REGULATIONS & STANDARDS
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Jeffrey N. Gibbs, JD, is a director at Hyman, Phelps & McNamara, a Washington, DC-based law firm, and is a member of IVD Technology’s editorial advisory board. He can be reached at jng@hpm.com. |
Case law on this subject is limited. Only a few courts have dealt with the complicated issue of ownership of biological tissues. However, a dispute that was recently decided in the federal courts has been described as “the case that could change everything.”1 In this important decision, the court of appeals affirmed the district court’s holding that study subjects do not retain ownership rights of their biological tissue samples provided for research.2 At first blush, the case appears to support a broad right for research institutions to use banked tissues. But the court was careful to limit its conclusions to the specific facts of the case.
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Anne Marie Murphy, JD, is an associate at Hyman, Phelps & McNamara, a Washington, DC-based law firm. She can be reached at amurphy@hpm.com.
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Washington University sued, seeking a declaratory judgment from the court that it owns the specimens. (In a declaratory judgment, a party asks the court to declare its rights, duties, or obligations with regard to some dispute.) The district court held in favor of the university, and Catalona and his patients appealed. The U.S. Court of Appeals for the Eighth Circuit heard oral arguments in the case in December 2006, and in June 2007, the court affirmed the lower court’s decision. The appeals court framed the issue narrowly and limited its holding to the facts presented.2 Thus, the diagnostics research industry should not assume that once collected, human tissue specimens could under all circumstances be freely used by researchers and institutions. Rather, this case underscores the importance of having clear documentation that study subjects intend to voluntarily contribute their tissue for research purposes.
The court’s holding—that research participants retained no ownership in the biological specimens they contributed to the university’s repository—is not new. It is consistent with what little legal precedent is available.3–5 Nonetheless, this case appears to be the first to address the ownership of the biological specimens themselves, as opposed to some improvement or attempt at commercialization (e.g., a cell line or patented gene). Particularly now that the court of appeals has weighed in, the decision might spur bioethicists, patients, and others to call for legislation that would grant research subjects more control over donated tissues, such as how they are used and by whom.
Indeed, Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University (Washington, DC), predicts there will be a swell of public demand for so-called tissue rights, or the right to control how tissue samples will be used, stored, and studied.1 Such a movement could dramatically affect research if banked samples could not be used, as they are currently, to develop new and better diagnostic tests.
Background
As chief of the urology division at Washington University, Catalona performed thousands of surgeries, including surgeries on prostate cancer patients, and participated in the establishment of a repository of human biological materials for research. Patients typically signed informed- consent agreements inviting them to participate in cancer research, which allowed for the collection of biological tissue samples. In 2003, Catalona left Washington University to take a position at Northwestern University (Chicago). Intending to continue his research on prostate cancer, Catalona sent letters to research participants informing them of his move to Northwestern and his plans to continue his research there. He asked them to sign a document that would purportedly authorize him to transfer their biological specimens from Washington University to Northwestern. Approximately 6000 research subjects signed the form and returned it to Catalona. Nonetheless, the court found that the forms were “void and ineffective to transfer ownership and/or possession” of the tissue samples from the University to Catalona.2,6
Ownership of Samples
Washington University argued that patients had made voluntary donations or gifts of their biological specimens to the university for research purposes. Catalona and the patients argued that the patients retained ownership rights to the specimens and could therefore direct that materials be transferred or used by third parties.
Looking to state law that governs gifts and ownership, the District Court agreed with the university. The court found that the university had at all times been in possession of and exercised control over and ownership of the biological specimens, thereby shifting the burden to Catalona and his patients to prove otherwise.7 The court looked at various factors that established the university’s possession of and control over the specimens, including funding and administration of the biological specimen repository, control over the specimens, legal and regulatory responsibility for complying with the requirements for carrying out federally-funded research, and the university’s own assertion of ownership in its intellectual property policies and material transfer agreements.
The court concluded that the patients were donors and their donations satisfied the elements of an inter vivos gift, namely the donor’s intent to make a gift, delivery to the donee, and acceptance by the donee.8
Informed Consent and Federal Regulation
In determining the patients’ intent to donate tissue specimens to Washington University, the district court looked to the informed-consent agreements signed by the patients prior to the surgeries during which the biological specimens were obtained. The court noted that the informed-consent agreements stated that the patients were agreeing to participate in research, bore the university’s medical center logo, and affirmed that they were not valid without the approval of the university’s institutional review board. Noting that no “specific language” is required from the donor, the court found that the circumstances surrounding the donation (i.e., including the language of the consent agreement) were sufficient to infer that the patients intended to donate their specimens to the university, and not “that they were entrusting their samples to Dr. Catalona only.”8,9
The court was not persuaded by Catalona’s and the patients’ challenge to the university’s claim of ownership on grounds related to the content of the consent agreements. For example, the patients argued that no gift could have been made because the consent form was flawed. The agreements included “exculpatory language,” which is prohibited by federal regulations governing human research.10
The Department of Health and Human Services’ regulations that govern human research prohibit inclusion in the informed-consent document of “exculpatory language through which the subject . . . is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.”11,12 The court concluded that this prohibition on exculpatory language is limited to language that would waive any legal rights that the subject had or relieve any party for negligence. The court noted that testimony “from all experts indicated that the research community consistently understood [the regulation] to bar . . . releases from malpractice or other negligence.”9 The court accepted this interpretation despite a guidance published by HHS’ Office for Human Research Protection (OHRP) that suggests a different interpretation.
Catalona and the patients cited the OHRP guidance for the proposition that language included in the university’s consent agreements to the effect that patients could not claim ownership rights were violative. The OHRP guidance provides examples of prohibitive language, including: “By consent 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.”13 However, the court characterized the OHRP guidance as an “opinion” that did not “affect the ownership interest” of the university.9 The court’s interpretation seemed to imply that the patients had no ownership rights in the first place, thus there were no rights that could have been given up by signing the form.
The court similarly rejected arguments that the patients’ right to discontinue participation in the research, which was stated in the consent agreements as required by federal regulation, amounted to a right to control, which encompassed, if they chose, the right to transfer the specimens to Catalona. Consistently focusing on state law, the court even went so far as to say that the consent agreements were “inconsequential” as to the issue of ownership.9 The court found that the right to discontinue participation in the research simply means that no additional biological specimens would be donated by the subject.14,15
With regard to his letter informing patients of his intent to continue the study at Northwestern and the attached authorization form, Catalona argued that these authorizations effectively carried out the subjects’ right to discontinue participation in the study. The court rejected this argument as well, noting that the circumstances surrounding Catalona’s letter were troubling. Because the patients to whom Catalona sent the letter were “emotionally tied to him,” the court said that the communications “smack[ed] of undue influence.”16 Ultimately, the court rejected every one of the patients’ and Catalona’s arguments, and the court held that the university owns the donated specimens and the patients retained no ownership rights that would allow them to direct how or by whom the specimens are used.
The Appeal
On appeal to the Eighth Circuit, Catalona argued that the district court erred on both substantive and procedural grounds. According to Catalona, the court misinterpreted state law pertaining to gifts by concluding that because delivery and acceptance occurred, the patients gifted their tissue to the university. The court arguably disregarded provisions of the consent agreement that suggested a different intent. The consent form, characterized by Catalona as an agreement entered into by the patients, placed certain conditions on the transfer of the patients’ tissue, such as the right to have the specimens identified and destroyed at some point in the future. According to Catalona, those conditions show that the transfer was not unconditional and therefore not a gift. He asserted that if someone gives a third party an item but retains the right to have it destroyed, then it is not a gift.
During the appeal process, the university characterized this dispute as an important but simple case. It framed the case as coming down to the narrow question of whether patients should be allowed, many years after contributing samples for research, to demand that those samples be moved somewhere else. The university countered each of Catalona’s arguments. To the extent that Catalona’s claim that patients should be able to control their tissue is based on the right required by federal regulations to withdraw from a study, the university argued that the regulations do not address ownership. The regulations allow a study subject to stop participating, but not to take back previously donated specimens.
The university also claimed that Catalona misconstrued state property law. In the university’s view, the specimens were unconditional gifts because ownership did not depend on some future event or contingency. Instead, the university asserted that it was free to use, or even consume, the samples for research purposes at any time, and it therefore obtained ownership upon acceptance of the samples.
Complex policy issues as well as legal issues surfaced during the proceedings. At oral argument, the university emphasized that disruption of medical researchers’ ability to use specimens—which would be the result if the lower court’s decision is not upheld—will drastically slow critical research efforts that are vital to the public.17 The appellants responded that in their view, the university had it backwards. The appellants argued that if patients cannot control their samples, they may be unwilling to participate in research in the first place. This is particularly true, the appellants argued, in an era in which insurance companies may reach for reasons to deny coverage, such as the information gleaned from an individual’s DNA.
The court of appeals affirmed the district court’s decision and agreed with the lower court and the university in virtually every respect. Notably, however, the appeals court framed the question presented very narrowly, and explicitly limited its holding to the facts of this case: Individuals who make an informed decision to contribute their tissue for medical research do not retain any ownership interest that would allow them to direct an institution to transfer the tissue to another party. In reaching this conclusion, the appeals court looked closely at the language of the informed-consent agreements and other background, and concluded that the patients had made a gift of their tissue to the university. The court also noted that the specimens could not be returned to the subjects because they were hazardous waste.
Nonetheless, institutions, researchers, and the IVD industry should not read Washington University v. Catalona or its holding to say that human tissue, once collected, may be used freely by researchers in all circumstances. Rather, this case underscores the importance of documenting in the informed-consent agreement the study subjects’ intent to donate the specimens for research purposes and their understanding that there are no means to control or change later the way the specimens can be used or studied. IVD companies would do well to keep this case in mind when drafting or reviewing informed-consent agreements relating to the use of banked tissue samples.
Conclusion
Biological tissue specimens are obtained under various circumstances. The common assumption seems to be that whoever possesses the specimens controls how the specimens are to be used. However, the court of appeals decision made it clear that such determinations are in fact specific. Ambiguous consent agreements can create legal uncertainties. This case has served to focus attention on a legal issue that has largely been ignored: Who owns human tissue specimens? IVD companies rely heavily on access to banked human specimens, both to develop tests and to support FDA approval. Given the narrow and fact-specific holding of the appeals court, before embarking on projects involving tissue repositories, IVD companies should review documentation of the study subjects’ intent to ensure that it is consistent with the company’s goals with respect to the use of specimens. Based on documentation of the subjects’ informed consent, companies should make their own informed judgments as to whether there may be any open issues with regard to ownership.
References
1. R Skloot, “Taking the Least of You,” New York Times Magazine, April 16, 2006; available from Internet: http://www.nasw.org/users/skloot/TakingTheLeast.pdf.
2. Washington University v. Catalona, 490 F.3d 667, 8th Cir. (2007).
3. Washington University v. Catalona, 437 F.Supp.2d 985, 995 (E.D. Mo. 2006).
4. Greenberg et al. v. Miami Children’s Hospital Research Institute Inc. et al., 264 F.2d 1064 (2003).
5. Moore v. The Regents of the University of California et al., 793 P.2d 479 (1990).
6. Washington University v. Catalona, 437 F.Supp.2d 1003 (E.D. Mo. 2006).
7. Washington University v. Catalona, 437 F.Supp.2d 994 (E.D. Mo. 2006).
8. Washington University v. Catalona, 437 F.Supp.2d 997 (E.D. Mo. 2006).
9. Washington University v. Catalona, 437 F.Supp.2d 998 (E.D. Mo. 2006).
10. Code of Federal Regulations, 45 CFR 46.
11. Code of Federal Regulations, 45 CFR 46.116.
12. Code of Federal Regulations, 21 CFR 50.20.
13. Washington University v. Catalona, 437 F.Supp.2d 992 (E.D. Mo. 2006).
14. Washington University v. Catalona, 437 F.Supp.2d 1000 (E.D. Mo. 2006).
15. Washington University v. Catalona, 437 F.Supp.2d 1000-1001 (E.D. Mo. 2006).
16. Washington University v. Catalona, 437 F.Supp.2d 1002 (E.D. Mo. 2006).
17. Washington University v. Catalona, 490 F.3d 667 (2007) [cited 24 July 2007]; available from Internet: ftp://8cc-www.ca8.uscourts.gov/OAaudio/2006/12/062286.mp3.
