24 Clinical Trials Flashcards
What is a clinical trial?
- Prospective experiment
- always looking forward (not looking at old data)
- Human subjects
- Testing a defined intervention
- drug/surgical technique/ method of care
- has to be able to be specifically described
- compared to a control group
- clearly defined
- With defined outcomes
- Again, must be specifically defined
What are four features of a clinal trial?
- Informed Consent
- risks and benefits to the subject
- must be up-front
- Can’t overstate benefits
- Randomization to tx group
- removes bias of tx assignment
- distributes other variables evenly
- age/comorbidities/genetics etc
- Blinding
- pt doesn’t know which tx they’ve received
- those assessing don’t know either (double-blind)
- have placebo that looks exactly the same as intervention drug
- smell/taste etc
- have placebo that looks exactly the same as intervention drug
- Placebo
Why do we need clinical trials?
- Best method to determine if a therapy works (ie has the intended effects)
- Pharmacology alone is not sufficient to determine if a treatment will work
- eg just because a drug strengthens the heart’s pumping doesn’t mean it improves pt outcome
- Individual clinician’s experience is insufficient to know whether a therapy works
- a clinician can never see enough pt’s and evaluate them in a systematic fashion to actually ever know that a tx works
What does Phase I of a clinical trial involve?
- Phase I: Dosing Studies
- Maximally tolerated dose
- Pharmacokinetic/pharmacodynamic studies
- blood samples to see how body handles drug
- small number of subjects enrolled
- 15-20
- usually enroll healthy subjects (exception is cancer drugs)
- low risk
- cancer drugs in phase I are given to pt’s with cancer
What is the goal of Phase II in clinical trials?
- Phase II: determine the Biologic Activity and Adverse Effects
- Generally 14-30 subjects
- First use in pt’s with disease
- too small to determine whether or not drug actually works
- give to a few people to see if the drug does what it’s intended to do
- Check for biologic activity
- Safety
- side-effects
- Not really enough subjects to get a decent view of the side effects but gives a signal as to whether or not there are any safety concerns
What is the goal of Phase III Clinical trials?
Phase III: Effectiveness Trials:
- Determine if drug actually works
- Establish its role in clinical practice
- The requirement for Notification of Compliance (NOC); ie drug approval
- Focus is on effectiveness and adverse effects
- Control group required (control = placebo or standard of care)
What is NOC and what is required in order to receive that?
NOC = Notification of compliance
ie = drug approval
Requires a Phase III clinical trial
What is the purpose of Phase IV Clinical Trials?
Phase IV: Long Term Effectiveness and Adverse Effects
- observational studies without control groups
- Evaluation across populations
- Detection of rare adverse effects
Provide the primary focus of each of the four phases of a clinical trial:
- Phase I
- Drug dosing/pharmacokinetics/pharmacodynamics
- Phase II
- trying it in people with disease
- Does it have biological activity?
- Phase III
- Does it really work to improve pt outcome
- Phase IV
- Long-term Observation after drug is on the market
A drug that has a very small difference between a therapeutic dose an a toxic dose is said to have a__________
A drug that has a very small difference between a therapeutic dose an a toxic dose is said to have a narrow therapeutic index
- would be difficult to use in older people because of lowered kidney fxn
What kind of trials fall under the category of health services research?
Trials of health services interventions, procedures, types of care
- Just because a therapy is proven, doesn’t mean that it is used (or used properly) in those who could benefit
- eg hypertension
- statins (high cholesterol)
- anticoagulation (blood thinners)
- Need evidence for new models of care
- improve application of phase III results
