Institutions that collect and maintain biological samples and associated clinical data should review and address the implications of Catalona.

Repositories of biological samples and clinical data are becoming increasingly important to biomedical research. They contain a critical mass of samples and data collected in the course of clinical care, previously conducted research studies, tissue requisition campaigns and other sources. As such, these repositories can streamline researchers’ ability to test theories against a wide variety of clinical, biological, chemical and genetic conditions, and develop innovative solutions to some of today’s most critical and complex medical and scientific challenges, such as the development of biomarkers and other predictive modeling research.

Who owns biological samples and data housed in these repositories—the individual from whom it is harvested, the physician or researcher who draws it, or the university or institution that provides facilities, funding or oversight for clinical care and research? This question, which is of critical significance to the future of biomedical research, has been the subject of much debate and confusion in recent years. Federal agencies and federal and state courts in various states have taken inconsistent positions and approaches. The Supreme Court of the United States’ decision to deny certiorari in Washington University v. William J. Catalona, et al. and thereby forego its opportunity to resolve the federal issues at stake is thus somewhat disappointing.

The arguments, findings and conclusions in the lower court decisions nonetheless provide important insights for institutions and researchers concerning the issues to address and the steps to take when undertaking the development of a robust repository that will provide a solid backbone for leading-edge biomedical research and innovation well into the future.

Background

During his tenure at Washington University of St. Louis, Dr. William Catalona collected biological samples and associated clinical data with the consent of his patients, and included such samples and data in the Genitor-Urinary Repository. When Dr. Catalona accepted a position at Northwestern University in 2003, he attempted to transfer the biological samples he had collected to Northwestern with the consent of many of the donor-patients without Washington University’s permission. Washington University sued to establish its ownership of the biological samples.

In March 2006, the U.S. District Court for the Eastern District of Missouri held that, on the basis of the facts presented, Washington University owns the biological samples and associated clinical data, and that research participants did not retain any ownership interest beyond the right to withdraw their samples from the repository. Therefore, Washington University successfully prevented Dr. Catalona from transferring the samples to Northwestern.

Dr. Catalona appealed this decision to the U.S. Court of Appeals for the Eighth Circuit, and the Eighth Circuit upheld the district court’s ruling on June 20, 2007. Dr. Catalona appealed the Eighth Circuit’s decision to the Supreme Court of the United States, but the Supreme Court denied certiorari without comment on January 22, 2008.

The Eighth Circuit’s Decision

The Eighth Circuit held that individuals who make an informed and voluntary decision to contribute their biological materials to a particular research institution for the purpose of medical research do not retain an ownership interest allowing such individuals to direct or authorize the transfer of such materials to a third party. Therefore, the court ruled that the university held sole ownership of the biological samples, and Dr. Catalona could not transfer the samples to a third party, even with the donors’ consent.

The court examined whether the research participants intended to part with the “right and dominion over the [biological samples] immediately and irrevocably.” The court reasoned that the research participants must have intended to give the samples, irrevocably, to the university, because the research participants signed informed consent documents on university stationery that characterized the transfer as a voluntary “donation” for use in studies by “Dr. William J. Catalona and/or colleagues,” and received a brochure that characterized the samples as a “free and generous gift.” The court wrote that research participants “unquestionably delivered their biological materials” to the university, and the university “retained absolute possession.” Accordingly, the court concluded that the research participants possessed present donative intent to make the gift to the university and delivered the samples, and that the university accepted the gift.

The court did acknowledge that the research participants had a right to withdraw (i.e., by destroying) their samples from the database, but did not conclude that a right to transfer the samples can be implied from the right to withdraw. The court noted that all informed consent forms expressly stated that research participants could discontinue their participation by having their samples destroyed upon request, but they did not state that participants could request return or transfer of their samples. Furthermore, the court highlighted that some federal and state regulations prohibit the return of biological samples to research participants.

Various factors supported the court’s finding that Dr. Catalona did not hold an interest in the samples. First, numerous material transfer agreements and research agreements that both the university and Dr. Catalona had signed acknowledged the university’s sole ownership of the biological samples. Second, the university’s intellectual property policy, to which Dr. Catalona was subject when he collected the biological samples, stated that “all intellectual property (including…tangible research property) shall be owned by the University if significant University resources were used or if it is created pursuant to a research project funded through corporate, federal or external sponsors administered by the University.” Finally, the university provided the majority of the funding for the maintenance and operation of the repository, and the remainder of the funding came from public and private grants to the university.

Supreme Court Denies Certiorari

Dr. Catalona and a group of his research participants filed a petition for a writ of certiorari, requesting the Supreme Court to review the Eighth Circuit’s holding that donors of biological samples obtained in the course of biomedical research did not have a right to transfer ownership of such samples for one research institution to another. More specifically, their petition asked the Supreme Court to consider whether the federal Common Rule, which protects human subjects in federally funded research, prohibited the research participants from waiving their rights to their biological samples. The Common Rule prohibits institutions from obtaining consent for medical research on human subjects by using “any exculpatory language through which the subject…is made to waive or appear to waive any of the subject’s legal rights.” 45 C.F.R. § 46.116. Dr. Catalona’s research participants signed a consent form that stated: “By consenting to participate in this research, I give up any property rights I may have in bodily fluids or tissue samples obtained in the course of the research.” In essence, Dr. Catalona asked the Supreme Court to rule that the Common Rule prohibited the university from asking the research participants to waive their ownership rights, and therefore the research participants still owned the samples and could direct their future disposition. The Eastern District of Missouri addressed the exculpatory language argument, finding that the Common Rule’s exculpatory language prohibition was limited to waivers or releases of liability, not ownership. The Eighth Circuit had not considered the effect or validity of such waiver language, because it felt such analysis was unnecessary in the context of a gift.

The research participants also filed a petition for writ of certiorari, asking the Supreme Court to consider the Common Rule issue from their perspective. In their petition, the research participants argue that they “expressly relied on the Common Rule to prevent a finding of transferred ownership.” They emphasized to the Supreme Court the potential adverse implications of the Eighth Circuit’s ruling, such as the sale of biological samples to for-profit institutions that might release the research participants’ genetic information, or the use of a research participant’s sample for further research in a field that the participant does not support. Importantly, the research participants warned the Supreme Court that if the Eighth Circuit’s decision is not overturned, research participants will be less likely to contribute their samples to a repository, since they will, in effect, be forced to relinquish control of their samples, and if they do contribute, they will be more likely to exercise their right to destroy the sample once it has been used for a narrowly framed purpose.

On January 22, 2008, the Supreme Court denied the petition for certiorari without comment, leaving unresolved such key issues as the application of the Common Rule’s prohibition against exculpatory clauses.

Important Implications

Catalona has important implications for any institution that collects and maintains biological samples and associated clinical data, and wishes to use such biological samples and clinical data for research activities.

Informed Consent and Authorization

A properly worded clinical care and research informed consent and HIPAA authorization are essential. Institutions will need to carefully balance the competing messages of the Eighth Circuit and the Common Rule concerning the ability of patients and research participants to transfer their ownership rights to their tissue. Institutions should review their informed consent and HIPAA authorization forms, as well as their HIPAA policies, procedures and forms to confirm that they (1) properly characterize any transfer of biological samples or clinical data as a donative gift, and state to whom the materials are transferred in order to provide the institution with flexibility to use the biological samples and data; and (2) make clear that individuals only retain the right to withdraw their biological samples from the research at any time, and language that appears to waive the subject’s rights should be carefully reviewed in light of the Common Rule’s prohibition against exculpatory language. The review for these purposes should also focus on whether the form clearly allows use of specimens for research (particularly if the form is a consent for clinical care as opposed to research).

Centralized Repository

At many institutions, individual investigators, individual clinical departments or other entities separately maintain biological samples and clinical data. Institutional officials and researchers often fail to communicate the existence of these samples and do not maintain proper documentation to demonstrate ownership. The lack of centralized oversight and control: (1) undermines institutional claims of ownership; 2) hampers institutional efforts to make sure that biological samples are collected pursuant to compliant consent and authorization policies, procedures and applicable law; and 3) may impede researchers’ ability to lawfully use the biological samples for future research if the samples are not collected and maintained appropriately. Institutions should conduct an internal audit to determine where biological samples and clinical data are currently stored and what ownership documentation exists. They should consolidate such samples and data into a central repository that is established, maintained and controlled pursuant to institutional policies and procedures.

Intellectual Property Policies and Agreement Provisions

As noted by the Eighth Circuit, the agreements to which both Dr. Catalona and Washington University were a party expressly stated that samples were owned by Washington University. The university’s intellectual property policies also expressly stated that “tangible research property” is owned by the university. The court’s reliance on these factors demonstrates the importance of laying the groundwork for any ownership claims through the use of express policy and agreement language. Institutions should revisit their intellectual property policies and intellectual property agreement provisions to confirm that they expressly secure the institution’s ownership rights to biological samples and associated clinical data vis a vis clinicians and researchers.

Personnel Training

Institutions can reduce internal institutional confusion regarding ownership of biological samples and clinical data by properly training investigators and other research personnel. Proper training establishes a mechanism by which institutions can articulate a consistent message to potential research participants so that those subjects are fully informed of their ownership rights (or lack thereof). Institutions should revisit their current training policies, procedures and training mechanisms to establish a uniform understanding of how collection, maintenance and ownership of biological samples and clinical data are handled within the institution.