Date and Version No:
Information on Clinical Trial Protocol Template
This protocol template has been designed primarily for Clinical Trials which are
subject to the Medicines for Human use (Clinical Trials) Regulations 2004 and
Amendment 2006. It has been specifically adapted for non-commercially sponsored
studies.
The template is available for use by all investigators who are carrying out clinical
trials sponsored by the NUH NHS Trust.
All advisory text and quotations from ICH GCP are highlighted in yellow. These
should all be deleted before finalising the document. All sample text is in ‘basic
text’ style. This text of course will be altered or deleted as required while you
produce the draft.
Repetition of information throughout the protocol is not necessary; it may be useful
to cross-reference other sections of the protocol to avoid repetition.
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Study title:
insert full title including brief reference to the design, disease or
condition being studied, and primary objective
Study acronym:
Sponsor
Nottingham University Hospitals NHS Trust
Funder
Insert name of funder
Funding Reference
Insert funding reference
Chief Investigator
Insert name of CI
EudraCT Number
Insert EudraCT number
ISRCTN Number
Insert ISRCTN number
REC Reference Number
Insert REC reference number
Sponsor Reference
Insert R&I number
Number
Number
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Version Number and
Insert version number and date
Date
Confidentiality Statement
This document contains confidential information that must not be disclosed to
anyone other than the Sponsor, the Investigator Team, host NHS Trust (s),
regulatory authorities, and members of the Research Ethics Committee.
TABLE OF CONTENTS
STUDY MANAGEMENT GROUP …………………………………………………………...........5
1. AMENDMENT HISTORY ………………………………………………………………………..7
2. PROTOCOL APPROVAL ……………………………………………………………………….8
3. ABBREVIATIONS………………………………………………………………………………...9
4. STUDY SUMMARY……………………………………………………………………………...10
5. INTRODUCTION………………………………………………………………………………...11
6. STUDY OBJECTIVES…………………………………………………………………………..11
6.1 OBJECTIVES…………………………………………………………………………..11
6.1.1 Primary Objective…………………………………………………………...11
6.1.2 Secondary Objective………………………………………………………..11
6.2 ENDPOINTS……………………………………………………………………………11
6.2.1 Primary endpoint…………………………………………………………….11
6.2.2 Secondary endpoint………………………………………………………...11
7. STUDY DESIGN………………………………………………………………………………….12
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8. STUDY POPULATION…………………………………………………………………………..12
8.1 NUMBER OF PARTICIPANTS……………………………………………………….12
8.2 INCLUSION CRITERIA………………………………………………………………..12
8.3 EXCLUSION CRITERIA………………………………………………………………12
9. PARTICIPANT SELECTION AND ENROLMENT…………………………………………...13
9.1 IDENTIFYING PARTICIPANTS………………………………………………………13
9.2 CONSENTING PARTICIPANTS……………………………………………………..13
9.3 SCREENING FOR ELIGIBLE PARTICIPANTS…………………………………….14
9.4 RANDOMISATION ……………………………………………………………………15
10. INVESTIGATIONAL MEDICINAL PRODUCT….…………………………………………..16
10.1 STUDY DRUG…..……………………………………………………………………16
10.1.1 Study drug administration……………………..……………….…………16
10.1.2 Study drug manufacturer………………………………………………….16
10.1.3 Marketing authorisation holder…………………………………………...16
10.1.4 Labelling and packaging...………………………………………………..16
10.1.5 Storage……………….…………………………………………………….16
10.2 PLACEBO……………………………………………………………………………..16
10.3 DOSING REGIME……………………………………………………………………16
10.4 PARTICIPANT COMPLIANCE……………………………………………………...16
10.5 OTHER MEDICATIONS……………………………………………………………..17
10.5.1 Permitted medications…………………………………………………….17
10.5.2 Prohibited medications……………………………………………………16
11. STUDY ASSESSMENTS………………………………………………………………..…….17
11.1SAFETY ASSESSMENTS……………………………………………………………17
11.2 STUDY ASSESSMENTS……………………………………………………………17
12. DATA COLLECTION…………………………………………………………………………..17
13. STATISTICS…………………………………………………………………………………….17
13.1 DESCRIPTION OF STATISTICAL METHODS……………………………………17
13.2 THE NUMBER OF PARTICIPANTS………………………………………………..17
13.3 THE LEVEL OF STATISTICAL SIGNIFIGANCE………………………………….18
13.4 CRITERIA OF THE TERMINATION OF THE TRIAL …………………………….18
13.5 PROCEDURE FOR ACCOUNTING FOR MISSING, UNUSED AND
SPURIOUS DATA………………………………………………………………………………………...18
13.6 PROCEDURES FOR REPORTING ANY DEVIATIONS(S) FROM THE
ORIGINAL STATISTICAL PLAN………………………………………………………….18
13.7 INCLUSION IN ANALYSIS………………………………………………………….18
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14. SAFETY REPORTING………………………………………………………………………...18
14.1 DEFINITIONS ………………………………………………………………………..18
14.1.1 Adverse Event (AE)……………………………………………………….18
14.1.2 Adverse Device Effect (ADE)…………………………………………….18
14.1.3 Serious Adverse Event (SAE)……………………………………………19
14.1.4 Serious Adverse Device Effects (SADE)……………………………….19
14.1.5 Unanticipated Adverse Device Effect (UADE)…………………………20
14.2 REPORTING OF AN AE…………………………………………………………….20
14.3 REPORTING PROCEDURES FOR ALL SAEs/ SADEs/ UADEs………………20
14.4 ANNUAL REPORTS…………………………………………………………………21
15. TRIAL MANAGEMENT………………………………………………………………………..21
15.1 TRIAL MANAGEMENT GROUP……………………………………………………21
15.2 TRIAL STEERING COMMITTEE…………………………………………………...21
15.3 DATA MONITORING COMMITTEE………………………………………………..21
15.4 INSPECTION OF RECORDS……………………………………………………….21
15.5 RISK ASSESSMENT………………………………………………………………...22
15.6 MONITORING………………………………………………………………………...22
16. GOOD CLINICAL PRACTISE………………………………………………………………...22
16.1 DECLERATION OF HELSINKI……………………………………………………..22
16.2 ICH GUIDELINES FOR GCP……………………………………………………….22
16.3 APPROVALS………………………………………………………………………….22
16.4 PARTICIPANT CONFIDENTIALITY………………………………………………..23
16.5 OTHER ETHICAL CONSIDERATIONS…………………………………………....23
16.6 DATA HANDLING AND RECORD KEEPING……………………………………..23
17. STUDY CONDUCT RESPONSIBILITIES……………………………………………………23
17.1 PROTOCOL AMENDMENTS……………………………………………………….23
17.2 PROTOCOL VIOLATIONS, DEVIATIONS AND SERIOUS
BREACHES……...23
17.3 STUDY RECORD RETENTION…………………………………………………….24
17.4 END OF STUDY……………………………………………………………………...24
17.5 INSRUANCE AND INDEMNITY…………………………………………………….24
17.6 FUNDING……………………………………………………………………………...24
18. REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS…………………..24
18.1 AUTHORSHIP POLICY……………………………………………………………...24
18.2 PUBLICATION………………………………………………………………………..25
18.3 PEER REVIEW……………………………………………………………………….25
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19. REFERENCES………………………………………………………………………………….25
APPENDIX 1 STUDY FLOW CHART…………………………………………………………….26
APPENDIX 2 SCHEDULE OF EVENTS…………………………………………………………27
STUDY MANAGEMENT GROUP
Chief Investigator
Co Investigators
Name:
Name:
Telephone:
Telephone:
Statistician
Study Management
Name:
Name:
Telephone:
Telephone:
Address:
Email:
Address:
Email:
Address:
Email:
Address:
Email:
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Study Coordination Centre (may not be applicable)
For general queries, supply of study documentation, and collection of data, please
contact:
Study
Coordinator:
Address:
Telephone:
Fax:
Email:
Clinical Queries
Clinical queries should be directed to xxx who will direct the query to the
appropriate person
Sponsor
Nottingham University Hospitals NHS Trust is the main research sponsor for this
study.
For further information regarding the sponsorship conditions, please contact
the Head of Regulatory Compliance at:
Nottingham University Hospitals NHS Trust
Research & Innovation
Nottingham Health Science Partners
C Floor, South Block
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
Email ResearchSponsor@nuh.nhs.uk
Funder
[Who is funding the study]
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This protocol describes the xxx study and provides information about procedures for
entering participants.
Every care was taken in its drafting, but corrections or
amendments may be necessary. These will be circulated to investigators in the
study.
Problems relating to this study should be referred, in the first instance, to
the Chief Investigator.
This study will adhere to the principles outlined in the NHS Research Governance
Framework for Health and Social Care (2nd edition). It will be conducted in
compliance with the protocol,
requirements as appropriate.
the Data Protection Act
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and other
regulatory
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1. AMENDMENT HISTORY
Amendment
No.
Protocol
Version No.
Date issued
Author(s) of
changes
Details of changes
made
List details of all protocol amendments here whenever a new version of the
protocol is produced.
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2. PROTOCOL APPROVAL
Insert study title:
______________________
______________________
______________
Chief Investigator
Signature
Date
______________________
______________________
______________
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Trial Statistician
Signature
Date
______________________
______________________
______________
Sponsor Representative
Signature
Date
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3. ABBREVIATIONS
Add or delete as appropriate.
AE
Adverse Event
CI
Chief Investigator
AR
CRA
CRF
CRO
CT
CTA
EC
GCP
GP
GTAC
IB
ICF
ICH
IEC
IMP
IRB
MHRA
NHS
NRES
PI
PIL
R&I
REC
SAE
SAR
SmPC/SPC
SOP
SUSAR
TMF
Adverse Reaction
Clinical Research Associate
Case Report Form
Clinical Research Organisation
Clinical Trials
Clinical Trials Authorisation
Ethics Committee (see REC)
Good Clinical Practise
General Practitioner
Gene Therapy Advisory Committee
Investigator Brochure
Informed Consent Form
International Conference of Harmonisation
Independent Ethics Committee
Investigational Medicinal Products
Independent Review Board
Medicinal Health Research Authority
National Health Service
National Research Ethics Service
Principle Investigator
Participant Information Sheet
Research & Innovation
Research Ethics Committee
Serious Adverse Event
Serious Adverse Reaction
Summary of Products Characteristics
Standard Operating Procedure
Suspected Unexpected Serious Adverse Reactions
Trial Master File
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4. STUDY SUMMARY
Study tile
R&I ref number
Clinical Phase
Trial Design
Trial Participants
Planned Sample Size
Number of Participants
Follow-up Duration
Planned Trial Period
Primary Objective
Secondary Objective
Primary End points
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Secondary End points
Investigational Medicinal
Product
Form
Dose
Route
5. INTRODUCTION
Include the following

Summarise briefly the main characteristics of the disease being studied and
any possible opportunity for better treatment.

Name, description and characteristics of the investigational medical product(s)
(may include mechanism of action).

A summary of findings from non-clinical studies (if relevant) that potentially
have clinical significance and from other clinical trials relevant to this trial).

Summary of the known and potential risks and benefits, if any, to human
participants.

Brief description of and justification for the route of administration, dosage,
dosage regimen, and treatment period(s)


Description of the population to be studied.
References to literature and data that are relevant to the trial, and that
provide background for the trial (reference list will be inserted later).
6. STUDY OBJECTIVES
6.1 OBJECTIVES
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There is usually only one primary objective, the rest are secondary objectives.
The wording of the objectives should be clear, unambiguous and as specific as
possible – the study will be judged on how and how well the objectives were
satisfied.
6.1.1 Primary objective
Detail primary objective
6.1.2 Secondary objective
Detail secondary objective
6.2 ENDPOINTS
Describe the end-points/outcome measures and how/when they will be measured
during the trial.
Endpoints/outcome measures should reflect the objectives. It is important that only
one primary endpoint/outcome measure is selected as it will be used to decide the
overall results or ‘successes of the trial. The primary endpoint/outcome measure
should be measurable, clinically relevant to participants and widely accepted by the
scientific and medical community.
6.2.1 Primary endpoint
Detail Primary endpoint
6.2.2 Secondary endpoint
Detail secondary endpoint
7. STUDY DESIGN
Summary of Trial Design
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
Describe the overall study design e.g., double-blind, placebo-controlled,
parallel design, open labelled.

Give the expected duration of participant participation, number of visits, and
a description of the sequence and duration of all trial periods e.g. screening
period, treatment period, post treatment follow up period, and possibly add a
flow chart here or as an appendix.


Points in the trial to measure the outcomes
Detail any stopping rules for the study
8. STUDY POPULATION
8.1 NUMBER OF PARTICIPANTS
Include



Number of participants
Number of sites
Length of recruitment period
8.2 INCLUSION CRITERIA
Example criteria (amend as appropriate):

Participant is willing and able to give informed consent for participation in the
study.


Male or Female, aged 18 years or above.
Diagnosed with required disease/severity/symptoms, any specific assessment
criteria for these), or, if healthy volunteer study: be in good health

(alter as required) Stable dose of current regular medication (specify type if
needed) for at least 4 weeks prior to study entry. Or (delete one or other), if
healthy volunteer study: have had no course of medication, whether prescribed
or over-the-counter, in the four weeks before first study dose and no individual
doses in the final two weeks other than mild analgesia, vitamins and mineral
supplements or, for females, oral contraceptives.
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
Female participants of child bearing potential and male participants whose
partner is of child bearing potential must be willing to ensure that they or their
partner use effective contraception during the study and for 3 months thereafter

Participants has clinically acceptable laboratory and ECG (specify any other
additional assessments) within <insert duration> of enrolment.

Able (in the Investigators opinion) and willing to comply with all study
requirements.

Willing to allow his or her General Practitioner and consultant, if appropriate, to
be notified of participation in the study.

Additional study specific criteria as required
8.3 EXCLUSION CRITERIA
Example criteria (amend as appropriate):
The participant may not enter the study if ANY of the following apply:

Female participants who is pregnant, lactating or planning pregnancy during the
course of the study.


Significant renal or hepatic impairment.
Scheduled elective surgery or other procedures requiring general anaesthesia
during the study.


Participant who is terminally ill or is inappropriate for placebo medication
Any other significant disease or disorder which, in the opinion of the
Investigator, may either put the participants at risk because of participation in
the study, or may influence the result of the study, or the participant’s ability to
participate in the study.

Donation of blood during the study. or, if healthy volunteer PK study within the
past 12 weeks

Participants who have participated in another research study involving an
investigational product in the past 12 weeks

Additional study specific criteria as required
9. PARTICIPANT SELECTION AND ENROLMENT
9.1 IDENTIFYING PARTICIPANTS
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Include

How will participants be identified eg, in clinic, database, invitation letters and
posters

Who will be responsible for identifying participants
9.2 CONSENTING PARTICIPANTS
You need to specify who will take informed consent, how and when it will be
taken. Informed consent should be obtained prior to any study related procedures
being undertaken.
Example:
The participant must personally sign and date the latest approved version of the
informed consent form before any study specific procedures are performed.
Written and verbal versions of the participant information and Informed consent will
be presented to the participants detailing no less than: the exact nature of the
study; the implications and constraints of the protocol; the known side effects and
any risks involved in taking part. It will be clearly stated that the participant is free
to withdraw from the study at any time for any reason without prejudice to future
care, and with no obligation to give the reason for withdrawal.
The participant will be allowed as much time as wished to consider the information,
and the opportunity to question the Investigator, their GP or other independent
parties to decide whether they will participate in the study. Written Informed
Consent will then be obtained by means of participant dated signature and dated
signature of the person who presented and obtained the informed consent. The
person who obtained the consent must be suitably qualified and experienced, and
have been authorised to do so by the Chief/Principal Investigator. A copy of the
signed Informed Consent will be given to the participants. The original signed form
will be retained at the study site.
*can be substituted parent/guardian or legally authorised representative, as
appropriate, make sure that the term is consistent throughout the document
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9.3 SCREENING FOR ELIGIBLE PARTICIPANTS

Detail how potential participants will be identified, approached, screened and
recruited.



If applicable, specify pre-screening procedures.
What is the maximum duration allowed between screening and randomisation?
Specify the recruitment procedures e.g. referral by GPs, screening medical
notes, using advertisements.
Describe the screening procedures in detail.
These are some of the headings and texts you may want to include. Alter or add
as necessary:
Demographics
The date of birth, gender, race, smoking and drinking habits (add as required)… will
be recorded.
Medical History
Details of any history of disease or surgical interventions in the following systems
will be recorded: Provide details as appropriate.
Concomitant Medication
All over-the-counter or prescription medication, vitamins, and/or herbal supplements
will be recorded on CRFs. Describe what information will be recorded.
Physical Examination
Height, weight and oral temperature will be recorded.
Resting pulse and blood pressure (BP) measurements will be measured after the
participant has sat for at least five minutes. Provide details as appropriate.
ECG Test
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A 12-lead ECG will be taken for each participant. At least the following ECG
parameters will be recorded: heart rate (HR), PR, QT and QRS intervals and QTC.
The report will be signed by the Investigator who will record in the CRF whether it
is normal, abnormal but not clinically significant, or abnormal AND clinically
significant. In the latter case the eligibility of the participants will be reviewed.
Laboratory Tests
Describe any laboratory tests e.g. biochemistry, urinalysis and pregnancy tests.
Sample text:
All laboratory results will be reviewed and the reports signed by the Investigator
who will record in the CRF whether they are normal, abnormal but not clinically
significant, or abnormal AND clinically significant. In the latter case the eligibility of
the participants will be reviewed.
9.4 RANDOMISATION (if applicable)
Describe how randomisation is going to be carried out, and who will provide the
randomisation codes. Will randomisation be done at the same visit as the baseline
visit, or must participants return for a randomisation visit? Will there be a run in
period?
Who will design the randomisation schedule (statistician, CRO), and who will hold it
(Pharmacy, independent organisation).
If the clinical condition of a participant necessitates breaking the code, who will do
this and how?
Will individual envelopes per participant per period be supplied so
that the code may be broken for a single participant without unblinding the whole
study? Or will the pharmacist access the randomisation schedule if required by the
Investigator and supply the needed information? Please refer to NUH SOP 9 on
Unblinding.
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State that if randomisation of a participant is unblinded during the study then data
for that participants will not be admitted to analysis.
Example
Subject numbers will be assigned sequentially as each subject enters the study.
The subjects will be assigned study drug through a randomisation schedule based
on the randomisation plan. The study drug will be labelled with the study number
and unique identification number. The two treatments x and y will be
indistinguishable. In the event of an emergency, the investigator is to decide the
necessity of unblinding the subject’s treatment assignment. The blinded treatment
assignments will be accessible to the investigator should a subject need to be
unblinded in an emergency using the unblinding envelopes provided to the hospital
pharmacy and X Toxicology Service. If unblinding occurs, the investigator or study
pharmacist must record the reason for unblinding, as well as the date and time of
the event. Corresponding information will be recorded on the CRF by the
investigator.
Or
A contract research organisation will be commissioned to implement the
randomisation process and provide the medication packs. Both the study drug X
and placebo will be formulated and supplied in identical capsules sealed in identical
medication packs. The allocation to placebo/X will be randomly assigned and the
medication packs will be consecutively numbered with the trial PIN. Sealed
randomisation envelopes will be kept unopened and in a secure place by the
pharmacy at Nottingham University Hospitals and the Investigators. The medication
packs will be kept in the hospital pharmacy which will dispense them to trial
participants. Participants will be enrolled and assigned a PIN consecutively, and
issued with the medication pack corresponding to the PIN. Both trial participants
and investigators will be blinded to the nature of the study medication dispensed
and all image and spectroscopic analysis will be conducted while blinded to study
treatment. Once all collected data has been analysed, the randomisation code will
be broken by the study investigators and the medication data entered into the
analysis. Should urgent un-blinding of a trial participant’s medication be required
(when requested by a clinician treating the participant), this will be provided by the
pharmacy at the Nottingham University Hospitals. This is normally a working-hours
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service, but in exceptional circumstances could operate at any time. The trial
investigators have reviewed the clinical safety of the study and do not feel that a
24-hour un-blinding service would be required for the appropriate treatment of
participants, either within the Nottingham University Hospitals or elsewhere.
10. INVESTIGATIONAL MEDICINAL PRODUCT
10.1 STUDY DRUG
10.1.1 Study drug administration
Detail


Full
name, generic name and UK trade name
What form does the IMP come in
10.1.2 Study drug manufacturer
Detail the name and address of the company that will supply the study drug
10.1.3 Marketing authorisation holder
Detail the name, address and MA number of the company manufacturing the study
drug.
10.1.4 Labelling and packaging
Detail the name and address of the company or pharmacy performing any
additional packaging that may be necessary and study labelling.
10.1.5 Storage
Detail storage conditions and location.
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10.2 PLACEBO
Detail what form the placebo will come in, who will manufacture it.
10.3 DOSING REGIME
Include



Dosage and any calculations
Duration of treatment period
When participants will receive the IMP/ Placebo
10.4 PARTICIPANT COMPLIANCE
You need to describe how compliance is assessed. Will you ask the participants to
keep a diary, bring all unused or part-used medication/vials and packaging from
used medication at each visit? You may want to define significant non-compliance
and what procedures will be taken if there is significant non-compliance.
Example:
The participants will be instructed to return all unused or part-used medication/vials
and packaging from used medication at each visit. The Investigator may withdraw
the participants if he considers dose compliance is unsatisfactory.
10.5 OTHER MEDICATIONS
10.5.1 Permitted medications
Detail drugs that maybe taken during the study.
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10.5.2 Prohibited medication
Detail other drugs that are not allowed during the study due to interaction with the
study drug or an effect on the study outcomes.
11. STUDY ASSESSMENTS
11.1 SAFETY ASSESSMENTS
Detail any specific safety assessment required for the study
11.2 STUDY ASSESSMENTS
Detail specific study assessments to be performed and split them into the visit
names. Refer to a schedule of events table in the appendices.
12. DATA COLLECTION
Define what will comprise source documents
Example:
Source documents are original documents, data, and records from which
participants’ CRF data are obtained. These include, but are not limited to, hospital
records (from which medical history and previous and concurrent medication may
be summarised into the CRF), clinical and office charts, laboratory and pharmacy
records, diaries, microfiches, radiographs, and correspondence.
CRF entries will be considered source data if the CRF is the site of the original
recording (e.g., there is no other written or electronic record of data). In this study
the CRF will be used as the source document for …<<add as required>>
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All documents will be stored safely in confidential conditions. On all study-specific
documents, other than the signed consent, the participant will be referred to by the
study participant number/code, not by name.
13. STATISTICS
Where possible the statistician should write this section.
The sub-headings given below are suggestions. However, if a Statistical Analysis
Plan is to be produced separately, state this here and condense the most relevant
information from the sub sections here.
13.1 DESCRIPTION OF STATISTICAL METHODS
Describe the statistical methods to be employed, including timing of any planned
interim analysis (es).
13.2 THE NUMBER OF PARTICIPANTS
State the approximate number of participants required to complete (commence).
Justify choice of sample size, including reflections on (or calculations of) the power
of the trial and clinical justification.
13.3 THE LEVEL OF STATISTICAL SIGNIFICANCE
State the level of significance to be used.
13.4 CRITERIA FOR THE TERMINATION OF THE TRIAL
Describe
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13.5 PROCEDURE FOR ACCOUNTING FOR MISSING, UNUSED AND
SPURIOUS DATA
Describe
13.6 PROCEDURES FOR REPORTING ANY DEVIATIONS(S) FROM THE
ORIGINAL STATISTICAL PLAN
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
protocol and/or in the final report, as appropriate).
13.7 INCLUSION IN ANALYSIS
The selection of participants to be included in the analyses (e.g., all randomised
participants, all dosed participants, all eligible participants, evaluable participants).
14. SAFETY REPORTING (REFER TO SOP X ADVERSE
EVENTS MONITORING, REPORTING AND RECORDING).
14.1 DEFINITIONS
14.1.1 Adverse Event (AE)
An AE or adverse experience is:
Any untoward medical occurrence in a patient or clinical investigation participants
administered a medicinal product, which does not necessarily have to have a
causal relationship with this treatment (the study medication).
An AE can therefore be any unfavourable and unintended sign (including an
abnormal laboratory finding), symptom or disease temporally associated with the
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use of the study medication, whether or not considered related to the study
medication.
14.1.2 Adverse Drug Reaction (ADR)
All untoward and unintended responses to a medicinal product related to any dose.
The phrase "responses to a medicinal products" means that a causal relationship
between a study medication and an AE is at least a reasonable possibility, i.e., the
relationship cannot be ruled out.
All cases judged by either the reporting medically qualified professional or the
sponsor as having a reasonable suspected causal relationship to the study
medication qualify as adverse reactions.
14.1.3 Serious Adverse Event (SAE)
A serious adverse event or reaction is any untoward medical occurrence that at any
dose:


Results in death,
Is life-threatening,
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in
which the participant was at risk of death at the time of the event; it does not refer
to an event which hypothetically might have caused death if it were more severe.




Requires inpatient hospitalisation or prolongation of existing hospitalisation,
Results in persistent or significant disability/incapacity, or
Is a congenital anomaly/birth defect.
Other important medical events*
*Other events that may not result in death, are not life threatening, or do not
require hospitalisation, may be considered a serious adverse event when, based
upon appropriate medical judgement, the event may jeopardise the patient and may
require medical or surgical intervention to prevent one of the outcomes listed
above.
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14.1.4 Expected Serious Adverse Events/Reactions
Give an outline of any serious adverse events/reactions that could be reasonably
expected when taking into account the likely course of the disease or condition
during the course of the study or expected from the study medication(s). Consider
carefully whether or not these require immediate reporting.
14.1.5 Suspected Unexpected Serious Adverse Reactions (SUSARs)
A serious adverse reaction, the nature or severity of which is not consistent with
the applicable product information (e.g., Investigator’s Brochure for an unapproved
investigational product or package insert/summary of product characteristics for an
approved product).
14.2 REPORTING PROCEDURES FOR ALL ADVERSE
All AEs occurring during the study observed by the investigator or reported by the
participant, whether or not attributed to study medication, will be recorded on the
CRF.
The following information will be recorded: description, date of onset and end date,
severity, assessment of relatedness to study medication, other suspect drug or
device and action taken.
Follow-up information should be provided as necessary.
AEs considered related to the study medication as judged by a medically qualified
investigator or the sponsor will be followed until resolution or the event is
considered stable. All related AEs that result in a participant’s withdrawal from the
study or are present at the end of the study, should be followed up until a
satisfactory resolution occurs.
It will be left to the investigator’s clinical judgment whether or not an AE is of
sufficient severity to require the participant’s removal from treatment (see section
6.6). A participant may also voluntarily withdraw from treatment due to what he or
she perceives as an intolerable AE. If either of these occurs, the participant must
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undergo an end of study assessment and be given appropriate care under medical
supervision until symptoms cease or the condition becomes stable.
The relationship of AEs to the study medication will be assessed by a medically
qualified investigator.
Any pregnancy occurring during the clinical study and the outcome of the
pregnancy should be recorded and followed up for congenital abnormality or birth
defect.
14.3 REPORTING PROCEDURES FOR SERIOUS ADVERSE
All SAEs, except those expected ones defined in section 14.1.4 (remove if not
applicable) that do not require immediate reporting must be reported to R&D within
one working day of discovery or notification of the event. As Sponsor R&D at
NUH will report all SUSARs to the Competent Authorities MHRA and the Research
Ethics Committee concerned. Fatal or life-threatening SUSARs must be reported
within 7 days and all other SUSARs within 15 days. The CI will inform all
investigators concerned of relevant information about SUSARs that could adversely
affect the safety of participants.
In addition to the expedited reporting above, the CI shall submit once a year
throughout the clinical trial or on request a Safety Report to R&D, the Competent
Authority MHRA and Ethics Committee.
If the University of Nottingham Clinical Trials Unit (CTU) is responsible for the Trial,
it is the CTUs responsibility to report to the MHRA , Ethics and then notify the
R&D.
14.4 ANNUAL REPORTS
In addition to the expedited reporting above, the CI shall submit once a year
throughout the clinical trial or on request a Safety Report to R&I, the Competent
Authority MHRA and Ethics Committee.
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15. TRIAL MANAGEMENT
15.1 TRIAL MANAGEMENT GROUP
Detail who will form part of the trial management group what their role will be and
what they will be responsible for.
15.2 TRIAL STEERING COMMITTEE
Detail who will form part of the trial steering committee what their role will be and
what they will be responsible for. If a TSC is not being set up then this will need
to be justified in this section.
15.3 DATA MONITORING COMMITTEE
Detail who will form part of the data monitoring committee what their role will be
and what they will be responsible for. If a DMC is not being set up then this will
need to be justified in this section.
15.4 INSPECTION OF RECORDS
Investigators and institutions involved in the study will permit trial related monitoring
and audits on behalf of the sponsor and regulatory inspection(s). In the event of
an audit or monitoring, the Investigator agrees to allow the representatives of the
sponsor direct access to all study records and source documentation. In the event
of regulatory inspection, the Investigator agrees to allow inspectors direct access to
all study records and source documentation
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15.5 RISK ASSESSMENT
A risk assessment will be performed by the Sponsor to determine if monitoring is
required and if so, at what level.
15.6 STUDY MONITORING
A Research Project Manager will visit the Investigator site prior to the start of the
study and during the course of the study if required, in accordance with the
monitoring plan. Monitoring will be performed according to ICH GCP. Data will be
evaluated for compliance with the protocol and accuracy in relation to source documents.
Following written standard operating procedures, the monitors will verify that the clinical trial
is conducted and data are generated, documented and reported in compliance with the
protocol, GCP and the applicable regulatory requirements.
16. GOOD CLINICAL PRACTICE
Describe ethical considerations relating to the trial. Include general and study
specific ethical considerations.
16.1 DECLARATION OF HELSINKI
The Investigator will ensure that this study is conducted in full conformity with the
current revision of the Declaration of Helsinki (last amended October 2000, with
additional footnotes added 2002 and 2004).
16.2 ICH GUIDELINES FOR GCP
The Investigator will ensure that this study is conducted in full conformity with
relevant regulations and with the ICH Guidelines for Good Clinical Practice
(CPMP/ICH/135/95) July 1996.
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16.3 APPROVALS
Consider the following text:
The protocol, informed consent form, participant information sheet and any proposed
advertising material will be submitted to an appropriate Research Ethics Committee
(REC), regulatory authorities (MHRA in the UK), and host institution(s) for written
approval.
The Investigator will submit and, where necessary, obtain approval from the above
parties for all substantial amendments to the original approved documents.
16.4 PARTICIPANT CONFIDENTIALITY
The trial staff will ensure that the participants’ anonymity is maintained. The
participants will be identified only by initials and a participants ID number on the
CRF and any electronic database. All documents will be stored securely and only
accessible by trial staff and authorised personnel. The study will comply with the
Data Protection Act which requires data to be anonymised as soon as it is practical
to do so.
16.5 OTHER ETHICAL CONSIDERATIONS
Include any other ethical considerations specific to the study e.g. use of placebo,
involvement of vulnerable participants.
16.6 DATA HANDLING AND RECORD KEEPING
Describe method of data entry/management
Example:
All study data will be entered on a <<quote software and validation procedure>>.
Note that ICH GCP (Section 5.5) requires that electronic data entry systems are
validated and that Standard Operating Procedures are maintained.
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The participants will be identified by a study specific participants number and/or code
in any database. The name and any other identifying detail will NOT be included in
any study data electronic file.
17. STUDY CONDUCT RESPONSIBILITITES
17.1 PROTOCOL AMENDMENTS
Amendments to the protocol must be submitted to the Sponsor for review before
submitting to the appropriate REC, Regulatory Authority and local R&D for approval.
17.2 PROTOCOL VIOLATIONS, DEVIATIONS AND SERIOUS BREACHES
The CI will not implement any deviation from the protocol without agreement from
the Sponsor, except where necessary to eliminate an immediate hazard to trial
participants.
In the event that the CI needs to deviate from the protocol, the nature of and
reasons for the deviation will be recorded in the CRF and notified to the Sponsor.
If this necessitates a subsequent protocol amendment, this will be submitted to the
Sponsor for approval and then to the appropriate REC, Regulatory Authority and
local NHS R&I for review and approvals as appropriate. It is Sponsor policy that
waivers to the Protocol will not be approved.
In the event that a serious breach of GCP is suspected, this will be reported to the
Sponsor immediately using the form “Notification to Sponsor of Serious Breach or
Serious Deviation”. Refer to SOP-RES-017 “Non-Compliance and Serious Breach
Reporting”
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17.3 STUDY RECORD RETENTION
All study documentation will be kept for 10 years from the protocol defined end of
study point. When the minimum retention period has elapsed, study documentation
will not be destroyed without permission from the sponsor.
17.4 END OF STUDY
The end of study is defined as the last participant’s last visit.
The Investigators and/or the trial steering committee and/or the co-sponsor(s) have
the right at any time to terminate the study for clinical or administrative reasons.
The end of the study will be reported to the REC and Regulatory Authority within
90 days, or 15 days if the study is terminated prematurely. The Investigators will
inform participants of the premature study closure and ensure that the appropriate
follow up is arranged for all participants involved.
A summary report of the study will be provided to the REC and Regulatory
Authority within 1 year of the end of the study.
17.5 INSURANCE AND INDEMNITY
NHS bodies are legally liable for the negligent acts and omissions of their
employees. If you are harmed whilst taking part in a clinical trial as a result of
negligence on the part of a member of the study team this liability cover would
apply.
Non-negligent harm is not covered by the NHS indemnity scheme. The Nottingham
University Hospitals NHS Trust, therefore, cannot agree in advance to pay
compensation in these circumstances. In exceptional circumstances an ex-gratia
payment may be offered.
17.6 FUNDING
Describe funding arrangements
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18. REPORTING, PUBLICATIONS AND NOTIFICATIONS OF
RESULTS
18.1 AUTHORSHIP POLICY
Ownership of the data arising from this study resides with the study team. On
completion of the study, the study data will be analysed and tabulated, and a
clinical study report will be prepared in accordance with ICH guidelines.
18.2 PUBLICATION
The publication policy should cover authorship, acknowledgements, and review procedures
for scientific publications. If there is a department or institution policy, or agreement, the
protocol can refer to it.
18.3 PEER REVIEW
Detail procedures for peer review – these may be funder specific or involve an
internal department.
19. REFERENCES
Insert references used in text.
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APPENDIX 1 STUDY FLOW CHART
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Optional
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APPENDIX 2 SCHEDULE OF PROCEDURES
Optional Alter as required, delete if not wanted
Procedures
Visits (insert visit numbers as appropriate)
Screening Baseline
Informed consent
Demographics
Medical history
Concomitant medications
Physical examination
ECG
Laboratory tests
Eligibility assessment
Randomisation
Assessment 1 (describe)
Assessment 2 (describe)
Assessment 3 (describe)
Assessment 4 (describe)
Adverse event
assessments
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