Clinical Trials

Question 1

what occurs in phase I

Answer 1

Test thesafetyof a new treatment

Small number of, usuallyhealthy, volunteers

Question 2

what occurs in phase II

Answer 2

biological effect. Test to see if the treatment isefficacious- at least in the short term
Continue to look atsafety
Afew hundred people usuallywith the condition

Question 3

what occurs in phase III

Answer 3

overall effectiveness. Comparethe new treatment with the current or placebo
Look at how well the new treatment works (effectiveness)
Continue to monitorside effects
Severalthousandpatients

Question 4

what occurs in phase IV

Answer 4

Afterthe drug has been marketed
Measure effect in various populations
Look out forrare side effects

Question 5

What is a clinical trial?

Answer 5

A planned experiment in humans designed to measure the effectiveness of an intervention (usually a drug but can be surgical procedures, vaccine, complementary therapy etc)

Question 6

what type of study are surveys, cross sectional, cohort, case control, ecological

Answer 6

observational studies

Question 7

what are the features of a clinical trial

Answer 7

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. This is known as blinding. 


Question 8

why are control groups required

Answer 8

to be sure why the outcome has occurred (could be due to the effectiveness of the new treatment or happened anyway)

Question 9

why are patients randomised

Answer 9

to eliminate allocation bias

Question 10

what are the methods of randomisation

Answer 10

Block Randomisation- assign people to group A or group B randomly
Stratification- done by centre - can be divided by important patient characteristics e.g. male/female
Minimisation- adaptive stratification - calculates imbalance and allocates to maintain balance

Question 11

what does blinding mean

Answer 11

the patient does not know whether they are getting the new treatment or not

Question 12

what is double blinding

Answer 12

neither the patient nor the doctor knows which treatment they are getting. This is to prevent measurement bias

Question 13

what is drug evaluation based on

Answer 13

efficacy - Thebiologicaleffect
Can it work?
Phase II
and effectiveness - The trueoveralleffect
Does it work in the real world?
Is it 'worth' it?
Phase III

Question 14

Identify the potential biases and limitations in clinical trials

Answer 14

Allocation Bias (randomisation. Measurement Bias
(Blinding- single, double). Reporting bias (Selective reporting:
positive trials most likely to be published
negative and neutral remain unpublished)So need access to all trial data. CONSORT ( Consolidated standards of reporting trials) ensures papers about trials include all relevant info.
Sample Size

Question 15

what do all clinical tried have to be (ethics)

Answer 15

be registered, reviewed by an independent scientific committee, be approved by a Research Ethics Committee and adhere to government and international guidelines

Question 16

who are the independent data monitoring committee

Answer 16

a group of independent researchers who can check progress during the trial; they will usually un- blind the results to see if there is any major difference in outcome (improvement or side effects) between the intervention and control groups. If there is a large difference they have the power to stop the trial.

Question 17

how are the outcomes presented at the end of the study

Answer 17

in terms of efficacy (the true biological effect of a treatment) or effectiveness (effect of a treatment when actually used in “normal” practice).

Question 18

what are the trial outputs

Answer 18

The experimental event rate (EER) = incidence in the intervention arm
Control event rate (CER) = incidence in the control arm
Relative risk = EER/CER
Relative reduction = (CER- EER)/ CER
Absolute risk reduction (ARR) = CER- EER
Number needed to treat (NNT) = 1/ARR

Question 19

how to minimise measurement bias

Answer 19

blinding. endpoint selection (objective/subjective, accurate and precise, consistent and repeatable, primary, secondary tertiary end points). loss to follow up (missing data, different between groups, intention to treat analysis)