Drug Development for medical students Flashcards
Major goal phase 1 clinical trial
Investigate safety of the drug
Major goal phase 2 clinical trial
Investigate efficacy of the drug
Major goal phase 3 clinical trial
Investigate efficacy of drug vs current standard of care
What type of study are phase 3 drug studies?
Done as final studies to get drug approved by
regulatory authorities
• Design: Double blind randomised EFFICACY study to
show the drug works for management of a condition
– Ideally against active comparator, often against placebo
– Standardised dosing regimen- sometimes low, high
• Population: homogeneous patients with condition and
without other issues
– Dementia but usually no other major comorbidities
• Size: sample size determined by effect expected from
previous studies
– Varies from a few hundred, to over 10,000
What information on safety can a phase 3 drug trial provide?
Able to get data on common mild adverse
events but usually not on rare, idiosyncratic, severe
ones
Describe two major pit falls of phase 3 drug trials
• Designed and powered for efficacy and not safety – For many drugs the important safety signals come after marketing approval • Population usually younger with fewer other issues and certainly do not have comorbidities – Real life populations where drugs are used have more comorbidities (efficacy of the drug may not be the same, more drug-disease interactions) and more drug interactions
Major function of phase 2 drug studies
• First EFFICACY study in population with the
disease
Most common study design for phase 2 drug studies
• Study design: randomised controlled trial, against
placebo
– If unethical to include placebo have short duration, or
clear rescue treatment (or done in countries who do
not have access to usual care)
– Can do against active comparator but study much
larger
– Also often done in those with early disease or failed
usual care
• Range of doses; usually low, medium, high
Ideal population for phase 2 drug studies
• Carefully selected to maximise sensitivity for
study efficacy
• Eg proven Alzheimers, no other medical
problems, likely to tolerate treatment, be
compliant, complete study assessment, have little
variability in assessment
• Avoid those with renal, liver, other conditions,
potential drug interactions
• Small sample size, very well selected population
Describe the type of safety information gathered in a phase 2 drug trial
• Information collected along the way but
depending on sample size of phase II studies,
only common adverse effects identified
• Population very highly selected, homogeneous
and no information on special populations,
drug interactions
Outline two major downfalls of phase 2 drug trials
• Most drugs fail in the development process
due to lack of efficacy
– Difficult to demonstrate efficacy in some
conditions as other drugs are available and
patients do not tolerate being untreated in
placebo arm
• Due to highly selected sensitive population
may see efficacy benefit which is not seen in
phase III studies
Population involved in phase 1 drug studies?
• Usually done in healthy volunteers
– Easier/faster to recruit (time=money)
– Do not have other conditions, symptoms (= easier
to tell subtle adverse effects) eg headache, unusual
head sensations, drowsiness, LFT changes
– Little known about interactions with other drugs at
this point and healthy subjects not on other
medicines
Goal of phase 1 drug trials?
SAFETY study to determine maximum tolerated
dose or dose likely to work in phase II
Describe how phase 1 drug trials are started. Starting doses, information collected etc.
• Usually start with single dose and escalate in
cohorts up to a certain maximum dose
– monitor for lab tests, vital signs, symptoms, ECG
– Test pharmacokinetics of drug
– Where possible collect biomarker of efficacy
• Then based on that information do multiple
ascending dosing
– E.g. daily dosing for 7 days or 2 weeks
– Similar assessment of safety and PK
