Cerebral palsy pilot study parent / guardian information sheet

Your child is being invited to take part in the NeuralNET Cerebral Palsy Pilot Study.

Before you decide if you want your child to take part, please take time to read why the research is being done and what it would involve for you and your child. Talk to others about the study if you wish. Please feel free to contact us if there is anything that is not clear or if you would like more information.

If you are happy with this information and wish your child to take part in this study, you will be asked to sign a consent form, which will also be signed by a member of the study team.

• Part 1 tells you the purpose of this study and what will happen if your child takes part.
• Part 2 gives you more detailed information about the study.

Part 1

What is the purpose of the NeuralNET cerebral palsy pilot study?

A type of genetic testing called whole genome sequencing (WGS) is now available to doctors in the NHS to help determine if some diseases such as cancer and neurological conditions have a genetic cause.

WGS involves reading someone’s whole genetic code and looking for changes that cause disease. There are a number of different causes of cerebral palsy and for most children the cause remains unknown. There is growing evidence to show that some children have cerebral palsy due to a change in their genetic code.

At the moment, cerebral palsy is not a condition for which WGS testing is offered by the NHS. This research study is offering WGS testing to children with cerebral palsy to learn more about the potential genetic causes of cerebral palsy in the UK and to help develop a new NHS WGS service at Addenbrooke’s Hospital in Cambridge. At the same time, the study will collect information from the families of these children to find out what they think and feel about WGS testing and the results they receive.

All of this information is needed to help the NHS decide whether or not to make WGS testing for cerebral palsy available to doctors. In general, only the genetic findings that are found in your child’s genetic code that are clearly disease-causing and that relate to their cerebral palsy will be fed back to you and your child’s doctor as part of this research study. In some rare cases, you may be told of some other medically important genetic findings that are not related to your child’s cerebral palsy diagnosis.

Why is this important?

Currently cerebral palsy cannot be cured but some children who get a genetic diagnosis could benefit by becoming eligible to take part in clinical trials, by having their treatment personalized with the addition of existing drugs, and/or by adjustment of their clinical management.

All of these things could potentially improve medical care and outcomes. Offering WGS to children with cerebral palsy and collecting feedback about the testing from families will help us understand their attitudes toward this type of testing. It will also help us to ensure that the NHS WGS service meets the needs of patients, families, and doctors.

Why has my child been invited to join the NeuralNET cerebral palsy pilot study?

We are inviting children with a clinical diagnosis of cerebral palsy seen by three NHS services in Cambridge, Colchester, and Newcastle to take part in this study. We aim to recruit 66 children and their families.

Do we have to take part?

No. It is completely up to you and your child to decide whether to join the study. If you do join, you are free to withdraw at any time and you don’t have to tell us a reason. If you decide not to join or if you join and later decide to withdraw, your decision will not affect the healthcare your child receives in any way.

What will the study involve if we take part?

We would like your child to take part in this study, which will require them to have a blood test. We are also asking biological parents to take part, wherever possible, and for their genetic codes to be read as well. This is because whole genome sequencing is more effective if a child’s genetic code can be compared to their biological mother’s and/or father’s genetic code.

If you agree for your child to take part in the study, we will ask you to do the following:

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Visit 1 (day 0)

Where: Face-to-face appointment or phone call or video call.

Procedures:

• informed consent
• arrangements made for blood test(s)
• Pre-test questionnaire completion

Visit 2 (3+ months)

Where: Face-to-face appointment or phone call or video call.

Procedures:

• WGS results discussion

Visit 3 (+15 months)

Where: Phone call or video call.

Procedures:

• Post-test questionnaire completion

Visit 4 optional (+15-16 months)

Where: Phone call or video call.

Procedures: Interview (optional)

If your child is adopted or not under the legal guardianship of either of their biological parents, they can still take part in this study. If this is the case and you agree for your child to take part in the study, we will ask you/their legal guardian to sign a consent form for their participation, to complete the questionnaires, and to participate in the optional interview, but you/their legal guardian will not need to provide a blood sample.

What happens at the visits?

Informed consent

• For children under the age of 16, you will sign a consent form on their behalf.
• Children between 6 and 15 years of age will be asked to sign an assent form as well, where appropriate.
• When a child reaches 16 years of age they will be asked to give their own consent as an adult to continue in the study. If they are unable to consent for themselves, a legal representative will be asked to consent on their behalf.
• We will record your child’s details (name, date of birth, NHS number) and your contact details. We need this information so that we can send blood samples to the NHS service for testing and so that we can contact you in the future.

Blood tests

• The blood test will involve your child donating a small blood sample (half to one teaspoon). Blood samples will also be collected from biological parents if taking part.
• DNA will be extracted from blood by the NHS East Genomics Laboratory Hub (NHS EGLH). Some of the DNA sample, labelled only with a study number, will be sent to a commercial company called Illumina who specialize in whole genome sequencing. They will read your child’s genetic code.
• The genetic code will then be sent back to NHS EGLH who will look for any changes in it that shouldn’t be there.

Questionnaires

• The questionnaires will collect information about you and your child, and also about your thoughts and feelings about WGS testing before and after testing.
• They will be online and can be completed on a phone/tablet/laptop. You will be able to go back to them if you’re not able to complete them in one go.
• If you can’t access them online, a paper copy will be given to you to complete.
• They will each take about 20-30 minutes to complete.
• The study team are available by phone or video call if you need help to read and/or complete the questionnaires.

Result

• We will ask your child’s doctor to provide information describing their cerebral palsy to help the NHS EGLH team decide if any changes in your child’s genetic code are important. The EGLH team will write a result report and send it to your child’s doctor.
• Your child’s doctor will tell you the result at a face-to-face appointment or by phone/video call.
• The result may tell you that there is:

1. A relevant finding - A genetic change has been found that has caused or contributed to your child’s diagnosis of cerebral palsy, or
2. No relevant findings – At the current time, no genetic changes have been found that have caused or contributed to your child’s diagnosis of cerebral palsy

• A genetic counsellor who is part of the study team will be available to answer any questions you may have about the result, and they can also be contacted at any time during the study if you have concerns or need further information.

Interview (optional)

We will ask families to be interviewed about their experience of WGS testing, but this is optional. The interview will be by phone/video call at a time that is convenient to you, it will be recorded (audio-only) and take about 30-45 minutes. Other family members taking part in the study could also take part in the interview, should they want to. Your child is welcome to take part in the interview if they wish.

Is there anything else involved?

We may need to collect additional relevant medical information about your child or check information provided by your child’s doctor. Therefore, we will ask your permission to access and use your child’s NHS records to be able to do this. After you receive your child’s WGS result, we will ask your child’s doctor to provide some information on what, if any, changes to your child’s clinical care and/or management plan occur as a consequence of the WGS testing.

We will also ask your permission to contact you and your child if there are new studies for which they may be eligible. Agreeing to be contacted about future studies does not mean that your child has to participate in them.

Part 2

Are there any risks of taking part?

Collecting a blood sample

Qualified staff will collect the blood sample from your child, and from you if you are a participating biological parent. The most common risks of any blood test are mild pain/discomfort, bleeding, bruising, and fainting. A numbing cream or spray may be used for your child to reduce discomfort.

WGS

The WGS result for your child will be returned to you and there are some potential risks linked to receiving this information. The WGS result might be one you were not expecting or that you may have difficulty adjusting to after it has been disclosed to you. It might be difficult for you to understand what the WGS result means for your child. This could be upsetting, particularly if you need to make decisions about potential changes to your child’s medical care. Although your child’s genetic code is unique to them, there are some parts of their genetic code that they share with their with parents, siblings, and other blood relatives. This means that learning your child’s WGS result could have genetic implications for blood relatives which might upset you or your family. Before joining the study, it might be helpful to talk with your wider family about whether they would want to know about a result. It is also possible that the test may disclose non-paternity (someone who is not the biological father), or some other previously undisclosed information about family relationships, such as adoption. The study team are available to sensitively and confidentially discuss any concerns you have about the risks of participating.

Questionnaires and interview:

Completing the questionnaires or taking part in the interview may mean that you think about your and your child’s wellbeing and/or other things that could be uncomfortable or painful to think about. You can decline to answer any of the questions, and you can take a break from completing the questionnaires or the interview at any point if you are feeling distressed. The member of the study team conducting the interview will check how you are feeling throughout the process. If you experience difficult emotions during the study, please let us know and a member of the study team can discuss this with you and provide limited short-term support. If it might be helpful for you to access additional mental health support during or after the study, you can seek advice from your own GP about local support and resources.

What are the potential benefits of taking part?

If your child receives a WGS result that says a genetic change has caused or contributed to their diagnosis of cerebral palsy, this may change your child’s care/management and might lead to improved outcomes. There are also potential benefits for other families like yours and for society in general because all the data collected will increase our understanding about genetic changes and cerebral palsy. You will be contributing to research on cerebral palsy and be helping us to improve the WGS service that the NHS may offer in the future.

Will my child’s participation and my own involvement in the study be kept confidential?

Yes. Best ethical and legal practice is followed to ensure that all information collected will be handled confidentially and stored securely.

Everyone taking part in the study will be given a unique study ID number which will be used instead of names and/or other personal identifiers on all data collected by the study or that is generated from the WGS testing. A database linking unique study ID numbers to personal details will be kept but it can only be accessed by authorised members of the study team. This database will be stored in the secure data Safe Haven at the University of Cambridge Clinical School Secure Data Hosting Service.

None of the data collected by this study will be used or made available for any purpose other than for research and improvements in health care. Responsible members from the University of Cambridge or NHS Trusts may be given access to information for monitoring and/or audit of the study to ensure that we care complying with regulations.

When your child’s blood sample is sent to the NHS East Genomics Laboratory Hub (EGLH) it will be labelled with their name, date of birth and NHS number because:

1. The NHS EGLH needs this information to process the sample through the WGS service that they have built,
2. The NHS EGLH might need to ask your child’s doctor for more information to help explain any genetic changes that they think might be important,
3. The NHS EGLH will need to add this information to the WGS report that they will send to your child’s doctor.

All information and samples stored in the NHS are stored securely and confidentially, following strict NHS data protection guidelines. When the NHS EGLH sends a DNA sample to the external laboratory (Illumina) for WGS, it will only be labelled with your child’s unique study ID number.

What will happen to my child’s DNA sample and data?

If you agree, your child’s personal details will be kept for 10 years so that we can invite them to take part in other, related research studies. We will also keep the study data collected from the questionnaires, the interview, and from your child’s clinician in databases for 10 years. The DNA sample collected during this study and the WGS data will be stored indefinitely in the NHS EGLH. The DNA samples may be accessed for additional NHS genetic testing for your child in the future if indicated and with appropriate prior consent. Your child’s DNA sample and / or data collected during the course of the study may also be used in the future for other ethically-approved research studies that cannot yet be specified by other external organisations, such as the NIHR BioResource, or commercial organisations. Anonymously sharing your child’s sample and/or information is the best way to make sure that their participation in this study can help as many people as possible. All research being undertaken by external organisations who want to use your child’s DNA sample and/or data would require prior review and approval by an ethics committee.

We specifically ask your permission to share your child’s data with the following groups:

Decipher

• Which children will have their data shared? Children who have a relevant genetic finding.
• What data will be shared? A description of your child’s medical problems A summary of the genetic finding.
• Why is data being shared? To increase medical and scientific knowledge about genetic changes.
• Who will have access to the data? Doctors and scientists.
• For further information visit: https://www.deciphergenomics.org/files/pdfs/decipher_infofam_v7_2020.pdf

NIHR BioResource

• Which children will have their data shared? All children.
• What data will be shared? WGS data. A description of your child’s medical problems.
• Why is data being shared? To help researchers understand more about the genetic causes of rare diseases.
• Who will have access to the data? Approved researchers running other ethically- approved research studies.
• For further information visit: https://bioresource.nihr.ac.uk/about-us/governance-and-ethics/confidentiality/

General Data Protection Regulations

The University of Cambridge and the Cambridge University Hospitals NHS Foundation Trust (CUH) are the sponsors for this study. The study team will be using relevant information from your child’s medical records to undertake this study and will act as the data controller for this study. This means that the study team are responsible for looking after the information about you and your child and for using it properly.

University of Cambridge and CUH will keep identifiable information about your child for 10 years after the study has finished.

You and your child can stop being part of the study at any time, without giving a reason, but the study team would keep information about you and your child that has already been anonymised and used in the research analysis.

For the research to be reliable, we need to manage your child’s research records in specific ways and so your rights to access, change or move your child’s information are limited. Individuals from the University of Cambridge and CUH and regulatory organisations may look at your child’s relevant medical and research records to check the accuracy of the research study.

The only people in the study team with access to information that identifies your child will be people who need to contact you to send out study information or audit the data collection process.

If you agree for your child to take part in this study, your child will have the option to take part in future research through the University of Cambridge.

Where can I find out more about how my child’s information will be used?

You can find out more about how we will use your child’s information by asking one of the study team directly, or via email cuh.neuralnetstudy@nhs.net or telephone (01223 768614), or by going to www.hra.nhs.uk/information-about-patients/ or to https://www.information-compliance.admin.cam.ac.uk/data-protection/research-participant-data

What will happen to the study results?

Study data will be kept securely for 10 years in the Department of Paediatrics in accordance with good research practice.

The interview audio files will be deleted at the end of the study.

Quotes from individuals, without any means of identifying the individuals involved, may be reported in conference presentations, and written up in journals.

Non-identifiable data may be shared with other researchers through reports or scientific publications, project leaflets and other media. This may include anonymised quotes from the interview, results from the questionnaires and other relevant information from the study (e.g., details of your child’s genetic change).

Under no circumstances would your child’s identity or your identity be disclosed in any publications or collaborations.

What if we don’t want to carry on with the study?

You are free to withdraw your child from all or part of the study at any time. You can withdraw the DNA sample and information that have already been collected, or simply stop any involvement in the future. Please note that it will not be possible to remove any information that has been already been anonymised and used in research analysis.

In the event of the death of a participant, data and samples provided by the donor would continue to be available for use in the study in perpetuity.

What if there is a problem?

We are happy to address any complaint about the way you or your child have been dealt with during the study or any possible harm you or your child might suffer as a result of participating in the study. In the event that you wish to complain about any aspect of the way in which you or your child has been approached or treated during the course of this study, you should contact Professor David Rowitch 01223 769386 or pahodpaeds@medschl.cam.ac.uk.

You can also contact the Patient Advice and Liaison Service at Cambridge University Hospitals NHS Foundation Trust if you have any concerns or want to complain about the study by emailing cuh.pals@nhs.net or phoning 01223 216756.

The University of Cambridge, as joint Sponsor, has appropriate insurance in place in the unlikely event that you or your child suffer any harm as a direct consequence of your participation in this study.

Will we be paid for taking part in the study?

Yes. You will receive £30 for your time at the end of the study. The end of the study will either be following completion of the questionnaire that will be sent to you 1 year after you receive the genetic test result or following the interview, if you choose to do it.

Who is funding and who is responsible for the study?

The NeuralNET Cerebral Palsy Pilot Study is funded by the Rosetrees Trust, Isaac Newton Trust, and NIHR Cambridge BRC. Illumina, a commercial company, is providing WGS for all study participants. The study is jointly sponsored by the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust and they are therefore jointly responsible for the study. The study was reviewed by [insert details of REC and ID numbers] and has been approved by the Health Research Authority to run in the NHS.

Further information

The Study is managed by Professor David Rowitch at the University of Cambridge. Please contact the Study Team on cuh.neuralnetstudy@nhs.net or telephone 01223 768614 for further information.

Department of Paediatrics, University of Cambridge, Box 116, Level 8, Cambridge Biomedical Campus, Cambridge CB2 0QQ

Thank you for reading this information and considering joining the NeuralNET Cerebral Palsy Pilot Study.

This patient information sheet - reference IRAS 319781_NeuralNER CP Pilot Study Parent / guardian PIS v2.0 has been converted to a web page.