Interventional Study Designs

Question 1

What study designs are thought to be the only ones that can prove causation?

Answer 1

interventional studies

Question 2

What are some other terms for interventional studies?

Answer 2

clinical trial, clinical study, experimental study, human study, investigational study

Question 3

What is the key difference between interventional and observational studies?

Answer 3

In interventional, investigator selects interventions and allocates study subjects to forced-intervention groups. They are more “rigorous” in ability to demonstrate causation.

Question 4

What is the pre-clinical phase of an interventional study?

Answer 4

study phase that does NOT involve humans; it may involve animals.

Question 5

In general, the higher the phase, the higher the _____

Answer 5

population.

Question 6

What is phase 1 of an interventional study?

Answer 6

phase in which healthy volunteers (20 - 80) are used to asses safety, dose, toxicity of a drug. It is a short duration.

Question 7

What is phase 2 of an interventional study?

Answer 7

phase in which 100 - 300 patients with condition of interest are used to determine efficacy; safety is still important. It is short to medium in duration.

Question 8

What is phase 3 of an interventional study?

Answer 8

Phase in which 1000 - 3000 patients with condition of interest are tested, with a PRIMARY purpose of efficacy. It also uses superiority, non-inferiority and equivalency formats.

Question 9

What is another word for placebo?

Answer 9

Dummy

Question 10

What is phase 4 of an interventional study?

Answer 10

Long term effects of a drug in a large population are assessed. The goal is maintain long-term safety. It may rely on registries and surveys and can also be considered an observational study.

Question 11

What kind of study is phase 4 sometimes considered to be?

Answer 11

observational

Question 12

What are the advantages of interventional trials?

Answer 12

they can show causation and they are the only studies used by the FDA.

Question 13

What are the disadvantages of interventional trials?

Answer 13

cost, time, ethics, and most importantly external validity - are the conditions of the study applicable to the general population?

Question 14

What is a feature of explanatory studies?

Answer 14

they are generally restrictive in the amount of dosages, etc. given to each patient. They do not have much flexibility.

Question 15

What is a feature of pragmatic studies?

Answer 15

they are more flexible - drug combinations may be compared, placebos may not be used, and regulat people with multiple comorbidities are studied.

Question 16

What is a simple interventional study?

Answer 16

A study in whcih patients are randomized only once. Patients are divided into two groups, and a single hypothesis is tested.

Question 17

What is a factoral interventional study?

Answer 17

A study in which subjects are randomized at least twice; groups are divided into sub-groups. It is used to test multiple hypotheses at the same time.

Question 18

What is a negative of a factorial study?

Answer 18

More participants are needed in order to answer more questions.

Question 19

What are benefits of a factorial study?

Answer 19

Efficiency, sample size, complexity are improved, and the study is not as generizable.

Question 20

What are parallel interventional studies?

Answer 20

Studies in which groups are randomized, and no switching of intervention groups occurs after that.

Question 21

What are two types of parallel studies?

Answer 21

simple and factorial

Question 22

What are cross-over studies?

Answer 22

Studies in which groups serve as their own control by crossing over from one intervention to another during a study. IT allows for a smaller sample size.

Question 23

What is the washout period?

Answer 23

The period in which subjects return to their baseline health (e.g. the drugs are out of their system).

Question 24

What is the run in/lead in phase of an interventional study?

Answer 24

Phase in which all study subjects are given one or more placebos for initial therapy (defined time-period) to determine an new baseline of disease.

Question 25

What are disadvantages of cross over designs?

Answer 25

they are only suitable for long-term conditions, effects may carry over into other groups, complexity in data analysis,

Question 26

What is the most important endpoint of a study?

Answer 26

the primary outcome. It is the main research question used for developing/conducting a study

Question 27

What is a composite outcome?

Answer 27

An outcome that combines multiple endpoints into a single outcome. It could be considered a primary outcome.

Question 28

What are patient-oriented outcomes?

Answer 28

Outcomes that are very significant; they can include death, stroke, hospitalization, etc.

Question 29

What are surrogate markers?

Answer 29

elements used in place of evaluating patient-oriented endpoints, such as blood pressure for risk of stroke.

Question 30

What are non-random sample selections/allocations?

Answer 30

Allocation in which subjects do not have an equal probability of being selected or assigned to each intervention group.

Question 31

What are random sample selections/allocations?

Answer 31

Allocation in which subjects have an equal probability of being assigned to each intervention group.

Question 32

What is the purpose of randomization?

Answer 32

To make the groups as equal as possible, based on known and unknown important factors (confounders).

Question 33

What does randomization not guarantee?

Answer 33

equality of groups.

Question 34

What is is simple randomization?

Answer 34

Randomization in which there is an equal probability for allocation within one of the study grups.

Question 35

What is blocked randomization?

Answer 35

ensures balance WITHIN each intervention groups (e.g. that they are equal in size).

Question 36

What is stratified randomization?

Answer 36

ensures balance with known confounding variables (e.g. there is an equal distribution of healthy and sick patients in each group).

Question 37

What is a single blind masking study?

Answer 37

Study subjects are not informed of the intervention they are receiving, but the clinicians are!

Question 38

What is a double blind masking study?

Answer 38

Neither clinicians nor patients are informred of the intervention one is receiving.

Question 39

What is a open-label study design?

Answer 39

everyone knowns which intervention each subject is receiving.

Question 40

What can post-hoc surveys be used for?

Answer 40

ensuring adequacy of blinding; if the subjects can easily guess which group they are in, the blinding was not successful.

Question 41

What is a placebo therapy?

Answer 41

a form of blinding in which the placebo treatments are identical to the active treatments. Double dummy is when more than 1 placebo is used.

Question 42

What is the placebo-effect?

Answer 42

Patients may think they are better due to the type of care they are receiving or the way they are asked questions.

Question 43

What is the hawthorne effect?

Answer 43

Patients report positive results in placebo because they desire the study to have successful results.

Question 44

What is post-hoc sub-group analysis?

Answer 44

When researchers compare groups in multiple ways in order to find some sort of correlation; it can be misleading and increases risk of type II errors.

Question 45

How are drop-outs or lost to follow-ups managed?

Answer 45

they are either included or not included in the study.

Question 46

What is intent-to-treat?

Answer 46

A researcher uses the information from a drop-out in the study, and converts all missed assessments to a null effect.

Question 47

What are the benefits of intent-to-treat?

Answer 47

it preserves the randomization process, baseline characteristics, group balance, and maintains statistical power.

Question 48

What is "as treated" management?

Answer 48

group assigments are ignored, and subjects are allowed to switch groups and be in groups they moved to, ended in, or stayed in the most.

Question 49

What is a disadvantage of per-protocol analysis?

Answer 49

it biases the estiamtes of effect (commonly over-estimates effect).

Question 50

How do researchers assess adherence (compliance)?

Answer 50

pill counts, bottle counter-tops and drug levels.

Question 51

How to researchers improve adherence (compliance)?

Answer 51

frequent follow-ups, treatment alarms/notifications, medication facts/dosage containers.