Lecture 5: Does This Drug Really Work? Flashcards
What occurs during Phase I of drug research?
- Small cohort of patients (20 - 100)
- Study how well tolerated the drug is and what are the pharmacokinetic properties of the drug
- Patients are given a few different doses to determine this
- See if patients experience any adverse side affects
What occurs during Phase II of drug research?
- 100 - 200
* Addresses efficacy: See if any patients derive benefit from the drug
What occurs during Phase III?
- 1000 - 6000 patients
- Randomized control trials where patients receive placebo and drug
- Both patients and clinicians are blind
- If drug sees some benefit it will be approved
What studies occur after the phase III trials?
The drug will still continue to be monitored after being released
What are Clinical trials?
Controlled human studies to assess dosage, administration, safety, efficacy
What is tested in phase I?
- Tolerable dosing ranges
- Bioavailability
- Excretion
What is tested in phase II?
- Efficacy
* Safety in greater numbers
What is tested in Phase III?
•Double blinded trials against placebo
Which phase tests for pharmacokinetics?
Phase I
What are Meta-analyses?
An approach to combine data from multiple trials often after a drug has been approved
How are meta-analyses often displayed?
As forest plots
What is an event on a metaanalysis?
The amount of times an outcome occurs such as a patient getting diabetes
What data does Statin plots provide data on?
- Number of trials
- Size of each trial
- Outcomes of trials
- Overall summary of all trials
What is the Odds Ratio?
The ratio of the event rate in treatment vs control (which one is favored in individual trials vs overall)
What characteristics must a drug have for it to be useful?
It must have a beneficial effect but must also be tolerable in terms of toxicity
What is the Therapeutic Index?
The ratio of the median toxic dose and effective dose
What is described using a Quantal Dose-Response Curve?
Effect or toxicity
How is a Quantal Dose Response Curve different from quantitative effect curves?
Quantal Dose Response Curves shows the cumulative number of patients who have a predefined response to a drug
What is the Effective Dose 50?
The dose that 50% of the patients will exhibit some beneficial response to a drug
What is the Toxic Dose 50?
The dose that 50% of the patients will exhibit some adverse response to a drug
Why is it good to have a big difference between the TD50 and the ED50?
Because then there is a bigger window to give patients that are not responding a slightly higher dose
What does a big therapeutic index mean?
It means that the drug is tolerated with minimal toxicity and gives a lot of flexibility for dosing
What is a drawback to the Therapeutic index?
There is a lot of variability in drug response for individuals
What other consideration must be taken into account for effect and toxicity?
Conditions like diet, liver function and kidney function
What should TI not be used for?
It should not be used as a rigid criteria for administration in a clinical setting
What is relative risk reduction?
A common parameter used to describe how drugs will reduce the likelihood of some undesirable event
What is an event?
Some outcome that is defined by whatever study is being performed ex. Heart attack or death
What is All cause mortality?
An event that means death by any means
What is the problem with relative risk reductions?
It doesn’t emphasize the real likelihood of risk in the general population and it may de-emphasize the risk of harms that may come up with taking the drug
What can Relative Risk Reduction be seen as misleading?
Because it emphasizes the benefits but not the risks
Why is the main reason relative risk reduction does not convey the risk?
It doesn’t capture the difference between a large reduction in something that is very infrequent versus something that is frequent
Give an example of a downside to relative risk reduction?
A high relative risk reduction may be seen in a drug that prevents something very rare but it may also be seen in a drug that prevents something that occurs relatively frequently
What is a more descriptive way to report the benefit of taking a drug?
Absolute Risk Reduction
What does the Absolute Risk Reduction describe?
The absolute number of cases that are prevented by taking a drug (rather than relative to baseline)
How do you interpret NNT?
The value given in the equation means that X number of people need to take the drug in order for one to benefit from it
Why would an NNT be so high?
Because the incidence of the event (purple eyeballs) is already so low
What NNT is optimal?
A low one like 1
What does an NNT of one mean?
That just about everybody taking the drug will receive the desired benefit
Why is a high NNT not good?
Because it mean that most people will not receive a benefit by taking a drug and be exposed to possible harms of the drug
What value of NNH is good?
A high number needed to harm is good
What does a negative absolute risk mean?
It means that an event has a higher rate in the experimental group, so you would describe 1/ARR as the NNH
When would you say the NNH instead of NNT?
When the ARR is negative
Why are some drugs with a high NNT given?
Because the potential outcomes that they are preventing are very severe like death
