Lesson: Designs Of clinical trials

Question 1

Pirámides del clinical trial designs!

Answer 1

Clinical Practice guidelines
Meta-Analysis Systemic Review
Randomized Controlled Trial
Cohorts Studies
Case control Studies
Case Report case series
Animal and Laboratory studies

Question 2

How are Clinical trial defined?

Answer 2

Clinical trial mean a systematic study of a new drug (therapy protocol, devices) in human subjects to generate data for discovering or verifying the clinical claims or pharmacological and adverse effects with an aim to determine the safety and efficiency of drugs in question.

Question 3

What are the phase 0 ?

Answer 3

of subjects: 10-15 healthy volunteers

First in man early trial to determine if drug engages it’s expected target.

Dose: single, low dose

Timing: can be conducted with prior approval while final IND review is pending

Question 4

What is phase 1 ?

Answer 4

subj: 20-80 healthy volunteers

Initial safety evaluation determine safe dosage range, identify common side effects study toxicity profile of the drug.

Dose: single dose ,SAD, MAD

Timing: together with phase 0 trial first clinical trial conducted in an IDN process

Question 5

What is phase II?

Answer 5

of Subj: 100-300 volunteers with a target medical condition. Multiple dose trials often conducted against placebo

Begin to explore efficacy while maintaining safety

Timing: conducted after report to FDA of results of phase I trial

Question 6

What is phase III?

Answer 6

of subj: 1000 -3000 with the target medical condition. Múltiples dose trials ascending doses.

Final confirmation of safety and efficacy

Timing: conducted after report to FDA of results of phase II

Question 7

What is phase IV?

Answer 7

Any trial conducted after FDA approval of the drug.

Dose: variable

Timing: conducted after release of the drug by the FDA for marketing

Question 8

What are pre-Clinical phase of a trial ?

Answer 8

Testing on animal for toxicity-> Investigational new drug application —> describes the manufacture plan in Clinical trials. If approved by FDA the manufacturer becomes the sponsor of an existing IDN

Question 9

What trial designs are used in each phase?

Answer 9

-Phase I CT: all patient receive the drug, thus an unblinded, open label trial is suitable.
-Phase II and III CT: parallel designs, cross over, factorial design are commonly used.
-Phaee IV: Nonblinding/Non experimental (observational ): these include epidemiology designs such as case control or cohort studies

Question 10

What is an adequate and well-controlled study?

Answer 10

21 CFR 314.126: must show effectiveness; a statistically significant effect on a meaningful endpoint.
1-Pre-specified objectives and analysis methods
2-Valid comparison with a control to provide a quantitative assessment of drug effect.
3-Methods of assigning participants to study group minimizes bias and helps assure comparability with other pertinent variables
4-Measure taken to minimize bias on the part of the subjects, observers and analysis of data.
5-Methods of assessment of response are well defined and reliable

Question 11

What the acronym PICO(T.T) means ?

Answer 11

P: patient/ population/ problem
I: intervention
C:comparison
O: outcome

T: type of question
T: type of study

Question 12

What are common types of bias?

Answer 12

Selection
Measurement
Expectancy
Social desirability
Observational
Losses to follow up bias
Response and non-response
Reporting

Question 13

How do we avoid bias in clinical trial ?

Answer 13

Randomization of subjects
Blinding of subjects as well as investigators
Monitoring of clinical trial
Checking original sources doc
Source data verification
Clinical data management
QC, and QA procedures

Question 14

What are the most common methods of randomization?

Answer 14

Simple randomization
Stratified randomization
Cluster randomization

Question 15

Types of blind ?

Answer 15

Single or single-masked: only the participants is unaware of the treatment received.

Double : the participants and the clinician/ data collectors are unaware of the treatment

Triple blind: participants, clinician, data collectors, outcome adjudicators/ data analyst are all unaware of the treatment the participants receive

Question 16

What to consider when selecting a design ?

Answer 16

Chronology events
Subject convenience
Trial cost

Question 17

What are traditional designs for clinical trials ?

Answer 17

A-parallel
B-cross over trial
C-Factorial design
D-add-on design (add a therapy later)
E-Randomized withdrawal design
F- Early escape design: remove from study if patient meets certain criteria

Question 18

What is special desinforme small clinical trial ?

Answer 18

A- N-of 1 design: drug and placebo administered sequentially in a random sequence, generally 3 or more drug-placebo pairs
B- Decision analysis-based design
C-Adaptive designs (sequential rolling )
D-risk based allocation design

Question 19

What are other clinical trial designs?

Answer 19

Cluster randomized designs
Enrichment
Placebo challenging
Blind reader
Trial with Zelen’s
Trial with Wennberg’s
Trial with Comprehensive cohort
Design using historical control

Question 20

What is parallel group designs?

Answer 20

Group comparison parallel design: In this methods, efficacy of treatment is using two groups (treatment vs control)

Question 21

What is matched pair parallel group designs?

Answer 21

País of subject are formed possessing the same characteristics and who might be expected to respond similarly to treatment
Matching of patient is done before randomization

Question 22

What is a crossover design?

Answer 22

Is a modified randomized block design in which each block receives >1 treatment at different dosing periods.
Used when: data for both efficacy and safety are obtained,chronic disease and drugs has short half-life treatment periods and washout periods.

Question 23

What is a split-person design?

Answer 23

Occasionally, it is possible to administer the two intervention at the same time

Very similar to that of the cross-over trial, but no periods or the wash out .

Question 24

What is a factorial design ?

Answer 24

Used when it is desired to study the influence of a number of factors on the treatment compared as well as their interaction with different treatment.

Question 25

What is an add-on design?

Answer 25

A placebo controlled trial of an experimental intervention is tested with people already receiving an established, effective treatment

Question 26

What is a randomized withdrawal design?

Answer 26

Individuals who responded positively to an experimental intervention are randomized to continue receiving that intervention or to receive a placebo

Question 27

What is a single subject/N-of-1 design?

Answer 27

They are cross over trials in which one participant receive the experimental and the control intervention.

Question 28

What is an adaptive sequential design?

Answer 28

Here the participants are sequentially enrolled in the study and are assigned a treatment (usually at random)

Question 29

What is an adaptive rolling design?

Answer 29

Can roll on continually by introducing new treatment options from the evidence accumulated, dropping those of either proven efficacy or if founds not to be effective

Make use of intermediate endpoints

Question 30

A major part of the Trial Protocol ?

Answer 30

Study objective
Investigational plan
Subject completion withdrawal
Study administration