Ethics controversial slides_07

Ethical Issues Ethical Issues in Human Subjects in Human Subjects

ResearchResearch

Judy Stone, MDJudy Stone, MD

The first step in the evolution of ethics is a sense of solidarity with other human eings.

— Albert Sweiter

1932–72 Tuskegee experiment on syphilis1939–45 Nazi experiments1944–74 Human radiation experiments by U.S. government1946 Nuremberg Trial of doctors responsible for the Nazi experiments1947 Nuremberg Code outlining ethical principles required for research1948 United Nations adoption of Universal Declaration of Human Rights

Milestones in Ethical Milestones in Ethical DevelopmentDevelopment


1953 NIH policy, the first U.S. federal policy introducing independent reviewers to

examine research, forerunners of the IRBs 1963–66 Willowbrook Study, involving hepatitis

research on mentally retarded children, raising issues access to care, consent, and coercion 1964 Declaration of Helsinki international

agreement on recommendations for the ethical conduct of medical research 1972 Public exposure of Tuskegee syphilis study 1974 First federal protections for human research

participants


1979 Belmont Report promoting three principles for research

1980 Food and Drug Administration regulations (CFR 21 (50)

1982 Council for the International Organization of Medical Sciences (CIOMS) publication of the International Ethics Guidelines for Biomedical Research Involving Human Subjects

1985 U.S. Public Health Service Task Force on Women’s Health issues report encouraging inclusion of women in research

1990 Society for Women’s Health Research


1993 Public exposure of U.S. human radiation experiments

1993 NIH Revitalization Act mandating inclusion of women and minorities in research

1993 NIH Office of Research on Women’s Health


1997 Food and Drug Modernization Act (FDAMA) requiring the FDA, NIH, and pharmaceutical industry to develop guidance on the inclusion of women and minorities in trials

1998 Pediatric Rule passed by Congress, stipulating that new drugs for children must include specific pediatric labeling information

2000 Further publicized ethical abuses prompting establishment of the Office of Human Research Protections (OHRP)

Belmont ReportBelmont Report

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

3 basic principles for research


Respect for persons, or an individual’s autonomy-

elements of the informed consent requiring that: Information necessary to make a decision must

be presented that is,the risks and benefits, if any, of participation.

The information must be presented at a level that can be understood by the patient or study subject.

Participation must be voluntary.


Benificience, or benefit to the Benificience, or benefit to the participantparticipant

Who decides whether there is Who decides whether there is benefit?benefit?

Belmont-BeneficenceBelmont-Beneficence

Loss of substantial benefits that might be gained from research

PaternalismPregnancyLife-threatening illness

(AIDS/Cancer)

Belmont-JusticeBelmont-Justice

Risks and benefits should be Risks and benefits should be equitably distributed among different populations “Do onto others…” rather than taking

advantage of

Vulnerable populations

Vulnerable Populations

Military Military 1944-1979: radiation, chemical,1944-1979: radiation, chemical,

Mustard gas, lewisiteMustard gas, lewisite Venezuelan equine encephalitis virus and the nervegas agent VX Operation Whitecoat (tularemia, anthrax, Q fever)

1994 Congressional review: the Department of Defense

“has demonstrated a pattern of misrepresenting the danger of various military exposures that continues today”

Vulnerable Populations

Unsuspecting civiliansUnsuspecting civilians Radiation experiments: atomic weapons Radiation experiments: atomic weapons

testing intesting in South PacificSouth Pacific Oak RidgeOak Ridge Los AlamosLos Alamos Hanford, WashingtonHanford, Washington Plutoniaum injections (ACHRE report)Plutoniaum injections (ACHRE report)

Vulnerable PopulationsVulnerable Populations

What studies are being done now under the guise of counter terrorism, hidden from the public by the “Patriot Act?”

Vulnerable Populations-Children

Pint-size people vs. real dataPint-size people vs. real data 10 drugs most commonly prescribed for

children that lacked pediatric labeling—drugs were prescribed more than 5 million times

HIV studies in foster children Too vulnerable? vs denying access to Too vulnerable? vs denying access to

potentially life-saving drugspotentially life-saving drugs (all HIV + kids were being offered the trials)(all HIV + kids were being offered the trials)

Vulnerable Populations-Women

PregnancyPregnancy PaternalismPaternalism Woman vs FetusWoman vs Fetus

Daily Ethical Encounters

Participants who are vulnerable Participants who are vulnerable from:from:

Abuse from Doctor-patient Abuse from Doctor-patient relationshiprelationship

““whatever you say, doc” syndromewhatever you say, doc” syndrome

Indigent patientsIndigent patients

Daily Ethical Encounters

Financial Pressures and Conflict of Financial Pressures and Conflict of InterestInterest FinancialFinancial

Income for DepartmentIncome for Department BonusesBonuses Structure of grant (pay per visit or end-loaded)Structure of grant (pay per visit or end-loaded) Pay for screeningPay for screening Pay for quality of data, rather than # of patientsPay for quality of data, rather than # of patients Avoid disincentives for dropping a patient (e.g., Avoid disincentives for dropping a patient (e.g.,

due to adverse reactiondue to adverse reaction Pressure re prestiege, publication, tenurePressure re prestiege, publication, tenure

Other Conflicts of InterestOther Conflicts of Interestat the Siteat the Site

Use of a class of drug in a study-e.g., Use of a class of drug in a study-e.g., Quinolones, that you might not use Quinolones, that you might not use otherwise otherwise

Access to care for indigent patientsAccess to care for indigent patients Access to novel drug (pt may lie)Access to novel drug (pt may lie) Adverse event classificationAdverse event classification

Yet more COIYet more COI

IRB relatedIRB related Voluntary, unpaidVoluntary, unpaid Lack of trainingLack of training Paid by drug companyPaid by drug company Pressure from administrationPressure from administration Personal competition/conflictPersonal competition/conflict

Mrs. G?Mrs. G?

Evaluating a StudyEvaluating a Study

Does the study ask an Does the study ask an important/valuable question?important/valuable question?

Is the study design reasonable?Is the study design reasonable?

Would I be willing to be in this trial?Would I be willing to be in this trial?

Evaluating a Potential Evaluating a Potential VolunteerVolunteer

Level of understanding based onLevel of understanding based on Education, life experienceEducation, life experience

MotivationMotivation Financial needFinancial need

vs. ethics of lack of universal health carevs. ethics of lack of universal health care What will happen to the pt when the study ends?What will happen to the pt when the study ends?

Stage of illnessStage of illness Risk vs. BenefitRisk vs. Benefit What do they have to lose?What do they have to lose?

Would I take this drug or give it to my family Would I take this drug or give it to my family member?member?

Politics of Research: Politics of Research: WomenWomen

Viewed as vulnerable populationViewed as vulnerable population PaternalismPaternalism Woman vs. fetusWoman vs. fetus

e.g. AIDs clinical trialse.g. AIDs clinical trials ReligionReligion

Exclusion of women from participation Exclusion of women from participation due to restrictions about contraceptive due to restrictions about contraceptive useuse

Politics of Research: Politics of Research: RaceRace

one-fourth of the U.S. population is made up of “people of color” Only 5% of trial participants

Legacy of distrust Tuskeegee HIV-foster children study (despite

evidence) Nigerian Pfizer meningitis trial =>

resistance to polio vacciination

Politics of Research: Race and Gender Overlap

1980 and 1983, fully one-fifth of contraceptive research was conducted in developing countries

Oral contraceptive research in Puerto Rico Adverse events analysis was inadequate

Quinacrine The effect of power inequities between men

and women Lack of social support for many women Coercion by medical providers or government

agencies

Quinacrine-Belmont Quinacrine-Belmont PrinciplesPrinciples

BeneficenceBeneficence No safety or toxicity studies of intrauterine No safety or toxicity studies of intrauterine

installationinstallation Distributive JusticeDistributive Justice

Almost all the women were Almost all the women were low income, poorly educated women of color in developing countries.

Respect for Persons, autonomy, self-determination No explanation of experimental nature of

quinacrine and no informed consent or offer of alternatives

Shifting ResearchShifting Research to Developing Countries to Developing Countries

United States accounts for ~ 4 percent of the world’s population vs. 84% for dev. Countries

90 percent of $ is spent on the illnesses of the wealthiest countries,

leaving 10 % of monies to care for 84 % of the global population

Vulnerable international populations

• Limited economic development• Inadequate protection of human rights• Inadequate community and cultural

experience with, or understanding of, scientific research

• Limited availability of healthcare and treatment options

• Limited ability of individuals in the community to provide informed consent due to illiteracy and language, educational, or cultural barriers


What standards should apply? Meningitis trialMeningitis trial

Maternal-fetal HIV transmission trialsMaternal-fetal HIV transmission trials

Absolute standard of care vs. local standard?Absolute standard of care vs. local standard? What if the local standard is to do nothing?What if the local standard is to do nothing? International consensus is that it is ethical if:International consensus is that it is ethical if:

it is based on a valid scientific purpose for using a lesser standard, provides social benefits for the local host community, and shows a favorable risk-benefit ratio for the individual research participants


Distributive justice is violated the local study populations will not

significantly benefit from the research if the new therapies will not be affordable to them, although they are taking a higher proportion of the risk.

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Ethics controversial slides_07