7 - Clinical trials Flashcards
Definition of clinical trials
a planned experiment in humans, designed to measure the effectiveness of an intervention
intervention is usually a new drug, but the method can equally be applied to the assessment of a surgical procedure, a vaccine, complementary therapy etc
clinical trials are the ONLY experimental design in epidemiology
(because most epidemiological studies (surveys, cross sectional, cohort, case control, ecological) are observational)
Bias definition
systematic error in design, conduct or analysis of a study which produces a mistaken estimate of treatment effect
Confounding definition
When a variable (or factor) is related to both the study
variable and the outcome so the effect of the study variable on the outcome is distorted
Features of a clinical trial
Experimental study
Must contain a CONTROL group
Prospective: participants are followed through time
Patients are enrolled, treated and followed over same period of time
Participants should be randomised to control or intervention groups
Ideally the participants and the researcher are unaware if a participant has been assigned to the treatment or control group = blinding
control group
study participants who do not receive the intervention under assessment
control group must be included otherwise you cannot be sure why the outcome happened
purpose of randomisation
to remove treatment ALLOCATION BIAS
double blind trial
neither the patient nor the doctor knows which treatment they are getting ->
prevents bias in reporting or measurement of the outcome, MEASUREMENT BIAS
outcomes are presented in terms of…
efficacy
effectiveness
efficacy definition
true biological effect of a treatment
effectiveness definition
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
experiment / control
Relative reduction
(CER- EER)/ CER
Absolute risk reduction (ARR)
CER- EER
Number needed to treat (NNT)
1/ARR
Phases of clinical trial
Phase I to IV
to ensure safety and effectiveness of drug
Phase I
tests safety of new treatment
looks at side effects
usually, small group of healthy volunteers
Phase II
tests new treatment in a larger group of people who have the disease for which the treatment is to be used, to see whether the treatment is promising
effective at least in the short term
a few hundred people are involved at this stage
also tests safety
Phase III
test new treatment in a larger group of people
compare new treatment with treatment currently in use, or with a placebo
look at how well new treatment works, and at any side effects it may cause
several thousand patients will be involved
Patients will be recruited from multiple locations and this might include several different countries
The smaller the expected advantage of a treatment, the more people will be needed to take part in a trial
Phase IV
done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use
Ethics
clinical trials should be:
regulated to ensure that patients are protected
registered, reviewed by an independent scientific committee
approved by a Research Ethics Committee
adhere to government and international guidelines
What occurs before phases of clinical trial
laboratory stage
process of laboratory stage
1) tissue samples
- computer stimulation
- other in vitro tests
2) animal testing
- mainly rodents
- tests for toxicity
3) MHRA and ethical bodies
- drug cleared for human testing
