=Paper=
{{Paper
|id=Vol-1309/paper7
|storemode=property
|title=Towards a common semantic representation of informed consent for biobank specimens
|pdfUrl=https://ceur-ws.org/Vol-1309/paper7.pdf
|volume=Vol-1309
}}
==Towards a common semantic representation of informed consent for biobank specimens==
https://ceur-ws.org/Vol-1309/paper7.pdf
Towards a Common Semantic Representation of
Informed Consent for Biobank Specimens
Frank J. Manion1*, Yongqun He2, Elizabeth Eisenhauer3, Yu Lin2, Alla Karnovsky4,
Marcelline R. Harris3
1
Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109
2
Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, and Center for Computational Medicine and Bioinformatics,
University of Michigan Medical School, Ann Arbor, MI 48109, USA
3
Division of Systems Leadership and Effectiveness Science, University of Michigan School of Nursing, Ann Arbor, MI 48109
4
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109
Abstract — Biospecimen-based research is rapidly growing in the may be collected under different models of consent. A typical
post genomic era, and includes the need to retrieve specimens from scenario might read something like this:
distributed biobanks of various size and complexity in a fashion that
ethically preserves the expressed wishes of specimen donors as “For my study, I want to use samples from my
represented by the informed consent process and its artifacts. This organizations’s biobank, collected under a blanket biobank
paper briefly describes existing work along these lines, presents some informed consent form. I discover that I will need more
challenges unique to biobanks, and presents our own work on an samples, so I contact another organization’s biobank to
ontology of informed consent. determine if they hold relevant and available specimens.
That organization’s samples were collected under a tiered
Keywords— BioBank, Informed consent; ontology; ICO; OBO biobank informed consent form. While some samples are
Foundry, Basic Formal Ontology (BFO), OBI ontology shared with me, I still need more samples to address the
requirements of my study. I then collect additional samples
I. INTRODUCTION using a consent form specific to my study.”
Research in the post-genomic era requires access to high
quality biospeciments, often annotated with or linked to In this example there are three informed consents forms to
clinical data. Many groups at varying levels of institutional account for – a blanket consent, a tiered consent, and the
complexity, ranging from small scale individual laboratories to investigator’s single study consent. In an effort to support the
distributed international collaboratives, have established and expressed wishes of the donors, informed consent documents
operate biorepositories (also refered to by various names such impose a series of legal and ethical restrictions, obligations,
as biobanks, biolibraries, and even collections). Often, there and permissions to biobank operators and research teams using
are needs to share data and specimens among multiple the specimens and data collected in these banks. Often these
biobanks [1-3]. The act of requesting specimens from a rights, obligations, and permissions accrue from multiple
biorespository may demand a complex series of transactions, sources of authority and are represented in multiple legal
each of which in turn may convey a series of rights, obligations, documents. Consequently, the biobanking domain presents a
and permissions for access to specimens and data. Despite over series of modeling challenges, including:
a decade of experience incorporating biospecimens in the The operational model of the biobank. A biobank can be a
research process, formal models that describe the use of single, dedicated resource that provides samples to single or
biorepositories in human research are a relatively recent closely allied groups of studies using a common consent
development. Without a common formal model of consent and model. It might be a virtual or distributed biorepository using
the associated permissions on collection and distribution of precoordinated consent models. Another organization structure
specimens and data, integration of data across the translational might be that of a shared biobank facility containing multiple
spectrum, or from multiple banks and institutions will remain a sets of tissues from multiple projects and attempting to
difficult, manually intensive problem. maximize use of these tissue resources by making them
In this paper we briefly review current efforts toward such available to requestors.
models, describe our own work toward a formal model for The consent model used for the biobank. This can be opt-in
informed consent, and describe what we consider challenges or opt-out. In the case of an opt-in consent model, a tiered
and opportunities for supporting biorespository-based research consent may be used to present the participant or volunteer
with ontologies. A simple example that provides a motivation with choices of the type of data the participant may want
for this effort follows. shared, and for what types of research or other constraints.
II. EXAMPLE OF THE CHALLENGE The protocol model the bank operates under. Typically a
biobank serving more than one project would operate under
Clinical or translational research often involves the
one or more Institutional Review Board (IRB)-approved
extraction and usage of biospecimen from humans. Different
collection protocols and Health Insurance Portability and
biospecimens may be stored and processed differently, and
Accountability Act (HIPAA) authorizations. Researchers
* Corresponding author.
61
subsequently requesting specimens and data would operate IV. THE INFORMED CONSENT ONTOLOGY (ICO)
under separate IRB-approved protocols, and depending on this Development of ICO, a BFO-based ontology represented in
protocol, separate consent and HIPAA authorization may be the Web Ontology Language (OWL2) [12], follows OBO
required for use of a previously banked specimen. Such a Foundry principles of openness and collaboration. ICO is
model is sometimes called a two-protocol model [4]. aligned with the BFO [13], making it possible to align and
Rights, obligations, and permissions accrue from multiple integrate with other BFO-based ontologies. The initial release
sources and must be consistent across time. Properly modeling of the ontology focuses on modeling informed consent
the decisions typically made by human review boards and documents. As for Aug. 14, 2014, ICO contains 471 terms
regulatory personnel considering sample and data distribution including 137 ICO-specific terms and other terms imported
for research requires modeling not just the consent documents, from other BFO-aligned ontologies. Detailed ICO statistics can
but the protocols, data use agreements, and possibly other be found on the Ontobee ICO web page:
information artifacts used in both depositing samples into a http://www.ontobee.org/ontostat.php?ontology=ICO. ICO is
biobank, and withdrawing them for subsequent research. released under an open Creative Commons 3.0 License.
In a research oriented university such as the University of The ontology was developed using a combination of top-
Michigan, thousands of informed consent forms have been down and bottom-up approaches. Protégé-OWL 4.2 was used
generated, and there are over 100 biobanks in the Medical for the ontology authoring and editing. To build the OBI-based
School alone. Queries supporting appropriate use of banked framework of ICO we manually identified informed consent
biospecimens and data must be linked to the signed informed concepts from existing OBO Foundry library ontologies. These
consent agremments with the biospecimen donor. were imported to ICO using Ontodog [14] and OntoFox [15]
which allowed for recursive inclusion of all defined axioms
III. EXISTING EFFORTS and related terms. The results were then manually reviewed for
Several current efforts are evident, focused on modeling final approval before inclusion in the ICO framework.
aspects of the biobanking domain. At least two BFO-aligned Bottom up construction proceeded by manually identifying
ontologies relate to biobanking. The Ontologized Minimum and extracting a list of candidate terms from two informed
Information About BIobank data Sharing (OMIABIS) consent templates used at the University of Michigan (one
expresses data concepts in an ontology of biobank from the Medical School Institutional Review Board, another
administration [5]. OMIABIS is based on work by Norlin and from the Health Sciences and Behavioral Sciences Institutional
colleagues [6] to develop a minimum data set for eight Review Board). We also identified terms from a consent form
countries participating in the EU Biobanking and Biomolecular used for the University of Michigan Medical School
Resources Research Infrastructure project. Limitations of this biorepository, and from World Health Organization (WHO)
effort are that it is intended to serve only as a description of a informed consent templates. The candidate terms identified
biobank contents, and does not describe collection critera, from these templates were then enriched with metadata
consenting, and protocol provenance of individual specimens. including definitions, concept identifiers, preferred terms,
A group at the University of Pennsylvania is developing an synonyms, and URIs extracted from three ontology
ontology for the representation of biobanks, although the work repositories: the National Library of Medicine’s Unified
is in early stages [7]. Similarly, we are aware that a group at Medical Language System (UMLS®) Metathesaurus [16]; the
Duke University is working on a collaborative effort to develop National Center for Biomedical Ontology (NCBO) BioPortal
a normative set of data elements and terms to recommend as [17]; and Ontobee [18]. When textual definitions were not
best practice to the International Society for Biological and provided, other sources such as clinical research glossaries or
Environmental Repositories (ISBER), although this work is not the current literature were used. These enriched candidate
yet published [8, 9]. terms were manually mapped to several pre-identified
There are also non-BFO aligned ontologies in related areas, resources containing terms and definitions developed and
including a Permission Ontology used for development and vetted by the United States regulatory community. This process
evaluation of software tools for reasoning about consent yielded candidate preferred terms contining definitions
permission, published by a group at the University of accepted as robust and well defined by that community.
California San Diego (UCSD) [10]. Related work to build a Resources used in this step included the National Cancer
Research Permission Management System was done at the Institute Thesaurus (NCIt), the Biomedical Research Integrated
Medical University of South Carolina (MUSC) to support a Domain Group (BRIDG) [19], the Ontology of Clinical
statewide research network [11]. A search of the term Research (OCRe) [20], the Consumer Health Vocabulary
“consent” in the NCBO biportal identified the notion of (CHV) and the University of California San Diego permission
informed consent at the class level in 19 different systems ontology [10].
(http://bioportal.bioontology.org/search). The pool of enriched candidate terms was organized into
Our efforts to develop a BFO-aligned informed consent categories of like terms according to their definitions. For
ontology (ICO) emphasizes the broad domain of informed example, the category ‘authorization’ included the terms
consent. Although motivated by a biobanking use case, initial ‘authorization for medical records release’, ‘authorization
development reported here is not restricted to that domain. documentation’ or ‘authorization’. Enriched candidate terms
grouped by categories formed to-be-included terms in ICO.
The final set of categories (or modeling units) was then
62
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