Nos. 06-2286 & 06-2301
IN THE
United States Court of Appeals for the Eighth Circuit
_______________________
THE WASHINGTON UNIVERSITY,
Plaintiff-Appellee,
v.
WILLIAM J. CATALONA,
Defendant-Appellant,
and
RICHARD WARD, ET AL.,
Defendants-Appellants.
_______________________
Appeal from the United States District Court
for the Eastern District of Missouri, Eastern Division
The Honorable Stephen N. Limbaugh, Senior District Judge
_______________________
BRIEF FOR AMICUS CURIAE THE AMERICAN CANCER SOCIETY
IN SUPPORT OF PLAINTIFF-APPELLEE AND AFFIRMANCE
_______________________
Mary Pauline Rouvelas
AMERICAN CANCER SOCIETY
901 E Street N.W.
Suite 500
Washington, D.C. 20004
Dated: September 5, 2006 Counsel for Amicus Curiae
RULE 26.1 CERTIFICATION
Pursuant to Rule 26.1 of the Federal Rules of Appellate Procedure, amicus
curiae the American Cancer Society states that it has no parent corporation and no
publicly held company owns 10 percent or more of its stock.
i
TABLE OF CONTENTS
Page
RULE 26.1 CERTIFICATION.................................................................... i
TABLE OF AUTHORITIES ....................................................................... iii
INTEREST OF AMICUS CURIAE ............................................................ 2
SUMMARY OF ARGUMENT ................................................................... 3
ARGUMENT ............................................................................................... 5
I. THE RULE OF LAW THAT DEFENDANTS PROPOSE
WOULD IMPEDE DISCOVERY OF DESPERATELY
NEEDED MEDICAL INNOVATIONS ........................................... 5
A. Biospecimen Research Is Essential In The Fight Against
Cancer...................................................................................... 9
B. Cooperative Tissue Banks Play a Crucial Role In Cancer
Research .................................................................................. 12
C. Defendants’ Proposal Would Jeopardize Research On
Cancer And Other Diseases..................................................... 16
II. THIS COURT IS NOT AN APPROPRIATE FORUM FOR
THE POLICY CHANGE DEFENDANTS REQUEST.................... 19
A. Congress And HHS Are The Proper Forums To Resolve
The Important And Complex Policy Issues That
Defendants’ Proposal Entails .................................................. 20
B. Congress Gave HHS—Not Courts—Sole Authority To
Adjudicate Disputes Arising Under The Common Rule ........ 24
CONCLUSION............................................................................................ 27
CERTIFICATE OF COMPLIANCE
CERTIFICATE OF SERVICE
ii
TABLE OF AUTHORITIES
Page
CASES:
Alexander v. Sandoval, 532 U.S. 275 (2001) ............................................ 24, 25, 26
Batanic v. INS, 12 F.3d 662 (7th Cir. 1993)..................................................... 23
Freeman v. Fahey, 374 F.3d 663 (8th Cir. 2004) ............................................. 26
Frison v. Zebro, 339 F.3d 994 (8th Cir. 2003).................................................. 24-25
Gonzaga Univ. v. Doe, 536 U.S. 273 (2002).................................................... 24, 25
Greenberg v. Miami Children’s Hosp. Research Instit., Inc.,
264 F. Supp. 2d. 1064 (S.D. Fla. 2003) ....................................................... 17
MM&S Fin., Inc. v. National Ass’n of Secs. Dealers, Inc., 364
F.3d 908 (8th Cir. 2004) .............................................................................. 24
Middlesex County Sewerage Auth. v. National Sea Clammers
Ass’n, 453 U.S. 1 (1981) ............................................................................. 25-26
Moore v. Regents of the Univ. of California, 51 Cal. 3d 120,
793 P.2d 479 (1990)................................................................................ 16, 20-21
Reno v. Flores, 507 U.S. 292 (1993) ................................................................ 21
Shaw v. McFarland Clinic, P.C., 363 F.3d 744 (8th Cir. 2004),
cert. denied, 543 U.S. 1081 (2005).............................................................. 21
Touche Ross & Co. v. Redington, 442 U.S. 560 (1979) .................................. 24
United States v. Gainey, 380 U.S. 63 (1965).................................................... 21
Wright v. Fred Hutchinson Cancer Research Ctr.,
269 F. Supp. 2d 1286 (W.D. Wash. 2002) .................................................. 24
iii
TABLE OF AUTHORITIES—Continued
Page
STATUTES:
Children’s Health Act, Pub. L. No. 106-310, 114 Stat. 1167, § 2701,
as amended Pub. L. No. 106-505, 114 Stat. 2350, § 1001(a) (Nov.
13, 2000) ...................................................................................................... 22
National Research Act, Pub. L. No. 93-348, 88 Stat. 342, § 201,
codified at 42 U.S.C. § 2891-1 .................................................................... 7
42 U.S.C. § 289(b)(1)........................................................................................ 22
42 U.S.C. § 289(b)(2)........................................................................................ 25
RULE:
Fed. R. App. P. 29............................................................................................. 1
REGULATIONS:
56 Fed. Reg. 28003 ........................................................................................... 21
45 C.F.R. Part 46, Subpart A ............................................................................ 20
OTHER AUTHORITIES:
American Cancer Society, Cancer Facts and Figures 2006, available at
http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_
Facts_Figures_2006.asp............................................................................... 19
American Cancer Society, “Institutional Research Grants, Policies and
Instructions” (2006), available at http://www.cancer.org/
downloads/RES/IRG_Policies_Instructions_Jan_2006.pdf ........................ 17, 18
American Cancer Society, Peer Review Committees, available at
http://www.cancer.org/docroot/RES/RES_4.asp?sitearea=RES ................. 18
iv
TABLE OF AUTHORITIES—Continued
Page
M. Bledsoe & R. Aamodt, “Resources Available to the Cancer
Research Community,” American Association for Cancer
Research, AACR Education Book (2005) ................................................... 13
F. Fend & M. Raffeld, “Laser Capture Microdissection in Pathology,”
53 J. Clin. Pathology (Sept. 2000), available at
http://jcp.bmjjournals.com/cgi/reprint/53/9/666.......................................... 11
GAO Report 01-775T, “Human Subjects Research, available at
http://www.gao.gov/cgi-bin/getrpt?GAO-01-775T..................................... 23
Andrew G. Glass, et al., “The Cooperative Breast Cancer Tissue
Resource: Archival Tissue for the Investigation of Tumor
Markers,” 7 Clinical Cancer Research (July 2001), available at
http://clincancerres.aacrjournals.org/cgi/reprint/7/7/1843 .......................... 15-16
HHS, OHRP, “OHRP’s Compliance Oversight Procedures for
Evaluating Institutions” (Oct. 19, 2005), available at
http://www.hhs.gov/ohrp/compliance/ohrpcomp.pdf.................................. 25
D. Korn, “Contribution of the Human Tissue Archive to the
Advancement of Medical Knowledge and Public Health,”
published in National Bioethics Advisory Commission, Research
Involving Human Biological Materials: Ethical Issues and Policy
Guidance, Vol. II (Jan. 2000) ............................................................... 11, 13, 16
B. Lauffart, et al., “Aberrations of TACC1 and TACC3 are Associ-
ated with Ovarian Cancer,” 5 BMC Women’s Health (May 2005),
available at http://www.biomedcentral.com/content/pdf/1472-
6874-5-8.pdf................................................................................................. 14-15
V. LiVolsi, et al., “The Cooperative Human Tissue Network: An
Update,” 71 Cancer 1391 (Feb. 1993) ......................................................... 14
Jonathan Melamed, et al., “The Cooperative Prostate Cancer Tissue
Resource: A Specimen and Data Resource for Cancer
Researchers,” 10 Clinical Cancer Research (July 2004), available
at http://clincancerres.aacrjournals.org/cgi/reprint/10/14/4614................... 15
v
TABLE OF AUTHORITIES—Continued
Page
National Biospecimen Network Blueprint, A. Friede, et al., eds.
(Sept. 2003), available at http://biospecimens.cancer.gov/nbn/
NBN_Blueprint.pdf...................................................................................... 8, 10
National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research, The Belmont Report:
Ethical Principles and Guidelines for the Protection of Human
Subjects of Research, Part A: Boundaries Between Practice and
Research (1979) ........................................................................................... 7
National Institute of Mental Health, Collaborative Genetic Studies on
Mental Disorders, available at http://nimhgenetics.org/.............................. 19
National Institute on Alcohol Abuse and Alcoholism, Collaborative
Studies on Genetics of Alcoholism, available at http://www.niaaa.
nih.gov/ResearchInformation/ExtramuralResearch/Shared
Resources/projcoga.htm............................................................................... 19
NCI, OBBR, “NCI Leadership Role in Biorepositories”, available at
http://biospecimens.cancer.gov/biorepositories/obbr_role_nci.asp............. 6
NCI, “Cooperative Human Tissue Network Purpose and Overview,”
available at http://www-chtn.ims.nci.nih.gov/purpose.html ....................... 14
NCI, “History of the Cooperative Human Tissue Network,” available
at http://www-chtn.ims.nci.nih.gov/history.html......................................... 14
NCI, OBBR, “Frequently Asked Questions: NCI and Biorepositories,”
available at http://biospecimens.cancer.gov/resources/faqs.asp.................. 10
NCI, OBBR, “Future of Biorepositories,” available at http://biospeci-
mens.cancer.gov/role/future.asp .................................................................. 12-13
NCI, “Scientific Advances Using CHTN Tissue,” available at
http://www-chtn.ims.nci.nih.gov/advances.html......................................... 14
vi
TABLE OF AUTHORITIES—Continued
Page
NIH Guide for Grants and Contracts, Request for Application 86-CA-
06 “Cooperative Human Tissue Network” (Feb. 28, 1996),
available at http://grants.nih.gov/grants/guide/historical/1986_02_
28_ Vol_15_No_03.pdf ............................................................................... 14
Anil Potti, et al., “A Genomic Strategy to Refine Prognosis in Early-
State Non-Small-Cell Lung Cancer,” 355 New Eng. J. Med.
(Aug. 2006), available at http://content.nejm.org/cgi/reprint/
355/6/570.pdf ............................................................................................... 9
Richard L. Schilsky, et al., “Cooperative Group Tissue Banks As
Research Resources: The Cancer and Leukemia Group B Tissue
Repositories,” 8 Clinical Cancer Research (2002), available at
http://clincancerres.aacrjournals.org/cgi/reprint/8/5/943 ............................ 15
Statement by Bernard A. Schwetz before United States House of
Representatives Subcommittee on Criminal Justice, Drug Policy
and Human Resources (Mar. 7, 2006) available at
http://www.hhs.gov/asl/testify/t060307.html .............................................. 23
U.S. Congress, Office of Technology Assessment, New
Developments in Biotechnology: Ownership of Human Tissues
and Cells (1987)........................................................................................... 16
vii
IN THE
United States Court of Appeals for the Eighth Circuit
_______________________
Nos. 06-2286 & 06-2301
_______________________
THE WASHINGTON UNIVERSITY,
Plaintiff-Appellee,
v.
WILLIAM J. CATALONA,
Defendant-Appellant,
and
RICHARD WARD, ET AL.,
Defendants-Appellants.
_______________________
Appeal from the United States District Court
for the Eastern District of Missouri, Eastern Division
The Honorable Stephen N. Limbaugh, Senior District Judge
_______________________
BRIEF FOR AMICUS CURIAE THE AMERICAN CANCER SOCIETY
IN SUPPORT OF PLAINTIFF-APPELLEE AND AFFIRMANCE
_______________________
Pursuant to Federal Rule of Appellate Procedure 29, and with the
consent of all parties, amicus curiae the American Cancer Society respectfully
submits this brief in support of plaintiff-appellee, Washington University, and
affirmance.
1
INTEREST OF AMICUS CURIAE
Since its inception in 1913, amicus curiae the American Cancer
Society (“ACS”) has been dedicated to winning the fight against cancer. Over the
past sixty years, ACS has contributed approximately three billion dollars to cancer
research and is now the single largest source of private, nonprofit cancer research
funding in the United States; only the Federal government spends more. ACS
currently funds hundreds of research studies at academic institutions in the United
States—thirty-seven of these, for example, in the states of the Eighth Circuit alone.
The ACS Research Program has helped produce key scientific
discoveries and better understanding of cancer and cancer treatment, thus
benefiting millions of people in the U.S. and around the world. ACS’s resources,
scope, and depth of experience make it a leader in sponsorship of high-impact
research for disease prevention, detection, and treatment. ACS has also established
biorepositories, consisting of some 110,000 blood and buccal cell (inner cheek)
samples matched with clinical and questionnaire data, that are being used to
provide valuable insights into the relationships between hormonal, dietary, genetic,
and other factors and cancer outcomes. Use of these samples has resulted in
successful collaboration with a cohort consortium that is conducting genetic
studies on breast and prostate cancer.
2
The American Cancer Society’s interest in this case is substantial.
ACS recognizes that not all of the important decisions in the fight against cancer
are made within a doctor’s office; ACS works with all levels and branches of
government to effect stronger policies, laws, and regulations aimed at reducing
cancer’s burden. ACS is committed to pursuing the political, legal, and economic
conditions necessary for the Nation’s research institutions to discover how to
prevent, detect, treat, and cure cancer. ACS is also dedicated to protection of the
millions of healthy and sick volunteers who participate in biomedical research.
If the Court adopts the rule Defendants urge—granting research-
specimen donors a continuing ownership right that includes the right to dictate
transfer of specimens—ongoing and future research would suffer, jeopardizing
discovery of desperately needed new disease detection tools, treatments, and cures.
For these reasons, amicus curiae the American Cancer Society respectfully
requests that this Court affirm the decision of the District Court.
SUMMARY OF ARGUMENT
Research using biological materials stored in biorepositories is an
indispensable tool in the national effort to discover new ways to detect, prevent,
and treat cancer and other diseases. Tissue sample research has been responsible
for key discoveries, from new diagnostic tests to breakthrough treatment drugs. As
the National Cancer Institute (“NCI”) has recognized, cutting-edge research in
3
progress depends on this important and limited resource, and millions of present
and future patients benefit from it. Biorepositories (many of them supported by
NCI) at academic medical centers play an important role by collecting and storing
high-quality specimens. These biorepositories provide a mechanism for inter-
institutional collaboration and scientifically and medically driven decision-making
about the research agenda. Affirmance of the decision below will promote stability
in this complex system, thus advancing cancer research for the benefit of countless
cancer patients.
If this Court grants tissue donors a continuing right to transfer
specimens, it will sow uncertainty about availability of previously collected
specimens and will disrupt the national system of biorepositories and peer review.
Discovery of potentially life-saving new diagnostic tests and treatments will be
placed at risk. Rather than serving the interests of participants in cancer research,
the rule of law Defendants seek would harm cancer patients. The Court should not
create unprecedented rights that interfere with the national policy of promoting
stability in biospecimen collections and enabling crucial research.
Not only are the continuing ownership and transfer rights that
Defendants seek harmful to cancer research, but this Court is not the right forum
for Defendants to pursue those rights. Adoption of Defendants’ proposal would
implicate serious policy concerns and technical judgments that Congress and the
4
U.S. Department of Health and Human Services (“HHS”) are better suited to
weigh. Judicial rule-making in the area of human subject protections is
particularly inappropriate. In fashioning the regulatory policy, known as the
Common Rule, Congress and HHS engaged in a thorough and broadly inclusive
policy-making process, and they continue to monitor and refine the rules from time
to time as needed. If a change were needed, the political branches could step in
and make it, with input from appropriate sectors.
Finally, Defendants’ effort to seek a judicial declaration of their rights
under the Common Rule is unavailing because, as courts have uniformly held, the
Common Rule does not authorize a private right of action. This Court may not
create rights or remedies where Congress did not explicitly authorize them.
ARGUMENT
I. THE RULE OF LAW THAT DEFENDANTS PROPOSE WOULD
IMPEDE DISCOVERY OF DESPERATELY NEEDED MEDICAL
INNOVATIONS.
Research using biological materials stored in tissue repositories is
essential in the fight against cancer. Biomaterials research has resulted in
breakthroughs that have saved lives and alleviated suffering for millions of people,
and important research now in the pipeline represents hope for countless others
who suffer from cancer and other serious diseases. Yet the expense and
complexity of assembling and maintaining the most scientifically productive
5
specimens makes biorepositories a fragile resource that must be protected and
preserved. “[T]he limited availability of carefully collected and controlled, high-
quality human biospecimens . . . has been repeatedly identified by the scientific
community as the leading obstacle to progress” in understanding cancer. National
Cancer Institute (“NCI”), Office of Biorepository and Biospecimen Research
(“OBBR”), “NCI Leadership Role in Biorepositories”.1 Appropriate maintenance
and accessibility of materials in biorepositories is a leading priority for cancer
research.
Defendants’ proposal would represent a major setback. It would
inject uncertainty and instability into researcher access to a crucial limited
resource. It would impede desperately needed collaboration on tissue research and
create confusion among researchers. It would also signal a major shift in the locus
of decision-making about the cancer research agenda, with broader scientific and
medical concerns giving way to the interests of persons willing to vie for the
attention of individual tissue donors. Needless to say, the results would be harmful
to research and the prospect of developing needed treatments and cures.
Underlying the central issue in this case is a fundamental distinction—
that between biomedical research and therapeutic care. The two serve markedly
1
Available at http://biospecimens.cancer.gov/biorepositories/obbr_role_
nci.asp.
6
different purposes. So important is the distinction that it formed a key theme of the
influential 1979 Belmont Report, in which a National Commission set out the
ethical and policy foundation for the Federal regulations that today govern human
subject research in the United States. See National Commission for the Protection
of Human Subjects of Biomedical and Behavioral Research, The Belmont Report:
Ethical Principles and Guidelines for the Protection of Human Subjects of
Research, Part A: Boundaries Between Practice and Research (1979).2 As the
Belmont Report explained, the purpose of therapeutic practice is “to provide
diagnosis, preventive treatment or therapy to particular individuals.” Id. (emphasis
added). It includes “interventions that are designed solely to enhance the well-
being of an individual patient or client and that have a reasonable expectation of
success.” Id. Research, by contrast, is “designed to test an hypothesis, permit
conclusions to be drawn, and thereby to develop or contribute to generalizable
knowledge” for the good of society. Id. (emphasis added).
2
In 1974, Congress established the National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research. It charged the
Commission with identifying the basic ethical principles that should underlie
research involving human subjects and developing guidelines to assure that
research is conducted in accord with those principles. See National Research Act,
Pub. L. No. 93-348, § 201. The Commission was directed to consider, among
other things, the boundary between biomedical and behavioral research and the
accepted and routine practice of medicine. See National Commission for the
Protection of Human Subjects of Biomedical and Behavioral Research, supra, Part
A: Boundaries Between Practice and Research.
7
The distinction between research and therapy helps to explain why
research participants may not reasonably expect to have any continuing interest in
biological specimens after they provide them to an academic medical center. It is
common, for example, for cancer patients undergoing biopsy or surgery involving
removal of malignant or benign tissue to consent to a small amount of the tissue
being stored for later research. Importantly, specimens are sent to a biorepository
only after all patient diagnostic needs have been met. See, e.g., National
Biospecimen Network Blueprint, A. Friede, et al., eds. (Sept. 2003), at ix, 31.3 The
motivation for providing samples is the desire to enhance understanding and
improve prospects for preventing, diagnosing, and treating cancer for a broad
group of individuals in the future. See, e.g., id. at viii. This distinction between
research and therapy helps explain why Federal regulations and the research
community do not recognize donors of tissue for research as having any continuing
right to control the specimens.
3
Available at http://biospecimens.cancer.gov/nbn/NBN_Blueprint.pdf. The
National Biospecimen Network Blueprint is a report representing “the
collaborative efforts of scientists, clinicians, industry representatives, and patient
advocates.” Id. at i. It was spearheaded by members of the National Dialogue on
Cancer, which includes researchers, NCI, patient advocacy groups, and the
pharmaceutical and medical diagnostics industries as equal partners united to
eliminate cancer as a major public health problem. Id. The report’s “ultimate
purpose [is] accelerating scientific discovery in the battle against cancer.” Id.
8
As explained below, the ability of medical centers to maintain stable
collections of tissue samples in biorepositories is essential to cancer research.
A. Biospecimen Research Is Essential In The Fight Against Cancer.
Tissue sample research has been the foundation for crucial
breakthroughs in the fight against cancer, from diagnostic tests and detection tools
to cutting-edge treatment drugs. Examples abound; one need look no further than
the August 2006 New England Journal of Medicine. There, researchers studying
biospecimens announced a new diagnostic test that each year could save the lives
of tens of thousands of patients with lung cancer, the leading cause of death among
American men and women. See Anil Potti, et al., “A Genomic Strategy to Refine
Prognosis in Early-State Non-Small-Cell Lung Cancer,” 355 New Eng. J. Med.
570 (Aug. 2006).4 While it is known that cancer recurs after surgery in about one-
third of patients with Stage IA non-small-cell lung cancer (“NSCLC”),5 doctors
previously had no reliable way to know whether a particular patient was in this at-
risk group and thus would benefit from adjuvant chemotherapy in addition to
surgery. Using tissue samples from several biorepositories, Duke University
researchers developed a new model that identifies with 93 percent accuracy those
patients at risk for recurrence of the disease. Id. at 571-579.
4
Available at http://content.nejm.org/cgi/reprint/355/6/570.pdf.
5
NSCLC accounts for 80 percent of lung cancer deaths in the United States.
Id. at 571.
9
Too, biospecimens have enabled the development of vital cancer
treatment drugs. One example is trastuzumab (Herceptin®), used to treat breast
cancer. By studying more than 1800 tissue samples—including 1200 from NCI’s
Cooperative Breast Cancer Tissue Resource—researchers discovered that a certain
gene, known as HER2, is “a pivotal biomarker in breast cancer.” See National
Biospecimen Network Blueprint, supra, Appendix A “Case Study: The Role of
Biospecimens for Discovery of a Targeted Cancer Therapy” at A-1. This
discovery “promoted the development of the revolutionary anti-cancer drug,
trastuzumab” to target overexpression of HER2. Id. As NCI explained,
The development of an antibody to this receptor (Herceptin) as a
therapeutic treatment might not have succeeded if it had been tested
on the general breast cancer patient population. The biospecimens,
however, pointed researchers toward a targeted, highly-effective
therapy for a sub-population of breast cancer patients.
NCI, OBBR, “Frequently Asked Questions: NCI and Biorepositories”.6
Tissue samples also played a crucial role in the development of laser
capture microdissection (“LCM”), a breakthrough technique that allows a pure cell
population, such as a group of tumor cells, to be dissected from a sample of breast,
prostate, or pancreatic tissue. See National Biospecimen Network Blueprint,
supra, Appendix C “Case Study: Cancer Tissue Samples Key to Development of
High-Precision Genomic Diagnostic Test”. Tissue samples are complex and may
6
Available at http://biospecimens.cancer.gov/resources/faqs.asp.
10
include, for example, both normal and cancerous cells. LCM was a major advance
in cancer research because it effectively solved the problem of tissue
heterogeneity; now researchers can perform molecular analysis on specific cell
populations in a complex tissue sample. See F. Fend & M. Raffeld, “Laser
Capture Microdissection in Pathology,” 53 J. Clin. Pathology 666-672 (Sept.
2000).7 By having access to a large number of specimens over an extended period
of time, researchers were able to develop a promising technique that significantly
advanced cancer research.
Many now-routine medical practices and now-widely-accepted
theories originally were discovered through biospecimen research. For instance,
research on human tissues led to a new understanding of cervical carcinoma
pathogenesis, providing impetus for development of the Pap (Palanicolaou) smear.
See D. Korn, “Contribution of the Human Tissue Archive to the Advancement of
Medical Knowledge and Public Health,” published in National Bioethics Advisory
Commission, Research Involving Human Biological Materials: Ethical Issues and
Policy Guidance, Vol. II at E-5 (Jan. 2000). Tissue studies also contributed to the
Surgeon General’s landmark 1964 report that linked smoking to lung cancer, by
showing that smoking exposure was linked directly to histopathological changes in
a person’s bronchial lining. Id. at E-6. Further, research using biological tissue
7
Available at http://jcp.bmjjournals.com/cgi/reprint/53/9/666.
11
enabled discoveries of risk factors for atherosclerotic cardiovascular disease and
hypertension, making treatment possible long before the onset of clinical disease
expression. Id. at E-8–E-9.
These and other breakthroughs would have been impossible had stable
sources of human tissue been unavailable. Yet Defendants’ novel theory would
threaten the future viability of important tissue resources. Adoption of that theory
would, in turn, jeopardize research that has the potential to save lives and alleviate
suffering.
B. Cooperative Tissue Banks Play a Crucial Role In Cancer
Research.
Biorepositories maintained by research institutions around the country
play an indispensable role in enabling research on cancer and other diseases. After
an individual provides informed consent for the donation of a tissue sample, the
professional staff of a biorepository take on the responsibility to store, maintain,
and track specimen samples. Biorepositories provide a mechanism for making
tissue available to researchers around the Nation and the world on the basis of the
scientific merit of a research proposal and its importance to the state of medicine.
For example, as NCI explained, “It is now well known that biorepositories are a
key resource for large-scale genomic- and proteomic-based research into cancer.”
12
NCI, OBBR, “Future of Biorepositories”.8 Defendants’ unprecedented theory
should not be permitted to undermine this resource and the future breakthroughs
that depend on its availability. Preserving high-quality, readily-accessible archived
human tissue samples is critical to “accelerating the evaluation and application of
novel new scientific insights and technologies to improve the understanding,
treatment, and even prevention of major human diseases.” Korn, supra, at E-8.
Defendants’ request—that this Court give tissue donors a never-before-recognized
right to transfer tissue samples—would, if granted, undermine the role of
biorepositories and impose uncertainty and instability on future cancer research.
A notable feature of many tissue banks is that they promote the inter-
institutional collaboration that is a cornerstone of modern cancer research. The
four NCI-funded cooperative tissue banks represent instructive examples. These
cooperative tissue resources—and numerous others (see M. Bledsoe & R. Aamodt,
“Resources Available to the Cancer Research Community,” American Association
for Cancer Research, AACR Education Book 315-318 (2005) (identifying other
cooperative tissue resources))—would be thrown into uncertainty under
Defendants’ proposal.
One of the NCI-funded resources is the large-scale Cooperative
Human Tissue Network (CHTN) at the Ohio State University, the University of
8
Available at http://biospecimens.cancer.gov/role/future.asp.
13
Alabama at Birmingham, the University of Pennsylvania, the University of
Virginia, Vanderbilt University, and the Columbus Children’s Hospital. See NCI,
“History of the Cooperative Human Tissue Network”.9 The network’s purpose is
“to stimulate for the good of the public, cooperative efforts to collect and distribute
human tumor tissues for cancer research.” NIH Guide for Grants and Contracts,
Request for Application 86-CA-06 “Cooperative Human Tissue Network” (Feb.
28, 1996)10; V. LiVolsi, et al., “The Cooperative Human Tissue Network: An
Update,” 71 Cancer 1391, 1391 (Feb. 1993). “Since its establishment in 1987, the
CHTN has provided more than 500,000 high quality specimens from a wide
variety of organ sites to over a thousand investigators.” NCI, “Cooperative Human
Tissue Network Purpose and Overview”.11 The more than 1400 publications that
have resulted from studies using CHTN specimens have ranged from discoveries
about the role of genetic alterations in cancer initiation, progression, and metastasis
to means of improving diagnostic accuracy and classification of tumors. See NCI,
“Scientific Advances Using CHTN Tissue”.12 In addition, CHTN specimens have
9
Available at http://www-chtn.ims.nci.nih.gov/history.html.
10
Available at http://grants.nih.gov/grants/guide/historical/1986_02_28_
Vol_15_No_03.pdf.
11
Available at http://www-chtn.ims.nci.nih.gov/purpose.html.
12
Available at http://www-chtn.ims.nci.nih.gov/advances.html. One example
of cutting edge work enabled by the CHTN is a study published last year linking
aberrations of the so-called TACC genes to ovarian cancer. See B. Lauffart, et al.,
“Aberrations of TACC1 and TACC3 are Associated with Ovarian Cancer,” 5 BMC
14
proved critical in the development of emerging technologies and the application of
those technologies to study cancer biology and to develop markers for diagnosis,
prognosis, and prediction of response to therapies. Id.
Three other cooperative human tissue repositories are funded by NCI
and relied upon by researchers around the country for cutting-edge work on cancer
diagnosis, prevention, and treatment:
• The Cooperative Cancer and Leukemia Group B Leukemia Tissue Bank at
the Ohio State University Cancer Center has collected more than 80,000
specimens of bone marrow, peripheral blood, and buccal swab samples since
it was established in 1996. See Richard L. Schilsky, et al., “Cooperative
Group Tissue Banks As Research Resources: The Cancer and Leukemia
Group B Tissue Repositories,” 8 Clinical Cancer Research 943, 943
(2002).13
• The Cooperative Prostate Cancer Tissue Resource—maintained since 1989
by George Washington Medical Center, the Medical College of Wisconsin,
New York University School of Medicine, and the University of
Pittsburgh—contains over 5000 specimens annotated with 130 standardized
data elements. See Jonathan Melamed, et al., “The Cooperative Prostate
Cancer Tissue Resource: A Specimen and Data Resource for Cancer
Researchers,” 10 Clinical Cancer Research 4614, 4614-16 (July 2004).14
• The Cooperative Breast Cancer Tissue Resource—run through four research
institutions, including Washington University—provides researchers with
access to over 9300 archival breast cancer specimens, most of them linked to
diagnostic and follow-up information. See Andrew G. Glass, et al., “The
Women’s Health 8 (May 2005) (explaining that the TACC gene expression in the
study was performed using tissue/tumor microarray slides from the Cooperative
Human Tissue Network), available at http://www.biomedcentral.com/content/pdf/
1472-6874-5-8.pdf.
13
Available at http://clincancerres.aacrjournals.org/cgi/reprint/8/5/943.
14
Available at http://clincancerres.aacrjournals.org/cgi/reprint/10/14/4614.
15
Cooperative Breast Cancer Tissue Resource: Archival Tissue for the
Investigation of Tumor Markers,” 7 Clinical Cancer Research 1843, 1843 &
1849 (July 2001).15
These and other biorepositories provide crucial research resources for
scientists around the country. As discussed below, these resources would be
threatened by the new rule of law that Defendants seek.
C. Defendants’ Proposal Would Jeopardize Research On Cancer
And Other Diseases.
In 1990, when the California Supreme Court decided Moore
v. Regents of the University of California, it recognized that the “exchange of
scientific materials, which still is relatively free and efficient, will surely be
compromised if each cell sample becomes the potential subject matter of a
lawsuit.” 51 Cal. 3d 120, 145, 793 P.2d 479, 495 (1990) (citing U.S. Congress,
Office of Technology Assessment, New Developments in Biotechnology:
Ownership of Human Tissues and Cells (1987) at 52). The Moore court’s wisdom
is especially applicable to biospecimen research, because this research is
characterized by cross-institutional collaboration, national access, and finite
biological resources. “The preservation and reaffirmation of the defining
characteristic of the human tissue archive, that it is a public treasure readily
accessible for medical research for the benefit of all humankind, should constitute
a priority of the highest order.” D. Korn, supra, at E-23–E-24.
15
Available at http://clincancerres.aacrjournals.org/cgi/reprint/7/7/1843.
16
In this case, Defendants ask the Court to remove decision-making
authority over the conduct of tissue sample research from the research community
and place it in the hands of individual tissue donors. If that model were adopted,
individuals would continue to exercise “a type of dead-hand control” allowing
them “to dictate how medical research progresses” years after donation of a tissue
sample. Greenberg v. Miami Children’s Hosp. Research Instit., Inc., 264 F. Supp.
2d. 1064, 1071 (S.D. Fla. 2003). That would represent a major shift, with
potentially grave harm to cancer research.
Academic institutions and governmental and private research sponsors
engage in careful review to determine which cancer studies to conduct and fund.
For example, ACS receives over 2,000 applications for research funding each year,
and these applications receive multiple levels of peer review to identify
scientifically and medically meritorious and innovative projects. See American
Cancer Society, “Institutional Research Grants, Policies and Instructions” 3
(2006).16 Grant applications are evaluated based on criteria such as: “(a) the
scientific merit, originality, and feasibility of the application; (b) the qualifications,
experience and productivity of the applicant, and the members of the investigative
team; (c) the facilities and resources available; and (d) the promise of the research
16
Available at http://www.cancer.org/downloads/RES/IRG_Policies_
Instructions_Jan_2006.pdf.
17
or training as related to the control of cancer or to the benefit to be gained by
persons with cancer.” Id. at 8. For decades, the American Cancer Society—with
its affiliated Scientific Program Directors and discipline-specific Peer Review
Committees—has funded research based on criteria such as these.17
Defendants’ proposal would turn this orderly system on its head. For
example: it would create uncertainty about which samples may remain available
throughout the duration of a study; individuals would be empowered to shop their
excised tissue to the highest bidder; commercial biorepositories could be expected
to engage in bidding wars on samples with proven value. The current system of
allocating tissue resources based on scientific review and expert assessment of
societal medical benefit would thus be undercut, to the detriment of current and
future generations of victims of cancer and other diseases.
Adoption of Defendants’ proposal would mean that individuals may
not make an unconditional gift of a biological sample for research, even if they
choose to do so. Tissue donors want research to succeed, and the doctrine of
unending individual control suggested by the Defendants would undermine that
very success. Hundreds of thousands of individuals have voluntarily participated
17
Each of ACS’s several discipline-specific Peer Review Committees is
composed of between twelve and twenty-five scientific advisors, or peers, who are
experts in their fields. See American Cancer Society, Peer Review Committees,
available at http://www.cancer.org/docroot/RES/RES_4.asp?sitearea=RES.
18
in biospecimen studies in the belief that the resulting research would be conducted
based on scientific principles in the pursuit of cures. For people with cancer, the
future direction of research is too important to allow Defendants’ flawed property
rights argument to hold sway. The stakes are enormous. In 2006 alone, there are
projected to be 1.4 million new cases of cancer. See American Cancer Society,
Cancer Facts and Figures 2006, at 4, 9-21.18 Current and future cancer patients are
best served by a national policy that increases opportunities for cure, and this Court
should not adopt a rule that interferes with such a policy.19
II. THIS COURT IS NOT AN APPROPRIATE FORUM FOR THE
POLICY CHANGE DEFENDANTS REQUEST.
As explained above, recognition of the ownership rights that
Defendants seek would represent a profoundly unwise policy choice. But
irrespective of the wisdom of the policy, the choice is not one that a court is well
18
Available at http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_
Facts__Figures_2006.asp.
19
Cancer research is not the only research jeopardized by Defendants’
proposal. Other path-breaking work in process also would be impaired, such as
research on genetic markers as predictors of particular diseases. See, e.g., National
Institute on Alcohol Abuse and Alcoholism, Collaborative Studies on Genetics of
Alcoholism (collaborative studies seeking to identify genes that affect the risk of
alcoholism and alcohol-related disorders), available at http://www.niaaa.nih.gov/
ResearchInformation/ExtramuralResearch/SharedResources/projcoga.htm;
National Institute of Mental Health, Collaborative Genetic Studies on Mental
Disorders (collaborative studies on genetic indicators for Alzheimer’s disease,
bipolar disorder, schizophrenia, autism, and depression using a repository of
biomaterials annotated with clinical data), available at http://nimhgenetics.org/.
19
positioned to make. Rather, if Defendants were correct that continuing ownership
rights in donated specimens were needed to protect research participants—and they
are not—that decision should be left to Congress and the expert Federal agencies
Congress has charged with making and enforcing the national policy on protection
of human subjects.
A. Congress And HHS Are The Proper Forums To Resolve The
Important And Complex Policy Issues That Defendants’ Proposal
Entails.
Defendants ground their property rights argument in federal
regulations, and particularly in the provisions that require consent forms (1) to
notify research participants that they may discontinue participation in research and
(2) to include no “exculpatory language.” See Brief of Ward, et al. 9-10, 27. Yet
the provisions Defendants cite say nothing about ownership rights; they certainly
do not establish the claimed right to transfer tissue samples. In effect, then,
Defendants ask the Court to infer from the Common Rule ownership rights that
neither Congress nor HHS has ever recognized. 20 The Court should decline the
invitation to make new policy in this area.
As the court explained in Moore, 51 Cal. 3d at 136, 793 P.2d at 488,
the question whether to grant research participants such rights is “more
20
The Common Rule, the uniform set of regulations that govern research
involving human subjects sponsored by seventeen Federal agencies, is set out in
Title 45 of the Code of Federal Regulations Part 46, Subpart A.
20
appropriately the subject of legislative deliberation and resolution” than judicial
declaration. Courts should exercise great caution when asked to settle what are
essentially public policy questions. See Reno v. Flores, 507 U.S. 292, 315 (1993)
(courts are distinctly not “ ‘a legislature charged with formulating public policy’ ”)
(citation omitted); Shaw v. McFarland Clinic, P.C., 363 F.3d 744, 750 n.8 (8th Cir.
2004). As in Moore, adopting the Defendants’ unprecedented ownership theory
would require the Court to engage in a balancing and weighing of competing
policy concerns—a task well-suited for Congress and expert Federal rulemaking
agencies, not courts. 51 Cal. 3d at 142, 793 P.2d at 493 (“[P]roblems in this area
are better suited to legislative resolution.”). Congress can gather empirical
evidence, solicit expert advice, commission studies, and hold hearings involving all
interested parties. Id. at 163, 793 P.2d at 496. “[S]ignificant weight should be
accorded the capacity of Congress to amass the stuff of actual experience and cull
conclusions from it.” United States v. Gainey, 380 U.S. 63, 67 (1965).
Congress and the Federal Executive have done just that in the area of
human research protections. Congress authorized, and seventeen Federal agencies
promulgated, the Common Rule only after the Federal government engaged in an
exhaustive, broadly inclusive policy-making process. See 56 Fed. Reg. 28003
(describing rulemaking process). After careful study by expert bodies—including
the National Commission that authored the Belmont Report—resulted in
21
recommendations, HHS on behalf of the other agencies issued proposed
regulations. Id. In promulgating the final policy, HHS took into account
comments from hundreds of parties, spanning the spectrum of perspectives on
human subjects research, from institutional review board members and staff to
principal investigators, and including associations representing the interests of
research participants, academic institutions, the medical profession and social
scientists. Id. Although Congress or HHS could have mandated in the resulting
regulations the property rights Defendants seek, they did not—and it would be
overreaching for this Court to do so in the absence of a directive from Congress.
If a change in policy were needed, Congress could intervene as it has
in the past. In the Children’s Health Act of 2000, for instance, Congress took
action to ensure that certain protections for research involving children applied to
all Federal agencies, after some agencies had failed to adopt them voluntarily.
Pub. L. No. 106-310, 114 Stat. 1167, § 2701, as amended Pub. L. No. 106-505,
114 Stat. 2350, § 1001(a) (Nov. 13, 2000). Congress has also mandated, for
example, that HHS have a program “under which requests for clarification and
guidance with respect to ethical issues raised in connection with biomedical or
behavioral research involving human subjects are responded to promptly and
appropriately.” 42 U.S.C. § 289(b)(1). Congress is well situated to legislate in this
area if needed.
22
Congress and HHS are attuned to the policy debates affecting human
subjects research. For example, the Director of the HHS Office for Human
Research Protections (“OHRP”) testified before a House subcommittee earlier this
year on OHRP’s role in protecting research participants. See Statement by Bernard
A. Schwetz before United States House of Representatives Subcommittee on
Criminal Justice, Drug Policy and Human Resources (Mar. 7, 2006).21 In addition,
the Government Accountability Office keeps Congress up-to-date on issues related
to human subject research. See, e.g., GAO Report 01-775T, “Human Subjects
Research.”22
At issue in Defendants’ argument are technical decisions with serious
consequences. If additional remedies were needed to protect tissue donors,
Congress and experts at HHS are better situated than a court to weigh and evaluate
the pertinent policy interests. See, e.g., Batanic v. INS, 12 F.3d 662, 665 (7th Cir.
1993) (An agency “when interpreting a statute which it administers in an area in
which it has expertise, is better able to evaluate and weigh the competing policy
interests in that field than is a generalist federal court.”).
21
Available at http://www.hhs.gov/asl/testify/t060307.html.
22
Available at http://www.gao.gov/cgi-bin/getrpt?GAO-01-775T.
23
B. Congress Gave HHS—Not Courts—Sole Authority To Adjudicate
Disputes Arising Under The Common Rule.
There is a further reason that it would be particularly inappropriate in
this case to give Defendants the judicial declaration they seek. The Common Rule
has been uniformly held not to be enforceable in private actions. See, e.g., Wright
v. Fred Hutchinson Cancer Research Ctr., 269 F. Supp. 2d 1286, 1289 (W.D.
Wash. 2002) (holding there is no private right of action under the Common Rule).
And where Congress did not intend to create rights enforceable in private actions,
there is no basis for a judicial remedy. See Gonzaga Univ. v. Doe, 536 U.S. 273,
286 (2002) (“[W]here the text and structure of a statute provide no indication that
Congress intends to create new individual rights, there is no basis for a private
suit”); MM&S Fin., Inc. v. National Ass’n of Secs. Dealers, Inc., 364 F.3d 908,
911 (8th Cir. 2004) (“ ‘The ultimate question is one of congressional intent, not
one of whether this Court thinks that it can improve upon the statutory scheme that
Congress enacted into law.’ ”) (quoting Touche Ross & Co. v. Redington, 442 U.S.
560, 578 (1979)). Defendants’ attempt to base their claimed property interest in
the Common Rule thus represents an improper effort to circumvent the absence of
a private right of action. Further, Defendants’ argument is particularly weak
because it is grounded in regulations, not in an act of Congress. See Alexander v.
Sandoval, 532 U.S. 275, 286 (2001) (“Like substantive federal law itself, private
rights of action to enforce federal law must be created by Congress.”); Frison v.
24
Zebro, 339 F.3d 994, 999 (8th Cir. 2003). Moreover, a private right of action
requires a statute with rights-creating language that “manifests an intent ‘to create
not just a private right but also a private remedy.’ ” See Gonzaga Univ., 536 U.S.
at 284 (quoting Alexander, 532 U.S. at 286 (2001)) (emphasis in original). The
Common Rule is devoid of the rights- and remedy-creating language that the
Supreme Court has held is required.
Instead of providing a private right of action, Congress chose a
different enforcement method for human subjects regulation: administrative
enforcement through complaints to OHRP. See 42 U.S.C. § 289(b)(2); HHS,
OHRP, “OHRP’s Compliance Oversight Procedures for Evaluating Institutions”
(Oct. 19, 2005).23 Congress “authorize[d] OHRP to, on behalf of HHS, establish a
compliance oversight process regarding violations of the rights of human subjects
of research conducted or supported by HHS. Pursuant to this authority, OHRP
may receive reports of such violations and take appropriate action.” Id.
Enactment of the OHRP administrative enforcement mechanism
confirms that Defendants have no right to a judicial determination of their rights
under the Common Rule. “The express provision of one method of enforcing a
substantive rule suggests that Congress intended to preclude others.” Sandoval,
532 U.S. at 290; Gonzaga Univ., 536 U.S. at 290; Middlesex County Sewerage
23
Available at http://www.hhs.gov/ohrp/compliance/ohrpcomp.html.
25
Auth. v. National Sea Clammers Ass’n, 453 U.S. 1, 20-21 (1981). The Eighth
Circuit has repeatedly recognized this principle. See, e.g., Freeman v. Fahey, 374
F.3d 663, 665 (8th Cir. 2004) (Congress’s establishment of administrative
enforcement for certain anti-discrimination provisions “suggest[s] Congress
intended to place enforcement in the hands of the Secretary [of Housing and Urban
Development], rather than private parties.”).
Important separation-of-power principles underlie the rule that courts
do not create and enforce rights that the political branches did not expressly create.
“[T]he judicial task is to interpret the statute Congress has passed.” Sandoval, 532
U.S. at 286. Without statutory intent, “a cause of action does not exist and courts
may not create one, no matter how desirable that might be as a policy matter, or
how compatible with the statute.” Id. at 286-287.
The absence of judicially enforceable rights in the Common Rule
reinforces the inappropriateness of Defendants’ reliance on the Federal regulations
for the relief they seek in this case. This Court should decline to engraft on the
Federal policy at issue a continuing ownership right in donated research specimens
that neither Congress nor the Executive has provided.
26
CONCLUSION
For the foregoing reasons and reasons in the Appellee’s brief, the
judgment below should be affirmed.
Respectfully submitted,
________________________
Mary Pauline Rouvelas
AMERICAN CANCER SOCIETY
901 E Street N.W., Suite 500
Washington, DC 20004
Dated: September 5, 2006 Counsel for Amicus Curiae
27
CERTIFICATE OF COMPLIANCE
Pursuant to Fed. R. App. P. 29(d), the attached Brief for Amicus Curiae the
American Cancer Society in Support of Plaintiff-Appellee and Affirmance is
proportionally spaced, has a typeface of 14 point, and contains 5,638 words as
calculated using the word count function of Microsoft Word 2003.
Mary Pauline Rouvelas
CERTIFICATE OF SERVICE
I hereby certify that on this 5th day of September 2006, two copies of the
foregoing Brief for Amicus Curiae the American Cancer Society in Support of
Plaintiff-Appellee and Affirmance were served by overnight delivery on the
following:
Thomas E. Wack, Esq.
Bryan Cave LLP
One Metropolitan Square
211 North Broadway
Suite 3600
St. Louis, MO 63102-2750
Counsel for Plaintiff-Appellee The Washington University
Gene C. Schaerr, Esq.
Andrew C. Nichols, Esq.
Winston & Strawn LLP
1700 K Street, N.W.
Washington, D.C. 20006-3817
Counsel for Defendant-Appellant William J. Catalona
Paul M. Smith, Esq.
Elaine J. Goldenberg, Esq.
Matthew S. Hellman, Esq.
Jenner & Block LLP
Suite 1200 South
601 Thirteenth Street, N.W.
Washington, D.C. 20005-3823
Counsel for Appellants-Defendants Richard Ward, et al.
_________________________
Mary Pauline Rouvelas
CERTIFICATE OF COMPLIANCE WITH
EIGHTH CIRCUIT RULE 28A(d)
Pursuant to Eighth Circuit R. 28A(d), the enclosed CD-ROM contains the
full contents of the Brief for Amicus Curiae the American Cancer Society in
Support of Plaintiff-Appellee and Affirmance. The brief is a single document in
PDF format generated from the original word processing file, and the file copied to
the CD-Rom has been scanned for viruses and is virus-free.
_________________________
Mary Pauline Rouvelas