EXPERIMENT : 16 DATE : 18.03.

2025

PROTOCOL DESIGN FOR CLINICAL TRIAL

Aim : To study the procedure of protocol designing for a clinical trial study.

Objective : The objective of a clinical protocol is to provide a concise plan outlining the rationale
for and design of a planned study. The protocol is a document that describes how a clinical trial will
be conducted (the objective(s), design, methodology, statistical considerations and organization of a
clinical trial,) and ensures the safety of the trial subjects and integrity of the data collected.

Theory : A clinical study protocol is an essential parameter for trial investigators, enabling them to
tick all the necessary boxes for a successful clinical trial. It is the first document that is drafted when
designing and planning a clinical trial. All related and involved documents, templates and forms,
digital interventions, etc. are in alignment with the protocol. Moreover, a clinical study protocol also
enables everyone working on a trial to adhere to stringent regulatory guidelines. This is critical to the
success of the trial, which is why multiple parties help to draft a protocol.

CLINICAL STUDY PROTOCOL

1 2 3 4 5 6 7 8 9

Site/Trial Data Drug

Research Data analysis Approval
Hypothesis Preparation Collection,
Sites, Trial Monitoring, Reporting of Data
PI or Trial result Archiving
Sponsor Sponsor, IRB Processing
Trial Sponsor Title Trial Sponsor
Sites Sponsor Sites

Protocol Trial Regulatory

Development Subject Management Submission
Trial sponsor Enrollment Title Sponsor Trial Sponsor
to agency Sites Sites To Agency

Fig 1: Protocol Design

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Designing a protocol for a clinical trial is a meticulous process that requires careful planning,
adherence to regulatory standards, and a thorough understanding of scientific principles. The
protocol serves as the blueprint for the trial, detailing every aspect of the study from objectives and
methodology to data management and ethical considerations.
Here's an in-depth look at the key components and considerations involved in creating a clinical trial
protocol:
1. Title and Overview:
• Title: The title should be descriptive and succinct, capturing the essence of the study. It
typically includes the intervention, patient population, and possibly the study design.
• Protocol Number: Each protocol should have a unique identifier to differentiate it from other
studies and to track its versions and revisions over time.
• Version and Date: Keeping track of the version and date of the protocol is crucial for
maintaining records and for making sure all parties are using the most current version.
2. Objectives:
• Primary Objective: This is the main goal of the study, such as determining the efficacy of a
new drug. It should be specific and measurable.
• Secondary Objectives: These are additional aims that provide supporting information about
the intervention, such as safety profiles, quality of life assessments, or pharmacokinetics.

3. Background and Rationale:

• Scientific Background: This section provides context by summarizing existing research and
data related to the disease and the intervention. It includes a literature review and a discussion
of previous studies.
• Rationale: This explains why the study is needed and what it aims to accomplish. It should
justify the selection of the intervention, the study design, and the population.
4. Study Design:
• Type of Study: Describe whether it is a randomized controlled trial (RCT), cohort study,
cross-sectional study, etc. The choice depends on the research question and objectives.
• Blinding: Specify if the study is single-blind, double-blind, or open-label. Blinding minimizes
bias.
• Control Group: Detail the control group, which could be a placebo, standard of care, or an
active comparator. The control group is essential for comparing the intervention's effect.
• Randomization: Explain the randomization process to ensure that participant assignment to
different groups is unbiased. Methods could include computer-generated random sequences.

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5. Study Population:
• Inclusion Criteria: List the characteristics that participants must have to be eligible for the
study. These might include age range, specific diagnosis, and severity of disease.
• Exclusion Criteria: Describe characteristics that disqualify potential participants, such as co-
morbid conditions, concomitant medications, or previous treatments that could interfere with
the study.
• Recruitment Strategy: Outline how participants will be identified and recruited, including
sites, advertising methods, and partnerships with clinics or hospitals.
6. Intervention:
• Description: Provide a detailed description of the intervention, including its composition,
formulation, and packaging.
• Dosage and Administration: Specify the dosage, route of administration, frequency, and
duration of treatment. Include any dose adjustments or titration plans.
• Duration: State the length of time participants will receive the intervention and the follow-up
period.
7. Outcome Measures:
• Primary Outcome: Define the main outcome to assess the intervention’s effect. This should
be a direct measure of efficacy or safety.
• Secondary Outcomes: Include other relevant outcomes that provide additional information,
such as biomarkers, patient-reported outcomes, or secondary clinical endpoints.
• Safety Measures: Outline how safety will be monitored, including adverse events, laboratory
tests, and vital signs.
8. Study Procedures:
• Schedule of Assessments: Provide a timeline of when assessments will occur. This typically
includes screening, baseline, follow-up visits, and final assessments.
• Detailed Procedures: Describe each assessment in detail, including physical examinations,
diagnostic tests, imaging, and questionnaires. Ensure consistency in data collection.
9. Statistical Considerations:
• Sample Size Calculation: Justify the number of participants required. This should be based on
statistical power calculations, considering the expected effect size, variance, and dropout
rates.
• Statistical Analysis Plan: Detail the methods for analyzing the data, including the primary and
secondary outcomes. Specify the statistical tests, significance levels, and handling of missing
data.
• Interim Analyses: If applicable, describe any planned interim analyses and the criteria for
early stopping or modifications to the study.

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10. Ethical Considerations:
• Informed Consent: Detail the process for obtaining and documenting informed consent from
participants. Include how information will be provided and how consent will be documented.
• Confidentiality: Explain how participant confidentiality will be maintained, including data
protection measures and access controls.
• Ethical Approvals: List the ethics committees and regulatory bodies that will review and
approve the study. Include timelines for submission and approval.
11. Data Management:
• Data Collection: Describe the methods and tools for data collection, such as electronic data
capture systems or paper forms.
• Data Monitoring: Outline the procedures for monitoring data quality and completeness. This
includes regular data reviews, query resolution, and audits.
• Data Analysis: Plan for data analysis, specifying software and statistical methods. Ensure
clarity on how data will be handled, analyzed, and reported.
12. Quality Assurance:
• Training: Provide a plan for training study personnel on the protocol, including training
materials and schedules.
• Monitoring: Detail the monitoring plan, including site visits, remote monitoring, and
compliance checks. Ensure that the protocol is followed consistently across sites.
• Audits: Describe plans for internal and external audits to ensure adherence to Good Clinical
Practice (GCP) and regulatory requirements.
13. Adverse Event Reporting:
• Definition of Adverse Events: Provide a clear definition and classification of adverse events
and serious adverse events.
• Reporting Procedures: Detail the process for recording and reporting adverse events,
including timelines and responsibilities.
• Safety Monitoring Committee: If applicable, describe the role of an independent safety
monitoring committee in reviewing safety data and making recommendations.
14. Dissemination of Results:
• Publication Plan: Outline the plan for disseminating study results, including timelines for
publication and target journals or conferences.
• Authorship: Define the criteria for authorship and acknowledge contributions from all study
personnel.

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15. Appendices:
• Study Tools: Include copies of all study tools, such as informed consent forms, case report
forms, questionnaires, and patient diaries.
• Reference List: Provide a comprehensive list of references cited in the protocol, ensuring that
all sources are properly credited.

Fig 2: Steps involved in drafting a Clinical Trial Protocol

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Conclusion:
Designing a clinical trial protocol requires a detailed and systematic approach to ensure the study is
scientifically sound, ethically conducted, and compliant with regulatory standards. The protocol
serves as a critical document guiding the execution of the trial, ensuring consistency, reliability, and
integrity in the research process. Each section must be meticulously crafted and reviewed to address
all aspects of the study, from rationale and design to data management and ethical considerations. By
adhering to these guidelines, researchers can design robust clinical trials that generate reliable and
meaningful data, ultimately contributing to the advancement of medical science and patient care.

References :
1. Stoney, Catherine M., and Laura Lee Johnson. "Design of clinical trials and studies."
Principles and practice of clinical research (2018): 249-268.

2. Meyer EL, Mesenbrink P, Dunger-Baldauf C, Fülle HJ, Glimm E, Li Y, Posch M, König F.

The evolution of master protocol clinical trial designs: a systematic literature review. Clinical
Therapeutics. 2020 Jul 1;42(7):1330-60.

Attendance Viva Manual Involvement Methods & Critical

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Total (40) =

Signature of the Faculty

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EXPERIMENT: 17 DATE: 19.03.2025

DESIGN OF ADR MONITORING PROTOCOL

Aim: To study the procedure of protocol designing for adverse drug reaction monitoring.

Objectives:
1. Detect & Identify ADRs:

• Identify previously unknown or rare ADRs.

• Monitor known ADRs for severity, frequency, and risk factors.

2. Assess Drug Safety & Risk-Benefit Ratio:

• Evaluate the impact of ADRs on patient health.

• Determine whether benefits outweigh risks for continued drug use.

3. Improve Patient Safety & Treatment Outcomes:

• Minimize harm by early detection of adverse effects.

• Provide guidelines for safer drug use in specific populations (e.g., elderly, pregnant
women).

4. Identify Risk Factors for ADRs:

• Study genetic, environmental, and patient-specific factors influencing ADRs.

• Identify drug interactions, co morbidities, and contraindications.

5. Support Regulatory Decision-Making:

• Provide data for drug labeling updates (e.g., new warnings, contraindications).
• Assist regulatory agencies (FDA, EMA, WHO) in modifying, restricting, or withdrawing
unsafe drugs.

6. Enhance Rational Drug Use:

• Educate healthcare professionals and the public on ADR risks.

• Promote evidence-based prescribing and dispensing.

7. Strengthen Pharmacovigilance Systems:

• Develop ADR reporting systems (e.g., WHO-Uppsala Monitoring Centre, FDA Med
Watch).
• Encourage voluntary and mandatory ADR reporting by healthcare professionals and
patients.

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Adverse Drug Reactions:
An adverse drug reaction (ADR) is an unwanted, undesirable effect of a medication that occurs
during usual clinical use. Adverse drug reactions occur almost daily in health care institutions and
can adversely affect a patient’s quality of life, often causing considerable morbidity and mortality.
Much attention has been given to identifying the patient populations most at risk, the drugs most
commonly responsible, and the potential causes of ADRs. Adverse drug reactions may cause patients
to lose confidence in or have negative emotions toward their physicians and seek self-treatment
options, which may consequently precipitate additional ADRs. Around 5% of all hospital admissions
are the result of an ADR, and around 10%– 20% of inpatients will have at least one ADR during
their hospital stay.

Classification:

ADRs

Type A Type B Type C Type Type E (End

(Augmented) (Bizarre) (Chronic) D(Delayed) Of use)

Fig 1: Classification of ADRs

Adverse Events:
An adverse drug event is “an injury resulting from the use of a drug. Under this definition, the term
ADE includes harm caused by the drug (adverse drug reactions and overdoses) and harm from the
use of the drug (including dose reductions and discontinuations of drug therapy).”1 Adverse Drug
Events may results from medication errors but most do not. Adverse events that occur with medical
treatment can include medication side effects, injury, psychological harm or trauma, or death.
Adverse events can be either preventable or unpreventable and are often associated with medication
errors. Adverse events can occur with any provision of care or treatments have a wide range of
severity.

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 Fig 2: Adverse Events

Feedback

Casuality Identifying
Asessment Probable adverse
events

Adverse Events
Surveillance

Investigations Notification

Fig 3: Adverse Events Detection

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NARANJO SCORE:

The Adverse Drug Reaction (ADR) Probability Scale was developed in 1991 by Naranjo and co-
workers from the University of Toronto and is often referred to as the Naranjo Scale. This scale was
developed to help standardize assessment of causality for all adverse drug reactions and was not
designed specifically for drug induced liver injury. The scale was also designed for use in controlled
trials and registration studies of new medications, rather than in routine clinical practice. The ADR
Probability Scale consists of 10 questions that are answered as either Yes, No, or “Do not know”.
Different point values (-1, 0, +1 or +2) are assigned to each answer.

The actual ADR Probability Scale form and instructions on how it is completed are provided below.
Total scores range from -4 to +13; the reaction is considered definite if the score is 9 or higher,
probable if 5 to 8, possible if 1 to 4, and doubtful if 0 or less.

Fig 4: Naranjo Score

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ADR REPORTING FORM:

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Fig 5: Details about Adverse events reporting

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References:

1) Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, et al. A method
for estimating the probability of adverse drug reactions. Clin Pharacol Ther. 1981;30:239–45.
2) J. R. Nebeker, P. Barach, M. H. Samore. Clarifying adverse drug events: a clinician’s guide
to terminology, documentation, and reporting. Ann. Intern. Med.,2004; 140(10): 795– 801.
3) Bhatt AD. Drug related problems and adverse drug events: Negligence litigation
and prevention. JAPI 1999;47: 715-2
4) Jose J, Rao PG. Pattern of adverse drug reactions notified by spontaneous reporting in an
Indian tertiary care teaching hospital. Pharmacol Res. 2006;54:226–33. doi:
10.1016/j.phrs.2006.05.003

Attendance Viva Manual Involvement Methods & Critical

(10) (10) Maintenance (4) Accuracy (4) Thinking (8)
(4)

Total (40) =

Signature of the Faculty

13