L1: Unmet medical needs Flashcards
how many drugs are made in north america?
prescriptions?
> 1000 drugs
3.4 billion prescriptions
what are first-in-class drugs
drug that targets a protien that hasnt been targeted before by another drug
what is a me-too drug
drug that targets a protein that has been targeted before by another drug
what are the phases in the drug development pipeline?
related to the flow in one direction of creating a drug
- prelinical/discovery
- IND
- phase I, II, III
- NDA
- Phase IV
how many years does each phase take and what is the test population, purpose and success rate for each? plus the intermediate trials
study the chart!!!!!!!!!
discovery/preclinical testing:
years: 6.5
test pop: lab and animal
purpose: assess safety, bio, and formulations
success rate: 5000 compounds evaluated
File IND to FDA:
purpose: propose the drug to he FDA and explain the new drug’s safety and potential efficacy based on preclinical studies. if approved, clinical trials begin
phase 1:
years: 1.5
test pop: 20-100 healthy people
purpose: safety and dosage
success rate: 5 drugs enter trials
phase 2:
years: 2
test pop: 100-500 patients
purpose: evaluate effectiveness and look for side effects
success rate: 5 drugs enter trials
phase 3:
years: 3.5
test pop: 1000-5000 patients
purpose: confirm effectiveness, long term effects
success rate: 5 drugs enter trials
File NDA at FDA:
purpose: the FDA, review the NDA to determine whether the drug is safe and effective for its intended use. if approved, drug can hit the market.
FDA:
years: 1.5
test pop: -
purpose: review and approval process
success rate: 1 drug approved
Phase 4:
purpose: additional post marketing testing required by FDA
how does the drug development pipeline reduce risk?
- de-risking drug candidate from one step to the next
- ethically it is dangerous to expose a drug that is not evaluated
phase 1: small experiments on drug
phase 2: if drug safe, continue clinical trials
phase 3: if drug perfoms well under clinical trials (efficacy), confirm with larger numbers
what is the list of essential medicines? what does it take into account (8 things) ?
book that posts the list of essential medicines. published every two years by the WHO.
Takes into account:
* prevalence
* how serious is the disease: impact on disability-adjusted life years, DALYs
* public health, community health
* evidence of efficacy (that the drug works)
* evidence that the drug is safe
* list includes cost-effective drugs
* value for $ - WHO has a global mandate
who decides what drugs are important for development (6 things)
all things considered, like:
- an evaluation of the therapeutic need
- global burden of the disease
- prediction of the trend of the disease’s burden
- patient voices
medical need
- Is the condition life-threatening or self-limiting?
- how long does the medical condition last
Availability of Current Therapy
– the current treatment satisfactory
would a new drug be better?
- increase efficacy?
- more safe?
– Fewer side effects?
– More convenient to take (once a day)
What are the steps in the drug discovery/preclinical phase of the pipeline?
what is a drug target and how does it relate to this phase?
Drug target: A molecule (usually a protein) involved in the disease, that the drug binds to, often inactivation the molecule
Steps of the drug discovery phase:
1. choose a disease mechanism and model
2. identify and validate the drug target of the disease. can a drug even bind to this protein (it has to be able to to be a drug target)
3. test thousands of chemicals against the drug target. if its a smaller chemical it can move in the body well, be safer, and have a better effect on the target
4. test the drug in at least two animal species as a safety requirement (by the FDA)
explain the purpose, design, and subjects in the phase 1 clinical trials
Purpose
– Determine a safe drug dose
– determine pharmacokinetics – what happens and how does the the drug move in the body.
Design
– cautious trials of dose escalation. do trials with a low dose then increase it to see which is the most effective.
Subjects
– healthy normal volunteers usually
– Sometimes patients with the disease (cancer) – not usual
– Must obtain informed consent from subjects
what do phase 1 ads include
usually specify what the requirement of the volunteer is:
- aka the age group and the fact that they are healthy
- brief intro to the clinical trial
explain the objective, subjects, and design in a phase 2 clinical trial
Objective
- To obtain preliminary information on the efficacy of the drug
- Efficacy: does the drug work to treat the medical condition? does it achieve its purpose?
Subjects
- Patients with the disease
Design
- Compare treated individuals to control individuals (placebo)
- compare results
what does a phase 2 clinical trial ad look like
- asks if the person has the disease they are looking to treat
- specifically states that they have to be experiencing symptoms
why do phase 2 clinical trials use placebos?
what is the placebo effect
Placebos
– Placebos look like real pills but contain no active drug ingredient
– serves as a baseline measurement. the scientists can measure the effect of the treatment vs no treatment, while accounting for the placebo effect
Placebo effect
- the placebo effect is the psychological effect of one taking a drug and thinking its working, even though it has no medicinal properties
how can the confidence in clinical trials (phase 2) be improved?
we can increase the confidence of our results by using blinding in the experimental method to reduce bias
* Single-blind: subjects unaware if they get the treatment or placebo
* Double-blind: neither subjects nor researchers know who took what drug
- the computer knows who took what
