Basic Research Methodology

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Basic Research Methodology

• Dr. J.P. Majra
• Associate Professor
• Community Medicine

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Research

• Research is mainly a process by which we answer a
  question, using a set of rules called scientific
  methods.
• Research essential for
• Advancement of scientific knowledge and/or
• development of newer technologies and treatment
• Todays research is tomorrow's medicine

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Researcher has to see what every one else has
seen and to think what no one else has thought.
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• Roosevelt
• Stalin
• Churchill

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• Paracetamol
• Kaolin pactin mixture

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• I keep six honest serving men
• They taught me all I know
• Their names are What and Why and
• When and How and Where and Who
• Rudyard Kipling-1903

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Why undertake research

• Academic requirements
• Participating in a scientific meet
• Career prospects
• Peer pressure
• Planning implementing and evaluating health care
  services
• Generating evidence for better/ effective
  management

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Remember

• Doing research is imperative
• Doing good research is a choice
• Doing beneficial research with sound methods is a
  possibility
• Generating evidence for improving clinical and
  public health outcomes is to be the goal.

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Characteristics of research

• Systemic and critical investigation into a
  phenomenon
• Purposive investigation- describing, interpreting
  and explaining phenomenon
• It adopts scientific methods
• It is objective and logical

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Characteristics of research

• It is based on observable experience or empirical
  evidence
• It is directed towards finding answer to
  pertinent questions to problems
• It emphasizes development of generalization and
  principles or theories.

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Objectives of research

• It provides answers for questions like what,
  where, when, how and why.
• Brings out information that might not be
  discovered in ordinary course of life
• It contributes to theory and generalizations
• Verifies existing theories and facts.

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Objectives of research.

• May enable us to predict events
• Helps in establishing inter-relationships and
  derive explanations
• Helps developing new tools, concepts and theories
  to study phenomenon.

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Research is a team work
Research process
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Research process

• Identification of the research problem
• Review of literature
• Formulation of the objectives of the study
• Protocol preparation
• Conducting the study
• Analysis of the data
• Preparation of report

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Identification of the research problem

• All studies should start with a research question
  that addresses what the investigator would like
  to know
• Levels of the research may be
• Basic
• Epidemiological /Analytical
• Clinical/ public health intervention

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Origin of research question

• Mastering the existing literature
• Being alert to new ideas and techniques
• Keeping the imagination at roaming
• Answering what, why, where, when, who, how, how
  much

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What makes a good research question
FINER

• Feasible
• Interesting
• Novel
• Ethical
• Relevant

• Technical expertise
• No. of subjects
• Manageable in scope
• Affordable (time money)

• Confirms the existing findings
• Extends existing findings
• Provides new findings

• To scientific knowledge
• To clinical and health practice
• To future research

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Review of literature

• How far similar research problem has been studied
• Understand limitations in those studies
• Critically assess the required modifications

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Protocol preparation

• Study is conducted under strict protocol
  particularly when multi- centric
• The protocol includes -
• Title and investigators
• Introduction
• Objectives

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The protocol includes

• Materials and methods
• Ethical considerations
• Limitations
• References
• Appendices

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Title and investigators

• Precise
• Attractive/smart
• Self explanatory

• Main objective
• Population to be studied
• Study design

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Introduction

• Describe the magnitude and quantum of knowledge
• Identify the gaps and controversies in existing
  knowledge
• Justify the relevance and significance of this
  particular research

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Objectives

• The objective should be SMART
• Specific
• Measurable
• Achievable
• Relevant
• Time based
• In addition to specific objectives, secondary
  objectives, if any should invariably be mentioned.

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Materials and methods

• Study design
• Target population
• Sample size and sampling method
• Inclusion and exclusion criteria
• Study period

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Materials and methods..

• Study variables and out come variables
• Definition of all terms and variables
• Methodology of data collection
• Method of analysis including computer packages
  and statistical methods

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Study design

• Can be classified by two ways
• by the way the researchers behave
• by the purpose of the study

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By the way the researchers behave

• .
• Observational studies
• Descriptive studies
• Analytic studies
• Interventional studies
• Randomised controled trials
• Non-randomised trials

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Observational studies

• Natural experiment
• The researchers do not actively manage the
  experiment
• The investigators observe the subjects and
  measure their outcomes.
• Provide less compelling evidence that the study
  treatment causes the expected effect on human
  health.

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Descriptive studies

• Are usually the first phase of epidemiological
  studies
• Such studies basically ask questions
• When is the disease is occurring ?
• Where is it occurring ?
• Who is getting the disease ?

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Analytical studies

• Ecological studies
• Cross-sectional studies
• Case-control studies
• Cohort studies

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Case-control v/s Cohort studies
?
Individuals with particular disease Individuals
without particular disease
CASE CONTROL STUDY
Cases
Factor(s) present Or Absent
?
Controls
PROSPECTIVE(COHORT) STUDY
Individual exposed to particular
factor(s) Individual unexposed to
particular factor(s)
?
Cases
Presence or absence of particular disease
?
Controls
Time
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Interventional studies

• The investigators give the research subjects a
  particular medicine or other intervention.
• Then the researchers measure how the subjects'
  health changes.
• Provide the most compelling evidence that the
  study treatment causes the expected effect on
  human health.

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• Clinical trial
• is a systematic study of pharmaceutical products
  on human subjects (patients or healthy
  volunteers) in order to discover or verify its
  role (in terms of efficacy and safety) as a
  diagnostic, preventive or therapeutic agent.
• evaluation of new surgical technique or
  therapeutic/diagnostic intervention

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Phases in clinical trials for new drugs

• Pre-clinical trials (lab and animal trials)
• Phase-0
• Phase-I
• Phase-II
• Phase-III
• approval from the authorities, sale in the
  market.
• The whole process takes about 10 years and costs
  about US 800-1200 million.
• Phase-IV

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Interventional studies

• Randomizes control trials
• Concurrent parallel study deign
• Cross over type of study deign
• Non-randomised trials
• Uncontroled trials
• Natural experiments
• Before after studies

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Concurrent parallel study deign
Follow up
Rx-1
G-1
End of the study
Patients
Rx-2
G-2
Time
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Cross over type of study deign
Follow up
Rx-1
Follow up
Rx-1
Patient s
G-1
G-2
End of the study
Rx-2
Rx-2
G-2
G-1
Time
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2. By the purpose of the study

• Treatment trials
• Prevention trials
• Diagnostic trials
• Screening trials
• Quality of Life trials

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Selecting the reference population

• Population to which findings of the trial will be
  applicable
• May as broad as mankind or limited to a
  geographic area, age group, sex, social or
  occupational group

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Selecting the experimental population

• Derived from the reference population
• Actually participate in the study
• Should be chosen randomly
• Should have same characteristics as the reference
  population

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Selecting the experimental population

• When selected, members are invited to participate
  in the study
• To avoid losses to follow up choose stable
  population

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Criteria to be eligible for participation

• Should be represent the reference population
• Should be qualified or eligible for trial
• Must give informed consent

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Criteria to be eligible for participation.

• Which patient to be included in the trial and
• Which patient to be excluded from the trial
• i.e. inclusion criteria and exclusion criteria

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Inclusion criteria

• A set of characteristics present in person that
  make him eligible for participation in a clinical
  research
• e.g. newly diagnosed (6 months) type 2 diabetic
  of both sexes aged 30-60 yrs, failed to dietary
  therapy alone (diagnosis based on American
  Diabetes Association)
• BMI 23Kg/m2
• Informed consent given

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Informed consent

• Information
• Disclosure and comprehension
• Consent
• Voluntariness and competence

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Exclusion criteria

• A set of characteristics presence of which makes
  a person unsuitable for participation in a
  clinical research
• e.g. age lt 30 yrs or gt60 yrs
• BMI lt23Kg/m2
• H/o allergy to any study drug
• Impaired renal functions
• Impaired hepatic functions
• Heart failure
• H/o alcohol abuse
• Pregnancy/lactation

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Size of the sample

• Why ?
• An adequate sample size gives the researchers a
  level of confidence with which they can say that
  the results they obtained could have been due to
  chance
• e.g.1 in 20 or 1 in 100 times.

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Why ? Size of the sample

• Qualitative Data
• n 4pq
• L2
• Quantitative Data
• n 4?2
• L2
• L is allowable error by age of p

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Sampling methods

• Probability sampling
• Non-probability sampling

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Probability sampling

• Simple random sampling
• Systematic random sampling
• Stratified random sampling
• Cluster sampling
• Multistage sampling
• Multiphase sampling

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Non-probability sampling

• Accidental or incidental sampling
• Judgment or purposive or deliberate sampling
• Quota sampling
• Convenience sampling

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Randomization

• A statistical procedure to for allocating
  participants in to the study or control group
• Eliminate bias and allow comparability
• Heart of a control trial gives confidence that
  groups are comparable so that like can be
  compared with like.

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Randomization

• Ensures that investigator has no control over
  allocation participants to the study or control
  group
• Thus eliminating selection bias
• By random allocation every individual gets equal
  chance of being allocated into either group or
  any of the trial groups.

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Randomization.

• If population is not homogenous then needs to be
  stratified into subgroups according to variables
  and individuals in each subgroup can then be
  randomly allocated to the study or control group
• Randomization is done only after the participant
  has entered the study
• Best done by using tables of random numbers

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Bias

• Subjective bias
• Observer bias
• Evaluation bias
• Neither Randomization nor sample size can
  guard against these sorts of bias.

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Blinding

• Single blind trial
• Participant is not aware whether he belongs
  to study or control group
• Double blind trial
• Neither participant nor the
  investigator is aware of the group allocation

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Blinding..

• Triple blind trial
• The participant, the investigator and the
  person analyzing the data are all blind
• Ideally Triple blind trial should be used.
• When outcome measured is death then blinding is
  not essential

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Blinding
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Single blinding
Double blinding
Triple blinding
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Standardization

• Standardization of working procedures and
  schedules as well as parties involved in the
  trial, up to the stage of evaluation of outcome
  of the study
• Aim is to prevent bias and reduce sources of error

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Permission/ Clearance

• from an independent ethical committee
• from the regulatory authorities
• Why?
• Human rights issue

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Basic ethical principles

• Autonomy right of self-determination
• Beneficence maximizing the benefit and no harm
• Justice fairness in distribution of the benefits
  and burden of the research (selection on
  scientific basis)
• Declaration of Helsinki an official policy
  document of World Medical Association.

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Pilot study

• Preliminary test run
• to find out the feasibility or operational
  efficiency of certain procedures
• or
• unknown effects or the acceptability of certain
  policies
• or
• to find out flaws

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Conducting the study

• Study is to conducted as per the protocol and
  data may be collected by
• Face to face interview
• Health examination
• Taking measurements on various instruments

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Attrition

• Some losses to follow up are inevitable due
  factors such as death, migration and loss of
  interest.
• If attrition is substantial it may be difficult
  to generalize the results of the study to the
  reference population
• Every effort should be made to minimize the
  losses to follow up.

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Compilation of data and presentation of results

• Results may be presented in the form of
• Frequency distribution tables or
• Using diagrams such as bar diagram, pie chart,
  pictogram, histogram, line diagram, scatter
  diagram etc.

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Assessment of the outcome

• Done in terms of end points
• Incidence of Positive/negative end points is
  rigorously compared in both groups and
• the difference if any are tested for statistical
  significance
• Sequentially or at the end of the trial.

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Various tests of significance

• For quantitative data
• Standard error of mean
• SE of difference between two means
• Z-test if sample large
• T-test if sample small
• Correlation (Karl Pearson)

• For qualitative data
• Standard Error of proportion
• SE of difference between two proportions
• Z-test if sample large
• Chi-square if sample small
• Spearmans rank

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Writing the report

• Title and investigators
• Summary
• Introduction
• Objectives
• Materials and methods
• Results and discussion
• Conclusion and recommendations
• Limitations
• References
• Appendices

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Limitations

• Flaws in study design
• Limitations in sampling methods and sample size
• The effect of confounders
• Selection bias and measurement bias
• Internal validity and external validity
• Limitations anticipating in analysis

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References

• Vancouver style or uniform requirements for
  manuscript submitted to biological journals
• Harvard style

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Appendices

• Letters of approval
• Questionnaire or data collection instrument
• Informed consent
• Time task chart
• Budget

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• Report is submitted
• After a rigorous peer review report if accepted
  may find a place in scientific journals or may be
  available for use.

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All that lives, lives neither by itself nor for
itself .
THANK YOU