Pharmacodynamics - Clinical Trials Flashcards
Phase I clinical trials involve which type of individuals?
Healthy individuals
What is pharmacology?
The body of knowledge gathered on the understanding of how therapeutic agents (Drugs) work
Effective therapeutic agents should improve what?
QoL
Life expectancy
What is the governing body of drugs in Canada?
U.S?
Canadian Department of Health and Welfare
US Food and Drug Administration
What are the main issues in which QA is needed by these drug governing agencies?
The drug has to be safe and effective
The drug needs to be able to be administred in a suitable fashion
When do we determine if a drug can be administered in a suitable fashion?
Preclinical and clinical trials
Preclinical trials are what?
Completed in-vitro in the lab or using an animal model
clinical trials are specific to humans
Patenting:
- Carried out as soon as a __________ useful drug is ________
- Carried out before ________ and ________ ______s
- ______ years of patent ______ are lost due to _____
- Patent a _______ of compounds rather than an ________ _________
- Also patent ________ ________
Carried out as soon as a [potentially] useful drug is [identified]
Carried out before [clinical] and [preclinical trials]
[Several] years of patent [protection] are lost due to [trials]
Patent a [group] of compounds rather than an [individual structure]
Also patent [production method]
What is the purpose of patent protection?
Protect the intellectual property which you dumped a substantial amount of money for R&D.
How is a patent lost?
If no new uses are found.
How lojng is the patent pending period?
around 10 years
Regulatory affairs of patenting:
- Drug must be approved by ______ ______ (ex?)
- Proper _______ is essential. Must demonstrate:
- ___
- ___
- ____
Drug must be approved by [regulatory bodies]
[ex: FDA, European Agency for the Evaluation of Medicinal Products]
Proper [record-keeping] is essential.
Must demonstrate:
- [GLP - good laboratory practice]
- [GMP - Good Manufacturing Practice]
- [GCP - Good Clinical Practice]
What are the three main components of Preclinical trials?
Toxicology (report)
Pharmacology (report)
Formulation (report)
What is involved for determing toxicology in pre-clinical trials?
In-vivo (gen. animals) and in-vitro tests for acute and chronic toxicity
What is acute toxicity?
Toxicity within 24 hours
What is chronic toxicity?
Toxicity for longer than 24 hours
What is the pharmacology portion of preclinical trials?
Pharmacokinetics - ADME - Identification of drug metabolites and their properties Pharmacodynamics Drug actions - selectivity of action at drug target
What is the formulation portion of preclinical trials?
Stability tests and method of delivery
In what trial and what portion are activation, transactivation, etc, properties determined?
Preclinical trials
- ADME studies
What is a stability test?
When the drug is made into a tablet form for example, left out in the sun or how a patient might leave it and see how long it stays stable
- determine expiry date from here.
What is the expiry date of a drug based on?
Time length before a drug’s change is over 5% of the purported value
When would using a drug after the expiry date really not be advised?
When the drug TI is low
Phase 1 Clinical trials
- Always carried out in ________ ________
- Useful in establishing _____ ______
- Useful for studying _______, including drug __________
Phase 1 Clinical trials:
- Carried out in [healthy volunteers]
- Useful for establishing [dose levels]
- Useufl for studying [pharmacokinetics], including drug [metabolism]
Phase 2 Clinical Trials:
- Carried out on ______
- Carried out as ______ _______ studies
- Demonstrates whether a drug is __________ useful
- Establishes a _______ regime
- Identifies ______ ______
Phase 2 Clinical Trials:
- Carried out on [patients]
- Carried out as [double blind] studies
- Demonstrates whether a drug is [therapeutically] useful
- Establishes a [dosing] regime
- Identifies (potential) [side effects]
Often, in phase 1 clinical trials, a ____ dose is given to healthy individuals.
low
Rather than giving a placebo in a double blind, what do doctors now give to patients not receiving the ‘treatment’?
A drug with a`similar effect that is already on the market, rather than the new drug being tested.
Phase 3 clinical trials:
- Carried out on a ______ number of patients
- Establishes _______ proof for _______ and ________
Carried out on a [larger] number of patients
Establishes [statistical] proof for [efficacy] and [safety]
Phase 4 Clinical trials:
- Continued after a drug reaches the _______
- Studies _____-term effects when used _______
- Identifies unusual ____ ______
Phase 4
Continued after a drug reaches the [market]
Studies [long]-term effects when the drug is used [chronically]
Idenitifes unusual [side effects]
Why is PMS (postmarketing surveillance) used?
Drugs are approved on the basis of clinical trials, which use a reduced number of individuals and do not present other medical conditions.
PMS allows one to understand how drugs may act in these instances.
PMS can further refine, or confirm or deny, the safety of a drug after it is used in the general population by: (two factors)
Applying the drug to a large number of people who have varying medical conditions
What are different surveillance methods or approaches used in PMS?
Spontaneous reporting databases Prescription event monitoring Electronic health records Patient registries Recording of linkages between health databases
