Clinical Trials Flashcards
What do clinical trials provide evidence of?
Drugs are safe and effective
How many prescriptions do GPs give out per day on average?
70
How much does the NHS spend on drugs each year?
£11.7 billion
What are examples of drugs that were developed before clinical trials were required, what does this explain?
Warfarin and digoxin which is why they have so many side effects
What is an observational study?
Observes individuals without manipulation or intervention
What are some problems with observational studies?
False positives
Replication is difficult due to bias/different criteria
What do clinical trials prove (in terms of putting theory into practice)?
What works in theory might not work in practice
Why does the process of getting a drug onto the market take years?
Need to go through all of the stages to be approved for a license
Who are clinical trials regulated by?
MHRA
What is tested during clinical trials?
Safety
Efficacy
How is the efficacy of a drug compared?
With placebo or another drug
What are some laws which cover drug trials?
UK Medicines Act 1968
The Medicines for Human Use (Clinical Trials) Regulations 2004 and 2014
What are the stages of drug development?
1) Drug discovery
2) Pre-clinical development
3) Clinical development
What is tested during pre-clinical development?
Amimal pharmacology
Animal toxicity
Tissue culture
What are the stages of clinical development?
1) Phase 1 (volunteer studies)
2) Phase 2 (given to patients)
3) Phase 3 (formal therapeutic trials)
4) Phase 4 (post marketing surveillance)
What is tested during phase 1 trials?
Clinical pharmacology in normal volunteers
How many subjects are used in phase 1?
100
What happens during phase 2?
Clinical investigations in patients to confirm kinetics and dynamics
Evidence of efficacy and likely dosage range
How many subjects are used during phase 2?
Up to 500
What happens during phase 3?
Formal therapeutic trials establish efficacy and evidence of safety
All data submitted as an application for a license to sell the drug
How many subjects are used during phase 3?
1000 - 3000
What happens during phase 4?
Post marketing surveillance to produce evidence of long term safety
How many people can phase 4 involve?
Tens to hundreds of thousands
When do tegenero trials happen?
During phase 1
What are tegerno trials?
Involves 8 patients:
6 given drug intravenously
2 given placebo
What do pilot studies test and what do they not test?
They do not test outcome but test the study design
What are examples of different pilot studies?
Double blind
Single blind
Prospective
Retrospective
What is a double blind study?
Patient and doctor are blinded
What is a single blind study?
Patient is blinded
What is a prospective study?
Protocol is decided beforehand
What is a retrospective study?
Looks backwards and examines exposure to risk factors in relation to outcome that are established at the start of the study
What can different studies involve comparisions with?
Placebo
Other therapy
Cross over design
What is a cross over design?
Patient is given additional treatment which is being tested
What is a randomised control study?
One where patients are assigned to one of the groups at random
What are some disadvantages of randomised control?
Generalised (subjects may not represent patient population)
Recruitment (twice as many new patients needed for the study)
Acceptability (some physicians or patients will refuse)
Administrative complexity (randomisation methods etc)
What does superiority design show?
New treatment is better than the control or standard treatment
What does non-inferiority design show?
Not worse than standard treatment by more than some margin
Would have beaten placebo if it had been included
What should the end points of a design be?
Simple, such as:
Death
Number of hospital admissions
Lowering of blood pressure
What do you need to consider when designing a study?
Choice of subjects (enough to be able to detect or reject differences between groups)
Choice of control drug (placebo or another drug)
Choice of patients (age, race, sex, diseases and drugs)
Exclusion and selection criteria (pregnant woman, children, seriously ill patients, elderly)
What are challenges with trials that involve the elderly?
They usually have multiple conditions
What do you need to consider when analysing and interpreting data?
Statistical test
Are differences due to chance
O<0.05 usually taken as significance
What are some ethics that must be considered?
Consent
Ethics committee
Placebos
Children
How long can overall development of the drug from initial research to its first launch take?
Up to 20 years
What is post marketting surveillance done by?
Medicines and Healthcare devices Regulatory Authority (MHRA)
Yellow card system
