09/H0304/13

Cambridgeshire 1 Research Ethics Committee

NHS Blood and Transplant

NHSBT Alloimmunisation Resource Version 2

NHSBT Alloimmunisation Resource Version 2

Permission to publish contact details not yet received

Permission to publish contact details not yet received

The National Health Service Blood and Transplant Alloimmune Resource (NHSBT AIR) will be a collection of blood samples and data from from individuals referred to NHSBT (formerly the National Blood Service) in England for investigation of immunisation against blood cells. Immunisation may have occurred during or following pregnancy, through transfusion of blood products due to ill health, or related to the receipt of a transplant.
We will plan to seek informed consent from each individual who agrees to enter the bank to:
- Collect and store a sample of DNA and plasma
- Collect and store data from existing clinical records and a questionnaire regarding medical history
- Undertake whole genome analysis for sequence variation (as subsequently detailed) and store the relevant data for further study
We will also ask each patient if they consent to further contact from the team for subsequent studies (any such study would require separate ethical approval).

Participants could be included in the resource in three ways: 1) those who are referred to NHSBT prospectively as they develop antibodies, 2) those who have been referred to the NHSBT previously who had developed antibodies, and 3) samples already held within the NHSBT. Samples from within the third category will differ from the others in that they are anonymised already so it will not be possible to seek further information from their donors. Some patients may have previously been involved in research relating to the development of antibodies against blood cells.

Samples may be collected in a number of different ways. Wherever possible we will try to use samples already collected during routine practice by using blood left over from routine clinical testing (samples will only be retained in the tissue bank where written consent is given). If this is not possible for any reason, an additional 10-25ml sample (approximately 2 to 5 teaspoons) may be taken the next time the patient’s blood is due to be tested for clinical purposes. If the patient is not due to undergo further blood tests then in some cases a separate 10-25ml blood sample may be collected. Occasionally, donors may be asked to give a saliva sample instead if DNA isolation from blood fails or if the individual does not wish to give a blood sample.

The blood samples will be used to perform immunological assays, to isolate cells, plasma, serum and nucleic acid (DNA & RNA). All these components of blood will be stored for future use at temperature controlled facilities at the NHSBT Cambridge Blood Centre. Plasma and serum can be stored frozen for an indefinite time span, and can be used for biomarker/immunological measurements (e.g. we will carry out measurements of the antibody level). DNA and RNA can also be stored indefinitely if frozen, and it can be used for analysing the genetic code (e.g. we will genotype samples and assess for copy number variation) or patterns of transcription (RNA).

After we have received the sample, information of every patient who gives consent will be downloaded from the NHSBT core computer system and the study participant will be asked to complete a questionnaire covering lifestyle and medical and obstetric history. We aim to collect up to 2,000 samples during the first year. Depending on funding, the panel might be extended to up to 10,000 donors. It is expected that collection can be completed within 60 months.

The NHSBT AIR aims to become a tissue bank that provides access to samples and data from individuals immunised against blood cells to the transfusion and transplantation research community. It is therefore difficult to foresee how many samples will be used annually. We do not plan to destroy samples, except for individuals who withdraw consent.

DNA samples will be used to genotype and perform genome wide screens (see e.g. www.wtccc.org) to determine genetic associations between specific genetic characteristics and the likelihood of immunisation against blood cell antigens. The plasma and serum samples will be used to carry out immunoassays and other measurements. On the basis of the results of these tests and the questionnaire, donors might be asked to participate in further studies. Such studies would have to obtain separate ethics approval. Only those participants who agree to further contact could be included in these additional studies. Other studies in which patients may be reapproached would be qualitative studies seeing to understand the experience of developing antibodies and taking part in a tissue bank. Again, such studies would require full separate ethical approval.

None

The NHSBT AIR is set up to collect blood (and sometimes saliva) samples from consenting patients. We wish to separate and store serum and DNA from these patients. The stored samples would be retained within the bank but also linked with relevant clinical information and with data generated by whole genome sequence analysis. We anticipate that the bank will be used in large scale genome wide association studies to try to link the clinical syndromes associated with immunisation against blood cells with specific genetic markers.
All data and samples would be pseudo-anonymised and identifiable information will not be released to researchers (but retained within the NHSBT systems). It is possible that future studies may wish to seek further information or samples from certain tissue bank participants. We would thus wish to ask particpants, at the time they enter the bank, whether they consent to be recontacted in future. Any studies requiring re-contact would require further ethical approval and could only utilise those particpants who have agreed to further contact. Any further contact could only be initiated by the NHSBT AIR team.
We wish to structure the tissue / data bank in this way so that the samples and data can usually be used in future work without the need to re-contact particpants or use link tables to obtain personal details (to protect anonymity). We would, however, expect that any projects using the data or samples would seek further ethical approval to do so. Where participants do consent to further contact, any studies requesting such contact would require further ethical approval to do so.

We would aim to make the samples and data available to researchers within the NHSBT and the University of Cambridge (subject to approval of the NHSBT AIR management team and to appropriate further ethical approval). If requests from researchers outside these domains are received they will be considered as well, and in principal every genuine researcher is allowed access. The study management committee will review requests from researchers to gain access, and make sure that samples are used for scientifically and clinically appropriate studies.
All researchers using the bank to gain access to samples will be obliged to publish results obtained on the samples through usual routes to reach the maximum possible benefit for health science and patient care. Ideally, the data accrued in any follow-up study would be uploaded in the study database to ensure the best possible cross-interrogation between datasets. The study database will be set up such that secure access can be obtained by registered users approved by the study team. Therefore, researchers using the tissue bank could be granted access to upload and view their results as well as published results by others.

Researchers who want access to the bank will approach the management committee with a written request describing the study and the selection criteria on which they would like to recall donors, e.g. genotype, phenotype, etc. If the management committee approves a study, the respective researcher would have to seek ethical approval. The recall of the donors and the consenting for the new study would be coordinated and handled by the AIR project team.

As part of this study we will be:
A) Sending a questionnaire to patient home addresses covering medical and obstetric questions. The information obtained through the questionnaire will help select participants for recall studies and will allow for associations between medical history and genetic markers to be made.
B) Carrying out biomarker and immunological measurements (e.g. antibody levels) in the stored plasma/serum samples.
C) Analysis of DNA sequence variation by the highest quality available technology (e.g genome wide typing array or whole genome sequencing) of the stored DNA samples so that frequency tables are available for disease markers. Some of the genotyping may be carried out under contract with approved providers within NHSBT, the University of Cambridge or externally (please see sections below). Samples released for genotyping under these circumstances will be pseudo-anonymised and not linked to any identifiable data. Data relating to the genotyping will be held within the NHSBTAir secure research database as described above.

Favourable Opinion

not yet received