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/SEPTEMBER/010917.htm

4. Historical and Current Contexts • Tuskegee • Nazi medical experiments • Milgram’s 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/infomail/0701/19.php • Gene-Therapy Death of Jesse Gelsinger at Penn - http://www.pbs.org/newshour/bb/health/jan-june00/gene_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/guidance/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 might be 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 – OPHR • Legal regulation (implications of Kennedy-Krieger?)

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/cu/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 • Intrusion by IRB into research design

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 • Informed Consent as deterrent • 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?