Bristol Children s Vaccine Centre Bristol Children s Vaccine Centre Level 6, UHB Education Centre, Upper Maudlin St., Bristol, BS2 8AE, UK Tel: +44 (0)117 342 0172, Fax: +44 (0)117 342 0209 E-mail: bcvc-study@bristol.ac.uk, valtyr.thors@bristol.ac.uk The First BCVC Nasal Flu Vaccine Study (The effects of live attenuated trivalent intranasal influenza vaccine on the nasopharyngeal bacterial colonisation of healthy children aged 2-4 years attending day care centres. A single centre, randomised intervention study.) Dear Parent/Caregiver, We are inviting all parents and children who go to your nursery to take part in a research study. Children taking part will be offered a vaccine against flu virus. The vaccine is given as a spray into the nose ( nasal ). All children in the study will have nasal swabs taken to look for bacteria which commonly live in children s noses. What is flu? Flu (influenza) epidemics happen every winter and are caused by a common virus which usually affects the nose, throat and lungs. It occurs in adults but is very common in young children. Every year, many days at work, school and nursery are missed because of flu. In some years more than one in three children get flu. The infection spreads easily from one person to another (by coughing, sneezing or touching), especially in places where children are in close contact including nurseries and playgroups. The commonest symptoms of flu are fever, muscle aches, cough, sore throat, blocked up nose and tiredness. Children can be unwell for from a few days up to several weeks. We also know that when children get infected with flu they sometimes get bacterial infections as well, including ear infections (otitis media), chest infections (pneumonia) and occasionally even serious blood stream infections. What is the flu vaccine used in the study? The flu vaccine used in this study has recently been licensed for use in children throughout Europe but is not yet widely available except in America. The vaccine has been used a lot in children since 2003 in the USA and, because it is available there, we are able to obtain supplies for the study. It is different from flu vaccines currently used in the UK because it is given as a spray in the nose rather than by injection and because it contains living flu viruses, which are weakened so that they grow just enough to stimulate the immune system against flu but not Page 1 of 6
enough to cause illness. This is similar to many other widely-used vaccines against viral infections. This nasal flu vaccine has been given to millions of children from the age of 2 years and adults in the USA. The vaccine is effective at preventing flu and associated illnesses like ear infections in most people who receive it and is about 50% more effective than injected flu vaccines in children. What other vaccines against flu are available? At present in the UK, apart from in 2009 when there was a pandemic of a new strain of flu called swine flu, healthy children are not offered flu vaccines. Instead, each autumn, injected flu vaccines containing killed flu viruses are only offered to some children and to adults who have medical conditions which put them at high risk of getting seriously ill when they get flu as well as to elderly people. It would be difficult to give flu vaccine injections to all healthy children during a short period of a few weeks every year. What is the purpose of this study? This study is not being done to find out if the nasal flu vaccine works and is safe, as this has previously been extensively studied. Instead we want to offer protection to children against flu using the vaccine and at the same time find out about the ways that the weakened viruses in the vaccine interact with the bacteria that normally live in the noses of healthy children. This is important because it may help us understand how normal strong flu viruses and other common viruses affect these bacteria too. We hope this will help us find new, better ways to prevent illnesses due to infections in children. We can do this by taking swabs (like small versions of the cotton wool buds you use to clean your ears) from each child s nose before and a few days after they receive doses of the vaccine. It would also be important and interesting to take swabs from children in the nursery who have not received vaccine. This would give us background information which would help us understand our results from the vaccinated children better. So children can still take part even if their parents don t want them to have the nasal flu vaccine. In children whose parents agree, we would also like to take a small sample once only at the second study visit, where we wash the inside of the nose with a teaspoonful of some slightly salty water and suck it back out again and keep it. This is called a nasal wash. It sounds uncomfortable but, actually, children don t generally mind it much. However children whose parents don t want us to do the nasal wash can still take part in the study. There is no need to take any blood samples or to give any injections in this study. What exactly happens in the study? Before taking part, you will need to read the information in this leaflet. We will arrange to meet with you to answer any questions you may have. If you wish to go ahead, we will ask you to initial, sign and date a form which shows you have agreed to take part and exactly which parts of the study you have agreed to. All children whose parents/carers agree will receive two doses of nasal spray with four weeks between each dose. The timing of these vaccines will be different between children so we can compare what happens to the nasal bacteria in children receiving vaccine with those not receiving the vaccine and be sure whether any changes are really due to the virus in the vaccine. The correct dose of flu vaccine is two doses so all vaccinated children in the study will get the right dose to protect against flu. This is further outlined in a flowchart (see below). Page 2 of 6
Flowchart Group 1 Visit 1. Day 0 Visit 2. Day 7-12 Nasal swab/(wash) Visit 3. Day 28-35 1st dose Visit 4. Day 7-12 after visit 3 Visit 5 Day 28-35 after visit 3 2nd dose Follow up telephone call 1 month after visit 5 Group 2 1st dose Nasal swab/(wash) 2nd dose Follow up weeks (max) 0 1(2) 4(5) 5(7) 8(10) 12(14) All enrolled children will be given two doses of vaccine but at different time points as they will be allocated to two groups. The first group will only have a nasal swab in visit 1, 2 and 4 and the vaccine together with a swab in visits 3 and 5. The second group will only have a nasal swab in visit 2, 4 and 5 and the vaccine together with a swab in visit 1 and 3. Which of these two options they get will be decided by chance (rather like tossing a coin). This is illustrated in the flow chart above. All children will take part in the study for approximately 12-14 weeks and will be seen by the study team five times. These visits will normally happen at the nursery but can happen somewhere else convenient if necessary. At the first visit, we will ask you about your child s past and current illnesses and medications, previous vaccines and about the health of other members of your household. A study doctor will examine your child, including their ears, chest and tummy. Whether or not s/he is having the spray, a small swab will be taken from his/her nose. If you agree to the vaccine and depending on which group your child is in, your child will have their first nasal spray dose at this visit. The vaccine will be sprayed into each nostril. We will stay and observe your child for 30 minutes after the vaccination. A second visit will take place 7 to 12 days after the first. The nurse or doctor will ask about your child s health since the first vaccination and take another swab from their nose. The third visit will take place 4 weeks after the first visit. After the same health check, a swab will again be taken from your child s nose and, if you agreed to the vaccine, s/he will receive a nasal spray at this visit. The fourth visit will take place 7 to 12 days after the third. Again the nurse or doctor will ask about your child s health since the first vaccination and take another swab from their nose. The fifth and final visit will take place 4 weeks after the third visit. After the same health check, a swab will again be taken from your child s nose and, depending on which study arm your child is in and if you agreed to the vaccine, s/he will receive a nasal spray at this visit. 4 weeks after the last visit we will give you a phone call to check that all is well and that you have no concerns. Page 3 of 6
Throughout the study you will have 24 hour access to the study team by phone in case you have any questions or concerns. Being in the study will not change the normal care your child receives in the nursery or your normal access to NHS services. What are the possible side effects of the vaccine and nasal swabbing? This flu vaccine has been given to very large numbers of people, including children aged 2 and older in the USA since 2003 and has not been linked to any serious side effects. In research studies in which children given vaccine and placebo were compared, vaccinated children had runny noses and fevers and were irritable and less active slightly more often over the next 10 days than those who received placebo, this difference being even less noticeable after the second dose. Other mild flu like symptoms (such as sore throat, cough, abdominal (stomach) pain, headache, chills, vomiting, muscle aches and diarrhoea) were no more common in the vaccine group than the placebo group. However, as with any medicine, this vaccine may involve other risks, which are not yet known about. As with other vaccines, severe allergic reactions may occur very rarely after receiving this vaccine. Taking nose swabs and nasal washes may cause mild discomfort for a few seconds. Why am I being asked to take part? You and your child are being asked to take part in this study because he/she is aged between 2 and 4 years and attends a nursery/day care centre. We expect that 200 children will take part in this study, which will take place in the city of Bristol in the UK. What will you have to do? If you want to take part in the study, you can do so by sending an e-mail to bcvc-study@bristol.ac.uk and state your interest or wait until the study team visits your child s nursery and approach them then. Parents of children taking part in the study will be asked to contact the study team if they have any concerns during the study. Bringing your parent held record Red Book to the vaccine visits is helpful, as we could then record the vaccine doses. What are the possible benefits of taking part? Your child will receive nasal flu vaccine and will therefore be better protected against flu this year. The study results may help us find new ways of protecting other children against getting flu and other serious infections in the future. Who should not take part in the study? Children who are aged less than 2 years. Children with a history of hypersensitivity to eggs, gentamicin or any other components of the vaccine should not receive vaccine Children receiving salicylate therapy (Aspirin) should not receive vaccine Children with a history of asthma or active wheezing should not receive vaccine Children who have already had flu vaccine this year should not receive vaccine Children with abnormally reduced immunity should not receive vaccine Page 4 of 6
What happens if I say no? Participation in the study is totally voluntary. If you decide to say no, this will not change your child s normal health or nursery care in any way. What if I say yes, but change my mind later? If you agree to take part you will be able to opt out at any point if you change your mind, without giving a reason if you don t want to and without affecting your child s normal care. Equally, we may decide to take your child out of the study if we feel it to be in their best interest. As part of the study, nasal swab/wash samples will be stored so researchers can learn more about infectious diseases and how the body responds to them. We hope that if your child did withdraw from the study, you would still allow us to use these samples. If, however, you did not feel that this was appropriate then we would destroy them. What if something goes wrong? In the very unlikely event that your child is injured and on the balance of probabilities this is due to taking part in this study, the University has taken out an insurance policy that will pay compensation to your child. This does not affect your or your child s statutory legal rights. What else do I need to know? We will make sure that you are kept informed of any new information that becomes available, which may influence your decision to continue. The vaccines are free. Records of your child s involvement in the study will be kept by the study team on special forms, which will have your child s initials and date of birth on them, but no full name. The regulatory authorities may ask to review study and medical records to ensure that all study information has been recorded correctly. Any information given to these organisations remains confidential and no one will be identified by name in any presentation or publication of the study results. At the end of the study when all the planned tests have been done, if there are any samples not completely used up, rather than throw them away, we would like to ask your permission to keep them so that if other important research questions about infectious diseases and immunity come up which they could be used to help answer, they could be used to do this either by researchers in Bristol or in other research organisations around the world. No information that could be used to identify your child will be given to anyone else. Neither the samples or anything in them or any information related to them will be sold or used to make money. Tests could, for example, involve looking for infectious bugs or looking at the DNA (genetic code) from your child to help understand susceptibility to infections and the developing immune system. However you do not need to agree to any of this in order to take part in the study. You can opt in or opt out of this extra future research or the use of DNA when you complete the consent form. What if I wish to complain about the way in which the study has been conducted? If you wish to complain or have any concerns about any aspect of the way you've been approached or your child has been treated during the course of this study, please contact Professor Adam Finn (contact details at the top of this document) in the first instance. Page 5 of 6
If you have any complaints or concerns, you may also contact Dr Birgit Whitman, Head of Research Governance, Research and Enterprise Development, University of Bristol, Tyndall Avenue, Bristol BS8 1TH, UK. Tel.: +44 (0)117 928 8676; birgit.whitman@bristol.ac.uk So, in summary, what will happen if we join the study? Send an e-mail to bcvc-study@bristol.ac.uk or talk to the study team when they arrive at the nursery and let them know you are interested. Your child will have five visits at their nursery from the study team over a period of about 10-14 weeks. Your child will have a total of five small swabs taken from his/her nose over a 3 month period, each one preceded by a short health check. If you agree, your child will receive two doses of nasal spray flu vaccine over the same period. This would significantly reduce her/his risk of getting influenza infection and related illness this winter. Finally, and again, only if you agree, s/he will have a nasal wash sample taken at the same time as the second swab. The study team will be available to you for any advice you might need, and will contact you a month after the last visit to enquire about your child s health. Yours sincerely, Professor Adam Finn Study Organiser Dr. Valtyr Thors Study Doctor Page 6 of 6