Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2015; 19: 4182-4186 Ethical governance in linked to electronic health records

L. CAENAZZO 1, P. TOZZO 1, A. BOROVECKI 2

Department of Molecular Medicine, Clinical Laboratory, University of Padova, Padova, Italy Department of Social Medicine and Organisation of Health Care, University of Zagreb, Zagreb, Croatia

Abstract. – In the last years an alternative to legally binding instruments or by general regula - traditional research projects conducted with pa - tory texts. Over the years, new questions, diffi - tients has emerged: it is represented by the pair - culties and solutions have appeared. The result is ing of different type of disease biobanks speci - mens with Electronic Health Records (EHRs). that there is lack of clarity and uniformity in Even if remains one of the regulation and consideration of this con - most contested issues of biobank policy, other fusing literature and procedures may be difficult ethical challenges still require careful attention, to understand . given that additional issues are related to the Nonetheless, it is reductive, on first view, to use of EHRs. try to capture in a single term a reality so varied: In this new way of doing research harmoniza - small and vast collections, managed by private tion of governance is essential in practice, with the aim to make the most use of resources at entities and public bodies, containing tumors, tis - our disposal, and sharing of samples and data sue, blood, plasma and other forms of DNA. In among researchers under common policies reg - fact, the term biobank is not yet entirely univer - ulating the distribution and the use. sal. A biobank-specific Ethics Committee could be Some prefer to talk about “biolibraries ”, oth - seen as a new and type of Ethics Committee, ers, such as the French legislature, of “biological that we suggest to be applied to each biobank, with possible different functions. sample collections ”, others still prefer to talk In particular, considering the possible use of about “biological resource centers ” (BRCs) or electronic health record data linked to biological “specimen banks ”. Other designations include specimens in biobanking research, this specific “genetic databases ” or “human genetic research Ethics Committee could draft best practice and databases ” (used by the OECD), “virtual ethical guidelines for the utilisation of the EHRs biobanks ” (the Human Genome Organisation and as a tool for genetic research, addressing con - the Institute for Genomic Research), “bioreposi - cerns on accessibility, and pri - vacy and help to educate patients and health - tories ” (OECD, International Society for Biologi - care providers. cal and Environmental Repositories), “tissue banks ”, “ gene banks ”, and “registries ”. These ex - Key Words: amples show just how varied the terminology is Ethics Committee, Biobanks, gov - and how unbridled the semantic imagination of ernance, HERs. those involved 1. However in general terms, a biobank has the following characteristics and elements: an infra - Introduction structure (that is, a place and equipment) man - aged by a public or private body, the accumula - Biobanking, the organised collection of bio - tion in an organized fashion and over a period of logical samples and associated data, ranges from time of biological samples (cells, tissue, urine, small collections of samples in academic or hos - genes, or DNA or RNA fragments) and data pital settings to large-scale national repositories. (clinical information about patients and their Different approaches to regulations of families, or even populations, genealogical or bi - biobanks have appeared both at the national and ological data, lifestyle information, etc.), for the international levels, sometimes through specific purpose of medical research.

4182 Corresponding Author: Luciana Caenazzo, MD; e-mail: [email protected] Ethical governance in biobanks linked to electronic health records

A biobank is composed of biological speci - tions, new research in both public and private mens and of the information related to the speci - contexts, and new ethical challenges in biobank - mens and their sources. Individual or patient in - ing 7,8 . formation is part of the biobank and has the same Even if informed consent remains one of the relevance as the tissue sample and for this reason most contested issues of biobank policy 9, other eth - collection of information should be accurate and ical challenges still require careful attention, given complete. that additional issues are related to the use of In the last years an alternative to traditional re - EHRs: these include the protection of vulnerable search projects conducted with patients has subjects, the safeguarding of privacy, the commu - emerged: it is represented by the pairing of dif - nication of research results to donors, the conflicts ferent type of disease biobanks specimens with over patenting, the access, the need for open sci - electronic medical/health records (EMRs/EHRs), ence, the rights of donors to retain a property claim for example the Electronic Medical Records and or control over their samples and data. In particular Genomics (eMERGE) network 2, the Vanderbilt it is necessary to pay attention to the management Electronic Systems for Pharmacogeomic Assess - of healthcare information collected from patients in ment (VESPA) Project 3 and the Estonian different research projects 10,11 that can overwhelm Biobank, that was the first country to implement the original purpose of the research and the related a nationwide electronic health records system for informed consent . Furthermore, the ethical policy all citizens 4,5 . In these models of research , a has to take in consideration the fact that some pa - healthcare facility collects biological samples of tient’s EHR data are collected for healthcare pur - patients (as indicated above) for research and poses, without specific informed consent. stores them in a biobank, maintaining a linkage Biobanking enables a new way of doing re - between the sample and the patient’s EHR data, search: research projects are now frequently that constitute the primary source of phenotypic global, involving international teams, cross-bor - information. der networks of expertise, members of interna - Incorporating health information from partici - tional scientific societies belonging to different pant in Biobanking research aids in correlating institutions around the world, which pool and phenotypic information with genetic data and en - share samples and data ; this is crucial in order to vironmental data. make investigations more robust, more targeted, The advantages of collecting EHRs related to and more economical . The use of EHRs related genomic information stored in biobanks are cost- to biobanks may enable this new way of doing effctiveness and the potential to reuse genetic research, and it could benefit from the creation of and phenotypic information collected during a teams for phenotyping and genetic data analysis, patient’s lifespan, beyond the original study. This facilitating communication and spread of exper - is particularly true for dense genetic data such as tise among research teams. thosegenerated through genome-wide association In this new way of doing research harmoniza - studies or large-scale sequencing data 6. tion of governance is essential in practice, with the aim to make the most use of resources at our Biobanking Governance disposal , and the sharing of samples and data Although biobanking is not new, what distin - among researchers under common policies regu - guishes the present from the past is that the gen - lating the distribution and the use. Furthermore eral scientific context has changed, and the scale governance harmonization among different of biobanking activities, both in terms of the biobanks in different countries could ensure an quantity of samples and data, as well as the range equal protection of autonomy, dignity and funda - of disease areas and institutions now involved in mental rights of patients and research partici - biobanking have increased considerably, espe - pants, helping researchers in their activity and cially with the emergence of EHRs-linked ensuring a flexible framework that should not be biobanks . The other significant change is that an obstacle for the technical progress of the these collections are being configured so that biobank, and offering to all communities the op - they can be used as a resource for the whole sci - portunity to benefit from the results obtained. entific community. Governance harmonization could guarantee ac - In these last years the importance of biobanks cess controls and security measures in order to is testified by the great increase, in the scientific avoid breach of partecipants’ privacy and the risk literature, of papers that consider new applica - of stigmatization of specific groups.

4183 L. Caenazzo, P. Tozzo, A. Borovecki

For these reasons biobank harmonization has development of a fair and equitable system of ac - become a key issue in the field of biobanking, cess for researchers wishing to use the biobanks both in terms of regulation and governance, with and the benefits of shared results 7. respect to peculiar challenges of EHRs-related In this context, the development of ethical biobank . guidelines and a systematic involvement of Ethics In response to biobanks challenges, different Committees – which should be networked – could regulation and governance mechanisms have be useful instruments to address and discuss new been proposed and adopted across Europe, and a kind of ethical issues, rarely encountered and so great effort has been made to achieve governance far applied only in the Ethics Committees of big harmonization and standardization of regulation national biobanks, such as the UK Biobank EGC in the European context, as shown in different (Ethics and Governance Council) 18 . European projects 12,13 . In general, regulation ap - plies to the formal structures of law and legally constituted regulatory bodies . In the specific field Biobanks and Ethics Committees of biobanking, it may be difficult to achieve ab - Governance has emerged as a prime principle solute standardization of regulating legal instru - in the role of different types of Ethics Commit - ments, given the great variability of national reg - tees when it comes to biobanking practices. ulatory frameworks, which are often fragmented. Ethics Committees have been permanent fix - Furthermore, research practices in different med - ture of healthcare provision during the last three ical areas could be different. All these factors decades. may cause conflicts between a necessary level of The function and the purpose of the research diversity in ethical positions and an indispensable Ethics Committee is to ensure that the research is common base of principles and procedures to designed in conformity to relevant ethical stan - manage these issues in order to harmonize the dards. However, it also has the task of assessing procedures. A European legal instrument cover - the adequacy of the design of the study re - ing clearly the requirements for biobanking is dif - viewed 19 . ficult to attain and diversity among Countries in The healthcare Ethics Committee (HEC) or the regulation of biobanks still remain 14-16 . For ex - clinical Ethics Committee or hospital Ethics ample there are different national requirement of Committee deals with making treatment deci - samples and data across borders which creates sions. HECs are usually not required by the law, difficulties when samples and data must be shared and they are composed of individuals from dif - within international biobanks consortia, re - ferent backgrounds with different professional searchers face with different levels of accessibili - perspectives and experiences who come together ty among countries, with the risk of multiple ap - and discuss problematic issues involving con - plications for the same research project to differ - flicting values in clinical settings. In general, ent regulatory institutions 17 . healthcare Ethics Committees have three func - Rather than regulation, governance should be tions: education, case review and recommenda - considered as an overarching concept that in - tion or formation of policies and guidelines 20,21 . cludes regulation and also less constructed mech - Another type of Ethics Committee is repre - anisms that indicate behavioral norms. For har - sented National Bioethics Committees, which are monization in governance, there is an urgent governmental bodies usually formed by the gov - need of an evaluation of existing governance sys - ernments according to specific legal require - tems to see how they should be modified, adapt - ments. Their main function is to issue recom - ed or improved to accommodate , among mendations and opinions on specific ethical is - biobanks, the different research practices . The sues, to participate in the drafting of legal provi - purpose of this harmonization is obtaining com - sions and to encourage and participate in public parable results and sharing useful biological sam - debate on current bioethical issues. Their recom - ples and data , maximizing the use, productivity, mendations are usually not binding, but rather of and value of biobanks. a consultatory nature 22 . New ethical issues coming into the biobanking The great variability of types of biobanks rais - debate concern the responsibilities and role of es different issues for different types of Ethics custodians of the biobank in relation to research Committees . participants and other stakeholders, the kinds of National Bioethics Committees could be es - ownership rights that exist over the samples, the sential in drafting general biobanking regulation

4184 Ethical governance in biobanks linked to electronic health records and National biobanks guidelines and their opin - tant, the patients’ and researchers’ representative, ion could be of paramount importance, in ab - the epidemiologist. sence of legal standards, as referring statement of With the widespread use of electronic health soft law, meaning a normative instrument “weak - records linked to biological specimens in health er” than the binding force of the traditional law. care, the Committee could draft The functions of a healthcare Ethics Commit - best practice and ethical guidelines for the utili - tee may be of importance in writing ethical sation of the EHRs as a tool for genetic research, guidelines establishing rules and procedures and addressing concerns on accessibility, return of in discussing particularly complex cases in - results and privacy and help in educate patients volved in biobanking management, for example and healthcare providers. Furthermore, bioethics particular donors’ requests on withdrawal of con - committee could be useful in providing ethically sent or samples, on the management of left over oriented strategies for combining consent to re - tissues from diagnostic or therapeutic procedures search with the management of access to EHR. or tissues procured form deceased individuals, It is clear that depending on the type of and communicating these guidelines both to biobank being developed the Ethics Committee healthcare professionals and patients . may have different functions and tasks . In certain Finally, when it comes to biobanking, it may cases it may be more of a research Ethics Com - be important, especially for biobanks with a large mittee, or may be more similar to a health care number of data samples, to establish their own Ethics Committee. Depending on the national Ethics Committee. A good biobank Ethics Com - level of biobank organization, it may have tasks mittee should embody all of the functions of a similar to a national bioethics committee but still healthcare Ethics Committee, research Ehics retain its primary function. Committee and national bioethics committee as a sort of a mixed type Ethics Committee. A biobank-specific Ethics Committee could be Conclusions seen as a new and type of Ethics Committee, dif - ferent from the three type of currently existing A biobank-specific Ethics Committee could be Ethics Committee that are: research Ethics Com - applied to each biobank with possible different mittee, healthcare Ethics Committee and national functions and tasks in relation to the type of bioethics committee . McHale has called it “spe - biobank. In particular, considering the possible cialist ethics or ethics and governance commit - use of electronic health record data linked to bio - tee” , for the first time referring to the UK logical specimens in biobanking research, this biobank project, as an independent guardian of specific Ethics Committee could draft best prac - the frameworks and legal instruments that safe - tice and ethical guidelines for the utilization of guard the project of UK Biobank. We suggest the EHRs as a tool for genetic research, address - this type of Ethics Committee to be applied to ing concerns on accessibility, return of results each biobank, with possible different functions. and privacy and help in educate patients and It may monitor and the inform the public about healthcare providers. the research done and functioning of the Specific focus groups within these committee biobank ; it could be useful in fostering interests should be aware of the specific incoming organi - of research participants, giving approval for data zational, ethical, legal and social challenges of exchange and transfer, revising guidelines and EHRs-related biobanks research, which may be working frameworks , if needed , regarding re - different from those routinely analyzed within cruitment access or handling complaints . Anoth - their daily activities. er function of this new Ethics Committee could A future effort towards implementation of rel - be monitoring and managing the collaboration evant ethical guidelines could help governance between public and private biobanks , with the harmonization in response to new challenges in purpose to guarantee equitable access to genome- these biobanks structure, as well as systematic related EHRs . Finally, one of its functions stands coordination and involvement of biobanks-spe - on its own and this is the function of governance cific Ethics Committees could ensure a consis - in a specific scope of that specific biobank 23 . The tent and coherent ethical framework for biobanks composition of this Ethics Committee can not be to operate successfully, empowering their en - separated by the presence of essential figures forcement and mitigating differences in samples such as the biobank’s director, the ethics consul - and data collection and management .

4185 L. Caenazzo, P. Tozzo, A. Borovecki

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