Clinical Trial Design Flashcards
1
Q
Why do a clinical trial?
A
Provides evidence, medical practice is evidence based but you you need to be able to critically evaluate evidence for what you do.
Use SIGN guidelines or Grampian Joint Formulary
2
Q
Preclinical development
A
- Animal pharmacology (dose, adverse effects)
- Animal toxicology (teratogenicity, fertility, mutagenicity)
- Tissue culture
3
Q
Phase I
A
- Volunteer studies
- Clinical pharmacology in normal volunteers generating pharmacokinetic, metabolic and pharmacodynamic data
- Usually involves around 100 subjects
- Certain drugs such as cytotoxics can bypass this phase
4
Q
Phase II
A
- Clinical investigation to confirm kinetic and dynamics in patients
- Provides some evidence of efficacy and identifies a likely dosage range
- Involve up to 500 patients
- Looks at how the drug behaves in patients that may have comorbidities that affect how the drug works
- In case of cytotoxics it could be patients with late stage cancer and nothing to lose
5
Q
Phase III
A
- Formal therapeutic trials where efficacy will be established and evidence safely obtained
- Involves 1000-3000 patients
- All data submitted on completion
6
Q
Phase IV
A
- Post-marketing surveillance to produce evidence of long term safety
- May have involved tens or hundred of thousands of patients worldwide
- Clinicians have to report on first 10,000 pts
- There may be secondary benefits on another group of diseases
7
Q
Types of trials
A
- Double blind: neither patient nor doctor knows
- Single blind: patient doesn’t know, doctor does
- Prospective: more robust
- Retrospective
8
Q
Placebo controlled study
A
- 50 patients on active drug and 50 patients on placebo: compare outcome.
- Then compare with other therapy so 50 on study drug and 50 on comparison
- Can then assess what is more effective
9
Q
Cross over design
A
- 50 patients on study drug and 50 on compared
- Cross over after a set amount of time and a wash out period
- Then the patients are swapped
10
Q
Randomised
A
- Gold standard
- Patients assigned at random to either treatments or control
11
Q
Disadvantages of randomised
A
Subjects may not represent general patient population
Tend to be better at complying with medication
Need twice as many patients
Administratively complex
Some physicians and patients refuse
12
Q
Designing a study
A
- Need definitive hypothesis and end point
- Superiority or non-inferiority? Better than control or not worse?
- Choice of placebo or control drug… 50% placebo effective for anxiety
- Choice of patients: age and sex matched, race, other disease and drugs
- Are pts going to drop out? Comply?
13
Q
Importance of statistical power
A
- Need to choose statistical test
- Analyse if differences are due to chance…
- p<0.05 is usually taken as significance
14
Q
How can something have statistical significance and lack clinical significance?
A
- A drug may prove to be statistically good but not any better than the one on market at the moment
- Or it might be that there’s evidence that there’s no long term effect e.g. statins and cholesterol
