Lesson: Designs Of clinical trials Flashcards
Pirámides del clinical trial designs!
Clinical Practice guidelines
Meta-Analysis Systemic Review
Randomized Controlled Trial
Cohorts Studies
Case control Studies
Case Report case series
Animal and Laboratory studies
How are Clinical trial defined?
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.
What are the phase 0 ?
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
What is phase 1 ?
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
What is phase II?
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
What is phase III?
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
What is phase IV?
Any trial conducted after FDA approval of the drug.
Dose: variable
Timing: conducted after release of the drug by the FDA for marketing
What are pre-Clinical phase of a trial ?
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
What trial designs are used in each phase?
-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
What is an adequate and well-controlled study?
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
What the acronym PICO(T.T) means ?
P: patient/ population/ problem
I: intervention
C:comparison
O: outcome
T: type of question
T: type of study
What are common types of bias?
Selection
Measurement
Expectancy
Social desirability
Observational
Losses to follow up bias
Response and non-response
Reporting
How do we avoid bias in clinical trial ?
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
What are the most common methods of randomization?
Simple randomization
Stratified randomization
Cluster randomization
Types of blind ?
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
What to consider when selecting a design ?
Chronology events
Subject convenience
Trial cost
What are traditional designs for clinical trials ?
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
What is special desinforme small clinical trial ?
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
What are other clinical trial designs?
Cluster randomized designs
Enrichment
Placebo challenging
Blind reader
Trial with Zelen’s
Trial with Wennberg’s
Trial with Comprehensive cohort
Design using historical control
What is parallel group designs?
Group comparison parallel design: In this methods, efficacy of treatment is using two groups (treatment vs control)
What is matched pair parallel group designs?
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
What is a crossover design?
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.
What is a split-person design?
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 .
What is a factorial design ?
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.
What is an add-on design?
A placebo controlled trial of an experimental intervention is tested with people already receiving an established, effective treatment
What is a randomized withdrawal design?
Individuals who responded positively to an experimental intervention are randomized to continue receiving that intervention or to receive a placebo
What is a single subject/N-of-1 design?
They are cross over trials in which one participant receive the experimental and the control intervention.
What is an adaptive sequential design?
Here the participants are sequentially enrolled in the study and are assigned a treatment (usually at random)
What is an adaptive rolling design?
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
A major part of the Trial Protocol ?
Study objective
Investigational plan
Subject completion withdrawal
Study administration
