The way things are going to be

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The way things are going to be

• Writing a protocol for an epidemiological study
• FETP India

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Competency to be gained from this lecture

• Write a protocol for an epidemiological
  investigation

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Key areas

• Concept paper
• First draft of the protocol
• Review

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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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The life cycle of an epidemiological investigation
Identifying data needs
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Working with public health managers to identify
data needs

• Identify public health problems
• Estimate public health importance
• Analyze problems
• Review what is being already done
• Identify the information needed to improve

Concept paper
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The research question

• Frames the problem in public health terms
• Focuses on one issue
• Is written in everyday language
• Can use more than one verb
• Is general
• Should link the question to the potential action
  that would be taken once the question is answered

Concept paper
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The research question Example

• We would like to understand why some tuberculosis
  patients do not complete their DOTs treatment so
  that we could address these issues and improve
  completion rate

Concept paper
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The study objectives

• Frame the problem in epidemiological terms
• Take the question in a few limited axis
• Is written using epidemiological language
• Make use of no more than one verb each
• May be sorted out as primary and secondary
• Should be clear about whether
• They call for testing a hypothesis
• They call for measuring a quantity

Concept paper
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Study objective Example

• Compare defaulters and non defaulters in terms of
  a number of characteristics that may be
  associated with observance among tuberculosis
  patients treated with Directly Observed Therapy
  (DOTs)

Concept paper
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First step, in practice

• Write a short presentation
• Summarize the background
• Start from a problem statement
• Document the importance of the problem
• Analyze causes and consequences
• Summarize what is being done to address it so far
• Make an inventory of the known and the unknown
• Write the research question
• Specify the study objective
• Anticipate what would be done with results in
  hands
• Share with public health managers, mentors
• Revise, revise and revise

Concept paper
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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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Rationale for using a one-page concept paper

• Time is precious
• For you
• For your supervisor
• Brevity forces focus
• Many concept papers are not developed
• Save time for an idea that may abort

Concept paper
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Outline of the one-page, bullet-style, concept
paper

• Background and justification
• Objectives
• Methods
• Expected benefits
• Budget

Concept paper
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Outline of the one-page, bullet-style, concept
paper

• Background and justification
• Importance of the problem
• What is being done to address it
• The information that is missing to prevent/
  control more effectively
• Objectives
• Methods
• Expected benefits
• Budget

Concept paper
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Background and justificationExample

• In India, anemia is common among adolescent
  girls, particularly tribes
• The Government of India supplements adolescent
  girls with iron and folic acid in several states,
  but not in Madhya Pradesh
• It is unclear whether it is feasible to
  supplement tribal adolescent girls with iron and
  folic acid in Madhya Pradesh

Concept paper
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Outline of the one-page, bullet-style, concept
paper

• Background and justification
• Objectives
• 2-3 objectives
• Can be general and specific
• Can be primary and secondary
• Methods
• Expected benefits
• Budget

Concept paper
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Objectives Example

1. To estimate the prevalence of iron deficiency
   anemia among adolescent girls before and after a
   pilot supplementation intervention
2. To identify the factors associated with coverage

Concept paper
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Outline of the one-page, bullet-style, concept
paper

• Background and justification
• Objectives
• Methods
• Outline of the methods
• One bullet per point
• Expected benefits
• Budget

Concept paper
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Outline of the methods

• Study design    
• Study population
• Operational definitions
• Sampling procedure
• Sample size
• Data collection
• Analysis plan
• Human subjects protection

Concept paper
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Methods Example (1)

• Study design
• Pilot intervention with pre and post cross
  sectional studies
• Study population
• Adolescent tribal girls aged 12-19 years, Mandla
  district, MP, India
• Operational definitions
• Use of WHO criteria to define anemia

Concept paper
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Methods Example (2)

• Sampling procedure
• Cluster sample of the study population
• Sample size
• Considering 95 confidence interval, 20 ? error,
  allowing 20 dropout, expecting a difference of
  1g of hemoglobin level, a total of 168
  adolescent girls will be required

Concept paper
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Methods Example (3)

• Data collection
• Field worker will collect data under supervision
  from primary investigator
• Baseline and post intervention estimation of Hb
  using cyanmethaemoglobin method
• Collection of data using semi-structure
  questionnaire on demographic characteristics,
  knowledge and socio-cultural practices after the
  intervention

Concept paper
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Methods Example (4)

• Analysis plan
• Descriptive and multivariate analysis of data to
• Estimate the prevalence of anemia before and
  after
• Identify factors associated with (a) tablet
  consumption and (b) anemia in the post
  intervention phase
• Human subjects protection
• Confidentiality protection
• Written informed consent will be obtained from
  adolescent girls and their guardians
• Protocol submitted for ethical clearance

Concept paper
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Outline of the one-page, bullet-style, concept
paper

• Background and justification
• Objectives
• Methods
• Expected benefits
• What action will be taken following results
• Future operational research agenda
• Budget

Concept paper
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Expected benefits Example

• Output
• Documented report shared with local health
  authorities
• Outcome
• Enable local authorities to implement the
  programme on a larger scale after taking
  cognizance of compliance issues identified
  through the study

Concept paper
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Outline of the one-page, bullet-style, concept
paper

• Background and justification
• Objectives
• Methods
• Expected benefits
• Budget
• 4-5 lines
• No detailed justification
• Divided in salaries/per diem, travel, equipment
  supply and miscellaneous

Concept paper
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Budget Example

• Per diem
• USD 1500
• Travel
• USD 1500
• Supplies
• Laboratory reagents, drugs, stationary)
• USD 2000
• Total
• USD 5000

Concept paper
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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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Dummy table for iodine deficiency study
(Analytical stage)

Prevalence Prevalence Prevalence ratio (95 confidence interval)
Exposures Exposed Unexposed Prevalence ratio (95 confidence interval)
Female sex XX/XX (XX) XX/XX (XX) XX (XX-XX)
Muslim XX/XX (XX) XX/XX (XX) XX (XX-XX)
Age gt 30 XX/XX (XX) XX/XX (XX) XX (XX-XX)
Below poverty line XX/XX (XX) XX/XX (XX) XX (XX-XX)
Schedule caste XX/XX (XX) XX/XX (XX) XX (XX-XX)
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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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The first draft of the protocol

• Thought as it is written
• Uses the concept paper outline
• Keeps concept paper as summary
• Does not exceed 2000 words
• Introduction lt 20 of length
• Contains 5 10 key references

First draft
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The outline of the protocol is identical to the
outline of the concept paper

• Background and justification
• Objectives
• Methods
• Expected benefits
• Budget

First draft
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Outline of the protocol

• Background and justification
• Objectives
• Methods
• Expected benefits
• Budget

Take from concept paper
First draft
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Outline of the protocol

• Background and justification
• Objectives
• Methods
• Expected benefits
• Budget

Expansion of the concept paper with full
sentences and few additional details
First draft
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Outline of the protocol

• Background and justification
• Objectives
• Methods
• Require many more additional details
• Expected benefits
• Budget

First draft
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Outline of the methods

• Study design   
• Description of the interventions     
• Study population
• Operational definitions
• Sampling procedure
• Sample size
• Data collection
• The analysis plan
• Quality assurance
• Human subjects protection

First draft
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Study design paragraph   

• Explains how the objectives lead to indicators
  and to the study design
• Describes the type of study
• Cohort
• Case control
• Cross sectional
• Describes logistical arrangements
• Prospective
• Retrospective

First draft
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Description of the interventions     

• Applicable if an intervention is planned
• Clinical trial
• Community intervention
• Describes the treatment applied to the
  intervention and control group
• Who?
• What?
• When?
• How?

First draft
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Study population paragraph

• Use time, place and person
• Inclusion criteria
• Exclusion criteria
• May be added as a separate section but do not
  differ conceptually from the inclusion criteria
• Do not confuse the study population and the study
  sample
• Ensure that the study population is suitable to
  address the objectives

First draft
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Operational definitions paragraph

• Spells out and justifies
• Key outcomes
• Key exposures
• Clarity and specificity essential
• References if applicable

First draft
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Sampling procedure paragraph

• Describes and justifies
• The type of sample used
• Convenience sample (Avoid if possible)
• Random sample
• Systematic sample
• Cluster sample
• The way the sample will be selected in practice
• Provides references if needed
• Explains randomization if applicable

First draft
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Sample size paragraph

• Details all parameters used to estimate the
  sample size
• Explains how the estimate was generated
• Software used
• Formula used
• Provides references if needed

First draft
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Data collection paragraph

• Lists the data that will be collected
• Headings
• Bullet points
• Specifies how the data will be collected
• Who?
• How?
• Type of instrument to be used
• Type of data collection method

First draft
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The analysis plan paragraph

• Data entry
• Software used
• Recoding stage
• Descriptive stage
• Prevalence, incidence
• Analytical stage
• Univariate
• Stratified
• Multivariate analysis

First draft
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Quality assurance paragraph

• Details the steps that will be used to ensure
  data quality at all stages
• Addresses
• Protocol writing
• Data collection
• Data entry
• Data analysis
• Reporting

First draft
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Human subjects protection paragraph

• Explains the steps that will be used to protect
  human subjects
• Addresses
• Minimization of risks (Confidentiality)
• Maximization of benefits
• Compensations (without undue incentive)
• Informed consent
• Approval procedures (Ethical committee)

First draft
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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Write the first draft of the protocol
4. Prepare instruments and annexes
5. Submit to peer review
6. Propose to ethical committee
7. Finalize

First draft
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Data collection instruments

• Present all data collection instruments
• Questionnaires
• Abstraction forms
• Structured observation guides
• Drafts may evolve as the protocol evolves

First draft
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Annexes

• Procedures
• Training framework for field workers
• Patient recruitment material
• Adverse event management form
• Consent forms

First draft
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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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Rationale of peer review

• Obtain feedback
• Ensure quality
• Facilitate ethical committee approval

Review
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Peer review

• Submit to experts and colleagues
• Methodological experts
• Subject matter experts
• Ask for comments and suggestions
• Document how comments and suggestions were
  addressed
• Inclusion of the suggestions
• Reason for non inclusion

Review
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The seven steps of a successful protocol

1. Identify topic, question and objectives
2. Outline a one-page concept paper
3. Prepare dummy tables
4. Write draft protocol
5. Prepare instruments and annexes
6. Submit to peer review
7. Seek ethical committee clearance

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Rationale of ethical committee

• Protect human subjects
• Document conformity to principles
• Ensure quality

Review
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What protocol are submitted to the ethical
committee?

• All research protocols
• Even if no intervention
• Evaluation protocols that may expose participants
  to risks
• Only the ethical committee can make a decision of
  exemption

Review
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Ethical committee approval

• Obtain guidance
• Prepare protocol and annexes
• Write cover letter
• Obtain feedback
• Follow directions and include requested changes

Review
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Finalizing a protocol

• Disseminate
• Keep and use for reference
• Use for report writing
• Archive

Review
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Take home messages

• Always start with a concept paper
• Unfold the protocol logically from the objectives
  
• Revise, revise and revise

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Additional resources on protocol writing

• Concept paper
• Example
• Template
• Case study on protocol writing (Scrub Typhus in
  Darjeeling, Volume 2)
• Template protocol
• Guide to common errors in protocols (with
  checklist)
• Dummy tables for field epidemiology