clinical trial design week 9 Flashcards
what are the stages in development of a new drug
- research (can take up to 10 years), within this time have to do toxicity studies, register intellectual property, decide what formulation they want
- then decision for development can take up to a year once they have evidence from their research
- then go into the development stages, 1,2,3, (phase 4 is post marketing)
what tests do they do pre-clinical development of a new drug
- animal pharmacology (dose, adverse effects)
- animal toxicology (teratogenicity, fertility, mutagenicity)
- tissue culture
what happens in phase 1 of clinical development
volunteer studies
- clinical pharmacology in normal volunteers generating pharmacokinetic, metabolic and pharmacodynamic data
- usually involves around 100 subjects (normally healthy individuals)
- certain drugs e.g. cytotoxic will bypass this phase (if developing drugs for cancer won’t give them to normal volunteers so bypass this stage)
what happens in phase 2 of development
- clinical investigation to confirm kinetics and dynamics in patients (who may have renal/liver/GI absorption problems)
- provides some evidence of efficacy and identifies a likely dosage range
- involves up to 500 patients
what happens in phase 3 of development
- formal therapeutic trials where efficacy will be established and evidence of safety obtained
- involves 1,000-10,000 patients
- at completion all data (pre-clinical, pharmaceutical and clinical data) is submitted as an application to the regulatory authority for a license to sell the drug
what is phase 4 of development
- post-marketing surveillance to produce evidence of long term safety
- may involve tens or hundreds of thousands of patients world wide
who are clinical trials regulated by
- MHRA
- test efficacy (compare with placebo, compare with another drug)
- test safety
what is an observational study
- if you don’t want to do a big study you can do a small one say 500 patients in Aberdeen
- although there are issues with replication and diversity, patients in Aberdeen may be very different to those in Japan
- can be issues with causation or correlation because it is a small study
- observational studies on their own are not robust enough to allow companies to give out drugs
what are pilot studies
- not to estimate outcome, they are to test study design
what is a double blind trial
- neither patient or doctor knows which compound the patient is getting
what is a single blind study
- patient blinded, doctor knows
what is a prospective study
- protocol is decided before hand
what is a retrospective study
- looking back at data, so more open for bias, can put your own spin on data
what are the different comparisons you can do to test efficacy in clinical trials
- compare with placebo
- compare with other drug
what is cross over design
- both groups get the two different compounds at some point with wash over period in between
- e.g. group 1 gets drug A, wash over period for 8 weeks, then group 1 gets drug B and vice versa for group 2
- allows you to use a smaller number of people
- can be useful if you can’t find enough people for two separate groups
- one of the issues is patient can change over time e.g. change their diets
what is a randomised control trial
- patients are assigned at random to either treatment or control
- gold standard
what are the disadvantages of randomised control trials
- generalised results, subjects may not represent general patient population, tend to be better at complying
- recruitment, twice as many patients needed for the study
- acceptability of randomised process, some physicians will refuse (PFO closure in US), some patients will refuse (want to know their treatment)
- administrative complexity
what is a parallel clinical trial
- used in phase 3
- compares two or more treatments
what is a withdrawal clinical trial
- used in phase 3 development
- the treatment is removed during one or more periods, aims to evaluate the optimal duration of treatment
what is a group/cluster trial
- used in phase 3 development
- type of randomised control trial in which groups of subjects (as opposed to individuals) are randomised
what is a randomised consent trial
- use in phase 3 development
- obtaining consent for treatment prior to randomisation into control or treatment groups
what is a factorial trial
- used in phase 3 development
- test the effect of two or more treatments simultaneously using various combinations of the treatments
what is a large simple trial
- used in phase 3 of development
- involves a large number of patients, typically over 1000
- due to its large scale entry requirements are usually very basic
what is an equivalence trial
- used in phase 3 development
- aims at showing that two treatments are not too different in characteristics
what is a non-inferiority trial
- used in phase 3 development
- shows that an experimental treatment is not worse than a standard treatment
what is a sequential trial
- used in phase 3 development
- pre-planned, repeated series of comparisons that are stopped as soon as a decision can be made as to whether one treatment can be regarded as superior to another or that both are equally effective
what is a superiority trial
- show that a new treatment is better than the control of standard (maybe a placebo)
what is p value in clinical trial
The p value is a statistical measure that indicates whether or not an effect is statistically significant
- p<0.05 is usually taken as significant
