Management of Ethical and Legal Considerations
| An overarching issue for the National Biospecimen Network (NBN) is to operate with the
highest possible ethical standards and legal compliance. This module examines ethical and legal
issues facing patients, clinicians, and scientists, which must be considered when formulating
plans for the development of the NBN. It presents the ethical framework under which the NBN
must operate in order to ensure maximum protection for donors of tissues and thus encourage
widespread participation in the system. The module also considers the issues of intellectual and
other property rights associated with biological specimens and medical information. |
2.1 Introduction
An overarching issue for the NBN is to operate with the highest possible ethical standards and
legal compliance. In addition, maintaining high ethical standards will help ensure support and
participation from patients while protecting their rights, and it will help garner the active
participation of surgeons, pathologists, researchers and other supporters.
The relationship between the patient and the NBN is critical, since the patient is the potential
donor of specimens. With the increases in genomic and proteomic research and heightened
concerns related to genetic privacy, it is even more important for the NBN to effectively address
patient concerns, particularly legal and ethical issues, and particularly with respect to interpreting
and managing clinically derived molecular information. Some potential donors also may be
concerned about residual rights to their tissues and medical information.
The primary ethical driver underlying the creation of the NBN must be the recognition that the
needs of the patient always must come first—as is true in medicine in general (primum non
nocere: First, do no harm). There is a need to balance scientific progress as a public good with
patient protection as an individual right. Within the United States, however, the complex mix of
social, cultural, and religious backgrounds of the American population has led to heterogeneous
views on blood, organ, and tissue donation. In general, however, there is ample evidence from
the National Bioethics Advisory Commission (NBAC) literature and other published information
that most Americans are in favor of their specimens being used for research. Because of the
complexities of the American landscape, it is critical that the “informed consent process” be of
the highest quality. The collection of the specimens must minimize privacy risks to patientdonors
and must be cognizant of their interests and needs. Finally, the consent process must also
anticipate the needs of future discoveries and therapeutic advances.
2.2 Background
In its 1999 report, NBAC stated that:
Any ethically sound policy for research uses of human biological materials must
reflect a defensible balance of the ethical reasons that support greater control over
National Biospecimen Network Blueprint
the use of human biological materials and stronger protections for subjects, on the
one hand, and the ethical reasons that support greater access to samples for
purposes of conducting clinically beneficial research and/or clinical interventions,
on the other hand. These reasons will vary in weight and impact depending on the
identifiability of the sample sources and on the probability and magnitude of
various wrongs and harms that may occur. 1
An understanding of the balance between the interests of society and the rights of individual
patients, which is central to the ethical use of human tissues and the use of clinical outcome
information for research, must underscore the development of any national tissue resource.
Human biological materials and associated health information fall into a number of categories,
based on when and where they were collected and the extent to which they can be associated
with their donors, or how “identifiable” they are. Different ethical standards guide the handling
of the different categories of materials, and existing legislation requires different standards of
care to be exercised, depending on the circumstances. Planning the NBN therefore requires an
understanding of the categories of specimens that will be needed to create an effective network,
the risks associated with each category, and the steps that can be taken to reduce these risks
while still collecting useful information.
2.2.1 Identifiability of Biospecimens and Information Collected and Used for
Research
Within a biospecimen repository, the identifiability of specimens may range from truly
unidentifiable specimens to identified specimens. The identifiability of specimens obtained by
researchers from these repositories can also vary, depending on the needs of the specific research
study for which the specimens are being sought. The more identifiable the specimens are, the
greater the risk to donors’ privacy and confidentiality. Therefore, the policies and procedures
established for the collection and distribution of specimens should reflect the level of risk and
possible harm posed to donors.
The two Federal regulations that address this issue of identifiability, and therefore pertain to the
creation and operation of a biospecimen repository, are the Federal Policy for the Protection of
Human Subjects (also known as the “Common Rule,” which is codified for the Department of
Health and Human Services [HHS] at subpart A of Title 45 CFR part 46) and the Standards for
Privacy of Individually Identifiable Health Information (also known as the “Privacy Rule,”
which is codified at Title 45 CFR Part 160 and subparts A and E of Part 164). The Common Rule
pertains to human subject research that is conducted or supported by HHS, or conducted under
an applicable assurance approved by the Office for Human Research Protections (OHRP).
Under the HHS regulations for the protection of human subjects at 45 CFR 46.102(f), “human
subject” is defined as a living individual about whom an investigator conducting research obtains
(1) data through intervention or interaction with the individual, or (2) identifiable private
information. Private information includes information about behavior that occurs in a context in
which an individual would reasonably expect that no observation or recording is taking place,
and information which has been provided for specific purposes by an individual and which the
individual can reasonably expect will not be made public (for example, a medical record).
If an investigator obtains private information about a living individual for research purposes that
retains a link to individually identifying information, such private information is not ordinarily
considered to be individually identifiable to the investigator if (1) the investigator and the holder
of the individually identifying information sign an agreement prohibiting the release of
individually identifying information to the investigator under any circumstances, or (2) there are
other legal requirements prohibiting the release of the link to the investigator.2
Under the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, covered
entities may use or disclose, without restriction, any health information that is deidentified by the
removal of 18 specified identifiers enumerated in the Privacy Rule.3 The covered entity also
must have no actual knowledge that the remaining information could be used alone or in
combination with other information to identify the individual who is the subject of the
information.
Covered entities may also use statistical methods to establish deidentification instead of
removing all 18 identifiers. Covered entities using the statistical method to establish
deidentification may obtain certification by “a person with appropriate knowledge of and
experience with generally accepted statistical and scientific principles and methods for rendering
information not individually identifiable.”4 There is a “very small” risk that the information
could be used by the recipient to identify the individual who is the subject of the information,
alone or in combination with other reasonably available information. The person certifying
statistical deidentification must document the methods used as well as the result of the analysis
that justifies the determination. A covered entity is required to keep such certification, in written
or electronic format, for at least 6 years from the date of its creation or the date when it was last
in effect, whichever is later.
Under the first method of deidentification under the Privacy Rule, unique identifying numbers,
characteristics, or codes must be removed if the health information is to be considered
deidentified. However, the Privacy Rule permits a covered entity to assign to, and retain with,
the health information a code or other means of record identification, if that code is not derived
from or related to the information about the individual and could not be manipulated to identify
the individual. The covered entity may not use or disclose the code or other means of record
identification for any other purpose and may not disclose its method of reidentifying the
information. For example, a randomly assigned code that permits reidentification through a
secured key to that code would not make the information to which it is assigned Protected Health
Information (PHI) because a random code would not be derived from or related to information
about the individual and because the key to that code is secure.
The issue of identifiability of biospecimens and information is an important one to the operation
of NBN. Tissue samples are more useful to researchers when accompanied by demographic and
clinical information, some of which may make them identifiable. In determining the extent to
which it will collect and maintain identifiable samples and information, NBN must balance the
needs of its end users with the ethical requirement to protect the confidentiality and privacy of
health information and samples, and must adhere to all existing regulations. While NBN itself is
not directly subject to HIPAA, tissue collection sites almost certainly will be. NBN must be able
to assure its partners in the system that they will not be at risk for privacy violation through their
relationship with NBN.
2.2.2 Ethical Considerations in Developing the NBN
There are a number of key ethical issues that the NBN must consider when developing its
operating principles and procedures. The act of collecting and storing human biological materials
and related health information in publicly available repositories and archives poses few risks to
donors, and those are primarily social risks. Developing strategies to mitigate these risks is a
fundamental ethical (and sometimes legal) responsibility of NBN. Communicating the steps
taken to the potential donor population will be important to encouraging patients to participate in
the NBN. This section discusses some of the ethical issues that concern donors, which must be
considered in the NBN design.
2.2.2.1 Possible Harm at the Time of Tissue Donation
Collection of specimens must first meet the needs of patient diagnosis. If specimens over and
above that required for clinical care are taken at surgery or biopsy, then the donation might pose
an increased risk to the donor. NBN will seek only the amount of tissue that poses minimal risk
to patients.
2.2.2.2 Loss of Privacy and Confidentiality
Potential donors may be concerned that information about them derived from tissues and medical
records may be released and harm them. One of the primary concerns is that employment and
insurance discrimination might result from exposure of information about health history, genetic
makeup, or familial predisposition to disease. Although there are anecdotal reports of
employment termination and denial of insurance coverage based on genetic predisposition to
disease, there is no definitive research on the extent of these risks; however, the perception is real
and the risk exists.
2.2.2.3 Donors’ Access to Research Results
The Privacy Rule provides research subjects (in this case, donors) with certain rights about how
their health information is used and disclosed. With few exceptions, the Privacy Rule guarantees
individuals access to their medical records and other types of health information, to the extent the
information is maintained by the covered entity or its business associate within a designated
record set. Research records maintained by a covered entity may be part of a designated record
set if, for example, the records are medically related or are used to make decisions about research
participants.
Patients may wish to receive information derived from research using their tissues. Such
information includes not only the results of research at issue, but also discoveries made when
preparing the specimens for banking, which may have medical significance for the donors. For
example, reexamination of the tissues by repository pathologists or researchers may lead to a
different diagnosis than that made by the hospital pathologist. In establishing the operational
procedures and developing the informed consent process, it will be critical to decide how these
situations will be handled.
Donors may also have questions about ownership, access to, and control over the specimens they
have been donated. Advances in medical science are likely to produce more sensitive diagnostic
and prognostic tests. Patients may wish to store tissues, such as tumor cells, against the
possibility of better tests to predict the likelihood of recurrence or progression of disease, or
sensitivity to treatment in the case of relapse.
It has been suggested that biospecimen banks agree to inform donors of future discoveries and
therapeutic advances as a quid pro quo for tissue and information contributions. Factors that
complicate this arrangement and may make it impractical include:
- The deidentification of tissues and data that make it difficult to recontact donors
- The progression of a patient’s disease, and subsequent treatment that may make it
difficult to determine the relevancy of the new information
- The very small likelihood that clinically or statistically validated results would be
available during the course of the patient’s active disease
- The sheer magnitude of the task of maintaining a valid patient-contact database.
The availability of research outcomes poses another, and seemingly contradictory, concern.
There is a risk that physicians may use preliminary research data communicated to them about
their patients for clinical decisionmaking before clinical usefulness is validated, posing a
different risk to the patients’ well-being. Recent debate over the breast cancer (BRCA) gene
mutations demonstrates the risk in sharing results prematurely. Early results suggested that the
presence of the BRCA mutation was strongly associated with the development of BRCA. Some
women, in particular those from populations known to carry the gene at a higher rate, were tested
for the presence of the mutation, and some opted for prophylactic surgical intervention, even
though the benefits for such an approach had not been demonstrated. Subsequent research
indicated that the association was less clear than originally supposed, and that the benefits of
prophylactic intervention overall remain unclear.5
2.2.2.4 Conflicts of Interest
A related area of potential concern to donors is the possible conflict of interest that arises for
physicians who have incentives to collect particular tissue specimens, perhaps to further their
research agenda or for the benefit of the institution. A physician choosing to undertake a more
invasive procedure may appear to be pursuing this course because he or she desires the
specimen. This issue is becoming increasingly pressing in light of new, noninvasive technologies
that are used with increasing frequency to diagnose cancer (e.g., radiology, laparoscopic
surgery), making more invasive procedures that result in collection of more tissue less necessary.
2.2.3 Informed Consent
Informed consent is a key mechanism NBN will employ for protecting the rights of donors: its
goal will be to ensure respect for persons, mutual understanding of research procedures, risks,
rights, and responsibilities, and continuous voluntary participation. The process will be designed
to provide information about a research protocol that the potential donor can understand and use
to make an informed decision about participation. Rather than being a simple form to sign,
informed consent is an educational process between the investigator (or tissue collector in this
case) and the prospective subject (or the subject’s legally authorized representative).
Five elements of informed consent that are derived from fundamental ethical principles have
been summarized by the NBAC:
- Informed consent must include full disclosure of all anticipated relevant risks and
benefits of the research. Derived from the principle of respect for persons, a participant
has the right to know the future use planned for his or her tissues or medical information.
- The principle of respect for persons also demands that the choice to participate be made
voluntarily and that a clear statement of choice (an expressed decision) to participate in
the research be made by the potential participants.
- The informed consent process performs an assessment and gives assurances of the
competence of the subjects to make a decision regarding whether to participate in the
research and to comprehend the relevant risks and benefits to the potential participants.
The requirement for assurances of competence and comprehension are derived from
recognition of individuals’ autonomy under the principle of respect for persons.6
Currently, a hierarchy of informed consent, from more open to more restrictive, exists in
practice. However, as testing methodologies advance, researchers likely will need access to
expanded minimum datasets for each sample to support deeper, more productive research.
Meaningful dialogue around the risks and benefits of augmented informed consent, up to and
including explicit universal consent, will need to take place among patients and advocates,
oncologists, surgeons, pathologists, scientists, institutional review boards (IRBs), and other
regulatory agencies. Patient advocacy groups have played a key role in the development of the
model consent forms and in educating patients about the benefits and precedents of consent.
(Various types of guidance on developing informed consent are included as Appendix H.)
Advances in medical research will require that the consent process be flexible and capable of
handling new demands placed on it by ever-greater needs for access to patient information.
Informed consent for medical research in the United States is based on the opt-in model. Under
this model, potential tissue donors give specific consent to participate in the research described
in the informed consent document. Another approach to consent is the opt-out model. Opt-out
models presume consent, unless a person specifically elects not to participate.7 Under the HHS
regulations for the protection of human subjects, this model would only be permitted if informed
consent could be waived by an IRB as stipulated at 45 CFR 46.116 (c) and (d). Although an optout
scheme would facilitate the creation of a national tissue repository, within the United States it
is not considered acceptable to require all patients to participate in a national tissue system if
they have a biopsy. Patients might prefer that their samples go to alternative tissue banks for
their own future use or specimen research, or they might object to banking of their tissue
entirely. However, it may be possible to have patients check a box that directs the transfer of
residual tissues to a national resource. Many ethicists agree that consent for unspecified use of
their specimens is an appropriate way to obtain consent for a biospecimen bank such as the
NBN. However, informed consent or a waiver of informed consent for specific studies using
specimens and identifiable data from the NBN may be necessary if identifiable specimens are to
be used by researchers. (The National Cancer Institute’s [NCI] tiered consent is discussed in
Appendix I.)
2.2.4 The Role of IRBs
The role of an IRB is to determine that the anticipated benefits of research are worth the risks to
patients. The IRB is expected to protect the interests of human research subjects, and as such,
IRBs can be expected to play an important role in the development of the NBN informed consent
process and protocols for collection of samples and associated patient data.
The OHRP delineated the role of IRBs in HHS-conducted or -supported human tissue
repositories in its 1997 guidelines, “Issues to Consider in the Research Use of Stored Data or
Tissues.” The guidance states that operation of a repository and its data-management center
should be subject to oversight by an IRB. The IRB should review and approve protocols that
specify the conditions under which specimens and data may be accepted and shared, ensuring
that there are adequate provisions to protect the privacy of subjects and maintain the
confidentiality of data. The guidance also states that an IRB should review and approve sample
collection protocols and informed consent documents for distribution to tissue collection sites
and their local IRBs, if specimens are sent to off-site repositories.
If a licensing approach is taken, submitting institutions would be granting usage rights to
biospecimens when they are turned over to the NBN, but not relinquishing control of these
specimens. The Early Detection Research Network (EDRN) has addressed parts of this issue in
deploying its distributed national specimen-sharing infrastructure. EDRN established a common
protocol for submission to IRBs that has greatly decreased both the variability and the time
required to achieve IRB approval.8 NBN would want to take steps to simplify this process as
much as possible, in order to increase the incentive for institutions to participate.
2.2.5 The HIPAA Privacy Rule
The HHS established the Privacy Rule to safeguard the privacy of individually identifiable health
information, as required under HIPAA (www.hhs.gov/ocr/hipaa). Many states also have enacted
statutes to protect the privacy of health information, and to prohibit discrimination on the basis of
genetic information in the provision of insurance or employment.
The Privacy Rule restricts the use or disclosure of PHI by covered entities (health plans, health
care clearinghouses, and certain health care providers). Many research organizations that handle
individually identifiable health information will not have to comply with the Privacy Rule,
because they are not covered entities; however, they still may be affected if they rely on covered
entities for research support or as sources for individually identifiable information for research.
There is a difference between informed consent and the authorization process (i.e., authorizing
the use of PHI). The informed consent process provides research subjects with an understanding
of the study and of any anticipated risks and/or benefits. This may include a description of how
the confidentiality of records will be protected. The Privacy Rule authorization is a permission
that discloses how, why, and to whom the PHI will be used and/or disclosed for research. The
informed consent and authorization request can be combined into one form.
Under the Privacy Rule, the development of a repository or database for future research projects
falls within the definition of research. If the organization creating or maintaining the repository
or database is not a covered entity, then HIPAA does not apply (although other state and Federal
regulations may come into play). Complications may arise if tissues are maintained in a
distributed network of entities, some of which are covered entities and some of which are not. If
the data are to be stored in a centralized location, its operations may be affected by whether it is
considered a covered or noncovered entity. (More details about allowable uses of PHI for
research can be found at: privacyruleandresearch.nih.gov/pr_02.asp).
2.2.6 Property Rights to Biospecimens within the NBN System
A primary issue in the property rights discussion is the question of who will ultimately profit
from the donated biospecimens.9 Profits most generally stem from inventions derived from
biospecimens plus associated analytic information, rather than from the biospecimens or baseline
information alone. These inventions are protected as intellectual property (IP). Current case law
would support the interpretation that only value-added contributions qualify as IP.10 Simple
possession of specimens does not confer IP rights. Some have argued that if the tissue specimen
could have been obtained from another patient and cannot be considered novel, it is not subject
to IP protection.
The NBN team agreed that, under the Common Rule and based on the principle of autonomy,
there is a legal and ethical requirement to allow donors to withdraw their specimens from the
repository before the specimens are distributed for research. This can be accomplished by
assigning a unique code to the sample at the collection site, which links donor to specimen.
Donors could apply to the collection site for withdrawal of their samples. The site then could
communicate to the NBN repository the donor’s request to withdraw a specific coded sample.
This is the practice currently being followed by some repositories. However, it is impossible to
withdraw from the system those samples that have been distributed to researchers.
2.2.7 Potential Sources of Liability
NBN will have many potential sources of liability, most of which are unlikely to happen, and
many of which can be mitigated with well-considered data-sharing agreements.11 These potential
sources include the following:
- Negligence in the collection, storage, and dissemination process
- Adverse outcome to the patient during the collection process
- Exposure to biohazard risk
- Tissue samples anticipated for the repository are cancer tissues and correspondingly
matched healthy tissues. Because of this collection strategy, specimens will not
necessarily be tested for other pathologies. It is possible that some specimens might
constitute a biohazard risk, and liabilities might arise in the transfer of affected materials
regarding possible exposure of individuals who are working with the materials.
- Violation of patent protections by a third party
- Breaches of privacy and confidentiality
- Lawsuits by groups of donors over access to profits. There is a slight risk that individuals
(or, more likely, groups) could initiate a lawsuit to try to gain access to profits (or
possibly information) from a patent/license that was based in part on their specimens or
information. Even if it is not the holder of the patent, a biospecimen repository system
that is licensing use of the biospecimens may be at risk in this situation.
2.3 NBN System Requirements and Recommendations
2.3.1 NBN Must Establish a Chain of Trust in Specimen Collection and Handling
NBN must encourage specimen donation to the system. It is recommended that NBN build the
system on a conceptual “Chain of Trust,” which begins with the patient and runs through to the
researcher. Each link in the chain of the NBN will be entrusted with the responsibility to ensure
the privacy and safety of donors, and to comply with their wishes. Entities that are involved in
each step of the process—from the IRBs that approve collection of samples and data, through the
parties responsible for collection and storage of tissues and information, to the qualified
researchers who use the samples and data for appropriate research purposes—will have specific
obligations to protect the donors. Operational policies, procedures, and structures can be
conceived as the materials out of which strong links in the chain of trust are forged. The strength
of the entire chain is the assurance that the NBN can give to potential donors to promote their
trust for the responsible use of their biospecimens and associated data.
2.3.2 NBN must Reflect a Diverse Population
One of the challenges facing NBN will be ensuring the participation of the broad range of racial
and ethnic groups that make up the American population. In order that a system be just, it must
allow for the equal sharing of both risks and benefits. In the NBN case, this will mean both
participation through donation and enjoyment of the benefits of the research, whether the
research leads to an increased knowledge about a particular health risk or, more importantly, an
improvement in health outcomes from group-specific disorders.
It is recommended that NBN pursue the selection of collection sites that will increase the genetic
and geographic diversity of its biospecimens, in order to accelerate scientific progress that will
benefit the diverse American population and help reduce health disparities.
2.3.3 Ethical and Legal Management of NBN
Appropriate ethical and legal management will be key to developing and operating the NBN.
The Design Team recommends the early creation of a Bioethics and Legal Advisory Board to
guide these activities, an approach followed by many biospecimen banks. It is recommended that
membership be drawn primarily from a group of external content experts. Other members could
be drawn from past and potential donors, as well as from parts of the NBN, including members
of the Governing Board, Operations Center, and Business Units. The Board would report to the
CEO, who would be charged with its formation and (ideally) would chair it. Like quality
assurance (QA), it would be an important executive function about which the Governing Board
would receive regular reports. Key activities of the Bioethics and Legal Advisory Board would
include:
- Development/review of the informed consent document and process
- Development of guidelines for the distribution and transfer of samples
- Review of the communications/education/outreach plans to ensure that appropriate target
audiences and messages have been selected
- Monitoring of the regulatory landscape (examples of existing ethics oversight committees
are included as Appendix J).
2.3.4 Effective Informed Consent Process
It will be critical that essentially the same fundamental informed consent process be followed at
all collection sites. NBN will require an approach that can be implemented early in the process,
preferably at the first contact between potential donors and medical personnel; the approach also
will be subject to QA. To implement this plan, these questions must be answered:
- What are the critical elements of consent?
- How will the consent process be administered?
- When and where will consent be obtained?
- Who will administer the consent process?
- Will the NBN consent be separate from other consents (such as the surgical consent)?
Numerous Federal agencies, professional organizations, and academic institutions have
developed approaches to informed consent. In planning the NBN, it will be important to evaluate
these approaches and determine an effective model, or to identify the elements needed for an
effective process.
The most efficient place for administering the informed consent may be when a patient is
admitted to a community-based facility for a diagnostic biopsy or treatment. Under these
circumstances, potential donors, as patients, are asked to sign a clinical informed consent for the
surgical process. The 1999 NBAC report recommends that the consent for collection of
specimens for research should be kept separate from consent for treatment/diagnosis. This report
also points out that asking patients to choose among a series of options in a tiered consent
process, just at a time when they are faced with the possible diagnosis of a serious illness, may
not be in the best interests of the patients. In this case, it was suggested that it might be
appropriate to use a more general consent for prospective use of tissue samples.
While it was originally thought that NBN would utilize a uniform document, this may prove to
be difficult because:
- Removal of different types of tissue from different sources represents varying levels of
risk to patients and will require different levels of informed consent
- IRBs have not routinely approved standardized consent forms and processes in the past
- Collection sites are unlikely to accept a standard form.
The Design Team noted that the consent process and the form itself would vary, depending on
the context. It is suggested that NBN consider the tiered consent form used by the NCI
cooperative groups (which has been highly successful) in the eventual design of the NBN
consent process. It will be important for NBN to identify the minimum information requirements
for both the informed consent document and process, which will be a requisite for collection site
participation.
2.3.5 Protection of Donors’ Privacy
NBN will require the protection of the privacy and confidentiality of donors and their family
members throughout the entire process of collection, storage, and use of biospecimens and
information. The Design Team suggests that this most likely will be accomplished through the
design of a secure bioinformatics system that offers maximum security for the protection of
health information in the NBN database. Further information regarding suggested security
procedures may be found in 4. Bioinformatics and Data Management.
2.3.6 Alignment with HIPAA Privacy Rule
The exact impact of the HIPAA Privacy Rule on the NBN will depend on a number of factors. It
will need to be determined whether the NBN repositories and databases themselves are (or will
be located) at covered entities. Further, the extent to which NBN’s various business units (such
as the collection sites and researchers using sample and information from NBN) are covered
entities also will potentially affect the operations of NBN. In general, the Privacy Rule prevails
unless state laws relating to privacy of health information are both contrary to and more stringent
than the Privacy Rule. In order to develop a process to reliably comply with HIPAA, it will be
necessary to understand state requirements and to develop an approach that meets the most
stringent requirements.
An element of the Privacy Rule that may affect NBN is the requirement to account for certain
disclosures of PHI for up to 6 years from the date of the request. Data disclosed as part of
deidentified data or minimal datasets with data use agreement are not subject to this type of
accounting; NBN may consider use of these types of data sets. Although there are several
methods for accounting for research-related disclosure (if this is necessary), all methods will
require that the process developed to manage the data disclosures within the NBN be designed in
advance.
Legislative and regulatory relief may facilitate the NBN’s establishment. The Design Team
recommends that a mechanism be established within NBN to monitor both the regulatory
landscape and any guidance from the Office for Civil Rights and the OHRP (perhaps via the
Bioethics and Legal Advisory Board).
2.3.7 Intellectual Property Rights
Some believe that IP issues will represent a major barrier for the creation of an NBN because of
concerns that third parties can demand royalties. To address these concerns, the following IPrelated
criteria should be built into the operations of the system:
- The governing body of the NBN should avoid asserting any patent or other enforceable
IP rights on materials it distributes, as asserting IP rights would hinder open access.
- Use of NBN tissues or information and subsequent patenting should not prevent future
use of materials or information in the repository.
- A strong disclaimer should be used to ward off third-party claims (an adequately
protective disclaimer should put the onus on the customers to obey all laws and
restrictions established within the market).
- To the extent possible, a free market approach with respect to IP issues should prevail.
The Design Team recommended that the NBN create a licensing system whereby NBN has
permission to use—and in turn gives permission to use—biospecimens and information.
The NBN should encourage researchers to patent discoveries made with the use of its resources.
However, use agreements with researchers should make clear that allocations for patents that
would block the use of any NBN biospecimens and information by others are not allowed.
While NBN may not wish to assert any ownership rights to tissues or information, it may, in the
course of developing the infrastructure, develop processes, process improvements, or
technologies that are patentable. NBN may wish to apply for patent protection for these
inventions, or it may wish to publish them, making them publicly available and preventing
another entity from patenting them. The latter approach is consistent with a desire to facilitate
public research on cancer. The former would, however, assist NBN in becoming self-sustaining.
However, use agreements should be reasonably designed to ensure that ultimate patent holders
agree to not interfere with the ability of others to utilize the NBN resources.
The existence of the repository should serve to remove IP barriers for all participants. The
NBN’s goal should be to develop a system with unencumbered use of the information and
samples, providing that peer review, privacy, payment, and similar constraints are met. Reachthrough
rights to future discoveries will be a disincentive to potential users, who must consider
the possible return on investment.
2.3.8 Engagement of Patient Advocates
Patient advocacy groups have been an increasingly powerful voice in protecting the interests of
their members and bringing to light issues surrounding particular diseases. There are a number of
characteristics of patient advocacy groups, which could make them effective partners in
developing and implementing the NBN. Typically, patient advocacy groups:
- Recognize the benefits of participating in the research process
- Serve as a voice for the patient population
- Provide access to the patient community (their membership)
- Have considerable influence over their constituencies
- Are powerful special-interest lobbyists
- Have an interest in the education of the patient population.
The advocacy community has played a key role in promoting research in cancer, genetic
disorders, and other diseases. Although advocacy groups vary in focus, size, and scope of
activities, their input can be invaluable to strengthening the design, development, and
implementation phases of the process, and to maximizing responsiveness and relevancy of the
NBN for patient needs. It will be important to design roles and expectations to guide their
participation in the process, so that their contributions are directed where they can be most
effective. For example, patient advocates could be asked to play a key role in identifying or
reviewing ethical and socio-cultural concerns of potential donors; in defining an optimal
informed consent process and raising sensitivity about practices and procedures that can
discourage participation; and in developing and helping to implement an education program
about the resource, tissue donation, and participation in research generally.
2.4 Summary of Key Requirements
Adherence to the highest possible ethical standards and legal considerations will be critical to the
success of NBN. The assurance that the donors’ best interests are at the heart of the system—
from the standpoint of both reducing the burden of cancer and protecting them from harm to the
greatest extent possible—will help to ensure the support and participation of the broadest donor
population possible. It also will help garner the active participation of researchers and other
supporters, who might be concerned with possible risks in using the system if such principles
were not at the foundation of the system. The key tactic to effecting this strategy will be the
establishment of a Bioethics and Legal Advisory Board early on, to guide the start-up NBN
activities. Other recommendations can be roughly divided into ethical and legal issues.
Ethical
- The establishment of a “Chain of Trust” to ensure the privacy, safety (protection from
harm), and compliance with the wishes of the donors. Other links in this chain include the
patient, IRBs, those responsible for the collection and storage of tissues and information,
and researchers.
- The NBN informed consent process must ensure that potential participants understand
how their specimens may be used and should use tiered consent procedures that provide
individuals with options for levels of participation.
- In general, donors will not be apprised of specific research results derived from their
particular specimens, but information about scientific discoveries made through the use
of biospecimens will be publicly available.
- NBN should pursue the selection of collection sites that will increase the genetic and
geographic diversity of its biospecimens.
- Specimen allocation should be equitable and ensure appropriate use by qualified
researchers in qualified organizations.
Legal
- NBN will adhere to applicable Federal, state, and local rules and regulations.
- NBN should avoid asserting any reach-through rights to IP that are generated through
researcher use of tissues and associated data, since attaching such rights may hinder
access by certain users and slow research.
- NBN should create a system whereby it has permission to use, and in turn gives
permission to use, all biospecimens and information.
- NBN will follow all applicable laws and regulations (including but not restricted to the
HIPAA Privacy Rule) that restrict the use and release of identifiable medical information
to insurers, employers, and others.
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