How to write a protocol?
Dr. Anirban Hom Choudhuri (MD, FICCM, PGDMLE, FIAMLE)
Professor (Critical Care)
GIPMER, New Delhi
Clinical research follows an action plan
Clear pathways must be existent & should be demonstrable
Must be approved and monitored by the IRB/IEC upon its
satisfaction that-
The project is worth undertaking for scientific gains
Investigator(s) have the necessary competence and work experience
No scope for ethical violations & infringements of participants’ rights
Requirements & limitations are adequately explained
All of these are documented in Research protocol
After the study is launched, the protocol cannot not
be altered during its course
What purpose does it serve?
Raises the research question and clarifies its importance
Serves as guide through the research
Forces time and budget estimates
More proper is the draft, more likelihood are chances of
scientifically sound conclusions being drawn
Components of the protocol
Title Methodology: Study design,
study population and methods of
recruitment, variables list, sample
Administrative details size, methods of data collection,
data collection tools, plan of
Project summary analysis (analysis of data)
Introduction Project management: Work
plan (Timeline - proposed
schedule)
Preliminary studies
Strengths and limitations
Study objectives
Prior approvals, if any
Biodata/CV
Title
Should carry maximum information in few words
Good to keep within 12-15 words
What is the study about, who are the targets, what is the
setting
Epidemiology and characteristics of VAP in Indian ICUs
Etiology, prevalence & course of VAP in Indian ICUs
Etiology, prevalence, clinical profile and outcome of VAP
in Indian ICUs
Administrative Details
Contents page - list of relevant sections and sub-sections with
corresponding page number
Signature page - signed by members of the research team and dated
to confirm that the version concerned has been approved by them
Contact details- for the PI listing postal, e-mail addresses and
telephone numbers
Project Summary
Distinctive and concise
Should sum up all the essentials of the protocol
Should stand on its own
Introduction (Background)
Should answer the importance of the topic, the gaps in the
literature, the purpose of the study and possible benefits
for the society from the study
The research question should be addressed concisely
The problem should be clearly recognizable to the reader
Positives, negatives and limitations of the earlier studies
Aims & Objectives
Aims- broad statements of desired outcomes, or the general
intentions of the research
Objectives are subsidiary to aims
Should be (SMART objective): Specific, Measurable,
Achievable, Relevant and Time based
Should not have too many aims and only include objectives
consistent with the aims
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.”
Generation of hypothesis
Statement based on scientific theory that recognizes the
predicted correlation between two or more variables
Transforms research questions into a statement that predicts
an expected outcome
Null hypothesis: a statement that there is no actual
relationship between variables (H0 or HN)
Alternative hypothesis: a statement that suggests a potential
outcome that the researcher may expect (H1 or HA)
Is there a difference in BNP levels between
heart failure with low EF and normal EF?
Null Hypothesis: There is no difference in BNP levels between heart failure with
low EF and normal EF
Alternate Hypothesis: There is difference in BNP levels between heart failure
with low EF and normal EF
The final conclusion of research will either accpet a null
hypothesis or reject it in favour of an alternative
hypothesis
Practically all hypotheses are stated in the null form,
because they have their inferential statistics
Aims should be logically linked and arranged
according to the tested hypothesis
Materials & methods
Should describe in detail - ‘Who’, ‘Where’ and ‘How’ will
conduct the research
Divided into various subheadings
Study design
Study population
Sample size (if calculated)
Proposed intervention, if any
Data collection methods & instruments
Study design
Proper explanation as to why a particular design is chosen
Ethics, logistic concerns, and scientific thoroughness
Object Common design
Prevalence Cross sectional
Incidence Cohort
Cause (in order of reliability) Cohort, case control, cross sectional
Prognosis Cohort
Treatment effect Controlled trial
Study population (Study subjects)
Definition for eligibility, inclusion, exclusion & discontinuation
In clinical trials, allocation of subjects to study arms
Concealment and randomization process, if applicable
Sample & sampling techniques
Sample size calculation is recommended for both economical
and ethical reasons
Power of the study
Sampling technique
Steps involved in the recruitment of subjects should be
described according to the selection criteria
“Informed consent”
Proposed intervention
When using drugs, both pharmacological and brand name
should be mentioned followed by the name of the
manufacturing company 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 and country
Who will be responsible for the interventions?
What activities each personnel will perform and with what
frequency and intensity?
Data collection methods & instruments
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
Data Management and Analysis Plan
The analysis plan and statistical tests that will be used to
answer the research question, with appropriate references
Chosen variables and their appropriate tests
For computer programs, their software versions
Good to write after seeking advice from a statistician
Project Management
Outline of activities of all the phases of the research to be carried
out according to an anticipated time schedule (‘Work plan’)
Proper time table for accomplishing each major step
Operational Planning and Budgeting
Head wise expenditure for the study-manpower,
transportation, instruments, laboratory tests, drugs etc.
Budget estimate as attached annexure
Costs including personnel, consumables, equipment,
supplies, communication, and funds for patients and data
processing
Justification
Annexure
Informed consent form (English, Hindi, vernacular)
Patient information sheet
Approval letters from departmental committees, other scientific
committees etc.
Photocopy of questionnaire , study instruments (if any)
Case Record Forms (CRFs)
Budget details & COI (if any)
CV of the investigators
Common Pitfalls to Avoid
Insufficient information about recent studies and improper
explanation of the problem
Underpowered sample size
Invalid or unreliable instrument
Improper statistics
Conclusion
Short yet comprehensive to clearly summarize the project
Language must be clear, free of typographical errors, accurate
and easy to read
Extra time spent to write a good protocol can save time at a
later stage
Not always easy!
