EBCR 3: Drug Development Process- Clinical Trials

Center for Drug Evaluation and Research

part of the FDA, grants drug therapy approval

what does CBER approve

biosimilars (highly similar to already approved biologics

What do investigators have to submit to the FDA?

-routes of administration

-testing drug formulas

-assessing the PK/PD and pharmacogenomics

-evaluating the effect of the IP on the subject's quality of life

Fast track designation

treat serious condition and fill an unmet medical need, based on promising animal or human data

breakthrough therapy designation

substantial improvement over standard therapy

Priority review designation

significantly improve treatment diagnosis or prevention

What is the ICH

international conference on Harmonization

- ethical/scientific standards for conducting clinical trials

What is a prevention trial

prevent or lower risk of condition

Screening/ detection trial

detect cancer in asymptomatic people

QOL and supportive care trial

quality of life

What do Preclinical studies include?

-Evaluate drug in tissue cultures and animals

-determine lethal dose in animals causing acute toxicity in 10% of aminals tested

-define organ-sensitive toxicity in sensitive animal models and the reversibility of toxic effects

-Define initial safe dosage to be used in Phase I human trials

What is required to begin investigational drug research in human subjects?

IND Application (FDA 1571)

T/F: all human trials require FDA approval

False, but still need to be IRB compliant

Main purpose of Phase I:

To find the proper dose to use in patients

Phase I characteristics:

-healthy patient volunteers

-20-80 participants

-discover PK/PD affects

What is the starting dose for trials in humans?

1/10th of LD of the most sensitive species tested

Define MAD

Maximum administered dose- highest dose which certain % patients develop DLT

Define DLT

dose limiting toxicity- one of a ser of unacceptable ADRs related to the study drug

Define MTD

Maximum tolerated dose

Dose level below the MAD

Recommended Phase 2 dose

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Rule based dose escalation

-No prior assumptions about dose-toxicity curve

-up or down depending on toxicity

Model based dose escalation

-Establishes dose-toxicity curve prior to enrollment

-utilizes statistical models to find a dose level based on toxicity data from all enrolled patients

Which uses preclinical information to base the dose, model or rule based?

model

Main purpose of Phase III Trials

Safety and efficacy at a fixed dose in specific indication

-screen out ineffective drugs and further evaluate promising drugs

-further define safety and toxicity

Starting dose in a phase II trial is:

One dose below the max dose

Two Stage Design Model

Phase II trial that starts with smaller number of patients, and move on to larger numbers if the results are promising

Population enrichment design

Targets populations that would benefit the most based on positive or negative biomarkers

Adaptive Clinical Trial Model

-Has preset points in time where researchers can analyze data they are gathering and make changes to the study

Umbrella Trial

Multiple Targeted therapies in a single disease

Basket trial design

single targeted therapy in multiple diseases/ subtypes

Platfrom design (teachers favorite)

Multiple targeted therapies in a single disease continuously

T/F: Platform trials are able to be changed overtime

True; they can add experimental arms at anytime