research methodology in medicine

1. Types of Studies in
Research
Dr Yashodhara Gaur
Professor, G.R. Medical College, Gwalior
President Obst Gynaecology Society Gwalior

2. Research Study
Statistical inference
Biological inference
Study sample
Conclusion about a population
(association)
Conclusion about scientific
theory(causation)

3. Observational study designs Experimental
study
 Descriptive studies (Interventional
study)
 Case reports Clinical trials
 Case series
 Analytical study designs
 Retrospective studies
 Case control study
 Prospective study designs
 Cohort study
Type of Research Studies

4. ____________________________________________________________________
Observational studies Interventional studies
____________________________________________________________________
Cross-sectional Case-control Cohort Clinical trials
Outcome Yes Yes No No
Exposure Yes Yes Yes Yes
Time of enquiry Still
(one time contact)
____________________________________________________________________________
__
Objective Descriptive Analytical studies
Burden of problem Causal relationship
Hypothesis generation Hypothesis generation & testing
Research Studies Eye-catching Point

5. Case Control Study

6. Case Control Study
 A case-control study is designed to help
determine if an exposure is associated with
an outcome (i.e., disease or condition of
interest)
 In theory, the case-control study can be
described simply. First, identify the cases (a
group known to have the outcome) and the
controls (a group known to be free of the
outcome)
 Then, look back in time to learn which
subjects in each group had the exposure(s),
comparing the frequency of the exposure in
the case group to the control group.
 By definition, a case-control study is always
retrospective because it starts with an
outcome then traces back to investigate
exposures

7. Case Control Study
 Both exposure and outcome(disease) have occurred before
the start of study
 The study proceeds backwards from effect to cause, and is
thus called retrospective
 It uses a control or comparison group to support or refute an
inference

8. Case Control: Study Design

9. Venous thromboembolism Without venous
present (cases) thromboembolism
(controls)
Oral contraceptive
Exposure present a b
Not exposed c d
Odds of disease in the exposed group: a/b
Odds of disease in the unexposed group: c/d
Odds Ratio= (a/b)/(c/d)=ad/bc
Case Control Study (Example)

10. Case control study
 Applications in research: Particularly appropriate for
 Investigating outbreaks: Study of endophthalmitis
following ocular surgery. When an outbreak is in
progress, answers must be obtained quickly
 Studying rare diseases or outcomes: Study of risk factors
for uveal melanoma, or corneal ulcers

11. Steps in conducting a Case-control study
 Define a study population
(source of cases and
controls)
 Define and select cases
 Define and select controls
 Measure exposure
 Estimate disease risk
associated with exposure

12. Case Control Study
Advantage & Disadvantage
Advantages
 Can obtain findings quickly
 Can often be undertaken with
minimal funding
 Efficient for rare diseases
 Can study multiple exposures
 Generally requires few study
subjects
Disadvantages
 Cannot generate incidence
data
 Subject to bias
 Difficult if record keeping is
either inadequate or
unreliable
 Selection of controls can be
difficult

13. Cohort Study

14. Cohort Study
 Group of people with defined
characteristics who are followed up to
determine incidence of, or mortality
from, some specific disease, all causes of
death, or some other outcome.”
 In a cohort study, an outcome or disease-
free study population is first identified by
the exposure or event of interest and
followed in time until the disease or
outcome of interest occurs
 Because exposure is identified before the
outcome, cohort studies have a temporal
framework to assess causality and thus
have the potential to provide the
strongest scientific evidence

15. Cohort Study: Design

16. Cohort Study
 Cohort studies are particularly advantageous for examining
rare exposures because subjects are selected by their
exposure status
 Additionally, the investigator can examine multiple outcomes
simultaneously.

17. Five steps in a cohort study
 Identify the study subjects; i.e.
the cohort population.
 Obtain baseline data on the
exposure; measure the
exposure at the start. (The
exposure may be a particular
event, a permanent state or a
reversible state.)
 Select a sub-classification of
the cohort—the unexposed
control cohort—to be the
comparison group.

18. Five steps in a cohort study
 Follow up; measure the outcomes using records, interviews or
examinations. (Note: Outcomes must be defined in advance and
should be specific and measurable.)
 Do the data analysis where the outcomes are assessed and
compared.

19. Cohort studies: Types
Prospective or Retrospective
 Prospective studies are carried out from the present time
into the future
 Because prospective studies are designed with specific data
collection methods, it has the advantage of being tailored to
collect specific exposure data and may be more complete
 The disadvantage of a prospective cohort study may be the
long follow-up period while waiting for events or diseases to
occur
 Thus, this study design is inefficient for investigating diseases
with long latency periods and is vulnerable to a high loss to
follow-up rate

20. Cohort studies: Types
Prospective or Retrospective
 Retrospective cohort studies, also known as historical cohort studies, are carried
out at the present time and look to the past to examine medical events or
outcomes
 In other words, a cohort of subjects selected based on exposure status is chosen
at the present time, and outcome data (i.e. disease status, event status), which
was measured in the past, are reconstructed for analysis
 The primary disadvantage of this study design is the limited control the
investigator has over data collection
 The existing data may be incomplete, inaccurate, or inconsistently measured
between subjects
 However, because of the immediate availability of the data, this study design is
comparatively less costly and shorter than prospective cohort studies.

21. Cohort Study: Advantages
 Gather data regarding sequence of
events; can assess causality
 Examine multiple outcomes for a given
exposure
 Good for investigating rare exposures
 Can calculate rates of disease in exposed
and unexposed individuals over time
(e.g. incidence, relative risk)

22. Cohort Study: Disadvantages
 Large numbers of subjects are required to
study rare exposures
 Susceptible to selection bias
 Prospective Cohort Study
 May be expensive to conduct
 May require long durations for follow-up
 Maintaining follow-up may be difficult
 Susceptible to loss to follow-up or
withdrawals
 Retrospective Cohort Study
 Susceptible to recall bias or information
bias
 Less control over variables

23. Snapshot
Temporal Design of Observational Studies

24.  STROBE stands for an international, collaborative initiative
of epidemiologists, methodologists, statisticians,
researchers and journal editors involved in the conduct and
dissemination of observational studies, with the common
aim of STrengthening the Reporting of OBservational
studies in Epidemiology.
 The STROBE Statement is being endorsed by a growing
number of biomedical journals
 https://www.strobe-statement.org/index.php?id=available-
checklists

25. Cross-sectional Study

26. Cross-sectional Study
 Cross-sectional study design is a type of observational study
design
 In a cross-sectional study, the investigator measures the
outcome and the exposures in the study participants at the
same time
 The investigator can study the association between these
variables
 It is also possible that the investigator will recruit the study
participants and examine the outcomes in this population
 The investigator may also estimate the prevalence of the
outcome in those surveyed

27. Cross-sectional study
Participants
recruited
based on
inclusion and
exclusion
criteria
Estimate the
prevalence (of
exposure and
outcome as well)
Calculate odds
ratio
Study the
exposure
and
outcome at
the same
time

28. Measurements in a Cross-sectional Study
 Cross-sectional study designs
may be used for population-
based surveys
 Cross-sectional studies may
also be used for estimating the
prevalence in clinic-based
studies. (What is the
prevalence of HIV in patients
presenting with an STI?)
 Cross-sectional studies may
also be used to calculate the
Odd-ratios

29. Strengths of a Cross-sectional Study
 Cross-sectional studies can usually be conducted relatively
faster and are inexpensive – particularly when compared with
cohort studies (prospective)
 These are studies are conducted either before planning a
cohort study or a baseline in a cohort study. These types of
designs will give us information about the prevalence of
outcomes or exposures; this information will be useful for
designing the cohort study
 These study designs may be useful for public health planning,
monitoring, and evaluation. For example, sometimes the
National AIDS Programme conducted cross-sectional sentinel
surveys among high-risk groups and ante-natal mothers every
year to monitor the prevalence of HIV in these groups.

30. Limitations of a Cross-sectional Study
 Since this is a 1-time measurement of exposure and
outcome, it is difficult to derive causal relationships from
cross-sectional analysis
 Careful about interpreting the associations and direction
of associations from a cross-sectional survey
 Prevalence of an outcome depends on the incidence of
the disease as well as the length of survival following the
outcome

31. Case reports and Case series

32. Case reports and Case series
 Case reports, which generally consist of
three or fewer patients, are prepared to
illustrate features in the practice of
medicine and potentially create new
research questions that may contribute
to the acquisition of additional
knowledge in the literature
 Case series involve multiple patients;
they are a qualitative research method
and include in-depth analyses or
experiential inquiries of a person or
group in their real-world setting

33. Case reports and Case series
Applications
 Clinical case reports and case series are
beneficial tools in graduate medical
education
 The preparation and presentation of case
studies can help students and residents
acquire and apply clinical competencies in
the areas of medical knowledge, practice-
based learning, systems-based practice,
professionalism, and communication
 In this aspect, case studies provide a tool for
developing clinical skills through problem-
based learning methods
 Descriptive studies that are prepared for
illustrating novel, unusual, or atypical
features identified in patients in medical
practice, and they potentially generate new
research questions

34. Advantages of Case reports & Case studies
One case to initiate a signal (case
report)
Provide stronger evidence with
multiple cases (cases series)
Observational
Educational
Easy to do (fast and no financial
support needed)
Identify rare manifestations of a
disease or drug

35. Disadvantages of case reports and case
studies
 No control (uncontrolled)
 Difficult to compare different cases
 Cases may not be generalizable
 Selection bias
 Unknown future outcome/follow-up

36. Clinical trials

37. Clinical trials
 A clinical trial is any research study that
prospectively assigns human participants
or groups of humans to one or more
health-related interventions to evaluate
the effects on health outcomes.
 Interventions include but are not
restricted to drugs, cells and other
biological products, surgical procedures,
radiological procedures, devices,
behavioural treatments, process-of-care
changes, preventive care, etc.

38. Why do a clinical trial ?
 To answer a clinical problem
 To gain new knowledge about a
new or established treatment
 To support a “claim”
For gaining government
regulatory approval
For marketing a drug, device, or
technique

39. Development of a Clinical Trial
Idea

Reviews from the experts(Sponsor or CRO)

First planning meeting (basic design features)

Second planning meeting (draft protocol)

Final protocol (ethical and scientific, signed by a statistician)

Evaluation (scientific review, IRB, funding)

Implementation

Final analysis and publication

40. Clinical Trials Design
 Randomized or Non-
randomized
 Parallel or Cross-over
study
 Blinded (Masking): Single/
Double blinded

41. Clinical Trials: Musk know
 New Drugs & Clinical Trials 2019
 Indian Good Clinical Practice
 Clinical Trial Registry in India
 Clinical Trial Compensation

42. Systematic reviews & Meta-
analysis

43. Systematic reviews & Meta-analysis
 Systematic review
 A systematic review collects all possible studies
related to a given topic and design, and
reviews and analyzes their results
 During the systematic review process, the
quality of studies is evaluated, and a statistical
meta-analysis of the study results is conducted
on the basis of their quality
 Meta-analysis
 A meta-analysis is a valid, objective, and
scientific method of analyzing and combining
different results
 In order to obtain more reliable results, a
meta-analysis is mainly conducted on
randomized controlled trials (RCTs), which
have a high level of evidence

44. Narrative review Systematic review
+ meta-analysis
1. Questions Broad Focused
2. Search strategy Limited Exhaustive,
reproducible
3. Quality
assessment
4. Study weight Same weight for all
studies
Higher weights to
precise studies
5. Statistical analysis
6. Bias High Low
Narrative vs Systematic review

45. Why do a Meta-analysis or Systematic
review?
 To find out relation between two
(or more) variables from pooled
available literature
 To make plethora of information
more digestible
 To settle controversy arising from
conflicting studies
 Increase power & precision
 Meta-analysis is level-I evidence

46. Flowchart illustrating a systematic review

47. Questions to ask when assessing the
quality of a systematic review
1. Was the review conducted according to a pre-specified protocol?
2. Was the question focused and well formulated?
3. Were the right types of studies eligible for the review?
4. Was the method of identifying all relevant information comprehensive?
a. Is it likely that relevant studies were missed?
b. Was publication bias considered?
5. Was the data abstraction from each study appropriate?
a. Were the methods used in each primary study appraised?
6. Was the information synthesized and summarized appropriately?
a. If the results were mathematically combined in meta-analysis, then
were the methods described in sufficient detail, and was it reasonable to do so?

48. Pros of Meta-analysis
 Systematic searches for clinical evidence
 Explicit and standardized methods for search and
selection of evidence sources
 Thorough appraisal of the internal validity of primary
studies
 Quantitative synthesis with increased statistical power
 Increased external validity by appraising the effect of
an intervention (exposure) across different settings
 Ability to control for between study variation
 Including moderators to explain variation

49. Cons of Meta-analysis
 Adds together apples and oranges
 GIGO phenomenon: garbage-in,
garbage-out
 Publication bias
 Not original research
 Big RCTs definitely better
 Average effect largely unapplicable to
individuals
Lau et al, Lancet 1998