Genetic research has taken a tremendous rise during the ...



Pediatric Biobanks: Recommendations of the European Society of Human GeneticsHens K, XXX for the European Society of Human GeneticsIntroductionGenetic research has made tremendous advances during the last decade. Such research tries to discover the functioning of genes in relation to certain conditions and traits. In order to effectively perform this research, collections of DNA are needed. Human biological material such as blood, extracted DNA and other tissue, often stored with medical data from the donor, is an important source for genetic research. A collection of such material is often referred to as a biobank, although opinions differ as to what is the actual definition of a biobank ADDIN REFMGR.CITE <Refman><Cite><Author>Desch&#xEA;nes</Author><Year>2001</Year><RecNum>47</RecNum><IDText>Human genetic research, DNA banking and consent: a question of &apos;form&apos;?</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>47</Ref_ID><Title_Primary>Human genetic research, DNA banking and consent: a question of &apos;form&apos;?</Title_Primary><Authors_Primary>Desch&#xEA;nes,Myl&#xE8;ne</Authors_Primary><Authors_Primary>Glass,Kathleen Cranley</Authors_Primary><Authors_Primary>Cardinal,Genevi&#xE8;ve</Authors_Primary><Authors_Primary>Knoppers,Bartha Maria</Authors_Primary><Date_Primary>2001</Date_Primary><Keywords>*DNA</Keywords><Keywords>chemistry</Keywords><Keywords>*Gene Library</Keywords><Keywords>*Genetics,Medical</Keywords><Keywords>commercialization</Keywords><Keywords>Confidentiality</Keywords><Keywords>Confidentiality</Keywords><Keywords>legislation &amp; jurisprudence</Keywords><Keywords>Consent</Keywords><Keywords>Consent Forms</Keywords><Keywords>Ethics,Medical</Keywords><Keywords>example consent form</Keywords><Keywords>genetic</Keywords><Keywords>Genetic Screening</Keywords><Keywords>legislation &amp; jurisprudence</Keywords><Keywords>Humans</Keywords><Keywords>Informed Consent</Keywords><Keywords>Research</Keywords><Keywords>Risk Assessment</Keywords><Reprint>Not in File</Reprint><Start_Page>221</Start_Page><End_Page>239</End_Page><Periodical>Clinical Genetics</Periodical><Volume>59</Volume><Issue>4</Issue><User_Def_1>Kaft E</User_Def_1><ISSN_ISBN>0009-9163</ISSN_ISBN><Web_URL> name="System">Clinical Genetics</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Elger</Author><Year>2006</Year><RecNum>18</RecNum><IDText>Consent and anonymization in research involving biobanks: differing terms and norms present serious barriers to an international framework</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>18</Ref_ID><Title_Primary>Consent and anonymization in research involving biobanks: differing terms and norms present serious barriers to an international framework</Title_Primary><Authors_Primary>Elger,Bernice S.</Authors_Primary><Authors_Primary>Caplan,Arthur L.</Authors_Primary><Date_Primary>2006</Date_Primary><Keywords>*Biological Specimen Banks</Keywords><Keywords>standards</Keywords><Keywords>Anonymous Testing</Keywords><Keywords>Confidentiality</Keywords><Keywords>Consent</Keywords><Keywords>Consent Forms</Keywords><Keywords>Europe</Keywords><Keywords>Guidelines</Keywords><Keywords>Humans</Keywords><Keywords>Research</Keywords><Keywords>Informed Consent</Keywords><Reprint>Not in File</Reprint><Start_Page>661</Start_Page><End_Page>666</End_Page><Periodical>EMBO Rep</Periodical><Volume>7</Volume><Issue>7</Issue><User_Def_1>Kaft B</User_Def_1><ISSN_ISBN>1469-221X</ISSN_ISBN><Web_URL><u> name="System">EMBO Rep</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Godard</Author><Year>2003</Year><RecNum>29</RecNum><IDText>Data storage and DNA banking for biomedical research: informed consent, confidentiality, quality issues, ownership, return of benefits. A professional perspective</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>29</Ref_ID><Title_Primary>Data storage and DNA banking for biomedical research: informed consent, confidentiality, quality issues, ownership, return of benefits. A professional perspective</Title_Primary><Authors_Primary>Godard,B&#xE9;atrice</Authors_Primary><Authors_Primary>Aym&#xE9;,S&#xE9;gol&#xE8;ne</Authors_Primary><Authors_Primary>Schmidtke,J&#xF6;rg</Authors_Primary><Authors_Primary>Cassiman,Jean-Jacques</Authors_Primary><Date_Primary>2003</Date_Primary><Keywords>*Biomedical Research</Keywords><Keywords>*Confidentiality</Keywords><Keywords>*DNA</Keywords><Keywords>*Information Storage and Retrieval</Keywords><Keywords>standards</Keywords><Keywords>*Informed Consent</Keywords><Keywords>*Ownership</Keywords><Keywords>*Quality Assurance,Health Care</Keywords><Keywords>Consent</Keywords><Keywords>Europe</Keywords><Keywords>France</Keywords><Keywords>Guidelines</Keywords><Keywords>Humans</Keywords><Keywords>Informed Consent</Keywords><Keywords>Ownership</Keywords><Keywords>Research</Keywords><Keywords>return of benefits</Keywords><Reprint>Not in File</Reprint><Start_Page>S88</Start_Page><End_Page>S122</End_Page><Periodical>EUROPEAN JOURNAL OF HUMAN GENETICS</Periodical><Volume>11Suppl2</Volume><Issue>December</Issue><User_Def_1>Kaft Algemeen</User_Def_1><ISSN_ISBN>1018-4813</ISSN_ISBN><Web_URL> name="System">EUROPEAN JOURNAL OF HUMAN GENETICS</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Rothstein</Author><Year>2005</Year><RecNum>24</RecNum><IDText>Expanding the ethical analysis of biobanks</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>24</Ref_ID><Title_Primary>Expanding the ethical analysis of biobanks</Title_Primary><Authors_Primary>Rothstein,Mark A.</Authors_Primary><Date_Primary>2005</Date_Primary><Keywords>Bankruptcy--Legislation and Jurisprudence</Keywords><Keywords>Consent</Keywords><Keywords>Consent--Legislation and Jurisprudence</Keywords><Keywords>Feedback</Keywords><Keywords>genetic</Keywords><Keywords>Health Insurance Portability and Accountability Act--Legislation and Jurisprudence</Keywords><Keywords>Informed Consent</Keywords><Keywords>privacy</Keywords><Keywords>Privacy and Confidentiality--Legislation and Jurisprudence</Keywords><Keywords>Research</Keywords><Keywords>Research Subjects</Keywords><Keywords>Research Subjects--Legislation and Jurisprudence</Keywords><Keywords>Risk Assessment</Keywords><Keywords>Tissue Banks--Legislation and Jurisprudence</Keywords><Keywords>United States</Keywords><Reprint>Not in File</Reprint><Start_Page>89</Start_Page><End_Page>101</End_Page><Periodical>Journal of Law, Medicine &amp; Ethics</Periodical><Volume>33</Volume><Issue>1</Issue><User_Def_1>Kaft Algemeen</User_Def_1><ISSN_ISBN>1073-1105</ISSN_ISBN><Web_URL> name="System">Journal of Law, Medicine &amp; Ethics</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(1,2,3,4). In the following text we shall take a functional approach: we shall use the term ‘biobank’ to refer to each collection of human biological materials and associated medical information that can or is used for non-therapeutic scientific research, especially genetic research. Collections of tissue samples exist in different forms. Some are founded with the study of one or some conditions in mind and contain tissue from patients with that disease. Some contain materials originally gathered for diagnostics purposes and then secondarily used for non-therapeutic research. For example, collections of genetic material in the genetic centers in university hospitals contain diagnostics material, but could form a resource to study specific diseases. Population or cohort studies often also have an associated biobank. Such studies collect phenotypic information from a cohort or part of a population and try to link this information with genetic information. Such studies extend over different years and form a research resource further therapeutic research, the purpose of which is often not defined at the inception of the study. Many biobanks contain samples and information from competent adults, which allows for individual informed consent. This paper will however focus on minors.In the last century, the status of children has significantly changed: children have now acquired specific rights. This culminated in the Convention on the Rights of the Child ADDIN REFMGR.CITE <Refman><Cite><Year>1998</Year><RecNum>66</RecNum><IDText>United Nations Convention on the Rights of the Child</IDText><MDL Ref_Type="Report"><Ref_Type>Report</Ref_Type><Ref_ID>66</Ref_ID><Title_Primary>United Nations Convention on the Rights of the Child</Title_Primary><Date_Primary>1998</Date_Primary><Keywords>Child</Keywords><Reprint>Not in File</Reprint><ZZ_WorkformID>24</ZZ_WorkformID></MDL></Cite></Refman>(5). This is a legally binding document containing principles founded on respect for the dignity and worth of each individual, regardless of race, color, gender, language, religion, opinions, origins, wealth, birth status or ability. It has as an aim to protect children, to help meet their basic needs and to expand their opportunities to reach their full potential. Also in medical research the status of children has changed. In the past, the history of children as medical research subjects has been characterized by malpractices, with little respect for understanding children’s rights and concerns ADDIN REFMGR.CITE <Refman><Cite><Author>Lederer</Author><Year>1994</Year><RecNum>8</RecNum><IDText>Historical overview: Pediatric experimentation</IDText><MDL Ref_Type="Book Chapter"><Ref_Type>Book Chapter</Ref_Type><Ref_ID>8</Ref_ID><Title_Primary>Historical overview: Pediatric experimentation</Title_Primary><Authors_Primary>Lederer,Susan E.</Authors_Primary><Authors_Primary>Grodin,Michael A.</Authors_Primary><Date_Primary>1994</Date_Primary><Keywords>children</Keywords><Keywords>ethics</Keywords><Keywords>Research</Keywords><Keywords>Research Subjects</Keywords><Keywords>SUBJECT</Keywords><Reprint>Not in File</Reprint><Start_Page>3</Start_Page><End_Page>25</End_Page><Title_Secondary>Children as Research Subjects. Science, Ethics &amp; Law</Title_Secondary><Authors_Secondary>Grodin,Michael A.</Authors_Secondary><Authors_Secondary>Glantz,Leonard H.</Authors_Secondary><Pub_Place>New York and Oxford</Pub_Place><Publisher>Oxford University Press</Publisher><ZZ_WorkformID>3</ZZ_WorkformID></MDL></Cite></Refman>(6). Nowadays, children are considered as subjects in need of extra protection due to their vulnerability. In this respect, the principle of minimal risk is often quoted to set some standard on the type of non-therapeutic research that can be performed with children ADDIN REFMGR.CITE <Refman><Cite><Author>Kodish</Author><Year>2005</Year><RecNum>69</RecNum><IDText>Ethics and research with children: An introduction</IDText><MDL Ref_Type="Book Chapter"><Ref_Type>Book Chapter</Ref_Type><Ref_ID>69</Ref_ID><Title_Primary>Ethics and research with children: An introduction</Title_Primary><Authors_Primary>Kodish,Eric</Authors_Primary><Date_Primary>2005</Date_Primary><Keywords>children</Keywords><Keywords>ethics</Keywords><Keywords>Research</Keywords><Reprint>Not in File</Reprint><Start_Page>3</Start_Page><End_Page>25</End_Page><Title_Secondary>Ethics and research with children. A case-based approach</Title_Secondary><Authors_Secondary>Kodish,Eric</Authors_Secondary><Issue>1</Issue><Pub_Place>Oxford and New York</Pub_Place><Publisher>Oxford University Press</Publisher><ZZ_WorkformID>3</ZZ_WorkformID></MDL></Cite><Cite><Author>Pinxten</Author><Year>2009</Year><RecNum>286</RecNum><IDText>Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>286</Ref_ID><Title_Primary>Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials</Title_Primary><Authors_Primary>Pinxten,W.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Date_Primary>2009/10</Date_Primary><Keywords>Adult</Keywords><Keywords>Belgium</Keywords><Keywords>Biomedical Research</Keywords><Keywords>ethics</Keywords><Keywords>Ethics,Research</Keywords><Keywords>European Union</Keywords><Keywords>Human Rights</Keywords><Keywords>Humans</Keywords><Keywords>legislation &amp; jurisprudence</Keywords><Keywords>Minors</Keywords><Keywords>Pediatrics</Keywords><Keywords>Research</Keywords><Keywords>Research Subjects</Keywords><Reprint>Not in File</Reprint><Start_Page>1225</Start_Page><End_Page>1234</End_Page><Periodical>Eur J Pediatr</Periodical><Volume>168</Volume><Issue>10</Issue><Address>Centre for Biomedical Ethics and Law, KULeuven, 3000 Leuven, Belgium. wim.pinxten@med.kuleuven.be</Address><Web_URL>PM:19142660</Web_URL><ZZ_JournalStdAbbrev><f name="System">Eur J Pediatr</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(7,8). Minimal risk is understood as a risk that is not higher than what a child would encounter in everyday life. Also, the risk is measured against the direct benefits of a procedure: if a participant receives much benefit from the procedure, the risk that he or she is allowed to endure may be higher ADDIN REFMGR.CITE <Refman><Cite><Author>Bernard-Bonnin</Author><Year>2009</Year><RecNum>249</RecNum><IDText>Les principes &#xE9;thiques de la recherche biom&#xE9;dicale avec les enfants</IDText><MDL Ref_Type="Book Chapter"><Ref_Type>Book Chapter</Ref_Type><Ref_ID>249</Ref_ID><Title_Primary>Les principes &#xE9;thiques de la recherche biom&#xE9;dicale avec les enfants</Title_Primary><Authors_Primary>Bernard-Bonnin,Anne-Claude</Authors_Primary><Date_Primary>2009</Date_Primary><Keywords>France</Keywords><Reprint>Not in File</Reprint><Start_Page>415</Start_Page><End_Page>424</End_Page><Title_Secondary>La recherche clinique avec les enfants: &#xE0; la crois&#xE9;e de l&apos; &#xE9;thique et du droit. Belgique, France, Qu&#xE9;bec</Title_Secondary><Authors_Secondary>Delfosse,Marie-Luce</Authors_Secondary><Authors_Secondary>Parizeau,Marie-H&#xE9;l&#xE8;ne</Authors_Secondary><Authors_Secondary>Amann,Jean-Paul</Authors_Secondary><Pub_Place>Louvain-la-Neuve</Pub_Place><Publisher>Anthemis</Publisher><ZZ_WorkformID>3</ZZ_WorkformID></MDL></Cite></Refman>(9). Indeed, another concept that is frequently used, especially in the context of pediatric clinical trials, is that of benefit. For example, in the European normative frameworks for clinical trials it is stated that research on minors can be done if there is a necessity to do so, either because there might be some direct benefit to the participant, or because the research would benefit children with the same condition ADDIN REFMGR.CITE <Refman><Cite><Author>Pinxten</Author><Year>2009</Year><RecNum>286</RecNum><IDText>Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>286</Ref_ID><Title_Primary>Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials</Title_Primary><Authors_Primary>Pinxten,W.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Date_Primary>2009/10</Date_Primary><Keywords>Adult</Keywords><Keywords>Belgium</Keywords><Keywords>Biomedical Research</Keywords><Keywords>ethics</Keywords><Keywords>Ethics,Research</Keywords><Keywords>European Union</Keywords><Keywords>Human Rights</Keywords><Keywords>Humans</Keywords><Keywords>legislation &amp; jurisprudence</Keywords><Keywords>Minors</Keywords><Keywords>Pediatrics</Keywords><Keywords>Research</Keywords><Keywords>Research Subjects</Keywords><Reprint>Not in File</Reprint><Start_Page>1225</Start_Page><End_Page>1234</End_Page><Periodical>Eur J Pediatr</Periodical><Volume>168</Volume><Issue>10</Issue><Address>Centre for Biomedical Ethics and Law, KULeuven, 3000 Leuven, Belgium. wim.pinxten@med.kuleuven.be</Address><Web_URL>PM:19142660</Web_URL><ZZ_JournalStdAbbrev><f name="System">Eur J Pediatr</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(8). The risks may also be proportional to the net benefits of the research for the child participating in the clinical trial. Another principle quoted in the context of non-therapeutic research with minors is that of subsidiarity: such research can only be done if it cannot be done on adults.Genetic research on stored tissue samples from children is growing steadily. Apart from acquired somatic mutations DNA remains stable throughout a lifetime. Most genetic research combines the study of DNA with medical and lifestyle data. Nowadays, the influence of external factors (even in utero) on gene expression is commonly accepted. Conditions such as allergies, asthma, food intolerances, diabetes and obesity can be attributed to a combination of genetic and lifestyle factors. Large-scale systematic research using tissue samples can shed some light on the development of these conditions. There are also different forms of pediatric biobanks. Large cohort studies follow children from birth onwards into adulthood, collecting phenotypic and lifestyle data together with genetic information. Conditions that occur during childhood, such as childhood cancer and birth defects are studied using material from children that have these conditions. Existing collections, such as blood spot cards, may also form a good resource for (anonymous) genetic epidemiological research and contain de facto material from children.Genetic research using tissue samples from children poses a number of ethical issues that are not analogous to those raised by adult biobanks or by pediatric clinical trials, as minors have no or limited autonomy and capacity to consent to research. Also, these questions are different from those raised by pediatric clinical trials, although many of the concepts, such as minimal risk and benefit, that are predominant in the literature and guidelines on pediatric biobanks, are deduced from the clinical trials context. However, the fact that we are talking here about genetic research, done on stored tissue samples rather than the child’s body, and the fact that such research is non-therapeutic per se and does not generate direct benefit for the participant, raises different issues. This makes the ethical discussion on clinical trials not directly transferrable to the context of pediatric biobanks. In this document we provide recommendations as to the use of stored tissue samples from minors for genetic research. We first provide some background as to the rationale behind these recommendations, followed by the recommendations themselves at the back of the document. In the rest of this document, we shall use the term ‘minor’ to denote individuals from birth onwards till they reach legal competence. A proportion of the minors donating tissue for genetic research will never reach legal competence. This issue raises specific ethical concerns which may not be totally covered by the recommendations in this document. For example, the section about reconsent may not apply. However, as this is an even more vulnerable population, the section about risks and benefits does apply also in this context.Genetic information can potentially reveal information about the health status of the individual. Research on genetic information should therefore be done in a context of good governance and data protection. Indeed, although questions about genetic privacy are important and are dealt with extensively in the literature on biobanks, risks related to privacy should be solved on two levels. First, society in general should operate in a framework of just institutions and genetic privacy laws. Secondly, the governance of the biobank is important and should consist of appropriate data protection policies of biobanks, especially when samples are shared. For example, samples and data should be coded, so that the identity of the donor is not available to the researcher using the sample. Such protections provide a solid basis for any biobank activity, whether the participants are minors or adults. Hence, in these recommendations we assume that these protections are already in place ADDIN REFMGR.CITE <Refman><Cite><Author>Hens</Author><Year>2011</Year><RecNum>281</RecNum><IDText>Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>281</Ref_ID><Title_Primary>Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research</Title_Primary><Authors_Primary>Hens,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Authors_Primary>Cassiman,J.J.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Date_Primary>2011/2/23</Date_Primary><Keywords>children</Keywords><Keywords>ethics</Keywords><Keywords>genetic</Keywords><Keywords>Research</Keywords><Keywords>solidarity</Keywords><Reprint>Not in File</Reprint><Periodical>J.Pediatr.</Periodical><Address>Centre for Biomedical Ethics and Law, Katholieke Universiteit Leuven, Leuven, Belgium</Address><Web_URL>PM:21349539</Web_URL><ZZ_JournalStdAbbrev><f name="System">J.Pediatr.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Hoedemaekers</Author><Year>2007</Year><RecNum>256</RecNum><IDText>Solidarity and justice as guiding principles in genomic research</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>256</Ref_ID><Title_Primary>Solidarity and justice as guiding principles in genomic research</Title_Primary><Authors_Primary>Hoedemaekers,R.</Authors_Primary><Authors_Primary>Gordijn,B.</Authors_Primary><Authors_Primary>Pijnenburg,M.</Authors_Primary><Date_Primary>2007/7</Date_Primary><Keywords>Consent</Keywords><Keywords>ethics</Keywords><Keywords>Ethics,Research</Keywords><Keywords>FUTURE</Keywords><Keywords>Genomics</Keywords><Keywords>health</Keywords><Keywords>Humans</Keywords><Keywords>Informed Consent</Keywords><Keywords>justice</Keywords><Keywords>Personal Autonomy</Keywords><Keywords>Research</Keywords><Keywords>Social Justice</Keywords><Keywords>solidarity</Keywords><Keywords>standards</Keywords><Keywords>trends</Keywords><Keywords>Universities</Keywords><Reprint>Not in File</Reprint><Start_Page>342</Start_Page><End_Page>350</End_Page><Periodical>Bioethics.</Periodical><Volume>21</Volume><Issue>6</Issue><Address>Dept of Ethics, Philosophy and History of Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, Netherlands. rhoed@hetnet.nl</Address><Web_URL>PM:17845458</Web_URL><ZZ_JournalStdAbbrev><f name="System">Bioethics.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(10,11). The ethical issues arising from diseased based collections may be different from those arising from population based studies, and may have a different governance structure. Disease based collections may be relatively small scale and patient organisations may play a role. Also, the ethical issues arising from the use of samples gathered in a diagnostic context may be different from those arising from the use of samples primarily for research. Where applicable, we shall make a distinction between different types of biobanks in the text below. ConcernsRisksWe assume that for medical research with the potential to aid and treat certain diseases researchers can appeal to the principle of solidarity to enroll participants ADDIN REFMGR.CITE <Refman><Cite><Author>Hoedemaekers</Author><Year>2007</Year><RecNum>256</RecNum><IDText>Solidarity and justice as guiding principles in genomic research</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>256</Ref_ID><Title_Primary>Solidarity and justice as guiding principles in genomic research</Title_Primary><Authors_Primary>Hoedemaekers,R.</Authors_Primary><Authors_Primary>Gordijn,B.</Authors_Primary><Authors_Primary>Pijnenburg,M.</Authors_Primary><Date_Primary>2007/7</Date_Primary><Keywords>Consent</Keywords><Keywords>ethics</Keywords><Keywords>Ethics,Research</Keywords><Keywords>FUTURE</Keywords><Keywords>Genomics</Keywords><Keywords>health</Keywords><Keywords>Humans</Keywords><Keywords>Informed Consent</Keywords><Keywords>justice</Keywords><Keywords>Personal Autonomy</Keywords><Keywords>Research</Keywords><Keywords>Social Justice</Keywords><Keywords>solidarity</Keywords><Keywords>standards</Keywords><Keywords>trends</Keywords><Keywords>Universities</Keywords><Reprint>Not in File</Reprint><Start_Page>342</Start_Page><End_Page>350</End_Page><Periodical>Bioethics.</Periodical><Volume>21</Volume><Issue>6</Issue><Address>Dept of Ethics, Philosophy and History of Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, Netherlands. rhoed@hetnet.nl</Address><Web_URL>PM:17845458</Web_URL><ZZ_JournalStdAbbrev><f name="System">Bioethics.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Chadwick</Author><Year>2001</Year><RecNum>81</RecNum><IDText>Solidarity and equity: new ethical frameworks for genetic databases</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>81</Ref_ID><Title_Primary>Solidarity and equity: new ethical frameworks for genetic databases</Title_Primary><Authors_Primary>Chadwick,Ruth</Authors_Primary><Authors_Primary>Berg,K&#xE4;re.</Authors_Primary><Date_Primary>2001</Date_Primary><Keywords>*Databases</Keywords><Keywords>legislation &amp; jurisprudence</Keywords><Keywords>*Ethics,Medical</Keywords><Keywords>Confidentiality</Keywords><Keywords>Consent</Keywords><Keywords>Databases</Keywords><Keywords>DNA</Keywords><Keywords>*genetics</Keywords><Keywords>genetic</Keywords><Keywords>Genetics,Medical</Keywords><Keywords>legislation &amp; jurisprudence</Keywords><Keywords>Humans</Keywords><Keywords>Informed Consent</Keywords><Keywords>Patents</Keywords><Keywords>Research</Keywords><Keywords>solidarity</Keywords><Reprint>In File</Reprint><Start_Page>318</Start_Page><End_Page>321</End_Page><Periodical>Nature Review Genetics</Periodical><Volume>2</Volume><Issue>4</Issue><User_Def_1>Kaft G</User_Def_1><ISSN_ISBN>1471-0056</ISSN_ISBN><Web_URL> name="System">Nature Review Genetics</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(11,12). However, when participants are minors, this principle only applies in a restricted sense. Minors have a limited autonomy and understanding, they are vulnerable subjects. Therefore, they should not be exposed to more than minimal risks ADDIN REFMGR.CITE <Refman><Cite><Author>Helgesson</Author><Year>2005</Year><RecNum>277</RecNum><IDText>Children, longitudinal studies, and informed consent</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>277</Ref_ID><Title_Primary>Children, longitudinal studies, and informed consent</Title_Primary><Authors_Primary>Helgesson,Gert</Authors_Primary><Date_Primary>2005</Date_Primary><Keywords>AUTONOMY-</Keywords><Keywords>Child</Keywords><Keywords>children</Keywords><Keywords>CHILDREN-</Keywords><Keywords>Consent</Keywords><Keywords>ETHICS-</Keywords><Keywords>information</Keywords><Keywords>Informed Consent</Keywords><Keywords>INFORMED-CONSENT</Keywords><Keywords>Longitudinal Studies</Keywords><Keywords>Parents</Keywords><Keywords>Research</Keywords><Reprint>Not in File</Reprint><Start_Page>307</Start_Page><Periodical>Medicine, Health Care and Philosophy</Periodical><Volume>8</Volume><Issue>3</Issue><User_Def_1>Kaft literature review</User_Def_1><ISSN_ISBN>1386-7423</ISSN_ISBN><ZZ_JournalFull><f name="System">Medicine, Health Care and Philosophy</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Hens</Author><Year>2011</Year><RecNum>281</RecNum><IDText>Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>281</Ref_ID><Title_Primary>Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research</Title_Primary><Authors_Primary>Hens,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Authors_Primary>Cassiman,J.J.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Date_Primary>2011/2/23</Date_Primary><Keywords>children</Keywords><Keywords>ethics</Keywords><Keywords>genetic</Keywords><Keywords>Research</Keywords><Keywords>solidarity</Keywords><Reprint>Not in File</Reprint><Periodical>J.Pediatr.</Periodical><Address>Centre for Biomedical Ethics and Law, Katholieke Universiteit Leuven, Leuven, Belgium</Address><Web_URL>PM:21349539</Web_URL><ZZ_JournalStdAbbrev><f name="System">J.Pediatr.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(10,13) (proportionality). Empirical research has shown that people worry most about the fact that non-therapeutic medical research should not burden children ADDIN REFMGR.CITE <Refman><Cite><Author>Hens</Author><Year>2011</Year><RecNum>280</RecNum><IDText>The Storage and Use of Biological Tissue Samples from Minors for Research: A Focus Group Study</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>280</Ref_ID><Title_Primary>The Storage and Use of Biological Tissue Samples from Minors for Research: A Focus Group Study</Title_Primary><Authors_Primary>Hens,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Authors_Primary>Cassiman,J.J.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Date_Primary>2011</Date_Primary><Keywords>Adult</Keywords><Keywords>Child</Keywords><Keywords>children</Keywords><Keywords>Decision Making</Keywords><Keywords>ethics</Keywords><Keywords>genetic</Keywords><Keywords>Genetic Research</Keywords><Keywords>information</Keywords><Keywords>methods</Keywords><Keywords>Minors</Keywords><Keywords>Parents</Keywords><Keywords>Qualitative Research</Keywords><Keywords>Research</Keywords><Keywords>SAMPLES</Keywords><Keywords>Trust</Keywords><Reprint>Not in File</Reprint><Start_Page>68</Start_Page><End_Page>76</End_Page><Periodical>Public Health Genomics</Periodical><Volume>14</Volume><Address>Centre for Biomedical Ethics and Law, Katholieke Universiteit Leuven, Leuven, Belgium</Address><Web_URL>PM:20389041</Web_URL><ZZ_JournalStdAbbrev><f name="System">Public Health Genomics</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Kaufman</Author><Year>2008</Year><RecNum>279</RecNum><IDText>Ethical implications of including children in a large biobank for genetic-epidemiologic research: A qualitative study of public opinion</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>279</Ref_ID><Title_Primary>Ethical implications of including children in a large biobank for genetic-epidemiologic research: A qualitative study of public opinion</Title_Primary><Authors_Primary>Kaufman,David</Authors_Primary><Authors_Primary>Geller,Gail</Authors_Primary><Authors_Primary>LeRoy,Lisa</Authors_Primary><Authors_Primary>Murphy,Juli</Authors_Primary><Authors_Primary>Scott,Joan</Authors_Primary><Authors_Primary>Hudson,Kathy</Authors_Primary><Date_Primary>2008</Date_Primary><Keywords>Adult</Keywords><Keywords>Attitude</Keywords><Keywords>Child</Keywords><Keywords>Cohort Studies</Keywords><Keywords>Consent</Keywords><Keywords>ethics</Keywords><Keywords>Genes</Keywords><Keywords>genetic</Keywords><Keywords>Guidelines</Keywords><Keywords>health</Keywords><Keywords>Parents</Keywords><Keywords>privacy</Keywords><Keywords>Public Opinion</Keywords><Keywords>Research</Keywords><Reprint>Not in File</Reprint><Start_Page>31</Start_Page><End_Page>39</End_Page><Periodical>American Journal of Medical Genetics, Part C Seminars in Medical Genetics</Periodical><Volume>148C</Volume><ZZ_JournalFull><f name="System">American Journal of Medical Genetics, Part C Seminars in Medical Genetics</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Goodenough</Author><Year>2004</Year><RecNum>36</RecNum><IDText>Ethical protection in research: including children in the debate</IDText><MDL Ref_Type="Book Chapter"><Ref_Type>Book Chapter</Ref_Type><Ref_ID>36</Ref_ID><Title_Primary>Ethical protection in research: including children in the debate</Title_Primary><Authors_Primary>Goodenough,T.</Authors_Primary><Authors_Primary>Williamson,E.</Authors_Primary><Authors_Primary>Kent,J.</Authors_Primary><Authors_Primary>Ashcroft,R.</Authors_Primary><Date_Primary>2004</Date_Primary><Keywords>children</Keywords><Keywords>Decision Making</Keywords><Keywords>Parents</Keywords><Keywords>Research</Keywords><Keywords>SUBJECT</Keywords><Reprint>Not in File</Reprint><Start_Page>55</Start_Page><End_Page>72</End_Page><Title_Secondary>Researchers and their &apos;subjects&apos;</Title_Secondary><Authors_Secondary>Smyth,Marie</Authors_Secondary><Authors_Secondary>Williamson,E.</Authors_Secondary><Issue>3</Issue><Pub_Place>Bristol</Pub_Place><Publisher>The Policy Press</Publisher><User_Def_1>Kaft literature review</User_Def_1><ZZ_WorkformID>3</ZZ_WorkformID></MDL></Cite></Refman>(14,15,16). The type of burden associated with biobank research depends on the type of biobank. Little burden is associated with research using collections that were gathered in a diagnostic context and that do not require further contact between participants and researchers. If new samples must be gathered, anesthetic creams should be used for venepunctures or, if possible, DNA should be gathered through mouth swabs in order to make the procedure less onerous for children. As small children’s wishes are unknown and as their preferences develop while they grow older, there is a risk that certain research would be counter to their wishes, especially since research on stored tissue samples can extend over time. Minors have the right to decide on the destination of their samples, and this right gradually increases when they develop more and more autonomy. Biobanks should make sure that they gradually put more emphasis on a child’s assent and eventually consent. This will be easier if the research requires extensive contact between researcher and participant. If such contact is not available, for example if diagnostics collections are reused for research purposes, a reasonable effort should be done to make young adults on the verge of majority aware that research is done on their samples and that there is a possibility to opt-out. For example, the ongoing or newly proposed research could be advertised on a website with the possibility to contact the researchers regarding the use of the samples.Benefits and subsidiarityAnother principle is that of benefit. Although the possibility of direct benefit to a minor is very small in case of non-therapeutic research, guidelines and literature mention also ‘group benefit’. This principle states that research on children can be done if it is for the benefit of other children with the same condition. This concept of clinical trials’ ethics cannot be easily transferred to genetic research, as there are more steps needed towards an actual cure or treatment of conditions ADDIN REFMGR.CITE <Refman><Cite><Author>Hens</Author><Year>2011</Year><RecNum>281</RecNum><IDText>Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>281</Ref_ID><Title_Primary>Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research</Title_Primary><Authors_Primary>Hens,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Authors_Primary>Cassiman,J.J.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Date_Primary>2011/2/23</Date_Primary><Keywords>children</Keywords><Keywords>ethics</Keywords><Keywords>genetic</Keywords><Keywords>Research</Keywords><Keywords>solidarity</Keywords><Reprint>Not in File</Reprint><Periodical>J.Pediatr.</Periodical><Address>Centre for Biomedical Ethics and Law, Katholieke Universiteit Leuven, Leuven, Belgium</Address><Web_URL>PM:21349539</Web_URL><ZZ_JournalStdAbbrev><f name="System">J.Pediatr.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(10). The principle of subsidiarity, that genetic research on stored tissue samples can only be done if the same research cannot be done on samples from adults is more straightforward. This principle can be interpreted rather broadly. For example, it does not only mean that genetic biobank research can be done regarding pediatric diseases, but also regarding other diseases that may be caused by factors that occur during childhood, or that in the case of scarce resources tissue of children can be used if adult tissue is unavailable. ConsentA much discussed issue in the context of biobanks in general is the question of consent. With pediatric biobanks, this question is even more complicated ADDIN REFMGR.CITE <Refman><Cite><Author>Shickle</Author><Year>2006</Year><RecNum>22</RecNum><IDText>The consent problem within DNA biobanks</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>22</Ref_ID><Title_Primary>The consent problem within DNA biobanks</Title_Primary><Authors_Primary>Shickle,Darren</Authors_Primary><Date_Primary>2006</Date_Primary><Keywords>*Biological Specimen Banks</Keywords><Keywords>ethics</Keywords><Keywords>*DNA</Keywords><Keywords>*Genetic Research</Keywords><Keywords>ethics</Keywords><Keywords>*Informed Consent</Keywords><Keywords>*Research Subjects</Keywords><Keywords>Adult</Keywords><Keywords>Attitude of Health Personnel</Keywords><Keywords>Cohort Studies</Keywords><Keywords>Consent</Keywords><Keywords>Consent Forms</Keywords><Keywords>Data Collection</Keywords><Keywords>Disclosure</Keywords><Keywords>DNA</Keywords><Keywords>Environment</Keywords><Keywords>Ethics</Keywords><Keywords>Great Britain</Keywords><Keywords>Health Status</Keywords><Keywords>Humans</Keywords><Keywords>information</Keywords><Keywords>Informed Consent</Keywords><Keywords>INFORMED-CONSENT</Keywords><Keywords>Life Style</Keywords><Keywords>Public Opinion</Keywords><Keywords>Research</Keywords><Keywords>Research Ethics</Keywords><Keywords>Research Subjects</Keywords><Keywords>Risk Factors</Keywords><Keywords>SUBJECT</Keywords><Keywords>United States</Keywords><Reprint>Not in File</Reprint><Start_Page>503</Start_Page><End_Page>519</End_Page><Periodical>Studies in History and Philosophy of Science</Periodical><Volume>37</Volume><Issue>3</Issue><User_Def_1>Kaft E</User_Def_1><ISSN_ISBN>1369-8486</ISSN_ISBN><ZZ_JournalFull><f name="System">Studies in History and Philosophy of Science</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(17). In the case of pediatric biobanks, parents or a legal guardian should give consent for the use of tissue samples from their children, although in some cases, such as epidemiological research on anonymized heel prick blood a notification may be sufficient. Although the consent of one parent is sufficient, we consider it best practice to enable both parents participate in the decision-making process. In the case of cohort studies or other studies where minors are enrolled specifically for research purposes the consent procedure will be straightforward as parents can be asked to consent and/or informed at the time of enrollment, although it will not always be possible to get consent from both parents. In the case where samples gathered in a diagnostic context are used for research, it may not always be possible to recontact parents. Dependant on requirements of local administrations consent need not always be written, but could also be accomplished by a system of notification, together with the possibility for withdrawing samples or for specifying whether samples gathered in a diagnostics context could be used for research.The scope of consent has two dimensions ADDIN REFMGR.CITE <Refman><Cite><Author>Hens</Author><Year>2011</Year><RecNum>283</RecNum><IDText>Children, biobanks and the scope of parental consent</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>283</Ref_ID><Title_Primary>Children, biobanks and the scope of parental consent</Title_Primary><Authors_Primary>Hens,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Authors_Primary>Cassiman,J.J.</Authors_Primary><Authors_Primary>Dierickx,K</Authors_Primary><Date_Primary>2011</Date_Primary><Keywords>biobanks</Keywords><Keywords>children</Keywords><Keywords>Consent</Keywords><Keywords>Parental Consent</Keywords><Reprint>In File</Reprint><Periodical>EUROPEAN JOURNAL OF HUMAN GENETICS</Periodical><ZZ_JournalStdAbbrev><f name="System">EUROPEAN JOURNAL OF HUMAN GENETICS</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(18). First there is the temporal scope of parental consent. In this respect, the fact that minors grow towards maturity and have a right to their own opinions implies that the temporal scope of parental consent is limited. Hence, young adults reaching the legal age of competence should be given the opportunity to withdraw their samples and data from biological sample collections if they do so wish. Preferably they should also be recontacted for renewed consent when they reach the legal age of competence. This may not in all cases be feasible, for example because many people change addresses. Therefore, the duty to recontact should be seen on a best effort basis. However, given the emergence of new technologies recontacting might become easier in the future. Moreover, pediatric research on stored tissue samples in the context of cohort studies or disease-specific studies in association with centers for medical genetics often assumes frequent contact between researcher and participant, which makes recontacting easier. In the case where there is frequent contact between the participant and the research team, the maturity of a minor to decide for themselves whether they would want to participate or not can be assessed by the researchers, parents and minors together on a case-by-case basis. If there was a one-time donation of the sample with no further contact with the participant, it will be hard to judge the maturity of the minor to decide. In such cases, a fixed age threshold can be used at which the minor is contacted or allowed to decide on the future of the sample and associated information. Or parents could be encouraged to recontact the center in order to fix a follow-up visit.Specific or broad consentThe content of consent is a second dimension. In the general discussion on consent and biobanks the question whether (adult) participants can be asked to consent to future unspecified consent (which is often referred to as broad consent) is still open ADDIN REFMGR.CITE <Refman><Cite><Author>Hansson</Author><Year>2006</Year><RecNum>208</RecNum><IDText>Should donors be allowed to give broad consent to future biobank research?</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>208</Ref_ID><Title_Primary>Should donors be allowed to give broad consent to future biobank research?</Title_Primary><Authors_Primary>Hansson,M.G.</Authors_Primary><Authors_Primary>Dillner,J.</Authors_Primary><Authors_Primary>Bartram,C.R.</Authors_Primary><Authors_Primary>Carlson,J.A.</Authors_Primary><Authors_Primary>Helgesson,G.</Authors_Primary><Date_Primary>2006/3</Date_Primary><Keywords>Confidentiality</Keywords><Keywords>Consent</Keywords><Keywords>ethics</Keywords><Keywords>Ethics,Medical</Keywords><Keywords>FUTURE</Keywords><Keywords>Genetic Predisposition to Disease</Keywords><Keywords>Humans</Keywords><Keywords>information</Keywords><Keywords>Informed Consent</Keywords><Keywords>INFORMED-CONSENT</Keywords><Keywords>Research</Keywords><Keywords>SAMPLES</Keywords><Keywords>Tissue Banks</Keywords><Keywords>Tissue Donors</Keywords><Keywords>Universities</Keywords><Reprint>Not in File</Reprint><Start_Page>266</Start_Page><End_Page>269</End_Page><Periodical>Lancet Oncol.</Periodical><Volume>7</Volume><Issue>3</Issue><Address>Centre for Bioethics at Karolinska Institute and Uppsala University, Uppsala, Sweden. Mats.Hansson@bioethics.uu.se</Address><Web_URL>PM:16510336</Web_URL><ZZ_JournalStdAbbrev><f name="System">Lancet Oncol.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Wendler</Author><Year>2006</Year><RecNum>186</RecNum><IDText>One-time general consent for research on biological samples</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>186</Ref_ID><Title_Primary>One-time general consent for research on biological samples</Title_Primary><Authors_Primary>Wendler,David</Authors_Primary><Date_Primary>2006/3/4</Date_Primary><Keywords>Biological Products -- Ethical Issues</Keywords><Keywords>Consent</Keywords><Keywords>Consent (Research) -- Ethical Issues</Keywords><Keywords>Consent -- Psychosocial Factors</Keywords><Keywords>Consumer Attitudes</Keywords><Keywords>Organ Procurement</Keywords><Keywords>PubMed</Keywords><Keywords>Research</Keywords><Keywords>Research,Medical -- Ethical Issues</Keywords><Keywords>SAMPLES</Keywords><Keywords>Transplant Donors -- Psychosocial Factors</Keywords><Reprint>Not in File</Reprint><Start_Page>544</Start_Page><End_Page>547</End_Page><Periodical>BMJ: British Medical Journal</Periodical><Volume>332</Volume><Issue>7540</Issue><User_Def_1>Kaft E</User_Def_1><ISSN_ISBN>0959-8146</ISSN_ISBN><ZZ_JournalStdAbbrev><f name="System">BMJ: British Medical Journal</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Caulfield</Author><Year>2009</Year><RecNum>263</RecNum><IDText>Broad Consent in Biobanking: Reflections on Seemingly Insurmountable Dillemas</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>263</Ref_ID><Title_Primary>Broad Consent in Biobanking: Reflections on Seemingly Insurmountable Dillemas</Title_Primary><Authors_Primary>Caulfield,T.</Authors_Primary><Authors_Primary>Kaye,J.</Authors_Primary><Date_Primary>2009</Date_Primary><Keywords>Consent</Keywords><Reprint>Not in File</Reprint><Start_Page>85</Start_Page><End_Page>100</End_Page><Periodical>Medical Law International</Periodical><Volume>10</Volume><ZZ_JournalFull><f name="System">Medical Law International</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(19,20,21). There seems to be some agreement that broad consent is a feasible option, provided participants have the right to withdraw their samples and that there is ethics committee oversight of research protocols. In case of pediatric stored tissue samples this issue is further complicated by the fact that parents give consent for their children. Can parents be allowed to give broad consent for any future research on their children’s samples? On the one hand, as we stated before, minors, as persons growing towards autonomy and acquiring their own values, should be given the opportunity to express these values. On the other hand, it may also be an administrative overhead to recontact minors and/or their parents for each small change in the research protocol. Science is, however, not value-free: there is much general support for research that would lead to treatment or better understanding of medical conditions. It may be alright to assume that such research is part of the original parental consent and that children would not object to this. Other types of research, such as those related to behaviour or IQ are much more value-laden. Parents or their older children should be made aware of such research, and given the opportunity (not) to participate. Ethics committees may decide when research changes considerably from the original spirit of the consent and whether recontact is necessary. In any case, websites could be used to ensure transparency of the research, especially for those cases where donors can no longer be tracked.Return of ResultsShould individual results be returned in pediatric biobank research? Much research has been done in the field of predictive genetic testing and carrier testing with regard to minors and the availability of genetic information ADDIN REFMGR.CITE <Refman><Cite><Author>Borry</Author><Year>2009</Year><RecNum>243</RecNum><IDText>Genetic testing in asymptomatic minorsBackground considerations towards ESHG Recommendations</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>243</Ref_ID><Title_Primary>Genetic testing in asymptomatic minorsBackground considerations towards ESHG Recommendations</Title_Primary><Authors_Primary>Borry,Pascal</Authors_Primary><Authors_Primary>Evers-Kiebooms,Gerry</Authors_Primary><Authors_Primary>Cornel,Martina C.</Authors_Primary><Authors_Primary>Clarke,Angus</Authors_Primary><Authors_Primary>Dierickx,Kris</Authors_Primary><Date_Primary>2009/3/11=online</Date_Primary><Keywords>genetic</Keywords><Reprint>Not in File</Reprint><Start_Page>711</Start_Page><End_Page>719</End_Page><Periodical>Eur J Hum Genet</Periodical><Volume>17</Volume><Issue>6</Issue><Publisher>Macmillan Publishers Limited</Publisher><ISSN_ISBN>1018-4813</ISSN_ISBN><Web_URL> name="System">Eur J Hum Genet</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(22). The issue of returning individual results is much discussed in case of adult biobanks ADDIN REFMGR.CITE <Refman><Cite><Author>Bookman</Author><Year>2006</Year><RecNum>261</RecNum><IDText>Reporting genetic results in research studies: summary and recommendations of an NHLBI working group&#xA;199</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>261</Ref_ID><Title_Primary>Reporting genetic results in research studies: summary and recommendations of an NHLBI working group&#xA;199</Title_Primary><Authors_Primary>Bookman,Ebony B.</Authors_Primary><Authors_Primary>Langehorne,AA</Authors_Primary><Authors_Primary>Eckfeldt,JH</Authors_Primary><Authors_Primary>Glass,KC</Authors_Primary><Authors_Primary>Jarvik,GP</Authors_Primary><Authors_Primary>Klag,M</Authors_Primary><Authors_Primary>Koski,G</Authors_Primary><Authors_Primary>Motulsky,A</Authors_Primary><Authors_Primary>Wilfond,B</Authors_Primary><Authors_Primary>Manolio,TA</Authors_Primary><Authors_Primary>Fabsitz,RR</Authors_Primary><Authors_Primary>Luepker,RV</Authors_Primary><Date_Primary>2006</Date_Primary><Keywords>Biomedical Research</Keywords><Keywords>*standards</Keywords><Keywords>Blood</Keywords><Keywords>Cardiovascular Diseases</Keywords><Keywords>genetics</Keywords><Keywords>genetic</Keywords><Keywords>Genetic information</Keywords><Keywords>Genetic Research</Keywords><Keywords>Genetic Screening</Keywords><Keywords>*standards</Keywords><Keywords>methods</Keywords><Keywords>genetic test</Keywords><Keywords>Guidelines</Keywords><Keywords>health</Keywords><Keywords>Humans</Keywords><Keywords>information</Keywords><Keywords>Persons</Keywords><Keywords>Physicians</Keywords><Keywords>Research</Keywords><Keywords>Truth Disclosure</Keywords><Reprint>Not in File</Reprint><Start_Page>1033</Start_Page><End_Page>1040</End_Page><Periodical>American Journal of Medical Genetics</Periodical><Volume>140</Volume><Issue>10</Issue><User_Def_1>Kaft lit review</User_Def_1><ISSN_ISBN>1552-4825</ISSN_ISBN><ZZ_JournalFull><f name="System">American Journal of Medical Genetics</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Cho</Author><Year>2008</Year><RecNum>251</RecNum><IDText>Understanding incidental findings in the context of genetics and genomics&#xA;3</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>251</Ref_ID><Title_Primary>Understanding incidental findings in the context of genetics and genomics&#xA;3</Title_Primary><Authors_Primary>Cho,M.K.</Authors_Primary><Date_Primary>2008</Date_Primary><Keywords>Consent</Keywords><Keywords>Disclosure</Keywords><Keywords>ethics</Keywords><Keywords>genetic</Keywords><Keywords>Genetic information</Keywords><Keywords>Genetic Research</Keywords><Keywords>Genomics</Keywords><Keywords>Humans</Keywords><Keywords>Incidental Findings</Keywords><Keywords>information</Keywords><Keywords>Informed Consent</Keywords><Keywords>INFORMED-CONSENT</Keywords><Keywords>Pediatrics</Keywords><Keywords>Research</Keywords><Keywords>Researcher-Subject Relations</Keywords><Keywords>SUBJECT</Keywords><Keywords>Universities</Keywords><Reprint>Not in File</Reprint><Start_Page>280</Start_Page><End_Page>5, 212</End_Page><Periodical>J Law Med Ethics</Periodical><Volume>36</Volume><Issue>2</Issue><Address>Department of Pediatrics at Stanford University, CA, USA</Address><Web_URL>PM:18547195</Web_URL><ZZ_JournalStdAbbrev><f name="System">J Law Med Ethics</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Clayton</Author><Year>2008</Year><RecNum>252</RecNum><IDText>Incidental findings in genetics research using archived DNA&#xA;1</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>252</Ref_ID><Title_Primary>Incidental findings in genetics research using archived DNA&#xA;1</Title_Primary><Authors_Primary>Clayton,E.W.</Authors_Primary><Date_Primary>2008</Date_Primary><Keywords>classification</Keywords><Keywords>Consent</Keywords><Keywords>Disclosure</Keywords><Keywords>DNA</Keywords><Keywords>ethics</Keywords><Keywords>Ethics Committees,Research</Keywords><Keywords>genetic</Keywords><Keywords>Genetic Research</Keywords><Keywords>genetic test</Keywords><Keywords>Humans</Keywords><Keywords>Incidental Findings</Keywords><Keywords>information</Keywords><Keywords>Informed Consent</Keywords><Keywords>psychology</Keywords><Keywords>Research</Keywords><Keywords>Researcher-Subject Relations</Keywords><Keywords>standards</Keywords><Keywords>Universities</Keywords><Reprint>Not in File</Reprint><Start_Page>286</Start_Page><End_Page>91, 212</End_Page><Periodical>J Law Med Ethics</Periodical><Volume>36</Volume><Issue>2</Issue><Address>Center for Biomedical Ethics and Society, Vanderbilt University, TN, USA</Address><Web_URL>PM:18547196</Web_URL><ZZ_JournalStdAbbrev><f name="System">J Law Med Ethics</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Ravitsky</Author><Year>2006</Year><RecNum>199</RecNum><IDText>Disclosing Individual Genetic Results to Research Participants</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>199</Ref_ID><Title_Primary>Disclosing Individual Genetic Results to Research Participants</Title_Primary><Authors_Primary>Ravitsky,Vardit</Authors_Primary><Authors_Primary>Wilfond,Benjamin S.</Authors_Primary><Date_Primary>2006</Date_Primary><Keywords>Consent</Keywords><Keywords>Disclosure</Keywords><Keywords>genetic</Keywords><Keywords>Genetic information</Keywords><Keywords>Genetic Research</Keywords><Keywords>information</Keywords><Keywords>Informed Consent</Keywords><Keywords>INFORMED-CONSENT</Keywords><Keywords>justice</Keywords><Keywords>Research</Keywords><Reprint>Not in File</Reprint><Start_Page>8</Start_Page><End_Page>17</End_Page><Periodical>The American Journal of Bioethics</Periodical><Volume>6</Volume><Issue>6</Issue><Publisher>Routledge</Publisher><ISSN_ISBN>1526-5161</ISSN_ISBN><Web_URL> name="System">The American Journal of Bioethics</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Matsui</Author><Year>2008</Year><RecNum>201</RecNum><IDText>Ethics of Future Disclosure of Individual Risk Information in a Genetic Cohort Study: A Survey of Donor Preferences</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>201</Ref_ID><Title_Primary>Ethics of Future Disclosure of Individual Risk Information in a Genetic Cohort Study: A Survey of Donor Preferences</Title_Primary><Authors_Primary>Matsui,Kenji</Authors_Primary><Authors_Primary>Lie,Reidar K.</Authors_Primary><Authors_Primary>Kita,Yoshikuni</Authors_Primary><Authors_Primary>Ueshima,Hirotsugu</Authors_Primary><Date_Primary>2008</Date_Primary><Keywords>Cohort Studies</Keywords><Keywords>Disclosure</Keywords><Keywords>ethics</Keywords><Keywords>FUTURE</Keywords><Keywords>genetic</Keywords><Keywords>health</Keywords><Keywords>information</Keywords><Keywords>methods</Keywords><Keywords>Research</Keywords><Keywords>SAMPLES</Keywords><Reprint>Not in File</Reprint><Start_Page>217</Start_Page><End_Page>224</End_Page><Periodical>Journal of Epidemiology</Periodical><Volume>18</Volume><Issue>5</Issue><ZZ_JournalStdAbbrev><f name="System">Journal of Epidemiology</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(23,24,25,26,27). Basically three stances can be distinguished. A first stance is that no individual results are returned, based on the idea that such results would generate anxiety, that it would enhance the therapeutic misconception and that it would burden the researchers. Moreover, as biobanks are research tools and not clinical settings, returning individual results would imply that too many resources would have to be allocated to the right setting of returning such results. Many biobanks therefore choose this first option. A second stance is that, based on respect of autonomy of the participants, results should be returned if they do so wish. A third approach is based on the potential benefits and states that results should be returned if they are clinically relevant and scientifically valid. However the complexity of interpretation and validation in deciding what is clinically relevant and scientifically valid should not be underestimated.(30) This also raises questions as to what results researchers are obliged to feed back. In the discussion, two dimensions can be discerned ADDIN REFMGR.CITE <Refman><Cite><Author>Hens</Author><Year>2011</Year><RecNum>285</RecNum><IDText>The return of individual research findings in paediatric genetic research</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>285</Ref_ID><Title_Primary>The return of individual research findings in paediatric genetic research</Title_Primary><Authors_Primary>Hens,K.</Authors_Primary><Authors_Primary>Nys,H.</Authors_Primary><Authors_Primary>Cassiman,J.J.</Authors_Primary><Authors_Primary>Dierickx,K.</Authors_Primary><Date_Primary>2011/3</Date_Primary><Keywords>Belgium</Keywords><Keywords>biobanks</Keywords><Keywords>children</Keywords><Keywords>ethics</Keywords><Keywords>genetic</Keywords><Keywords>Genetic Research</Keywords><Keywords>Guidelines</Keywords><Keywords>health</Keywords><Keywords>information</Keywords><Keywords>Minors</Keywords><Keywords>Parents</Keywords><Keywords>Research</Keywords><Keywords>Research Subjects</Keywords><Keywords>SAMPLES</Keywords><Keywords>solidarity</Keywords><Keywords>SUBJECT</Keywords><Reprint>Not in File</Reprint><Start_Page>179</Start_Page><End_Page>183</End_Page><Periodical>J.Med.Ethics</Periodical><Volume>37</Volume><Issue>3</Issue><Address>Katholieke Universiteit Leuven, Centre for Biomedical Ethics and Law, Kapucijnenvoer 35/3 Box 7001, 3000 Leuven, Belgium. kristien.hens@med.kuleuven.be</Address><Web_URL>PM:21059631</Web_URL><ZZ_JournalStdAbbrev><f name="System">J.Med.Ethics</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>(28). First, there is the question of the right of participants to such information. Second there is the question about the duty of the researcher to provide such information. Especially when participants are children, these two dimensions become apparent. First, as children do not enrol themselves in the research, the question is related to the parent’s right to know and not to know certain genetic information about their children. Parents do not have the right to opt out of receiving information that may be relevant to the health of their children, if they decide to enrol their children in non-therapeutic research. In this respect, the potential benefits of the child in case of preventable or treatable early-onset diseases override parental autonomy. In the case of genetic research, this would refer to early-onset treatable and preventable disorders. We admit that the occurrence of such discoveries will be very rare, and will only be applicable to genetic conditions such as familial adenomatous poliposis (FAP) or hypertrophic cardiomyopathy (HCM), where preventive actions can be taken during childhood. Also, parents do not have the right to know all possible information that such research should generate. Revealing information about conditions that are not early-onset, treatable and preventable should hence be postponed until the young person reaches the age of competence and can decide for him or herself, or should not be given at all. It is part of the right of the minor to an open future that he or she can decide whether certain genetic information is given back to him or her or not ADDIN REFMGR.CITE <Refman><Cite><Author>Feinberg</Author><Year>1980</Year><RecNum>241</RecNum><IDText>The Child&apos;s Right to an Open Future</IDText><MDL Ref_Type="Book Chapter"><Ref_Type>Book Chapter</Ref_Type><Ref_ID>241</Ref_ID><Title_Primary>The Child&apos;s Right to an Open Future</Title_Primary><Authors_Primary>Feinberg,Joel</Authors_Primary><Date_Primary>1980</Date_Primary><Keywords>Adult</Keywords><Keywords>Child</Keywords><Keywords>children</Keywords><Keywords>FUTURE</Keywords><Keywords>Parents</Keywords><Reprint>Not in File</Reprint><Start_Page>124</Start_Page><End_Page>153</End_Page><Title_Secondary>Whose Child? Children&apos;s Rights, Parental Authority and State Power</Title_Secondary><Authors_Secondary>Aiken,William</Authors_Secondary><Authors_Secondary>LaFollette,Hugh</Authors_Secondary><Pub_Place>Totowa</Pub_Place><Publisher>Rowman and Littlefield</Publisher><ZZ_WorkformID>3</ZZ_WorkformID></MDL></Cite></Refman>(29). In the dimension of the duty of the researcher, the duty to return information about early onset preventable or treatable conditions is more stringent in the case of pediatric biobanks than in case of adults, as children are a vulnerable population and are not participants out of their own volition. From a practical point of view, studies involving children often involve more direct contact between researchers and children and are done in a clinical setting. This restriction is dependent on the type of collection, the feasibility of providing genetic counselling and the possibility to check the findings for clinical validity and utility. For example epidemiological research that puts no burden on children and that implies no contact between researcher and the child, and where it may be harder to clinically validate the findings may be exempt from this duty.RecommendationsGenetic research on stored tissue samples from minors can only be done if it cannot be done on adults or would not be feasible due to scarce resources (subsidiary principle).During the collection of tissue samples from minors the physical or emotional burden should be limited as much as possible , The focus of the right to decide on the collection, storage and use of samples gradually shifts from the parents to the minor as he or she grows older.Minors should receive information about the collection, storage and use of samples depending on their maturity level and a child’s assent or dissent should be respected. Minors should be given the opportunity to contact researchers and to withdraw their samples when they reach the age of understanding or the age of majority. In case of research that implies frequent contact between researchers and minors, the maturity of a minor can be assessed. In case of a one-time donation of samples, a fixed age threshold, for example the legal age of competence, for contacting minors and allowing them to make their own decision on consent could be used.Parents and minors should be notified of ongoing and new research done on their samples and given the opportunity to refuse to participate to research if they object to it. This should be done on a best effort basis. If there is no frequent contact between researchers and the families, at least there should be transparency, for example through websites.Biobanks should have a policy about returning information about preventable or treatable early onset conditions when participants are minors. If collections are gathered in a diagnostics setting and such findings can be validated according to guidelines and standards that are applied to clinical settings, researchers should consider returning such information.The right of parents to receive or not receive genetic information about their children is limited. In the rare case that information about a preventable or treatable early-onset disease is found, they should be notified regardless of their wishes providing the findings are subject to assessment of clinical validity and utility. On the other hand, they do not have the right to access all possible information that research on their children’s DNA might generate.References ADDIN REFMGR.REFLIST 1. Deschênes,M, Glass,KC, Cardinal,G, Knoppers,BM: Human genetic research, DNA banking and consent: a question of 'form'? Clinical Genetics 2001; 59: 221-239.2. Elger,BS,Caplan,AL: Consent and anonymization in research involving biobanks: differing terms and norms present serious barriers to an international framework. EMBO Rep 2006; 7: 661-666.3. Godard,B, Aymé,S, Schmidtke,J, Cassiman,J-J: Data storage and DNA banking for biomedical research: informed consent, confidentiality, quality issues, ownership, return of benefits. A professional perspective. EUROPEAN JOURNAL OF HUMAN GENETICS 2003; 11Suppl2: S88-S122.4. Rothstein,MA: Expanding the ethical analysis of biobanks. Journal of Law, Medicine & Ethics 2005; 33: 89-101.5. United Nations Convention on the Rights of the Child: 1998.6. Lederer,SE, Grodin,MA: Historical overview: Pediatric experimentation; in Grodin,MA, Glantz,LH eds: Children As Research Subjects. Science, Ethics & Law. New York and Oxford, Oxford University Press, 1994, pp 3-25.7. Kodish,E: Ethics and research with children: An introduction; in Kodish,E eds: Ethics and Research With Children. A Case-Based Approach. Oxford and New York, Oxford University Press, 2005, pp 3-25.8. Pinxten,W, Dierickx,K, Nys,H: Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials. Eur J Pediatr 2009; 168: 1225-1234.9. Bernard-Bonnin,A-C: Les principes éthiques de la recherche biomédicale avec les enfants; in Delfosse,M-L, Parizeau,M-H, Amann,J-P eds: La Recherche Clinique Avec Les Enfants: à La Croisée De L' ?thique Et Du Droit. Belgique, France, Québec. Louvain-la-Neuve, Anthemis, 2009, pp 415-424.10. Hens,K, Nys,H, Cassiman,JJ, Dierickx,K: Risks, Benefits, Solidarity: A Framework for the Participation of Children in Genetic Biobank Research. J.Pediatr. 23-2-2011; 11. Hoedemaekers,R, Gordijn,B, Pijnenburg,M: Solidarity and justice as guiding principles in genomic research. Bioethics. 2007; 21: 342-350.12. Chadwick,R,Berg,K: Solidarity and equity: new ethical frameworks for genetic databases. Nature Review Genetics 2001; 2: 318-321.13. Helgesson,G: Children, longitudinal studies, and informed consent. Medicine, Health Care and Philosophy 2005; 8: 30714. Hens,K, Nys,H, Cassiman,JJ, Dierickx,K: The Storage and Use of Biological Tissue Samples from Minors for Research: A Focus Group Study. Public Health Genomics 2011; 14: 68-76.15. Kaufman,D, Geller,G, LeRoy,L, Murphy,J, Scott,J, Hudson,K: Ethical implications of including children in a large biobank for genetic-epidemiologic research: A qualitative study of public opinion. American Journal of Medical Genetics, Part C Seminars in Medical Genetics 2008; 148C: 31-39.16. Goodenough,T, Williamson,E, Kent,J, Ashcroft,R: Ethical protection in research: including children in the debate; in Smyth,M, Williamson,E eds: Researchers and Their 'Subjects'. Bristol, The Policy Press, 2004, pp 55-72.17. Shickle,D: The consent problem within DNA biobanks. Studies in History and Philosophy of Science 2006; 37: 503-519.18. Hens,K, Nys,H, Cassiman,JJ, Dierickx,K: Children, biobanks and the scope of parental consent. EUROPEAN JOURNAL OF HUMAN GENETICS 2011; 19. Hansson,MG, Dillner,J, Bartram,CR, Carlson,JA, Helgesson,G: Should donors be allowed to give broad consent to future biobank research? Lancet Oncol. 2006; 7: 266-269.20. Wendler,D: One-time general consent for research on biological samples. BMJ: British Medical Journal 4-3-2006; 332: 544-547.21. Caulfield,T,Kaye,J: Broad Consent in Biobanking: Reflections on Seemingly Insurmountable Dillemas. Medical Law International 2009; 10: 85-100.22. Borry,P, Evers-Kiebooms,G, Cornel,MC, Clarke,A, Dierickx,K: Genetic testing in asymptomatic minorsBackground considerations towards ESHG Recommendations. Eur J Hum Genet 11-3-2009; 17: 711-719.23. Bookman,EB, Langehorne,A, Eckfeldt,Jet al.: Reporting genetic results in research studies: summary and recommendations of an NHLBI working group199. American Journal of Medical Genetics 2006; 140: 1033-1040.24. Cho,MK: Understanding incidental findings in the context of genetics and genomics3. J Law Med Ethics 2008; 36: 280-5, 212.25. Clayton,EW: Incidental findings in genetics research using archived DNA1. J Law Med Ethics 2008; 36: 286-91, 212.26. Ravitsky,V,Wilfond,BS: Disclosing Individual Genetic Results to Research Participants. The American Journal of Bioethics 2006; 6: 8-17.27. Matsui,K, Lie,RK, Kita,Y, Ueshima,H: Ethics of Future Disclosure of Individual Risk Information in a Genetic Cohort Study: A Survey of Donor Preferences. Journal of Epidemiology 2008; 18: 217-224.28. Hens,K, Nys,H, Cassiman,JJ, Dierickx,K: The return of individual research findings in paediatric genetic research. J.Med.Ethics 2011; 37: 179-183.29. Feinberg,J: The Child's Right to an Open Future; in Aiken,W, LaFollette,H eds: Whose Child? Children's Rights, Parental Authority and State Power. Totowa, Rowman and Littlefield, 1980, pp 124-153. 30. Berg, Jonathan S.; Khoury, Muin J.; Evans, James P.Genetics in Medicine. 13(6):499-504, June 2011. ................
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