Study design (Biostats)

Question 1

Case reports, case series, cross-sectional studies, and correlational (ecologic) studies, are all _________ studies.

Answer 1

Descriptive studies

Question 2

What study design could develop a sense of the disease prevalence?

Answer 2

Disease prevalence can be addressed in a cross-sectional study

Question 3

What is the main question addressed by a cross-sectional study?

Answer 3

“What is happening?” It assesses the frequency of disease and risk factors simultaneously. A cross-sectional study (prevalence study) is characterized by the simultaneous measurement of exposure and outcome. It is a snapshot study design frequently used for surveys.

Question 4

What is the goal of a cross-sectional study?

Answer 4

To determine disease prevalence and assess potential risk factor associations at a single point in time.

Question 5

What is the tactical advantage of a cross-sectional study?

Answer 5

It has the advantage of being cheap and easy to perform.

Question 6

What is the major limitation of cross-sectional studies?

Answer 6

They assess disease prevalence but cannot establish causality or temporal relationships between exposure and outcome.

Question 7

Does a cross-sectional study address causality?

Answer 7

No, a cross-sectional study can only show the risk factors associated with a disease, but can not establish causality.

Question 8

Why can cross-sectional studies show associations but not causality?

Answer 8

They do not establish a temporal relationship between exposure and outcome.

Question 9

When a study design analyzes several individual patients with the
same diagnosis, treatment, or outcome, and only provides a description of clinical findings and symptoms, but has no comparison group, this is/these are … ?

Answer 9

Case-series or case series

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These only provide descriptions of individual patient cases or a group of cases sharing the same diagnosis.

Question 10

In what scenario is a case report or case series used?

Answer 10

To describe rare diseases or unusual presentations when comparison groups are not available. Typically, case reports and case series describe unusual cases that may provide greater understanding of the disease or that may have public health significance.

Question 11

Can a case-series study link risk factors to a disease?

Answer 11

No, case studies cannot show risk factor association with disease.

Question 12

What study would be preferred for a study small infectious outbreaks or rare diseases?

Answer 12

A case-control study.

Question 13

What type of study compares diseased and non-diseased groups to assess prior exposure in a retrospectively manner?

Answer 13

A case-control study.

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Retrospectively compares a group of people with disease to a group without disease.

Question 14

What question does a case-control study answer?

Answer 14

“What happened?” It retrospectively assesses exposure in cases and controls. For example, patients with COPD had higher odds of a smoking history than those without COPD.

Question 15

What is the primary measure of association in case-control studies?

Answer 15

Odds ratio (OR).

Question 16

What distinguishes a cohort study from a case-control study?

Answer 16

Cohort studies start with exposure and follow participants over time for outcomes, whereas case-control studies start with outcomes and look back for exposure. Case-control studies do not directly determine the risk of the disease based on exposure, rather, the odds ratio is a measure of association that compares the odds of exposure in cases with the odds of exposure in controls.

Question 17

How is the control determined in a case-control study?

Answer 17

In a case-control study, the control group is carefully selected to represent the population from which the cases arose, matching relevant characteristics. The controls are individuals who do not have the outcome of interest but are otherwise similar to the subjects in the case. The primary purpose of the control group is to provide a basis for comparison to estimate the association between exposure and the outcome.

Question 18

Why are case-control studies preferred for rare diseases?

Answer 18

They are efficient, cost-effective, and focus on comparing past exposures in cases and controls.

Question 19

When is relative risk calculated, and when is odds ratio calculated?

Answer 19

Relative risk is used in cohort studies (prospective or retrospective), and odds ratio is used in case-control studies.

Question 20

Which study type can assess the natural course of a disease?

Answer 20

Cohort studies, as they follow individuals over time to observe progression.

Question 21

Does a cohort study always need to be prospective?

Answer 21

A cohort study can be prospective, retrospective, or ambidirectional. It does not always need to be prospective, as retrospective cohort studies rely on historical data to assess exposures and outcomes. The choice between these designs depends on the research question, available resources, and the nature of the exposure and outcome being studied.

Question 22

What question does a cohort study answer?

Answer 22

“What will happen?” It investigates the risk of disease based on exposure.

For example, people who smoke had a higher risk of developing COPD than people who do not.

Question 23

The disease (prevalence or incidence) is developed with a cohort study?

Answer 23

‘disease incidence’

Question 24

What is the primary measure of association in cohort studies?

Answer 24

Relative risk (RR).

Question 25

What is the “time-to-event” analysis in cohort studies?

Answer 25

Survival analysis, which tracks outcomes over time, focusing on when events occur. The measure of association is the Hazards Ratio.

Question 26

One of the most famous and influential cohort study is the … ?

Answer 26

The Framingham Heart Study. This study identified major risk factors for cardiovascular disease.

Question 27

A study that found that the prevalence of COPD was higher in more polluted cities most likely used a _______ study.

Answer 27

ecological

Question 28

How can ecological studies mislead findings?

Answer 28

They are prone to ecological fallacy, where population-level associations may not apply to individuals. The major limitation with correlational studies is the potential for erroneous conclusions regarding the exposure-disease relationship on an individual level drawn from the population-level information. This type of erroneous conclusion is called ‘ecologic fallacy’.

Question 29

What would be an example of an ecological study?

Answer 29

The decline in the sale of cigarettes is associated with a decrease in ischemic heart disease in the same period. Essentially, this compares frequency of disease and frequency of risk-related factors across populations.

Question 30

Which study type is most appropriate to test a new drug’s efficacy?

Answer 30

Randomized clinical trials, as they involve exposure assignment and assess cause-effect relationships.

Question 31

What is the defining characteristic of a randomized clinical trial?

Answer 31

The exposure is assigned by investigators, making it an interventional study.

Question 32

What question does a randomized controlled trial answer?

Answer 32

“What is the effect of an intervention?” It determines cause-and-effect relationships.

Question 33

What is a single-blinded, double-blinded, and triple-blinded study in a RCT?

Answer 33

A single blinded study is when the subject is unaware that he/she is in the treatment or control (placebo) group. A double-blinded study is when neither subject nor researcher knows whether the subject is in the treatment or control group. A triple-blind study refers to additional blinding of the researchers analyzing the data.

Question 34

What type of RCT compares the effect of a series of 2 or more treatments on a subject, where subjects receive a treatment in a randomized fashion, then will have a washout period between treatments, and the subjects to serve as their own controls?

Answer 34

Crossover clinical trial

Question 35

When all subjects are analyzed according to their original, randomly assigned treatment, where no one is excluded, to avoid bias from attrition, crossover, and nonrandom noncompliance, but may dilute the true effects of intervention, this is called?

Answer 35

Intention-to-treat analysis

Question 36

What are the advantages in using “intention-to-treat?”

Answer 36

Intention-to-treat is an important principle used in the analysis of randomized clinical trials. Intention-to-treat means that the patient’s treatment status at the point of randomization is analyzed. If a patient who is assigned to the placebo group begins taking the medication assigned to the treatment group sometime after study initiation, or if a patient in the treatment group stops taking the prescribed medication, the data from these patients is still analyzed along with their original group. The value in the intention-to-treat approach is that it preserves the benefits of randomization and prevents bias due to selective non-compliance.

Question 37

What can be used as an alternative to “intention-to-treat?”

Answer 37

Investigators may alternatively use the ‘as treated’ rule, which is the opposite of intention-to-treat (i.e. if a patient switches therapy they are counted as members of the new group during analysis).

Question 38

What is the affect where subjects who fail to complete treatment as originally, randomly assigned are excluded?

Answer 38

Per-protocol analysis.

This increases the risk for bias. just like “As-treated analysis” where all subjects are analyzed according to the treatment they actually received.

Question 39

What does open label mean in a RCT?

Answer 39

In a Randomized Controlled Trial (RCT), “open-label” refers to a study design in which both the participants and the investigators are aware of which treatment or intervention each participant is receiving. This contrasts with “blinded” studies (single-blind, double-blind, triple-blind), where some or all parties are unaware of the treatment assignments.

Question 40

What phase involves a very small number of healthy volunteers or patients with disease of interest (Open label).

Answer 40

Phase 0

Initial pharmacokinetic and
pharmacodynamic assessment via
microdosing.

Question 41

Do most RCT include phase 0?

Answer 41

No.

Often skipped.

Question 42

What phase in an RCT performs the safety assessment via dose escalation to determine the maximum tolerable dose on a small number of healthy volunteers or patients with disease of interest and an open label?

Answer 42

Phase 1

Question 43

What phase in an RCT evaluates the efficacy assessment (does it work?), providing additional data on short-term adverse effects on moderate number of randomized, controlled, anonymized patients for a disease of interest?

Answer 43

Phase 2

Question 44

What phase of an RCT tests the effectiveness via comparison with current standard of care/placebo in a large number of randomized, controlled, anonymized, patients with disease of interest?

Answer 44

Phase 3

Question 45

What phase of an RCT provides data on long-term or rare adverse effects and attempts to answer the question, can it stay on the Market (is an open label again at this point)?

Answer 45

Phase 4

Question 46

Clinical trails are carried out to the … ?

Answer 46

End-point (outcome).

Question 47

What group of principles provide limited support (ie, necessary but not sufficient criteria) for establishing evidence of a causal relationship between presumed cause and effect?

Answer 47

Bradford Hill criteria