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[Please ensure this Protocol template V02 is the most recent version: by logging on to
http://www.ucl.ac.uk/jro/standingoperatingprocedures/document-library]
Text in red is for instruction only and should be deleted.
Text in blue should be included if appropriate for the trial.
Full title of trial
[Click here and type full descriptive trial title]
Title to include phase, design (e.g. double-blind,
randomised,
placebo-controlled),
single-
site/multi-site, name of IMP, target disease, and
subject population.
Short title
[Click here and type short title]
The full and short title must be the same on all
trial documents e.g. patient information sheet.
Version and date of protocol
[Type
'Draft'
here
if
applicable]
Version
[Insert version number], [insert date]
[The protocol you send to the MHRA and REC
should be V1]
Sponsor:
University College London (UCL)
Sponsor protocol number
[Type sponsor protocol number]
Funder (s) :
[Names of ALL organisations providing funding for
this trial]
EudraCT no
[Type EudraCT No]
ACTIVE IMP(s):
[Insert trial medication]
PLACEBO IMP(s):
[Insert trial medication] If Applicable
Phase of trial
Phase [Insert phase of trial]
Sites(s)
[Single site]/[Multi-site] Delete as appropriate
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Chief investigator:
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Sponsor Representative:
[Insert name, title, address and contact details]
Insert Name/ email address – JRO to Add
Joint UCLH/UCL Biomedical Research Unit, 1st Floor
Maple House,
149 Tottenham Court Road,
London W1T 7NF.
Postal address:
Joint Research Office, UCL
(1st Floor, Maple House),
Ground Floor, Rosenheim Wing,
25 Grafton Way,
London WC1E 6DB.
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Signatures
The Chief Investigator and the JRO have discussed this protocol. The investigators
agree to perform the investigations and to abide by this protocol
The investigator agrees to conduct the trial in compliance with the approved protocol,
EU GCP and UK Regulations for CTIMPs (SI 2004/1031; as amended), the UK Data
Protection Act (1998), the Trust Information Governance Policy (or other local
equivalent), the Research Governance Framework (2005’ 2nd Edition; as amended),
the Sponsor’s SOPs, and other regulatory requirements as amended.
Chief investigator
[Insert name of CI]
Signature
Date
Signature
Date
Sponsor Representative
JRO to Add
UCL
This Protocol template is intended for use with UK sites only.
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Contents
Signatures ............................................................................................................................. 3
Contents ................................................................................................................................ 4
List of abbreviations ............................................................................................................... 7
1
Trial personnel .............................................................................................................. 9
2
Summary..................................................................................................................... 10
3
Introduction ................................................................................................................. 11
3.1
Background .................................................................................................... 11
3.2
Preclinical data ............................................................................................... 11
3.3
Clinical data .................................................................................................... 11
3.4
Rationale and risks/benefits ........................................................................... 11
3.5
Assessment and management of risk............................................................ 12
4
Objectives ................................................................................................................... 12
5
Trial design ................................................................................................................. 12
Overall design ................................................................................................ 12
5.1
6
Selection of Subjects ................................................................................................... 13
6.1
Inclusion criteria ............................................................................................. 13
6.2
Exclusion criteria ............................................................................................ 13
7
Recruitment................................................................................................................. 14
8
Study procedures and schedule of assessments......................................................... 14
8.1
Informed consent procedure .......................................................................... 14
8.2
Randomisation procedures ............................................................................ 15
8.3
Unblinding....................................................................................................... 15
8.4
Screening Period ............................................................................................ 17
8.5
Baseline assessments ................................................................................... 18
8.6
Treatment procedures .................................................................................... 18
8.7
Subsequent assessments .............................................................................. 18
8.8
Flowchart of study assessments .................................................................... 19
8.9
Methods .......................................................................................................... 19
8.9.1
Laboratory procedures ............................................................................. 19
8.10
Definition of end of trial .................................................................................. 19
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8.11
9
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Discontinuation/withdrawal of participants and ‘stopping rules’ .................... 19
Name and description of all drugs used in the trial ...................................................... 19
9.1
Treatment of subjects ..................................................................................... 20
9.2
Concomitant medication................................................................................. 20
10
Investigational Medicinal Product ................................................................................ 20
10.1
Name and description of investigational medicinal product(s)Error! Bookmark
not defined.
10.2
Name and description of each NIMP ............. Error! Bookmark not defined.
10.3
Summary of findings from non-clinical studies .............................................. 22
10.4
Summary of findings from clinical studies ..................................................... 22
10.5
Summary of known and potential risks and benefits ..................................... 22
10.6
Description and justification of route of administration and dosage .............. 22
10.7
Dosages, dosage modifications and method of administration..................... 22
10.8
Preparation and labelling of Investigational Medicinal Product..................... 22
10.9
Drug accountability ......................................................................................... 22
10.10 Source of IMPs including placebo ....................................................................... 23
10.11
Dose modifications ......................................................................................... 23
10.12
Assessment of compliance ............................................................................ 23
10.13
Post-trial IMP arrangements .......................................................................... 24
11
Recording and reporting of adverse events and reactions ........................................... 24
11.1
Definitions ....................................................................................................... 24
11.2
Recording adverse events ............................................................................. 25
11.4
Procedures for recording and reporting Serious Adverse Events ................. 27
11.4.1
Notification of deaths ................................................................................... 29
11.4.2
Reporting SUSARs ...................................................................................... 29
11.4.3
Development Safety Update Reports ....................................................... 29
11.4.4
Annual progress reports........................................................................... 30
11.4.5
Pregnancy (If applicable) ......................................................................... 30
11.4.6
Overdose ................................................................................................. 30
11.4.7
Reporting Urgent Safety Measures .......................................................... 30
11.5
The type and duration of the follow-up of subjects after adverse events…… 31
11.5.1
Notification of Serious Breaches to GCP and/or the protocol (SPON/S15) .... 31
12
Data management and quality assurance ................................................................... 31
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12.1
Confidentiality ................................................................................................. 31
12.2
Data collection tools and source document identification ............................. 32
12.3
Data handling and analysis ............................................................................ 32
13
Record keeping and archiving ..................................................................................... 33
14
Statistical Considerations ............................................................................................ 33
14.1
Outcomes ....................................................................................................... 34
14.1.1
Primary outcomes .................................................................................... 34
14.1.2
Secondary outcomes ............................................................................... 34
14.2
Sample size and recruitment ......................................................................... 34
14.2.1
Sample size calculation ........................................................................... 34
14.2.2
Planned recruitment rate.......................................................................... 35
14.3
Statistical analysis plan .................................................................................. 35
14.3.1
Summary of baseline data and flow of patients ........................................ 35
14.3.2
Primary outcome analysis ....................................................................... 35
14.3.3
Secondary outcome analysis ................................................................... 35
14.3.4
Sensitivity and other planned analyses .................................................... 36
14.4
Randomisation methods ................................................................................ 36
14.5
Interim analysis .............................................................................................. 36
14.6
Other statistical considerations ...................................................................... 37
15
Name of Committees involved in trial .......................................................................... 37
16
Direct Access to Source Data/Documents ................................................................... 37
17
Ethics and regulatory requirements ............................................................................. 37
18
Monitoring requirement for the trial .............................................................................. 38
19
Finance ....................................................................................................................... 38
20
Insurance .................................................................................................................... 38
21
Publication policy ........................................................................................................ 39
22
Statement of compliance ............................................................................................. 39
23
References.................................................................................................................. 39
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List of abbreviations
Commonly used abbreviations – add or delete as applicable:
AE
Adverse Event
AR
Adverse Reaction
CA
Competent Authority
CI
Chief Investigator
CRF
Case Report Form
CRO
Contract Research Organisation
CTA
Clinical Trial Authorisation
CTIMP
Clinical Trial of Investigational Medicinal Product
DMC
Data Monitoring Committee
DSUR
Development Safety Update Report
EC
European Commission
EMEA
European Medicines Agency
EU
European Union
EUCTD
European Clinical Trials Directive
EudraCT
European Clinical Trials Database
EudraVIGILANCE
European database for Pharmacovigilance
GAfREC
Governance Arrangements for NHS Research
Ethics
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
IB
Investigator Brochure
ICF
Informed Consent Form
IDMC
Independent Data Monitoring Committee
IMP
Investigational Medicinal Product
IMPD
Investigational Medicinal Product Dossier
ISF
Investigator Site File
ISRCTN
International Standard Randomised
MA
Marketing Authorisation
MHRA
Medicines and Healthcare products Regulatory
Agency
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MS
Member State
Main REC
Main Research Ethics Committee
NHS R&D
National
Health
Development
PI
Principal Investigator
PIS
Participant Information Sheet
QA
Quality Assurance
QC
Quality Control
QP
Qualified Person for release of trial drug
RCT
Randomised Control Trial
REC
Research Ethics Committee
SAR
Serious Adverse Reaction
SAE
Serious Adverse Event
SDV
Source Document Verification
SOP
Standard Operating Procedure
SmPC
Summary of Product Characteristics
SSA
Site Specific Assessment
SUSAR
Suspected
Reaction
TMG
Trial Management Group
TSC
Trial Steering Committee
UCL Protocol template V2, 27/01/2012
Service
Unexpected
Research
Serious
Adverse
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&
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Short title: Sponsor code: [Type sponsor protocol number]
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Trial personnel
Chief Investigator (CI)
[insert name and address]
e-mail: [add email address]
tel: [tel no.] fax: [fax no.]
Sponsor’s representative [insert name and address]
e-mail: [add email address]
tel: [tel no.] fax: [fax no.]
Statistician
[insert name and address]
e-mail: [add email address]
tel: [tel no.] fax: [fax no.]
Central laboratories
[insert name and address]
e-mail: [add email address]
tel: [tel no.] fax: [fax no.]
Add appropriate name (eg Head of Department) and address of any
central core services i.e laboratories, medical and/or technical
departments (e.g. imaging, radiology), and any external Contract
Research Organisation (CRO) or Clinical Trials Unit (CTU) involved in
the trial.
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Summary
This summary should be 1–2 pages only. It should give the reader sufficient
information to understand the rationale for the trial, its objectives and the
methods that will be used to achieve these objectives.
Title:
Short title:
Trial medication:
List all IMPs to be used in the trial. (including Placebo is
applicable)
Phase of trial:
Insert development phase (I, II, II or IV).
Objectives:
Summarise primary and secondary objectives.
Type of trial:
Example: Phase [N], open/single-blind/double-blind, randomised,
crossover/partial crossover/parallel group, single/multi-site trial in
[insert patient population].
Trial
design
and
methods:
Give brief summary of trial design, including dosing regime and
the assessments that will be made to achieve the primary and
secondary objectives.
Trial
duration
per
ie. from consent to last trial assessment.
trial
I.e. from when first patient enrolled to last patient follow-up.
participant:
Estimated
total
duration:
Planned trial sites:
Single-site or multi-site.
If multi-site, include number of planned
sites.
Total
number
of
Include planned number to be enrolled for the whole trial.
participants planned:
Main inclusion/exclusion
Include the main disease/area to be investigated and the key
criteria:
inclusion/exclusion criteria.
Statistical methodology
Briefly describe the statistical methodology to be used in the
and analysis:
study.
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Introduction
3.1
Background
This section should describe:

The disease to be studied in the trial, including its incidence.

The trial population.
3.2
Preclinical data
Add in any preclinical/non clinical studies and finding undertaken in summary
form. Please cross refer to IMPD/IB/SPC.
3.3
Clinical data
Previous clinical trials conducted/ or clinical use of the IMP (or where relevant
inference to a similar class of medicine) in support for this clinical trial
3.4
Rationale and risks/benefits
Include the rationale or “problem statement” i.e. the research question (the
hypothesis to be tested).
The current available treatment(s) and their limitations, and why you think the
IMP(s) might be an improvement on those treatments.
If the IMP(s) is to be used outside its licence, you should include a
risk/benefit analysis.
Justification should be provided to support that the IMP could achieve clinical
improvement over current practice (and indicate its relevance to healthcare
practice).
This justification is particularly important if the trial proposes to use the IMP:

in children or in adults unable to consent for themselves;

in higher doses;

for longer duration;

in a subject population that might handle it differently (e.g. hepatic or
renally impaired patients, children, elderly, immunocompromised);

it is being used in combination with another medicinal product; or

the indication/ medical condition compromises the subject’s tolerance.
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Assessment and management of risk
Include a section on risk management. What are the risks, how high is the
risk compared to normal standard practice and how will risk be minimised?
Consider the starting dose, dose increments, administration of doses,
resources available particularly in terms of facilities and staff, procedures,
type of patients, staff training required.
Please refer to the following documentation is preparing this section:
http://www.mhra.gov.uk/home/groups/l-ctu/documents/websiteresources/con111784.pdf
This trial is categorised as: (delete as appropriate)
• Type A = No higher than the risk of standard medical care
• Type B = Somewhat higher than the risk of standard medical care
• Type C = Markedly higher than the risk of standard medical care
4
Objectives
Primary:
Secondary:
5
Trial design
5.1
Overall design
This section of the protocol should include the following information:

Purpose of research (e.g. non commercial trial, licensing).

Clear description and justification of the type of design (e.g. open label,
blind, parallel group, crossover, placebo-controlled, sequential, cluster
randomised and equivalence).

If Applicable Include detail and justification for:
o level of blinding to be used – double-blind or single-blind
o how blinding of investigator team and participant will be
implemented (e.g. through use of active and matching placebo
treatment)
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
For a trial with a crossover design, information about possible carry over
effects, detail of treatment ordering, washout (/in) periods.

Schematic diagram(s) of overall trial design.

Description and justification of the duration of treatment, subject
participation and trial follow-up.

Criteria for dose escalation if applicable.
Selection of Subjects
Please consider each criterion carefully as there must be NO
deviations from it during the trial. You are defining these criteria and
you are expected to comply with them. You need to know which
document you will use to assess compliance with the criteria.
These criteria need to be defined in such a way that a monitor/inspector
can clearly identify from the CRF and medical notes that the CI is
compliant with the eligibility criteria.
Please add criteria as appropriate (for example, consider contra-indications
to trial treatments, incompatible concurrent treatments, recent involvement in
other research), and include points below if appropriate:
6.1
Inclusion criteria
1.
Age
2.
Gender
3.
Clinical Parameters. Compliance with EACH parameter for each subject
will need to be clearly documented.
6.2
Exclusion criteria
1. Females of childbearing potential and males must be willing to use an
effective method of contraception (hormonal or barrier method of birth
control; abstinence) from the time consent is signed until 6 weeks after
treatment discontinuation. [If the SmPCs of the IMPs state that the IMPs
are not teratogenic you might be able to state that this is NA for your
trial]. Please note that the MHRA advise double contraception
2. Females of childbearing potential must have a negative pregnancy test
within 7 days prior to being registered for trial treatment. [If the SmPCs
of the IMPs state that the IMPs are not teratogenic you might be able to
state that this is NA for your trial]. NOTE: Subjects are considered not of
child bearing potential if they are surgically sterile (i.e. they have
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undergone a hysterectomy, bilateral tubal
oophorectomy) or they are postmenopausal.
ligation,
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or
bilateral
3. Females must not be breastfeeding.
Consider contraindications to trial treatment (e.g. as listed in SmPc),
incompatible concurrent treatments, recent involvement in other research.
4. Allergies to excipients of IMP and placebo
7
Recruitment
In this section you need to describe recruitment methods such as the use of
adverts, websites, PICs (Patient Identification Centres) and the involvement
of different centres.
8
Study procedures and schedule of assessments
8.1
Informed consent procedure
Specify who will take informed consent, how and when it will be taken.
Informed consent must be obtained before any trial-related procedures are
completed.
The person taking consent must be GCP trained, suitably qualified and
experienced, and have been delegated this duty by the CI/PI on the
delegation log.
Please include if applicable:
It is the responsibility of the Investigator, or a person delegated by the
Investigator to obtain written informed consent from each subject prior to
participation in the trial, following adequate explanation of the aims, methods,
anticipated benefits and potential hazards of the study.
“Adequate time” must be given for consideration by the patient before
taking part. The PI must record when the patient information sheet (PIS) has
been given to the patient. [If the amount of time between the PIS being given
and the date of consent is less than 24 hours, the PI needs to explain the
rationale for this].
The Investigator or designee will explain the patients are under no obligation
to enter the trial and that they can withdraw at any time during the trial,
without having to give a reason.
No clinical trial procedures will be conducted prior to taking consent from the
participant. Consent will not denote enrolment into trial.
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A copy of the signed Informed Consent form will be given to the participant.
The original signed form will be retained at the study site and a copy placed
in the medical notes.
If new safety information results in significant changes in the risk/benefit
assessment, the consent form will be reviewed and updated if necessary and
subjects will be re-consented as appropriate
If the trial is in children or adults unable to consent for themselves please
include
appropriate
procedure.
Refer
to
NRES
website
(http://www.nres.npsa.nhs.uk/applications/guidance/).
8.2
Randomisation procedures
We strongly advise that for double blind trials, you enlist the service of
a CTU or a specialist company (e.g. www.sealedenvelope.co.uk) to do
randomisation, unblinding as they can offer 24/7 cover. You should
cost for this in your grant application.
Describe the type of randomisation to be used e.g. simple, block, stratified,
minimisation. Refer to specific statistics section for more details if applicable.
Include information regarding how randomisation will be implemented
(include who will be doing it, where and how including the procedure to be
used out of hours if applicable). Specify who will hold the randomisation list.
Describe how subjects will be assigned to treatment groups e.g. through
consecutive allocation of subject numbers, and the use of a Trial Subject
Log.
You should ensure to have a clear process on randomisation taking into
consideration interaction between single centre and/or multicentre trials
Describe the procedure for replacements.
Describe the approach to be used to conceal allocation (e.g. sealed
envelopes, telephone central allocation office).
8.3
Unblinding
Specify the procedure(s) to be used for un-blinding for the following
situations:
Emergency Unblinding
The study code should only be broken for valid medical or safety reasons
e.g. in the case of a severe adverse event where it is necessary for the
investigator or treating health care professional to know which treatment the
patient is receiving before the participant can be treated. Subject always to
clinical need, where possible, members of the research team should remain
blinded.
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The code breaks for the trial are held [please add relevant department] and
are the responsibility of [please add personnel].
In the event a code is required to be unblinded a formal request for
unblinding will be made by the Investigator/treating health care professional.
If the person requiring the unblinding is a member of the Investigating team
then a request to the holder of the code break envelope/list, or their delegate
will be made and the unblinded information obtained.
If the person requiring the unblinding is not the CI/PI then that health care
professional will notify the Investigating team that an unblinding is required
for a trial subject and an assessment to unblind should be made in
consultation with the clinical and research teams.
On receipt of the treatment allocation details the CI/PI or treating health care
professional will deal with the participant’s medical emergency as
appropriate.
The CI/PI documents the breaking of the code and the reasons for doing so
on the CRF/data collection tool, in the site file and medical notes. It will also
be documented at the end of the study in any final study report and/or
statistical report.
The CI/Investigating team will notify the JRO (acting on behalf of the
Sponsor) in writing as soon as possible following the code break detailing the
necessity of the code break.
The CI/PI will also notify the relevant authorities.
[Delete as appropriate] The written information will be disseminated to the
Data Safety Monitoring Committee for review in accordance with the DSMC
Charter.
Unblinding for the submission of SUSAR reports: Amend as appropriate.
The following procedure will be used to unblind for the submission of a
SUSAR report to the regulatory agencies.




A member of the JRO sponsor’s office will contact the pharmacy via
telephone on ____________ in the first instance, requesting unblinding
information from the randomisation list.
The pharmacist will provide their email address and name for the
request to be formalised in an email.
The Sponsor will provide in the email the protocol number and trial
name, name of the requester, reason for unblinding, patient name,
subject name and timeline to receive the unblinded information.
The Sponsor will provide the unblinded information on the e-SUSAR
website form and CIOMS form if applicable.
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
8.4
Short title: Sponsor code: [Type sponsor protocol number]
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This information will not be forwarded to the trial team and kept in the
JRO site TMF.
Screening Period
Need to list all the planned screening assessments, including Physical
Examination, Medical History and Concomitant Medication. Any assessments
and or procedures performed as part of routine care which will be used to
screen patients for eligibility will require defined timelines (e.g x-rays within
the last 6 months). If applicable you may wish to define time period for overall
screening i.e. screening has to be completed within 28 days.
a. Baseline visit will occur 28 days of Screening visit
b. During treatment phase, visits should occur +/- x days of the scheduled
date.
c. Follow up period should be 21 days after Visit 7 or Early Discontinuation
visit.
d. Randomisation is the last procedure to be completed at Baseline visit.
e. Routine tests used to determine eligibility criteria as defined in
Inclusion/Exclusion criteria
Please note screening does not necessarily constitute enrolment.
Screen failures i.e. patients who do not meet eligibility criteria at time of
screening maybe eligible for rescreening subject to acceptable parameters.
This will need to be discussed with the Sponsor.
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Baseline assessments
Need to list all the planned baseline assessments that will be performed once
the patient has been entered into the trial and before their first dose of the
IMP.
Visit #
Screening
Baseline a
1
2
Day – X
Day-1
Informed Consent
X
Medical
History/Physical
exam
X
X
Vital Signs
X
X
Eligibility
determination
Add ALL Protocol
Assessments
including
bloods/urine etc
as applicable both
trial specific and
routinee
Treatment Phase b
Follow Up
c
3
4
5
6
7
8
Day 0
Week 4
Week 6
Week 8
Week 10 / Early
Discontinuation
visit
F-UP
X
X
X
Randomisation d
X
IMP
administration
Adverse Events
review
Concomitant
Medication review
Physician’s
Withdrawal
Checklist
X
X
X
X
X
X
X
X
X
X
X
X
X
X
8.6
Treatment procedures
Add IMP dosing details.
8.7
Subsequent assessments
Describe all study procedures and assessments, including those that are part
of routine care. Breakdown into visit numbers as appropriate.
If home dosing, compliance should be checked at each visit. Diary cards
should be checked at each visit.
Include any follow-up assessments.
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Flowchart of study assessments
Add table of all procedures/tests/IMP administration to be completed at each
visit.
8.9
8.9.1
Methods
Laboratory procedures
The following samples will be processed at Local Labs:
The following samples will be processed at Central Labs: (delete as
appropriate) Please obtain accreditation certificate and ref ranges.
For any specialist sample handling, processing and or shipment please refer
to lab manual.
8.10 Definition of end of trial
Define the end of the trial. In most cases the end of the trial will be the date of
the last visit/ telephone follow up/ home visit by the last participant. Any
exceptions should be justified.
8.11 Discontinuation/withdrawal of participants and ‘stopping rules’
The protocol should:

describe under what circumstances and how subjects will be withdrawn
from the trial

give details of documentation to be completed on subject withdrawal
(including recording reasons for withdrawal and any follow-up information
collected with timing)

state whether withdrawn subjects would be replaced and how.

state under what circumstances the trial might be prematurely stopped.
Remember the safety profile of the IMP(s) and the objective(s) of the trial. It
may be necessary to give the circumstances under which treatment may be
resumed.
9
Name and description of all drugs used in the trial
For this section of the protocol you might find the following document useful
to read:
“Guidance on Investigational Medicinal Products (IMPs) and other medicinal
products used in Clinical Trials”
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This document can be downloaded at:
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/guidance-onimp_nimp_04-2007.pdf
This section of the protocol should list all the drugs to be used in the trial.
9.1
Treatment of subjects
Investigational product/treatment
Please give a description of the intervention (medicinal product, medical
device, food supplement, radiation, surgery, behavioural interventions, etc).
Also use of comparator or placebo should be described If the trial uses a
licensed drug, specify the generic name only, unless a specific brand must
be used, for example as per an IMP supply agreement (e.g. if IMP is to be
supplied free of charge by the manufacturer). Also, please add statement
that any brand of the IMP can be used, if that is the case.
9.2
Concomitant medication
Medication(s)/treatment(s) permitted and not permitted before and/or during
the trial (specify time restrictions).
Consider possible interactions or effects that could confound the results and
conclusions.
Please do not confuse this with NIMPs, refer to section 9.9 for further details
10 Investigational Medicinal Product
According to the definition of the EU clinical trial directive 2001/20/EC, an
investigational medicinal product is a pharmaceutical form of an active
substance or placebo being tested or used as a reference in a clinical trial,
including products already with a marketing authorisation, but used or
assembled (formulated or packaged) in a way different from the authorised
form, or when used for an unauthorised indication, or when used to gain
further information about the authorised form. Thus in this section also
information about the comparator product/placebo should be given.
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Name and description of investigational medicinal product(s)
Please refer to the following guidance for classification of IMPs:
http://ec.europa.eu/health/files/pharmacos/docs/doc2006/07_2006/def_imp_
2006_07_27_en.pdf
The description of IMP should de proportional to the development status of
the IMP (e.g. for marketed products reference to the authorized medicinal
product with at least details of strength dosage form and PL holder should
be given, for new or modified products a full although concise description
should be given
10.2
Name and description of each NIMP
Please refer to the following guidance for classification of NIMPs:
http://ec.europa.eu/health/files/pharmacos/docs/doc2006/07_2006/def_imp_
2006_07_27_en.pdf
A similar system to that required for IMPs needs to be implemented if the
NIMPS are unlicensed (i.e might come from another EU country or a country
outside EEA)
In all other cases
• Host sites are responsible to maintain a system which allows adequate
reconstruction of NIMP movements there should be a procedure that permit
recording which patients received which NIMPs during the trial with an
evaluation of the compliance. (Delete the previous sentence if the text in blue
is applicable)
Eg. Rescue medication (if applicable)
Please describe type, dose per unit and maximum dose allowed
10.3
Summary of findings from non-clinical studies
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Please refer to the Investigator’s Brochure (IB), Investigational Medicinal
Product Dossier (IMPD), Summary of Product Characteristics (SPC) or a
similar document (if applicable), by mentioning the relevant pages in that
document. Be sure that the information is up to date and references to peer
reviewed papers in (biomedical/scientific) journals should be given where
appropriate.>
10.4
Summary of findings from clinical studies
See explanatory text of chapter 10.2
10.5
Summary of known and potential risks and benefits
See explanatory text of chapter 10.2
10.6
Description and justification of route of administration and
dosage
Also should be included technical modalities if applicable (i.e if the product is
to be given in a syringe and is a powder and needs to be reconstituted, this
should be described here
10.7
Dosages, dosage modifications and method of administration
This section should be precise and complete. Remember to include dosage
for all subjects throughout the trial period, taking particular care to changes
doses as infants and children grow. You should include the frequency and
timing of dose in each part of the trial, methods for individualised doses, etc.
10.8
Preparation and labelling of Investigational Medicinal Product
Preparation and labelling of the investigational medicinal products should be
completed in accordance with the relevant GMP guidelines. Text for labels
used for the Investigational Medicinal may be obtained by the IMP
compliance Manager
10.9
Drug accountability
Please describe the procedures for the shipment, receipt, distribution, return
and destruction of the investigational medicinal products.
10.10 Source of IMPs including placebo
If the IMPs to be used in the trial are being provided or manufactured by a
company specifically for use in the trial please provide details of the
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arrangement. If the IMPs are being sourced from hospital stock please insert
the following statement, and list the IMPs as applicable:
‘The following IMPs will be sourced from routine hospital stock and their
handling and management will be subject to standard procedures of the
pharmacy’. Sourcing of IMP is also discussed in the IMP management plan.
10.11
Dose modifications
You should give details here on required dose modifications if applicable, for
example in the case of certain adverse events (specify the exact dose
modifications and events), and also the stopping rules (see also section
8.11).
10.12
Assessment of compliance
Compliance includes both adherences to IMP and Protocol study procedures.
Percentage of noncompliance acceptable for patient to continue on the trial
is: e.g. <80% noncompliance equates to patient withdrawal (this includes
compliance with IMP and study procedures i.e. visit window, refusal of study
specific assessments)
Percentage of IMP compliance acceptable for patient to continue on the trial
is (insert percentage):
Noncompliance to the Protocol study procedures will be documented by the
investigator and reported to the Sponsor as agreed. Persistent
noncompliance may lead the patient to be withdrawn from the study.
Define procedures for:

Monitoring (e.g. watching subject swallow pills and checking their
mouth afterwards, getting patients to complete a diary card, package
returns).

Recording of subject compliance information (what will be recorded,
when and where).

Details of follow-up of non-compliant subjects.
10.13
Post-trial IMP arrangements
Describe what arrangements are in place should the IMP be provided to trial
subjects post trial participation. If there are not arrangements then you need
to state that there will be no arrangements.
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11
Short title: Sponsor code: [Type sponsor protocol number]
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Recording and reporting of adverse events and reactions
Under this section, the protocol needs to include the following definitions:
11.1
Definitions
Term
Definition
Adverse Event (AE)
Any untoward medical occurrence in a patient or clinical
trial subject administered a medicinal product and which
does not necessarily have a causal relationship with this
treatment.
Adverse
(AR)
Reaction Any untoward and unintended response in a subject to
an investigational medicinal product which is related to
any dose administered to that subject.
This includes medication errors, uses outside of protocol
(including misuse and abuse of product)
Serious adverse
event (SAE), serious
adverse reaction
(SAR) or unexpected
serious adverse
reaction
Any adverse event, adverse reaction or unexpected
adverse reaction, respectively, that:

results in death,

is life-threatening,

requires hospitalisation or prolongation of
existing hospitalisation,

results in persistent or significant disability or
incapacity, or

consists of a congenital anomaly or birth
defect
Important Medical
Event
These events may jeopardise the subject or may require
an intervention to prevent one of the above
characteristics/consequences. Such events should also
be considered ‘serious’.
Unexpected adverse
reaction
An adverse reaction the nature and severity of which is
not consistent with the information about the medicinal
product in question set out:
(a) in the case of a product with a marketing
authorization, in the summary of product
characteristics
for
that
product,
(b) in the case of any other investigational
medicinal product, in the investigator's brochure
relating to the trial in question.
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SUSAR
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Suspected Unexpected Serious Adverse Reaction
11.2
Recording adverse events
All adverse events will be recorded in the medical records and CRF following
consent. Those trials whereby nIMPs or trial specific procedures are
administered prior to the IMP administration, adverse events will be required
to be recorded. (Reporting of AEs normally occurs following IMP
administration if AE data is collected before it should be recorded in the CRF,
medical notes and AE log but not reported to the sponsor). (Please amend as
appropriate).
If you do not plan to record certain adverse events in the CRF (for example, if
your trial is a phase IV trial of a licensed medication used within its license
with a well-established safety profile) please state it here and provide
justification. However, all SERIOUS adverse events must be recorded in the
CRF and SAE log.
If the investigator suspects that the subjects’ disease has progressed faster
due to the administration of the IMP, then he will record and report this as an
unexpected adverse event.
Clinically significant abnormalities in the results of objective tests (e.g.
laboratory variables, x-ray, ECG – make specific to trial) will also be recorded
as adverse events. If the results are not expected as part of disease or IMP,
these will also be recorded as unexpected. (Delete if inappropriate to trial)
All adverse events will be recorded with clinical symptoms and accompanied
with a simple, brief description of the event, including dates as appropriate.
All adverse events will be recorded until (insert as appropriate)
All adverse events will be reportable to the Sponsor up to 30 days post last
IMP administration. (Amend as appropriate)
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11.3 Assessments of Adverse Events
Each adverse event will be assessed for the following criteria:
11.3.1 Severity
Category
Definition
Mild
The adverse event does not interfere with the volunteer’s daily
routine, and does not require intervention; it causes slight
discomfort
Moderate
The adverse event interferes with some aspects of the volunteer’s
routine, or requires intervention, but is not damaging to health; it
causes moderate discomfort
Severe
The adverse event results in alteration, discomfort or disability
which is clearly damaging to health
11.3.2 Causality
The assessment of relationship of adverse events to the administration of IMP is a
clinical decision based on all available information at the time of the completion of the
case report form. The following categories will be used to define the causality of the
adverse event:
Category
Definition
Definitely:
There is clear evidence to suggest a causal relationship,
and other possible contributing factors can be ruled out.
Probably:
There is evidence to suggest a causal relationship, and
the influence of other factors is unlikely
Possibly
There is some evidence to suggest a causal relationship
(e.g. the event occurred within a reasonable time after
administration of the trial medication). However, the
influence of other factors may have contributed to the
event (e.g. the patient’s clinical condition, other
concomitant events).
Unlikely
There is little evidence to suggest there is a causal
relationship (e.g. the event did not occur within a
reasonable time after administration of the trial
medication). There is another reasonable explanation for
the event (e.g. the patient’s clinical condition, other
concomitant treatments).
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Not related
There is no evidence of any causal relationship.
Not Assessable
Unable to assess on information available.
11.3.3 Expectedness
Category
Definition
Expected
An adverse event that is classed in nature as serious and
which is consistent with the information about the IMP
listed in the Investigator Brochure (or SmPC if Licensed
IMP) or clearly defined in this protocol.
Unexpected
An adverse event that is classed in nature as serious and
which is not consistent with the information about the IMP
listed in the Investigator Brochure (or SmPC if Licensed
IMP)
The reference document to be used to assess expectedness against the IMP
is (add in either SPC/IB). The protocol will be used as the reference
document to assess disease related and/or procedural expected events.
11.3.4 Seriousness
Seriousness as defined for an SAE in section 11.1.
Collection, recording and reporting of adverse events (including
serious and non-serious events and reactions) to the sponsor will be
completed according to the sponsor’s SOP(INV/S05).
11.4
Procedures for recording and reporting Serious Adverse Events
All serious adverse events will be recorded in the hospital notes and the
CRF, and the sponsor’s SAE log. The SAE log will be reported to the
sponsor at least once or twice per year (amend as appropriate)
All serious adverse events will need to be reported to the sponsor on a SAE
form unless stated in the protocol that some expected SAEs will not be
reported to the sponsor, with a justification as to why they will not be
reported.
For patients on the control arm of a trial, SAEs may not have to be reported
to the sponsor but will be recorded in the CRF and medical records.
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The Chief or Principal Investigator will complete the sponsor’s serious
adverse event form and the form will be faxed to the sponsor on 020 3108
2312, within one working day of his / her becoming aware of the event. The
Chief or Principal Investigator will respond to any SAE queries raised by the
sponsor as soon as possible.
You may choose not to report EXPECTED SAEs to the sponsor for example
if they are expected to occur on a regular basis and offer no further new
information to your safety profile e.g. neutropenic sepsis. These events must
continue to be recorded in the source data and CRF, however you may state
that you will not complete an SAE form and forward it to the sponsor. Please
provide the rationale for doing so.
All SUSARs must be notified to the sponsor immediately (or at least within
one working day) according to the sponsor’s written SOP.
Example of exception:
Example: As the IMPs used in this trial are licensed in the UK and used
within their marketing authorization, EXPECTED SARs (as outlined in the
SmPCs and listed below – please list) will be RECORDED in the subjects’
hospital notes and in the CRF. However, SAE forms will not be completed
and sent to the sponsor.
It is important to note that the SmPC will only refer to reactions that are
expected to occur in the indication for which the drug has a marketing
authorisation. Please document which version of the SmPC is being
referenced but add that the most up-to-date version of the SmPc will be used
during the trial.

Managing serious adverse events in a multi-centre trial
The protocol needs to have clear instructions for the reporting lines and
timeframe for serious adverse events. These instructions will need to include
where the investigator (PI) will send the reports to: e.g. if the PI sends the
report directly to the sponsor, or whether the CI reviews the report first before
it is notified to the sponsor and how safety information will be disseminated to
all other PI sites.
Reporting to the sponsor will be completed as per the sponsor’s SOP and
using the UCL SAE form (INV/S05).
11.4.1 Notification of deaths
The protocol needs to be explicit as to whether, how and when the chief
investigator will notify deaths (expected or unexpected) to the sponsor. The
following statements are examples of what needs to be stated in the protocol:
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“All deaths will be reported to the sponsor irrespective of whether the death is
related to disease progression, the IMP, or an unrelated event”. This
statement should be used for phase I/FTIM trials.
“Only deaths that are assessed to be caused by the IMP will be reported to
the sponsor. This report will be immediate”.
“All deaths, including deaths deemed unrelated to the IMP, if they occur
earlier than expected will be reported to the sponsor”.
The protocol needs to specify the timelines of such reports.
11.4.2 Reporting SUSARs
The sponsor will notify the main REC and MHRA of all SUSARs. SUSARs
that are fatal or life-threatening must be notified to the MHRA and REC within
7 days after the sponsor has learned of them. Other SUSARs must be
reported to the REC and MHRA within 15 days after the sponsor has learned
of them.
In a double-blind trial, the procedure for unblinding in the event of a SUSAR
must be described (refer to sponsor’s SOP on randomisation, blinding and
code-breaking for more information (INV/S06).
11.4.2.1
Reporting SUSARs
in
International
Trials
(include
if
applicable)
The overall sponsor of the trial is responsible for reporting SUSARs which
occur outside of the UK to the MHRA. UCL, as sponsor of the UK site only,
will report SUSARs occurring in the UK to the MHRA.
11.4.3 Development Safety Update Reports
The sponsor will provide the main REC and the MHRA with Development
Safety Update Reports (DSUR) which will be written in conjunction with the
trial team and the Sponsor’s office. The report will be submitted within 60
days of the Developmental International Birth Date (DIBD) of the trial each
year until the trial is declared ended
11.4.4 Annual progress reports
An annual progress report (APR) will be submitted to the REC within 30 days
of the anniversary date on which the favourable opinion was given, and
annually until the trial is declared ended.
The chief investigator will prepare the APR.
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11.4.5 Pregnancy (If applicable)
Describe the procedure in place to:

record and notify pregnancies to the sponsor (use sponsor’s SOP),

follow-up of pregnant subject: Describe in detail the process for
monitoring and managing a pregnancy.

follow-up of child born to a pregnant trial subject, including male trial
subject who is the partner of the pregnant woman. (How long will followup be for).
11.4.6 Overdose
Describe the procedure in place to:

record and notify overdoses to the sponsor (this information should be
placed on the deviation log)

Where can overdoses be observed from (pill counts, diary cards, drug
charts or patient comment)

How will it affect you final analysis. Will patients be taken withdrawn from
the trial? Consider what will constitute an overdose that warrants trial
discontinuation

If an SAE is associated with the overdose ensure the overdose if fully
described in the SAE report form
11.4.7 Reporting Urgent Safety Measures
If any urgent safety measures are taken the PI/Sponsor shall immediately
and in any event no later than 3 days from the date the measures are taken,
give written notice to the MHRA and the relevant REC of the measures taken
and the circumstances giving rise to those measures.
Please refer to the following website for details on clinical trials safety
reporting:
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Clin
icaltrials/Safetyreporting-SUSARSandASRs/index.htm
11.5
The type and duration of the follow-up of subjects after adverse events.
This section needs to describe the type and duration of follow-up care for
subjects following an adverse drug reaction.
This section of the protocol also needs to specify how long after the last dose
of IMP has been administered to the subjects will adverse events and
reactions be recorded and reported.
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Please include ‘Any SUSAR related to the IMP will need to be reported to the
Sponsor irrespective of how long after IMP administration the reaction has
occurred.’
11.5.1 Notification of Serious Breaches to GCP and/or the protocol
(SPON/S15)
A “serious breach” is a breach which is likely to effect to a significant degree
–
(a) the safety or physical or mental integrity of the subjects of the trial;
or
(b) the scientific value of the trial.
The sponsor of a clinical trial shall notify the licensing authority in writing of
any serious breach of –
(a) the conditions and principles of GCP in connection with that trial; or (b)
the protocol relating to that trial, as amended from time to time, within 7 days
of becoming aware of that breach.
The sponsor will be notified immediately of any case where the above
definition applies during the trial conduct phase. The sponsor’s SOP on the
‘Notification of violations, urgent safety measures and serious breaches’ will
be followed.
12
Data management and quality assurance
12.1
Confidentiality
Include: All data will be handled in accordance with the UK Data Protection
Act 1998.
The Case Report Forms (CRFs) will not bear the subject’s name or other
personal identifiable data. The subject’s initials, date of birth and trial
identification number, will be used for identification.’
12.2
Data collection tools and source document identification
Describe procedures for data collection and recording. The protocol must
specify which data is to be recorded directly onto the Case Report Form
(CRF) and which data is recorded firstly into source documents, such as
medical notes and patient questionnaires. If data is not to be recorded in the
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CRF but only recorded in source documents this must be clearly identified.
Include a table or list identifying source documentation, and whether or not
this is to be transcribed into the CRF.
Describe whether the data are from a standardised tool (e.g. McGill pain
score) or involves a procedure (in which case full details should be supplied).
If a non standard tool is to be used, detail on reliability and validity should be
given.
The methods used to maximise completeness of data should be described
(e.g. telephoning subjects who have not returned postal questionnaires) and
data collection forms should be included as appendices.
Include statement: ‘It will be the responsibility of the investigator to ensure
the accuracy of all data entered in the CRFs. The delegation log will identify
all those personnel with responsibilities for data collection and handling,
including those who have access to the trial database.’
12.3
13
Data handling and analysis

Describe what software (e.g. Access, MACRO) is to be used for data
entry (NB Excel is not a suitable system for data entry in a clinical trial).

Provide detailed methods implemented to ensure validity and quality of
data (e.g. double entry, cross validation etc)

Describe how data will be stored and backed up, and how security will be
ensured and whether data will be transferred. If data are to be
transferred, describe the secure method of transfer. Document if there is
a disaster recovery plan.

Consider management of data across sites if multi-site trial. Where data
are transferred electronically this must be in accordance with the UK
Data Protection Act 1998 as well as UCL Information Security Policy and
Trust Information Governance Policy. There should be a documented
record of data transfer and measures in place for the recovery of original
information after transfer.

Statement of who is responsible for data entry and quality, and who is
responsible for data analysis. Data analysis should be performed
independently of data entry.
Record keeping and archiving
Archiving will be authorised by the Sponsor following submission of the end
of study report.
Specify location and duration of record retention for:
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
Essential documents

the trial database
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Please include the statement ‘Chief Investigators are responsible for the
secure archiving of essential trial documents (for each site, if multi-site trial)
and the trial database as per their trust policy. All essential documents will be
archived for a minimum of 5 years after completion of trial.
Destruction of essential documents will require authorisation from the
Sponsor.
14
Statistical Considerations
[Insert statistician’s name] is the trial statistician who will be responsible for
all statistical aspects of the trial from design through to analysis and
dissemination.
Please note that the trial statistician should be appropriately qualified and
experienced to undertake this work and be a fully engaged member of the
research team. If the statistician is not employed by UCL, a contract will need
to be put in place.
For international trials whereby UCL are the named sponsor for UK sites
only, you will need to be explicit within the section below in terms of what
information relates to the trial as a whole such as sample size and what
relates to the UK sites only (i.e. sample size for the UK sites), and whether
the sample size calculation is based on UK sites only or on all sites in all
countries involved.
14.1
Outcomes
14.1.1 Primary outcomes
A full description of the primary outcome; its definition, when it is measured,
any rules, references or programs for calculation of derived values and what
form it will take for analysis (e.g. continuous, categorical, ordinal).
14.1.2 Secondary outcomes
For each secondary outcome, detail as for primary outcome above.
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Short title: Sponsor code: [Type sponsor protocol number]
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Sample size and recruitment
14.2.1 Sample size calculation
Details of the precision or power calculation used to estimate the required
sample size (for analysis of the primary outcome), should contain all
information required to reproduce the sample size calculation including:

estimates used (e.g. Standard deviation, size of the clinically important
effect to be detected, correlations, dropout and noncompliance rates)
with relevant justifications in the form of appropriate references, pilot data
or clinical arguments.

assumptions made (e.g. assumptions of Normality, proportional hazards)

allowance for planned subgroup and interim analysis and clustering
effects

chosen levels of significance and power

methods / formula / software used with reference
For international multi-centre trials only, if the power of the trial is based on
the UK centres only, you must insert the following statement:
‘The power of the trial based on the UK centres alone is x%.’
If x<80%, the following statement should be added as well:
‘Therefore only descriptive analyses will be performed using the UK data.
Tests of efficacy of the intervention will only be performed after combining the
data with those from the other international centres.’
14.2.2 Planned recruitment rate
An estimate of the recruitment period for the trial (calculated based on the
expected number of eligible and recruited participants available per
month/year) with justification that the required sample size will be attainable
in practice.
14.3
Statistical analysis plan
14.3.1 Summary of baseline data and flow of patients

List variables to be used to assess baseline comparability of the
randomised groups including for each factor: a definition, any rules,
references or programs for calculation of derived values, what form it will
take for analysis (e.g. continuous, categorical, ordinal) and how it will be
reported (e.g. means, standard deviations, medians, proportions).
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
Short title: Sponsor code: [Type sponsor protocol number]
Plans to produce
statement.org/),
a
consort
flow
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diagram
(http://www.consort-
14.3.2 Primary outcome analysis
Plans for statistical analyses of the primary outcome including:

Summary measures to be reported

Method of analysis (justified with consideration of form of the data ,
assumptions of the method and structure of the data (e.g. unpaired,
paired, clustered) etc)

Plans for handling multiple comparisons, missing data, non-compliers,
spurious data and withdrawals in analysis

Plans for predefined subgroup analyses

Statement regarding use of intention to treat (ITT) analysis

Description of any non-statistical methods that might be used (e.g.
qualitative methods)
14.3.3 Secondary outcome analysis
Plans for statistical analysis of each secondary outcome. Note that use of
hypothesis tests may not be appropriate if the study has not been powered to
address these and use of estimates with confidence intervals is preferred.
Secondary analyses should be considered as hypothesis generating rather
than providing firm conclusions.
14.3.4 Sensitivity and other planned analyses
A decription of plans for sensitivity and other analyses. For example
sensitivity to missing data or non-compliance.
Please note that a more detailed statistical analysis plan should be produced as a
separate document at some point prior to the final analysis (as recommended by the
ICHE9 guidelines). In this document, a more technical and detailed elaboration of the
principal features stated in the protocol should be included. The plan may include
detailed procedures for executing the statistical analysis of the primary and
secondary variables and other data. The plan should be reviewed and possibly
updated as a result of the blind review of the data and should be finalised before
breaking the blind. Formal records should be kept of when the statistical analysis
plan was finalised as well as when the blind was subsequently broken.
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14.4
Short title: Sponsor code: [Type sponsor protocol number]
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Randomisation methods
Include detail for each of the following:

subject / cluster randomised design (randomising individuals or groups
(eg general practices, wards)

type of randomisation to be used - simple, block, stratified, minimisation
(block size should not be stated in the protocol to maintain blinding)
o if using stratified randomisation or minimisation, include
definition of stratification/minimisation variables (should only
consider variables that are likely to be strongly prognostic of the
outcome)
o if using blocked randomisation consider varying block sizes.

14.5
use of equal or unequal allocation between treatment arms
Interim analysis
Detail of approach for interim analyses (e.g. timing and statistical methods)
and criteria for early termination of the trial
Stopping / discontinuation rules and breaking of randomisation code:
14.6

define completion and premature discontinuation of the trial

describe procedure regarding decisions on discontinuation of the trial
(e.g. interim analyses, role of data monitoring committee)

state documentation to be completed if
discontinued

describe circumstances under which the randomisation codes may need
to be broken and the procedure for this.
part / all of the trial is
Other statistical considerations
Procedures for reporting any deviation(s) from the original statistical plan
(any deviation(s) from the original statistical plan should be described and
justified in the protocol and/or in the final report, as appropriate).
15
Name of Committees involved in trial
Please insert any applicable committees and their remits.
Describe which of the three committees will be in place for the trial: Trial
Management Group (TMG) (all trials should have a TMG), Independent Data
Monitoring Committee (IDMC) and Trial Steering Group (TSC). The terms of
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reference for these committees will need to be provided in separate
documents.
Please note for ALL phase I trials, an IDMC must be in place prior to trial
start up, and the sponsors IDMC charter must be completed and signed off
by IDMC members. For Phase I/II trials the safety committee will be asked if
an IDMC is required. Each member will need to sign the UCL IDMC charter
prior to becoming a member.
16
Direct Access to Source Data/Documents
Include the following statement:
The investigator(s)/ institution(s) will permit trial-related monitoring, audits,
REC review, and regulatory inspection(s), providing direct access to source
data/documents. Trial participants are informed of this during the informed
consent discussion. Participants will consent to provide access to their
medical notes.
17
Ethics and regulatory requirements
In this section you need to describe any ethical issues that need to be
considered and how these will be addressed.
The sponsor will ensure that the trial protocol, patient information sheet,
consent form, GP letter and submitted supporting documents have been
approved by the appropriate regulatory body (MHRA in UK) and a main
research ethics committee, prior to any patient recruitment. The protocol and
all agreed substantial protocol amendments, will be documented and
submitted for ethical and regulatory approval prior to implementation.
If the trial involves the use of radiation, document here if an Administration of
Radioactive Substances Advisory Committee (ARSAC) licence is needed.
Before the site can enrol patients into the trial, the Chief Investigator/Principal
Investigator or designee must apply for NHS permission from their Trust
Research & Development (R&D) and be granted written permission. It is the
responsibility of the Chief Investigator/ Principal Investigator or designee at
each site to ensure that all subsequent amendments gain the necessary
approval. This does not affect the individual clinician’s responsibility to take
immediate action if thought necessary to protect the health and interest of
individual patients (see section 11.4.7 for reporting urgent safety measures).
Within 90 days after the end of the trial, the CI/Sponsor will ensure that the
main REC and the MHRA are notified that the trial has finished. If the trial is
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terminated prematurely, those reports will be made within 15 days after the
end of the trial.
The CI will supply the Sponsor with a summary report of the clinical trial,
which will then be submitted to the MHRA and main REC within 1 year after
the end of the trial.
18
Monitoring requirement for the trial
Include the following statement:
A Trial specific monitoring plan will be established for studies. The trial will
be monitored with the agreed plan.
19
Finance
A statement of the finance for the trial such as details of funding body.
20
Insurance
Include the following:
“University College London holds insurance against claims from participants
for injury caused by their participation in the clinical trial. Participants may be
able to claim compensation if they can prove that UCL has been negligent.
However, as this clinical trial is being carried out in a hospital, the hospital
continues to have a duty of care to the participant of the clinical trial.
University College London does not accept liability for any breach in the
hospital’s duty of care, or any negligence on the part of hospital employees.
This applies whether the hospital is an NHS Trust or otherwise.
Participants may also be able to claim compensation for injury caused by
participation in this clinical trial without the need to prove negligence on the
part of University College London or another party. Participants who sustain
injury and wish to make a claim for compensation should do so in writing in
the first instance to the Chief Investigator, who will pass the claim to the
Sponsor’s Insurers, via the Sponsor’s office.
Hospitals selected to participate in this clinical trial shall provide clinical
negligence insurance cover for harm caused by their employees and a copy
of the relevant insurance policy or summary shall be provided to University
College London, upon request.”
If a medical device is to be used in the trial, there must also be indemnity
arrangements in place, with the manutacturer, to cover the malfunction and
breakdown of the device.
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Short title: Sponsor code: [Type sponsor protocol number]
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Publication policy
All proposed publications will be discussed with Sponsor prior to publishing
other than those presented at scientific forums/meetings. Please refer to UCL
publication policy.
22
Statement of compliance
Include the following statement:
The trial will be conducted in compliance with the approved protocol, the UK
Regulations, EU GCP and the applicable regulatory requirement(s).
23
References
List of the literature and data that are relevant to the trial, and that provide
background for the trial. Please ensure the text contains appropriate cross
references to this list
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