This presentation will give you insight of the Guidelines for preparation of Clinical Document such as Protocol, Investigator Brochure and Case Report Form. This will help you to learn deeply about the Clinical documentation.

1. Dr. Rajendra Gode Institute of Pharmacy,
University - Mardi Road, Amravati - 444602
Guided by
Prof. Pranali Chandurkar
Assistant Professor
M. Pharm (Pharmacology)
Clinical Research and Pharmacovigilance
(MPL 204T)
“ Guidelines to the preparation of documents: Preparation
of Protocol, Investigator Brochure and Case Report Form ”
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Presented by
Miss. Shraddha Raut
M. Pharm (Ist year)

2.  Contents :
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Guidelines to the preparation of documents
1) Preparation of Protocol
Definition
Aims
Benefits
Components
2) Investigator Brochure
3) Case Report Forms
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Clinical Trials
The International Conference of Harmonization
defines a clinical trial as, “Any investigation in human
subjects intended to discover or verify the clinical,
pharmacological or other pharmacodynamic effects of an
investigational product, or to identify any ADR to an
investigational drugs, or to study ADME of drug with the
objective of ascertaining the safety and efficacy”.
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 Introduction
• Documents : All records in any form that describe the methods to conduct the
trial, result and factors affecting the trial is known as document and process is
called as documentation.
• The Essential Documents for Clinical Trial are as follows:
1) Clinical Study Protocol
2) Investigator’s Brochure
3) Case Report Form
4) Informed Consent Form
5) Clinical Study Report
Guidelines to the Preparation of Document
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Preparation of Protocol
Protocol : It is a document that describes the objectives, design,
methodology and an organization of trial.
Aims :
1) To clarify the importance of research
2) To collect existing knowledge by Literature Survey
3) To formulate hypothesis and objectives
4) To suggest methodology to achieve objectives
5) To discuss requirements for achieving objectives
 Introduction
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Conti….
Approval of Protocol
• Protocol must be submitted to the IRB for approval before it is implemented.
• If there is any amendment, same should be put up before the IRB before starting
the research.
Benefits :
1) Allows the researcher to plan and review the project’s steps
2) Serves as a guide throughout the research
3) Can identify time and budget estimates
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 Components
Title of study and General Information
Administrative details
Project summary
Introduction (Background)
Study objectives
Methodology
Data Management and Analysis Plan
Project management (Timeline)
Strengths and Limitations
Ethical Considerations
Budget Summary
References
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Conti….
• Title should be accurate, short and concise.
• Keep the title within 12-15 words.
• Protocol - title, identifying number and date.
• Name and address of the sponsor and monitor.
• Name and address of the person authorized to sign the protocol and the protocol
amendments for the sponsor.
• Name, address and telephone number of medical expert for the trial.
• Name and address of the investigator who is responsible for conducting the trial,
and the address and telephone number of the trial site.
1) Title of Study and General Information
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Conti….
• Name, address, and telephone number of the qualified physician who is
responsible for all trial-site related medical decisions.
• Name and address of the clinical laboratory and other medical or institutions
involved in the trial.
2) Administrative details
• Contents page list of relevant sections and sub-sections with corresponding page
number.
• Signature page is signed by senior members of research team and dated to
confirm that the version concerned has been approved by them.
• Contact details for the research team members listing postal, e-mail addresses
and telephone numbers.
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Conti….
3) Project Summary
• It should be concise
• It should sum up all the essentials of protocol
4) Background Introduction
• Name and description of the investigational product.
• A summary of findings from nonclinical studies that potentially have clinical
significance and from clinical trials that are relevant to the trial.
• Summary of the potential risks and benefits, if any, to human subjects.
• Description of and justification for the route of administration, dosage regimen
and treatment period.
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Conti….
5) Study Objectives
• A statement that the trial will be conducted in compliance with the protocol and
the applicable regulatory requirements.
• 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.
• It should be restricted to the intention of project.
• The objectives should be SMART (Specific, Measurable, Achievable, Relevant
and Time based)
• It must include Primary and Secondary objective and also Hypothesis.
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Conti….
6) Methodology
• It should be describe in detail Where, Who and How the research will be conducted.
• It is an important part of protocol which assures that the hypothesis will be confirmed
and rejected.
• It must include : a) Study design
b) Study population
c) Informed Consent Form process
d) Treatment of the subject
e) Data Collection method
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Conti….
a) Study design
• There are various methods like cross-sectional, case-control, cohort study, etc.
• Proper explanation should be given as to why a particular design was chosen.
• Include the information that is needed to answer the research question.
• Include the study design e.g. single, double-blind, observational, experimental, etc.
• A schematic diagram of the study design would be helpful.
• Include the amount of dosage, dosing regimen of the drug, packaging and labelling
of the experimental drug.
• Identify possible benefits of the study.
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Diag. Study Design
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b) Study population
• Proper definition of eligibility, inclusion, exclusion and
discontinuation criteria of study subject should be stated.
• Include enrolment of person to ensure that the benefits of the
research study are distributed in an equitable manner.
Conti….
c) Informed Consent Form Process
• Provide information about regulatory requirements of the consent
form and which languages will be used.
• Include a copy of the proposed informed consent along with
protocol.
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d) Treatment of the subject
• List all the treatments to be administered including product’s name, dose, route of
administration and the treatment period for subjects.
• Include all medication permitted before and during the clinical trial.
• Include the procedures for monitoring subject compliance.
Conti….
e) Data Collection method
• Description of instruments, tools used for data collection as well as methods used to test
validity and reliability of instrument should be provided.
• Data collection tools are – Retrospective data (medical records)
Questionnaires
Interviews
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• It should be written following statistical advice from a statistician.
• The analysis plan and which statistical tests will be used to check the significance to the
research question/hypothesis with appropriate references should be described.
• Name of statistical analysis that will be performed to assess the outcome should be listed.
• If computer programs are to be applied, it is important to mention the software used and
its version.
Conti….
7) Data Analysis
8) Project Management
• Proper work plan to accomplish each step of study should be defined.
• Personnel involved in study/data collection should be properly trained.
• A short paragraph stating when you plan to start and complete the study.
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9) Strength and Limitations
Conti….
• It is important to mention the strengths or limitations of the study.
i.e., what study can achieve or cannot achieve is important, so as to prevent wasteful
distribution of resources.
10) Ethical consideration
• Study should not start until approval from IRB is received.
• The following points should be explained:
1) The benefits and risks for the subjects involved.
2) Information should be provided on free informed consent of the participants.
3) Information must be kept confidential.
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Investigator’s Brochure
The Investigator's Brochure (IB) is a compilation of the clinical and nonclinical
data on the investigational product that are relevant to the study of the product in human
subjects.
• Purpose :
1) To provide information to the Investigators and others involved in the trial
2) To provide insight to support the clinical management of the study subjects
during the course of the clinical trial.
3) It enables a clinician or potential investigator to understand it and make his/her own
unbiased risk- benefit assessment of the proposed trial.
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Conti….
A complete Investigator Brochure should include the following :
• Title Page
A. Sponsor name
B. The identity of each investigational product (i.e., research number, chemical or approved
generic name and trade name)
C. The Release Date.
• Confidentiality Statement
A statement which reminds Investigators and other recipients to treat the Investigator’s
Brochure as a confidential document and an important resource for the Investigators team and
the Institutional Review Boards (IRBs) and Independent Ethics Committee (IEC).
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 Contents of IB :
Table of Contents
Summary
Introduction
Description of IP
Non-clinical studies
Effect on Human
Summary of Data and Guidance for the Investigator
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1) Table of Contents
Conti….
2) Summary
• Not exceeding 2 pages.
• Highlighting the significant physical, chemical, pharmaceutical, pharmacological,
toxicological, pharmacokinetic, metabolic and clinical information available of IP.
3) Introduction
• It includes chemical name, active ingredients, pharmacological class, therapeutic/
diagnostic indication.
• General approach to be followed in evaluating the IP.
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4) Description of IP
Conti….
5) Non-clinical Studies
• Physical, Chemical and pharmaceutical properties of I.P.
• For safety measures, a description of the formulations to be used including excipients
should be provided and justified.
• Storage and handling of I.P.
• Any structural similarity with the other known compound given.
• The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic and
investigational product metabolism studies should be provided in summary form.
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The information provided may include:
• Species tested
• Number of sex in each group
• Unit dose, e.g., milligram/kilogram (mg/kg)
• Dose interval
• Route of administration
• Duration of dosing
Conti….
5.1 Non clinical pharmacology:
• A summary of the pharmacological aspects of the investigational product studied in
animals should be included.
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Conti….
5.2 Pharmacokinetics and Product Metabolism in Animals:
• A summary of the pharmacokinetics (ADME) and biological transformation of the
investigational product in all species studied should be given.
5.3 Toxicology
A summary of the toxicological effects found in relevant studies conducted in different
animal species.
• Single dose
• Repeated dose
• Carcinogenicity
• Special studies (irritancy, sensitisation)
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Conti….
• Reproductive toxicity
• Genotoxicity (mutagenicity)
• A thorough discussion of the known effects of the investigational product in humans
should be provided, including information on pharmacokinetics, metabolism,
Pharmacodynamics, dose response, safety, efficacy, and other pharmacological
activities.
(a) Pharmacokinetics and Product Metabolism
(b) Safety and Efficacy
6) Effects in Human
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Conti….
7) Summary of Data and Guidance for Investigator
• This section should contain nonclinical and clinical data of IP.
• IB - provide the investigator a clear understanding of
1) The possible risks
2) Adverse reactions
3) Observations & precautions needed for the clinical trial.
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Case Report Form (CRF)
Definition:
• The CRF is the tool that is used to collect pre-defined data from subject in a clinical
trials.
• The ICH guidelines for Good Clinical Practice define the CRF as: A printed or
electronic document designed to record all of the required information to be reported to
the sponsor on each trial subject.
Type of CRFs:
• There are two types of CRFs:
1) Paper CRF
2) Electronic CRF
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1) Study title and number
2) Trial site and Investigator’s name
3) Study subject and ID
4) Information of the Informed Consent
5) Demographic data and Medical history
6) Detailed description of dosage regimens of investigational drug
7) Concomitant treatment
8) Adverse events
9) Conclusion on subject’s health
10) Investigator’s signature and date
 Contents of CRF :
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 CRF Development Process :
• CRF should be designed during protocol development or after protocol
finalization.
• The CRF development process is discussed using a four stage model:
1. Predevelopment
2. Content Designing
3. Style Design
4. Review
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 References
1) Al-JunDi, A., & SAkkA, S. (2016). Protocol writing in clinical research. Journal of clinical and
diagnostic research: JCDR, 10(11), ZE10.
2) https://drive.google.com/uc?id=1cgHuttkz0Uh2_E9irAyKYnxKQlWzZg4o&export=download
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Any question