Royal College of Paediatrics and Child Health

Insert application name Insert version number Date. BRITISH PAEDIATRIC SURVEILLANCE UNIT ROYAL COLLEGE OF PAEDIATRICS AND CHILD HEALTH 5-11 Theobalds Road, London WC1X 8SH Telephone: 0207 092 6173/4 Email: [email protected]

Phase 2 Appl i cati on Form

Please use the space provided to complete this form. Please read questions carefully as failure to provide sufficient detail may lead to a delay in processing the application or its rejection. More detailed guidelines are available in the BPSU study application handbook (available at: www.rcpch.ac.uk/bpsu/resources)

There is no word limit but please try to complete application succinctly.

Titl e of the study ( max 250 characters, i ncluding spaces)

Insert study title here

2) Titl e of the study to appear on orange card ( max 75 characters, i ncluding spaces)

Insert study title here

3) I nvesti gators

Please list all investigators involved in the study, their job title, affiliation, and planned contribution to this study. Please also indicate clearly the principal contact for correspondence on this application, giving a full contact address, e-mail address and telephone number. (If more than 4, please insert additional rows as needed).

Principal Investigator Job title and affiliation Contribution to the study Click to enter name and contact Enter text here. Enter text here. details.

Other Investigators Job title and affiliation Contribution to the study 1 Click to enter name and email Enter text here. Enter text here. details. 2 3 4

Have you identified an Irish contact to support the study in Ireland?

Yes No Version 26, May 2017 1 Insert application name Insert version number Date.

Have you identified a contact in other countries not included in the main study team?

Country Job title and Contribution to the Other Investigators affiliation study 1 Enter text here. Click to enter name and Enter text here. Enter text here. email details. 2 3 4

4) Lay Summary ( max 250 words)

Please describe briefly in LAY terms the purpose of your study. Do not use complicated medical terms as this summary will be used to inform the public of your intended study – if approved.

Enter text here.

5) Descri be the study i n l ay terms

Briefly describe in LAY terms under the following headings:

a) Background to the study - Please describe the rationale for the study and main aims and objectives, including the condition’s known epidemiology, clinical and public health importance.

Enter text here.

b) Study outputs and impacts - Please identify the outputs and potential impact of the study in terms of i) scientific knowledge, ii) public health and/or service benefit, iii) clinical practice, iv) potential benefits to patients and families.

Enter text here.

6) Proposed durati on of study

a) Proposed duration of surveillance (period on the orange report card) - Please state the duration of case reporting (13 months min) and length follow-up of cases, and briefly justify these.

Enter text here.

7) Case defi ni ti on and reporti ng i nstructi ons

Please give careful thought to providing a precise and practical definition (based on symptoms/signs/investigations) that will be understood by general paediatricians. Use an Version 26, May 2017 2 Insert application name Insert version number Date. internationally accepted case definition if at all possible and reference previous studies if relevant. Examples of previous BPSU case definitions and reporting instructions are available from the BPSU office.

The surveillance case definition is the definition that will be provided to the reporting physicians. In many cases it may be less specific and therefore more ‘inclusive’ than the analytic case definition (which is the definition used for the analysis), to ensure that all potential cases are reported. However, there are instances where the surveillance case definition is very specific (e.g. unequivocal laboratory result in a defined group of patients), and therefore matches the analytic case definition. a) Surveillance case definition

Enter text here. b) Analytic case definition – a definition that maybe more aligned to DSM 5/ICD 10 or requires specific tests to confirm – Sometimes this definition can be same as a) See guidance handbook for further advice

Enter text here. c) Age range for cases (NB. if you are including children aged >15 years, provide some evidence that children of this age are likely to be seen by a paediatrician)

Enter text here. d) Reporting instructions

Enter text here. e) Are you considering convening an expert panel to review cases and make a decision about inclusion or classify them based on the analytic case definition?

Yes No

If yes, identify panel members below.

Enter text here.

8) Expected numbers

Please supply an estimate of the number of cases expected each year, i.e. yearly incidence rate. Provide a reference for this estimate if possible. More than 300 cases a year would normally be considered on the high side for the BPSU. If you expect more please explain how you will reduce the burden on the reporting clinicians and describe in detail the extra administrative support required to manage the work. a) Expected numbers (per year)

Enter text here. b) If a denominator to those numbers is required for your study objectives, please specify what the denominator is and how will you obtain this data

Version 26, May 2017 3 Insert application name Insert version number Date. Enter text here.

9) Research questi ons/ survei l l ance obj ecti ves

Clearly state the specific research questions that will be answered by this study. These questions must be answered through BPSU methodology a) without any direct contact with patients, b) without seeking investigations that would not have normally been undertaken by the paediatrician and c) without recruiting a comparison or control group through the BPSU. These could include but are not limited to: Incidence/birth prevalence, Clinical presentation, Clinical Management, Outcome, Other.

Enter text here.

10) Methods

Please provide clear details of the study methodology you intend to employ to answer your research questions. Finally please answer the two questions below.

Study methodology:

Enter text here. a) Do any of your methods vary from conventional BPSU surveillance methods?

Yes No

If yes, please give details and the justification for doing so

Enter text here.

11) Alternati ve sources of data

Will alternative sources of data, other than the BPSU, be used for case ascertainment (e.g. data collected through other surveillance methods)?

Yes No

If yes, please: a) Describe the sources you intend to use (add any statements of support as appropriate)

Enter text here. b) Describe the purpose of this additional source

Enter text here. c) Describe how data will be collected and then matched between sources, and how patient confidentiality will be ensured

Enter text here. d) Describe the proposed analysis you intend to conduct using the data analysis plan template supplied Version 26, May 2017 4 Insert application name Insert version number Date.

Enter text here.

12) Publ i c pati ent i nvol vement

BPSU take public patient involvement very seriously as we believe that such engagement will lead to a more effective study. Guidance on this is available in our toolkit that can be located HERE

Consultation Researchers consult members of the public about the research e.g. through individual contacts, one-off meetings

Collaboration This includes active, on-going partnership between researchers and the members of the public e.g. involvement of members of the public on the project steering group, or as a research partners on a project.

Prior involvement a) How have you consulted affected families/patient support organisations/members of the public about your research question and the BPSU approach?

Enter text here.

b) What feedback did you receive and how did you respond?

Enter text here. c) How have you involved affected families/patient support organisations/members of the public in writing the public information leaflet/poster?

Enter text here. d) What feedback did you receive and how did you respond?

Enter text here.

Plans for involvement e) How will you keep the patients or patient/public representatives informed and engaged throughout the study?

Enter text here. f) Will you involve patients or patient/public representatives in the conduct of your study? If so, how do you plan to involve them?

Enter text here.

Version 26, May 2017 5 Insert application name Insert version number Date. g) How will you involve patients or patient/public representatives in the dissemination of the findings of the study? Please provide details of planned involvement in any of the following:

Enter text here.

13) Proforma

Please note that the BPSU has instructions for the design of proforma and has made available a template for investigators to use and modify as required. These can be found at www.rcpch.ac.uk/bpsu/resources. It is strongly advised that you liaise with the scientific coordinator and designated Medical Advisor before submitting your proforma as failure to do so may lead to delay in processing your application or its rejection.

Finally please answer the three questions below. a) Have service users/patient interest groups/patient representative contributed to the development of the study protocol and/or the proforma?

Yes No b) Has your proforma been piloted with general paediatricians?

Yes No

If yes, please provide details of changes.

Enter text here. If no, please justify.

Enter text here. c) Is a follow-up proforma planned?

Yes No

If yes, please give details below.

Enter text here.

Please supply a short data analysis plan with your proforma(s). A template data analysis plan can be found at www.rcpch.ac.uk/bpsu/resources

List the identifiers you propose to collect from the list below and the justification for their collection. Initials are not allowed.

Identifier Yes No Justification

NHS/CHI Number Enter text here. Hospital Number Enter text here. Date of Birth Enter text here. Sex Enter text here.

Version 26, May 2017 6 Insert application name Insert version number Date. Partial Postcode Enter text here. Ethnicity Enter text here. Other (specify) Enter text here. Enter text here.

14) Ethi cal Approval

Studies require REC, and CAG, incl (IG Toolkit approval). NHS permissions approvals are also required for Wales and Scotland and in latter case Public Benefit Privacy Panel approval. The BPSU will help you with the process as part of the contribution fee. There is also guidance on matters such as confidentiality, consent and data handling and further information is available from the BPSU office.

Please state your REC approval reference (to supply once known).

Enter text here.

Do you require assistance in preparing your IRAS paperwork?

Yes No

If Yes, i) advice and review ii) Complete and manage (cost attached, please enquire)

15) Fundi ng arrangements

The BPSU requests a contribution charge for facilitating research. From 1st April 2017 the contribution for the first year (for 13 months) is £15,000 and £8,500 a year for subsequent years for research teams supported by academic grants or for non-for profit organisations.

Those seeking funding from commercial sources should seek £25,000 and £12,000 for subsequent years – this representing the current full economic cost to the BPSU.

These amounts will be invoiced for at the start of each year. Any additional printing required will be charged to the applicant.

Funding arrangements should not only cover BPSU costs but also administrative costs including research assistance/secretarial salaries.

Please outline the funding arrangements for your study.

Enter text here.

16) Organi sati onal arrangements

Please state the person responsible for the following: Day-to-day administration (receiving reports, sending Enter text here. out questionnaires, correspondence with the BPSU Scientific management of the study Enter text here.

Version 26, May 2017 7 Insert application name Insert version number Date. Responding to clinical questions Enter text here. Collating and analysing results Enter text here. Additional academic or statistical support Enter text here.

17) Attached documents checkl i st

Please ensure that copies of all draft questionnaires and covering letters are attached.

Attached Documents Yes No

Covering letter/supporting statement from applicants Questionnaire (initial and follow-up if applicable) Data analysis plan Covering letters to reporting clinicians Supporting letters from specialty group and/or patient groups Public information leaflet/poster

Other relevant paperwork Enter text here. Please note that in addition to the above documents, successful applicants will be required to complete before the study can commence: a) BPSU service level agreement b) HRAR&D-CAG/REC application forms c) NHS IG Toolkit Confirmation d) PBPP form for Scotland

18) Signature

Signed by

Name Enter text here.

Date Enter date here. Application version Enter text here.

Developing a case definition

The case definition along with the research objectives are often the most important factor in the success or failure of a surveillance study and may be the main reason for the BSC to require revisions to the application. Failure to be able to apply a clear unambiguous case definition will result in the application being rejected. Please give careful thought to the case definition and if necessary seek advice from the BPSU office.

If you are developing a case definition, consider which symptoms, signs and tests you use to make the diagnosis. Symptoms and signs, such as fatigue or fever, which are common to many conditions are unlikely to be useful elements of a case definition on their own, however they may Version 26, May 2017 8 Surveillance case definition

Insert application name Insert version number Date. be clearly diagnostic of a disorder when found in association with other specific symptoms or signs.

The surveillance case definition defines clinically the cases that investigators are aiming to identify. It should state the age range, clinical symptoms and signs and results of investigations which would indicate a child is definitely or is likely to be a case. The surveillance case definition may be broader (less specific) than the analytic case definition applied using information from the proformas. For example, the surveillance case definition may include suspected but unconfirmed cases, whilst the analytic case definition for incidence estimates should include confirmed cases only. The reporting instructions are based on the surveillance case definition and state simply which cases should be notified to the study by clinicians.

Example reporting instructions & case definitions

Vitamin D Deficiency

Please report any child under 16 years of age who has had a first episode of a hypocalcaemic seizure secondary to vitamin D deficiency within the last month. Please report all suspected cases, even if the results of investigations are Reporting instructions pending.

Any child under 16 years of age who develops a suspected seizure* in the Case notified/proforma sent out presence of BOTH of the following biochemical criteria: 1. Low serum corrected calcium: <2.0 mmol/L 2. Low serum 25-hydroxy vitamin D (25-OH-D) level: < 50 nmol/L (<20 ng/ml)

Excluding children with a history of a previous hypocalcaemic seizure due to vitamin D deficiency (prior to this presentation)

Review of proformas and full details of *Include cases where the event is felt to most likely represent a true seizure, as opposed to another paroxysmal event. A seizure can be defined as a paroxysmal, cases by study team or expert panel time-limited change in motor activity and/or behaviour that results from abnormal electrical activity in the brain. Any child under 16 years of age who develops a suspected seizure* in the presence of BOTH of the following biochemical criteria:

1. Low serum corrected calcium: <2.0 mmol/L 2. Low serum 25-hydroxy vitamin D (25-OH-D) level: < 50 nmol/L (<20 ng/ml) Analytic case definition And in the absence of any of the following exclusion criteria:

1. Vitamin D deficiency associated with any of the following underlying diseases; fatmalabsorption, liver disease, renal disease, or illnesses necessitating total parenteral nutrition. 2. Vitamin D deficiency secondary to heritable disorders of vitamin D metabolism, including: i) 1-hydroxylase deficiency (pseudo-vitamin D deficiency rickets) ii) Vitamin D receptor defects (hypocalcaemic vitamin D resistant rickets) 3. A previous hypocalcaemic seizure due to vitamin D deficiency (prior to thispresentation) * Include cases where the event is felt to most likely represent a true seizure, as opposed to another paroxysmal event. A seizure can be defined as a paroxysmal, time-limited change in motor activity and/or behaviour that results from abnormal electrical activity in the brain.

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