A Legal Approach to the Use of Human Biological Materials (HBM) for Research

Purposes

Marshall B. Kapp, JD, MPH Florida State University Center for

Innovative Collaboration in Medicine & Law

Why a Legal Approach?

• Role of law: Set boundaries within which ethics operate

– Duty

– Power

– Limits

• The function of the law is not to delay or expedite research, but to protect actual or potential participants. Paternalistic bias.

Sources of HBM

• Excess HBM left over and kept from a prior clinical procedure done for diagnostic or treatment purposes

• Obtained for use in a current, but different, research process

• Obtained today for potential use in future, new, presently undefined research protocols

• Cadavers (not “human subjects research”)

• HBM stored in, and supplied by, biobanks/repositories

• Also, HBM may be obtained for reproductive purposes.

Overview of Research Regulation

• What is research (contra therapy)?

– Systematic collection and analysis of data from which generalizable conclusions may be drawn that may aid in improving future care of currently unknown beneficiaries

• Federal “Common Rule”

– 45 Code of Federal Regulations, part 46

– IRB review

– Informed consent

– HBM material may avoid Common Rule if it is not identifiable: • 45 CFR § 46.102(f)—Not “human subjects” research

• 45 CFR § 46.101(b)(4)—”Existing” HBM exempted

• OHRP - Guidance on Research Involving Coded Private Information or Biological Specimens, Oct. 16, 2008, www.hhs.gov/ohrp/policy/cdebiol.html

• July 25, 2011, DHHS Advance Notice of Proposed Rulemaking (ANPRM), “Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators”

• FDA regulates investigational drugs and devices

• April 25, 2006 FDA Guidance OK-ing research on leftover HBM (collected for routine clinical care that would otherwise have been discarded) as long as HBM are not individually identifiable

• Institutions should have policies in place that designate the individual or entity authorized to determine whether research involving coded private information or HBM constitutes “human subjects research.”

• State statutes and regulations

• Private civil actions

– Tort claims (malpractice)

– Property claims

Relevance of International Statements for U.S.

• Aspirational

• Not legally binding unless specifically ratified or part of an Executive Order

Informed Consent

Why?

Right of autonomy=liberty=bodily integrity

• Consent Parameters

HBM removal (with consent) as part of treatment, person is asked for permission to use piece of HBM in a related ongoing study—

Is study an integral part of the treatment protocol (treatment may be conditioned on research participation)? Or

Is study a separate investigation (secondary use of the HBM, separate patient choice)?

HBM removal for the current research project, which can be described

• For future, unknown research project:

– HBM removal (with consent) as part of treatment, ask patients for generic (blanket) approval for the current banking of HBM, on condition that use of the HBM in specific research protocols in the future would require an additional consent, based on specific information about the particular study at that later point in time.

– HBM removal for future research project

• For retrospective studies using HBM obtained and archived long ago for non-research purposes, exemption from Common Rule for “existing” HBM applies. Otherwise, obtaining informed consent would be impossible.

• Alternatives:

– General/blanket consent as adequate?

– Implied consent when HBM is taken as part of a diagnostic or therapeutic procedure to which the participant gave express consent? Patient has “abandoned” the excess HBM that would be thrown out anyway.

– Hybrid approach: People execute advance directives agreeing to have their HBM used in subsequent, unforeseen research protocols that meet certain broad conditions

• July 25, 2011 DHHS ANPRM proposes that a standard, brief, general form be used to obtain consent for the future open-ended use of “biospecimens” in research. Further, such a form would not need to be signed each time a specimen is collected. Rather, researchers or hospitals could ask people to sign one form in which they agree to future research use of all specimens (existing or to be collected in the future).

• Informed consent requires disclosure of material information about risks

– Compromise of privacy

– Misuse of one’s personal genetic information by insurers, employers, educators, or others, despite Genetic Information Nondiscrimination Act (GINA) of 2008

• Other disclosures

– Reasons for collecting the HBM (i.e., research, rather than therapy)

– Collection procedure/intervention

– Duration of the research

– Associated costs to the source

– Financial incentives of HBM collectors and researchers, $$ conflicts of interest, the HBM source’s lack of ownership interest

• How the research data will be used (e.g., commercial applications)

• Confidentiality provisions

• Compensation for injuries

• Alternatives to participating/Right to refuse/ Right to withdraw

• Reasons person might decline participation in a genetic study:

– Concern about personal risks

– Concerns about potential meaning of some types of genetic information for the community to which one belongs—i.e., cultural objections, fear of stigma

– The nature of future studies—i.e., ethical or political objections

– Feeling that HBM communicates one’s identity or character

– Objection to others profiting

– Religious objections

– Distrust of medicine +/or research

Neb. Admin. R.& Regs. Title 181, Ch. 5, Attachment C

• “After a full discussion of the risks, benefits and alternatives [relating to predictive genetic testing], I agree to be tested.

• “For a short time after testing, the lab will keep any remaining sample in case the test must be repeated. After that, the lab may destroy the sample, or it may remove all identifying information and use the sample for research.”

• “Two additional options are storage of the sample for your future use (for a fee), or participation in research as an identified subject.

– “_____I want my sample to be stored for my future use. I will be charged for this.

– “_____I am willing to be contacted if research options are available, and I will decide whether to participate.”

Privacy

• 4 ways that HBM may be maintained:

– Identified: HBM and resulting data remain linked to the source

– Identifiable: HBM and resulting data can be unlinked from the source but the linkage can be restored through a code

– De-identified: Code to re-link available only to an intermediary

– Unidentified: HBM collected anonymously

• Query: Should the extent of informed consent required vary with the extent of privacy protection?

• Query: Does unlinking the HBM and the source’s individual medical record decrease the scientific research value of the HBM?

• Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule

– Requires specific (not blanket) written patient permission before anyone may use or disclose “protected health information” about that person for research purposes.

– “Protected health information” (PHI)=“individually identifiable health information” transmitted or maintained by a “covered entity.”

• Biobanks are not “covered entities” subject to the Privacy Rule unless they also clinically diagnose or treat patients. The hc provider sending HBM to a biobank triggers HIPAA, not the recipient’s act in maintaining a repository.

• “Protected health information” only includes HBM when it is accompanied by specific patient identifiers.

Commercial or Ownership (Property) Interests in HBMs

• Investigators and biobank owners ordinarily have a proprietary $$ interest in products that may be developed based on the HBM research being conducted.

• Source of HBM has autonomy (liberty) right to decide whether HBM may be taken and stored, but no enforceable ownership or property interest in the HBM or commercially valuable products developed out of the research conducted with the HBM. All the marbles are on informed consent process and privacy protections.

• Right to control use of and information about=Limited Ownership

• The owner of the HBM is the entity to which the source originally made the donation or gift. Once the HBM is “donated,” the source cannot transfer it to someone else.

– Moore v. Regents of Univ. of Calif., 793 P.2d 479 (Cal. 1990)

– Greenberg v. Miami Children’s Hosp. Research Inst., 264 F.Supp.2d 1064 (S.D.Fla. 2003)

– Washington University v. Catalona, 490 F.3d 667 (8th Cir. 2007)

– A few other cases raising similar issues have privately settled (no legal precedent set)

– A few cases in which private contracts were executed beforehand

• OHRP and FDA, Draft Guidance on Exclupatory Language in Informed Consent (Aug. 19, 2011), Federal Register Vol. 76, No. 173, pp. 55390-91 (Sept. 7, 2011):

– “[A] subject’s waiver of any rights he or she may have with respect to a biospecimen obtained by investigators for research purposes would not be exculpatory because it does not have the effect of freeing the investigator, sponsor, institution or others involved in the research from malpractice, negligence, blame, fault, or guilt.

“Accordingly, including such waiver language in an informed consent document would be permissible…”

• Problems with a property rights model:

– Can I sell, use, trade, destroy, or give away my body or its parts for any purpose? Much harder for state to restrict freedom to contract about something I own.

– Do my heirs inherit the rights to my body when I die? Could they take back my previous donation?

• Uniform Anatomical Gift Act (adopted by all states)—Family may donate organs for transplantation

• Family has an interest in the proper treatment of the deceased’s body, but not a property/ownership interest

• Alternatives:

– Federal legislation permitting and regulating the buying and selling of HBM for research purposes/HBM as commodity or commercial property

– State legislation (bills in Mass. + Vermont)

– Create community trusts to hold ownership rights to HBM for the general public or communal good

Conclusion

• Culturally and personally emotionally sensitive area

• Research depends upon credibility and trust.

• Liability risks are small.

• But the law does have an important role and how we categorize the rights involved (autonomy/liberty, privacy, property, or contract) makes a big difference.