Framing a Research Question and writing a Protocol

Dr. Biju George

What is protocol
Formal document outlining the proposed study and helps the researcher(s) to get organized. Submitted to an academic institution such as a teaching hospital, research facility or funding agency to get an approval.

Protocol should explain the study in terms of answers to the following questions
Why ? Sets out the questions and the relevant background information. Why we should embark on this particular research problem. How ? Describes the study design and the rational for choosing it. Also describes Instruments / techniques to be used Who ? Defines the targets and the study population and sample size.

Protocol should explain the study in terms of answers to the following questions
What? Identifies the variables to be measured and outcomes to be analyzed. Where? Explain the study setting, and why it is most suited for the purpose When? Describe the study period and duration of study, follow up, frequency of follow up etc. So What? Expected significance of results and contribution.

Components of protocol
Title Introduction Objective(s) / research question Methodology / material and methods References Performa / questionnaire / data collection sheet

Title
Concise titles are easier to read and understand. Indicate the studys design with a commonly used term in the title. Omit waste words such as "A study of... "Investigations of ..." "Observations on ..."

Introduction
Explain the scientific background and rationale for the intended study Places your work in the current information context Provide only directly pertinent references Should catch the readers attention Gives readers enough information to appreciate your objectives This should naturally lead to your objectives

Objective(s) / Research Question

State specific objectives/ question(s) Primary/ Secondary objectives

Arise directly from your research question

How to find questions

Pure inspiration (rare) Critical reading of published papers A conference or seminar Observing/talking to a patients Speaking to other researchers / colleague New technologies bring in new questions

Good ideas come only to..

The prepared mind One with a skeptical attitude about prevailing beliefs.

Framing the research question

A general idea has to be converted into a research question by

1. 2. 3. 4.

What measurable variables Who subjects, controls Where - location How method

Characteristics of a good question

Novel Relevant Measurable Feasible Impact Ethical

Novelty

Can seek to provide new findings or refute or extend previous findings All studies need not be novel
Different study population Confirmatory study avoiding weaknesses of the previous study Some previous observations need to be replicated

Improved technology or new methods

Trans-cuteaneous Bilirubinometer
Is TCB measurement can be used to replace serum TB measurements Is their a good correlation between TCB measurement and serum TB measurement Can TCB measurement on day 1 predict the neonatal hyperbilirubinemia Will skin colour affect the TCB measurements Is TCB measurement correlate well with serum TB in preterm / term / LBW babies

Is it of importance here and now?

Relevance

Advance scientific knowledge by resolving uncertainties in a given area Lead to changes in existing clinical and health policy Provide direction to future research
Post traumatic stress disorders in people who had whiteness the gas tanker explosion Health consequences of loud noise for over 3 hours a day for over six months? What are the practices by traditional midwives that may be hazardous to the babys health?

Measurability

Provide details of methodology- doing what, to whom, for how long, to achieve what effect? Be as specific as possible
moderate reduction of Cholesterol habit 40% reduction in average cholesterol level Reduction of cholesterol by 20 mg% obesity replaced by body mass index Regular Exercise replaced by Walking at moderate speed for 30 minutes at least 5 times a week for 2 months

Feasibility
Can I do it ?

Manageable in scope, Affordable in time and money, Required technical expertise Number of subjects should be realistic but large enough to eliminate random error

Diagnostic efficacy of rapid detection kit in identification of malarial infection compared to peripheral smear examination? Campaign of Rubella vaccination in the state resulting in reduction in incidence of birth defects?

Impact
Reduction in mortality/ disease occurrence / complication / severity of disease Identification of prognostic factor / risk factor / risk group Clinical picture description / mortality pattern / morbidity description / disability description

from research topic to research question

Topic - Apthous ulcer
Magnitude of the disease Risk factors of the disease Treatment Prevention methods Cost related Large scale program effectiveness

How to go about

from research topic to research question

Topic - Apthous ulcer
Magnitude of the disease

How to go about

What id the prevalence of apthous ulcer What is the incidence of apthous ulcer

from research topic to research question

Topic - Apthous ulcer
Risk factors of the disease

How to go about

What are the risk factors of the Apthous ulcer Is Stress in the past 2 days, an important risk factor foe development of Apthous ulcer

from research topic to research question

Topic - Apthous ulcer
Treatment

How to go about

Is predinisolon tablet powder applied in the lesion produce early cure than saline gargle

from research topic to research question

Topic - Apthous ulcer
Prevention methods

How to go about

Will gargling mouth with Tulsi extracts prevent development of apthous ulcer compared to saline gargling

Research question to Refined Research question

The research question

1. Topic ALL (Acute Lymphoblastic Leukemia) 2. Idea ALL in North Kerala - What are the causes? Is nearness to saw mill a cause? 3. Question What are the causes of ALL? 4. Operationalizing the question What are the risk factors of ALL 5. Refine the question further

Refining the question further

What are the risk factors of ALL What are the risk factors for ALL in patients admitted to IMCH, Calicut, as compared to control children with ARI admitted in pediatrics wards of the same hospital?

1. What measurable variables

Risk factors ALL Patients admitted Controls who do not have ALL ( patients with ARI) IMCH, Calicut Medical college Compare

2. Who subjects, controls

3. Where location 4. How method

 Is the antibiotic X effective in mild leptospirosis? Is the antibiotic X (500 mg orally 6th hourly) effective in mild leptospirosis? Is the antibiotic X (500 mg orally 6th hourly) effective compared to Inj. crystalline Penicillin (given every 6th hourly) in mild leptospirosis? Is the antibiotic X (500 mg orally 6th hourly) effective compared to Inj. crystalline Penicillin (given every 6th hourly) in faster clinical and biochemical improvement in mild leptospirosis?

 Is the antibiotic X (500 mg orally 6th hourly) effective compared to Inj. crystalline Penicillin (given every 6th hourly) in faster clinical and biochemical improvement in patients with fever and a leptospiral IgM ELISA positivity but without heapto-renal involvment?

Methodology
Design
Case series, cross sectional, cohort, case control, RCT

Randomized Controlled Trials

Cohort Studies

Case Control Studies

Case Reports/ Case Series

The most basic descriptive study. Link between clinical medicine and epidemiology Hypothesis generating. Rarely the evidence can even be strong!!

Case Series
Australian gynaecologist, Dr. McBride of Sydney, suspected that thalidomide was the cause of limb and bowel malformations in three children he had seen at Crown Street Women's Hospital. 1956

Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency 1981 Dec 10;305(24):1425-31. MS Gottlieb, R Schroff, HM Schanker, JD Weisman, PT Fan, RA Wolf, and A Saxon

Methodology
Setting and study period
Describe the setting, locations, and why you have choose the specific location. Biases related with it. Relevant time periods related to the study, including periods of recruitment, follow-up, and data collection

Methodology
Participants
Selection of participants , including eligibility and exclusion criteria and a description of the source population. If only samples will be taken, explain the sampling procedure. Researcher should explain why only certain groups were included or why some groups were excluded

Methodology
Variables
Study variables, Exposure factors, outcome factors, Baseline factors. Primary and secondary exposure factors / outcome factors Definition of variables Composite variables explain components New scoring, its rationale

Methodology
Data source
Questionnaires Interview Case records Clinical examination Investigation data

Methodology
Measurements
Data collection methods- BP mercury sphygmomanometer / electronic , position Equipments used Way of measurements

Methodology
Interventions

if RCT

Details of interventions Dose, frequency, route of administration, stoppage rules

Randomization
Process, allocation ratio, block size, concealment

Blinding
Single blinding / double blinding

Methodology
Sample size
Number proposed in each group of study Justification

Proposed Statistical analytic strategy

Propose statistical methods in enough detail

Ethical aspects
Consent confidentiality

References
Provide only directly pertinent key references related to
Key articles in this area and their results Lack of information in the topic Key articles in related to the methodology

Few number of reference only

Performa / questionnaire / data collection sheet

Collect only those data which are absolutely needed for achieving for the objective ( both primary and secondary objectives) May be coded in the sheet it self

Additional requirements for funding agencies

Budgeting Manpower requirements Time line chart Intended beneficial effects from this research A synopsis of protocol

Reporting Guidelines
Use it to prepare the protocol to get all subheading

STROBE Statement STrengthening the Reporting of OBservational studies in Epidemiology observational epidemiology www.strobe-statement.org/

CONSORTCONsolidated Standards of Reporting Trials

for RCT parallel trials www.consort-statement.org/

STARD Statement STAndards for the Reporting of Diagnostic accuracy studies

for diagnostic evaluation studies www.stard-statement.org/

STREGA statements STrengthening the REporting of Genetic Associations www.medicine.uottawa.ca/public-healthgenomics/web/eng/strega.html

Thank you