L11 Drug Discovery and Clinical Trials Flashcards
What are the three broad processes in the pathway to a new drug?
- Drug discovery
- Pre-clinical development
- Clinical development
What are the 4 major aspects of the drug discovery process?
- Disease characterization
- Target selection and identification of drug hits
- Lead optimization
- Pharmacological profiling
What are the 3 major aspects of pre-clinical development?
- In-vitro and in-vivo animal models
- Pharmacokinetics and toxicology
- Formulation and synthesis scale up
What are the 3 major aspects of clinical development?
- Clinical trials
- Safety and efficacy
- Pharmacokinetics and toxicity
What are the two possible approaches to the drug discovery process?
- Compound-centered
2. Target-centered
What is the compound-centered approach?
Take a compound with interesting activity/chemistry and screen biological systems for interesting biological functional effects
What is the target-centered approach?
Identify a protein target with known disease association/activity and screen large chemical libraries to identify drug hits that interact with the target and modify activity
What happens in lead optimization?
A new drug lead is identified; it may not exhibit ideal drug properties. Chemically-modified variants are developed and screened for an increased pharmacological profile.
What is the outcome of the lead optimization process?
New Chemical Entity (NCE)
After a new drug lead is optimized, what happens?
It is tested for efficacy in pre-clinical animal and cellular models of disease.
What is the primary role of the CDER?
Ensure all prescription and OTC drugs are safe and effective; review all applications for new and generic drugs; monitor compliance with good manufacturing practice
Describe the process of a drug candidate becoming an approved new drug.
- Investigational New Drug (IND) application
- FDA IND review/IRB review
- Clinical trial phase I, II, III
- NDA
- FDA NDA Review
- New drug
What provides exemption from the federal law that only approved drugs may be shipped across state lines?
Investigational New Drug (IND) Application
What are the three types of investigational new drug application (IND)?
- Investigator: study an unapproved drug/approved drug for new indication or some other change
- Emergency use: authorizes an experimental drug for a single patient with a serious condition
- Treatment: allows promising experimental drugs not yet approved to be used in patients with serious conditions
What is a set of conditions that must be met in order to participate in a clinical trial?
Inclusion critera
What are standards used to determine whether a person may or may not participate in a trial?
Exclusion criteria
What is the gold standard trial for causality?
Randomized controlled clinical trial
What is something not directly related to the endpoint that can influence the outcome?
Confounder
What is a trial where both physician and patient know which treatment is administered?
Open label
What is a trial designed to demonstrate that one treatment is clinically better to either the placebo or another drug?
Superiority trial
What is a trial designed to demonstrate that one drug is not appreciably less effective than the standard therapy?
Non-inferiority trial
What is done in a crossover study?
Alternating period of administration of placebo and test drug; reduces problems with confounders
Describe the number and type of volunteer, the questions asked, and the length of time for a Phase I clinical trial.
- 20-100 healthy volunteers
- Is it safe and tolerable? What are the pharmacokinetic parameters?
- Months
Describe the number and type of volunteer, the questions asked, and the length of time for a Phase II clinical trial.
- 100-200 patients
- Does it work in patients? What is the appropriate dosing?
- 1-2 years
Describe the number and type of volunteer, the questions asked, and the length of time for a Phase III clinical trial.
- 1000-6000 patients
- Does it work in large patient populations?
- 3-5 years
What happens after Phase III trials?
Regulatory approval
What is Phase IV?
Post-marketing surveillance for adverse effects, interactions, and complications
What happens after the completion of Phase II trials?
FDA meets with the drug sponsor to establish the safety of proceeding with Phase III
When does a drug withdrawal happen?
Unacceptable toxicity or new adverse reactions; manufacturer agrees to cease marketing
What is a drug recall?
Temporary removal of a drug from the market
What is a Class I recall?
Reasonable probability that use of drug will cause serious health consequences of death
What is a Class II recall?
Use of drug will cause temporary adverse health conditions, although probability of serious health consequences is remote
What is a Class III recall?
Use of drug is unlikely to cause adverse health consequences
How long is patent protection for new drugs?
20 years
What is an abbreviated new drug application used for?
Marketing of a generic version of the drug
