Each year, thousands of individuals participate in clinical trials for purposes of evaluating the safety and efficacy of medicines and medical devices. Perhaps less visible, however, is the significant portion of clinical research that does not involve the active participation of individuals but instead involves the use of biological samples and clinical data obtained from individuals and stored in repositories. In a variety of ways, individuals provide biological samples and clinical data to a hospital, university or research institution specifically to be used in clinical research activities. For example, individuals may give their permission to the inclusion of any incidental, unused/unnecessary, excised tissue following a standard of care surgery; individuals may give their permission for additional tissue to be excised during surgery (e.g., specifically taking extra bone marrow so that the excess tissue may be included in the repository); or, individuals may participate in a tissue banking exercise for a specific research study.
There is widespread agreement that repositories of these biological samples and databases are critical components of biomedical research, but there is widespread disagreement regarding who owns the repositories of such materials and the intellectual property rights associated with and derived from them. This ownership question, which is critical both to use of such repositories for future research and to commercialization of products based on such use, is the subject of the recent decision in The Washington University v. William J. Catalona, et al.
The Catalona Decision
On March 31, 2006, Judge Stephen Limbaugh issued his much anticipated opinion in The Washington University v. William Catalona, et al., offering some preliminary answers to this central question. The facts of Catalona are simple: Dr. William Catalona, a highly esteemed urologist and researcher employed by Washington University, was instrumental in assisting the University in establishing and growing its Genitor-Urinary Repository, which houses approximately 100,000 biological samples. In 2003, Dr. Catalona left Washington University and accepted a position at Northwestern University, where he intended to continue his prostate cancer research. Prior to his departure, Dr. Catalona sent a letter to approximately 60,000 research participants notifying them of his departure and requesting that recipients sign and return a form requesting that Washington University release their biological samples to Dr. Catalona. Approximately 6,000 subjects returned the signed forms. Washington University asserted that it, not Dr. Catalona or the individuals who provided the samples, owned the samples.
The court stated that the "sole issue determinative" of the lawsuit is ownership and ruled that Washington University was the sole and exclusive owner of all biological samples and associated clinical data in the Repository and that investigators and research participants have no legally recognized ownership right. Under Missouri law, the court found that it is "well-established that exclusive possession and control of personal property is prima facie evidence of ownership and anyone else claiming such property bears the burden of proof." The court found that it was "undisputed" that Washington University had been in "exclusive possession" of the Repository, in part because the University was solely responsible for the maintenance of the Repository housed on University property and because the University signed all material transfer agreements pursuant to which outside parties could request samples from the Repository for research at the discretion of the University. Further, the court noted that the University had consistently asserted its ownership interests in the materials stored in the Repository through its intellectual property policy. The court stated that the University "alone bears all legal, regulatory and compliance risks associated with respect to all research done in connection" with the Repository. It found no compelling federal authority prohibiting Washington University from asserting an ownership interest in the samples in the informed consent pursuant to which the research participants provided the samples.
The court characterized the research participants as providing an "inter vivos" gift to the University. The court rejected Dr. Catalona’s arguments that (a) the exculpatory language in the informed consent forms invalidated the gift, and (b) that the research participants’ right to discontinue participation included a right to control and transfer the provided samples.
In addition to setting forth the legal basis for its conclusion, the court also outlined public policy considerations supporting its decision. First, "medical research can only advance if access to these materials by the scientific community is not thwarted by public agendas," and such open access is best assured by placing responsibility for and authority over biological samples with institutions. Second, if research participants were able to direct all future uses and recipients of biological samples they provided, biological samples "would become nothing more than chattel going to the highest bidder." Third, it is "antithetical to the goals of science and public health to allow research participants to direct the recipient or beneficiary of the sample" and doing so would be "tantamount to a blood donor being able to dictate that his/her blood can only be infused into a person of a certain ethnic background." The court’s public policy discussion also suggests the view that institutional rather than individual ownership would avoid the buying and selling of human tissue to the highest bidder.
Although the court principally relied on Missouri law governing ownership and gifts, the Catalona case has important implications for any institution collecting and maintaining biological samples and clinical data, and for an institution relying upon biological samples and clinical data for research activities:
▪ Intellectual Property Policy: The court cited heavily from the Washington University’s intellectual property policy, which clearly stated that the University owns all intellectual property (including tangible research property) used or created during research projects funded through corporate, government or industry sponsors. Such an intellectual property policy is the foundation to securing ownership of biological samples and a data repository.
▪ Scope of the Research Program: Washington University’s intellectual property policy made it clear that its intellectual property policy applied to all research "administered by the University," and this policy was in effect at all times during the creation and maintenance of the Repository. This broad description of the scope of research to which the policy applied made it difficult for Dr. Catalona reasonably to argue that the intellectual property policy did not apply to the Repository. An institution must establish the boundary of its research program to which its assertion of intellectual property applies to support the assertion of ownership over repositories of biological samples and data generated pursuant to clinical trials within the program.
▪ Centralized Repository: The samples at issue in the Catalona decision were housed in a centralized repository maintained by the University. In some institutions, however, individual investigators or clinical departments create and maintain their own repositories. Institutional officials have little idea what repositories exist, what samples they contain, and who controls them. This lack of centralized oversight and control not only undermines institutional claims of ownership, but hampers institutional efforts to make sure that biological samples are collected pursuant to compliant consent and authorization procedures and forms, and that retaining and using such samples otherwise complies with applicable law. The use of a centralized repository separate and apart from a pathology department makes clear that the samples are intended for research purposes only and are not necessary for the ongoing or future clinical needs of the individuals who provided them. This distinction between treatment and research further minimizes any claim of individual ownership or control since the samples are not necessary for their own treatment needs. Institutions should conduct an internal review to determine whether one or more decentralized repositories of data and/or biological samples exist within the institution and seek to consolidate such samples into a centralized repository that is established, maintained and used pursuant to a consistent set of compliance requirements and handled subject to consistent policies and procedures.
▪ Exculpatory Language: The Common Rule prohibits the use of exculpatory language in informed consent forms in which the subject "waives any of the subject’s legal rights." Although the Common Rule does not elaborate on the exculpatory language prohibition, a 1996 Office of Human Research Protections (OHRP) guidance document listing examples of prohibited exculpatory language includes a waiver of rights to tissue or commercialized products. The Catalona court concluded that the Common Rule regulation only barred exculpatory language dealing with releases from negligence, and found that the OHRP guidance document was not binding on the University. The court did not address what its decision would have been had the OHRP 1996 guidance been incorporated into the regulations and thus been binding on the University. Accordingly, in the wake of the Catalona decision, institutions will need to carefully balance the laudable desire to be clear and candid with research participants with regard to the institution’s assertions of ownership over the provided samples with the competing desire to avoid judicial invalidation of the informed consent process. Institutions should review informed consent language addressing ownership and commercialization of tissue samples in light of the exculpatory language prohibition and related guidance document.
▪ Informed Consent and Authorization: Another important consideration in creating data and tissue repositories is whether research participants sign informed consents that expressly authorize the creation of the tissue and data repositories. Although the Common Rule does not directly address this consent issue, the Privacy Regulations enacted under the Health Insurance Portability and Accountability Act (HIPAA) do, and institutions are continuing to struggle to amend their consent process and forms to reflect the new requirements. A faulty consenting/authorization process could undermine an institution’s assertion of ownership over repository samples and data. Institutions should review their consent and authorization policies, procedures, and forms to confirm that they comply with HIPAA and applicable state law so as to secure the institution’s future flexibility with respect to the disposition of those biological samples and data.
The Catalona case will not end the debate over ownership of data and tissue repositories and their associated intellectual property rights. Public awareness and attention to the use of human tissue in clinical research is on the rise. An April 16, 2006, New York Times Magazine’s headline article, "Taking the Least of You," chronicled the various legal and ethical viewpoints concerning this issue. The Catalona decision is sure to fuel this debate.
As the debate continues and key legal and ethical questions are addressed, universities, hospitals and research institutions should take steps to confirm that (a) their repositories comply with applicable law, (b) policies and procedures are in place with respect to necessary consent and authorization for creation and use of tissue and data repositories, and (c) intellectual property ownership expectations are clear and understood by patients, clinicians and researchers.