Protocol Writing in Clinical Research

Assistant Professor
Essam Ahmed Al-Moraissi
Department of Oral and Maxillofacial Surgery
Faculty of Dentistry, Thamar University
Starting Point – Identify a Research Idea

• It is generally thought within the scientific community that the difference between good and
poor research is the distinction between asking a good or poor question.
• Good research starts with a good idea! The idea will help you define the problem that needs to
be addressed and formulate a research question.
• A well-crafted research question can help you to design a study properly so as to arrive at a
precise conclusion.

• Subsequently, you need to ask yourself if that question is already answered.

Starting Point – Identify A Research Idea

• A thorough literature review is therefore mandatory. If you have a truly

good idea, you might find out that you are not the first one having it.
• You do not want to spend a lot of time and energy into a project only to
find out later that there have been already a substantial number of trials,
quantitative studies, systemic reviews or a meta-analysis already
performed and your research question is answered.
Starting Point – Identify A Research Idea

• It is not only important to know how much was already published on that topic, but
also what the quality of the current evidence is.
• Rarely in dentistry does a question have a definitive answer.
• If you are trying to compare two interventions for a certain condition, after performing a
thorough literature search, you have to ask yourself the following questions:
• 1) Are there already multiple case series published on that topic? If yes, then it
might not be worth it to add another case series to the literature.
Starting Point – Identify A Research Idea

• However, this may be your chance for the first comparative study (cohort study or
randomized controlled trial).
• 2) Are there already multiple comparative studies? If yes, are they cohort studies or
randomized controlled trials (RCT)? If there are no RCTs may be you should do
one.
• 3) Are there already multiple RCTs published? If yes, what are the results and what
is their sample size? Maybe they were underpowered? If yes, you might consider
doing a meta-analysis of the existing RCTs and, subsequently, a larger trial
Starting Point – Identify A Research Idea

• The idea that leads to your research question not only needs to be novel as
mentioned above, but also needs to be feasible with the availability of adequate
subjects, technical expertise, time, money and most importantly scope.
• The idea most definitely needs to be interesting to the investigator, relevant to
scientific knowledge and future research directions and last but not least,
ethical.
How To Select The General Area Of Your Research

• 1. The first step must be to decide in general terms what you want to do, ie
your area of interest - or at least where to start (because the findings from
the first part of the work may affect future directions).
• 2. If you have a choice of supervisors it should help to find out what you
can about all of them. Most will be knowledgeable and helpful, but some
may have so many outside commitments that they may not be able to give
students the attention that they would like.
How To Select The General Area Of Your Research

• Good relationships with supervisors are essential for success, so orientate

your topic to one that a 'good' supervisor will want and be able to
supervise.
Selecting a Topic

• The ability to develop a good research topic is an important skill. An

instructor may assign you a specific topic, but most often instructors
require you to select your own topic of interest.
• When deciding on a topic, there are a few things that you will need to do:
Selecting a Topic

• brainstorm for ideas

• choose a topic that will enable you to read and understand the literature
• ensure that the topic is manageable and that material is available
• make a list of key words
• be flexible
• define your topic as a focused research question
• research and read more about your topic
• formulate a thesis statement
Selecting a Topic

• Be aware that selecting a good topic may not be easy.

• It must be narrow and focused enough to be interesting, yet broad enough
to find adequate information.
• Before selecting your topic, make sure you know what your final project
should look like.
• Each class or instructor will likely require a different format or style of
research project.
Step 1: Brainstorm for ideas

• Choose a topic that interests you. Use the following questions to help generate topic ideas.

• Do you have a strong opinion on a current social or political controversy

• Did you read or see a news story recently that has piqued your interest or made you angry or
anxious?
• Do you have a personal issue, problem or interest that you would like to know more about?
• Do you have a research paper due for a class this semester?
• Is there an aspect of a class that you are interested in learning more about?
• Look at some of the following topically oriented Web sites and research sites for ideas.
Step 1: Brainstorm for ideas

• Write down any key words or concepts that may be of interest to you.
• Could these terms help be used to form a more focused research topic?
STEP 2: READ GENERAL BACKGROUND
INFORMATION
• Pubmed
• Google schoolar
• Sciencedirect
STEP 3: FOCUS ON YOUR TOPIC

• Keep it manageable

• A topic will be very difficult to research if it is too broad or narrow. One way to narrow a
broad topic such as "the environment" is to limit your topic.
STEP 4: MAKE A LIST OF USEFUL KEYWORDS

• Keep track of the words that are used to describe your topic.

• Look for words that best describe your topic

• Look for them in when reading literature
• Find broader and narrower terms, synonyms, key concepts for key words to widen your
search capabilities
• Make note of these words and use them later when searching databases and catalogs
STEP 5: BE FLEXIBLE

• It is common to modify your topic during the research process. You can never be sure of
what you may find.
• You may find too much and need to narrow your focus, or too little and need to broaden
your focus.
• This is a normal part of the research process. When researching, you may not wish to
change your topic, but you may decide that some other aspect of the topic is more
interesting or manageable.
STEP 6: DEFINE YOUR TOPIC AS A FOCUSED
RESEARCH QUESTION
• You will often begin with a word, develop a more focused interest in an aspect of
something relating to that word, then begin to have questions about the topic.
STEP 7: RESEARCH AND READ MORE ABOUT
YOUR TOPIC
• Use the key words you have gathered to research article databases, and Internet search
engines.
• Find more information to help you answer your research question.
• You will need to do some research and reading before you select your final topic.
• Can you find enough information to answer your research question? Remember,
selecting a topic is an important and complex part of the research process
STEP 8: FORMULATE A THESIS STATEMENT

• Write your topic as a thesis statement.

• This may be the answer to your research question and/or a way to clearly state the
purpose of your research.
• Your thesis statement will usually be one or two sentences that states precisely what is to
be answered, proven, or what you will inform your audience about your topic.
• The development of a thesis assumes there is sufficient evidence to support the thesis
statement.
Identifying A Good Research Topic

• The inexperienced researcher who is having problems identifying a pertinent topic needs
to have a prepared mind and be alert to new ideas.
• He or she can draw inspiration from other researchers and exploit similar ideas, rather
than absolutely unique ones. Also, one can repeat or reproduce what someone else has
done.
• For example, one can challenge the hypothesis of certain studies or confirm if the study
is true for a population of a different ethnicity.
Identifying A Good Research Topic

• A topic which has been studied on a small scale can be studied again on a
larger study group or with a longer duration of follow-up.
• A study can be conducted on the same topic sometime later, especially for
efficacy of drugs.
• For example, one can study whether an anti-microbial drug, with
previously proven efficacy, is still efficacious against a particular micro-
organism after a certain period of time.
Identifying A Good Research Topic

• Identify an area of importance in your country. The prevalence of diseases is different in

different countries e.g.
• Pakistan has one of the highest occurrences of oral sub-mucous fibrosis. Also, for example,
the need to draft a national oral health policy incorporating issues such as the need for
routine check-ups, early replacement of missing teeth, basic oral hygiene, adequate
sterilization procedures to avoid contraction of Hepatitis B and C and awareness regarding
the consequences of consuming antibiotics and water with a high fluoride content during
pregnancy etc can play a crucial role in educating the public on a national level
WHAT IS A PROTOCOL?

• Clinical research is conducted according to a plan (a protocol) or an action plan. The protocol
demonstrates the guidelines for conducting the trial.
• It illustrates what will be made in the study by explaining each essential part of it and how it is
carried out. It also
• describes the eligibility of the participants, the length of the study, the medications and the related
tests.
• A protocol is directed by a chief researcher. The health of the participants’ will be regularly checked
by members of the research team to ultimately ensure the study’s safety and effectiveness.
Purpose of a Research Proposal

• 1) To raise the question to be researched and clarify its importance.

• 2) To collect existing knowledge and discuss the efforts of other researchers who have
worked on the related questions (Literature review).
• 3) To formulate a hypothesis and objectives.
• 4) To clarify ethical considerations.
• 5) To suggest the methodology required for solving the question and achieving the
objectives.
• 6) To discuss the requirements and limitations in achieving the objectives
Benefits of the Proposal to a Researcher

• Allows the researcher to plan and review the project's steps. Serves as a guide throughout
the research. Forces time and budget estimates
• The key points of the proposal should include justification for the need of the project and a
detailed plan for the investigation :
• What is the question? (Hypothesis) What is it to be investigated?
• Why is the study important? (Significance)
• Where and when it will take place?
• What is the methodology? (Procedures and methods to be used).
• How are you going to do it? (Research design)
• Proposed time table and budget.
• Resources required (technical, scientific, and financial)
• Drafting the protocol correctly will increase the likelihood that the conclusions drawn
from the research are scientifically sound.
• Recommendations and suggestions should be sought from colleagues and experts so that
researchers can develop their plans.
• However, once the study is launched, the protocol should not be altered during the
progression of the study or trials.
• If the changes during progress of study are minor, then that part of the study should be
excluded from the analysis.
• Unless unexpected complications occur during the conduct of the trial, it is
advisable to reconsider and rewrite the protocol where the whole process is
started again provided that the original research topic is still considered to be
relevant.
• If complications are anticipated, it is suitable to run a pilot study, to check the
feasibility of the study and find answers to the potential areas of the trial
Components of A Research Protocol

• 1) Title of the study

• 2) Administrative details
• 3) Project summary
• 4) Introduction to the research topic, background (Literature review)
• 5) Preliminary studies
• 6) Study objectives and/or questions. Statement of the problem.
Components of A Research Protocol

• 7) Methodology: Study design, study population and methods of recruitment, variables

list, sample size, methods of data collection, data collection tools, plan of analysis
(analysis of data)
• 8) Project management: Work plan (Timeline - proposed schedule)
• 9) Strengths and limitations of the study
• 10) Issues for ethical review and approvals
Writing The Protocol
• Protocol writing allows the researcher to review and critically evaluate the
published literature on the interested topic, plan and review the project
steps and serves as a guide throughout the investigation.
• The proposal is an inevitable document that enables the researcher to
monitor the progress of the project .
1) Title of The Study:

• Title of proposal should be accurate, short, concise, and identify

• What is the study about, Who are the targets, Where is the setting of the study and
When it is launched, if applicable
1) Title Of The Study:

• It should make the main objective clear, convey the main purpose of the research and
mention the target population.
• Carry maximum information about the topic in a few words; it is a good practice to
keep the title to within 12-15 words.
• It should convey the idea about the area of research and what methods are going to be
used in a compact, relevant, accurate, attractive, easy to understand, and informative way
2) Administrative Details:

• The following administrative details and a protocol content summary should follow the
title page:
• Contents page list of relevant sections and sub-sections with corresponding page
number.
• Signature page is signed by senior members of the 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
3) Project Summary:

• The summary should be distinctive, concise and should sum up all the
essentials of the protocol
4) Introduction (Background):

• the background to the project should be concise and refer to the subject straight forwardly.
• In writing the review, attention should be drawn to the positives, negatives and
limitations of the studies quoted.
• Introduction is concluded by explaining how the present study will benefit the community.
• The literature review should logically lead to the statement of the aims of the proposed
project and end with the aims and objectives of the study.
4) Introduction (Background):

• The review should include the most recent publications in the field and the
topic of the research is selected only after completing the literature review
and finding some gaps in it.
• Introduction should briefly answer the importance of the topic, the
gaps/lacunae in the literature, the purpose of the study and benefits for the
society, from the study
4) Introduction (Background):

• The research question should be described precisely and concisely.

• It is going to be the basis of designing the project.
• The definition of the problem should be clear so that a reader can straight forwardly
recognize the real meaning of it
5) Study Objectives (Aims):

• The aims should be explicitly stated. These should be confined to the intention of the project and
they should arise from the literature review. State the goal you need to achieve.
• The study aims or objectives emerge from the study questions/ hypothesis.
• They are answers to what are the possible responses to the research question or hypothesis under
analysis and measure.
• Aims should be logical and coherent, feasible, concise, realistic, considering local conditions,
phrased to clearly meet the purpose of the study and related to what the specific research is
intended to accomplish.
5) Study Objectives (Aims):

• For example, to evaluate knowledge level regarding dental caries in primary school
children in Yemen (this is not detailed).
• The following should be added: Causes, treatment, preventive measures, etc.
• The objectives should be (SMART objective): Specific, Measurable, Achievable,
Relevant and Time based
Specific Aims:

• Details of each objective that will finally lead to the achievement of the goal should be stated.
Specific aims one by one should be listed concisely.
• It is good practice not to include too many aims in the study (2-5 best); too many objectives often
lead to inaccurate and poorly defined results.
• Furthermore, aims should be achievable, realistic and specific with no general and ambiguous
statements.
• They 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.”
Secondary Objectives (Optional):

• These are referred to as ancillary and minor objectives that could be studied during the
course of the study.
• The formulation of objectives helps to focus the study and to avoid the collection of any
unnecessary data and hence organize the study in clear and distinct stages
HYPOTHESIS:

• It is a statement based on sound scientific theory that recognizes the predicted correlation
between two or additional assessable variables .
• It is always developed in response to the purpose statement or to answer the research
questions posed.
• Furthermore, hypothesis transforms research questions into a format amendable to testing
or into a statement that predicts an expected outcome
HYPOTHESIS:

• Types of hypothesis statements:

• Null hypothesis:
• A null hypothesis is a statement that there is no actual relationship between variables (H0 or HN).
• It may be read as there is no difference between the groups to be compared and no relationship between the exposure
and outcome under investigation.
• H0 states the contradictory of what the researchers expect.
• The final conclusion of the investigators will either keep a null hypothesis or reject it in support of an alternative
hypothesis.
• It does not essentially mean that H0 is accurate when not rejecting it as there might not be an adequate proof against it.
HYPOTHESIS:

• Alternative hypothesis
• An alternative hypothesis is a statement that suggests a potential outcome that the researcher may
expect (H1 or HA). This hypothesis is derived from previous studies where an evident difference
between the groups to be compared is present.
• It is recognized only when a null hypothesis is rejected.
• Practically, hypotheses are stated in the null form, because they have their inferential statistics.
• Such hypotheses of no difference will be challenged by researchers and the result of the statistical
testing gives the probability that the hypothesis of no difference is true or false.
HYPOTHESIS:

• Aims should be logically linked and arranged according to the tested hypothesis statement.
Example:
• Research question: Is there a difference in fluoride release between the Compomer and
Glass- ionomer cement?
• Null Hypothesis: There is no difference in fluoride release between the Compomer and
Glass- ionomer cement.
• Alternate Hypothesis: There is a difference in fluoride release between the Compomer
and Glass-ionomer cement
HYPOTHESIS:

• The statement of the problem should provide a summary of exactly what the project is
trying to achieve.
• What exactly do you want to study?
• Why is it worth studying?
• Does the proposed study have theoretical and/or practical significance?
• Does it contribute to a new understanding of a phenomenon? (i.e., Does it address new
or little known material or does it treat familiar material in a new way or does it challenge
an existing understanding or extend existing knowledge?)
HYPOTHESIS:

• The justification of the research should be a convincing statement for the need to
do it:
• 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?
6) METHODS AND MATERIALS:

• It should describe in detail the ‘Where’, ‘Who’, ‘How’ the research will be conducted.
• It explains the study design and procedures and techniques used to achieve
the proposed objectives.
• It defines the variables and demonstrates in detail how the variables will be measured. It details the proposed
methodology for data gathering and processing.
• Methodology composes an important part of the protocol. It assures that the hypothesis will be confirmed or
rejected. It also refers to a thorough strategy to attain the objectives

• The methods and materials are divided into various subheadings:

6) METHODS AND MATERIALS:

• a) study design (cross-sectional, case-control, intervention study, RCT, etc.):

• Proper explanation should be given as to why a particular design was chosen (on the basis
of proposed objectives and availability of resources).
• A study design is in fact the researcher’s general plan to acquire the answer (s) to the
hypothesis being tested. Here, strategies will be applied to develop balanced, correct,
objective and meaningful information
• It explains the methods that will be used to collect and analyze data. Proper selection of
the study design is important to attain reliable and valid scientific results
6) METHODS AND MATERIALS:

• Ethics, logistic concerns, economic features and scientific thoroughness will determine
the design of the study.
• Here, a chief concern is given to the legality of the results including potential bias
mystifying issues.
• Randomized controlled clinical trial is the best to document a causal relationship between
an exposure and its outcome
6) METHODS AND MATERIALS:
6) METHODS AND MATERIALS:

• b) study population (study subjects): Where are you going to do the research and who is the
study population (why doing research in this place and why selecting this population?).
• It describes in detail about the study subjects, all aspects of the selection procedure and sample
size calculation.
• Proper definition of eligibility, inclusion, exclusion and discontinuation criteria of the study
subjects should be stated.
• Allocation of subjects to study arms should be explained and described in details bearing in
mind the concealment and randomization process
6) METHODS AND MATERIALS:

• c) sample size:
• Sample size calculation is recommended for economical and ethical reasons
• The calculation of the sample size must be explained including the power of the sample.
The sampling technique should be mentioned, e.g., randomization that will be used in order to obtain
a representative sample for your target population.
• Each step involved in the recruitment of the study subjects should be described according to the
selection criteria (inclusion and exclusion criteria)
• “Informed consent” should be mentioned (Permission granted in full knowledge of the possible
consequences).
6) Methods and Materials:

• d) Proposed intervention: Full description of proposed intervention should be given. Here, all the activities
and actions should be recorded and thoroughly explained in their order of occurrence.
• When using drugs, both scientific and brand name should be mentioned followed by the name of the
manufacturing company, city, and country.
• Drug route, dosage, frequency of administration, and total duration of treatment with the drug should be
mentioned.
• When using apparatus its name should be given followed by the name of the manufacturer, city and country.
Involved personnel should precisely define:
• Who will be responsible for the interventions?
• What activities each personnel will perform and with what frequency and intensity?
6) Methods And Materials:

• e) Data collection methods, instruments used:

Data collection tools are:
• Retrospective data (medical records)
• Questionnaires
• Interviews (Structured, Semi-Structured)
• Laboratory test (literature or personal knowledge should be referenced, if established test, or
description should be provided in details, if not established)
• Clinical examinations
• Description of instruments, tools used for data collection, as well as the methods used to test the
validity and reliability of the instrument should be provided
7) Data Management And Analysis Plan

• This section 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.
• Names of variables that will be used in the analyses and the 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
8) Project Management:

• Work plan-A work plan is an outline of activities of all the phases of the research to be
carried out according to an anticipated time schedule.
• Proper time table for accomplishing each major step of the study should be defined.
Assigning time frame to each step in the trial will be helpful in organizing the structure of
the research trial.
• The personnel (investigators, assistants, laboratory technicians etc.)
involved in the study or data collection should be properly trained
9) Strengths And Limitations

• 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 allocation of
resources
10) Ethical Considerations (Issues For Ethical Review
And Approvals)
• It should indicate whether the procedures to be followed are in accord with the Declaration of
Helsinki.
• In any case, study should not start unless approval from ethics committee is
received .
The following points should be explained:
• The benefits and risks for the subjects involved. The physical, social and psychological implications
of the research.
• Details of the information to be given to the study patients including alternative
treatments/approaches.
10) Ethical Considerations (Issues For Ethical Review
And Aprovals):
• Information should be provided on the free informed consent of the participants.
Information form should contain:
• Justification for research, outline of study, risks, confidentiality, and voluntary
participation should be told patients about the freedom to withdraw from the study
whenever they wish to.
• Confidentiality indicates how the personal information obtained from the patient will be
kept secret (Data safety).
11) Operational Planning And Budgeting (Budget Summary):

• Outline the budget requirement showing head wise expenditure for the study-manpower,
transportation, instruments, laboratory tests, and cost of the drug. Budget estimate is to be
attached in the annexure.
• All costs including personnel, consumables, equipment, supplies, communication, and
funds for patients and data processing are all included in the budget.
• Each item should be justified
12) Reference System:

• Referencing is the regular method of recognizing information taken from other

researchers’ work. A
proper citation will enable the readers to follow-up any reference of interest.
• Plagiarism refers to claiming and acquiring someone else’s ideas, an action that is
considered a criminal action.
• Failure to reference an idea that you have found in your research, or to acknowledge the
work of other team members in a team assignment falls under the category of plagiarism.
12) Reference System:

• Therefore referencing is an extremely important aspect of the research protocol.

• The two most commonly used citation systems in clinical writing are the Vancouver system
and the Harvard system.
• The choice of referencing system is dependent upon the funding organizations where the
research protocol is being submitted.
• These frequently identify their preferred system of referencing and
• this should be strictly adhered to. The most common style used in the dental literature is
Vancouver style.
13) Annexure

• The following annexes are to be attached at the end of the protocol:

1. Informed consent form.
2. Letters from ethics committees.
3. Study questionnaire (copies of any questionnaires or draft questionnaires).
4. Case Record Forms (CRFs).
5. Budget details.
6. Curriculum Vitae (CV) of the chief investigator and coinvestigator and their role in the study. It
will ensure that the role of each investigator is well defined.
How To Judge A Good Protocol?

• The protocol should adequately answer the research question.

• The research design must be sound enough to yield the expected knowledge.
• It should provide enough detail (methodology) that can allow another
investigator to do the study and arrive at comparable conclusions.
• Here, the proposed number of participants is reasonably justifed and the
scientifc design is adequately described
Common Mistakes (Common Pitfalls To Avoid)

• Incorporating insufficient elements regarding proposed studies and inadequate

explanation for the implication of the problem must be shunned as well as
suggesting far more work than can be practically done during the study period.
• Furthermore, underpowered sample size should be justified, invalid or
unreliable instrumentation should be tested and improper statistics should be
adequately analyzed
CONCLUSION

• The most difficult stage of conducting a research project is the preparation of a protocol
that results in a short yet comprehensive document that clearly summarizes the project.
Such proposal is considered successful when it is clear, free of typographical errors,
accurate and easy to read.
• It is important to understand the steps in developing a research protocol in order to
perform an appropriate study and obtain reliable results.
CONCLUSION

• Extra time spent to write a good protocol will save failures at a later stage besides helping
analysis.
• If the protocol is poorly prepared and not adhered to, it is unlikely that the project will
yield the information that you hope for and in all probability the chances of selling your
idea to the reviewers of a granting agency would beless .