Damietta Clinical Research Department

Kareem A. Attallah
PhD candidate in Biochemistry:
Thesis title ‘Early Detection of Clinical Scholar, Egypt Clinical
Hepatocellular Carcinoma Using Scholar Research Training (ECSRT),
Biochemical Techniques.’ Faculty of Harvard Medical School (2021-C).
Pharmacy, Cairo University, 2024.

MSc in Biochemistry and Molecular

Biology: Thesis title “Biochemical
BSc in Pharmacy & Pharmaceutical
Studies on Nuclear Matrix Protein in
Science, Faculty of Pharmacy,
Colon Cancer Patients". University
Ahram Canadian University, Egypt,
of Sadat City, Genetic Engineering
2016. (5 years)
and Biotechnology Research
Institute, 2019. (4 years)

BSc in Science Zoology – Chemistry,

Postgraduate Diploma in Biochemistry,
Faculty of Science, Damietta
Faculty of Science Damietta University,
Branch, Mansoura University, Egypt,
Egypt, 2012. (1 year)
2011. (4 years)
Ministry of Health & Population
Damietta Directorate for Health Affairs
Training and Schools Administration
Clinical Research Department

Protocol Writing

Kareem A. Attallah
BSc, BSc Pharm, PgD Biochem, MSc Biochem, PhD Candidate

Monday, January 22, 2024

 Learning Objectives

1. Understand the fundamental components of a clinical research

protocol.

2. Draft a mock section of a clinical research protocol.

3. Identify common pitfalls and best practices in protocol writing.

Introduction & Fundamentals
• Understanding Protocols
Definition, purpose, components, and types.
• Essentials of a Good Protocol
Clarity, ethical considerations, and regulatory compliance.
• Protocol Design & Structure
Title, objectives, study design, etc.
• Workshop Activity
Drafting a mock protocol section.
• Feedback & Discussion
Review of mock protocols, common pitfalls, and best practices.
As a researcher, why I have to do a protocol?
• To clarify the research question
• To compile existing knowledge
• To formulate a hypothesis and objectives
• To decide about a study design
• To clarify ethical considerations
• To apply for funding
• To have a guideline and tool for the research team
Understanding Protocols
• Originates from the Greek “Protokollon," referring
to the first sheet of a papyrus roll.

• Definition: a protocol is a detailed plan or set of

guidelines that outlines the objectives, design,
methodology, statistical considerations, and
organization of a clinical study.

• It serves as a comprehensive blueprint or roadmap

that researchers and study personnel follow to
ensure the study is conducted in a systematic,
ethical, and scientifically rigorous manner.
The research proposal must address the following
questions regardless of your research area and the
methodology you choose:

•What you plan to accomplish?

•Why do you want to do it?
•How are you going to do it?
Main purposes of a protocol
1. Guidance and Standardization: Provides a structured framework

and standardized guidelines for consistent study conduct across

various settings.

2. Protection of Participants: Emphasizes ethical considerations and

safeguards the rights, safety, and well-being of study participants.

How to judge a good protocol?
• Is it adequate to answer the research question(s), and achieve
the study objective?
• Is it feasible in the particular set-up for the study?
• Does it provide enough detail (methodology) that can allow
another investigator to do the study and arrive at comparable
conclusions?
Key components and aspects typically addressed
in a clinical research protocol include
1. Study Objectives: Clearly defined goals and aims of the research, including primary and

secondary outcomes.

2. Study Design: Description of the overall design, such as randomized controlled trial,

observational study, or other specific designs, including details like inclusion and exclusion

criteria.

3. Participant selection: Detailed procedures, intervention (if applicable).

4. Data collection: Survey (Questionnaire), Interview-Based, and Secondary Data Analysis

Key components and aspects typically addressed
in a clinical research protocol include
5. Interventions: Description of any treatments, procedures, or
interventions being tested or administered to participants.

6. Endpoints: Definition of primary and secondary endpoints or outcomes

that will be evaluated to determine the study's success or results.

7. Statistical Considerations: Plans for sample size determination,

randomization procedures, data analysis methods, and handling of
missing or incomplete data.
Key components and aspects typically addressed
in a clinical research protocol include
8. Ethical Considerations: Measures to ensure the protection of participants' rights,

safety, and well-being, including informed consent procedures, confidentiality

safeguards, and oversight by ethics committees or institutional review boards.

9. Regulatory Compliance: Adherence to relevant local, national, and international

regulations, guidelines, and standards governing clinical research.

10. Data Management: Protocols for data collection, recording, validation, storage, and

security to ensure data integrity and reliability.

Key components and aspects typically addressed
in a clinical research protocol include
11. Safety Monitoring: Plans for monitoring participant safety, adverse

events reporting, and interim analyses, if applicable.

12. Quality Control and Assurance: Procedures for ensuring the quality

and reliability of the study data and results, including monitoring

visits, audits, and inspections.

Basic content of the protocol
The content of research protocols might vary according the content
and context of the study
• Principal components:
❖ Introduction/rationale of the study
❖ Objectives/hypotheses
❖ Methodology
❖ Plan of analysis
❖ Timeline
❖ Ethical considerations
❖ Budget
❖ Bibliography
Title of a research project
• Accurate, short, concise
• Descriptive: should make the main objective clear,
should mention the target population
• Key words: should contain key words for referencing
• i.e. „HCV in CRC patients“
• Better: „Incidence of hepatitis C virus in colorectal cancer
patients in Egypt during 2020-2024“
Project summary (optional)
• Concise, one page (about 300 words)

• Stands on its own – no reference to protocol content

• Summarizes central elements (rationale, methodology,

populations, time frame, expected outcomes)
Introduction
 (i) Statement of the problem
Logical flow of statements:
Magnitude, frequency, and distribution: Affected geographical areas and population
groups. Ethnic and gender considerations.

Probable causes of the problem: What is the current knowledge of the problem and its
causes? Is there consensus? Is there controversy? Is there conclusive evidence?

Possible solutions: In what ways have solutions to the problem been attempted? What
has been proposed? What are the results?

Unanswered questions: What remains to be answered? What areas have not been
possible to understand, determine, verify, or test? (Knowledge Gap)
(ii) Literature review
• Prevents duplication of work, which has been done

• Clarifies, what others have found addressing the problem

• Familiarizes with potential methodologies and

methodological errors

• Should convince, that the research is needed!

(iii) Justification of research
Should be a convincing statement for the need to do this research
• How does the research relate to the priorities of the region and
the country?
• What knowledge and information will be obtained?
• What is the ultimate purpose that the knowledge obtained from
the study will serve?
• How will the results be disseminated?
• How will the results be used, and who will be the beneficiaries?
Research objectives
Define a GENERAL OBJECTIVE and drive SPECIFIC OBJECTIVES

The formulation of objectives will help to:

• Focus the study (narrowing it down to essentials)

• Avoid the collection of data which are not strictly necessary for
understanding and solving the problem you have identified

• Organize the study in clearly defined parts or phases

Research objectives
Objectives should be:
• Logical and coherent
• Feasible
• Realistic, considering local conditions
• Defined in operational terms that can be measured
• Phrased to clearly meet the purpose of the study
(relevant)
Objectives should be stated in action verbs that illustrate their purpose:
i.e. “To determine…, To compare..., To verify..., To calculate...,To reduce..., To describe..., etc.
 General objective
e.g. To determine whether or not a
Specific objectives new vaccine should be incorporated
in a public health program.
e.g. To determine the degree of protection that
Primary is attributable to the new vaccine in a study
population by comparing the vaccinated and
unvaccinated groups.

e.g. To study the cost-effectiveness of this

Secondary
programme.
Research hypothesis
Independent Intervention, Observation, Dependent
variable Control variable variable

• Describes the relationship between INDEPENDENT variables (risk

factors, predisposing factors) and DEPENDENT variables (outcome)

• Determines the type of data to be collected and the type of analysis

to be conducted
Specific objectives and Hypotheses

• List the specific objectives & hypotheses one by one concisely

• Not too many; 2-4 best

• Be specific, no general and ambiguous statements

• Be realistic, no unachievable objectives

• Objectives & hypotheses should be logically linked and arranged in a sequence

When you divide a section into subsections,
all the pieces should be of the same pie
Methodology
Important aspect of the protocol
• Assures, that the hypothesis will be proved or disproved,
using the right tools
• Presents a detailed strategy, how the objectives are achieved
Consider
• Operational definitions
• Study design
• Definition of variables
• Sample size
• Ethical aspects
Methodology
Study design
• The decision on study design needs to be based on
ethics, logistic consideration, economic aspects and
scientific thoroughness.

• The validity of the results including potential bias,

confounding, and the generalizability of the results
needs to be a prime concern defining the study design.
Methodology
Study design
Methodology
Definition of variables
Methodology
Measurement of observations
• Describe how, when and where the observations are
made? Describe instruments used!
• Questionaire (attach to the protocol)
• Type of interview (describe structure of the Interview)
• Laboratory test (refer to literature or personal knowledge,
if established test, or describe in detail, if not established)
• Clinical examinations (describe gadget/procedure)
Describe all instruments or refer to literature if tools are established.
Methodology
Subjects/ participants
Depending on the type of study, answer the following questions:

•What are the criteria for inclusion or selection?

•What are the criteria for exclusion?

•In intervention studies, how will subjects be allocated to index and

comparison groups (Randomization procedure)?

•What are the criteria for discontinuation?

Methodology
Data quality control
• Describe measures of data quality control:
• Double data entry
• Consistancy checking
• Data monitor
• Verfication procedures of source data
Methodology
Sample size why
• Sample size calculation is recommeded for
economical and ethical reasons

• Level of error, power and expected impact of

exposure on outcome have to be set
Activity!
Ethical considerations
One of the most important aspects of biomedical research!

Important aspects to consider:

• Data safety / confidentiality
• Any possibly harm/ side effects/ consequences
• Right of discontinuation at any time
• Role of data safety and monitoring board (in trials)
• Alternative treatments/ approaches (in trials)
• Incentives/ Rewards
Ethical considerations
Informed consent
Outline how, when and where the patient will be consented!

Information form should contain:

• Justification for research
• Responsibilities (Who)
• Outline of study
• Risks
• Confidentiality
Data management and analysis
Based on objectives consider:
• Coding for variables/ type of variables
• Analysis plan depending on type of variables
• Statistical tests implicated
• (Style of presentation i.e. tables, graphs)
• Data safety and storage
References/Bibliography
• Use of standard referencing system:
• Harvard style
• Name and publication year
in text
• Alphabetical bibliography
• Vancouver style
• Numbered references
• Continous referencing in
text
• Make use of software
• Reference Manager
• Endnote software
Work plan
(Time framework)

Who?
Tasks
When?
Where?
Budget
The budget should be broken down by:
• Items
• Personnel
• Consumables, equipment, supplies, communication, funds
for patients, data processing
• Budget justification
• Jusitify the use of each item, considering the workplan of
the study
Annexes
• Case Record Forms (CRFs)

• Questionnaires

• Patient information form (in required languages)

• Consent form (in required languages)

• CV of investigators
Common mistakes

• Including too little detail about proposed studies and insufficient

justification for the significance of the problem

• Proposing far more work than can be reasonably done during the

grant period
 General Writing Stages

1. Getting in the Mood 2. Writing the First Draft

Save multiple copies

of your draft

3. Revising, Revising, Revising 4. Finishing

Activity!
Take-home Messages
• Protocols are essential for guiding clinical research.

• Clarity, ethics, and regulatory compliance are paramount in

protocol writing.

• Continuous learning and peer feedback enhance protocol

quality.
References
• Sudheesh K, Duggappa DR, Nethra SS. How to write a research proposal? Indian J Anaesth. 2016 Sep;60(9):631-634. doi:
10.4103/0019-5049.190617. [Link]

• Al-Riyami A. How to prepare a Research Proposal. Oman Med J. 2008 Apr;23(2):66-9.

[Link]

• Singh NA, Clements KM, Fiatarone MA. A randomized controlled trial of the effect of exercise on sleep. Sleep. 1997 Feb;20(2):95-101. doi:
10.1093/sleep/20.2.95. [Link]

• Mohammadbeigi A, Asgarian A, Moshir E, Heidari H, Afrashteh S, Khazaei S, Ansari H. Fast food consumption and
overweight/obesity prevalence in students and its association with general and abdominal obesity. J Prev Med Hyg. 2018 Sep
28;59(3):E236-E240. doi: 10.15167/2421-4248/jpmh2018.59.3.830. [Link]

• Ulaganathan V, Kandiah M, Shariff ZM. A case-control study on the association of abdominal obesity and
hypercholesterolemia with the risk of colorectal cancer. J Carcinog. 2018 Sep 25;17:4. doi: 10.4103/jcar.JCar_2_18.
[Link]
 Kareem A. Attallah
+2 0122 0834 797, +2 0100 66 12 402

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