This document describes the detailed information of clinical trial protocol and protocol design. The protocol includes the key information of study designs. This document is downloaded as a PDF and viewed online.

1. DEVELOPING CLINICAL TRIAL
PROTOCOL
Presented by
N. Sangeetha
M.S.V. Maha Lakshmi
B. Pharmacy - 4th year
NRI college of pharmacy- Pothavarappadu.

2. *

3. DEFINITION: A Clinical research protocol is a document that describes the background,
rationale, objectives, designs, enrollment, criteria, methodology, data recording requirements,
statistical considerations, and organization of a clinical research study. A protocol is directed by a
chief researcher.
What is a protocol?
A Protocol is a live master document and the guidelines IchE6 defines a protocol as the document
that describes, the objective(s), designs, methodology, statistical considerations, and organization of
a clinical trial; and ensures the safety of the trial subjects and integrity of the data collected.

4.  In case of any amendments to the protocol, the same should be put up before the IRB for approval
before it is implemented.
 The current regulator CDSCO [Central Drug Standard Control Organization], Established in India by
the Drug and Cosmetic Act 1945, has provided guidelines regarding the contents of a clinical trial
protocol.
 The actual writing of a protocol is a team effort with contributions from a medical expert, a
statistician , a pharmacokinetics expert, the clinical research coordinator, and the project manager,
who all provide input to the medical writer to produce the final document.

5.  The sponsor is responsible for ensuring the trial is conducted in accordance with sound scientific
principles and GCP standards by selecting qualified investigators, providing them the protocol and
ensuring protocol compliance.
 Clinical trial template is a suggested format for writing a comprehensive clinical trial protocol that
meets the standard outlined in the ICH-E6.
 The current regulator CDSCO [Central Drug Standard Control Organization], Established in India
by the Drug and Cosmetic Act 1945, has provided guidelines regarding the contents of a clinical
trial protocol.

6. The actual writing of a protocol is a team effort with contributions from a medical expert, a
statistician , a pharmacokinetics expert, the clinical research coordinator, and the project manager,
who all provide input to the medical writer to produce the final document.
The sponsor is responsible for ensuring the trial is conducted in accordance with sound scientific
principles and GCP standards by selecting qualified investigators, providing them the protocol
and ensuring protocol compliance.
Clinical trial template is a suggested format for writing a comprehensive clinical trial protocol that
meets the standard outlined in the ICH-E6.

7. Development of clinical research protocol
Every clinical investigation begins with the development of a clinical protocol. The protocol in a
document that describes how a clinical trial will be conducted and ensures the safety of the trial subjects
and the integrity of the data collected. The clinical trial should be carried out by a written protocol agreed
upon and signed by the investigator and the sponsor.
 A protocol is a carefully designed and controlled study plan to safeguard the health of the participants
as well as to answer specific research questions.
 The protocol describes what clinical trial experts will do in the study; what types of people may
participate in the trial; the schedule of tests, procedures, medications, dosages; and the length of the
study.

8.  After researchers test new drugs, therapies or procedures in vitro and in animals (pre-clinical study),
the experimental treatments with the most promising laboratory results are moved into clinical trials.
 During a trial, an exhaustive information is gained about an experimental treatment to determine its
safety and effectiveness in humans.
 Health of the participant is checked before the commencement of the trial, specific instructions are
given for participation, regular monitoring of the participant is done carefully during the whole study
and stay in touch is required even after the trial is completed

9. Tools of protocol:
 It ensures the safety and health of all study participants.
 It provides a particular study plane.
 It is required to get an ethical approach from the institutional review board.
 It manages the trial and should be strictly followed by all the study investigators.
 It compares the knowledge across the investigators.

10. To formulate a hypothesis and objectives.
To raise the questions to be researched and clarify its importance
To suggest the methodology required for solving.
To discuss the requirements and limitations in achieving the objectives.
 The objective in the goal of a protocol. It study state explicitly the purpose of the clinical
research project.
In the brief description of the products to be used, the safety and effectiveness, and the type of
subject population to be evaluated should be included. And should be stated succinctly.
Aims and objectives of protocol:

11. According to the ICH good clinical practice guidelines, a trial protocol should include the following topics.
However, site-specific information may be provided on separate protocol page(s), or addressed in a separate
agreement, and some of the information listed below may be contained in other protocol-referenced
documents, such as an Investigators Brochure.
A protocol should include the following topics
1. General information.
2. Background information.
3. Study trial protocol.
4. Study design.
5. Selection and withdrawal of subjects.
CLINICAL TRIAL PROTOCOL

12. 6. Treatment of subjects.
7. Assessment of Efficacy
8. Assessment of Safety
9. Statistics.
10. Compliance with protocol.
11. Quality control and Quality assurance
12. Ethics.
13. Data management.
14. Financing and insurance.
15. Publication Policy.
16. Supplements.

13. 1. GENERAL INFORMATION :
 Title page introduced and documented, its title, precise number, sponsor, and author to the reader.
 Protocol title, protocol identifying number, and date. Any amendment(s) should also bear the
amendment number(s) and date(s).
 Name and address of the sponsor and monitor (if other than the sponsor).
 Name and title of the person(s) authorized to sign the protocol and the protocol amendment(s) for the
sponsor.
 Name, title, address, and telephone number(s) of the sponsor's medical expert (or dentist when
appropriate) for the trial.
 Name and title of the investigator(s) who is (are) responsible for conducting the trial, and the address and
telephone number(s) of the trial site(s).

14.  Name, title, address, and telephone number(s) of the qualified physician (or dentist, if applicable),
who is responsible for all trial-site related medical (or dental) decisions (if other than investigator).
 Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical
department(s) and/or institutions involved in the trial.
2. BACKGROUND INFORMATION:
 The product name and description for the experimental product (s).
 A list of the benefits if any and known risks to human subjects.
 An overview of results from clinical trials that are important to the trial as well as nonclinical
research that may have clinical significance.

15.  An explanation and safety of the dosage, schedule, route of administration, and duration of
treatment(s).
 A declaration that the trial will be carried out following the applicable regulatory requirement(s),
GCP, and protocol.
 An explanation of the population under study.
 The references to studies and information related to the trial that serve as a context for the trial.
3. STUDY TRAIL PROTOCOL:
A detailed description of the major ( primary) and minor(secondary and exploratory), objective,
and purpose of a trial.

16. 4. STUDY DESIGN:
The scientific integrity of the study and the credibility of the data obtained from the study largely
depend on the study design.
This section of the protocol should describes,
 Primary and secondary endpoints to be measured
 A description of the type/design of the trial to be conducted (e.g double-blind, placebo-controlled,
parallel design) and a schematic diagram of trial design, procedures, and stages.
 A description of the measures taken to minimize/avoid bias, including
a) Randomization.
b) Blinding.

17.  A description of the trial treatment(s) and the dosage and dosage regimen of the investigational
product(s). Also include a description of the dosage form, packaging, and labeling of the
investigational product(s).
 A description of the "stopping rules" or "discontinuation criteria" for individual subjects, parts of the
trial and entire trial.
 Maintenance of trial treatment randomization codes and procedures for breaking codes.
 The identification of any data to be recorded directly on the CRFs (i.e. no prior written or electronic
record of data), and to be considered to be source data.

18. 5. SELECTION AND WITHDRAWAL OF SUBJECTS:
 1. Subject inclusion criteria.
 2.Subject exclusion criteria.
 3.Subject withdrawal criteria (i.e. terminating investigational product treatment/trial treatment)
and procedures specifying:
 a) When and how to withdraw subjects from the trial/ investigational product treatment.
 b) The type and timing of the data to be collected for withdrawn subjects.
 c) Whether and how subjects are to be replaced.
 d) The follow-up for subjects withdrawn from investigational product treatment/trial treatment.

19. 6. TREATMENT OF SUBJECTS:
 The treatment(s) to be administered, including the name(s) of all the product(s), the dose(s), the
dosing schedule(s), the route of administration, and the treatment period(s), including the follow-up
period(s) for subjects for each investigational product treatment/trial treatment group.
 Treatment(s) permitted (including rescue medication) and not permitted before and/or during the
trial.
 Procedures for monitoring subject compliance.

20. 7. ASSESSMENT OF EFFICACY:
This section describes the methods that will be used to determine the success of the treatment
including :
 Criteria for determining the effectiveness of the treatment
 Methods and timing for assessing, recording, and analyzing efficacy parameters.
8. ASSESSEMENT OF SAFETY:
 The methods and timing for assessing, recording, and analyzing safety parameters.
 Procedures for eliciting reports of and for recording and reporting adverse events and inter current
illnesses.

21. 9. STATISTICS:
 A description of the statistical methods to be employed, including the timing of any planned
intermittent analysis.
 The number of subjects planned to be enrolled. In multi center trials, the number of enrolled subjects
projected for each trial site should be specified. Reason for choice of sample size, including
reflections on the power of the trial and clinical justification.
 The level of significance to be used.
 Criteria for the termination of the trial.
 Procedure for accounting for missing, unused, and spurious data.
 Procedures for reporting any deviation(s) from the original statistical plan.

22. 10. COMPLIANCE WITH PROTOCOL:
 The investigator/institution should conduct the trial in compliance with the protocol agreed by the
sponsor and, if required, by the regulatory authorities ) and which was given approval/ favorable
opinion by the IRB/IEC. The investigator/institution and the sponsor should sign the protocol, or an
alternative contract, to confirm the agreement.
11. QUALITY AND QUALITY ASSURANCE:
A detailed quality assurance plane describing the set of standards and controls that are in place to
conform that the execution of each step follows the agreed upon plan is usually submitted as a separate
document. The protocol should provide a general description of the quality assurance methods.

23. 12.ETHICS:
This section should describes ethical considerations relating to the study and measures taken to protect
human participants and maintain confidentiality of clinical trial study data management.
13.DATA MANAGEMENT:
The data management plan describes the procedure that will ensure data integrity throughout study
and at all study sites including
 A description of data system design and development.
 Data collection methods and activities.
 Methods of data entry and editing.
 Procedures for data monitoring reporting and transfer.
 Data recipient and procedures for data publication.

24. 14.FINANCING AND INSURANCE:
This section describes how study will be financed and insured. In some research networks, issues are
addressed in a separate agreement and need not be included in the protocol.
15.PUBLICATION POLICY:
 The policies and procedures relating to publication of findings from the study.
 In some research networks, policies and guidelines are established for research for the publications
planning process.
 The trail results will also be published on public websites.
 The public websites will not identify participants, but will provide a resource for clinical trial
participants and those seeking clinical trial involvement ,to inform themselves.

25. TYPES OF CLINICAL TRIAL DESIGN
Data credibility and scientific integrity of a clinical trial depend on the trial design
included in the protocol.

26. 1.Cohort study:
Cohort study in clinical trials is a type of observational study that follows a group of people who share a
common characteristic or experience over a period of time, to see how certain factors affect their health
outcomes. For example, a cohort study could compare the health of smokers and non-smokers over several
years. Cohort studies can be either prospective (looking forward in time) or retrospective (looking backward in
time). They are often used in medicine, pharmacy, nursing, psychology, and social science to Identify risk
factors for diseases and potential interventions.
2.Case control study:
A case-control study in clinical trials protocol is a document that describes the rationale, objectives, design,
methods, and ethical considerations of a case-control study that is conducted as part of a clinical trial.

27. A case-control study is a type of observational study that compares a group of patients who have a specific
outcome or condition (cases) with a group of patients who do not have the outcome or condition (controls),
and examines the association between exposure to a factor (such as a treatment or a risk factor) and the
outcome or condition.
3.Cross sectional:
A cross-sectional study in clinical trials protocol should follow the standard reporting guidelines and
formats, such as the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology)
statement and checklist, and the SPIRIT (Standard Protocol Items: Recommendations for Interventional
Trials) statement and checklist.

28. 1-2 weeks
Days - weeks
2 - 4weeks
one week
Months -years
Months -years
Few Months
Weeks-Month

29. - Step 1: Creation (Time varies, could be days to weeks) : This is the initial phase where the
protocol is created. It involves planning, designing, and documenting the protocol.
- Step 2: Submission (1-2 weeks) : The protocol is then submitted for approval or review. This
could be to a regulatory body, ethics committee, or other overseeing authority
- Step 3: Review (2-4 weeks) : The submitted protocol undergoes a thorough review process to
ensure it meets all necessary criteria and standards.
- Step 4: Activation (1 week) : Once approved, steps are taken to activate or initiate the protocol.
This could involve preparatory activities before full-scale implementation.

30. - Step 5: Conduct (Time varies greatly depending on the project, could be months to years) : The
protocol is conducted according to plan. Data collection and other activities occur during this phase.
- Step 6: Oversight(Concurrent with Step 5) : Oversight ensures that the conduct of the protocol
adheres to all guidelines and standards. It’s an ongoing process throughout the conduct phase.
- Step 7: Publication(Few months) : Results and findings are published after completion of the
study or experiment. It involves data analysis, writing up results, peer review submission etc.
- Step 8: Closeout (Few weeks to a month) : Final administrative tasks are completed; ensuring all
aspects of the protocol are concluded efficiently