Flashcards in *Cornerstone of epidemiology: Clinical Trials Deck (16):
LO1: Recognise the unique significance of, and key components in, the clinical trial design
LO2: Identify the potential biases and limitations in clinical trials
Interpret the findings presented from clinical trials
LO3: Evaluate the appropriateness of the clinical trial design for particular research questions
Control group is the group of participants who do not receive the intervention under assessment. They must be included to ensure that the outcome happened due to the new treatment and would not occur anyway. They can either receive a placebo (inacive substance such as a sugar pill or water injection) or standard treatment.
Randomization is done to avoid treatment allocation bias.
Without randomization there is a risk that the investigator will choose different patients for each group.
Blind or double-blind
Blinding: patient does not know if they are receiving the new medication or not.
Double-blind: patient nor doctor know which treatment patient is receiving
This is to avoid bias in reporting or measurment of the outcome - measurement bias.
People knowingly receiving something report improvements in symptoms because they are hopeful and enthusiastic.
If doctors know, they may look for more improvements.
Control group is the group of participants who do not receive the intervention under assessment. They must be included to ensure that the outcome happened due to the new treatment and would not occur anyway. They can either receive a placebo (inactive substance such as a sugar pill or water injection) or standard treatment.
At the end of the trial, the data is analyzed.
Presentation depends on the specific trial.
Outcomes presented in terms of:
- efficacy: true biological effect of a treatment
- effectiveness: effect of a treatment when actually used in normal practice.
- Experimental event rate (EER) = incidence in the intervention arm
- Control event rate (CER) = incidence in the control arm
- Relative risk = EER/CER
- Relative risk reduction = (CER-EER)/CER :: (there was a % reduction in events in people taking the new treatment compared with controls)
- Absolute risk reduction (ARR) = CER-EER :: (the risk of an event was % lower in those taking the new treatment)
- Number needed to treat (NNT) = 1/ARR :: (You would need to treat # people with the new treatment for an average of three years to avoid one additional ___ event)
Clinical trials are now expected to be reported according to the CONSORT guidelines.
This ensures that papers about trials include all relevant information for reader to critically appraise them.
Phases of clinical trials
1. Before clinical trials (Tissue samples, animal trials, MHRA (Medicines & Healthcare products Regulatory Agency)).
2. Clinical trials: Phase 1, Phase 2, Phase 3, Phase 4.
Before clinical trials
1. Tissue samples, computer simulations, other in vitro tests
2. Animal testing - mainly rodents, tests for toxicity
MHRA (Medicines & Healthcare products Regulatory Agency) and ethical bodies. Drug cleared for human testing
Clinical trials: Phase 1:
○ Test safety of new treatment: look for side-effects (does it make people sick, raise their blood pressure?)
○ Small number of healthy people
Clinical trials: Phase 2:
○ Test new treatment in large group of people who have disease for which the treatment is devised, to see if the treatment is promising - effective atleast in the short term
○ A few hundred people involved at this stage
○ Also look at safety
Clinical trials: Phase 3:
○ Test new treatment in large group of people
○ Compare new treatment with current treatment or placebo
○ Look at how well new treatment works and any side-effects it may cause
○ Several thousand patients involved
○ Patients recruited from several different locations - can include different countries
○ The smaller the expected advantage of the treatment, the more people will have to take part in the trial
Clinical trials: Phase 4:
○ Trials after treatment is licensed and marketed, to gather information on the drug's effect in various populations and any long-term side-effects