Regulation of Research with Human Subjects

1
Regulation of Research with Human Subjects

• Class 10

2
Grimes v. Kennedy Krieger Institute, 362 Md. 29
(2001)

• Parents consented to allow children to
  participate in non-therapeutic research trial
  regarding a partial lead paint removal
  demonstration project
• KKI is affiliated with Johns Hopkins University,
  JHU IRB reviewed protocol, manipulated language
  to avoid federal compliance
• Landlord received subsidies for improvements, KKI
  encouraged them to rent premises to families with
  children (and in at least one case, required it)
• Measures
• Air was tested for presence of lead dust
• Children were tested periodically for evidence of
  lead in blood

3

• Risks were anticipated based on prior research
• Non-therapeutic program, so how were risks and
  benefits calculated?
• Nothing about the research was designed for
  treatment of the subject children. They were
  presumed to be healthy at the commencement of the
  project. As to them, the research was clearly
  non-therapeutic in nature. The experiment was
  simply a for the greater good' project.
• Families who rented these houses were poor, often
  minorities, and were beneficiaries of reduced
  rents
• Were rents subsidized by experimenters payments
  to landlords?
• Court finds that informed consent has the power
  of a contract special relationship of
  researcher and research subject
• KKI and JHU reaction
• Public Statement
• http//www.hopkinsmedicine.org/press/2001/SEPTEMB
  ER/010917.htm

4
Historical and Current Contexts

• Tuskegee
• Nazi medical experiments
• Milgrams Obedience Experiment
• Administration of LSD to soldiers
• Exposure of U.S. soldiers and Navajo miners to
  radiation
• Recent abuses, even after 45 CFR 46
• Asthma death of Ellen Roche at Johns Hopkins
  University Medical Center - http//www.ahrp.org/in
  fomail/0701/19.php
• Gene-Therapy Death of Jesse Gelsinger at Penn -
  http//www.pbs.org/newshour/bb/health/jan-june00/g
  ene_therapy_2-2.html
• Grimes et al. v. Kennedy Krieger Institute
  lead paint exposure of children

5
Formalizing Normative Concerns

• Nuremberg Accords
• Declaration of Helsinki
• The Belmont Report
• Standards of Professional Organizations
• American Psychological Association
• American Medical Association
• Numerous bioethics studies and commissions
• Yielded the Common Rule and a federal apparatus
  for regulating research conduct with human
  subjects

6
Human Subjects Research

• 45 CFR 46 sets forth the institutional structure
  and requirements for review of research
  procedures to protect human subjects see OHRP
  Guidelines http//www.hhs.gov/ohrp/humansubjects/g
  uidance/45cfr46.htm -- each institution must be
  certified via a FWA
• Columbia Policies - http//www.columbia.edu/cu/irb
  /policies.html
• What research triggers IRB review?
• Research means a systematic investigation,
  including research development, testing and
  evaluation, designed to develop or contribute to
  generalizable knowledge
• When private (individually identifiable
  information) is collected

7
When Do Regulations Apply?

• Regulations for the protection of human subjects
  apply when
• There is interaction with a researcher,
  especially in an intervention context, but also
  for survey research and other general forms of
  social and psychological inquiry
• Identifiers or private information are obtained
  (Protected Health Information)
• Some research is exempt from review
• normal educational practice
• educational tests or observational studies or
  surveys
• unless individual identifiers are collected
• disclosure would lead to liability
• elected or appointed officials
• Existing records (assuming no identifiers)
• Consumer studies

8
Who Regulates?

• Universities
• Implementation of federal guidelines FWA
• What do private research institutions do? (E.g.,
  Brookings Institution)
• Sponsoring institutions (funding agencies)
• Most lack the capacity for independent regulation
• E.g., drug companies?
• Government FWA, OPHR
• Legal regulation (implications of Maryland case?)

9
Current Regulatory Framework

• Principles
• Beneficence, respect, justice
• Dimensions of Ethical Conduct
• Risks and benefits
• Accurate assessment of risks
• Specific risks
• Health, psychological, social stigma, privacy
  exposure
• Accurate presentation of these to subjects
• Duty to warn (see Tarasoff)
• Deception
• Privacy

10

• Coercion subject must voluntarily consent, can
  withdraw at any time even after research has
  started
• Question are stipends or other forms of
  compensation coercive?
• Autonomy Informed Consent that acknowledges
  complete comprehension of risks and benefits
• A sample consent form -- http//www.columbia.edu/c
  u/irb/documents/consent.doc
• Comprehension
• Protection of minors who lack decisional
  competence to consent
• Below 18 (??)
• Parental Consent plus assent of child/minor
• Conflict with other doctrines (e.g., best
  interests of child)
• Distributive justice selection of patients or
  subjects to maximize opportunities to receive
  benefits, such as possibility of new and
  effective medications
• Translates to population diversity requirements

11
How It Works

• Research projects certified by independent body
  within sponsoring or hosting institution (IRB)
• Initial review and continuing review
• Certification of procedures, risk/benefit ratios
• Monitoring for adverse effects of research
• Community representation (including prisoner
  advocates)
• Certification by the IRB of all participating
  research entities
• KKI in Maryland case was collaborating
  institution, and subject to federal regulations
• Linked to budget
• No access to research funds without IRB
  certification

12
Confidentiality Shields

• Certificates of confidentiality for protection of
  research information from subpoena
• Effective? See People v. Neuman (32 N.Y.2d
  379 cert. denied 414 U.S. 1163 (1973))
• Analogies to journalists?
• What information is protected?
• Sensitive information
• Concurrent interests require disclosure of
  certain types of information that pose danger to
  research subject or others
• Child maltreatment
• Threats of violence toward self or others (see
  Tarasoff)
• Knowledge of a felony that would aid prosecution

13
Problems in the Current Design

• Egregious errors still occur, with severe harm to
  subjects
• Inadequate procedures to ensure that subjects are
  informed
• Inadequate screening of subjects
• Weaknesses in IRB oversight
• Conflict of interest between IRB and researcher
• COI between researcher and funding source

14
Remedies for Researcher Abuses

• Civil penalties levied by government
• Shutdown of research institutions until review
  problems are corrected, and changes are certified
  by OPHR.
• Exposure to negligence actions and torts
• Difficult to recover
• Exposure to other civil action
• Alvino proposal material breach recasting
  Informed Consent as contractual obligation, in
  which research subject is 3rd party beneficiary
  to special relationship between researcher and
  regulating entity

15
Remedies for IRB Abuses

• Free speech challenge?
• Gaming the system
• Withdrawal or resistance
• Privatization of regulation
• Create triangle between University, regulator and
  researcher, strengthening accountability by
  introducing 3rd party

16
Effects of Regulation on Research

• Censoring of research subjects
• Disincentives to participate
• Lack of incentives
• Scared off by technicalities of consent
• Censoring of research topics
• Taboo topics
• Whose estimation of harm?
• Attenuation of experimental conditions
• Limited range of TX conditions weakens validity

17
Redesigning Human Subjects Regulation

• What set of institutional arrangements can
  reconcile these tensions?
• Is there a better model?
• Are the rules procedurally adequate to ensure
  protection
• Or are they so standardless as to invite abuse
  that creates problems for all parties
  (researcher, subject, funder, research
  institution), including the stakeholder
  professional audiences?
• Is this a free speech issue? And how would
  deregulating human subjects research address
  systemic problems in regulation?