STUDY DESIGNS

By:
Fernandez, Balgomera, Nuñez
Disclosure
None
 RESEARCH DESIGN
● Is a framework, or the set of methods and procedures used to collect
and analyze data
● The type of study design used to answer research question is based
on:
○ Nature of question
○ Goal of research
○ Availability of resources

Ranganathan, P., & Aggarwal, R. (2018). Study designs: Part 1 - An overview and classification. Perspectives in clinical research, 9(4), 184–186. https://doi.org/10.4103/picr.PICR_124_18
 Overview
TYPE OF STUDY ALTERNATIVE NAME UNIT OF OBSERVATION
OBSERVATIONAL

1. DESCRIPTIVE

Case Report Single patient

Case series Group of patients

Ecological Study Correlational

Cross-sectional Prevalence study

2. Analytical

Cross-sectional Prevalence Individuals

Case-control Case reference Individuals

Cohort Follow-up Individuals

Silverberg, J. (2015) Study Designs in Dermatology. Journal of American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2014.08.029
 Descriptive Studies Analytical Studies
Describes the distribution of Concerned with determining
cases by the variables of person, causes of disease occurrence
time and place

Used if little is known about Purpose is to test the hypothesis

event or phenomenon. The because you already know the
purpose is to generate a relationship of events.
hypothesis.

Silverberg, J. (2015) Study Designs in Dermatology. Journal of American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2014.08.029
 Observational Study

● Allows nature to take its course

● The investigator observes or measures but does not
intervene

Example: Factors related to treatment-seeking behavior among

acne patients seen in a tertiary hospital in the Philippines

Ranganathan, P., & Aggarwal, R. (2018). Study designs: Part 1 - An overview and classification. Perspectives in clinical research, 9(4), 184–186. https://doi.org/10.4103/picr.PICR_124_18
CASE REPORT
Case Report

● A detailed description of disease occurence, diagnosis,

treatment, response to treatment and follow-up after
treatment of an individual
● Describes an unusual or novel occurrence and as such,
remain of the cornerstones public health progress and
provide new ideas in public health
● Unusual features of the case may suggest new hypothesis
Case Report
● Considered the lowest level of evidence, but the first line of
evidence (where issue and ideas emerge)
● If multiple case reports show similarity → Next step: case
control study to determine relationship between relevant
variables
Case Report
Case report should provide the ff. details:
● Case description (socio-demographic information)
● Case history
● Physical exam results
● Results of pathological tests and other investigations
● Treatment plan
● Expected outcome of the treatment plan
● Actual outcome
Case Report

● When to use it?

○ When there is atypical or abnormal behaviour or
development
○ When there is an unexplained outcome to
treatment
○ When there is an emerging disease or condition
Case Report
● Strengths: ● Limitations
○ Can help in identification of ○ Cases may not be

new trends or disease generalizable

○ Can help detect new side ○ Not based on systematic

effect and potential use of studies

treatment ○ Causes or associations may

○ Can help share lessons have other explanation

learned (educational)
CASE SERIES
Case Series

● A group of patients with similar diagnoses or undergoing the same

procedure followed over time
● Primary purpose: generation of hypotheses → may be tested in studies
of greater methodological rigor.
Case Series

● Useful for describing potential effectiveness of new

intervention and describing the effectiveness of interventions
on unusual diagnoses and describing unusual responses to
interventions.
● May be done retrospectively or prospectively.
● No randomization
 Case Series
● When to use it?
○ When a more cautious description of intervention in several
settings is required
○ To report on novel diagnostic or therapeutic strategies

Ranganathan, P., & Aggarwal, R. (2018). Study designs: Part 1 - An overview and classification. Perspectives in clinical research, 9(4), 184–186. https://doi.org/10.4103/picr.PICR_124_18
Case Series
Case Series
Case Series
Case Series
OBSERVATIONAL DESCRIPTIVE
TYPE OF STUDY ALTERNATIVE NAME UNIT OF OBSERVATION
OBSERVATIONAL

1. DESCRIPTIVE

Case Report Single patient

Case series Group of patients

Ecological Study Correlational

Cross-sectional Prevalence study

2. Analytical

Cross-sectional Prevalence Individuals

Case-control Case reference Individuals

Cohort Follow-up Individuals

Cross-sectional Survey
○ Descriptive
○ Prevalence of comorbid exposures and outcomes
○ Examines the occurrence of disease in a defined population at a
particular point in time
○ It cannot establish temporality
NON-EXPERIMENTAL OBSERVATIONAL STUDIES
TYPE OF STUDY ALTERNATIVE NAME UNIT OF OBSERVATION
OBSERVATIONAL

1. DESCRIPTIVE

Case Report Single patient

Case series Group of patients

Ecological Study Correlational

Cross-sectional Prevalence study

2. Analytical

Cross-sectional Prevalence Individuals

Case-control Case reference Individuals

Cohort Follow-up Individuals

 ● Cross-sectional
Analytical ● Case Control
Epidemiology ● Cohort
Analytical Epidemiology
● Determining causes of disease occurrence or determining risk of having
the disease
● Activities related to identifying possible causes for the occurrence of
diseases include:
a. Surveillance
b. Diagnostic testing
c. Natural history of disease
d. Prognostic factors
e. Testing new treatments
Cross-sectional
Cross-sectional Analytic
● Relationship between diseases and other variable of interest
● Subject selection at random
Cross-sectional
Uses:

1. Assess burden of disease in a population

2. Compare prevalence of disease in different population
3. Examine trends in disease prevalence or severity over time
Cross-sectional
Advantages Disadvantages

Efficient and fast Can identify potential correlations,

associations and relationships
between variables. However, often
they cannot define direct causation

Multiple variables can be Risk of participation bias, or low

investigated at the one time response rates

Provides data on a disease rate in a

population and descriptive
information on other characteristics
Case-control
studies
Case-Control
● A study design in which individuals with an event or condition of interest
(CASES) are identified and then compared with regard to one or more
exposures to individuals without the event or condition of interest
(CONTROLS).
Case-control
Case-control
● Groups (cases and control) are compared with respect to having a history
of exposure to the suspected factor
● Exposure is determined in a retrospective manner, that is one must look
back in time to assess exposure status before a person became a case
● Cause and effect relationship can be inferred between the factor and the
disease by measure of association = ODDS RATIO
Case-control
WHEN TO USE: If the disease condition (case) is rare
ODDS RATIO: provides an indirect measure of relative risk
Interpretation: the probability of having been exposed is x
Case-control
ODDS RATIO: is the odds of exposure given disease divided by the odds of
exposure given no disease

CASE CONTROL

Exposed a b a+b

Unexposed c d c+d

a+c b+d
Case-control
The strength of association in a case control study is measured using the odds
ratio

Interpretation:

O.R. = 1 then exposure is NOT related to disease

O.R. > 1 then exposure is POSITIVELY related to disease

O.R. < 1 then exposure is NEGATIVELY related to disease

Case-control
Advantages Disadvantages

Useful for studying rare Recall bias

conditions

Helps find the source of existing Does not provide clear causal
illness relationship bet. Risk factors
and illnesses

Quick and easy to conduct

Looks at different risk factors

Cohort studies
Cohort
● An epidemiologic design in which the incidence of a disease (or condition)
is compared among exposed and unexposed individuals
● Can be retrospective or prospective
● Subjects are followed up over a period of time to assess the occurrence of
disease or outcome of interest.
Cohort
Cohort •Retrospective: if
the outcome has
already occurred,
then it is a
retrospective study
•involve data
collection before
study initiation and
are affected by less
rigorous planning
Cohort •Prospective: If the
outcome has not
occurred at the
start of the study,
then it is a
prospective study
Cohort
RELATIVE RISK
● measures the strength of relationship or the association between the
factor and the outcome
DISEASE NO DISEASE

Exposed a b a+b

Unexposed c d c+d

a+c b+d N
Cohort
INTERPRETATION

•If RR >1, there is ______x increased risk of developing disease for the
exposed group as compared to the unexposed group.
Cohort
Advantages Disadvantages

Directly investigates risk of disease and the Prospective: Time-consuming

factors contributing to it

Multiple outcomes can be measures Retrospective: less control over variables,

information and recall bias

Costly
Summary
Cross-sectional Case-control Cohort

“What is happening?” “What happened?” “Who will develop the disease?”

“Who developed the disease?”

Assess frequency of disease (and Compares a group of people with Compares a group with a given
related risk factors) at a particular disease (Cases) to a group without exposure to a group without
point in time disease (Control) exposure

Looks for prior exposure or risk Looks to see if exposure increases

factor the likelihood of disease

Disease prevalence Odds ratio (OR) Relative risk (RR)

Can show risk factor association
with disease, but does not
establish causality
EXPERIMENTAL STUDIES
RANDOMIZED CONTROLLED TRIALS
● Considered as the highest level of evidence to
establish causal associations in clinical research
● Measures the efficacy on an intervention or
treatment
● Subjects are randomly assigned to either

a. EXPERIMENTAL GROUP - receives the

intervention being studied

b. CONTROL GROUP - receives a placebo or sham

intervention
Subtypes
ACTIVE CONTROL

1. Superiority Study - “experimental treatment is superior to the standard of

care treatment”
2. Equivalence Study - “experimental treatment is similar to the standard of
care treatment”
3. Non-inferiority Study - “experimental treatment is not much less effective
than the standard-of-care treatment”
Subtypes
PLACEBO CONTROL - seeks to show that the experimental treatment is
superior to the placebo

MULTIPLE ARM

1. Multiple dose levels or regimen

2. Single treatment arm with multiple control arms (active control and
placebo control)
Subtypes
CLUSTER RANDOMIZED - groups of subjects are randomized

-More common in health services and policy research

ADAPTIVE DESIGN - allows more patients to be accrued to the arm that is

showing more promise, thus reducing ethical concerns about continuing
enrollment on fixed randomization designs in the face of possibly increasing
evidence that one of the treatments under study is superior and allowing
more patients in the course of the trial to be given more effective
treatments or doses
Subtypes
PLATFORMS STUDY -

describe multiple-arm studies with the potential to include control and

experimental arms that can be opened or closed for enrollment throughout
the course of the trial based on decision rules regarding efficacy

In this way, ineffective treatments can be discontinued before many patients

have been treated with them and newly emerging treatment can also be
added
RANDOMIZATION
● Minimizes differences in characteristics of the groups which may influence the
outcome

Methods for Randomization

1. Simple Randomization
2. Permuted Block Randomization
3. Stratified Randomization
4. Minimization
5. Outcome adaptive randomization
METHODS FOR RANDOMIZATION
1. SIMPLE RANDOMIZATION - may be conducted with a flip of a coin or any
procedure that assigns each enrolling patient to an arm with an equal
probability

2. PERMUTED BLOCK RANDOMIZATION - divides patients into blocks over time

and balances the randomization to each arm within each block.
For example, with treatment labels A and B, possible blocks might be: ABBABA, BABBAA, and
AABABB. As each block is filled, the trial is guaranteed to have the desired allocation to each
group.
METHODS FOR RANDOMIZATION
3. STRATIFIED RANDOMIZATION - simple randomization is conducted within
groups based on important prognostic characteristics
For example, patients over age 65 years may be randomized separately from patients under 65.

4. MINIMIZATION - Alternative to stratified randomization

METHODS FOR RANDOMIZATION
4. MINIMIZATION - Alternative to stratified randomization
METHODS FOR RANDOMIZATION
5. OUTCOME ADAPTIVE RANDOMIZATION = randomization procedures that
adjust the allocation ratio as the study progresses
Advantages of RCTs
- Reduces confounding from both known and unknown sources
- The dosage, timing, frequency, and duration of treatment can be
controlled, and blinding may be possible.
Blinding
Blinding prevents outcomes from being influenced by knowledge of treatment
assignment

Single-blind study - patients do not know which treatment they are receiving.

Double-blind study - neither the patient nor the provider knows the
treatment assignment. This additionally ensures that any care given by the
provider or provider-assessed outcomes are not biased by knowledge of
treatment assignment.
Disadvantages of RCTs
● Expensive
● Takes a long time
● Highly controlled inclusion and exclusion criteria limits generalizability of
the results to broader populations
● Tends to study treatment in idealized environments which may not be in-
line with real world usage of treatment
SYSTEMATIC REVIEW AND META-ANALYSIS
A systematic review answers a defined research question by collecting and summarizing all
empirical evidence that fits pre-specified eligibility criteria.
A meta-analysis is the use of statistical methods to summarize the results of these studies.

Systematic reviews use explicit, systematic methods that are selected with a view to
minimizing bias, thus providing more reliable findings from which conclusions can be drawn
and decisions made
➔ collect and analyze data from included studies to minimize bias
SYSTEMATIC REVIEWS
Should have

● clearly stated objectives with pre-defined eligibility criteria for studies

● explicit, reproducible methodology
● a systematic search that attempts to identify all studies
● assessment of the validity of the findings of the included studies (e.g. risk
of bias)
● systematic presentation, and synthesis, of the characteristics and findings
of the included studies
WHY DO WE NEED A SYSTEMATIC REVIEW
● Avoid personal bias inherent in traditional reviews and expert opinion
● Results from systematic reviews are the cornerstone for developing practice
guidelines
● To increase the number of patients in clinically relevant subgroups
● To resolve uncertainty when the results of primary studies seem conflicting
● To draw a reliable conclusion based on a summary of all relevant studies
● To plan new studies when there is lack of adequate evidence
Steps to conducting a systematic review and meta-analysis

1. Frame questions for a review

2. Identify relevant work
3. Assessing the quality of studies
4. Summarizing and displaying results (eg, using forest pots and a summary
of findings table, as shown in the figure
5. Interpret findings
Five Steps in Conducting A Systematic Review
STEP 1: FRAMING THE QUESTION
● The problems to be addressed by the review should be specified in the
form of clear, unambiguous and structured questions before
beginning the review work.
● Once the review questions have been set, modifications to the protocol
should be allowed only if alternative ways of defining the populations,
interventions, outcomes or study designs become apparent
Five Steps in Conducting A Systematic Review
STEP 2: IDENTIFY RELEVANT WORK

The search for studies should be extensive.

Multiple resources (both computerized and printed) should be

searched without language restrictions. The study selection criteria
should flow directly from the review questions and be specified a
priori. Reasons for inclusion and exclusion should be recorded.
Five Steps in Conducting A Systematic Review
STEP 3: ASSESS THE QUALITY OF STUDIES
Selected studies should be subjected to a more refined quality assessment by use
of general critical appraisal guides and design-based quality checklists
Five Steps in Conducting A Systematic Review
STEP 4: SUMMARIZE THE EVIDENCE

Data synthesis consists of tabulation of study characteristics, quality and effects

as well as use of statistical methods for exploring differences between studies and
combining their effects (meta-analysis).
Five Steps in Conducting A Systematic Review
Publication Bias - defined as the failure to publish the results of a study on the basis of the
direction or strength of the study findings. This may mean that only studies which have
statistically significant positive results get published and the statistically insignificant or
negative studies do not get published

Outcome reporting bias – refers to the concern that a study may only include outcomes that
are favorable and significant in the published report, while non-significant or unfavorable
outcomes are selectively not reported.
META-ANALYSIS
● It is a systematic review that uses quantitative methods to synthesize and
summarize the results.
● Goes beyond critique and integration and conducts secondary statistical
analysis
● The rationale for a meta-analysis is that, by combining the samples of the
individual studies, the overall sample size is increased, thereby improving the
statistical power of the analysis as well as the precision of the estimates of
treatment effects
STEPS IN META-ANALYSIS

1st stage : Calculation of a measure of treatment effect (such as odds ratio and
relative risks) with its 95% CI for each individual study
2nd stage: an overall treatment effect is calculated as a weighted average of the
individual summary statistics
Comparison of Vaccine A vs Placebo
Five Steps in Conducting A Systematic Review
STEP 5: INTERPRET FINDINGS

The risk of publication bias and related biases should be explored. Exploration for
heterogeneity should help determine whether the overall summary can be trusted,
and, if not, the effects observed in high-quality studies should be used for
generating inferences. Any recommendations should be graded by reference to
the strengths and weaknesses of the evidence
QUIZ TIME
REFERENCES
1. Silverberg, J. (2015) Study Designs in Dermatology. Journal of American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2014.08.029
2. Ranganathan, P., & Aggarwal, R. (2018). Study designs: Part 1 - An overview and classification. Perspectives in
clinical research, 9(4), 184–186. https://doi.org/10.4103/picr.PICR_124_18
3. Zabor, E. C., Kaizer, A. M., & Hobbs, B. P. (2020). Randomized Controlled Trials. Chest, 158(1S), S79–S87.
https://doi.org/10.1016/j.chest.2020.03.013
4. Tawfik, G. M., Dila, K. A. S., Mohamed, M. Y. F., Tam, D. N. H., Kien, N. D., Ahmed, A. M., & Huy, N. T. (2019). A
step by step guide for conducting a systematic review and meta-analysis with simulation data. Tropical medicine
and health, 47, 46. https://doi.org/10.1186/s41182-019-0165-6
5. Khan, K. S., Kunz, R., Kleijnen, J., & Antes, G. (2003). Five steps to conducting a systematic review. Journal of the
Royal Society of Medicine, 96(3), 118–121. https://doi.org/10.1177/014107680309600304
6. UpToDate. (n.d.). Retrieved January 15, 2023, from https://www.uptodate.com/contents/systematic-review-and-
meta-analysis
Choose the best answer
1. Which of the following is a study design where a group of patients with similar
diagnoses followed over time?
a. Cohort
b. Case Study
c. Case Control Study
d. Case Series
Choose the best answer
2. Which of the following is not part of the case report?

a. Causality statement
b. Case description
c. Case history
d. Actual outcome
Choose the best answer
3. Which of the following statement/s is or are true?

a. Case series may be prospective and retrospective

b. We may draw cause and effect relationship in case series
c. Case study results may be generalizable
d. All of the above
Choose the best answer
4. Which of the following study design examines the occurrence of disease in
a defined population at a particular point in time?

a. Case Series
b. Cross-sectional
c. Cohort
d. Case-control
Choose the best answer
5. What is the measure of association for a cohort study design?
a. Prevalence odds ratio
b. Prevalence rate
c. Odds ratio
d. Relative risk
6. A case-control study would be better than a cohort study under which of the
following circumstances?
a. The disease being studied is rare
b. The etiology of the disease is known
c. Exposure to the suspected cause of the disease is rare
d. The suspected factor is probably not the cause of the disease
Choose the best answer
7. Which of the following is a randomization procedure that adjust the allocation ratio as
the study progresses?
A. Simple randomization

B. Permuted block randomization

C. Outcome adaptive randomization

D. Minimization
8. IDENTIFY: This is considered as the standard for reporting evidence in systematic reviews and meta-
analyses.

9. TRUE OR FALSE: Articles for systematic reviews should be homogenous at all times.

10. TRUE OR FALSE: All systematic reviews should have meta-analysis and all meta-analysis are systematic
reviews.
ANSWERS
Choose the best answer
1. Which of the following is a study design where a group of patients with similar
diagnoses followed over time?
a. Cohort
b. Case Study
c. Case Control Study
d. Case Series
Choose the best answer
2. Which of the following is not part of the case report?

a. Causality statement
b. Case description
c. Case history
d. Actual outcome
Choose the best answer
1. Which of the following statement/s is or are true?
a. Case series may be prospective and retrospective
b. We may draw cause and effect relationship in case series
c. Case study results may be generalizable
d. All of the above
Choose the best answer
4. Which of the following study design examines the occurrence of disease in
a defined population at a particular point in time?

a. Case Series
b. Cross-sectional
c. Cohort
d. Case-control
Choose the best answer
5. What is the measure of association for a cohort study design?
a. Prevalence odds ratio
b. Prevalence rate
c. Odds ratio
d. Relative risk
6. A case-control study would be better than a cohort study under which of the
following circumstances?
a. The disease being studied is rare
b. The etiology of the disease is known
c. Exposure to the suspected cause of the disease is rare
d. The suspected factor is probably not the cause of the disease
Choose the best answer
7. Which of the following is a randomization procedure that adjust the allocation ratio as
the study progresses?
A. Simple randomization

B. Permuted block randomization

C. Outcome adaptive randomization

D. Minimization
8. IDENTIFY: This is considered as the standard for reporting evidence in systematic reviews and meta-
analyses. PRISMA

9. TRUE OR FALSE: Articles for systematic reviews should be homogenous at all times. FALSE

10. TRUE OR FALSE: All systematic reviews should have meta-analysis and all meta-analysis are systematic
reviews. FALSE