Why are clinical trials necessary?
To provide evidence.
Why do ethics play a role in clinical trials?
Ethics play a huge role because trials often involve the use of human participants, and can involve drugs that have not been fully explored.
What are observational studies and why are they less effective than clinical trials?
Observational trials are where a drug is simply introduced into a population and the effects are studied. The issues. include issues with cause/causation, replication bias and the fact that not all things work in practice effectively.
What aspects of drugs are evaluated in clinical trials?
Efficacy and safety
What are the stages in clinical trial development?
What happens with in the drug discovery stage?
DRUG DISCOVERY- the process from chemical structure to licensed drug is thought to take around 10 years and cost £100million.
What happens during the pre-clinical development stage?
PRE-CLINICAL DEVELOPMENT- animal pharmacology (dosage, adverse effects), animal toxicology (teratogenicity, fertility, mutagenicity), tissue cultures.
What are the 4 stages of clinical development?
Phase I (Volunteer Studies) Phase II (Patient Studies) Phase III (Further Patient Studies) Phase IV (Post-Regulation Studies)
What happens during Phase I?
Phase I (Volunteer Studies)
• Clinical pharmacology is assessed in normal volunteers, generating pharmokinetic, metabolic and pharmacodynamic data.
• Usually involves around 100 subjects.
• Certain drugs (e.g. cytotoxics) will bypass this phase.
What happens during Phase II?
Phase II (Patient Studies)
• Clinical investigation to confirm the kinetics and dynamics in patients (who may have renal/liver/GI issues)
• Provides some evidence of efficacy and identifies a likely dosage range.
• Involves around 500 patients.
What happens during Phase III?
Phase III (Further Patient Studies)
• Formal therapeutic trials where efficacy will be established and evidence of safety will be obtained.
• Involves 1000-10,000 patients
• At completion, all data (pre-clinical, pharmaceutical and clinical) is submitted as an application to the regulatory authority for a license to sell the drug.
What happens during Phase IV?
Phase IV (Post-Regulation Studies) • Post-marketing surveillance to produce evidence of the long-term safety of the drug. Involves 10/100,000 patients.
What are pilot studies designed to do?
Test the experimental design, not test for results.
What are placebos intended to do?
Used to compare the outcome in two different groups of patients.
What is a double blind trial?
Double blind- both patient/doctor are blinded.
What is a single blind trial?
Single blind- patient is blinded.
What does it mean if a trial is prospective?
The protocol is established beforehand.
What does it mean if a trial is retrospective?
The trial is less good as protocol can be altered and so is open to increased bias.
What is cross-over design?
A divided group on separate treatments cross over after 8 weeks and switch drugs in a wash-out period.
What are the disadvantages of randomised design?
Acceptability of randomisation
What is the difference between superiority design and non-inferiority design?
Superiority design will show that a particular drug is BETTER than the current one. Non-inferiority will show that it is just AS GOOD- alright but not better choice.