Data collection and the

importance of good

follow-up

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Study overview

A multi-centre, randomised, placebo-controlled

trial to determine health and economic outcomes

of the treatment of a large Patent Ductus

Arteriosus (PDA)

in extremely preterm babies with ibuprofen within

72 hours of birth

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Research Question

Whether the pharmacological closure of a large

PDA (identified by echocardiography) with

ibuprofen within 72 hours of birth, improves short

and long term health and economic outcomes, in

extremely preterm babies.

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10 in total

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Description of DCFs…

• Form 1: Trial Entry

• Form 2: Trial Medication

• Form 3: ECHO Results around 3 weeks of age

• Form 4: 36 Week Form

• Form 5: Open Treatment of PDA*

• Form 6: Baby Outcomes

• Form 6a: Necrotising Enterocolitis Report Form *

• Form 7: Baby withdrawal *

• Form 8: Serious Adverse Event Report Form (CTIMP) *

• Form 9: Incident reporting *

* Optional – complete whenever appropriateVersion 5, 13/07/16

DCF completion (1)

Form 1: Trial Entry

Section A

Form 1: Trial Entry

Sections B - G

Form 2: Trial Medication

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DCF completion (2)

Form 6:

Baby

Outcomes

Form 6a: NEC

Report Form

Form 5: Open

Treatment of

PDA

Form 3:

ECHO

Results

around 3

weeks

Form 4: 36

Weeks

Form 7: Baby

withdrawal

Form 8: SAE

(CTIMP)

Form 9:

Incident

reporting

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Checklist

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Consent Forms

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• Consent Forms: If the father consents for the baby to

participate into the trial, ensure the mother countersigns

in the space provided

– we need her consent for some of the maternal data collected at

trial entry/randomisation.

Form 1: Trial Entry

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• Must be signed by a medically qualified doctor

• Do not state names, only list the ‘relationship’ to the infant:

• This questions forms part of calculating social deprivation:

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Form 2: Trial Medication

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• Completed 7 days after the last dose of trial medication.

• Culture proven sepsis?

– A blood/CSF culture proven sepsis ONLY

and

– does not require multiple samples

– We do not intend to include: ET tip/long line/UVC/UVC positive sepsis

– Record the results of the first culture proven sepsis

• Space to record test results, or tick if test was not done:

• Cerebral ultrasounds

Form 4: 36 Weeks Form

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• Complete at 36 weeks of postmenstrual age or at discharge

if discharged home earlier.

• If the infant dies before reaching 36 weeks, we would not

expect to receive a Form 4.

Form 6: Baby Outcomes (1)

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• Supplementary oxygen and respiratory support:

– When counting days use the highest level of support e.g. if a baby is

ventilated for 1 hour, then on CPAP for the rest of the day, both

would be counted.

• An infant might not be ‘screened’ for ROP at your hospital,

but ROP may be present; B12 and B13 are independent of

one another.

Form 6: Baby Outcomes (2)

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• There should only be one outcome selected as one form is

completed per admission/stay.

Form 6: Baby Outcomes (3)

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• When collecting the contact details of ‘Other family members’

– do not list names

– There is no space to record a person’s name (other than the mother)

– We only require recording the relationship to the infant

If a baby transfers…

• Phone the NPEU Co-ordinating Centre

01865 617 965

• Carry out 3 week ECHO scan and complete

Form 3 (if appropriate)

• Carry out 36 week ‘Oxygen Reduction Test’,

complete Form 4 (if appropriate) OR record on

transfer envelope date test due

• Complete Form 6: Baby Outcomes; in Section C,

complete tab B only

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If a baby dies…• Complete data collection forms as fully as

possible up to the time of death

– Including ‘Mothers contact details’

– We will be careful with the data, but may in very rare

incidences have a duty to contact them

• Health and Social Care Information Centre will

tell us about deaths that occur after discharge

however this may take several weeks

• If you become aware of a death that occurs after

discharge, please let us know

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Query prevention

• Please, write clearly!

• Answer all questions

• Avoid ambiguous answers

– ‘Not known’

– ‘Not available’

• NPEU must query missing data if no explanation

given.

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What to send to Baby-OSCAR

Co-ordinating Centre?All originals of completed forms

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Data Collection File

For your Data Collection File copy any completed

forms (1 – 9) plus a completed ‘Enrolment Log’

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Blinded endpoint review

• Given the subjective nature and complexity of diagnosis

for the outcomes listed below, a small number of

clinicians, as well as an independent radiologist, will

review all of the data relating to outcomes listed below

for the internal pilot phase and at least 10% for the main

trial.

– Severe intraventricular haemorrhage (IVH) (grade 3/4 with

ventricular dilation or intraparenchymal bleeding)

– Cystic periventricular leukomalacia (PVL)

– NEC definitive and/or complicated (Bell stage II and above)

confirmed by radiography and / or histopathology.

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The importance of good

follow-up

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What if the follow-rate is only 80%

overall?

• “80% is acceptable”

• What if the incidence of the primary outcome is

low?

− e.g. death, moderate or severe BPD at 36 weeks,

little outcome data at 36 weeks

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Does 100% follow-up make a

difference? (Cont’d 2)• 818 babies discharged from hospital after

being born at 32 weeks, outcome severe

disability

• Follow-up

− without difficulty (709, 87%) – 6.9% severe disability

− with some difficulty (40, 5%) – 17.5% severe disability

− with great difficulty (47, 6%) – 55.3% severe disability

Total disability changed from 6.9% to 11%

because of complete follow-up

Tin W, Fritz S, Wariyar U. Hey E. Outcomes of very preterm birth: children reviewed with ease at

2 years differ from those followed up with difficulty. Arch Dis Child Fetal Neonatal Ed.

1998;79(2):F83-7Version 5, 13/07/16

Protocol

• Assuming the risk of a child dying before 2 years of age is

10%

• The proportion of infants surviving to 2 years without

moderate or severe neurodevelopmental disability in the

control group is expected to be 55% [Mangham et al, 2009]

• 80% power to detect an increase in survival without

moderate or severe neurodevelopmental disability of 11%

from 55% to 66% and 90% to detect an increase of 13%

from 55% to 68%.

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• Increase rate of follow-up

• Other methods to get outcome data?

- Reminding parents; change of address

cards (spares are found in the

documentation box)

- Use of notes

- 2 year hospital visits; prompting parents

- Stressing the importance of follow-up

• Other suggestions..?

Solutions

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Contact details

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