Drug Development Flashcards
What are the stages of drug development
1- Drug Discovery
2- preclinical studies
3-Clinical development ; phase 1, phase 2 and phase 3
4- Post marketing surveillance - phase 4
What happens in the drug discovery phase?
1- Random screening
2- Serendipity
3- Rational drug designing
4- Target-centred approach
What is involved in random screening?
this is a blind hitting procedure where chemical compounds are screened for different types of biological activity
Tests include studies on animal behaviour, animal models of the human diseases and on isolated tissues
What is serendipity
The discovery of something by chance e.g. penicillin, lignocaine and phenytoin (antiarrhythmics), methotrexate, anticancer drug also used for psoriasis
Rational drug Design
This uses a compound centred and target centred approach. Promising agents, through compound centred approach could be obtained from natural products
Drugs can be developed from pharmacological data obtained from structure activity relationships of a drug
Target Centered Approach
Biochemical or molecular targets are used to search for compounds, not sure of compound so target is looked at to design a suitable compound
CADD
Computer-aided drug design- these are used in target centered approaches
Lead optimisation
This is used to identify one or two drug candidates with the best possible:
Balance of potency
Target selectivity
Pharmacokinetics and safety
Aim
This process requires 3 too 5 years
What is involved with pre clinical studies?
Tested in vitro models to show pharmacological profile
Generally done on a rodent (rat, rabbit, guinea pig) then a larger animal (cat, donkey, pig, monkey)
What are the objectives of the pre clinical studies?
- Activity
- Toxicity
- Selectivity and specificity
- Mechanism of action
- Drug metabolism
What types of tests are used?
- Pharmacodynamic studies
- Tests on isolated organs, bacterial cultures
- Tests on animal models of human diseases
- General observational test
- Confirmatory tests and analogous activities
- Mechanism of action
- Toxicological studies
- System pharmacology
What is the assessment of safety index?
- Maximum tolerated dose
- Therapeutic index
- No observable adverse effects Level (NOAEL)
- Human Equivalent Dose
What are clinical trials?
To determine how effective something is in the human population- dose administration, drug formulation, effect of therapies on quality of life
What are the types of clinical trials?
- Treatment
- Prevention
- Early detection screening
- Diagnostic
What are the clinical trial phases?
- Safety : side effects, does it move through body, can it be used at the same time as other medications
- Efficacy : effective dosage, does it relieve, reverse or stop progression of condition
- Follow up : long term benefits/risks?
- Confirmation
If anything happens that causes injury or harm, clinical trials stop until a reason can be provided as to why it happened e.g one of the volunteers had an underlying health condition etc
Who are the players in clinical trials?
- Human subject volunteers
- Physician Investigators
- Research nurses
- Pharmacists
- Lab techs
- Social workers
- Data managers
Research Protocol
Code of Federal Regulations (CFR)
What does a research plan include
- Objective of the study
- Background and rationale
- Subject selection criteria
- Treatment plan
- Study procedures
- Responsible Evaluation criteria
- Statistical Section
What is the IRB
Institutional review board
They approve all clinical trials and monitor them. It is an independent committee of physicians, nurses, statisticians
They ensure a clinical trial is ethical and the rights welfare of study participants are protected
Ethics Committee
They approve clinical trials before it can be conducted. They don’t allow clinical trials to be conducted if they feel potential risk is greater than potential benefit. The EC is designed to protect participants from unscientific research. It also ensures the INFORMED CONSENT FORM explains the trial properly in a language that is clear and understandable and participants sign before participating
What are the eight elements of informed consent?
1 - Trial involves research - purpose
2 - Description of any reasonably foreseeable risks
3 - A description of any reasonable benefits subject may expect from research
4- Alternative procedures or treatment that may be available
5 - Extent of confidentiality
6 - Any compensation/medical treatments available in case of injury
7- Contact person for questions about research
8 - A statement that participation is voluntary
Patient Recruitment
Strategies:
- Physician trust and contact
- Study staff contact
- Speaking to community groups
- News paper and radio ads
- Internet websites
- Physician referrals
Data Collection and reporting
Data is collected on case report forms
Who do you report to in case of serious injury from research
- Sponsor
- FDA
- IRB
