The use of cells from cystic fibrosis patients in research: A model consent form

Abstract

The European Cystic Fibrosis Thematic Network is a project approved under the fifth framework program from the European Union. The philosophy of the network is based on the need for closer interactions between the patient organisations and the clinical profession as well as those involved in fundamental research on CF [[1]See the website of the CF network at http://www.cfnetwork.be/.Google Scholar]. In the context of this Cystic Fibrosis European Network, questions were raised about the recommended policies for the use of cells from cystic fibrosis patients for CF research and quality control. The legal and ethical workgroup of the Project therefore proposed to draft a consent form that would integrate the legal and ethical requirements for the use of human biological materials. A meeting with the researchers of the Center for Human Genetics at the University of Leuven quickly made it clear that the cells that were to be removed from the CF patients (enrolled as human subjects in a research protocol) would not only be used for specific CF research and quality control but would also be stored for later research purposes. The consent form would therefore have to deal with broader issues than those of human subjects research only. Questions on the secondary (further) use of stored human biological materials also had to be answered. A draft version of the consent form was presented at a meeting with representatives of national and international CF patient organisations in Leuven in 2001. After adaptation based on some of the remarks, it was sent to seven national CF associations for further comments [[2]Belgian CF Association, Vaincre la Mucoviscidose (France), Swedish CF Association, Danish CF Association, Nederlandse CF Stichting, German CF Association, Federacion Espanola contra la Fibrosis Quistica, ICF(M)A.Google Scholar]. These comments have been thoroughly discussed and integrated in the consent form. The consent form presented below has been drafted to ask human subjects (CF patients) for consent to the (further) use of their cells removed in the context of a research protocol. The cells are removed specifically for CF research purposes, but the subjects are also asked to consent to the use of the cells for other (future) purposes. The consent form traditionally presented to research subjects therefore had to be adapted [[3]This is not the only context in which human biological materials for research are obtained. Cells and biopsies could also be removed from patients during the diagnostic or therapeutic process and be used later on as research material. A specific consent form has to be drawn up for these situations because of the different target group.Google Scholar]. Consent is not only a prerequisite for human subjects to participate in research, consent is also necessary to use stored human biological materials for research purposes [[4]See for example Convention on Human Rights and Biomedicine, art. 22 (disposal of a removed part of the human body): “when in the course of an intervention any part of a human body is removed, it may be stored and used for a purpose other than that for which it was removed, only if this is done in conformity with appropriate information and consent procedures”.Google Scholar]. Only patients 16 years and older are considered in the consent form because there is still much uncertainty on the legal conditions surrounding consent from minors for the use of their cells and tissues for research purposes. [[5]The most important question is the one of the right of the minor (not) to know. How can a minor exercise that right once he is an adult, when his representatives have already consented to research use years before?Google Scholar] Presumably, the proxy consent given by parents on behalf of a minor could be ratified or withdrawn by the subject when he/she becomes an adult, in accordance with the provision given to adult donors (Information Leaflet, statement 8) but this has not been tested in the courts. The choices made throughout this consent form and the legal arguments upon which these choices were based will not be analysed in this article, this would exceed its scope, which is to briefly present the consent form. An analysis of the underlying legal arguments for the need to ask consent and a description of the international background to the research use of (stored) human biological materials can be consulted [[6]Trouet C. Sprumont D. Biobanks: investing in regulation.Baltic Yearbook of International Law. 2002; Google Scholar]. We hope this information leaflet and consent form offer some useful ideas to facilitate research on human biological materials while respecting the rights of patients. The consent form is written in the context of the CF network project and is not adjusted to specific regulation different European countries might have. It can serve as a model for use in other projects, if reviewed by the local ethics committee. INFORMATION LEAFLET INFORMATION PRECEDING THE REMOVAL, PRESERVATION AND USE OF HUMAN CELLS FOR RESEARCH AND/OR QUALITY ASSESSMENT This information leaflet gives you information to help you decide whether you want a sample of your cells to be removed, preserved and used for medical research and/or quality assessment. It will inform you on what will or could happen, now and in the future, with your biological material and how your privacy will be guaranteed. If you have any question, do not hesitate to contact your treating physician or the Centre for Human Genetics, Campus Gasthuisberg, Herestraat 41, 3000 Leuven, Tel. no. 016-34-58-81. 1. Use of human cells for research and/or quality assessment a. Research You are asked to supply a sample of cells (for example a blood sample) to be used for research/quality assessment. No direct benefits for yourself can be promised from your participation to this research. Research on the genetic condition you inherited (mucoviscidosis or CF) could however be of importance for other persons, who are tested for or who suffer from the same disease and for the understanding and treatment of genetic diseases in the future. Your sample of biological material is not only important to conduct scientific research on cystic fibrosis, but it could also be essential for research on other (genetic) diseases or research done to understand the functioning of cells. We cannot predict all possible future tests which may be developed as our understanding grows, so we cannot give you more precise information on its nature at this moment. We therefore offer you the option either to consent only to CF research and quality control, or to consent to other research on the condition that you receive extra information on the nature of this latter research before it is done. You may also choose to donate your sample for future medical research without requiring to be notified. b. Quality control Furthermore, your biological materials can be used for quality assessment to ensure quality control of laboratory DNA-tests. Your sample of biological material or the cell lines derived from it will make it possible to assess and improve the quality of CF diagnostic tests in a large number of laboratories in Europe and other continents. The need to assess regularly the quality of the diagnostic tests follows from the fact that new methods and techniques are constantly being introduced in the diagnostic labs. This requires that these methods have to be validated first with samples containing known mutations. In addition regular participation in external quality assessments will identify unexpected errors in the laboratory procedures. Such errors can seriously affect the quality of the results communicated to the families. Therefore, it is important that such errors can be detected. The DNA that is extracted from your cells can also be used to determine all possible variants in the composition of your disease gene. In this way, an international DNA standard for the gene can be obtained, which can be used by all laboratories in the world in quality assessments as described above. 2. Removal of the cells A sample of your cells (usually a blood sample) will be taken, free of charge, by your general practitioner or specialist in the usual way. This sample will be forwarded to our laboratory. 3. Creation of cell lines Cells obtained from your body may be used to establish a cell line. This means that it will be possible to preserve your biological material for a long time (in principle for an indefinite period). This cell line creates an inexhaustible source of DNA that can be used for quality assessment and for scientific research in the future. Cell lines may be useful because of the characteristics of the cells and/or the products they may produce. 4. Supply to third parties of the cells or cell lines created by using your sample The cells and cell lines may be supplied in the future to third parties (other researchers, international institutions collecting cell lines). The purpose of this will always be the use of them for scientific research or for quality assessment. It is possible that the requesting researcher will be asked to pay a contribution to the costs (costs for processing in the lab, mailing costs) if the number of requests for such cell lines should increase. Any personal financial profit for the researchers is excluded. The decision to supply a cell line to another research institution or organisation will be evaluated by a supervisory board specifically set up for this purpose. For the University of Leuven, this supervisory board is composed by researchers of the Center of Human Genetics, the Center of Biomedical Ethics and Law and representatives of the patients' organisations. It will evaluate every request for a cell line from a medical, ethical and legal point of view. It also will see to it that the contribution paid by the requesting party will be used only for research purposes and that your privacy is protected. 5. Protection of your privacy During the quality assessment, the CF research as well as during other scientific research by third parties for which your biological material is used, your identity will always remain unknown to the researchers. This is especially the case when cell lines are supplied to third parties for scientific research or quality control. This is done in order to protect your privacy. In practice, we will proceed as follows: during the research in Leuven, your biological material will only be identifiable in an indirect way. This means that your biological material will be given a code (for instance, a combination of letters and figures) that refers to your personal data (name, sex, age, etc.). Identifying information will not be connected directly to the biological material itself. This code will be attributed by an administrative unit within the Centre for Human Genetics (thus not by the researchers of the Centre). The key of the code makes it possible to link the sample to your identity. This key will never be communicated to the researcher. This makes it impossible for any researcher to know whose human biological material he is using. The key will remain in the hands of the above-mentioned supervisory board. When your cells leave Leuven, the code will be removed. There will be no possibility for the third party to link the cells to your identity. 6. New findings Except when your cells are supplied to third parties, they will not be completely anonymised (i.e. they will still have a code). This is necessary for laboratory identification of the sample and to avoid duplicating tests, but also because it may be necessary to contact you if the research reveals new information concerning your health status. This could be information about your present as well as your future health (for instance, information about an illness which for the moment still has not got an appropriate treatment). We ask you to indicate on the consent form whether or not you want to be notified about significant new findings concerning your health status. You will only be contacted if you indicate on the consent form that you want to be informed, by the doctor who has taken your biological sample. 7. Inventions, patents and commercial applications It is conceivable that the research making use of your cells could possibly lead to medical (biotechnological) inventions. In order to legally protect these inventions, it will be necessary to apply for patent protection. If an invention is patented, its owner has an exclusive right to exploit the invention during 20 years. Other people who want to make use of the invention have to obtain a license and have to pay for it. We ask your consent in order to be able to apply for a patent, in case such an opportunity arises, for any invention resulting from the research making use of your biological material. Moreover, it may be possible that that this invention leads to industrial or commercial applications, for instance, the development of a new medicine or a diagnostic kit. The financial profits that derive from these applications as well as from the licenses to make use of the invention, will for a considerable part be re-invested in scientific research on CF. You cannot claim any of these profits. 8. Withdrawal of the consent—destruction of human biological materials The consent you give to remove, preserve and use your cells can be withdrawn at any time in the future. When you withdraw your consent, you may also request that your sample will be destroyed. This destruction will not be possible if your cells have already been anonymised, because in that case we cannot link them any more to your identity. If your cells are already used in a research protocol, the withdrawal of your consent (and the request to destruction) can only have effect as from the ending of this research. CONSENT FORM TO REMOVE, PRESERVE AND USE HUMAN CELLS FOR RESEARCH AND/OR QUALITY ASSESSMENT I ………………………… (last name and first name) have read and understood the accompanying information. I understand the nature and purposes of the scientific research and quality assessment that will be performed with my cells. I understand that they can be supplied to third parties in a way that will protect my privacy. I have had the opportunity to ask any question regarding the use of my cells for scientific research and/or quality assessment and I confirm that all my questions have been answered in a satisfactory way. I have been informed that my identity will be kept secret from the researchers and that the identification of the cells can only be done through a unique code that will remain in the hands of the supervisory board. I am aware that the original cells will not be destroyed and will be preserved for research in the future unless I withdraw my consent and request explicitly for their destruction. I understand that I will not receive any financial remuneration for participating and that financial profits derived from industrial or commercial applications will for a considerable part be re-invested in scientific research on CF. Herewith I give my explicit, informed and free consent for (cross out whatever does not apply):1.the use of my cells for:a. quality assessment of CF-diagnosisb. quality assessment and CF researchc. quality assessment, CF research and other (genetic) research on condition that I will get more information about this other research in advanced. quality assessment, CF research and other (genetic) researchthe supply of cell lines to third partiesthe possible application for patents for inventions for which my cells have been usedthe possible development of commercial and industrial applications of these inventions. I wish/I do not wish (delete what is not applicable) to be contacted if, in the course of the above-mentioned scientific research and/or quality assessment during which my cells have been used, new information is revealed concerning my present or future health status. This consent form has been made in three authentic copies of which I received one. Read and approved, Name Address Telephone number Signature Place and date Grant support: the European Cystic Fibrosis Thematic Network is a project approved under the 5th framework program of the European Union, QLK3-CT99-00241, 1/02/2000-31/01/2004.