At the end of a clinical trial it is important to analyse data in detail and present it well. Writing a report is a regulatory requirement and only on submitting the report complete with proceedings of the trials and results on analysis of data gathered during the trial will the next step in the development plan of a drug be granted.
Steps to writing a good Clinical Study Report include a good knowledge of widely accepted contents of the report. ICH has a whole guidance devoted to writing a clinical study report (E3). It is a detailed document on contents of the report.
Each section will be discussed below:
Definition of a Clinical Study Report (CSR) : CSR is a-
1. Integrated full report of an individual study I.e., where in clinical and statistical descriptions, presentations and analyses are integrated into a single report.
2.Report of any drug which can be for therapeutic, diagnostic or prophylactic use
3 . Report of a study conducted in patients
4. Report in which Tables and figures are incorporated in the main text of the report or at end of text while the appendices of the report contain protocol, sample CRF, investigator related information, information related to test drug/investigational product, technical statistical document, related publication, patient data listings, technical statistical details such as derivations , computations, analyses and computer output.
The report should provide a clear explanation of how the critical design features of the study were chosen and enough information on plan, method and conduct of the study so that there is no ambiguity on how the study was carried out.
The report and its appendices should provide enough individual patient data,including demographic data, baseline data and details of analytical methods used so as to enable replication of result if authorities wish to do so.
Structure and Content of the report:
As per ICH format, there are 16 sections in total of the study report. The 16 sections are mentioned below in the order described in the guidance.
1. TITLE PAGE
2. SYNOPSIS
3. TABLE OF CONTENTS
4. LIST OF ABBREVIATIONS
5. ETHICS
6. INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
7. INTRODUCTION
8. STUDY OBJECTIVES
9. INVESTIGATIONAL PLAN
10. STUDY PATIENTS
11. EFFICACY EVALUATIONS
12. SAFETY EVALUATIONS
13. DISCUSSION AND OVERALL CONCLUSION
14. TABLE, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN TEXT
15. REFERENCE LIST
16. APPENDICES
The details of each section is presented below:
1. TITLE PAGE:
The title page should contain
I. Study title
II. Name of the test drug/investigational product
III. Indication studied
IV. If not apparent from the title then a brief description of the study design
V. Name of the sponsor
VI. Protocol identification ( code or number)
VII. Study initiation date(first patient enrolled), date of early study termination, study completion date(last patient completed)
VIII. Name and affiliation of principal or coordinating investigator or sponsors responsible medical officer
IX. Name of sponsors signatory
X. Statement indicating that the study was performed in compliance with Good Clinical Practice, including archiving of essential documents.
XI. Date of report.
2. SYNOPSIS
The synopsis should summarise the study and should generally
Be limited to 3 pages. The synopsis should include numerical data to represent results and not just text and p values. Basically a clear understanding of the CSR should be possible from the synopsis.
3 . TABLE OF CONTENTS
It should have details of each section and the page numbers at which these sections are located
4. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
A list of abbreviations and unusual terms should be provided in this section . Abbreviated terms should be spelled out and the abbreviations indicated I the parenthesis in the first appearence in the text.
5. ETHICS
Ethical conduct of a trial is an important aspect of GCP and this section is devoted to giving evidence on the same. Under this section details of ethics committee involved in the trial, ethical principals followed during the trial and freely given informed
consent are mentioned.
6. INVESTIGATOR AND STUDY ADMINISTRATIVE STRUCTURE
Details of the team at site I.e., the principal Investigator,
coordinating investigator; details of steering committee , CRO's, statistician, monitoring, central laboratory , author of the report should be mentioned.
7. INTRODUCTION
The introduction should contain a brief statement generally of one page which should clearly mention the place the study in the Context of the development programme. It should mention the rationale, aims, target population, treatment, duration, primary endpoints of the trial. Any guidance referred to during predation of the protocol or any meetings / discussion with the regulatory authority with respect to protocol development can be mentioned here.
8. STUDY OBJECTIVES
The overall purpose of the study should be mentioned here.
9. INVESTIGATIONAL PLAN
9.1 Overall study design and plan should be described briefly and clearly by using charts or diagrams.
The information to be provided is:
- Treatment studied
- Population and number of patients studied
- level and method of blinding and masking
- kind of control used
- method of assignment to treatment
-sequence and duration of all study periods
- preferably display of the design graphically with a flow chart
9.2. Discussion of study design, including choice of control groups
Blinding, randomization and choice of control should be discussed. Merits and demerits to be mentioned
9.3. Selection of Study Population
Inclusion, exclusion and withdrawal criteria should be mentioned
9.4 Treatments
Treatments administered (dose, route, method of administration), identity of the investigation product (batch number, formulation, strength) , if more than one batch is used then the patients receiving each batch should be identified , source of investigational product and comparator should be provided, method of resupply in case of limited shelf lives,method of assigning to different treatment groups, selection of doses in the study, selection and timings of dose for each patient, blinding, prior and concomitant medication, treatment compliance.
9.5 Efficacy and Safety variables
9.6 Data quality assurance
9.7 statistical methods used in the protocol and determination of sample size.
9.8 changes in conduct of the study or planned analysis.
10. STUDY PATIENTS
Disposition of patients, protocol deviations
11. EFFICACY EVALUATIONS
Data sets analysed, demographic and other baseline characteristics, measurement of treatment compliance, efficacy results and tabulations of individual patient data.
12. SAFETY EVALUATIONS
Safety related data to be analysed at 3 levels. First , the extent of exposure; second, more common adverse events; third serious adverse events and other significant adverse events should be identified.
13. DISCUSSION AND OVERALL CONCLUSION
The efficacy and safety results and the relationship of risks and benefits should be briefly summarised and discussed.
14. TABLES FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN TEXT - self explanatory
15. REFERENCE LIST
A list of articles referred to in the text should be provided.
16. APPENDICES
16.1
I. Protocol and protocol amendments
II. Sample CRF
III. List of IRBs/IECs
IV. List of investigators including CVs
V. Signature of investigators or sponsors responsible medical expert
VI. Listing of patient receiving test drug/ investigational products
VII. Randomization schemes and codes
VIII. Audit Certificates
IX. Documentation of statistical methods
X. Documentation of inter laboratory standardisation methods and quality assurance
XI. Publications based on the study
XII. Important publications referenced in the report
16.2
PATIENT DATA LIST ING
16.3
CRF
16.4
Individual patient data listings
Steps to writing a good Clinical Study Report include a good knowledge of widely accepted contents of the report. ICH has a whole guidance devoted to writing a clinical study report (E3). It is a detailed document on contents of the report.
Each section will be discussed below:
Definition of a Clinical Study Report (CSR) : CSR is a-
1. Integrated full report of an individual study I.e., where in clinical and statistical descriptions, presentations and analyses are integrated into a single report.
2.Report of any drug which can be for therapeutic, diagnostic or prophylactic use
3 . Report of a study conducted in patients
4. Report in which Tables and figures are incorporated in the main text of the report or at end of text while the appendices of the report contain protocol, sample CRF, investigator related information, information related to test drug/investigational product, technical statistical document, related publication, patient data listings, technical statistical details such as derivations , computations, analyses and computer output.
The report should provide a clear explanation of how the critical design features of the study were chosen and enough information on plan, method and conduct of the study so that there is no ambiguity on how the study was carried out.
The report and its appendices should provide enough individual patient data,including demographic data, baseline data and details of analytical methods used so as to enable replication of result if authorities wish to do so.
Structure and Content of the report:
As per ICH format, there are 16 sections in total of the study report. The 16 sections are mentioned below in the order described in the guidance.
1. TITLE PAGE
2. SYNOPSIS
3. TABLE OF CONTENTS
4. LIST OF ABBREVIATIONS
5. ETHICS
6. INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
7. INTRODUCTION
8. STUDY OBJECTIVES
9. INVESTIGATIONAL PLAN
10. STUDY PATIENTS
11. EFFICACY EVALUATIONS
12. SAFETY EVALUATIONS
13. DISCUSSION AND OVERALL CONCLUSION
14. TABLE, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN TEXT
15. REFERENCE LIST
16. APPENDICES
The details of each section is presented below:
1. TITLE PAGE:
The title page should contain
I. Study title
II. Name of the test drug/investigational product
III. Indication studied
IV. If not apparent from the title then a brief description of the study design
V. Name of the sponsor
VI. Protocol identification ( code or number)
VII. Study initiation date(first patient enrolled), date of early study termination, study completion date(last patient completed)
VIII. Name and affiliation of principal or coordinating investigator or sponsors responsible medical officer
IX. Name of sponsors signatory
X. Statement indicating that the study was performed in compliance with Good Clinical Practice, including archiving of essential documents.
XI. Date of report.
2. SYNOPSIS
The synopsis should summarise the study and should generally
Be limited to 3 pages. The synopsis should include numerical data to represent results and not just text and p values. Basically a clear understanding of the CSR should be possible from the synopsis.
3 . TABLE OF CONTENTS
It should have details of each section and the page numbers at which these sections are located
4. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
A list of abbreviations and unusual terms should be provided in this section . Abbreviated terms should be spelled out and the abbreviations indicated I the parenthesis in the first appearence in the text.
5. ETHICS
Ethical conduct of a trial is an important aspect of GCP and this section is devoted to giving evidence on the same. Under this section details of ethics committee involved in the trial, ethical principals followed during the trial and freely given informed
consent are mentioned.
6. INVESTIGATOR AND STUDY ADMINISTRATIVE STRUCTURE
Details of the team at site I.e., the principal Investigator,
coordinating investigator; details of steering committee , CRO's, statistician, monitoring, central laboratory , author of the report should be mentioned.
7. INTRODUCTION
The introduction should contain a brief statement generally of one page which should clearly mention the place the study in the Context of the development programme. It should mention the rationale, aims, target population, treatment, duration, primary endpoints of the trial. Any guidance referred to during predation of the protocol or any meetings / discussion with the regulatory authority with respect to protocol development can be mentioned here.
8. STUDY OBJECTIVES
The overall purpose of the study should be mentioned here.
9. INVESTIGATIONAL PLAN
9.1 Overall study design and plan should be described briefly and clearly by using charts or diagrams.
The information to be provided is:
- Treatment studied
- Population and number of patients studied
- level and method of blinding and masking
- kind of control used
- method of assignment to treatment
-sequence and duration of all study periods
- preferably display of the design graphically with a flow chart
9.2. Discussion of study design, including choice of control groups
Blinding, randomization and choice of control should be discussed. Merits and demerits to be mentioned
9.3. Selection of Study Population
Inclusion, exclusion and withdrawal criteria should be mentioned
9.4 Treatments
Treatments administered (dose, route, method of administration), identity of the investigation product (batch number, formulation, strength) , if more than one batch is used then the patients receiving each batch should be identified , source of investigational product and comparator should be provided, method of resupply in case of limited shelf lives,method of assigning to different treatment groups, selection of doses in the study, selection and timings of dose for each patient, blinding, prior and concomitant medication, treatment compliance.
9.5 Efficacy and Safety variables
9.6 Data quality assurance
9.7 statistical methods used in the protocol and determination of sample size.
9.8 changes in conduct of the study or planned analysis.
10. STUDY PATIENTS
Disposition of patients, protocol deviations
11. EFFICACY EVALUATIONS
Data sets analysed, demographic and other baseline characteristics, measurement of treatment compliance, efficacy results and tabulations of individual patient data.
12. SAFETY EVALUATIONS
Safety related data to be analysed at 3 levels. First , the extent of exposure; second, more common adverse events; third serious adverse events and other significant adverse events should be identified.
13. DISCUSSION AND OVERALL CONCLUSION
The efficacy and safety results and the relationship of risks and benefits should be briefly summarised and discussed.
14. TABLES FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN TEXT - self explanatory
15. REFERENCE LIST
A list of articles referred to in the text should be provided.
16. APPENDICES
16.1
I. Protocol and protocol amendments
II. Sample CRF
III. List of IRBs/IECs
IV. List of investigators including CVs
V. Signature of investigators or sponsors responsible medical expert
VI. Listing of patient receiving test drug/ investigational products
VII. Randomization schemes and codes
VIII. Audit Certificates
IX. Documentation of statistical methods
X. Documentation of inter laboratory standardisation methods and quality assurance
XI. Publications based on the study
XII. Important publications referenced in the report
16.2
PATIENT DATA LIST ING
16.3
CRF
16.4
Individual patient data listings
No comments:
Post a Comment