Results of the Inquiry and Citation Review

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Bioethics issues in human studies


Legal status and storage of samples and data in a biobank

State of discussion

Keeping the samples (especially from smaller studies) for further genomics research or the generation of large population-based biobanks has become a relatively frequent practice in the recent past, and therefore not many international documents explicitly give comprehensive explanation on the legal status of existing and evolving bio or DNA banks. Most of the large collections in Europe are not older than 10 years [23] and the rules and regulations for biobanking and exchange of samples are still at an early stage [16, 24]. The status of biological material collections and data bases is not well defined and most institutions have no written policies or agreements regarding biobanking [24]. However, some European countries such as United Kingdom, Netherlands, Sweden, Denmark, and Germany have national laws and documents being applied within the countries. However, the existing and started multinational new collections are increasingly attracting scientists as well as industrial partners and an international standard is needed.

According to the Recommendations of the European Society of Human Genetics [24] the central questions in connection with biobanking are the:

A further aspect is the quality assurance for biobanking [25]. Strict guidelines on quality control should be in place before sampling begins.

Status of collections:

In studies where individuals just serve as the donator of biological material for DNA extraction, the identification of the source is not necessary. However, in studies where the genetic information needs to be supplemented by other information such as family medical history, anthropometry, demographics, social features and others, the ability to identify the source of the sample, might be essential (in case a follow-up on disease status or even causes of death would be of future interest).

Generally, is should be kept in mind that, whatever the degree of identification is, with modern DNA identification techniques, it is possible to identify an individual even in anonymized sample collections if he or she donates a fresh sample for matching [25].

In their empirical survey on bio banking of human genetic material and data in six European countries Hirtzlin et al. found that completely anonymous samples are the exception. Generally, coded samples are used in the frame of research applications and identified samples within a clinical setting for medical care purposes [23]. As stated by the American Society of Human Genetics (ASHG), studies that maintain identified specimens, even if measures are taken to keep subject's confidentiality (the information derived from these samples are not be provided to anyone other than the subject and persons designated by the subject in writing), it cannot be guaranteed absolute confidentiality [27].

The most protective status when identification is potentially required is to code the samples preferable by a third party who keeps the codes inaccessible unless specific circumstances emerge where the code needs to be broken. This is the opinion of the National Bioethics Advisory Commission (NBAC), the Danish Council of Ethics, the Human Genetics Commission, the Human Genome Organization (HUGO), the World Health Organization (WHO), and the Swedish Medical Research Council. The risk is remarkable decreased when the code must be kept within public institutions (as in Sweden). The Health Council of Netherlands wants wherever possible anonymous or anonymized samples to be used. Identifiable samples should be restricted to studies that could not otherwise be performed. In the United Kingdom, the Human Genetics Commission recommends researchers to use encrypted identifiers and to support the research that develops robust methods of encryption (making them reversible where necessary) [25].

Consent requirement for new collections:

Anyone who collects biological material and associated information about individuals that is to be stored must obtain informed consent for this from the research participant. The information must include details about storage procedures, storage time, and the person in charge of the biobank. In addition, it must be clear that the material may be used for future research, which in such case will be reviewed and approved by the research Ethics Committee, and that the donors may be contacted again. Further, the donors must be informed of the possibility that their samples may be destroyed at any time on their request.

The International Bioethics Committee in their Preliminary Study on the Collection, Processing, Storage and Use of Human Genetic Data [13] states in Guideline 14 that donors of samples for genetic testing, both individuals and communities, should be informed prior to giving consent whether their samples and genetic data will be stored identified, coded but identifiable, or not identifiable (anonymized); and the meaning of these terms should be clearly explained.

Guideline 15 of the above document [13] refers to the fate of material after DNA extraction and analysis. Donors of identified samples must consent to whether their samples will be stored or disposed. If stored, the donor must be told where the sample will be stored. The tissue or DNA should not be exported without the consent of the donor.

For further aspects please see section (informed consent).

Consent requirements for existing collections

The majority of existing bio banks are relatively small collections (no more than 1000 samples) devoted to specific diseases. A number of different types of institutions have bio banks, including public hospitals or laboratories (which obviously have a key role), private clinics, medical laboratories, forensic medical services, public research laboratories, private or semi-public associations, charities and companies in the pharmaceutical, diagnostic or biotechnology industries. These bio banks will remain important in the future and therefore should not be destroyed. In addition, large-scale population-related bio banks as well as bio banks within large scale epidemiologic studies are being set up in some countries [23].

Generally, a fundamental problem with consent for biobanking concerns the need to collect samples today for research needs that may arise tomorrow.

In the European Union, the directive approved by the European Parliament restricts access to data unless previous consent has been obtained from the subject, but permits member states to make exceptions in the case of health-related research in the public interest [28].

The Swedish Act on Biobanks [29] which became effective in 2003 is very strict about the need of informed consent for each new purpose. General information where the patient consents to the use of collected material for unspecified future research cannot be accepted. The research Ethics Committee may depart from the main rule of new informed consent in certain cases. a) if only strictly coded material is used; or b) the purpose, problem, and type of analysis in the new research project are very close to the one about which the subject has been informed previously and to which consent has been granted; or c) if such a large number of individuals is included in the study that individual informed consent in reality would make the study impossible.

In the UK, the Working Group for the Royal College of Physicians Committee on Ethical Issues in Medicine [30] proposed that research requiring access to medical records or to stored biological samples, without direct patient participation, may not require the explicit consent of patients nor even review by an independent institutional review board, as long as explicit consent is obtained from the person officially responsible for the records or from the physician caring for the patient, and as long as the confidentiality of the information is guaranteed by the professional ethical code.

The German National Ethics Council [31] stated that the requirement of consent must also apply whenever samples and data obtained for other reasons - e.g. diagnosis or therapy - are subsequently to be used for research. This kind of multiple sample use is extremely valuable for medical research, but in the past it usually took place without explicit consent. To ensure that these samples remain available for research in the future, the process of obtaining consent must not be unnecessarily complicated. A form-based declaration that the samples may also be used for medical research subject to appropriate donor protection ought to suffice (according to [31]).

If samples and data lawfully obtained for diagnostic or therapeutic reasons are subsequently used for medical research, the requirement of consent is inapplicable if the samples and data are completely anonymized. Since no relation to the person then exists, donor interests calling for protection are not an issue. However, if the donor has expressed a contrary wish at the time of collection of the samples, it must always be respected. Under Germany's current data protection legislation, the requirement of consent may also be waived in the case of samples and data lawfully obtained for diagnostic or therapeutic purposes to be used for research purposes in a personalized (identifiable) form, if the scientific interest of the research project substantially outweighs any interest of the donor in exclusion from use, and if the purpose of the research cannot be achieved in any other way, or can be achieved only with disproportionate effort and expense. Even so, donor consent to the research should be obtained if reasonably possible. Exceptional situations also include personalized samples and data obtained with donor consent for a specific research project, to be used for another research on further diseases. This exception is possible where wide-ranging consent was granted at the time of collection of the samples.

The Public and Professional Policy Committee (PPPC) of the European Society of Human Genetics (ESHG) produced recommendations which where discussed with 51 experts from 15 European countries and therefore are expected to reflect the views of the scientific community. Regarding requirements for existing sample collections they recommend [24]:

(9) Regarding already stored anonymous samples, irretrievable unlinked to the name, these may be used for other purposes than originally intended.

(10) The decision to strip samples of identifiers irreversibly needs careful consideration. The benefit of having unlinked anonymized samples is to secure absolute confidentiality and thereby allows further use of the samples. However, retaining identifiers, while requiring further consent from the subject, will permit more effective biomedical research and the possibility of re-contacting the subject when a therapeutic option becomes available.

(11) Anonymized samples are acceptable in order to allow sample and information sharing for research purpose with minimum risk. Anonymization techniques should be standardized to ensure their robustness. Demographic and clinical data attached to anonymized samples should be coded with international nomenclatures wherever possible.

(12) In the case of existing collections, investigators should be required to re-contact subjects to obtain consent for new studies. If it is impracticable to gain consent, an appropriate ethics review board should give its consent for further use of the samples based on the notion of minimum risk for the donor.

(13) Concerning post-mortem use of samples, a policy of unrestricted access cannot be justified on the grounds that the risk of harm for the subject is no more an issue. If individuals restrict use of their sample when they are still alive, those restrictions apply after their death.

(14) Old collections should be regarded as abandoned and therefore usable for new research purposes as long as Ethics Committee approval is obtained.

In their preliminary guidelines generated by the International Bioethics Committee of the UNESCO [13], Guideline 18 is about historical or archived collections: The obtaining of human genetic data for medical research purposes from historical collections of human tissue should only be undertaken without the consent of the donor of the sample if the sample is anonymized. If the sample is not anonymized, the consent of the donor should be obtained, provided that the donor can be traced with reasonable effort.

Withdrawal of consent

Study participants should at any time have the opportunity to withdraw their consent. It has to be regulated whether the sample in this case has to be removed. From the point of the researcher, withdrawals with a complete removal of sample and data could cause methodical implications for the study. Therefore, the Deutsche Forschungsgemeinschaft (DFG) states that it should be possible in the donation agreement to limit the period of time within which the withdrawal also includes the disposal of the specimen [22].

The International Declaration on Human Genetic Data [14] states about withdrawal of consent that:
(b) When a person withdraws consent, the person's genetic data, proteomic data and biological samples should no longer be used unless they are irretrievable unlinked to the person concerned.
(c) If not irretrievable unlinked, the data and biological samples should be dealt with in accordance with the wishes of the person. If the person wishes cannot be determined or are not feasible or are unsafe, the data and biological samples should either be irretrievable unlinked or destroyed.

The Swedish Act on Biobanks [29] states: The patient shall have the possibility to change his consent at any time. Such change of consent may be a change in allowed purposes or the wish to have the sample destroyed. Consent can be revoked wholly or partially at any time. If the revocation refers to all use, the sample shall be destroyed or all identification labels removed.

The German National Ethics Council [31] similarly declares that donors must have the right to withdraw their consent to the use of their samples and data at any time. It should not be possible to waive this right. However, there should be provision for donors to allow samples and data to continue to be used, in the case of withdrawal, if they are anonymized - that is, if their personalization has been eliminated.

Access to the biobank, sharing and ownership of samples

Please see section

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