Drug Discovery and Development (Raymond V. Oliva, MD) Flashcards
What was menoxidil originally designed for?
Treatment of colds (vasodilator)
However, it was eventually marketed as an anti-hypertensive.
Then, it was marketed to prevent baldness.
T/F: Drugs can target more than one part of the complicated process.
False
How long does it take to develop a new drug?
10 - 15 years
What is the average cost of drug development?
$800 M - $1 B
What do you call herbal products that were dropped from development before being approved?
Nutraceuticals
Describe: Pre-discovery phase
Understanding the disease and its underlying cause
What is avastin?
It’s a chemotherapeutic drug.
Enumerate the ways of finding a new molecule
- Nature
- De Novo
- High throughput screening
- Biotechnology
How are safety tests conducted?
- Cells
- Animals
- Computation Models
These include PCR and HPLC
What are CERA and epoietin beta for?
Treating chronic anemia
How would you describe CERA’s binding affinity to its receptor?
Lower association
What is lead optimisation?
The process of altering lead compounds to make them safer.
What factors are considered in lead optimisation?
- Formulation
- Route of Administration
- Large Scale Manufacturing
What are the types of pre-clinical testing?
- In vitro tests
2. In vivo tests
Why is pre-clinical testing performed?
To ensure the drug is safe for humans
How long do pre-clinical tests take on average?
1 - 5 years
What is the first step in the drug developmental process?
Filing an Investigational New Drug (IND) before testing
All clinical trials must be reviewed by which entity?
Investigational Review Board (IRB)
What is the ideal clinical trial for drug testing?
Placebo-controlled trial
Randomized
Double-blinded
What question is asked in Phase 1?
Is the treatment safe?
What is the sample size for Phase 1?
N = 20 - 100
Who are the subjects in a Phase 1 trial?
Healthy individuals
What is the purpose of a Phase 1 trial?
Determine the safe dosing range
How long does a Phase 1 trial usually take?
6 - 9 months
What is the question asked in Phase 2?
Does the treatment work?
Who are the subjects in a Phase 2 trial?
Diseased patients
What is the sample size for a Phase 2 trial?
N = 100 - 500
How long does a Phase 2 trial usually take?
6 months - 3 years
What can you say about the doses included in a Phase 2 trial?
Presence of low and high dose and negative control
It is concerned with the maximum therapeutic threshold.
Phase IIA studies are also known as?
Proof of concept studies
T/F: Phase IIA studies are well controlled clinical trials conducted to evaluate safety and efficacy in selected populations of patients.
False
They are pilot clinical trials.
What do objectives of Phase IIA studies focus on?
Dose-response
Type of patient
Dosing frequency
What phase of clinical trials represents the most rigorous demonstration of a medicine’s efficacy?
Phase IIB
T/F: Phase IIB studies are sometimes referred to as pivotal studies.
True
What are the questions asked in Phase III?
Will the treatment prolong life?
Does the new treatment work better than the standard treatment?
What experimental design does Phase III utilise?
Randomized controlled trial (RCT)
What is the sample size for Phase III studies?
N = 1000 - 5000 (except for cancer studies)
What is the objective of a Phase III study?
To generate significant data on efficacy, safety and overall benefit-risk of the drug
How long does a Phase III study usually take?
1 - 4 years of testing
The Philippines is involved in several Phase III studies for what types of drugs?
Anti-hypertensive
Anti-diabetic
Phase IIIA trials are conducted prior to submission of what to the FDA?
New Drug Application (NDA)
Phase IIIA clinical trials are conducted in what kind of population?
The population for which the medicine is intended
Trials of which phase provide much of the information contained in the package insert?
Phase IIIA
T/F: Clinical trials for special groups or under special conditions are also conducted in Phase IIIA
True
Can placebos be used on anti-asthmatic drugs?
No, but they can be used for drugs for diabetes mellitus
When does Phase IIIb occur?
After submission of the NDA but prior to medicine’s approval and launch
Describe the nature of Phase IIIb trials
Supplement earlier trials
Complete earlier trials
Directed towards new types of trials or Phase IV evaluation
With regards to manufacturing, a company must meet the FDA guidelines for what?
Good Manufacturing Practices (GMP)
What is the question asked in Phase IV studies?
Is the treatment safe over time?
What is the only approved COX-2 inhibitor in the US?
Celebrex
What COX-2 inhibitor marketed by Merck & Co. was withdrawn from the market for allegedly causing CVDs?
Viox (Rofecoxib)
What anti-diabetic drug marketed by GlaxoSmithKline was withdrawn from the market for allegedly causing heart failure and stroke?
Avandia (Rosiglitazone)
T/F: A drug in Phase III trial cannot be given to pregnant women, children, insulin-dependent patients and patients with New York Heart Failure Classification 3 and 4
True
How long do the drug discovery and pre-clinical stages take on average?
3 - 6 years collectively
How long do Phases I - III of clinical trials take?
6 - 7 years collectively
How long does an FDA review of a drug take?
0.5 - 2 years
