Introduction to Clinical Protocol
Topics To be Covered
• What is Protocol
• Protocol Outline
• Protocol Design
• Study Procedure
• Informed Consent process
• Subject Confidentially
• Data Recording
• GCDMP
• Data Management Plan
• Data Capture
• Data Quality Assurance
• Data Validation
• Query Management Plan
• Best Practice for CRF
• Statistical Analysis
• Data Locking
• Appendices / Supplements
• Conclusion
 Protocol
• A protocol is a document that states the reasoning
behind and structure of a research project

• Protocol also defined as a document that describes the

background, rationale, objectives, design,
methodology, statistical consideration and
organization of trial

• The Study protocol can be viewed as a written

agreement between the investigator , the participants
and the scientific community
 Protocol Outline
A typical protocol has the following elements:

• Title Page
• Objectives
• Signature Page
• Study Design
• Background Information and scientific rationale
• Study Population
 Protocol Design

• Study Procedure
• Informed Consent process
• Statistical Considerations
• Literature References
• Subject Confidentiality
• Supplements / Appendices
 Title Page
1. Title pages introduce the document, their title,
precise number, sponsor and author to the reader
• Protocol title, protocol identifying number, and
date
• Any amendments should also bear the amendment
number and date
• The protocol number must clearly indicate the
version number, whether it is final or draft and date
of this version
Continue…Elements

Full title should include:

1. Summary study 5. Placebo

design 6. Indication
2. Medicinal products 7. Patient population
3. Nature of the 8. Setting (ex: in-
treatment patient, outpatient)
(ex: treatment, 9. Randomized
prophylaxis and 10. Double Blind
diagnosis) 11. Multiple Studies
4. Comparator
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2. Name and address of the sponsor and monitor. Sponsor names

and list of responsibilities with agreed allocations

3. Name and title of the person authorized to sign the protocol

and the protocol amendments for the sponsor. Generally,
Chief Investigator for multiple center trials or Principal
Investigator for single center trials

4. Name, title, address and telephone number of the sponsor

medical expert for the trial
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5. Name and title of the investigator who is responsible for
conducting the trial, and the address and telephone numbers of
the trial site

6. Name, title , address and telephone number of the qualified

physician who is responsible for all trial site related medical
decisions

7. Name and address of the clinical laboratory and other medical

and /or technical department and /or institution involved in the
trial
 Protocol Summary/Synopsis
• This summary should be only one to two pages long

• It should give the reader sufficient information to

understand the rationale for the trial, its objective
and the methods that will be used to achieve these
objectives
 Study Objective/Aims
• A clinical trial often has both primary and
secondary objective, and these should be identified
as such in the protocol

• Ideally, no more than 1 or 2 of each should be

included in a clinical trial
 Signature Page
• Signature page of the healthcare professional in the
trial including contact details of participating site,
sponsor and sponsor medical advisor if not already
given above.
 Content Page

• This helps navigating through the document by

large number of different people that will be
needed throughout the life of the trial
 Study Design
A description of the trial design should include:

1) A description of the design of trial to be conducted

ex: double blind, placebo controlled, parallel design

2) A description of the measure taken to minimize/

avoid bias
A) Randomization
B) Blinding
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3) A description of the trial treatment and the dosage

and dosage regimen of the IP. Also, include a
description of the dosage form, packaging and
labeling of the IP

4) The expected duration of subject participation , and

description of the sequence and duration of all trial
periods, including follow up any.

5) A description of “stopping rile” or “Discontinuation

Criteria”
 List of Abbreviation
• All abbreviations used should be listed and defined

• Accepted international medical abbreviations should

be used

• Project specific abbreviations should be

standardized with each project
 Compliance Statement

• The protocol should include a trial statement with

the protocol, GCP and the applicable regulatory
requirements
 Background Information
• Name and description of the investigational product

• A summary of finding from nonclinical studies that

potentially have clinical significance and form
clinical trials that are relevant to the trial

• Summary of the known and potential risks and

benefits, if any, to human subjects

• Description and justification for the route of

administration, dosage, dosage regimen and
treatment period
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• Description of the population to be studied

• In short, the data in this background information

should be able to justify the need for this study
 Selection and Withdrawal
of Subjects
1. Subject Inclusion Criteria

2. Subject Exclusion Criteria

3. Subject Withdrawal Criteria

 Treatment of Subjects
i) The treatment to be administered, including the
name of all the products, dose, the dosing schedule,
the route/mode of administration and the treatment
period

ii) Medication/ treatment permitted and not permitted

before and/ or during the trial.

iii) Procedure for monitoring subject compliance

 Assessment of Safety
i) Specification of safety parameters

ii) The methods and timing for assessing, recording,

and analyzing safety parameters

iii) Procedure for eliciting reports of and recording and

reporting adverse event and inter current illnesses
 Direct Access to Source Data
Document
• Sponsor ensures that it is specified in the protocol
or other written agreement that the investigator
will permit trial related monitoring, audits, IEC
review, and regulatory inspection by providing
direct access to source data/documents
 Informed Consent
• Defined as: a patient is being given adequate
information about a clinical trial;
understanding and voluntarily accepting the
terms of a clinical trials and agreeing to
cooperate in its conduct
• The following slides are the key concepts to be
considered while designing the protocol, which
impact the Clinical Data Management

1. Data Recording
2. Data Quality Assurance
3. Statistical Analysis Plan
 Data Handling and Record
Keeping
• Indicate how data will be collected. If detailed instructions
have been prepared, specify their location (study manual,
appendix)
• Discuss the use and management of source documents
• Discuss the procedure for correcting errors

1. GCDMP
2. Data Management Plan
3. Data Capture
4. CRF
 Data Handling and Record Keeping

1. Good Clinical Data Management Practices

• Provides assistance to clinical data managers in their
implementation of high quality Clinical Data Management
processes
• Used as a reference tool for clinical data managers
• Review and approval of new medications or medical
devices
• Clinical and laboratory information must be collected and
converted to digital form for analysis and reporting
purposes
Data Handling and Record Keeping

2. Data Management Plan

• Record all the most important information on how data
management was carried out for a study
• The documents are more accurate when written at the start
of the study
• Provides a focus for identifying the work to be performed,
who will perform the work, and what is to be produced as
documentation of the work
Data Handling and Record Keeping

2. Data Management Plan

Continued…
• Touches the elements of the data management process for
the study in question
• Becomes an approximate table of contents
• Used as a source document for internal quality assurance
audits
Data Handling and Record Keeping

3. Data Capture

• Electronic Data Capture

• EDC systems deliver clinical trial data from the investigation sites to the
sponsor
• Eliminates the need for double-key data entry
• Data management planning and implementation are completed even
before data entry is initiated
• EDC systems are improved for site activities during a
clinical trial
Data Handling and Record Keeping

4. Best Practice for CRF

• A tool used to collect pre- defined data from a subject in a
clinical trial
• Design the CRF along with protocol
• Keep questions, prompts and instructions clear and concise
• Design the CRF to follow the data flow from the perspective of the
person completing it
• Avoid referential and redundant data points within the CRF
• Design the CRF with the primary safety and efficacy endpoints in mind
• Establish and maintain a library of standard forms
• Make the CRF available for review at the clinical site prior to approval
 Data Quality Assurance

• Describe procedures for assessing subject compliance

• Discuss source document review
• Provide assurance on good clinical practice, quality of data
collection and refer to monitor and their role

1. Data Validation
2. Query Management
 Data Quality Assurance

1. Data Validation
 Important role within the drug development program
involving many people, multiple systems, and several
data transfers
 Automated and manual procedures to detect missing
entries, illogical data
 Ensures Data accuracy and Completeness
 Helps to inform Data Managers about data issues in
timely fashion
 Once data validation is completed it is time for Data
Treatment stage
 Data Quality Assurance

1. Data Validation
Continued…
• Factors affecting the quality of data
1. CRF design
2. Field Monitoring Guidelines
3. Source data verification
4. Missing data/ CRF pages
5. Data conventions
6. Electronic laboratory data
 Data Quality Assurance

2. Query Management
• Performance metrics are tracked routinely and analyzed periodically
to ensure maintenance of the highest data management quality
standards
• All discrepancies are identified automatically by the system that are
reviewed by a data manager
• These are resolved internally through inspection of the CRF
 Data Quality Assurance

2. Query Management
Continued…
• Following actions can be taken based on project specific guidelines
• Closing discrepancy per internal connection
• Generating a query to the investigator
• Creating queries
• Sending queries
• Tracking queries
• Resolving queries
• Re-quering
 Data Quality Assurance

2. Query Management
Continued…

 Turning a discrepancy into a query

 Resolving queries
• Applying the Resolution
• Quality assurance and control
 Statistical Analysis Plan

• It is critical to specify in the protocol the precise definition of the

primary variable as it will be used in the statistical analysis.
• Oversees the processes that group, summarize, analyze, and
otherwise present trial data for clinical interpretation
• Statement of the planned sample size
• Classification of the study variables
• Information about the timing and purpose of any planned interim
analysis
• Handling of missing or non- evaluable data
 Statistical Analysis Plan

1. Data Locking
• Once the patient’s data has been collected, the study needs to be
locked in an expeditious manner
• The list involves many steps:
• Collecting final data
• Resolving outstanding queries
• Reconciling against other databases
• Performing final QC
• After these tasks are done, data manager reviews with the
clinical group and the study is considered locked- no data will
be changed, from the first patient in through to database lock
 Appendices
Based on the protocol, relevant appendices as elaborated should be
attached:

• Summary of Product characteristics, data sheer for IP

• Measurement tools and their validation

• Pharmacy information, shelf lives, dispensing procedure

• Methods for collecting patient samples, their storage,

dispatch and handling conditions
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• Clinical labs and tests

• Adverse reaction grading systems for particular
safety parameters
• Scoring systems of efficiency parameters
• Analysis diagram
• Declaration of Helsinki
• Patients and parent/legal guardian consent form
• Subject information sheet for informed consent
• Method of recruitment of patients/subjects to the
trial
 Conclusion
• Protocol is a blue print for a study. It contains all the information
necessary
• Certain Information is required by regulation to be into protocol
• The following are the key points that follow Data Management
Protocol:
1. Data Recording
• GCDMP
• DMP
• Data Capture
• CRF Practices
2. Quality Assurance
• Data Validation
• Query Management
3. Statistical Analysis
• Data Locking