The New Crisis in The New Crisis in Human Subject Human Subject

Protection: Protection: Is Accreditation the Is Accreditation the

Answer?Answer?

Steven SmithSteven SmithCalifornia Western School of California Western School of

LawLawApril 15, 2005April 15, 2005

SummarySummary

The use of human subjects in medical The use of human subjects in medical and social science research is critical and social science research is critical to the advancement of medicine. to the advancement of medicine.

Continued support for this research Continued support for this research is, however, threatened by the is, however, threatened by the disclosure of research misconduct.disclosure of research misconduct.

The medical and higher education The medical and higher education communities should take steps to communities should take steps to maintain confidence in human studies, maintain confidence in human studies, and to some extent are doing so.and to some extent are doing so.

The extent of the use of The extent of the use of humans in research is not humans in research is not known, but it is estimated known, but it is estimated

that in the U.S.:that in the U.S.: More than 20 million people participate in human More than 20 million people participate in human

studies annually.studies annually. More than $60 billion is spent on biomedical More than $60 billion is spent on biomedical

research annually.research annually. Perhaps 60,000 researchers conduct clinical Perhaps 60,000 researchers conduct clinical

trials in the U.S.trials in the U.S. The number of clinical trials in the US may The number of clinical trials in the US may

exceed 100,000 annually.exceed 100,000 annually. There are 3 to 5,000 IRBsThere are 3 to 5,000 IRBs (I have no faith in most of these data)(I have no faith in most of these data)

Public ConfidencePublic Confidence 83% of adults believe it is essential or very important 83% of adults believe it is essential or very important

to test new drugs or treatments on humans in clinical to test new drugs or treatments on humans in clinical trials before they are approved for general usetrials before they are approved for general use

Only 24% are very confident that patients in clinical Only 24% are very confident that patients in clinical trials are treated as patients and not “guinea pigs”trials are treated as patients and not “guinea pigs”

25% are very confident they are “told honestly of the 25% are very confident they are “told honestly of the risks”risks”

Only 20% are very confident that doctors and hospitals Only 20% are very confident that doctors and hospitals do not recruit them “so they can make more money”do not recruit them “so they can make more money”

Minority respondents were generally less confident in Minority respondents were generally less confident in the legitimacy and safety of participating in human the legitimacy and safety of participating in human studiesstudies

From Harris Interactive Survey, 2002 From Harris Interactive Survey, 2002

““Human experimentation Human experimentation has existed throughout has existed throughout

human history”human history”

“ “God created man”God created man”

““So God caused a deep sleep to fall So God caused a deep sleep to fall upon the man and while he slept took upon the man and while he slept took one of his ribs and closed up its lace one of his ribs and closed up its lace

with flesh [and] the rib he made into a with flesh [and] the rib he made into a woman.”woman.”

Traditional Control of Traditional Control of Medical Experiments on Medical Experiments on

HumansHumans

Tort LiabilityTort Liability

Criminal LiabilityCriminal Liability

License DisciplineLicense Discipline

Human Subject Protection Human Subject Protection Crisis ICrisis I

"Permissible Medical Experiments.""Permissible Medical Experiments." Trials of War Criminals before the Nuremberg Military Trials of War Criminals before the Nuremberg Military

Tribunals under Control Council Law No. 10. Nuremberg Tribunals under Control Council Law No. 10. Nuremberg October 1946 - April 1949, Washington. U.S. Government October 1946 - April 1949, Washington. U.S. Government

Printing Office, vol. 2., pp. 181-182.Printing Office, vol. 2., pp. 181-182.

1. The voluntary consent of the human subject is absolutely 1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have essential. This means that the person involved should have legal capacity to give consent; should be situated as to be able legal capacity to give consent; should be situated as to be able to exercise free power of choice, without the intervention of to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion, and should have other ulterior form of constraint or coercion, and should have sufficient knowledge and comprehension of the elements of the sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an subject matter involved as to enable him to make an understanding and enlightened decision. This latter element understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come the effects upon his health or person which may possibly come from his participation in the experiment. from his participation in the experiment.

The duty and responsibility for ascertaining the quality of the The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with responsibility which may not be delegated to another with impunity.impunity.

2. The experiment should be such as to yield fruitful results for 2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature. of study, and not random and unnecessary in nature.

3. The experiment should be so designed and based on the 3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study natural history of the disease or other problem under study that the anticipated results will justify the performance of the that the anticipated results will justify the performance of the experiment. experiment.

4. The experiment should be so conducted as to avoid all 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. unnecessary physical and mental suffering and injury.

5. No experiment should be conducted where there is an a priori 5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental except, perhaps, in those experiments where the experimental physicians also serve as subjects. physicians also serve as subjects.

6. The degree of risk to be taken should never exceed that 6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to determined by the humanitarian importance of the problem to be solved by the experiment. be solved by the experiment.

7. Proper preparations should be made and adequate facilities 7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even provided to protect the experimental subject against even remote possibilities of injury disability or death. remote possibilities of injury disability or death.

8. The experiment should be conducted only by scientifically 8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who be required through all stages of the experiment of those who conduct or engage in the experiment. conduct or engage in the experiment.

9. During the course of the experiment the human subject should 9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the reached the physical or mental state where continuation of the experiment seems to him to be impossible. experiment seems to him to be impossible.

10. During the course of the experiment the scientist in charge 10. During the course of the experiment the scientist in charge must be must be prepared to terminate the experiment at any stage, if he has prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required by him that a superior skill and careful judgment required by him that a continuation of the experiment is likely to result in injury, continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.disability, or death to the experimental subject.

WORLD MEDICAL WORLD MEDICAL ASSOCIATION DECLARATION ASSOCIATION DECLARATION

OF HELSINKIOF HELSINKI   Ethical Principles for Medical Ethical Principles for Medical ResearchResearch

Involving Human Subjects Involving Human Subjects Adopted by the 18th WMA General Assembly, Helsinki, Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by theFinland, June 1964, and amended by the29th WMA General Assembly, Tokyo, Japan, October 197529th WMA General Assembly, Tokyo, Japan, October 197535th WMA General Assembly, Venice, Italy, October 198335th WMA General Assembly, Venice, Italy, October 198341st WMA General Assembly, Hong Kong, September 198941st WMA General Assembly, Hong Kong, September 198948th WMA General Assembly, Somerset West, Republic of 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996South Africa, October 1996and the 52nd WMA General Assembly, Edinburgh, and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 Scotland, October 2000 Note of Clarification on Paragraph 29 added by the WMA Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002General Assembly, Washington 2002Note of Clarification on Paragraph 30 added by the WMA Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 2004 General Assembly, Tokyo 2004

INTRODUCTION INTRODUCTION

The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data.subjects includes research on identifiable human material or identifiable data.

It is the duty of the physician to promote and safeguard the health of the people. The physician's knowledge and conscience are It is the duty of the physician to promote and safeguard the health of the people. The physician's knowledge and conscience are dedicated to the fulfillment of this duty.dedicated to the fulfillment of this duty.

The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of my patient will be The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of my patient will be my first consideration," and the International Code of Medical Ethics declares that, "A physician shall act only in the patient's my first consideration," and the International Code of Medical Ethics declares that, "A physician shall act only in the patient's interest when providing medical care which might have the effect of weakening the physical and mental condition of the interest when providing medical care which might have the effect of weakening the physical and mental condition of the patient." patient."

Medical progress is based on research which ultimately must rest in part on experimentation involving human subjects.Medical progress is based on research which ultimately must rest in part on experimentation involving human subjects.

In medical research on human subjects, considerations related to the well-being of the human subject should take precedence In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society.over the interests of science and society.

The primary purpose of medical research involving human subjects is to improve prophylactic, diagnostic and therapeutic The primary purpose of medical research involving human subjects is to improve prophylactic, diagnostic and therapeutic procedures and the understanding of the aetiology and pathogenesis of disease. Even the best proven prophylactic, procedures and the understanding of the aetiology and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic methods must continuously be challenged through research for their effectiveness, efficiency, diagnostic, and therapeutic methods must continuously be challenged through research for their effectiveness, efficiency, accessibility and quality. accessibility and quality.

In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures involve risks and In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures involve risks and burdens. burdens.

Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection. The particular needs of the economically and Some research populations are vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from the research and for those for whom the research is combined with care. the research and for those for whom the research is combined with care.

Research Investigators should be aware of the ethical, legal and regulatory requirements for research on human subjects in their Research Investigators should be aware of the ethical, legal and regulatory requirements for research on human subjects in their own countries as well as applicable international requirements. No national ethical, legal or regulatory requirement should own countries as well as applicable international requirements. No national ethical, legal or regulatory requirement should be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.

BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH

It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human subject. It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human subject.

Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation.appropriate, animal experimentation.

Appropriate caution must be exercised in the conduct of research which may affect the environment, and the welfare of animals Appropriate caution must be exercised in the conduct of research which may affect the environment, and the welfare of animals used for research must be respected.used for research must be respected.

The design and performance of each experimental procedure involving human subjects should be clearly formulated in an The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. This protocol should be submitted for consideration, comment, guidance, and where appropriate, experimental protocol. This protocol should be submitted for consideration, comment, guidance, and where appropriate, approval to a specially appointed ethical review committee, which must be independent of the investigator, the sponsor or approval to a specially appointed ethical review committee, which must be independent of the investigator, the sponsor or any other kind of undue influence. This independent committee should be in conformity with the laws and regulations of any other kind of undue influence. This independent committee should be in conformity with the laws and regulations of the country in which the research experiment is performed. The committee has the right to monitor ongoing trials. The the country in which the research experiment is performed. The committee has the right to monitor ongoing trials. The researcher has the obligation to provide monitoring information to the committee, especially any serious adverse events. researcher has the obligation to provide monitoring information to the committee, especially any serious adverse events. The researcher should also submit to the committee, for review, information regarding funding, sponsors, institutional The researcher should also submit to the committee, for review, information regarding funding, sponsors, institutional affiliations, other potential conflicts of interest and incentives for subjects. affiliations, other potential conflicts of interest and incentives for subjects.

The research protocol should always contain a statement of the ethical considerations involved and should indicate that there is The research protocol should always contain a statement of the ethical considerations involved and should indicate that there is compliance with the principles enunciated in this Declaration. compliance with the principles enunciated in this Declaration.

Medical research involving human subjects should be conducted only by scientifically qualified persons and under the Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent. medically qualified person and never rest on the subject of the research, even though the subject has given consent.

Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject or to others. This does not preclude the participation of burdens in comparison with foreseeable benefits to the subject or to others. This does not preclude the participation of healthy volunteers in medical research. The design of all studies should be publicly available.healthy volunteers in medical research. The design of all studies should be publicly available.

Physicians should abstain from engaging in research projects involving human subjects unless they are confident that the risks Physicians should abstain from engaging in research projects involving human subjects unless they are confident that the risks involved have been adequately assessed and can be satisfactorily managed. Physicians should cease any investigation if the involved have been adequately assessed and can be satisfactorily managed. Physicians should cease any investigation if the risks are found to outweigh the potential benefits or if there is conclusive proof of positive and beneficial results. risks are found to outweigh the potential benefits or if there is conclusive proof of positive and beneficial results.

Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and burdens to the subject. This is especially important when the human subjects are healthy volunteers. burdens to the subject. This is especially important when the human subjects are healthy volunteers.

Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research. benefit from the results of the research.

The subjects must be volunteers and informed participants in the research project.The subjects must be volunteers and informed participants in the research project.

The right of research subjects to safeguard their integrity must always be respected. Every precaution should be taken to respect the The right of research subjects to safeguard their integrity must always be respected. Every precaution should be taken to respect the privacy of the subject, the confidentiality of the patient's information and to minimize the impact of the study on the subject's physical privacy of the subject, the confidentiality of the patient's information and to minimize the impact of the study on the subject's physical and mental integrity and on the personality of the subject.and mental integrity and on the personality of the subject.

In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw the discomfort it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. After ensuring that the subject has understood the information, the physician consent to participate at any time without reprisal. After ensuring that the subject has understood the information, the physician should then obtain the subject's freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the should then obtain the subject's freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the non-written consent must be formally documented and witnessed. non-written consent must be formally documented and witnessed.

When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent relationship with the physician or may consent under duress. In that case the informed consent should be obtained by a well-informed relationship with the physician or may consent under duress. In that case the informed consent should be obtained by a well-informed physician who is not engaged in the investigation and who is completely independent of this relationship. physician who is not engaged in the investigation and who is completely independent of this relationship.

For a research subject who is legally incompetent, physically or mentally incapable of giving consent or is a legally incompetent minor, the For a research subject who is legally incompetent, physically or mentally incapable of giving consent or is a legally incompetent minor, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. These investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. These groups should not be included in research unless the research is necessary to promote the health of the population represented and groups should not be included in research unless the research is necessary to promote the health of the population represented and this research cannot instead be performed on legally competent persons. this research cannot instead be performed on legally competent persons.

When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about participation in research, the When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about participation in research, the investigator must obtain that assent in addition to the consent of the legally authorized representative. investigator must obtain that assent in addition to the consent of the legally authorized representative.

Research on individuals from whom it is not possible to obtain consent, including proxy or advance consent, should be done only if the Research on individuals from whom it is not possible to obtain consent, including proxy or advance consent, should be done only if the physical/mental condition that prevents obtaining informed consent is a necessary characteristic of the research population. The physical/mental condition that prevents obtaining informed consent is a necessary characteristic of the research population. The specific reasons for involving research subjects with a condition that renders them unable to give informed consent should be stated specific reasons for involving research subjects with a condition that renders them unable to give informed consent should be stated in the experimental protocol for consideration and approval of the review committee. The protocol should state that consent to in the experimental protocol for consideration and approval of the review committee. The protocol should state that consent to remain in the research should be obtained as soon as possible from the individual or a legally authorized surrogate.remain in the research should be obtained as soon as possible from the individual or a legally authorized surrogate.

Both authors and publishers have ethical obligations. In publication of the results of research, the investigators are obliged to preserve the Both authors and publishers have ethical obligations. In publication of the results of research, the investigators are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or otherwise publicly available. Sources of funding, accuracy of the results. Negative as well as positive results should be published or otherwise publicly available. Sources of funding, institutional affiliations and any possible conflicts of interest should be declared in the publication. Reports of experimentation not in institutional affiliations and any possible conflicts of interest should be declared in the publication. Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication. accordance with the principles laid down in this Declaration should not be accepted for publication.

ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARECARE

The physician may combine medical research with medical care, only to the extent that The physician may combine medical research with medical care, only to the extent that the research is justified by its potential prophylactic, diagnostic or therapeutic the research is justified by its potential prophylactic, diagnostic or therapeutic value. When medical research is combined with medical care, additional standards value. When medical research is combined with medical care, additional standards apply to protect the patients who are research subjects.apply to protect the patients who are research subjects.

The benefits, risks, burdens and effectiveness of a new method should be tested against The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists. prophylactic, diagnostic or therapeutic method exists.

At the conclusion of the study, every patient entered into the study should be assured of At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study. identified by the study.

The physician should fully inform the patient which aspects of the care are related to the The physician should fully inform the patient which aspects of the care are related to the research. The refusal of a patient to participate in a study must never interfere with research. The refusal of a patient to participate in a study must never interfere with the patient-physician relationship.the patient-physician relationship.

In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or have been ineffective, the physician, with informed consent methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic and from the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician's judgement it offers hope of saving life, re-therapeutic measures, if in the physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering. Where possible, these measures should establishing health or alleviating suffering. Where possible, these measures should be made the object of research, designed to evaluate their safety and efficacy. In all be made the object of research, designed to evaluate their safety and efficacy. In all cases, new information should be recorded and, where appropriate, published. The cases, new information should be recorded and, where appropriate, published. The other relevant guidelines of this Declaration should be followedother relevant guidelines of this Declaration should be followed

Crisis II EventsCrisis II Events

1962-- Fetal abnormalities from 1962-- Fetal abnormalities from ThalidomideThalidomide

1964-- Brooklyn Jewish Chronic 1964-- Brooklyn Jewish Chronic Disease Hospital Disease Hospital ExperimentsExperiments

1966-- Beecher article in NEJM1966-- Beecher article in NEJM 1971-- Willowbrook School for the 1971-- Willowbrook School for the

Mentally Retarded ExperimentsMentally Retarded Experiments 1972-- Tuskegee Syphilis Study1972-- Tuskegee Syphilis Study

Legal Response Legal Response

National Research Act 1972National Research Act 1972

Belmont ReportBelmont Report

HEW/FDA regulations establishing HEW/FDA regulations establishing IRBsIRBs

Department of Health, Education, and WelfareDepartment of Health, Education, and Welfare Office of the SecretaryOffice of the Secretary

PROTECTION OF HUMAN SUBJECTSPROTECTION OF HUMAN SUBJECTS

BELMONT REPORT:BELMONT REPORT: ETHICAL PRINCIPLES AND GUIDELINESETHICAL PRINCIPLES AND GUIDELINES

FOR THE PROTECTION OFFOR THE PROTECTION OF HUMAN SUBJECTS OF RESEARCHHUMAN SUBJECTS OF RESEARCH Report of the National Commission Report of the National Commission 

for the Protection of Human Subjects of for the Protection of Human Subjects of Biomedical and Behavioral ResearchBiomedical and Behavioral Research

Table of ContentsTable of Contents        

SummarySummary Members of the CommissionMembers of the Commission The Belmont Report: An IntroductionThe Belmont Report: An Introduction

Boundaries Between Practice and ResearchBoundaries Between Practice and Research Basic Ethical PrinciplesBasic Ethical Principles

Respect for PersonsRespect for Persons BeneficenceBeneficence JusticeJustice

ApplicationsApplications Informed ConsentInformed Consent Assessment of Risk and BenefitsAssessment of Risk and Benefits Selection of SubjectsSelection of Subjects

           

The Age of the IRBThe Age of the IRB

Decentralized decision-making Decentralized decision-making Community-based decisions Community-based decisions

reflecting the values of the reflecting the values of the communitycommunity

Subject of Federal Guidelines, but Subject of Federal Guidelines, but little federal oversightlittle federal oversight

The “Common Rule”The “Common Rule” The FDA and HHSThe FDA and HHS

Roles of the IRBRoles of the IRBIn reviewing proposed research involving human In reviewing proposed research involving human

subjects, generally the IRB is to determine:subjects, generally the IRB is to determine:(1) that risks to subjects are minimized through the (1) that risks to subjects are minimized through the

use of a sound research design;use of a sound research design;(2) that risks are reasonable in relation to (2) that risks are reasonable in relation to

anticipated benefits;anticipated benefits;(3) that the selection of subjects is equitable;(3) that the selection of subjects is equitable;(4) that appropriate informed consent will be (4) that appropriate informed consent will be

sought from each subject;sought from each subject;(5) that the informed consent will be appropriately (5) that the informed consent will be appropriately

documented;documented;(6) that if appropriate, the research plan will (6) that if appropriate, the research plan will

provide for monitoring of data; andprovide for monitoring of data; and(7) that if needed there are adequate provisions to (7) that if needed there are adequate provisions to

protect subjects' privacy and maintain protect subjects' privacy and maintain confidentiality of data. confidentiality of data.

A Third Crisis DevelopsA Third Crisis Develops 1996--General Accounting Office - heavy 1996--General Accounting Office - heavy

workloads, lack of preparedness of IRB, workloads, lack of preparedness of IRB, limited resourceslimited resources

1998--Office of Inspector General, DHHS - 1998--Office of Inspector General, DHHS - IRBs overwhelmed; issued a warning signalIRBs overwhelmed; issued a warning signal

1999--Jesse Gelsinger died in U. Pa. in gene 1999--Jesse Gelsinger died in U. Pa. in gene therapy studytherapy study

2000--Suit filed in U. of Oklahoma 2000--Suit filed in U. of Oklahoma melanoma vaccine studymelanoma vaccine study

2001--Ellen Roche, a healthy volunteer, 2001--Ellen Roche, a healthy volunteer, died in an asthma study at Hopkinsdied in an asthma study at Hopkins

Potential Legal ControlsPotential Legal Controls

Civil LiabilityCivil Liability Criminal LiabilityCriminal Liability License DisciplineLicense Discipline Direct RegulationDirect Regulation Indirect Regulation (e.g., FDA)Indirect Regulation (e.g., FDA) Federal FundingFederal Funding

Suspensions of Federally Suspensions of Federally Supported ResearchSupported Research

March 1999 Greater Los Angeles Health March 1999 Greater Los Angeles Health Care Care System, West System, West

Los Angeles Los Angeles May 1999May 1999 Duke University Medical Duke University Medical

CenterCenter August 1999August 1999 University of Illinois, ChicagoUniversity of Illinois, Chicago January 2000January 2000 Virginia Commonwealth Virginia Commonwealth

June 2000 University of Oklahoma June 2000 University of Oklahoma Health Health Sciences CenterSciences Center

July 2001 July 2001 Johns Hopkins Medical Johns Hopkins Medical

FDA warning letters to FDA warning letters to IRBsIRBs

VIOLATION THEMEVIOLATION THEME Number of IRBs (%) Number of IRBs (%) with this violationwith this violation

Inadequate written proceduresInadequate written procedures 50 (96%)50 (96%)

Inadequate documentation of IRB Inadequate documentation of IRB activitiesactivities

47 (90%)47 (90%)

Inadequate continuing reviewInadequate continuing review 36 (69%)36 (69%)

Inappropriate membership/quorum Inappropriate membership/quorum requirementsrequirements

30 (58%)30 (58%)

Inappropriate consent processInappropriate consent process 19 (37%)19 (37%)

Inadequate initial reviewInadequate initial review 11 (21%)11 (21%)

52 Warning Letters were issued to IRBs from Jan 1997 to July 2004

Ref: Bramstedt, A and Kassimatis, K. Clin Invest Med 27:6 (Dec 2004): 316-323

LiabilityLiability Gelsinger v. Trustees of the Univ. of Gelsinger v. Trustees of the Univ. of

PennsylvaniaPennsylvania Robertson v. McGeeRobertson v. McGee Wright v. HutchinsonWright v. Hutchinson Berman v. HutchinsonBerman v. Hutchinson Grimes v. Kennedy Krieger Inst.Grimes v. Kennedy Krieger Inst. Heinrich v. SweetHeinrich v. Sweet Sexton v. United StatesSexton v. United States Whitlock v. Duke Univ.Whitlock v. Duke Univ. Doe v. Ill. Masonic Med. Ctr.Doe v. Ill. Masonic Med. Ctr.

Problems with the Current Problems with the Current Approach to Subject Approach to Subject

ProtectionProtection There are inherent problems with There are inherent problems with institutionalinstitutional reviews (inconsistency, reviews (inconsistency, pressure from local officials)pressure from local officials)

Some research is not subject to any Some research is not subject to any review (not subject to federal law or review (not subject to federal law or avoided illegally)avoided illegally)

There is very little federal oversight of There is very little federal oversight of the operation of IRBsthe operation of IRBs

There is no continuing, organized There is no continuing, organized national system to address recurring national system to address recurring issues and problemsissues and problems

There is an inadequate and excessively There is an inadequate and excessively technical focus on informed consenttechnical focus on informed consent

Problems with IRBsProblems with IRBs

Inadequate IRB resources and staffing Inadequate IRB resources and staffing Inadequate training of IRB members and Inadequate training of IRB members and

staffsstaffs Inadequate review of implementation of Inadequate review of implementation of

IRB limits on approved studiesIRB limits on approved studies Inadequate continuing reviewInadequate continuing review Inadequate reporting of adverse eventsInadequate reporting of adverse events Increase in numbers and complexity of Increase in numbers and complexity of

studies is outpacing IRBs’ ability to keep studies is outpacing IRBs’ ability to keep upup

Problems Caused By Problems Caused By Changing ConditionsChanging Conditions

Internationalization of researchInternationalization of research Multicenter studies are poorly handledMulticenter studies are poorly handled Commercialization of research and Commercialization of research and

conflicts of financial interest conflicts of financial interest complicate matterscomplicate matters

Inadequate mechanisms of Inadequate mechanisms of compensating those injured in studiescompensating those injured in studies

Declining public confidenceDeclining public confidence

Problems With Error Problems With Error ReductionReduction

IRBs receive very little feedback of any kindIRBs receive very little feedback of any kind There is little systematic IRB collection of There is little systematic IRB collection of

error data on which improvements could be error data on which improvements could be basedbased

There is no national recordkeeping of There is no national recordkeeping of approved studies and the experience of approved studies and the experience of IRBsIRBs

There is limited education of researchers There is limited education of researchers and limited commitment to the highest and limited commitment to the highest ethical principles in researchethical principles in research

Accreditation as a Partial Accreditation as a Partial SolutionSolution

The goal of accreditation is said to be The goal of accreditation is said to be to protect “the rights and welfare of to protect “the rights and welfare of research participants by fostering and research participants by fostering and advancing the ethical and professional advancing the ethical and professional conduct of persons and organizations conduct of persons and organizations that engage in research with human that engage in research with human participants.”participants.”

In fact, it may be to provide sufficient In fact, it may be to provide sufficient self-regulation to avoid more difficult self-regulation to avoid more difficult outside regulation.outside regulation.

Association for the Association for the Accreditation of Human Accreditation of Human

Subject Protection Subject Protection Programs Programs Founding Members:Founding Members:

Association of American Medical CollegesAssociation of American Medical Colleges Association of American UniversitiesAssociation of American Universities Consortium of Social Science AssociationsConsortium of Social Science Associations Federation of American Societies for Federation of American Societies for

Experimental BiologyExperimental Biology National Association of State Universities National Association of State Universities

and Land-Grant Collegesand Land-Grant Colleges National Health CouncilNational Health Council Public Responsibility in Medicine and Public Responsibility in Medicine and

ResearchResearch

Accredited OrganizationsAccredited Organizations Baylor College of MedicineBaylor College of Medicine Baylor Research InstituteBaylor Research Institute Catholic Medical CenterCatholic Medical Center Cedars-Sinai Medical CenterCedars-Sinai Medical Center Chesapeake Research Review, Inc.Chesapeake Research Review, Inc. Children’s Hospital BostonChildren’s Hospital Boston Copernicus Group IRBCopernicus Group IRB Dana Farber/Harvard Cancer CenterDana Farber/Harvard Cancer Center East Tennessee State UniversityEast Tennessee State University Fox Chase Cancer CenterFox Chase Cancer Center Hunter Holmes McGuire VAMCHunter Holmes McGuire VAMC Indiana University – Purdue University, Indianapolis (IUPUI)Indiana University – Purdue University, Indianapolis (IUPUI) Iowa Health – Des MoinesIowa Health – Des Moines Johns Hopkins Medical InstitutionsJohns Hopkins Medical Institutions Massachusetts General Hospital and Brigham & Women’s Hospital as part Massachusetts General Hospital and Brigham & Women’s Hospital as part

of Partners Healthcare Systemof Partners Healthcare System Michigan State UniversityMichigan State University

Accredited Institutions Accredited Institutions (2)(2)

New England Institutional Review BoardNew England Institutional Review Board Newton-Wellesley HospitalNewton-Wellesley Hospital Saint Francis Hospital and Medical CenterSaint Francis Hospital and Medical Center The University of ArizonaThe University of Arizona The University of IowaThe University of Iowa The University of New Mexico Health Sciences CenterThe University of New Mexico Health Sciences Center The University of South DakotaThe University of South Dakota University of Arkansas for Medical SciencesUniversity of Arkansas for Medical Sciences University of California, IrvineUniversity of California, Irvine University of California, San FranciscoUniversity of California, San Francisco University of LouisvilleUniversity of Louisville University of Maryland, BaltimoreUniversity of Maryland, Baltimore University of MinnesotaUniversity of Minnesota University of PittsburghUniversity of Pittsburgh Vanderbilt UniversityVanderbilt University Washington University in St. LouisWashington University in St. Louis Western Institutional Review BoardWestern Institutional Review Board

Accreditation standardsAccreditation standards

Human Research Protection ProgramHuman Research Protection Program Domain 1: OrganizationDomain 1: Organization Domain 2: Research Review Unit (IRB)Domain 2: Research Review Unit (IRB) Domain 3: InvestigatorDomain 3: Investigator Domain 4: Sponsored ResearchDomain 4: Sponsored Research Domain 5: Participant OutreachDomain 5: Participant Outreach

Benefits of accreditation – Benefits of accreditation – For organizationsFor organizations

Improves overall quality of research Improves overall quality of research program through better and more effective program through better and more effective processes that are appropriate to volume processes that are appropriate to volume and nature of research conducted by the and nature of research conducted by the organizationorganization

Promotes culture of responsible conduct of Promotes culture of responsible conduct of researchresearch

Improves protections for research subjectsImproves protections for research subjects

Ensures compliance with regulationsEnsures compliance with regulations

Better enrollment in clinical trialsBetter enrollment in clinical trials

Is There Salvation in Is There Salvation in Accreditation?Accreditation?

Where Do We Go From Where Do We Go From Here?Here?

The Domains: The Domains: OrganizationOrganization

OrganizationOrganizationThe "Organization" is the entity that assumes The "Organization" is the entity that assumes responsibility for the Human Research Protection responsibility for the Human Research Protection Program and applies for accreditation. The entity Program and applies for accreditation. The entity may be an academic institution, clinic, hospital, may be an academic institution, clinic, hospital, managed care organization, contract research managed care organization, contract research organization, or a corporate entity, such as a organization, or a corporate entity, such as a pharmaceutical or biotechnology company, or an pharmaceutical or biotechnology company, or an independent review board. Despite great independent review board. Despite great dissimilarities in how such entities are structured, dissimilarities in how such entities are structured, the Organization domain identifies those elements the Organization domain identifies those elements that must be evident, albeit in various different that must be evident, albeit in various different forms, in an entity that seeks accreditation for its forms, in an entity that seeks accreditation for its Human Research Protection Program. Human Research Protection Program.

The Domains: Research The Domains: Research UnitUnit

Research Review UnitResearch Review UnitThe domain of “Research Review Unit” refers to the arrangements The domain of “Research Review Unit” refers to the arrangements that the Organization has made for an independent review of that the Organization has made for an independent review of ethical and scientific aspects of each research protocol involving ethical and scientific aspects of each research protocol involving human participants. Such activities are generally carried out by an human participants. Such activities are generally carried out by an institutional review board (IRB). Organizations with multiple IRBs institutional review board (IRB). Organizations with multiple IRBs might have a general oversight office or an individual with might have a general oversight office or an individual with oversight responsibility. In these complex structures the functions oversight responsibility. In these complex structures the functions and activities are split between the oversight office or individual and activities are split between the oversight office or individual with such responsibility and the IRBs. In recognition of these with such responsibility and the IRBs. In recognition of these complex structures, the term “Research Review Unit” is used to complex structures, the term “Research Review Unit” is used to describe the domain rather than IRB. The review and other describe the domain rather than IRB. The review and other activities of the IRB are concerned with protecting the rights and activities of the IRB are concerned with protecting the rights and welfare of the participants. In the review process, IRBs must welfare of the participants. In the review process, IRBs must ensure that the scientific validity of a research protocol is ensure that the scientific validity of a research protocol is considered as well as the risks and potential benefits to considered as well as the risks and potential benefits to participants and benefits that might accrue to society. In addition, participants and benefits that might accrue to society. In addition, IRBs are responsible for reviewing research on an ongoing basis, IRBs are responsible for reviewing research on an ongoing basis, monitoring reports of new information affecting risks and monitoring reports of new information affecting risks and potential benefits, and assuring that the interests of research potential benefits, and assuring that the interests of research participants are protected. participants are protected.

Domains: InvestigatorDomains: Investigator InvestigatorInvestigator

The "Investigator" domain includes the various The "Investigator" domain includes the various arrangements that the Organization has made arrangements that the Organization has made for assuring that individuals who plan to for assuring that individuals who plan to conduct research — whether as a principal conduct research — whether as a principal investigator, co-investigator, or other member investigator, co-investigator, or other member of a research team — understand and fulfill of a research team — understand and fulfill their responsibilities. Fundamentally, these their responsibilities. Fundamentally, these responsibilities stem from the fact that an responsibilities stem from the fact that an individual conducting research enters into individual conducting research enters into arrangements that may intentionally expose arrangements that may intentionally expose human participants to some degree of risk — human participants to some degree of risk — whether physical, psychological, economic, whether physical, psychological, economic, legal, or social — for scientific purposes. legal, or social — for scientific purposes.

The Domains: Sponsored The Domains: Sponsored ResearchResearch

Sponsored ResearchSponsored ResearchThe "Sponsored Research" domain includes the The "Sponsored Research" domain includes the Organization’s arrangements for structuring its Organization’s arrangements for structuring its relationships with those who fund or initiate research relationships with those who fund or initiate research external to the Organization, such as federal agencies, external to the Organization, such as federal agencies, foundations, individual donors, and corporations (e.g., foundations, individual donors, and corporations (e.g., pharmaceutical or biotechnology companies); usually pharmaceutical or biotechnology companies); usually referred to as sponsored research. The Organization referred to as sponsored research. The Organization seeking accreditation must apply its Human Research seeking accreditation must apply its Human Research Protection Program to all sponsored research and Protection Program to all sponsored research and address any special issues that might arise. These address any special issues that might arise. These issues include, but are not limited to, the ethical issues include, but are not limited to, the ethical conduct of research, dissemination of knowledge conduct of research, dissemination of knowledge gained from research, and availability of health care to gained from research, and availability of health care to injured research participants. injured research participants.

The Domains: Participant The Domains: Participant OutreachOutreach

Participant OutreachParticipant OutreachThe "Participant Outreach" domain refers to the The "Participant Outreach" domain refers to the arrangements the Organization has made for arrangements the Organization has made for understanding the social, psychological, and physical understanding the social, psychological, and physical needs and concerns of research participants and their needs and concerns of research participants and their communities. Organizations and investigators who communities. Organizations and investigators who provide education to participants relevant to their provide education to participants relevant to their participation in the research process should provide participation in the research process should provide them with tools and resources to assume an active, them with tools and resources to assume an active, responsible role in research. Participants might responsible role in research. Participants might provide important feedback to investigators about provide important feedback to investigators about their experience during the informed consent process their experience during the informed consent process and during the research itself, which can be helpful and during the research itself, which can be helpful in design of future studies. in design of future studies.

Accreditation standards:Accreditation standards:

Research Review Unit, including IRBsResearch Review Unit, including IRBs Accreditation standards:Accreditation standards:

Research Review Unit, including IRBsResearch Review Unit, including IRBsThe following are AAHRPP The following are AAHRPP accreditation standards related to the research review unit / accreditation standards related to the research review unit / IRB...IRB...STANDARD II-1:STANDARD II-1:The structure and composition of the Research Review Unit are The structure and composition of the Research Review Unit are appropriate to the amount and nature of the research reviewed. appropriate to the amount and nature of the research reviewed. ELEMENTSELEMENTSII.1.A. The Research Review Unit has and follows written II.1.A. The Research Review Unit has and follows written policies and procedures requiring protocols to be reviewed by individuals policies and procedures requiring protocols to be reviewed by individuals with appropriate scientific or scholarly expertise. II.1.B. The IRB has a with appropriate scientific or scholarly expertise. II.1.B. The IRB has a process for obtaining additional expertise when reviewing a specific process for obtaining additional expertise when reviewing a specific protocol. II.1.C. The Research Review Unit has and follows written policies protocol. II.1.C. The Research Review Unit has and follows written policies and procedures so that IRB members and consultants do not participate in and procedures so that IRB members and consultants do not participate in the review of protocols in which they have a conflict of interest, except to the review of protocols in which they have a conflict of interest, except to provide information requested by the IRB. II.1.D. The IRB has a qualified provide information requested by the IRB. II.1.D. The IRB has a qualified IRB chair, members, and staff, whose membership and composition are IRB chair, members, and staff, whose membership and composition are periodically reviewed. The IRB administrator, staff, chair, and members periodically reviewed. The IRB administrator, staff, chair, and members have knowledge, skills, and abilities appropriate to their respective roles. have knowledge, skills, and abilities appropriate to their respective roles. II.1.E. The IRB membership roster includes sufficient information about II.1.E. The IRB membership roster includes sufficient information about members to permit appropriate representation at the meeting for each members to permit appropriate representation at the meeting for each protocol under review. One or more unaffiliated members are represented protocol under review. One or more unaffiliated members are represented on the IRB and one or more members can represent the general on the IRB and one or more members can represent the general perspective of participants. II.1.F. The IRB meets regularly and members perspective of participants. II.1.F. The IRB meets regularly and members have sufficient time to review materials prior to meeting. have sufficient time to review materials prior to meeting.

STANDARD II-2:STANDARD II-2:The Research Review Unit systematically evaluates each research study to The Research Review Unit systematically evaluates each research study to ensure the protection of participants. ensure the protection of participants.

ELEMENTS ELEMENTS II.2.A. The Research Review Unit has and follows written policies and II.2.A. The Research Review Unit has and follows written policies and

procedures for conducting initial and continuing review, and procedures procedures for conducting initial and continuing review, and procedures for handling modifications to research studies. for handling modifications to research studies.

II.2.B. The Research Review Unit has and follows written policies and II.2.B. The Research Review Unit has and follows written policies and procedures to conduct reviews by the expedited procedure. procedures to conduct reviews by the expedited procedure.

II.2.C. The Research Review Unit receives and reviews the relevant II.2.C. The Research Review Unit receives and reviews the relevant information to evaluate research studies during initial review. information to evaluate research studies during initial review.

II.2.D. The Research Review Unit receives and considers relevant II.2.D. The Research Review Unit receives and considers relevant information to conduct continuing reviews of research studies and, when information to conduct continuing reviews of research studies and, when appropriate, requests changes. appropriate, requests changes.

II.2.E. The Research Review Unit receives and considers the relevant II.2.E. The Research Review Unit receives and considers the relevant information to evaluate proposed amendments to research studies.information to evaluate proposed amendments to research studies.

STANDARD II-3: STANDARD II-3: The Research Review Unit maintains documentation of its activities. The Research Review Unit maintains documentation of its activities.

ELEMENTSELEMENTS II.3.A. The Research Review Unit maintains a complete set of materials II.3.A. The Research Review Unit maintains a complete set of materials

relevant to review of the research study in each protocol file. relevant to review of the research study in each protocol file. II.3.B. The Research Review Unit retains required records for a period of II.3.B. The Research Review Unit retains required records for a period of

time sufficient to meet federal, state, and local regulations, sponsor time sufficient to meet federal, state, and local regulations, sponsor requirements, and organizational policies and procedures. requirements, and organizational policies and procedures.

II.3.C. The IRB documents pertinent discussions and decisions on II.3.C. The IRB documents pertinent discussions and decisions on research studies and activities. research studies and activities.

. . STANDARD II-4:STANDARD II-4:

The Research Review Unit systematically evaluates risks to participants and The Research Review Unit systematically evaluates risks to participants and potential benefits as part of the initial review and ongoing review of research. potential benefits as part of the initial review and ongoing review of research.

ELEMENTSELEMENTS II.4.A. The Research Review Unit has and follows written policies and procedures II.4.A. The Research Review Unit has and follows written policies and procedures

for identifying and analyzing potential sources of risk and measures to minimize for identifying and analyzing potential sources of risk and measures to minimize risk, including physical, psychological, social, legal, or economic risks. The risk, including physical, psychological, social, legal, or economic risks. The analysis of risk includes a determination that the risks to participants are analysis of risk includes a determination that the risks to participants are reasonable in relation to potential benefits to participants and to society. reasonable in relation to potential benefits to participants and to society.

II.4.B. The Research Review Unit reviews the plan for data and safety monitoring II.4.B. The Research Review Unit reviews the plan for data and safety monitoring in research protocols, when applicable, and determines that the plan provides in research protocols, when applicable, and determines that the plan provides adequate protection for participants. adequate protection for participants.

II.4.C. The Research Review Unit has and follows written policies and procedures II.4.C. The Research Review Unit has and follows written policies and procedures for determining the risks to vulnerable populations as defined in applicable for determining the risks to vulnerable populations as defined in applicable federal regulations, and specifically for determining the required risk categories federal regulations, and specifically for determining the required risk categories in protocols involving children and prisoners. in protocols involving children and prisoners.

II.4.D. The Research Review Unit has and follows written policies and II.4.D. The Research Review Unit has and follows written policies and procedures for suspending or terminating previously approved research if procedures for suspending or terminating previously approved research if warranted by findings in the continuing review or monitoring process. warranted by findings in the continuing review or monitoring process.

STANDARD II-5:STANDARD II-5:The Research Review Unit systematically evaluates recruitment and participant The Research Review Unit systematically evaluates recruitment and participant selection practices. selection practices.

ELEMENTS ELEMENTS II.5.A. The Research Review Unit has and follows written policies and procedures II.5.A. The Research Review Unit has and follows written policies and procedures

to evaluate the equitable selection of participants from various populations and to evaluate the equitable selection of participants from various populations and sub-populations, when applicable, and considers whether inclusion and exclusion sub-populations, when applicable, and considers whether inclusion and exclusion criteria impose fair and equitable burdens and benefits. criteria impose fair and equitable burdens and benefits.

II.5.B. The Research Review Unit reviews proposed participant recruitment II.5.B. The Research Review Unit reviews proposed participant recruitment methods, advertising materials, and participation payment arrangements, and methods, advertising materials, and participation payment arrangements, and permits them when fair, honest, and appropriate. permits them when fair, honest, and appropriate.

STANDARD II-6:STANDARD II-6:The Research Review Unit systematically evaluates the protection of privacy interests of The Research Review Unit systematically evaluates the protection of privacy interests of research participants and the confidentiality of data in proposed research. research participants and the confidentiality of data in proposed research.

ELEMENTS ELEMENTS II.6.A. The Research Review Unit has written policies and procedures to evaluate the proposed II.6.A. The Research Review Unit has written policies and procedures to evaluate the proposed

arrangements for protecting the privacy interests of research participants during and after arrangements for protecting the privacy interests of research participants during and after their involvement in the research. their involvement in the research.

II.6.B. The Research Review Unit has written policies and procedures to evaluate proposed II.6.B. The Research Review Unit has written policies and procedures to evaluate proposed arrangements for protecting the confidentiality of identifiable data, when appropriate, during arrangements for protecting the confidentiality of identifiable data, when appropriate, during and after the conclusion of the investigation. and after the conclusion of the investigation.

STANDARD II-7:STANDARD II-7:The Research Review Unit has and follows written policies and procedures that require The Research Review Unit has and follows written policies and procedures that require informed consent to be solicited from participants or their legally authorized representatives, informed consent to be solicited from participants or their legally authorized representatives, and it verifies that this requirement is met. and it verifies that this requirement is met.

ELEMENTS ELEMENTS II.7.A. The Research Review Unit evaluates compliance with policies and procedures on II.7.A. The Research Review Unit evaluates compliance with policies and procedures on

seeking informed consent from participants or their legally authorized representatives, and seeking informed consent from participants or their legally authorized representatives, and assent, when possible, from participants who cannot give consent. assent, when possible, from participants who cannot give consent.

II.7.B. The Research Review Unit has and follows written policies and procedures requiring II.7.B. The Research Review Unit has and follows written policies and procedures requiring that prospective participants whose decision-making capacity is in question be appropriately that prospective participants whose decision-making capacity is in question be appropriately protected. protected.

II.7.C. The Research Review Unit reviews the content of the consent process, including the II.7.C. The Research Review Unit reviews the content of the consent process, including the consent document, and the process through which informed consent is obtained from each consent document, and the process through which informed consent is obtained from each participant, focusing on measures to improve participant understanding and voluntary participant, focusing on measures to improve participant understanding and voluntary decision-making. decision-making.

II.7.D. The Research Review Unit has and follows written policies and procedures requiring II.7.D. The Research Review Unit has and follows written policies and procedures requiring that the investigator has and follows a procedure for properly documenting informed consent. that the investigator has and follows a procedure for properly documenting informed consent.

II.7.E. The Research Review Unit has and follows written policies and procedures for II.7.E. The Research Review Unit has and follows written policies and procedures for approving waiver or alteration of the consent process and the waiver of consent approving waiver or alteration of the consent process and the waiver of consent documentation. documentation.

II.7.F. The Research Review Unit has and follows written policies and procedures for making II.7.F. The Research Review Unit has and follows written policies and procedures for making exceptions to informed consent requirements in protocols for emergency situations, and exceptions to informed consent requirements in protocols for emergency situations, and appropriately reviews such protocols. appropriately reviews such protocols.

II.7.G. The Research Review Unit has procedures for observation of the informed consent II.7.G. The Research Review Unit has procedures for observation of the informed consent process in ongoing research, when appropriate. process in ongoing research, when appropriate.

STANDARD II-8:STANDARD II-8:The Research Review Unit has procedures for review The Research Review Unit has procedures for review and oversight of research conducted at multiple sites. and oversight of research conducted at multiple sites.

ELEMENTSELEMENTS II.8.A. The Research Review Unit has and follows II.8.A. The Research Review Unit has and follows

policies and procedures for communication among policies and procedures for communication among IRBs, when appropriate, for research conducted at IRBs, when appropriate, for research conducted at multiple sites (e.g., multi-site clinical trials, multiple sites (e.g., multi-site clinical trials, epidemiology studies, or educational surveys). epidemiology studies, or educational surveys).

II.8.B. The Research Review Unit has and follows II.8.B. The Research Review Unit has and follows policies and procedures for management of policies and procedures for management of information obtained in multi-site research that may information obtained in multi-site research that may be relevant to the protection of research participants, be relevant to the protection of research participants, such as reporting of unexpected problems or interim such as reporting of unexpected problems or interim results. results.