Contents Guidelines for Preparation of Documentation Clinical Study Reports Clinical Trial Monitoring Safety Monitoring in clinical trials Introduction Proper documentation is critical to the success of a clinical study. Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations. Investigator’s Brochure (IB) List of Abbreviations Contents & Summary Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product. Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results. The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.

1. Seminar on-
Guidelines for Preparation of Documents, Clinical Study Report Clinical
Trial Monitoring Safety Monitoring in Clinical Trial
Guided by:
Dr. (Mrs) Nirzarini N. Shah
Associate professor
(M. Pharm, Ph. D)
Head of Department of Pharmacology
Presented By:
Presented by:
Dinesh M. Gangoda
M. Pharm (sem-II)
Enrollmentno:212010825004
Enrollment no:
212010825004
Subject: Clinical Research and Pharmacovigilance
A.R. College of Pharmacy and G.H. Patel Institute of Pharmacy
(Affiliated with Gujarat Technological University Ahemdabad)
Vallabh Vidya Nagar Anand-388120

2. 2
CONTENTS
• Guidelines for Preparation of Documentation
• Clinical Study Reports
• Clinical Trial Monitoring
• Safety Monitoring in clinical trials
• References

3. 1.1 Introduction
 Proper documentation is critical to
the success of a clinical study.
 Every aspect of the study must be
documented in order to obtain
useful data and demonstrate
compliance with Good Clinical
Practice (GCP) guidelines and with
all applicable regulations.
3
Guidelines for Preparation of Documentation

4. 1.2 Documentation Requirements in GCP and Federal Regulations
• GCP guidelines list the essential documents (ICH GCP E6 Section 8) that,
at a minimum, must be maintained for every clinical study.
• These documents are to be maintained by the site and the sponsor, and are
classified according to the stage of a study at which they are normally
created.
• These documents may be maintained in multiple locations, depending on
whether they are stored with regulatory files or as participant documents.
• The sponsor and the investigator/institution should maintain a record of
the location(s) of their respective essential documents, including source
documents.
4

5.  1.3 Examples of Other Sponsor-Required Documents
 In addition to the essential documents included in the GCP guideline, the
sponsor may require other documentation. The following lists examples of
other documentation that may apply to clinical trials.
 1.4 Certificate of Confidentiality
 A Certificate of Confidentiality provides an additional level of protection
for the privacy of participants in alcohol and drug abuse research studies.
5

6. 1.5 Quality Assurance Documents
Quality assurance documents may
include the following:
Research site Initiation Activation
Form, which indicates that a site is
ready to start study enrollment.
Site visit logs, to record visits to the
research site by quality assurance
monitors and other personnel.
6

7. 1.6 Training Documents
 A training plan and verification of compliance with the training plan, including:
 All training documentation form for each staff.
 Documentation of required assessments training per the study training plan.
 Documentation of study–specific training.
 Pertinent certifications for clinical staff implementing a study intervention.
7

8. 1.7 Behavioral Therapy Documents
Many CTN studies involve behavioral interventions. Behavioral studies
may require essential documents different from, or in addition to, those
required by GCP guidelines.
These documents may include therapy manuals and materials, audio and
videotapes of treatment sessions, and other documents specific to the
behavioral intervention that is being studied.
8

9. 1.8 Source Documents
 Source documents are original
documents, data, and records
e.g., hospital records, clinical
and office charts, laboratory
notes, subjects’ diaries or
evaluation checklists,
pharmacy dispensing records,
and records kept at the
pharmacy, at the laboratories
and technical departments
involved in the clinical trial.[1] 9
Source
documents
Hospital
records
Pharmacy
dispensing
records
Evaluation
checklists,
X-rays,
Subject file
Automated
instruments

10. 1.9 Trial Master File (TMF)
Guideline E6 states that trail master file should be
established at the beginning of the trial, both at the
investigator/institution site and at the sponsors office.
A final close-out of a trail only be done when the
monitor has reviewed both the investigator/institution
and sponsor files and confirm that all necessary
documents are in the appropriate files.
The file maintained at the site is often called, The Site
Master File . The file is generally the responsibility of
a designated member of the investigating team at the
site of the monitor at the sponsors office.
10

11. 1.10 Essential Documents
Essential Documents are those documents which individually and
collectively permit evaluation of the conduct of a trial and the quality of
the data produced.
These documents serve to demonstrate the compliance of the investigator,
sponsor and monitor with the standards of Good Clinical Practice and
with all applicable regulatory requirements.
These documents are also the ones which are usually audited by the
sponsor's independent audit function and inspected by the regulatory
authority as part of the process to confirm the validity of the trial conduct
and the integrity of data collected.
11

12. 1.10.1 Essential Documents For Clinical Trials
The Essential Documents For Clinical Trials are as Follow:
12
1. Investigator's Brochure
2. Clinical Study Protocol
3. Case Report Form (CRF)
4. Informed Consent Form
5. Clinical Study Reports

13. 1.10.2 Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
 Introduction provides the chemical name (and generic and trade names,
if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the
medicinal product. Non-clinical studies & Clinical Studies and their
results.
The Investigator's Brochure should be reviewed at least annually and
revised as necessary in compliance with a standard procedures
established by drug development company. 13

14. 1.10.3 Clinical Study Protocols
• The Guideline ICH E6 defines the protocol as, A document that describes the
objective(s), design, methodology, statistical considerations, and organization
of a trial.
• The protocol usually also gives the background and rationale for the trial but
these could be provided in other protocol referenced documents also.
14

15. 1.10.2.1 Parts of Protocol
Introduction/Abstract
 Objectives
Background/Rationale
Eligibility criteria
 Study design/methods (including drug/device info)
Safety/adverse events
Regulatory guidance
Statistical section (including analysis & monitoring)
Human subjects protection/informed consent
15

16. 1.10.3 Case Records/Report Form (CRF)
CRF is a paper or electronic document designed to record all the information
for an individual study subject required by the Study protocol.
All CRF's should include the following data:
oStudy title and number
oInvestigator's name
oStudy subject/patient ID (number and initials)
oDetailed description of dosage regimens of investigational drug
oAdverse events (side effects and intercurrent diseases)
oConclusion on subject's health
oInvestigator's signature and date.
16

17. 1.10.5 Informed Consent
Informed consent is a process by which a subject voluntary confirms
his/her willingness to participate in one or another clinical trial, after
having been informed of all aspects of the study.
Informed consent should be documented by means of a written, signed
and dated Informed Consent Form (ICF).
17

18. 2.1 Introduction
Report: It is a document that
summarizes all the incidences and
facts that occurred at a given point of
time, places or situation.
Clinical Trial: A research activity that
involves administration of a test
treatment to some experimental unit in
order to evaluate the treatment. (1) 18
Clinical Study Reports

19. CONT...
CSR A Clinical Study Report (CSR) is one of many types of regulatory
documents that comprise a marketing application for a drug, biologic, or
device. A CSR is a descriptive account of a single clinical trial accompanied
by tables, listings, and figures displaying all study data and results.
CSR is an extensive and complete document which has to be submitted for
obtaining a marketing authorization of IMP to the European Union or the US.
19

20. 2.2 ICH E3 Guidelines for Clinical Study Reports
Structure of a full Clinical Study Report according to the International
Conference on Harmonization of Technical Requirements for registration
of pharmaceuticals for Human Use (ICH E3) guideline.
1. Title Page
2. Synopsis
3. Table of Contents
4. List of Abbreviations and Definitions of Terms
5. Ethics
6. Investigators and Study Administrative Structure
20

21. CONT..
7. Introduction
8. Study Objectives
9. Investigational Plan
10. Study Patients
11. Efficacy Evaluation
12. Safety Evaluation
13. Discussion and Overall Conclusions
14. Tables, Figure and Graphs Referred to But Not Included in the Text
15. Reference List
16. Appendices 21

22. Section 1. Title Page
Study Title
Name of test drug/investigational product
Studied indication, study design
Sponsor name and address
Protocol identifier
Dates of initiation, early termination, termination, completion of the study
Completion name and address of Principal Investigator
22

23. Section 2. Synopsis:
Synopsis summarizes the study in brief.
Section 3. Table of contents for the individual clinical study report.
This section contains the table include summary tables, figures and
graphs.
Section 4. List of Abbreviations: This section in a list of abbreviations
Section 5. Ethics:
Independent Ethics Committee
Patient information and consent
23

24. Section 6.0. Investigator and administrative structure contain
The administrative structure of the study,
Principal investigator,
Coordinating investigator,
Administration,
 Monitoring and evaluation committees,
Statistician,
 Central laboratory facilities,
Contract research organization (C.R.O.)
24

25. Section 7.0. Introduction contains
Context of the development of the test drug/investigational product.
Relating the critical features of the study to that development.
Section 8.0-Study Objectives
A statement describing the overall purposes of the study should be
provided.
Section 9.0-Investigational plan
oSection 9.1-Overall study design and plan – Description
Treatments studied (specific drugs, doses and procedures)
Patient population studied and the number of patients to be included
25

26. oSection 9.2 –Discussion on study design and choice of control groups.
The specific control chosen and the study design used.
oSection 9.3 – Selection of Study Population
9.3.1 Inclusion Criteria
9.3.2 Exclusion Criteria
9.3.3 Removal of patients from therapy or assessment Section
26

27. oSection 9.4- Treatments
9.4.1 Treatment administered
The precise treatments or diagnostic agents to be administered in each
arm of the study, for each period of the study, route and mode of
administration, dose and dosage schedule.
9.4.2 Identity of Investigational Product
A brief description of the test drug(s) /investigational product(s)
(formulation, strength, batch number(s)
27

28. Section 10.0 – Study Patients
oSection 10.1 – Disposition of Patients
Clear accounting of all patients who entered the study.
The numbers of patients who were randomized, who entered and
completed each phase of the study, (or each week/month of the study)
. Reasons for all post-randomization discontinuations, grouped by
treatment and by major reason (lost to follow-up, adverse event, poor
compliance etc.).
oSection 10.2 – Protocol Deviations
All important deviations related to study inclusion or exclusion
criteria, conduct of the trial, patient management or patient
assessment and their impact on analysis. 28

29. Section 11.0 – Efficacy Evaluation
o11.1 Data Sets Analyzed
o11.2 Demographic and other baseline characteristics
o11.3 Measurements of treatment compliance
o11.4 Efficacy results and tabulations of individual patient data
Section 12. Safety Evaluation
Extent of exposure (dose, duration, number of patients)
Most common adverse events, laboratory test changes etc.
Serious adverse events and other significant adverse events 29

30. Section 13. Discussion And Overall Conclusions
The efficacy and safety results of the study and the relationship of risks
and benefit.
Section 14. Tables, figures and graphs referred to but not included in the text
o14.1 Demographic Data :Summary figures and tables
o14.2 Efficacy Data :Summary figures and tables.
o14.3 Safety Data :Summary figures and tables
Section 15. Reference List
A list of articles from the literature pertinent to the evaluation of the study
Copies of important publications should be attached in an appendix.
30

31. Section 16. Appendices
This section should be prefaced by a full list
of all appendices available for the study
report.
31

32. 3.1 Introduction
Monitoring
The act of overseeing the progress of a clinical trial, and of ensuring that it is
conducted, recorded and reported in accordance with the protocol, SOPs, GCP,
and any regulatory requirements”. [1]
Monitoring Reports
A written report form the monitor to the sponsor after each site visit and other
trial related communication according to the sponser SOPs.
32
Clinical Trial Monitoring

33. 3.2 Purpose of Monitoring
1. Protection of rights and wellbeing of human participants.
2. Ensure consent in place for record access.
3. Trial data are accurate, complete and verifiable from source documents.
3.3 Qualities of a good Monitor
Appropriately trained, Adequate scientific and/or clinical knowledge. -
Documented with training logs and CVs.
Thoroughly familiar with: - IMP - Protocol - Consent form - Sponsor & trial
SOPs - GCP Knowledge of local laws, regulations, customs & local
language.
33

34. 3.4 Types of Monitoring in Clinical Trials
 Trial Management Group- TMG; This should include individuals
responsible for day- to day management of the trial such as principal
investigator, statistician, trial coordinator, research nurse, data
management personnel etc.
Trial Steering Committee- TSC; Which provides overall supervision of
the trial and ensures it is being conducted as per regulatory requirements
and GCP Good Clinical Practice. The committee monitors the progress of
a trial including data completeness and ensures there are no major
deviations.
34

35. 3.4 Participant in Monitoring of Clinical Trial
Participant in monitoring of clinical trial is the CRA Clinical Research
Associate and other members including the project manager, medical
monitor, data manager and statistician.
Sponsor’s Monitor or Clinical Research Associate CRA
Interface with investigative site on behalf of or CRO. May be involved in
any or all of the following;
Site evaluation and initiation
35

36. • Project Manager- responsible for overall implementation of trial; oversee
progress of trial; global trial communications; reporting to regulators, budget
and cost control.
• Medical Monitor- individual with expertise in trial related therapeutic area;
involved in protocol devlopments, safety reporting, interpretation of data and
clinical findings.
• Data Manager- generate data queries to ensure quality of data; maintain
ongoing data entry; monitor data analysis and provide reports.
• Statistician- analysis of data – provide reports for data safety monitoring
board DSMB
36

37. 37
3.5.1 Before Monitoring visit
• Review the status of data entry
• Review action item from last visit
• Review regulatory binder.
3.5.2 During Monitoring visit
• Site, Staffing, research labs or other facilities.
• Regulatory files and study records
• Any problems and issues
3.5 Monitoring Process

38. 38
3.5.3 After Monitoring visit
• Complete site visit report
• Submit the report to the
sponsor

39. 4.1 Introduction
Monitoring patient safety during clinical trials is a critical component
throughout the drug development life cycle. Pharmaceutical sponsers must
work proactively and collaboratively with all stakeholders to ensure a systemic
approach to the safety Monitoring.
39
Safety Monitoring in clinical trials

40. 40
1. Sponsor
2. Subjects
3. Investigators
4.2 Stakeholders in Safety Monitoring

41. Sponsors
Clinical trials sponsor, usually pharmaceutical companies, are responsible for
developing the clinical trial protocol describes every aspect of the research,
including the rationale for the experiment, objectives, trial populations with
detailed inclusion and administration of the investigational therapies, trial
procedures, data collection standard, endpoint and sample size.
41

42. Subjects
• Subject are patients or healthy volunteers who
agree to participate in a Clinical trial and have
signed. Other information provides important
safety information so the subjects can make an
informed decision on whether to participate in
a trial.
42

43. Investigators
• Investigators are qualified individuals who are trained
and experienced to provide medical care to subjects
enrolled in the clinical trials. Investigators identify
potential subjects and educate them about the trial
participation to ensure that can make an informed
decision.
• They are responsible for notifying their institutional
review boards and the sponsor of any issues during that
Safety and subjects.
43

44. Institutional review board/ Ethics Committee
• The institutional review board (IRB), also known as the ethics committee, is
changed with protecting the rights and welfare of human subjects recruited to
participate in research protocols.
• The IRB review all clinical trial protocols involving human subjects that the
particular institution is involved with and has the authority to approve,
disapprove or require modifications to the protocols.
44

45. Data& Safety Monitoring Board
• The data and safety Monitoring Board(DSMB) also called data monitoring
committee (DMC).
• The DSMB may review efficacy data at pre- defined in term oints to and
evidence of efficacy.
• Not all clinical trials require a formal DSMB. DSMB are most common in
double blind randomized phase-3 trials, members of DSMB typically
including clinical trial Physians with the biostatician and possibly persons.
45

46. Regulatory Authorities
• In the US, prior to initiation of a first in human clinical trial, pharmaceutical
sponsers must submit an Investigational New Drug (IND) application to the
FDA as required by law.
• The FDA review the IND (typically within 30 days) for safety to ensure that
research subjects will not be subjected to unreasonable risk.
• The European Medicines Agency (EMA) is European union’s FDA
equivalent. The agency has several scientific committee that carry out
pharmaceutical companies.
46

47. Medical community and patients
• Clinical trials generate data that contribute to the body of the knowledge
about the treatment and the disease that benefit the border medical
community and ultimately the patients.
• Communicating Sefety Information among Stakeholders
• Timely communication among the various stakeholders is critical to ensure
subject Sefety in clinical trials, sponsors of clinical trials are accountable for
monitoring the subjects.
47

48. CONT…
• However, Sefety Information may come from sources outside the immediate
clinical trial. The sponsor is required to promptly review all information
relevant to the safety of the drug and to update subjects, investigators, IRBs
and regulatory authorities of any new risks associated with the use of the
investigational drug from Clinical trial or other sources.
• The goal of safety Monitoring in clinical trials is to identify evaluate,
minimize and appropriately manage risks.
48

49. REFERENCES
1. M’U.R. Naidu, P.Usha Rani. ‘‘A practical Guide to human Research and
Clinical Trials.’’ PharmaMed press, sultan Bazar, Hedrabad; (2011): pp no-
203to 214.
2. Dr. Ravindra B. Ghooi, Sachin C. Itkar. ‘‘Essential of clinical Research’’.
Nirali Prakashan, Sivaji Nagar, Pune. 5th edition April (2019), PP- 1.5 to
1.14.
3. Images- From Google website
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