lecture 8 Flashcards
what’s involved in preclinical testing
lab testing
animal short + long term testing
what is included in clinical trials
phase 0/1
phase 2
phase 3
what is included in post marketing surveillance
phase 4
it’s basically just a different name for if
whqt must be done between preclinical and clinical studies
IND submission
investigational new drug application
what must be done between phase 2 and post marketing surveillance
NDA submission ( new drug application)
regulatory approval
what is an ind
investigational new drug
how many types of IND are there
3
what are the 3 types of IND
- investigator IND
- emergency use IND
- treatment IND
what is an investigator IND
- application submitted by the physician who initiated and conducted the investigation.
- can be submitted to propose the idea of studying an unapproved drug or further studying an approved product (new population etc)
what is an emergency use IND
it allows the FDA to authorise the use of an experimental drug in an emergency situation where this is no time to submit a normal investigator IND.
happened for ebola
what is a treatment IND
submitted for experimental drugs showing promise in clinical testing for serious// life threatening conditions while the final clinical work is conducted + FDA review takes place
what are the 2 types of IND
research (non commercial)
commercial
what 3 things must an IND contain
- animal pharmacology + toxicology studies
- manufacturing info
- clinical protocols and investigator info
why is animal pharmacology and toxicology studies needed in an IND
- it’s preclinical data that shows whether the product is safe for clinical trials
what is manufacturing information in IND
- info about the composition, manufacturer, stability + controls used for manufacturing the drug substance + product.
consistent batches of drugs
what are clinical protocols and investigator info in IND
- detailed protocols that show if initial phase trials would expose subjects to unnecessary risks
- info about the physicians/investigators qualifications
- commitments to obtain informed consent from the research subjects
what are clinical trials
they’re research that studies new tests + treatments + evaluated their effects on human health
in clinical trials,, what do ppl volunteer to test
- cells
- drugs
- biological products
- medical devices
- surgical procedures
before clinical trials occur,, what must be done,,aka what must be done for them to occur
it must be designed, reviewed, completed + approved before.
u must have planned it ages in advance with all the info needed
what’s the range of ages that can take part in a clinical trial
ppl of all ages can take part
how many phases are there in clinical trials
4
what are the 4 phases in clinical trials
- phase 0/1
- phase 2
- phase 3
- phase 4
brief phase 0/1
test new drugs on a small group of ppl for the first time
evaluate a safe dosage range + identify side effects
brief phase 2
tests treatments that appear to be save from phase 1 but need more subjects to monitor for any adverse effects
brief phase 3
conducted on larger populations + in different regions// countries
this is the step before the drug is approved
brief phase 4
takes place after country approval
there is a need to test a wide population over a longer timeframe
what can clinical tests be used for doing
to see if:
treatment approach
prevention approach
behaviour approach
are safe + effective
types of clinical trials
epidemiology
behavioural
health services
clinical trials
epidemiology clinical trials
understand disease by studying patterns, causes, effects of health + disease in specific groups
behavioural clinical trials
understanding human behaviour + how it relates to health + disease
health service clinical trials
how ppl access health care providers + health services.
the cost of service + the results of this care
clinical trial clinical trials
evaluate the effects of intervention on health outcomes
why is the first phase called phase 0/1
bc it’s hard to discern between them
what the goal of phase 0/1
to see if the drug behaves in the same way researchers expected it to based on their lab studies
how many ppl are involved in phase 0
less than 15
what type of dose is given to phase 0
very small dose so side effects are low
no therapeutic effect
no drug safety or tolerance being studied
what info is taken from phase 0
drugs engagement with the target
drug pharmacokinetics
MOA
drug pharmacodynamics
what happens if in phase 0,, the drug does not perform the way researchers expected based on preclinical studies
they must return back to preclinical trials then decide on whether they should continue clinical trials or not.
are healthy patients always tested in phase 1
no,, sometimes,, in oncology,, actual patients can also take part
how many participants are there in phase 1
20-100 ppl
healthy volunteers
ages of participation in phase 1 clinical trials
18-55 year olds
what is measured in phase 1
tolerability
the best dosage form
duration of drug effectiveness
analysis of drug metabolites
phase 1 tolerability meaning
finding the correct dose that doesn’t lead to evident side effects
phase 1: best dosage administration form
oral
intravenous
etc
what is phase 2 about
analysing the therapeutic efficacy in a particular patient population to find if the drug should continue to phase 3, finding the correct dose + treatment regime
in phase 2 what must the participants have
they must have the condition of interest
how many patients are chosen for phase 2 clinical trials
100-300 patients
what is important about the chosen participants for phase 2
there is a strict inclusion/exclusion criteria
in pree for them to be homogenous
what does homogeneous mean
all the same
all have the same type of smt
phase 2 can be split into what
phase 2a and 2b
how long is phase 2a
1 year
what does phase 2a focus on
dosing requirements
what happens in phase 2a
there’s a small number of patients that are administered the drug in diff quantities to evaluate if there is a dose response relationship
what is the point of phase 2b
to test the efficacy of the drug in terms of how successful it is in treating/preventing/diagnosing the disease
what is a limitation of phase 2 clinical trials
the fact that there is no control group,, aka there is no way in comparing the placebo and non placebo groups.
cannot see the effect of the drug being analysed
phase 2:: two armed study
either drug or placebo
50 get the drug,, then they undergo interim analysis to check if dose is okay,, then they give the dose to 50 others. if the 50 have bad reactions,, clinical trials are cancelled
if u have a good phase 2 trial does that mean phase 3 will also be good
no!!
why doesn’t a good phase 2 trial correlate to a good phase 3 trial
bc phase 2 was trialed in a homogeneous group of ppl.
phase 3 is trialed on a heterogeneous group of ppl.
we cannot confirm that results can be replicated.
what % of good phase 2 trials also lead to good phase 3 trials
roughly 60%
what must the data found in phase 2 undergo in order for phase 3 to occur
it must go under thorough examination!! bc phase 3 is very expensive and money does not want to be wasted!!
what’s special about phase 3 clinical trials
the most expensive!!!
money is given by a sponsor organisation,, normally a big pharmacy company
sometimes the drug formulation, production and manufactures are too expensive for
clinical trials to occur
continuing phase 3 trials possesses a large amount of
risk
what is the goal of phase 3
confirm the efficacy and safety of the compound in a broad patient population
how many ppl take place in phase 3
1000-3000 patients
compounds normally undergo phase 3 in how many clinical trial sites
a lot!!!
there must be a lot of different clinical sites in a bunch of different countries
what must also be present in phase 3 clinical trials
institutional review board (IRB)
how long does phase 3 take
2.5 to 5 years
depends on the nature of disease and the patient population though
components of a successful phase 3 trial
- 2 studies that prove compound safety + efficacy
- resulting info can be given to health care providers
- end results can be extrapolated onto gen pop
- more phase 3 trials can occur by the sponsor company in order to collect necessary data for market approval.
why must there be 1000-3000 ppl in phase 3 trials
- to provide a statistically significant result
- bc it depends on the expected effect.
in phase 3,, how many ppl should get a therapeutically relevant dose
more than 1500
out of the 1500 getting a therapeutic dose in phase 3,, how many should be studied for a minimum of 6 months
300-600
in phase 3: out of the 1500 ppl getting a therapeutic dose, how many should reach the year mark
100
whqt should be decided for phase 3
if all the participants will be given the test therapy
what cool thing can be done for phase 3
there can be a double blind trial
what is the proper name for a phase 3 double blind trial
double blind randomised controlled trial
RCT
in phase 3: double blind randomisation controlled trial,, what is meant by randomisation controlled
randomisation is used to put ppl in either the placebo or non placebo group
why is phase 3 controlled by randomisation
in order to prevent unconscious + deliberate human influence when it comes to assigning groups
why does the trial being double blind have importance
bc it ensures that treatment and analysis of outcomes is not influenced by prejudice.
prevents the researcher and patient from knowing who was administered the drug and who was given the placebo.
what is a placebo pill
an inactive substance
no therapeutic effect
sugar pill!!
same taste, colour and characteristics as the actual drug but without the active principle//ingredients
when can phase 4 occur
once the drug being studied has successfully completed 2 well controlled studies
what’s another name for phase 4
post marketing surveillance studies
in order for marketing approval to occur what must be complete
phase 2
post marketing surveillance studies
objectives in post marketing surveillance studies aka phase 4
- compare safety + efficacy of this compound vs competitors
- identity low frequency adverse effects (aka u continue safety monitoring to better characterise the risks)
- find potential drug - drug interactions
- establish treatment guidelines for paediatric and geriatric population
- determine the drugs real world efficacy
difference between phase 3 and phase 4 in terms of ppl
ppl in phase 4 are more heterogeneous + larger groups of ppl
what conditions in phase 4 (post marketing surveillance study) take the drug off the market
- if there is already a more effective therapy present // available
- if the drug doesn’t fulfil its anticipated goals in a more broader population of ppl
