the study involves research, an explanation of the research, an explanation of the purposes of the research and the purposes of the research and the expected duration of the subject's expected duration of the subject's participation, a description of the participation, a description of the procedures to be followed, and procedures to be followed, and identification of any procedures which identification of any procedures which are experimental are experimental

Required ElementsRequired Elements……..•• Foreseeable risks or discomforts Foreseeable risks or discomforts •• Benefits to the subject or to others Benefits to the subject or to others •• Appropriate alternative proceduresAppropriate alternative procedures•• Extent to which confidentiality will be Extent to which confidentiality will be

maintained maintained •• Whether any compensation or treatments are Whether any compensation or treatments are

available if injury occursavailable if injury occurs•• Whom to contact Whom to contact •• Statement that participation is voluntary, Statement that participation is voluntary,

refusal to participate will involve no penalty refusal to participate will involve no penalty or loss of benefits or loss of benefits

Waiver of ConsentWaiver of Consent•• The research involves no more than minimal The research involves no more than minimal

risk to the subjects;risk to the subjects;•• The waiver or alteration will not adversely The waiver or alteration will not adversely

affect the rights and welfare of the subjects;affect the rights and welfare of the subjects;•• The research could not practicably be carried The research could not practicably be carried

out without the waiver or alteration; andout without the waiver or alteration; and•• Whenever appropriate, the subjects will be Whenever appropriate, the subjects will be

provided with additional pertinent provided with additional pertinent information after participation.information after participation.

Waiver of Documentation of ConsentWaiver of Documentation of Consent

•• The only record linking the subject and The only record linking the subject and research would be the consent document research would be the consent document and the principal risk would be potential and the principal risk would be potential harm resulting from a breach of harm resulting from a breach of confidentiality ORconfidentiality OR

•• The research presents no more than minimal The research presents no more than minimal risk of harm to subjects and involves no risk of harm to subjects and involves no procedures for which written consent is procedures for which written consent is normally required outside of the research normally required outside of the research context.context.

Additional Protections ForAdditional Protections For……

•• Pregnant Women, Human Fetuses and Pregnant Women, Human Fetuses and Neonates Neonates

•• Prisoners Prisoners •• ChildrenChildren

Examples of Exculpatory Examples of Exculpatory Language Language

•• By agreeing to this use, you should By agreeing to this use, you should understand that you will give up all understand that you will give up all claim to personal benefit from claim to personal benefit from commercial or other use of these commercial or other use of these substances substances

•• I waive any possibility of compensation I waive any possibility of compensation for injuries that I may receive as a for injuries that I may receive as a result of participation in this research result of participation in this research

Examples of Acceptable Examples of Acceptable Language Language

•• By consenting to participate, you By consenting to participate, you authorize the use of your bodily fluids authorize the use of your bodily fluids and tissue samples for the research and tissue samples for the research described above described above

•• This hospital is not able to offer This hospital is not able to offer financial compensation nor to absorb financial compensation nor to absorb the costs of medical treatment should the costs of medical treatment should you be injured as a result of you be injured as a result of participating in this research participating in this research

Required TrainingRequired Training----CUMCCUMC

•• GCPGCP•• HIPAAHIPAA

•• Research involving childrenResearch involving children

Certificate of Confidentiality Certificate of Confidentiality

•• So that researcher is not compelled in So that researcher is not compelled in any Federal, State, or local civil, any Federal, State, or local civil, criminal, administrative, legislative, or criminal, administrative, legislative, or other proceedings to identify research other proceedings to identify research participantsparticipants

•• Issued by NIH (only after IRB approval)Issued by NIH (only after IRB approval)

Levels of IRB ReviewLevels of IRB Review

•• Full BoardFull Board•• ExpeditedExpedited

•• ExemptExempt

Expedited ReviewExpedited Review

•• Review by IRB Chair or a designated Review by IRB Chair or a designated voting member or group of voting voting member or group of voting members, rather than by the entire IRB members, rather than by the entire IRB Committee. Federal rules permit Committee. Federal rules permit expedited review for certain kinds of expedited review for certain kinds of research involving no more than research involving no more than minimal risk and for minor changes in minimal risk and for minor changes in approved research. approved research.

ExpeditableExpeditable Criterion 1Criterion 1

•• Clinical studies of drugs and medical Clinical studies of drugs and medical devices whendevices when–– Research on drugs for which an Research on drugs for which an

investigational new drug application (IND) investigational new drug application (IND) is not required.is not required.

–– Research on medical devices for which (i) Research on medical devices for which (i) an investigational device exemption (IDE) an investigational device exemption (IDE) is not required; or (ii) the medical device is is not required; or (ii) the medical device is cleared/approved for marketing and the cleared/approved for marketing and the device is being used in accordance with its device is being used in accordance with its cleared/approved labeling.cleared/approved labeling.

ExpeditableExpeditable Criteria 2Criteria 2--44•• Collection of blood samples by finger stick, Collection of blood samples by finger stick,

heel stick, ear stick, or heel stick, ear stick, or venipuncturevenipuncture..•• Prospective collection of biological Prospective collection of biological

specimens for research purposes by specimens for research purposes by noninvasive means. noninvasive means.

•• Collection of data through noninvasive Collection of data through noninvasive procedures (not involving general anesthesia procedures (not involving general anesthesia or sedation) routinely employed in clinical or sedation) routinely employed in clinical practice, excluding procedures involving xpractice, excluding procedures involving x--rays or microwaves. rays or microwaves.

ExpeditableExpeditable Criteria 5Criteria 5--77•• Research involving materials that have been Research involving materials that have been

collected, or will be collected solely for collected, or will be collected solely for nonresearchnonresearch purposes. purposes.

•• Collection of data from voice, video, digital, Collection of data from voice, video, digital, or image recordings made for research or image recordings made for research purposes. purposes.

•• Research on individual or group Research on individual or group characteristics or behavior or research characteristics or behavior or research employing survey, interview, oral history, employing survey, interview, oral history, focus group, program evaluation, human focus group, program evaluation, human factors evaluation, or quality assurance factors evaluation, or quality assurance methodology. methodology.

ExpeditableExpeditable Criterion 8Criterion 8•• Continuing review of research previously Continuing review of research previously

approved by the convened IRB as follows: (a) approved by the convened IRB as follows: (a) where (i) the research is permanently closed where (i) the research is permanently closed to the enrollment of new subjects; (ii) all to the enrollment of new subjects; (ii) all subjects have completed all researchsubjects have completed all research--related related interventions; and (iii) the research remains interventions; and (iii) the research remains active only for longactive only for long--term followterm follow--up of up of subjects; or (b) where no subjects have been subjects; or (b) where no subjects have been enrolled and no additional risks have been enrolled and no additional risks have been identified; or (c) where the remaining identified; or (c) where the remaining research activities are limited to data research activities are limited to data analysis. analysis.

ExpeditableExpeditable Criterion 9Criterion 9

•• Continuing review of research not Continuing review of research not conducted under an investigational conducted under an investigational new drug application or new drug application or investigational device exemption investigational device exemption where categories do not apply, but where categories do not apply, but the IRB has documented at a the IRB has documented at a convened meeting that the convened meeting that the research involves no greater than research involves no greater than minimal risk and no additional minimal risk and no additional risks have been identifiedrisks have been identified. .

ExpeditableExpeditable Criteria 10Criteria 10--1212•• Minor change in previously approved Minor change in previously approved

research during the period (of one year or research during the period (of one year or less) for which approval is authorized. less) for which approval is authorized.

•• Facilitative Review for Cooperative Facilitative Review for Cooperative Amendment (CA/IAA) Amendment (CA/IAA)

•• Administrative Review Administrative Review -- Certain types of Certain types of awards (e.g., program project and center awards (e.g., program project and center grants) support multiple projects involving grants) support multiple projects involving numerous investigators. numerous investigators.

Exempt Determination (IRB)Exempt Determination (IRB)

•• Research conducted in established or Research conducted in established or commonly accepted educational commonly accepted educational settings, involving normal educational settings, involving normal educational practices or educational testspractices or educational tests

•• Study of existing data or specimens, if Study of existing data or specimens, if publicly available or if the information publicly available or if the information is recorded by the investigator in such is recorded by the investigator in such a manner that subjects cannot be a manner that subjects cannot be identified identified

ExemptionsExemptions•• Research conducted by or subject to Research conducted by or subject to

approval of Department or Agency heads approval of Department or Agency heads designed to study:designed to study:(i) Public benefit or service programs; (ii) (i) Public benefit or service programs; (ii) procedures for obtaining benefits or services procedures for obtaining benefits or services under those programs; (iii) possible changes under those programs; (iii) possible changes in or alternatives to those programs or in or alternatives to those programs or procedures; or (iv) possible changes in procedures; or (iv) possible changes in methods or levels of payment for benefits or methods or levels of payment for benefits or services under those programs.services under those programs.

•• Taste and food quality evaluation and Taste and food quality evaluation and consumer acceptance studies consumer acceptance studies

Other Review ProcessesOther Review Processes•• Cancer CommitteeCancer Committee•• Radiation Safety CommitteeRadiation Safety Committee•• Conflict of Interest CommitteeConflict of Interest Committee•• Hazardous Materials Committee (even for Hazardous Materials Committee (even for

blood draws)blood draws)•• Stem cell researchStem cell research•• Prisoner researchPrisoner research•• Individual departments (e.g. pediatrics)Individual departments (e.g. pediatrics)•• IRB is last to approve after all these!IRB is last to approve after all these!

HIPAA and ResearchHIPAA and Research

•• Many researchers need to address the Many researchers need to address the Privacy Standard of HIPAA Privacy Standard of HIPAA

•• This may require submission of This may require submission of authorization, waiver of authorization, or authorization, waiver of authorization, or preparatory to research documents to the preparatory to research documents to the Privacy BoardPrivacy Board

•• This is separate from IRB review This is separate from IRB review

Investigational New Drug (IND)Investigational New Drug (IND)

•• Application is filed with the FDA when a Application is filed with the FDA when a pharmacological agent is being tested pharmacological agent is being tested for safety and effectiveness in humans for safety and effectiveness in humans or when an FDA approved drug is being or when an FDA approved drug is being used in a different dosage, for a used in a different dosage, for a different purpose, or in a different different purpose, or in a different population than previously approved population than previously approved by the FDA by the FDA

Investigational Device Investigational Device Exemption (IDE)Exemption (IDE)

•• Mechanism by which new medical devices Mechanism by which new medical devices that could impose that could impose ““significant risksignificant risk”” to to subjects are tested subjects are tested

•• IDE allows an investigational device to be IDE allows an investigational device to be used in a study to gather data on safety and used in a study to gather data on safety and efficacy (effectiveness) of the device. efficacy (effectiveness) of the device.

•• IDE is also required for an approved device IDE is also required for an approved device which is being used offwhich is being used off--label in a research label in a research study study

Humanitarian Use Device (HUD)Humanitarian Use Device (HUD)

•• A designation given to devices that may A designation given to devices that may benefit patients being treated for a disease benefit patients being treated for a disease that affects less than 4,000 individuals in the that affects less than 4,000 individuals in the U.S. per year. U.S. per year.

•• Because device manufacturers may be less Because device manufacturers may be less inclined to put resources towards devices for inclined to put resources towards devices for diseases in so few individuals, HUD diseases in so few individuals, HUD provisions were created to provide greater provisions were created to provide greater access for the use of such devices. access for the use of such devices.

Center for Drug Evaluation and Center for Drug Evaluation and ResearchResearch

•• ((http://http://www.fda.gov/cderwww.fda.gov/cder))•• Largest of FDA's five centers, with a Largest of FDA's five centers, with a

staff of about 1,800. staff of about 1,800. •• Responsibility for both prescription Responsibility for both prescription

and overand over--thethe--counter drugs. counter drugs. •• Investigational New Drug (IND) Investigational New Drug (IND)

applications are administered by CDER applications are administered by CDER

Center for Devices and Center for Devices and Radiological HealthRadiological Health

•• ((http://http://www.fda.gov/cdrhwww.fda.gov/cdrh) ) •• Oversees investigational device Oversees investigational device

exemptions (IDE) and humanitarian exemptions (IDE) and humanitarian device exemptions (HDE) device exemptions (HDE)

Emergency Use ProtocolsEmergency Use Protocols•• When there is need to use an investigational When there is need to use an investigational

device in a manner inconsistent with the device in a manner inconsistent with the approved investigational plan or by a approved investigational plan or by a physician who is not part of the clinical physician who is not part of the clinical study. study.

•• Emergency use of an unapproved device Emergency use of an unapproved device may occur before an IDE is approved. may occur before an IDE is approved. –– LifeLife--threatening or serious disease or condition threatening or serious disease or condition –– No alternative No alternative –– No time to obtain FDA approval No time to obtain FDA approval

Compassionate useCompassionate use•• For patients who do not meet the For patients who do not meet the

requirements for inclusion in the clinical requirements for inclusion in the clinical investigation but for whom the treating investigation but for whom the treating physician believes the device may provide a physician believes the device may provide a benefit in treating and/or diagnosing their benefit in treating and/or diagnosing their disease or condition. disease or condition.

•• Typically approved for individual patients but Typically approved for individual patients but may be approved to treat a small group.may be approved to treat a small group.–– Serious disease or condition Serious disease or condition –– No alternative No alternative

New York State LawNew York State Law•• No human research in the absence of the No human research in the absence of the

voluntary informed consent in writing by the voluntary informed consent in writing by the human subject. human subject.

•• For minors, consent in writing by the For minors, consent in writing by the minor`sminor`sparent or legal guardian. parent or legal guardian.

•• For those legally unable to render consent, For those legally unable to render consent, such consent shall be subscribed to in such consent shall be subscribed to in writing by such other person as may be writing by such other person as may be legally empowered to act on behalf of the legally empowered to act on behalf of the human subject. human subject.

What Kind of Review?What Kind of Review?

•• Relationship between sleeping Relationship between sleeping patterns and actingpatterns and acting--out behavior in out behavior in hospitalized psychiatric patients hospitalized psychiatric patients

•• Effects of a new drug treatment for Effects of a new drug treatment for diabetic patients diabetic patients

•• Cardiovascular effects of exercise Cardiovascular effects of exercise following acute MIfollowing acute MI

•• Comparison to two teaching methods Comparison to two teaching methods for insertion of central linesfor insertion of central lines

What Kind of ReviewWhat Kind of Review

•• Chart review of Chart review of neurologicneurologic outcomes of outcomes of patients following one type of patients following one type of neurosurgeryneurosurgery

•• Hormonal levels in normal women Hormonal levels in normal women during the menstrual cycleduring the menstrual cycle

•• Random digit dialing interviews in NYC Random digit dialing interviews in NYC to assess rates of influenzato assess rates of influenza--type type symptomssymptoms