Clinical Study Report
[Study Title]
[Study number]
[Dd month yyyy]
CONFIDENTIAL
Signature pages for clinical study report
I have read this report and confirm that to the best of my knowledge it accurately describes the
conduct and results of the study.
Signed:
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1
TITLE PAGE
Study title:
Name of Test Drug:
Indication studied:
Study description:
Sponsors:
Protocol:
Clinical Phase:
Study dates:
Investigators:
Medical Officer:
Sponsor signatory:
GCP Statement:
This study was performed in compliance with ICH Good Clinical
Practise (GCP) including the archiving of essential documents
Date of report:
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2
SYNOPSIS
NAME OF SPONSOR
NAME OF FINISHED PRODUCT
N/A
NAME OF ACTIVE INGREDIENT(S)
INDIVIDUAL STUDY TABLE
REFERRING TO MODULE 5
OF THE CTD
(FOR NATIONAL
AUTHORITY USE
ONLY)
Volume:
Page:
Title of Study
Investigator(s)
Study centre(s)
Publication
N/A
Study period
From:
To:
Primary Objective
Objectives
Phase of development
Phase
Secondary Objective
Methodology
Number of
patients
Planned:
Analysed:
Diagnosis and
main criteria for
inclusion
Test product, dose
and mode of
administration
Duration of
treatment
Criteria for
evaluation
Primary:
Secondary:
Statistical methods
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NAME OF COMPANY
NAME OF FINISHED PRODUCT
NAME OF ACTIVE INGREDIENT(S)
N/A
INDIVIDUAL STUDY TABLE
REFERRING TO MODULE 5
OF THE CTD
(FOR NATIONAL
AUTHORITY USE
ONLY)
Volume:
Page:
SUMMARY CONCLUSIONS
EFFICACY RESULTS
SAFETY RESULTS
CONCLUSION
DATE OF THE REPORT:
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3
TABLE OF CONTENTS
1 TITLE PAGE .............................................................................................................................. 3
2 SYNOPSIS ................................................................................................................................. 4
3 TABLE OF CONTENTS ............................................................................................................. 6
4 LIST OF ABBREVIATIONS & DEFINITION OF TERMS .......................................................... 8
5 ETHICS AND REGULATORY APPROVAL .............................................................................. 9
5.1
INDEPENDENT ETHICS COMMITTEE APPROVAL ............................................................9
5.2
ETHICAL CONDUCT OF THE STUDY ..................................................................................9
5.3
PATIENT INFORMATION AND CONSENT ...........................................................................9
5.4
REGULATORY APPROVAL ................................................................................................10
6 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ....................................... 10
7 INTRODUCTION ...................................................................................................................... 11
7.1
[THERAPEUTIC AREA] .......................................................................................................11
7.2
RATIONALE FOR THE STUDY ...........................................................................................11
8 STUDY OBJECTIVES.............................................................................................................. 12
9 INVESTIGATIONAL PLAN ...................................................................................................... 12
9.1 OVERALL STUDY DESIGN AND PLAN ..............................................................................12
9.1.1
STUDY TIMING.............................................................................................................. 12
9.1.2
STUDY LOCATION ........................................................................................................ 12
9.2
DISCUSSION OF STUDY DESIGN .....................................................................................12
9.3 SELECTION OF STUDY POPULATION .............................................................................12
9.3.1
INCLUSION CRITERIA .................................................................................................. 12
9.3.2
EXCLUSION CRITERIA ................................................................................................. 12
9.3.3
WITHDRAWAL OF PATIENTS FROM THERAPY OR ASSESSMENT ........................ 12
9.4 TREATMENTS .....................................................................................................................13
9.4.1
TREATMENTS ADMINISTERED ................................................................................... 13
9.4.2
DESCRIPTION OF INVESTIGATIONAL PRODUCTS .................................................. 13
9.4.2.1
9.4.2.2
9.4.3
9.4.4
9.4.5
9.4.6
9.4.7
[PRIME] ......................................................................................... ERROR! BOOKMARK NOT DEFINED.
[BOOST] ........................................................................................ ERROR! BOOKMARK NOT DEFINED.
METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUPS ............................ 13
SELECTION OF DOSES IN THE STUDY ..................................................................... 13
SELECTION AND TIMING OF DOSE FOR INDIVIDUAL PATIENTS ........................... 13
PRIOR AND CONCOMITANT THERAPY ..................................................................... 13
TREATMENT COMPLIANCE ........................................................................................ 13
9.5 EFFICACY AND SAFETY VARIABLES ...............................................................................13
9.5.1
EFFICACY AND SAFETY MEASUREMENTS ASSESSED .......................................... 13
9.5.2
APPROPRIATENESS OF MEASUREMENTS .............................................................. 16
9.5.3
IMMUNOGENICITY VARIABLES .................................................................................. 16
9.6
DATA QUALITY ASSURANCE ............................................................................................16
9.7 STATISTICAL METHODS PLANNED IN THE PROTOCOL & DETERMINATION OF
SAMPLE SIZE ................................................................................................................................16
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9.7.1
9.7.2
STATISTICAL AND ANALYTICAL PLANS .................................................................... 16
DETERMINATION OF SAMPLE SIZE ........................................................................... 16
9.8 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES ...................16
9.8.1
PROTOCOL AMENDMENTS ........................................................................................ 16
10 STUDY POPULATION ............................................................................................................. 16
10.1 DISPOSITION OF PATIENTS..............................................................................................16
10.2 PROTOCOL DEVIATIONS ..................................................................................................18
11 RESULTS ................................................................................................................................. 19
11.1 DATA SETS ANALYSED .....................................................................................................19
11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ......................................19
11.3 MEASUREMENTS OF TREATMENT COMPLIANCE .........................................................19
11.4 STUDY DURATION .............................................................................................................19
11.5 IMMUNOGENECITY RESULTS AND TABULATIONS OF PATIENT DATA.......................20
11.5.1 ANALYSIS OF IMMUNOGENECITY ............................................................................. 20
11.5.2 STATISTICAL/ANALYTICAL ISSUES ........................................................................... 20
11.5.2.1
11.5.3
11.5.4
11.5.5
11.5.6
HANDLING OF DROPOUTS OR MISSING DATA ..................................................................... 20
TABULATION OF INDIVIDUAL RESPONSE DATA ...................................................... 20
VACCINE DOSE AND RELATIONSHIP TO RESPONSE ............................................. 20
BY-PATIENT DISPLAYS ............................................................................................... 20
IMMUNOGENECITY CONCLUSIONS .......................................................................... 20
12 SAFETY EVALUATION ........................................................................................................... 20
12.1 EXTENT OF EXPOSURE ....................................................................................................20
12.2 ADVERSE EVENTS (AE’s) ..................................................................................................20
12.2.1 BRIEF SUMMARY OF ADVERSE EVENTS ................................................................. 20
12.2.2 TREATMENT EMERGENT ADVERSE EVENTS .......................................................... 20
12.2.3 TREATMENT RELATED ADVERSE EVENTS .............................................................. 20
12.2.4 IMMUNISATION TOLERANCE ...................................................................................... 20
12.3 SERIOUS ADVERSE EVENTS AND OTHER SIGNIFICANT ADVERSE EVENTS ...........21
12.4 DEATHS ...............................................................................................................................21
12.5 CLINICAL LABORATORY EVALUATION ............................................................................21
12.5.1 EVALUATION OF EACH LABORATORY PARAMETER .............................................. 21
12.6 VITAL SIGNS, PHYSICAL FINDINGS AND OTHER OBSERVATIONS RELATED TO
SAFETY 21
12.7 CONCOMITTANT MEDICATION USE ................................................................................21
12.8 SAFETY CONCLUSIONS ....................................................................................................21
13 DISCUSSION AND OVERALL CONCLUSIONS .................................................................... 21
14 TABLES, FIGURES AND GRAPHS ........................................................................................ 21
15 REFERENCES ......................................................................................................................... 21
16 APPENDICES .......................................................................................................................... 21
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4
LIST OF ABBREVIATIONS & DEFINITION OF TERMS
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5
ETHICS AND REGULATORY APPROVAL
5.1 INDEPENDENT ETHICS COMMITTEE APPROVAL
The study protocol and all its amendments, and the patient information sheet(s) were
reviewed and approved by the appropriate independent ethics committees as detailed in
table one below.
Table I:
Ethics committees
Centre name and number
Investigator
Ethics committee
Chairman
Date of approval of the final
protocol
Date of approval of
amendment 1
Date of approval of
amendment 2
Date of approval of
amendment 3
5.2 ETHICAL CONDUCT OF THE STUDY
The study was performed in accordance with the current version of the declaration of
Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000). The trial
was conducted in agreement with the International Conference on Harmonisation (ICH)
guidelines on Good Clinical Practise (GCP)
5.3 PATIENT INFORMATION AND CONSENT
All patients provided written informed consent to participate in the study prior to being
screened.
The patient information sheet detailed the procedures involved in the study (aims,
methodology. potential risks, anticipated benefits) and the investigator explained these
to each patient. The patient signed the consent form to indicate that the information had
been explained and understood. The patient was then allowed time to consider the
information presented before signing and dating the informed consent form to indicate
that they fully understood the information, and willingly volunteered to participate in the
study. The patient was given a copy of the informed consent form for their information.
The original copy of the informed consent was kept in a confidential file in the
Investigators centre records. A sample of the patient information sheet and consent form
can be found at appendix [insert]
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5.4 REGULATORY APPROVAL
The study was performed in compliance with the requirements of the [regulatory
authorities]. The study gained full regulatory approval from the on [date], SPONSOR
was issued with the following EudraCT number [ ]. A copy can be found in appendix
[insert]
The study gained full approval from [EC] on [insert] a copy can be found in appendix
[insert]
6
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
Table II shows the principal study personnel involved in the study.
Table II: Principal study personnel
Title
Principal
Investigator
Principal
investigator
Sponsor
Name and affiliation
Sponsor
Project
Managers
Project Leaders
Clinical
Research
Associate(s)
Medical Adviser
Laboratory
investigator
Data
Management
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7
INTRODUCTION
7.1
[THERAPEUTIC AREA]
7.2
RATIONALE FOR THE STUDY
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8
STUDY OBJECTIVES
Primary Objective
Secondary Objective
9
INVESTIGATIONAL PLAN
9.1
OVERALL STUDY DESIGN AND PLAN
9.1.1
STUDY TIMING
Figure I
Schematic chart of Protocol
9.1.2
STUDY LOCATION
This study was conducted at the following locations:
9.2
DISCUSSION OF STUDY DESIGN
9.3
SELECTION OF STUDY POPULATION
9.3.1
INCLUSION CRITERIA
9.3.2
EXCLUSION CRITERIA
9.3.3
WITHDRAWAL OF PATIENTS FROM THERAPY OR ASSESSMENT
Patients were free to withdraw from the study at any time without giving a reason.
Patients were advised that if they requested to withdraw from the study, at any time
during the trial, then this would have no negative consequences.
The investigator could also withdraw patients from the trial if they deemed it appropriate
for safety or ethical reasons or if it was considered to be to be detrimental to the wellbeing of the patient. Patients who withdrew or were withdrawn underwent a final
evaluation at [visit]. Patients who did not complete the study through to [visit], unless
removed due to toxicity, could have been replaced
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Full documentation was made of any withdrawals that occurred during the study in the
CRF. The Investigator documented the date and time of the withdrawal and results of
any assessments made at this time. If the patient withdrew because of an adverse event
(AE) or a serious adverse event (SAE) then details were forwarded to the Ethics
committee as required. The investigator also forwarded details to SPONSOR.
SPONSOR forwarded details to the regulatory authorities as appropriate.
9.4
TREATMENTS
9.4.1
TREATMENTS ADMINISTERED
9.4.2
DESCRIPTION OF INVESTIGATIONAL PRODUCTS
9.4.3
METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUPS
9.4.4
SELECTION OF DOSES IN THE STUDY
9.4.5
SELECTION AND TIMING OF DOSE FOR INDIVIDUAL PATIENTS
9.4.6
PRIOR AND CONCOMITANT THERAPY
9.4.7
TREATMENT COMPLIANCE
All study treatment was administered by the study investigator or designated member of
staff. To ensure drug accountability the investigator or designated deputy maintained
accurate records of the dates and amounts of drug received, to whom it was dispensed
and accounts of any supplies which were accidentally or deliberately destroyed; these
details were recorded on a drug accountability form. All unused clinical supplies and the
drug accountability forms were returned to SPONSOR at the end of the study.
9.5
EFFICACY AND SAFETY VARIABLES
9.5.1
EFFICACY AND SAFETY MEASUREMENTS ASSESSED
Performance status
CT Scan (Disease status)
ECG
Clinical Assessment of Injection Site
Clinical Examination
Vital Signs
Safety
Laboratory Tests
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Haematology
Serum chemistry
Urinalysis
HBV, HCV, HIV and pregnancy
Cellular immunology
Table III shows the schedule of examinations and procedures.
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Table III
[Schedule of examinations and procedures]
Study day
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9.5.2
APPROPRIATENESS OF MEASUREMENTS
9.5.3
IMMUNOGENICITY VARIABLES
9.6
DATA QUALITY ASSURANCE
9.7
STATISTICAL METHODS PLANNED IN THE PROTOCOL & DETERMINATION
OF SAMPLE SIZE
9.7.1
STATISTICAL AND ANALYTICAL PLANS
9.7.2
DETERMINATION OF SAMPLE SIZE
9.8
9.8.1
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES
PROTOCOL AMENDMENTS
10 STUDY POPULATION
10.1 DISPOSITION OF PATIENTS
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PATIENTS SCREENED
N=
SCREENING FAILURES
N=
PATIENTS RANDOMISED
N=
GROUP A
N=
COMPLETED
N=
GROUP B
N=
WITHDRAWN N=
COMPLETED
N=
WITHDRAWN
N=
LOST TO FOLLOW UP (0)
ADVERSE EVENT (0)
DEATH (0 )
OTHER ( )
RECEIVED [Prime]
RECEIVED [Prime]
RECEIVED [Boost]
RECEIVED [Boost]
ATTENDED [visit]
COMPLETED [Visit]
Table IV
RECEIVED [Prime]
RECEIVED [Prime]
RECEIVED [Boost]
RECEIVED [Boost]
ATTENDED [visit]
COMPLETED [Visit]
Disposition of patients
Group A
(N=)
Group B
(N=)
Total
(N=)
Enrolled
Received at least one injection
Received all [x] injections and
attended [vist]
Completed [visit]
Withdrawn:
Lost to follow up
Adverse event
Death
Other
Source Data: Listing xx:
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10.2 PROTOCOL DEVIATIONS
Table V gives details of study protocol deviations.
Table V
Protocol deviations
Deviation
Entry criteria
Withdrawal criteria
Incorrect dosing regimen
Concomitant
treatment/medication
Other
Site:
Site:
0
0
0
0
0
0
0
0
0
0
Full details of the protocol deviations can be found in appendix 16.2.2
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11 RESULTS
11.1 DATA SETS ANALYSED
11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS
Table XX Demographics of the Study Patients
Group A
(N=)
Gender
Male
Female
Age (years)
n
Mean
Min
Max
Height (m)
n
Mean
Min
Max
Weight (kg)
n
Mean
Min
Max
BMI (kg/m2)
n
Mean
Min
Max
Group B
(N=)
See appendix XX for by-patient tabular listings of demographic details.
11.3 MEASUREMENTS OF TREATMENT COMPLIANCE
11.4 STUDY DURATION
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11.5 IMMUNOGENECITY RESULTS AND TABULATIONS OF PATIENT DATA
11.5.1
ANALYSIS OF IMMUNOGENECITY
11.5.2
STATISTICAL/ANALYTICAL ISSUES
11.5.2.1 HANDLING OF DROPOUTS OR MISSING DATA
How if any dropouts were handled- why they dropped out, how long they were in the
study for. Analysis of a pattern for patient drop out rates, determining factor, common
variant. Missing data, incomplete CRF’s, how this is handled, and why this took place.
11.5.3
TABULATION OF INDIVIDUAL RESPONSE DATA
11.5.4
VACCINE DOSE AND RELATIONSHIP TO RESPONSE
11.5.5
BY-PATIENT DISPLAYS
11.5.6
IMMUNOGENECITY CONCLUSIONS
12 SAFETY EVALUATION
12.1 EXTENT OF EXPOSURE
12.2 ADVERSE EVENTS (AE’s)
12.2.1
BRIEF SUMMARY OF ADVERSE EVENTS
12.2.2
TREATMENT EMERGENT ADVERSE EVENTS
12.2.3
TREATMENT RELATED ADVERSE EVENTS
12.2.4
IMMUNISATION TOLERANCE
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12.3
SERIOUS ADVERSE EVENTS AND OTHER SIGNIFICANT ADVERSE
EVENTS
12.4
DEATHS
12.5
CLINICAL LABORATORY EVALUATION
12.5.1
EVALUATION OF EACH LABORATORY PARAMETER
12.6
VITAL SIGNS, PHYSICAL FINDINGS AND OTHER OBSERVATIONS
RELATED TO SAFETY
12.7
CONCOMITTANT MEDICATION USE
12.8
SAFETY CONCLUSIONS
13
DISCUSSION AND OVERALL CONCLUSIONS
14 TABLES, FIGURES AND GRAPHS
15 REFERENCES
16 APPENDICES
16.1
STUDY INFORMATION
16.1.1
Protocol and Protocol Amendments
16.1.2
Case Report Form
16.1.3
Ethics Committees and Subject Information
16.1.4
Regulatory Approval
16.1.5
Investigators and Study Personnel
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16.1.6
Sponsor and Investigator Signatures
16.1.7
Randomisation Code
16.1.8
Study Drugs
16.1.9
Audit Certificate
16.1.10
Statistical Analysis Plan
16.1.11
Laboratory quality assurance
16.1.12
Publications based on the study
16.1.13
Publications referenced in the report
16.2
PATIENT DATA LISTINGS
16.3
CASE REPORT FORMS
16.3.1
CRFs for deaths, other serious adverse events and withdrawals for AE
16.3.2
Other CRFs submitted
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