Epi - L2 - Interventional Studies

Question 1

What other terms could be used or “interventional studies”

Answer 1

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

Question 2

what are the key differences between interventional studies and observational studies?

Answer 2

• investigator selects “interventions” and allocates study subjects to forced-intervention groups
• more ‘rigorous’ in its ability to show cause-and-effect
  • can demonstrate causation

Question 3

What are the phases of interventional studies?

Answer 3

phase 0, 1, 2, 3, 4

Question 4

what are the differentiating factors as the phases progress?

Answer 4

1. purpose/ focus of the study
2. population studies (healthy/ diseased)
3. sample size
4. duration

Question 5

what occurs before phase 0?

Answer 5

Pre-Clinical:

• bench research; animal research.
• research prior-to human investigation

Question 6

Phase 0

Answer 6

aka Exploratory; Investigational New Drug

1. Assess drug-target actions and possibly pharmacokinetics in single or ‘a few’ doses (FIRST-IN-HUMAN USE) **does it or does it not DO what we EXPECT it to do based on pre-clinical stage)
2. Healthy (or diseased patients ) volunteers
3. Very small N (eg: <20)
4. Very short duration (eg: a single dose to just a few days)

YOU DO NOT SEE SAFETY OR EFFICACY

Question 7

Exam Freebie:

Answer 7

Phase 0 and Phase 1 are the only ones you can see healthy patients in // Phase 4 = NEVER use healthy people

Question 8

Phase 1

Answer 8

aka Investigational New Drug

1. assess SAFETY/ TOLERANCE and pharmacokinetics of one or more dosages (first-in-human/ early-in-human use)
2. Healthy or Disease volunteers (depends on disease)
3. Small N (eg: 20-80)
4. Short duration (eg: just a few weeks)

*classic sign: SAFETY and PHARMACOKINETICS for the first time here –> how does the body handle the drug?

Question 9

Phase 2

Answer 9

aka Investigational New Drug

classic sign: EFFICACY of drug; dose escalation: different groups with different doses to see who has best results

1. assess effectiveness (continue to assess safety/tolerability; expands on Phase 1 purpose)
2. Diseased volunteers
   - may have narrow inclusion criteria for isolation of effects
3. Larger N (100-300)
4. short- to-medium duration (weeks to months)

Question 10

Phase 3

Answer 10

(Investigational New Drug; Indication/ Population)

classic detail: P3 is the last phase before FDA approval

1. Assess effectivness
2. Diseased volunteers
   - may expand inclusion and comparison groups for delineation of effects
   - various statistical-perspectives can be taken in studies: superiority; noninferiority; equivalency
3. Larger N (500-3000)
4. Longer duration (few months to a year+)

Question 11

Phase 4

Answer 11

aka post FDA-Approval

1. assess long-term safety, effectiveness, optimal use (risk/ benefits)
2. diseased volunteers (expand use criteria

Question 12

what are the advantages of Interventional trials?

Answer 12

• cause precedes effects, can demonstrate causation

- only designs used by FDA for “approval” process (on-label)

Question 13

what are some disadvantages of Interventional Trials?

Answer 13

• cost
• complexity/ time
• ethical considerations (risk vs benefit evaluation)
• generalizability (aka; external validity) - is study pop similar to general population and will methodology and findings be applicable to them?

Question 14

what are the terms explaining how many RANDOMIZATION steps must the enrolled participant go through before they’re in the final group?

Answer 14

• simple

- factorial

Question 15

all studies can either be:

Answer 15

simple or factorial;
and
parallel or series

Question 16

Simple interventional study

Answer 16

• subjects are divided (randomized) exclusively into 2 groups
• a SINGLE randomization process
• commonly used to test a SINGLE hypothesis at a time

Question 17

Factorial interventional study

Answer 17

2 or more randomization steps

• divides subjects into 2 or more groups and then further sub-divides each of those groups into 2 or more additional groups
• used to test MULTIPLE hypotheses at the same time

Question 18

what are the advantages and disadvantages of Factorial Interventional studies?

Answer 18

ADVANTAGES

• improves efficiency for answering clinical questions
• increases study population sample size (due to incr. group #)

DISADVANTAGES

• incr. complexity (which may be a barrier to recruitment)
• incr. risk of drop out (due to complexity)
• may restrict generalizability

Question 19

what are two other designs of Interventional studies?

Answer 19

parallel and cross-over

Question 20

parallel

Answer 20

they stay in the same group throughout the study, whether simple or factoral

• groups simultaneously and exclusively managed
• NO SWITCHING of intervention groups after initial randomization

Question 21

Cross-Over

Answer 21

aka Self-Control

• groups serve AS THEIR OWN CONTROL by CROSSING OVER from one intervention to another during the study
• allows for smaller N

Question 22

differentiate ‘wash out’ and ‘lead in’ phases

Answer 22

….

Question 23

what is the purpose of Randomization?

Answer 23

to make groups as equal as possible; based on known and unknown important factors (confounders)

• attempts to reduce systematic differences (bias) between groups which could impact results/ outcomes
• TABLE 1 customarily shows you whether groups are equal
• EQUALITY OF GROUPS NOT GUARANTEED

Question 24

Examples of Forms of Randomization

Answer 24

• simple
• blocked
• stratified

Question 25

simple

Answer 25

aka standard

• flip of the coin (FOTC)
• equal probability for allocation within one of the study groups

Question 26

blocked

Answer 26

*if we can’t afford to run the risk of having 4:1 probability with FOTC, we do Blocked Randomization

• ensures balance within each intervention group
  
  • when researches want to assure that all groups are equal in size
• researches can take quick peeks at the groups to make sure they’re balanced and evened out. if it starts to get too heavy on one side, you start doing blocked randomization; “ok, every 5th person will go here, cuz shits too hectic over there.”

Question 27

Stratified

Answer 27

ensures balance with KNOWN CONFOUNDING VARIABLES

• examples: gender, age, disease severity
• can also pre-select LEVELS to be balanced within each interfering factor (confounder)