Abstract
The National Blood Centre, the National Transplant Centre, and the Bioethics Unit of the Istituto Superiore di Sanità have compared the information leaflets and forms regarding the collection of informed consent used by each of the 18 biobanks that comprise the Italian network. With a view to harmonize the provision of information to couples and the collection of informed consent within the Italian Cord Blood Network, the 3 organizations have prepared a standard information leaflet and informed consent form to be used for the collection, storage, and allogeneic use of cord blood. The proposed model can be a useful tool for the development of specific informed consent forms for cord blood banking that comprises the minimum information necessary to meet ethical and regulatory requirements also in other countries.
Introduction
The collection, characterization, storage, and distribution of cord blood in Italy are performed by cord blood banks comprising the Italian Cord Blood Network (ITBCN). 1 The ITCBN is coordinated by the National Blood Centre, which cooperates with the National Transplant Centre in matters relating to the clinical use of cord blood: its operational standards are dictated by requisites and guidelines laid down in Italian (specifically, Decree No. 191 of November 6, 2006 2 and Decree No. 16 of January 25, 2010 3 ) and international (specifically, NetCord-FACT standards 4 ) regulations.
In Italy, cord blood banks are public health facilities that collect, store, and distribute cord blood hematopoietic stem cells on behalf of the National Health Service. Eighteen facilities are currently operating in 10 regions.
The Ministerial Decree of November 18, 2009 “Provisions concerning the storage of UCB stem cells for autologous-directed use”
5
allows the following functions:
• the conservation of cord blood for allogeneic use—in other words, for persons other than those from whom the cells were harvested—for philanthropic purposes, in dedicated public health facilities; • storage for the benefit of the newborn or of a consanguineous child suffering, at the time of the collection or previously, from a pathology that is clinically appropriate to treat with cord blood stem cells; • storage for autologous/directed use in cases of specific pathologies not yet evident (listed in the annex to the decree) for which there is proven scientific evidence for potential use, including for clinical experimentation.
The same decree also provides for the possibility to export the sample of UCB for autologous use, at the expense of the exporter and after authorization and counseling have been given in accordance with the Agreement between the State and the Regions (Act No. 62 of April 29, 20106,7).
The procedures for storage allowed by current Italian regulations require that the parents be given an information leaflet and that they subsequently give written informed consent.
Materials and Methods
The National Blood Centre, the National Transplant Centre, and the Bioethics Unit of the Istituto Superiore di Sanità have compared the information leaflets and forms regarding the collection of informed consent used by each of the 18 biobanks that comprise the Italian network. 8 With a view to harmonize the provision of information to couples and the collection of informed consent within the ITCBN, the 3 organizations have prepared a standard information leaflet and informed consent form to be used for the collection, storage, and allogeneic use of cord blood.
Preliminary discussions concerning the information leaflet and the form for informed consent were held with representatives of the 18 Italian biobanks. The final versions take into account all of the suggestions received and have been formally agreed upon with all members of the ITCBN.
The information leaflet and the informed consent form are offered to the Italian network for the purpose of improving the completeness, precision, and uniformity of the information given to donor mothers within the National Health Service. Each biobank may modify or add to both documents in accordance with specific requirements.
Below are English translations of the forms for informed consent and the information leaflet prepared by the Bioethics Unit of the Istituto Superiore di Sanità, the National Transplant Centre, and the National Blood Centre in agreement with members of the ITCBN.
Informed Consent for the Collection and Allogeneic Storage of Cord Blood
We, the undersigned
Name (mother) _______________________________________
Place of birth _________________________________________
Date of birth_________________
Address: _____________________________________________________
Post Code ____________ Telephone _____________________
Mobile phone _____________________
e-mail __________________________________________
and
Name (father) ________________________________________
Place of birth _________________________________________
Date of birth________________
Address _____________________________________________________
Post Code ____________ Telephone _____________________
Mobile phone ____________________
e-mail _______________________________________________
have been given and read the information contained in the “Information leaflet” and declare the following:
I/we have been informed of the possible uses of UCB. I/we have understood the information and have asked for and received clarification. I/we understand that refusal to authorize the collection of cord blood will in no way affect the quality of healthcare. I/we understand that the procedure for collecting UCB will not incur risks for mother or child. I/we understand that the blood may be collected after either a natural birth or Caesarean section. I/we understand that if the unit is suitable it will be placed at the disposal of patients requiring a transplant. I/we understand that I/we will derive no financial benefit and acquire no rights from this donation. I/we consent to be interviewed for the purpose of gathering a personal and family medical history and, if necessary, to be contacted in the future in order to provide further information. I (mother only) agree to provide a venous blood sample, which will be tested in accordance with the laws concerning the safety of blood donations, including tests for HIV, and to be informed in the event of a positive result. I/we agree that a sample of my/our blood may be stored by the Bank and used for further tests if these are requested by the Transplant Center. I/we agree that these tests may also be performed on a sample taken from the UCB. I/we agree to be contacted in future for necessary checks to provide information on the state of health of the child. I/we agree to inform the Bank of changes in the health status of my/our child. Date_________________________________________________ Mother's signature _______________________________ Father's signature (if agreeable) ______________________ Physician/healthcare operator who obtained consent ______________________________________ Name ………………………………………………………… Qualification …………………………………………………. Department/Institution Tel/Fax …………………………. Date ……………………………. Signature……………………………………….
Informed Consent for the use of Cord Blood for Research and for other Potential Uses of Units Not Suitable for Transplantation
We, the undersigned
Name (mother) _______________________________________
Place of birth _______________________________________
Date of birth_________________
Address _____________________________________________________
Post Code ____________ Telephone _________________
Mobile phone _____________________
e-mail _____________________________________________
and
Name (father) ______________________________________
Place of birth _______________________________________
Date of birth_________________
Address _____________________________________________________
Post Code ____________ Telephone _________________
Mobile phone ____________________
e-mail _____________________________________________
have been given the information contained in the “Information leaflet” and have been informed that:
• the biological material collected may be stored with the……………bank; • any sample that is not suitable, or that ceases to be suitable, for storage for therapeutic purposes may be used for research purposes, if I/we give my/our consent; • the confidentiality of all personal data will be protected in accordance with the law; • my/our participation is voluntary; • should I/we require further information I/we can address our queries to the Director of the cord blood bank, Mr./Dr.………… .
□ I/we agree □ I/we do not agree
that the biological material may be used for scientific studies or research as indicated in the information leaflet;
□ I/we agree □ I/we do not agree
that the anonymized biological material may be transferred to another Center connected to the Bank, for purposes of research.
Date ________________________________________________
Mother's signature ____________________________________
Father's signature (if agreeable) _________________________
**Physician/healthcare operator who obtained consent:
Name …………………………………………………………….
Qualification …………………………………………………….
Department/Institution
Tel/Fax ………………………….
Date …………………………….
Signature…………………………………….
*If the details are the same as those on the form for consent to donation, only the name of the mother and father need be given.
**If the physician/healthcare operator is the same as the person who obtained the consent to donation, only the name and signature need be given.
Treatment of personal information
N.B.
Pursuant to Legislative decree No. 196 of 30 June 2003 containing “Code for the protection of personal data,” you are informed that your and your child's personal data will be recorded electronically. These data are indispensable for the storage of the biological material and for its inclusion in the registry of available biological samples.
The only persons who will, if necessary, have access to this information are (name) ……………….
No personal or sensitive information will be disclosed to third parties.
Informed Consent to the Treatment of Personal Details
We, the undersigned
Name (mother) ………………………………………………….
Place of birth ________________________________________
Date of birth_________________
Address _____________________________________________________
Post Code ____________ Telephone _________________
Mobile phone _____________________
e-mail _____________________________________________
and
Name (father) _________________________________
Place of birth _______________________________________
Date of birth_________________
Address ____________________________________________________
Post Code ____________ Telephone _________________
Mobile phone ____________________
e-mail ___________________________________
have been given the information regarding the treatment of personal and sensitive data:
□ I/we agree □ I/we do not agree to the treatment of my/our personal and sensitive data and that of my/our child. Date _____________________________ Mother's signature ___________________________________ Father's signature (if willing) __________________________ **Physician/healthcare operator who obtained consent: Name ……………………………………………………………. Qualification ……………………………………………………. Department/Institution Tel/Fax …………………………. Date ……………………………. Signature………………………………………. *If the details are the same as those on the form for consent to donation, only the name of the mother and father need be given. **If the physician/healthcare operator is the same as the person who obtained the consent to donation, only the name and signature need be given.
Allogeneic Donation of Cord Blood Information Leaflet
The blood contained in the umbilical cord (UCB) that is collected at birth represents a precious source of hemopoietic stem cells; these cells are also contained in peripheral blood and bone marrow and are able to generate blood cells (red and white blood cells and platelets).
Like bone marrow and peripheral blood stem cells, cord blood can be used in transplants for patients suffering from numerous hematological disorders (eg, leukemia and lymphoma) and genetic diseases such as Mediterranean or Cooley's anemia.
Cord blood collected at birth is stored in a public cord blood bank, the main objective of which is the storage of voluntary donations of cord blood that comply with specific quality requisites in order to make them available for transplants for Italian and foreign patients who in this way can receive treatment with a real chance of being cured.
The banks operate within the Italian National Health Service (SSN) as well as collect and store voluntary donations of cord blood and preserve UCB for directed use, in other words, for all cases in which it can be used for a family member suffering from a disease that can be cured through the use of hematopoietic stem cells or in cases wherein the family is at a high risk of genetic disorders that could affect future children. This service is offered free of charge to the patient and his/her family by the bank on receipt of documented clinical evidence.
The collection and storage of UCB for the above purposes can be ensured only if you, and your partner where possible, give informed consent. If the unit of blood meets the requisites for therapeutic use, it will be subjected to a series of tests and made available to Italian and foreign transplant centers. If it is found to be compatible with a patient awaiting a transplant, the unit will be released by the bank to the transplant center for that purpose.
UCB is a biological product of human origin and can therefore transmit infectious diseases such as hepatitis B, hepatitis C, AIDS, and syphilis as well as other potentially infectious agents. It is therefore necessary for you, and your partner if possible, to agree to a strictly private interview with a medical specialist or other properly trained healthcare operator, who will compile your medical history as well as your partner's and that of your family. You will be asked to fill in a questionnaire containing, amongst others, questions about your sexual behavior: we hope you will answer these questions so that every potential risk factor involved in the transmission of these infections can be excluded. The medical specialist or healthcare operator will also ascertain your health status and the course of your pregnancy so as to exclude the presence, at the time of the interview, of any factor that might lead to a possible risk for you or your child at the time of birth. An obstetrician will assess your case as the end of your pregnancy approaches.
To ensure the complete safety of the UCB, it will be necessary that you agree to give a sample of blood at the time of delivery and at an interval of 6–12 months from that date to be tested for the above transmissible diseases, including a test for HIV: you will also be asked to agree to provide documentary evidence of the health status of your child (pediatric certificate, pediatric record, etc.) whenever the bank asks you, and to give notice to the bank if your child should develop any relevant disorder, so that the bank can make the appropriate evaluation concerning the unit you donated. This information is extremely important for the decision whether or not to use the unit you donated in a transplant. Your blood, and the UCB, will be tested in order to evaluate their compatibility. The cord blood will also be tested for congenital hemoglobinopathies and additional tests may be carried out for other genetic disorders if these are expressly requested by the transplant center in which case you will be informed of any results that may be useful for the health of your child. A sample of your blood will be stored by the Bank and possibly used for further tests if the transplant center should require them.
Your frozen blood sample may be transferred to the transplant center so that any tests that may be required in connection with the therapeutic use of UCB can be performed there.
If any of the tests carried out on your blood should give a positive result, the bank will contact you to inform you of the fate of your donation and explain matters to you: this will be done in full respect for your privacy and for the confidentiality of this information.
Donation of UCB is completely voluntary and you may wish to consult a physician of your choice before giving informed consent. In any case you may withdraw consent at any time before the sample is taken. If you decide not to participate or to withdraw your participation in this program, you do not have to justify your decision: it will not lead to any manner of discrimination on the part of healthcare operators or in any way influence the treatment given to you or your child. If a donation is made for philanthropic purposes, consent cannot be withdrawn after the sample has been taken and you may not claim any rights in respect of UCB.
Some of the questions you will be asked are of a personal nature and may cause embarrassment; you may read these questions in the questionnaire regarding suitability before deciding whether or not to participate.
You may at any time ask for information regarding the availability and/or possible use of the unit of UCB you have donated and may ask for information concerning the scientific research studies carried out by the bank even if these are not strictly relevant to your health.
In the event that a member of your family should need the UCB you donated for clinical purposes and it is still available, the unit will be released to you at the request of a healthcare operator and after verification of its suitability, at no cost to yourself. You will receive a copy of the informed consent form you signed. It is understood that the biological material you donated and all data relating to the donation may be used exclusively for the purposes described on the informed consent form.
Collection, Banking, Storage, and Use of UCB
Collection
UCB may be collected exclusively during uncomplicated spontaneous full-term deliveries (≥37 weeks) or caesarean sections elected by trained and qualified healthcare personnel; collection takes only a few minutes and involves no changes in the delivery procedure; it is performed after the umbilical cord has been cut and the child has been removed from the delivery area to be given appropriate care. The collection procedure thus does not carry any risk for either mother or child and consists in placing the blood that has remained in the umbilical cord in a special sac. The sac and all other materials used are sterile and have been validated for this specific use: the procedures used guarantee high levels of safety and are strictly monitored.
Banking and storage
The unit of UCB will be transferred to the cord blood bank and subjected to a series of controls and tests aimed at characterizing the blood and establishing its suitability for storage and therapeutic use. Only cord blood units that meet legally defined requisites of quality and safety will be banked, to ensure that only safe and effective units are offered. The unit will be banked only if all the tests for infectious agents are negative and if it contains the minimum number of cells necessary for its use in a transplant. If the unit is found to be suitable it will be frozen so as to ensure its long-term viability and stored in liquid nitrogen at a temperature of −196°C in constantly monitored storage containers equipped with a recording and alarm system. All the procedures are rigorously recorded to ensure the unit's traceability and its immediate availability in the event of a request from a transplant center for a patient needing a stem cell transplant.
Use
The data relating to the UCB unit are entered in an International Stem Cell Donor Registry, where they will be identifiable only by a code. The registry allows the selection of a UCB unit compatible with a given patient, in which case the unit is released and used for hematopoietic stem cell transplant.
Expected Benefits
• The opportunity and satisfaction of performing “a major act of altruism”: the donation of cord blood may save the life of a child or an adult suffering from diseases that can be cured by a transplant of hematopoietic stem cells;
• Your contribution to establishing an inventory of UCB units for use in transplants may even benefit your child: your unit may still be available in the event that someone in your family should need it; or a compatible unit could be identified among those stored.
• If the unit has not yet been used by other patients, it may still be available for your child or other human leukocyte antigen (HLA)-compatible siblings in case of need. In this case the stored cord blood will be made available to you. If the unit has already been used but your child is confirmed as being HLA-compatible with the family member needing a transplant, the stem cells can be collected from your child's bone marrow or peripheral blood. However, if your child should become ill, the stem cells collected at his or her birth may already contain disease markers, making them unusable for treatment. But it will still be possible to consult the international registries, where the details of more than 450,000 units of cord blood and more than 14,000,000 classified donors are available.
• The possibility to offer
• The availability of significant biological resources necessary for research, if your unit is not found suitable for therapeutic purposes and you decide to offer it instead for research purposes.
Risks and Possible Discomfort
The collection of UCB is absolutely painless, safe, and noninvasive for mother and newborn. It is performed by professionally qualified and specially trained healthcare operators while other healthcare personnel are caring for the mother and the newborn, who remain the top priority.
Only a few milliliters of peripheral venous blood need to be collected from the mother to test for infectious diseases: any discomfort that may be caused will be slight and in any case identical to that caused by the collection of blood for other purposes.
Alternatives
The alternatives to the philanthropic donation of cord blood for allogeneic use are listed below:
1. Nonparticipation in the donation scheme (self-exclusion on personal, health or religious grounds); in this case your child's UCB will be treated as regular health refuse and discarded together with the placenta and other material; 2. Storage of your child's UCB in foreign private cord blood banks, where it will be available for autologous and/or intrafamily use, in accordance with the export procedures provided in current legislation. The storage of cord blood for autologous use is not permitted in Italy because there is no scientific evidence to support it and it is not a basic necessity. All the costs incurred for the export procedure will be payable by the applicants; 3. In the event that your child's cord blood is found unsuitable for therapeutic purposes, the unit can be eliminated or, with your consent, used for research purposes.
Scientific Research and Other Potential Uses of Cord Blood that is Not Suitable for Transplants
In the event your donation does not meet the quality requirements for use in a transplant, it can become an important resource for research purposes. Units that are stored with a view to their use in a transplant may be used for research purposes only if unforeseen circumstances render them unsuitable for further storage. This potential use for research purposes may involve monitoring of quality, storage techniques, freezing, and thawing; basic and applied research in the fields of hematology, transplants, and transfusions. Cord blood will be used exclusively by the bank or, if you agree, by other research groups associated with the bank, which operate in compliance with current regulations and guidelines regarding the ethical aspects of scientific research. Any of the biological samples that are transferred to other centers for research purposes will have been rendered irreversibly anonymous. No personal details regarding either you or your child will be transferred; they will instead be kept by the bank of origin, where only authorized personnel will have access to them. In no case will any biological sample be passed to third parties for profit.
Any scientifically significant results will thus be anonymous and will be published without any reference to the sources of biological materials and in aggregate form.
No research will at any time be performed for profit. Neither you nor your child will derive any economic advantage from such research.
Costs and Compensation
You will not have to pay any costs and will receive no compensation for making a philanthropic donation. Your healthcare is provided as part of the Basic Levels of Healthcare.
Consent
If you consent to donate UCB, please sign the consent form. You are reminded that consent cannot be withdrawn after the cord blood has been collected.
You are also asked if you wish to give separate consent for the use of the UCB for research purposes in the event it is not suitable for storage or becomes unsuitable for therapeutic purposes. In the latter case you and your child (when he/she is able to give valid consent) may withdraw your consent, but only for the use of UCB for research; in this case, if the sample should become unsuitable for use for therapeutic purposes it will be eliminated and not used for research.
We cannot guarantee that your child's cord blood will be collected and stored, and your agreement does not represent an obligation on the part of health operators to collect it; however, professional and dedicated are the staff, and despite every effort on the part of the health facility to ensure support for the program, clinical, procedural, or organizational circumstances may arise (priority in the delivery room is given to care for the mother and child) that make it impossible to collect and/or to store the unit.
Further Information
This document has been prepared in accordance with key statements on ethics and codes of medical ethics.
Whatever you decide, we thank you for your time. If you consent, you will be doing something for the community that holds the hope of a cure, which may contribute to scientific research.
All the information you give will be treated in accordance with Italian legislation for the protection of personal data (Legislative Decree 196/2003 and subsequent provisions).
For further information, please refer to the Manager of the ……………Cord Blood Bank ………………………………………………………………, Tel………………….
Or to the Manager of the Center for Collection ……………………. Tel……………………
The person responsible for processing your personal details is ………………………….
Tel …………………….
Conclusions
The information leaflet and consent form are here offered to a broader Italian and international scientific community in the belief that they may be helpful not only to those professionally involved in this field but also, more generally, to all those interested in the storage of biological materials of human origin.
A number of informed consent forms have been proposed in the literature and have been adapted to the specific case of the storage in biobanks and use of biological samples of human origin. Some of these proposals took into account formats already in use by various institutions. Among the best known are those proposed by T.A. Caulfield et al., 9 by the Medical Research Council, 10 by Sobel and Hansen, 11 and, more recently, by Porteri and Borry 12 and Salvaterra et al. 13
The definition of a standard information leaflet and consent form for use throughout the Italian network aims to respond to the need to foster the completeness, precision, and uniformity of information provided to donor mothers/fathers in the area of cord blood storage, while leaving individual biobanks free to supplement the above documents in accordance with their specific requirements.
The decision to place the Italian documents at the disposal of the international scientific community was taken, because these documents have the following uses:
• offer a summary but essential description of the regulations currently in force in Italy in the matter of procedures for storing cord blood and the related clinical applications; • are prepared on the basis of the most authoritative international standards, particularly those issued by NetCord.FACT; • include proposals on the issue of possible uses for research purposes of cord blood units that are found to be unsuitable for clinical use and address the repercussions that this alternative use can have on formulating informed consent; • also address issues of privacy and the protection of personal data.
Footnotes
Author Disclosure Statement
No competing financial interests exist.