Freeing Archival Research From The Accidental And Overbearing IRB Regulation That Costs ...

79 Pages·2014·0.52 MB·English

by  Adam J. Rooks

FREEING ARCHIVAL RESEARCH FROM THE
ACCIDENTAL AND OVERBEARING IRB REGULATION
THAT COSTS HUMAN LIVES

William K. Briggs*

I. INTRODUCTION

Few kinds of biomedical research have contributed more and can
contribute more to saving human lives and protecting human health
than “archival research.” Several kinds of medical institutions, such
as biobanks, have stored samples of human tissue, blood, urine, sali-
va, and other biological material, often with associated health and
demographic data.1 With over 300,000,000 such specimens stored in
the U.S. in over 150 biobanks, researchers can examine large popula-
tions and see otherwise invisible patterns.2 The result is “faster,
cheaper, and better research,”3 which society depends upon for such
medical advances as the discovery of the underlying molecular basis
for diseases, more efficient development of drugs, and the uncovering

*William K. Briggs is an associate in the Los Angeles office of Irell & Manella
LLP. He holds a B.A. and a J.D. from the University of Michigan, and is a former
law clerk for Hon. Robert Holmes Bell, U.S. District Court for the Western District
of Michigan. He would like to thank Professor Carl E. Schneider (University of
Michigan Law School) for his invaluable advice, comments, and guidance.
1 See Karen J. Maschke, Biobanks: DNA and Research, FROM BIRTH TO DEATH AND
BENCH TO CLINIC: THE HASTINGS CENTER BIOETHICS BRIEFING BOOK FOR
JOURNALISTS, POLICYMAKERS, AND CAMPAIGNS (2008), archived at
www.perma.cc/8Y2U-QBTX (listing biospecimens that biobanks typically store).
2 See id. (estimating the amount of specimens stored in biobanks in the United
States); see also Global Directory Of Biobanks, Tissue Banks and Biorepositories,
SPECIMENCENTRAL.COM (2012), archived at www.perma.cc/3X9Q-P4EW (listing
biobanks located across the United States and worldwide).
3 Virgilia Toccaceli et al., Research Understanding, Attitude and Awareness To-
wards Biobanking: A Survey Among Italian Twin Participants to a Genetic Epi-
demiological Study, BMC MEDICAL ETHICS (2009), archived at
www.perma.cc/656L-R6VY.

Copyright © 2014 Journal of High Technology Law and William Briggs. All
Rights Reserved. ISSN 1536-7983.
238 JOURNAL OF HIGH TECHNOLOGY LAW [Vol. XIV: No.2
of personalized treatment and prevention methods.4 After all, this is
the type of research which allowed Richard Doll and A. Bradford Hill
to detect the link between cigarette smoking and lung cancer much
earlier than would otherwise have been possible.5

Archival research has another benefit. Unlike some kinds of bi-
omedical research, it does not put human bodies at risk.6 Yet this ex-
ceptionally safe research has come to be regulated just as fiercely as
the most dangerous research with human beings.7 Indeed, it has be-
come regulated so fiercely that archival research—research which is
at the forefront of finding a cure for society’s most hated diseases and
cancers—is routinely impeded, impaired, and even made impossible.8
Institutional review boards (“IRBs”), hospital and university commit-
tees with unreviewable discretion, are at the forefront of this overreg-
ulation.9

Two such restrictions frequently implemented by IRBs are the
right to withdraw and mandatory re-consent for future research.10
The right to withdraw allows donors to withdraw their tissue and flu-
ids from studies whenever they wish and no matter the cost.11 Such a
requirement results in selection bias and statistical significance prob-
lems that can kill the usefulness of this beneficial scientific re-

4 See EU ‘Biobank’ to Help Boost Drug Discovery, EURACTIV (May 30, 2008), ar-
chived at www.perma.cc/9WGZ-QAU7 (describing the importance of biomedical
research databases).
5 See Richard Doll & A. Bradford Hill, Lung Cancer and Other Causes of Death in
Relation to Smoking, 2 BRIT. MED. J. 1071, 1071 (Nov. 10, 1956), archived at
www.perma.cc/ZVB5-TLM7 (providing an example of important biomedical re-
search on the effects of long term smoking).
6 See Maschke, supra note 1 (citing commentary that the risk to human participants
is incredibly low).
7 See Alok Jha, Thousands Dying Due to Bureaucracy on Patient Data, Scientists
Warn, THE GUARDIAN (Jan. 17, 2006), available at www.perma.cc/Y7RE-73SX
(explaining that researchers find it increasingly difficult to get past regulatory in-
terpretation).
8 See id. (describing the consequences of over regulating biomedical archival re-
search).
9 See Maschke, supra note 1 (defining the scope of institutional review boards).
10 See Human Research Protection FAQs Related to Informed Consent, U.S. DEP’T
OF HEALTH & HUMAN SERV. (Jan. 23, 2014), archived at www.perma.cc/Y8NX-
DW4E (detailing federal requirements specific to rights to withdraw and consent).
11 See id. (stating that subjects should freely decide whether to initially enroll in the
research, or later, to withdraw or continue participating in the research).
2014] FREEING ARCHIVAL RESEARCH FROM IRB REGULATION 239
search.12 Similar problems are presented by re-consent, a require-
ment that forces researchers to obtain repeated consent from prior
donors for each new use of their material, no matter how impractical
it is to seek them out.13 Such a requirement not only runs contrary to
the wishes of the vast majority of donors, but also consumes valuable
resources in tracking down donors and creates disincentives to start-
ing new research projects using already gathered material.14

While there is no particular regulation at fault for these two prac-
tices, scholarship and biobank consent forms reveal a strong pattern
of practice.15 The right to withdraw and re-consent is often viewed
by scholars, and IRBs themselves, as essential features of the IRB’s
job of regulating archival research.16 Unfortunately, the costs of such
regulations have to be counted in human lives.17 In the United King-
dom, for example, it is estimated that tens of thousands of lives are
lost every year because regulations, such as the right to withdraw,
prevent medical researchers from obtaining the patient data necessary
for large population-scale studies.18

Unfortunately, these costly restrictions on this valuable research
serve little purpose.19 The “regulationists” who advocate them sug-
gest that the right to withdraw and mandatory re-consent protect the

12 See Amy L. McGuire & Laura M. Beskow, Informed Consent in Genomics and
Genetic Research, NAT’L INST. OF HEALTH (Nov. 15, 2011), archived at
www.perma.cc/FWR7-8T5S (acknowledging requirements for specific consent for
each research use may have significant negative consequences both for research
participants and the research enterprise).
13 See id. (discussing concern about excessive contact and lack of benefit to scien-
tific process and subjects).
14 See id. (identifying the negative implications of re-contact as causing significant
costs and delays and having an adverse effect on validity).
15 See id. (explaining the reliance on consent forms to mitigate areas of concern).
16 See id. (advocating for researchers to have an IRB-approved protocol and to ob-
tain participants’ informed consent specifically for this banking activity).
17 See id. (noting strict adherence to requiring specific consent for each research use
may have significant negative consequences both for research participants and the
research enterprise).
18 See Jha, supra note 7 (quantifying the cost in human lives for bureaucratic limita-
tions for scientists who obtain patient data).
19 See Jha, supra note 7 (recognizing the "undue emphasis on privacy" by regula-
tors).
240 JOURNAL OF HIGH TECHNOLOGY LAW [Vol. XIV: No.2
autonomy and privacy of donors, as well as their dignitary interests.20
Yet while these interests are of great importance, they are not pro-
moted by these regulations; donors stand only the most trivial chance
of losing their privacy, and this interest is already protected by a mul-
titude of statutes and regulations.21 As for autonomy and dignity,
these restrictions actually cause harm to these interests.22 Donors, the
overwhelming majority of whom desire to provide unrestricted use of
their material, are prevented from freely contracting to waive the
right to withdraw or the need for future re-consent.23

As a result, society is left with restrictions, which harm and even
prevent the research it depends upon for the saving of lives and pro-
tection of health, without receiving any compensating benefits. It is
time to free archival research—and society itself—from these re-
strictions.

II.VALUE OF ARCHIVAL RESEARCH

It is important to start by explaining the value of archival re-
search. Answering the questions of why and how this research means
so much to society sets the stage for quantifying just how damning
the right to withdraw and mandatory re-consent are.24 The “why” is
explained by the both the nature of archival material—its composi-
tion, source, and ability to be stored—and the nature of research on
this material—cheap and risk-free.25 To answer the “how,” one need

20 See McGuire & Beskow, supra note 12 (detailing privacy and confidentiality
recommendations as well as ethical obligations).
21 See Rose Li, Custodianship and Ownership Issues In Biospecimen Research,
OFFICE OF BIOREPOSITORIES AND BIOSPECIMEN RESEARCH, (May 2008), available
at www.perma.cc/8UXU-2TSS (introducing standard privacy measures applied in
procedures specific to biospecimen research).
22 See McGuire & Beskow, supra note 12 (noting that people are concerned about
excessive contact and lack of benefit).
23 See McGuire & Beskow, supra note 12 (criticizing withdrawal practices that do
not allow full withdrawal of stored specimens after distribution to secondary users).
24 See Sandra A. McDonald et al., A New Paradigm for Biospecimen Banking in the
Personalized Medicine Era, Nat’l Inst. of Health (Nov. 27, 2012), archived at
www.perma.cc/SW3G-MUVY (acknowledging that banking of appropriately con-
sented human tissue is crucial for the understanding of disease pathogenesis and
translation of such knowledge into improvements in patient care).
25 See id. (explaining the importance of this research as the cornerstone to the revo-
lution of personalized medicine).
2014] FREEING ARCHIVAL RESEARCH FROM IRB REGULATION 241
not look further than archival research’s continuing track record of
catalyzing medical advances across an array of fields.26

A. Why is it so Valuable?

It is uniqueness which makes archival material so useful to re-
searchers. From the breadth of its composition and the nature of its
sources to its ability to be preserved long-term, archival material
permits valuable research otherwise impossible.27 But not only does
archival material make this research possible, it also allows for such
research to be risk-free to the donors and incomparably cheap.28

Consider first the virtues of the material studied. To start with,
archival material allows researchers to study large populations of bio-
logical samples along with associated health and demographic data.29
The breadth of samples available, even in the United States alone, is
only limited by the extent of the human body.30 Tissue samples, both
those healthy and those ravaged by diseases and various forms of
cancer, are available for any organ in the body.31 The same is true
for a diverse range of stem cells, such as embryonic, dental, and
cord.32 Urine, bones, marrow, protein, blood cells, plasma, platelets,

26 See e.g., Alice Park, 10 Ideas Changing the World Right Now: Biobanks, TIME
(Mar. 12, 2009), archived at www.perma.cc/9UF5-CARK (reporting how biospec-
imen research has resulted in dozens of genes being linked to cancers including
BRCA 1 and 2, which are behind 5% to 10% of breast cancers).
27 See D. G. Jones et al., Stored Human Tissue: An Ethical Perspective on the Fate
of Anonymous, Archival Material, 29 J. MED ETHICS 343, 343-44 (2003) (defining
archival as long-term preservation of tissue or organs and also in reference to
pathological archives of slides, stained blood, and bone marrow films).
28 See Maschke, supra note 1 (stating commentators contend that the risk of harm
from research with biospecimens is low); see also Toccaceli, supra note 3 (noting
that one of the benefits of archival material is lower research costs).
29 See Jyotishman Pathak et al., Applying Semantic Web Technologies for Phe-
nome-Wide Scan Using an Electronic Health Record Linked Biobank, J. OF
BIOMEDICAL SEMANTICS (Dec. 2012) (discussing how biospecimens can be linked
to electronic health records to meet research needs).
30 See Maschke, supra note 1 (explaining that human tissue samples are collected
during clinical and surgical procedures).
31 See Monya Baker, Biorepositories: Building Better Biobanks, NATURE (Oct.
2012), archived at www.perma.cc/F5W5-DZ25, (emphasizing that the more infor-
mation that is available about the specimen the more valuable it becomes).
32 See Global Directory of Biobanks, Tissue Banks and Biorepositories, supra note
2 (listing the materials held within biobank, tissue banks, and biorepositories).
242 JOURNAL OF HIGH TECHNOLOGY LAW [Vol. XIV: No.2
teeth—basically anything biological—can all be found.33 And sam-
ples available are as small as cell lines and DNA, and as large as eyes
and brains.34

But not only do biobanks preserve this wide array of biological
samples, they also preserve individualized data for each.35 Each
sample is associated with loads of information regarding the donor,
including medical and family history, demographic information—
age, sex, occupation, residence, body fat, bone density, etc.—, and
behavioral data such as smoking, prescription drug use, exercise
tendencies, and sleeping habits.36 Combining the large numbers of
samples with this associated data allows archival research to take on
unmatched depth.37

The breadth of samples and information available is especially
valuable because studies are not limited to tissue and data within a
single laboratory.38 Instead researchers can bring together samples
from multiple archives, making possible studies that extend world-
wide and reach staggering population sizes.39 The numbers of sam-
ples involved in such archival research can be staggering.40 For ex-
ample, the U.K. Biobank recruited over 500,000 volunteers who

33 See Global Directory of Biobanks, Tissue Banks and Biorepositories, supra note
2 (providing a comprehensive directory of the world’s biobanks that collect a vast
myriad biosamples).
34 See Baker, supra note 31 (stating that samples can range in size from cells to or-
gans).
35 See UK Biobank: Protocol for a Large-scale Prospective Epidemiological Re-
source, at 3, BIOBANK UK, (2007), archived at www.perma.cc/F9QB-JZ5Z (ex-
plaining that biobanks store personal information along with tissue specimens).
36 See id. at 18-22 (categorizing UK Biobank information into numerous groups in-
cluding, “socio-demographics and occupation; lifestyle exposures; early life expo-
sures; psychological state; cognitive function; family history of illness; and medical
history and general health”).
37 See id. at 3 (keeping detailed records allows more accurate identification of a
wide range of human conditions and diseases).
38 See Emmanuelle Lévesque et al., Return of Research Results: General Principles
and International Perspectives, 39 J.L. MED. & ETHICS 583, 583 (2011) (describing
the large target population, worldwide access and long-term storage of data and
samples).
39 See id. (discussing the increasing international collaboration and wide population
coverage of samples in biobanks).
40 See id. (stating a sample population of more than 100,000 individuals in some
biobanks).
2014] FREEING ARCHIVAL RESEARCH FROM IRB REGULATION 243
provided over 1,000,000 samples of blood, urine, and saliva, along
with detailed personal information resulting from physical tests and
personal interviews.41 Similarly, the Coriell Personalized Medicine
Collaborative, a United States Air Force initiative, aims to enroll at
least 100,000 donors to provide saliva samples.42

This ability to aggregate large, diverse populations, not only
through access to biological samples but also associated data, makes
possible otherwise impossible scientific discoveries.43 These large
numbers allow researchers to see patterns that would otherwise be in-
visible.44 For example, with enough samples researchers can pick out
the gene profiles of those suffering from a certain disease and begin
to screen other individuals for such profiles, potentially allowing for
discovery of the disease in individuals at an earlier stage.45 With
such early discovery, it opens up the “next generation of treatments
for disease” by allowing for more aggressive and more effective
treatment.46 But, without access to samples from as large and diverse
a group of individuals as possible, this type of research, and this
“next generation of treatment,” is not possible.47

41 See Angela Saini, Britain’s Biobank is Open for Business, SCI. MAGAZINE (Mar.
29, 2012), www.perma.cc/U64Q-JBDT (reporting the high volume of collected
health data and samples available in the UK Biobank).
42 See John M. Conley et al., Enabling Responsible Public Genomics, 20 HEALTH
MATRIX 325, 342 (2010) (stating Coriell Personalized Medicine Collaborative’s
intention to gather a cohort of 100,000).
43 See Gail Javitt, Why Not Take All of Me? Reflections on the Immortal Life of
Henrietta Lacks and the Status of Participants in Research Using Human Speci-
mens, 11 MINN. J.L. SCI. & TECH. 713, 713-14 (2010) (asserting that biobanks have
allowed researchers to make genetic discoveries by studying samples in the aggre-
gate).
44 See id. at 714 (stating biobanks allow us to make discoveries otherwise impossi-
ble through the study of a single individual).
45 See Park, supra note 26 (discussing the manner in which biobanks allow for early
treatment by utilizing an expansive number of samples from affected and unaffect-
ed people).
46 See Park, supra note 26 (describing the emergence of biobanks allows for more
efficient screening and treatment of individuals).
47 See Park, supra note 26 (implying that biobanks allow scientists to discover
breakthrough treatment).
244 JOURNAL OF HIGH TECHNOLOGY LAW [Vol. XIV: No.2
But the value of archival material extends beyond its breadth.48 It
also comes from its sources: waste generated in the ordinary course
of hospital care and generous human donations.49 The former in-
cludes material excised during surgeries.50 Everything, from cancer-
ous tumors and failed organs to less serious removals like excess skin
tissue, tonsils and wisdom teeth, is valuable.51 Researchers find simi-
lar value in the material that is gathered non-surgically from patients
for testing, such as blood samples, saliva swabs, and hair follicles.52
Even the urine of patients staying for extended periods of time is use-
ful.53 The commonality among all these different types of material is
that, without biobanks and archival research, they would find them-
selves in the trash.54 Once the patients leave the hospital they are
completely uninterested in what is done with their scrap tissue.55
The second main source is voluntary donors.56 These are people
like the 500,000 U.K. Biobank volunteers and the 100,000 donors of
saliva to the Coriell Collaborative.57 Such donors freely provide bio-
logical samples and personal information in a desire to contribute to

48 See William McGeveran et al., Deidentification and Reidentification in Return-
ing Individual Findings from Biobank and Secondary Research: Regulatory Chal-
lenges and Models for Management, 13 MINN. J.L. SCI. & TECH. 485, 488, 496
(2012) (asserting other avenues through which archival materials obtain value).
49 See id. (indicating that biobanks collect data from individuals and hospitals that
contribute specimens).
50 See Maschke, supra note 1 (explaining that biospecimens can be extracted during
the ordinary course of surgical procedures).
51 See Global Directory Of Biobanks, Tissue Banks and Biorepositories, supra note
2 (listing various biobanks that collect dental specimens); see also Baker, supra
note 31 (explaining the importance of collecting cancerous tissue samples in order
to detect cancerous biomarkers).
52 See Park, supra note 26 (noting that doctors are considering collecting DNA
samples as part of routine examinations in order to better detect diseases).
53 See Fredric L. Coe, The Costs and Benefits of a Well-Intended Parasite: A Wit-
ness and Reporter on the IRB Phenomenon, 101 NW. U. L. REV. 723, 725-26
(2007) (explaining the significance of urine samples).
54 See id. (acknowledging that urine samples are often wasted or discarded by pa-
tients).
55 See Valerie J. Janosky, Stem Cells: Potential Cures or Abortion Lures?, 6
DEPAUL J. HEALTH CARE L. 111, 151-52 (2002) (describing the stance of the ma-
jority of Americans on the research use of embryonic cells extracted from tissue).
56 See Conley et al., supra note 42, at FN 42 and accompanying text (providing an
example of a volunteer-reliant study).
57 See Conley et al., supra note 42, at 342 (providing the volume of participants
willing to volunteer their saliva samples to research).
2014] FREEING ARCHIVAL RESEARCH FROM IRB REGULATION 245
the betterment of science.58 Some are motivated by the general de-
sire to help others and the promise of future disease treatment and
prevention breakthroughs that archival research holds.59 These types
of donors give their own regenerable material like blood, urine, sali-
va, eggs, or sperm.60 Others are motivated by their own fights with
diseases, like breast cancer survivors who donate their excised breast
tissue, or inspired by the fights of those closest to them.61 These do-
nors are among the most committed to finding cures through re-
search.62 And like the patients whose scrap tissue is saved, they have
no desire to limit the research done on their material.63

This material gathered from hospital leftovers and donations is
even more valuable because it is able to be stored for many years,
which allows for the gathering of more information and makes possi-
ble future research that may be impossible today due to technological
limitations.64 One illustration of this benefit is the discovery of the
large genetic heterogeneity—lack of one genetic background—of
acute leukemia.65 This discovery was not made through the study of
recently gathered tissue samples, but instead through research on
samples obtained 10-20 years earlier.66 As a result of the preserva-
tion of those samples, individualized therapy and treatment for leu-

58 See Participant Information, MAYO CLINIC BIOBANK, archived at
www.perma.cc/A4YQ-KRHE (describing the requirements for eligibility and the
means of participating in the Mayo Clinic Biobank).
59 See Joseph Shapiro & Sandra Bartlett, Calculating the Value of Human Tissue
Donation, NATIONAL PUBLIC RADIO (July 17, 2012), archived at
www.perma.cc/WD22-UD7A (discussing incentives and motivations of tissue do-
nors).
60 See Maschke, supra note 1 (listing the various forms of human donations).
61 See Shapiro & Bartlett, supra note 59 (discussing personal reasons for donating
tissue).
62 See Shapiro & Bartlett, supra note 59 (considering personal reasons for advocat-
ing research).
63 See Biobanking at the Princess Margaret, infra n. 354 (discussing the general
willingness of patients to donate samples for the greater scientific good).
64 See Lévesque et al., supra note 38, at 583 (introducing the benefits of long-term
storage of biotissue).
65 See Mats G Hansson et al., Should Donors be Allowed to Give Broad Consent to
Future Biobank Research?, 7 THE LANCET ONCOLOGY 266, 267 (2006) (discussing
the great potential of biobank-related research in investigating large populations).
66 See id. (noting how the large genetic heterogeneity of acute leukemia was dis-
covered from “analyses of retrospective biobank samples obtained 10-20 years
ago.”).
246 JOURNAL OF HIGH TECHNOLOGY LAW [Vol. XIV: No.2
kemia is undertaken today and an increasing number of patients have
been cured.67

This type of result is not uncommon.68 The older the samples are
the more valuable they become in general.69 One reason is that do-
nors undergo change, which provides more information to associate
with the sample.70 For example, a healthy person’s donation of blood
to the U.K. Biobank holds limited value today.71 But in ten years, if
that person develops a disease like colon cancer, his blood sample
and associated data become immensely more valuable because re-
searchers can group them with the blood samples and data of other
donors who developed colon cancer.72 Such grouping may allow sci-
entists to discover genetic triggers in the biological material or a cor-
relation in the demographic information that may result in better co-
lon cancer prevention, treatment, and maybe even a cure.73 And even
if the study is unsuccessful, the sample is still made more valuable
for other researchers because the information attached to it is never-
theless increased.74

67 See Clara D. Bloomfield, Importance of Genetic Heterogeneity in Curing Adult
Acute Leukemia (AL), 27 J. OF CLINICAL ONCOLOGY (2009) (observing that the dis-
covery of heterogeneity in acute leukemia has increased survival rates).
68 See id. (noting that an “increasing number of patients” have increased cure rates
with specifically targeted therapy for acute leukemia treatment).
69 See Alfredo Ribeiro-Silva et al., RNA Extraction from Ten Year Old Formalin-
Fixed Paraffin-Embedded Breast Cancer Samples: A Comparison of Column Puri-
fication and Magnetic Based Technologies, 8 BMC MOLECULAR BIOLOGY 118,
118 (2007) (demonstrating the value of archived samples in molecular studies).
70 See Recommendations for the Establishment of a National Cancer Biobank,
HEALTH RESEARCH BOARD, 31-32 (2008), archived at www.perma.cc/CSA5-2JRV
[hereinafter National Cancer Biobank] (stating benefits to research and long-term
donors when studies include older samples).
71 See Ribeiro-Silva et al., supra note 69, at 118 (suggesting older samples are of
greater value).
72 See National Cancer Biobank, supra note 70, at 67 (highlighting the usefulness
of clinical follow up for the delivery of care and research, including the opportunity
to collect additional samples).
73 See Jocelyn Kaiser, African-American Population Biobank Proposed, 300 SCI.
MAG. 1485, 1485 (June 6, 2003) (illustrating one application of demographic
grouping and correlations in biospecimen research).
74 See National Cancer Biobank, supra note 70, at 35 (illustrating one research
study in which donors from ten European countries were followed for ten years).