History of Research Protections for Individuals and Communities

1
History of Research Protections for Individuals
and Communities

• Northern Plains Tribal Epidemiology Center
• Aberdeen Area Tribal Chairmens Health Board
• May 2, 2004

2
William L. Freeman, MD, MPH, CIP

• Director of Tribal Community Health Programs,
• Human Protections Administrator
• Northwest Indian College
• 360-392-4284 fax [phone] wfreeman_at_nwic.edu
  
  
• with material by
• Warren Ashe (Howard University)
• Jeffrey Cohen (formerly, Office for Human
  Research Protection--OHRP)
• Dale Hammerschmidt (University of Minnesota)

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Hyshqe siam -Thank you, respected teachers

• Community members, community IRB members
• Sam Deloria, Lisa Preston, and others
• IRB members
• Dr. Francine Romero, and others
• IRB staff
• Helen McGough, Moira Keane, Susan Kornetsky, and
  others
• Researchers
• Participants
• Carolyn Robbins - Wife

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Objectives

• To know the basic chronology of the development
  of the ethics and regulations of protection for
  individuals in research
• To understand the basic intent, nature, and
  limitations of those regulations
• To discuss 3 controversies concerning the
  regulations
• To understand protection of communities in
  research, and how it can be accomplished

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Early problematic research

• Infected prostitutes and children with syphilis
  to test immunity by serum from syphilitic
  patients, without consent (Germany, 1892)
• BCG (TB vaccine) disaster--77 of 256 children
  died (Germany, late 1920s)
• Poor children, especially orphans (1800s-early
  1900s, USA others)
• Hebrew Infant Asylum, no orange juice to orphans
  to study development of scurvy (NYC)
• Medical profession changed, to prevent
  anti-research groundswell
• Susan Lederer Subjected to Science Human
  Experimentation in America Before the Second
  World War 1997.

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Research atrocities by Nazis, WWII

• In concentration camps (Dachau) and killing camps
  (Auschwitz)
• Immerse prisoners in cold water
• until they died the intent of the research
• Decompress prisoners in high-altitude chambers
• until they died the intent of the research
• Inject many prisoners with typhus
• many died
• Nuremberg Medical Trial, 1946-47
• tried 23 defendants (20 physicians)
• convicted 15

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The Nuremberg Code, Aug. 19, 1947

• 10 rules for Permissible Medical Experiments
• voluntary consent, without coercion,
• good science, done by good scientists,
• potential benefits justify experiment,
• harms minimized,
• degree of risk less than potential benefit,
• subjects can end their participation, and 4
  more
• A start, but with limited applicability
• medical research only, only on normal subjects
• asked "When is research criminal?"
• http//www.hhs.gov/ohrp/references/nurcode.htm

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After WWII

• Radiation experiments (1950s)
• consent absent, or inadequate deceptive
• Willowbrook (1950s)
• deliberately infected mentally retarded children
  with hepatitis virus
• coercion of parents
• Jewish Chronic Disease Hospital (1960s)
• injected live cancer cells into 22 elderly
  patients, some with dementia, some spoke only
  Yiddish
• consent deceptive, inadequate, not translated
• guardians not asked for permission
• Lerner BH. Sins of omission cancer research
  without informed consent. NEJM 2004
  351(7)628-630.

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Henry Beecher

• 1966 article summarized 22 recent unethical
  medical experiments (out of 50 examples
  accumulated)
• in major medical centers, by prominent
  researchers, funded by respected sources,
  published in prestigious journals (including
  NEJM)
• perform heart catheterizations on patients
  getting a bronchoscopy look at breathing
  passages through a tube
• placebo control groups in life-threatening
  diseases with known effective treatments --
  several
• randomize soldiers with strep throat to
  penicillin vs. treatments known-to-be-ineffective
  ineffective treatment may lead to rheumatic
  heart disease
• I.E., ethical problems were mainstream, not
  fringe
• "Ethics and clinical research" NEJM 1966 vol 274,
  p. 1354-60

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US Public Health Service Syphilis Study

• Natural history of untreated syphilis in
• 405 African American men
• impoverished sharecroppers around Tuskegee, AL
  1932-72
• Researchers lied to the men
• said they treated them for "bad blood"
• Highly "successful"
• dropout rate only 1 over 40 years
• Why was it so successful?
• The reason it was "culturally sensitive"
• paid for funeral, African American nurse some
  doctors
• Not secret!
• Updated results published about every 5 years

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

• By the 1974 National Research Act
• First, it proposed regulations
• required Institutional Review Boards (IRBs)
• for research done or conducted by HEW (now DHHS)
• 45 CFR 46 (Title 45 Code of Federal Regulations
  Chapter 46)
• http//www.hhs.gov/ohrp/humansubjects/guidance/45c
  fr46.htm

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Then issued The Belmont Report

• Basic ethical principles underlying its proposed
  regulations ( - and their application)
• Respect for persons
• Informed Consent
• Beneficence
• Assessment of potential risks harms and
  benefits
• Justice
• Selection of people to be in the research
• http//www.hhs.gov/ohrp/humansubjects/guidance/bel
  mont.htm

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Principle Beneficence

• "Do no harm" - "Do benefit"
• Assessment of risks harms and benefits
• Minimize harms to participants
• Use least harmful methods to achieve the
  scientific end
• Favorable Benefit-to-Risk comparison
• maximize Benefit-to-Risk ratio
• maximize benefits to participants and society

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Principle Justice

• "Treat individuals fairly"
• Selection of subjects / participants
• Equitable distribution of research harms and
  benefits
• Equitable selection of subjects / participants
  within a population
• Equitable selection of population

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Principle Respect for Persons

• "Individual autonomy"
• Informed consent
• full information
• full comprehension
• voluntary
• without coercion
• Protect individuals with reduced capacity to
  exercise autonomy

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CONTROVERSY 1 "The regulations are designed
only forexperimental medical research."

• A common complaint of some behavioral or
  non-experimental researchers.
• Many ethically problematic studies were medical
  research.
• Lets examine the sentence
• experimental research
• medical research.

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"The regulations are for 'experimental research'
only."

• Tuskegee was not an experiment.
• It was observational research.

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Definition of research

• "a systematic investigation, including research
  development, testing and evaluation, designed to
  develop or contribute to generalizable
  knowledge.... (S)ome demonstration and service
  programs may include research activities."
• 45 CFR 46.102 (d)
• The definition is not limited to "experimental."
• Nevertheless, were the ethically problematic
  studies primarily medical research?

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Behavioral research with problematic ethics - 1

• Milgram (1963)
• Behavioral study of obedience
• a few participants still quite distressed when
  queried well after the experiment
• not medical
• Humphries (1970)
• Tearoom Trade Impersonal Sex in Public Places
• concerns of confidentiality and privacy
• neither medical nor experimental

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Behavioral research with problematic ethics - 2

• The Monster Study
• so named by people who stutter researchers of
  stuttering
• by Mary Tudor Wendell Johnson (1939,
  unpublished)
• Randomized trial 12 normal-speaking orphans in
  IA orphanage
• Researcher purposefully criticized the speech of
  6 orphans--to induce stuttering
• Some may have developed stuttering, a few for
  life.
• Another example of orphan kids used in research
• Franklin Silverman "The monster study" Journal
  of Fluency Disorders 1988 vol. 13, p. 225-231

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Behavioral research with problematic ethics - 3

• Social science in the service of eugenics
• In the state of Vermont VT, the first third of
  20th century
• Surveys of "dumb" or "delinquent" children and
  their families
• Dumb or delinquent families were usually poor
• Catholic French Canadians, Abenaki Indians, or
  migrants
• Led to VT sterilizing some of the identified
  dumb or delinquent children -- "to protect
  the gene pool"
• Poor science did not measure "dumbness" or
  "delinquency"
• Nancy L. Gallagher Breeding Better Vermonters
  The Eugenics Project in the Green Mountain State
  1999.
• Please do not turn the page of the handout until
  asked to do so

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Non-experimental behavioral research - 4

• What do you think has been the general kind of
  research that has caused the most harm to the
  most people in 20th century America?
• USPHS syphilis study in Tuskegee?
• radiation experiments?
• eugenics?
• other?

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My vote

• IQ research comparing blacks and others
• observational behavioral research (not medical)
• contributed to and reinforced racial
  stigmatization of African Americans and others,
  including American Indian, Alaska Native,
  Canadian First Nation, and Inuit students and
  people
• harmed primarily those communities, and all
  people in those communities
• What will historians 40 years from now say about
  our research today?
• Please turn page of handout

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CONCLUSION 1

• All types of research, both experimental and
  non-experimental, both medical and behavioral,
  has caused (and can cause) major harms
• Harms to communities when community members
  not in the original research are directly harmed
  by the results of the research
• The IRB should have the expertise to assess all
  potential harms, including harms to communities,
  in the research it reviews
• behavioral research may require special expertise
• e.g., qualitative, ethnographic

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CONTROVERSY 2 The place of regulations in human
research protection

• 1900 - Germany, Prussian Minister of Religious,
  Educational, and Medical Affairs
• Directive - included consent "unequivocally"
• 1930 - Germany, Reich Minister of the Interior
• "Regulations on New Therapy and Human
  Experimentation"
• had almost all points in Nuremberg Code
• Nazis did ethically atrocious research despite
  regulations
• Michael Grodin "Historical origins of the
  Nuremberg Code," in George Annas Michael Grodin
  (eds) The Nazi Doctors and the Nuremberg Code
  1992 p. 121-144 Paul Weindling "The origins of
  informed consent the International Scientific
  Commission on Medical War Crimes, and the
  Nuremberg Code" Bulletin of the History of
  Medicine 2001 vol. 75, p. 37-71.

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USA Medical University IRB - 1

• 1994 - MU IRB reviewed the Prenatal Clinic policy
• to test pregnant women with a urine drug screen
• without fully informing the women that a
  positive test would be reported to the court, and
• that the court likely would jail test-positive
  women and could take their newborn and other
  children
• Most were poor black women.
• Preliminary outcome results were reported in
  state medical journal final results were
  promised soon
• planned to send final results to a major
  obstetrical journal
• "Was this research?"

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Medical University IRB - 2

• A few members voted that, by 1994, it had become
  prospective research, and would have disapproved
  the protocol, because
• the consent process was incomplete and deceptive,
  and
• the potential harm to the women by the procedures
  outweighed the potential benefit of the research
  to each woman and society.
• The majority voted that it was not research.

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Medical University IRB - 3

• Many IRB members felt that, even if it was
  research, and for all other research on those
  subjects
• Drug-abusing pregnant women were harming their
  fetus,
• And the women were doing illegal behavior ...
• thus the women did not deserve to be protected
• What is wrong with this picture?
• From the investigation by OPRR in 1994, and
  discussion with an IRB member, and Edgar O Horger
  et al "Cocaine in pregnancy confronting the
  problem" Journal of the South Carolina Medical
  Association Oct 1990 vol. 86, p. 527-531.
• Also the US Supreme Court, March 22, 2001,
  reviewed a legal case from this project (not
  about the research), and ruled against the city
  and MU (Ferguson v. City of Charleston et al).

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CONCLUSION 2

• Good regulations are necessary, but are not
  sufficient, for human research protection.
• Also necessary are that researchers and IRB
  members
• understand and agree with the purpose of the
  regulations,
• and apply the regulations to everyone,
• especially to people whom society or the IRB
  members consider to be morally or socially
  "inferior"
• or even despise.

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CONTROVERSY 3 What were the good, the bad,
the ugly in AI/AN research and how to avoid the
bad ugly?

• Research with AI/AN people/communities/tribes is
  not listed in the catalog of problematic research
• A common feeling among many tribal people
  research has harmed AI/AN people
• What is behind that feeling?

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Older current good history / research

• Tuberculosis was a killer, major cause of AI/AN
  death
• last half 19th, first half of 20th, centuries
• Clinical trial of INH isoniazid in the Navajo
  Rez in early 1950s proved INH was an effective
  treatment, saved many AI/AN lives
• Diabetes is a killer
• - Diabetes Prevention Program DPP proved
  that intense counseling for lifestyle change
  could prevent type 2 diabetes reduce calories,
  especially fats moderate exercise 30 minutes a
  day 5 times a week reduce weight by 7
• Community-Based Participatory Research
• - Kahnawake Schools Diabetes Prevention
  Project
• - People Awakening Project with Alaska
  Native groups, about resiliency and strengths in
  dealing with alcoholism

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Older bad history - 1

• Research with radioactive iodine (I131)
• early 1950s, USAF
• "Do ANs survive the cold by having higher
  metabolism?"
• Gave I131 to Alaska Native people
• same amount as then used for thyroid scan
• almost all ANs did not speak English
• 3 AN women in research were breast feeding
  children!
• Long term effects of thyroid scan not then known
• (ANs not higher metabolism know how to dress
  and eat)
• Involved radiation a feared modern hazard

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Older bad history - 2

• Navajo uranium miners, 1950s
• Dust in U mines known to cause lung cancer
• AEC refused to regulate mining
• PHS study, natural history
• health exam Q2Yrs, tracked deaths
• "pile up bodies at the door"
• did not inform participants of known health
  effects or reason for study
• Bodies piled up by 1960s -gt regulation started

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Implications of older bad history

• I131 and uranium studies have complex issues
• children who were breast feeding may not have
  been followed up
• so what would you do to get the US to establish
  health regulations for mining, against the power
  of the AEC?
• The problem was basic protocol design

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Recent bad history - 1

• Barrow, Alaska study on alcoholism
• 1970s, researchers from northeastern US
• announced findings in press conference
• held at their northeastern university
• Internal stigmatization by people from Barrow
  nearby communities
• Bonds on Wall Street adversely affected
• Impact of research results?
• no positive change in/by Barrow

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Recent bad history - 2

• Haida Gwai anthropologic research, 1970s?
• PhD student -gt worked as a schoolteacher
• Documented effects of alcohol
• incest, murder, etc.
• instances not widely or legally known in the
  community
• Book published 1990s, names hidden
• to outsiders -- but not to community members!
• Author almost physically assaulted in next visit

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Recent bad history - 3

• Congenital syphilis epidemic, 1980s
• Rez not named in publication
• gave precise 1980 US Census pop.
• Rez children taunted "Your mama's ..."
• Gas stations refused to let Rez people use
  restrooms

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Recent good bad history - 4

• Hantavirus, summer 1993
• 50 of infected people died
• first recognized on the Navajo Rez
• CDC found cause lt10 days--a virus from deer mice
• Good helped NNDOH develop prevention programs
• NNDOH asked CDC not to give Navajo place names in
  scientific articles
• Bad 1st 2 articles, CDC named the Navajo
  Chapters
• where the people lived who were infected first
• where the deer mice and other animals were
  trapped
• Navajo approved no research for gt13 months

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Implications of recent bad history

• Major community harm was disruption
• Major individual harm was internal
  self-stigmatization
• All subsequent research in many of those
  communities was adversely affected
• The problem was publication-dissemination

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Current bad research 1

• Nuu-chah-nulth First Nations western Vancouver
  Island, BC, Canada, severe unusual arthritis
• early 1980s, UBC rheumatology genetic
  researchers studied their problem, took blood
  specimens
• geneticist kept specimens with him UBC -gt U
  Utah -gt Oxford U, report migration genetic
  research results
• Community found out 3 years ago
• major adverse publicity across Canada
• Community wanted the specimens back to finish the
  arthritis research
• geneticist died early 2004, had stated to return
  specimens

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Current bad research 2

• Havasupai
• early 1990, tribe approved a diabetes study
  including genetic analysis, by ASU researchers
• no NLM-listed journal articles on genetic
  analysis of T2DM among Havasupai, one article on
  nutrition
• HLA, inbreeding, migration genetic research
  also done using the specimens
• sources
• Rubin P. Indian givers. Phoenix New Times 2004
  May 27
• Dalton R. When two tribes go to war. Nature
  2004 430500-2
• Editorial. Tribal culture versus genetics.
  Nature 2004 430489
• Pubmed Havasupai OR Markow TAuthor OR Martin
  JFAuthor OR Benyshek DAuthor OR Zuerlein
  KAuthor
• Paul Rubin personal communication

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Implications of current bad history

• The old NIH policy and researcher practice, of
  sharing genetic specimens usually anonymized for
  identity of the individual is no longer
  appropriate
• Tribal approval of research extends to future
  uses
• of genetic biological specimens
• of data
• Tribes vary about their degree of favorable or
  unfavorable attitude toward research in general
• extent to which they see research as an enemy of,
  or a friend of, the tribes future physical and
  cultural survival
• The values and relationships of the tribes and
  researchers are changing

43
Current ugly research

• Havasupai there is more
• concurrently with T2DM study was schizophrenia
  study
• apparently researchers told neither tribe nor
  individuals
• apparently research team obtained information
  from clinic charts surreptitiously, after hours,
  with no approval
• apparently the ASU IRB did not comply with own
  procedures requirements
• Was this amateur night?
• Now prime example of ugly research in Indian
  Country
• major adverse publicity in Arizona, major law
  suit by Havasupai
• Better tribal or IRB review could have prevented
  this!

44
Current good research and practices

• Kennewick Man is an example of bad practice
• skeleton found 08/96, 1st scientist said was
  caucasoid
• Kwaday Dan Tsinchi - Long Ago Man Found
• Champagne-Aishihik First Nations FN, d.
  1415-1445
• glacier in Tatshenshini-Alsek Park, British
  Columbia BC
• body found 08/99, plan developed, studied to
  12/2000
• returned to the Champagne-Aishihik
• cremated, potlatch, ashes scattered where found
  07/2001
• head found 08/2003, studied, laid to rest 10/2004
• final ceremonies being planned
• FN community BC government set up a joint group
  to oversee the research within cultural limits
• People Awakening Project

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Values present in the regulations

• Respect for persons
• Minimize harms to persons
• Maximize benefits to persons
• Justice for persons
• But the regulations 45 CFR 46 do not cover
• Publication of private communal knowledge
• CDC's Hantavirus articles
• Desecration of bones in archaeologic remains
• because archaeology is not human research of
  identifiable living human beings

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Native values not explicit in the regulations

• Protection of communities
• except obliquely
• Respect for elders knowledge of community
• ethnographic interviews published or archived by
  outsiders
• Respect Native communities, strengths, and
  survival
• much research focuses on how bad things are
• not on how/why people survived and do well
• Promote resiliency, help activate the community
• Respect and promote tribal sovereignty

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Protect communities, respect elders, and
respect communities

• Typical research on alcoholism or domestic
  violence document how bad things are
• attacks the value of community
• Rather, research how/why people stopped domestic
  violence, or became and stayed sober and thus
  promote resiliency, help activate the community
• People Awakening Project

48
Rely on others to protect communities?

• Yes
• 1967 - Indian Health Service policy required
  approval by the tribal government of all research
• 1976 - "Permission to conduct this investigation
  was granted by the Indian Health Service, the
  Bureau of Indian Affairs and appropriate Navajo
  tribal authorities, including local school
  boards."
• New England Journal of Medicine Vitamin C and
  acute illness in Navajo school children 1976,
  vol 295, p. 973-977.
• No
• Before the publication, the Navajo Area IHS IRB
  asked CDC to change the Hantavirus articles -gt no
  change
• The IHS Research Program Director Chair of its
  IRB demanded deletion of the place names -gt no
  deletion

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My summary of the evidence - 1

• Some research has been good for AI/AN individuals
  and tribes
• Some research has been bad for AI/AN individuals
  and tribes
• Some research has been both good and bad
• Some research has been ugly
• The regulations do not include some important
  AI/AN concerns
• Tribes and TCUs need to protect themselves
• in addition to relying on others the
  regulations

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My summary of the evidence - 2

• Researchers are more ethical
• IRBs do protect individuals
• The regulations are valuable
• and should be understood and used
• IRBs the regulations are a floor, not a ceiling
• IRBs are necessary and quite valuable,
• but they are not sufficient for tribes, tribal
  people, and TCUs.

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Steps to protect tribal individuals,tribal
communities, TCUs

• Establish an IRB
• tribal, TCU, or combined TCU-tribal
• Learn the regulations and how to use them
• Tribal governments and TCUs maintain an active
  process to review research
• Solicit allies from other IRBs and researchers
  with goodwill
• Protect communities by building beyond the floor
  of the regulations