Trial of probiotic to prevent necrotising
enterocolitis and infection
PiPS Training
Trial Procedures and Documentation
Paul Heal
PiPS Trial Co-ordinator
Presentation Overview
• Where to find Trial Documentation
• Enrolment & Informed Consent
• Data Collection
• Baby Transfer
• Adverse Event Reporting
• Stool Sample Collection
• Completion of Trial Intervention Course and Reconciliation
Trial Documentation
• PiPS Documentation Box (stored on the NICU)
– This contains stock documentation for the day-to-day running of the trial:
data collection forms, information on trial procedures, Consent Forms, Parent
Information Leaflets, freepost envelopes, Transfer Packs, labels, etc.
• PiPS Site File (stored securely)
– This file is a documentation reference store for the Principal Investigator
containing all trial documentation and copies of approvals, contracts,
information on sponsorship, indemnity, unblinding, monitoring, etc.
• PiPS Data Collection File (stored securely)
–
This file is for storage of signed Consent Forms, data collection summaries,
received Transfer Checklists and copies of certain partially completed Data
Collection forms. The Trial Participant Log is also kept in the front of this file.
Trial Documentation
• In the front of each documentation store there is an index listing all the
contents.
• There is also an Index for Site Document Files; this lists the contents of
each documentation Box and File used in the trial.
Trial Procedures and Guidance
Guidance Sheet 1: Recruitment of babies: eligibility criteria
Guidance Sheet 2: Randomisation of babies to the trial
Guidance Sheet 3: Preparation and administration of the Trial Intervention
Guidance Sheet 4: Reconciliation of the trial intervention
Guidance Sheet 5: Completion of data collection forms
Guidance Sheet 6: Transfer of babies to other hospitals for continuing care
Guidance Sheet 7: Procedures when the intervention finishes
Guidance Sheet 8: Pharmacovigilance and safety monitoring
Guidance Sheet 9: Procedures for emergency queries
Guidance Sheet 10: Trial intervention stock control
Step by Step Guide: Baby Enrolment & Stool Collection
Enrolment
Identify and
establish eligibility
of baby
Eligibility
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Consent Form Completion
Correct Consent Form completion:
- Ensure all fields are completed
- Dates and study number
- Names and signatures
- If multiple birth, state birth order
- Hospital name NOT number
- Question boxes MUST be initialled!
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Form 1: Trial Entry
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Within 48hrs of birth
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Enrolment
The randomisation printout will list the
following details:
• Where, when and who completed
randomisation
• Baby identifiable information
• Allocated study number and package
• Intervention course start and finish
dates
• Stool sample collection dates
These details can be printed any time by
logging onto the randomisation website
and selecting the ‘Print randomisation
details’ link.
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Add allocated Study
Number and Package ID
Number to Form 1
Form 1: Trial Entry
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Locate Intervention
Package and add
baby’s details to label
Add allocated Study
Number and Package ID
Number to Form 1
PiPS Trial Intervention Package
Check the Package ID Number is the same as the one allocated by the
randomisation program. Enter the baby’s Name, DOB and the Study
Number allocated to the baby in the space provided.
PiPS Trial Intervention Package
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add allocated Study
Number and Package ID
Number to Form 1
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Complete Trial
Participant Log in PiPS
Data Collection File
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add allocated Study
Number and Package ID
Number to Form 1
Prescription of Trial Intervention
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Complete Trial
Participant Log in PiPS
Data Collection File
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add identifiers to documentation and package
Add allocated Study
Number and Package ID
Number to Form 1
Enrolment
Identify and
establish eligibility
of mother or baby
Informed
Consent
Obtain all
signatures on
Consent Form
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Complete Trial
Participant Log in PiPS
Data Collection File
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add identifiers to documentation and package
Prescribe the
Intervention on the
baby’s drug chart
Add allocated Study
Number and Package ID
Number to Form 1
Prescription of Trial Intervention
The trial intervention must be prescribed on the baby’s drug chart to be given
enterally once daily using the wording ‘PiPS intervention nnnnn, 1ml daily,
within 3hr of preparation’. The ID number ‘nnnnn’ (1 letter + 4 digits) of the
allocated package is an essential component of the prescription.
Enrolment
Identify and
establish eligibility
of mother or baby
Obtain all
signatures on
Consent Form
Informed
Consent
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Complete Trial
Participant Log in PiPS
Data Collection File
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add identifiers to documentation and package
Prescribe the
Intervention on the
baby’s drug chart
Administer the
Intervention as soon
as possible
Begin trial treatment as soon as possible
Add allocated Study
Number and Package ID
Number to Form 1
Enrolment
Identify and
establish eligibility
of mother or baby
Obtain all
signatures on
Consent Form
Informed
Consent
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Complete Trial
Participant Log in PiPS
Data Collection File
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add allocated Study
Number and Package ID
Number to Form 1
Add identifiers to documentation and package
Prescribe the
Intervention on the
baby’s drug chart
Administer the
Intervention as soon
as possible
Begin trial treatment as soon as possible
Complete Form 1 and
return to the Trial
Office within 7 days
Start Form 2: Daily
Data Collection
Enrolment
Identify and
establish eligibility
of mother or baby
Obtain all
signatures on
Consent Form
Informed
Consent
Complete Part
A of Form 1:
Trial Entry
Randomise baby into
the trial using online
randomisation program
Within 48hrs of birth
Complete Trial
Participant Log in PiPS
Data Collection File
Add Study Number to
Consent Form and file
away copies
Locate Intervention
Package and add
baby’s details to label
Add allocated Study
Number and Package ID
Number to Form 1
Add identifiers to documentation and package
Prescribe the
Intervention on the
baby’s drug chart
Administer the
Intervention as soon
as possible
Begin trial treatment as soon as possible
Complete Form 1 and
return to the Trial
Office within 7 days
Start Form 2: Daily
Data Collection
Informed Consent
• What is informed consent?
–
A process by which a participant or legal guardian voluntarily confirms his or her willingness to participate in a particular trial,
after having been informed of all aspects of the trial that are relevant to the participant's decision to take part in the clinical
trial.
• Who is eligible to seek informed consent?
–
Consent can be sought and obtained by any health care professional who has received PiPS and GCP training, and who is
registered to do so on the site delegation log. N.B. The Consent Form must be signed or counter-signed by a trained and
delegated doctor.
• Who is eligible to give consent?
–
Mothers automatically have parental responsibility for their children and can be the sole signatory on the consent form
although consent should be ideally sought from both parents. Fathers can only act as sole signatory if married to the mother or
if formally designated by the mother as able to consent.
• When should consent be sought?
–
Parents cannot formally give consent before the baby is born but whenever possible staff should try to begin the process of
talking to parents about the trial before the onset of labour; the objective is to give them as much time as possible to consider
their decision. If this has not been possible then they should be approached as soon as seems reasonable after birth.
• Can babies be recruited into multiple studies?
–
There is no theoretical reason why babies should not be actively involved with other trials or non-intervention studies while
participating in the PiPS trial.
Informed Consent
• Can babies be recruited from parents who do not speak English?
–
Parents who do not speak English should only be approached if an appropriate adult interpreter is available.
• Do I need separate Consent Forms for twins, triplets…?
–
Each baby must have a separate signed consent form. It should be explained to parents that the babies will be randomised as
individuals; thus siblings may be in different arms of the trial.
• Key points to be covered in discussion with the parent(s)
3
3
3
3
3
3
3
3
3
3
Has the parent(s) had an opportunity to read the Parent Information Leaflet?
Have you explained, and has the parent(s) understood, the aim of PiPS?
Have you explained what the trial entails, i.e. proposed treatment and description of procedures?
Have you explained the potential benefits and potential risks of taking part in PiPS?
Have you explained what a placebo is?
Have you explained what a ‘randomised controlled trial’ is?
Have you explained that if the parent(s) decline, the baby’s care is unaffected?
Have you explained that the parents are free to withdraw their baby (i) at any time, (ii) without having to give a reason and (iii)
without affecting their baby’s medical care?
Have you told the parent(s) that their GP will be informed of their baby’s participation in PiPS?
Has there been enough opportunity for the parent(s) to ask questions?
Data Collection
• There are 4 data collection forms that should be completed for all babies
in the trial:
– Consent Form
– Form 1: Trial Entry
– Form 2: Daily Data Collection
– Form 3: Baby Transfer, Discharge or Death
• There are a further 3 data collection forms in the Documentation Box
that may be needed for some babies:
– Form 4: Abdominal Pathology
– Form 5: SAE and SUSAR
– Form 6: Intervention discontinuation or trial withdrawal
Transfer of PiPS Babies
• As soon as it is known that a baby may possibly be transferred please
contact the PiPS Trial Office.
• Transfer Packs can be found in the PiPS Documentation Box and contain
the Transfer Check List and a letter to the admitting doctor.
• Prepare the baby’s Transfer Pack using the Transfer Checklist.
• When you receive a transferred baby ensure you also have a Transfer
Pack with a completed Transfer Checklist.
• Place the received Transfer Checklist in the PiPS Data Collection File and
update the Trial Participant Log.
• Give the parent(s) of the transferred baby a Transfer Contact Sheet.
Stool Sample Collection
• Two stool samples are required from each participating baby, one to be
collected as close as possible to 2 weeks post-natal age and another as
close as possible to 36 weeks post-menstrual age.
• If discharged before 36 weeks and 0 days post-menstrual age the second
sample should be taken just before discharge home.
• Please collect 2 - 3 heaped scoops or at the very least one heaped scoop
although we realise this may not always be possible.
• Please remember to add the date the stool sample was collected, the
baby’s Study Number and date of birth on the sample bottle label.
• Stool collection bottles, protective packages and plastic Freepost
envelopes can be found in the PiPS Consumables Box.
End of Intervention Treatment
•
The daily administration of the trial intervention should continue until the
baby is 36 weeks and 0 days post-menstrual age.
•
The intervention may be discontinued sooner if the baby is discharged from
hospital, dies or at the request of a clinician or parent.
•
In all instances cancel the prescription and retain the unused sachets in the
allocated package, then apply a ‘Course Finished’ label over the broken silver
security tab on the front of the package.
•
Do not throw away unused sachets or packages! A PiPS research nurse will
come to site periodically to collect the used packages.
•
N.B. If the intervention is stopped for any reason (except if there is a request
for a complete withdrawal from the trial by a parent) data and stool sample
collection must be continued until discharge or death.
Intervention Reconciliation
• We need to be able to account for every single sachet of the PiPS trial
intervention that is sent to site from the supplier.
• There are three documents involved in tracking allocated intervention
use:
− on the baby’s drug chart the daily administration and when
applicable any omitted or additional doses of the allocated
intervention
− in Form 3 at transfer, discharge or death the total number of days for
which the trial intervention was discontinued and at the end of the
intervention course the date the last dose was given
− on the Intervention Wastage Log whether any of the sachets were
wasted because of spillage etc.
Trial Logs
There are 4 Logs that need to be kept for monitoring participants, intervention
wastage, training and delegation of trial activities at your hospital.
Incident Reporting
The PiPS Incident Form should be
completed when:
• There has been a deviation from the
trial Protocol
• There has been a deviation from the
procedures described in the Guidance
Sheets
• An incident that you believe needs to
be reported or recorded
It is important that you contact the
Trial Office as soon as an incident has
been identified and before you start to
complete an Incident Form.
Other Trial Documentation and Materials
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Protocol & Summary Protocol
Neonatal Staff Training Documents booklet
PiPS Handbook
Cot Cards
Trial Information Poster for staff
Intervention Preparation Poster
PiPS Logo Labels
‘I’m Taking Part in PiPS’ Labels
Intervention Course Finished Labels
Freepost envelopes
Documentation and consumables re-order form
Trial Documentation on the PiPS Website
Please visit the PiPS website
which is constantly updated
with the latest trial
documents, information,
recruitment figures, and
training materials:
https://www.npeu.ox.ac.uk/pips/
Or search for ‘pips trial’ in any
internet search engine.
Contact Details & Emergency Queries