Clinical Trials

Question 1

What are the different stages of the drug development process?

Answer 1

discovery research
preclinical trials
clinical trials - phase 1, 2 and 3
marketing authorisation and monitoring - phase 4

Question 2

What is the difference between preclinical and clinical trials?

Answer 2

preclinical trials
- laboratory development and animal testing/toxicology

clinical trials
- testing volunteers and patients

Question 3

What is a clinical trial?

Answer 3

any form of planned experiment involving volunteers/patients to identify the most appropriate treatment of future patients with a given medical condition

assess the benefit:risk ratio of new treatment against a control

looks at the pharmacokinetics, pharmacodynamics, adverse drug reactions, safety and efficacy exhibited by the investigated product

Question 4

What is the purpose of clinical trials?

Answer 4

assesses the safety and efficacy of

• a new medication or device on a specific kind of patient
• a different dose of a medication that is commonly used
• an approved medication or device on a new kind of patient

assess whether the new medication or device is more effective for the patient’s condition than the the already used gold standard

Question 5

What is phase 1 of clinical trials?

Answer 5

looks at the pharmacology and toxicology of the drug
- pharmacokinetics, pharmacodynamics, dosage, metabolism, safety and efficacy

starts the human volunteers at the lowest dose possible and is gradually escalated
- calculated from the animal studies

Question 6

What is phase 2 of clinical trials?

Answer 6

therapeutic confirmation
- looks safety and efficacy

uses a large sample size to determine statistic validity

is randomised

uses a variety of designs
- concurrent control, comparison with baseline, crossover, blind/double blind

tests different doses to determine the therapeutic dose
- explores dose-response relationship

Question 7

What is randomisation?

Answer 7

process of assigning clinical trial participants to treatment groups
- gives each participant a known chance of being assigned to each group

Question 8

Why is randomisation needed?

Answer 8

explains the difference in outcomes between the treatment groups
- proves the intervention exhibits real effect and the difference is solely due to chance

Question 9

What are the different methods of randomisation?

Answer 9

simple randomisation
permuted block randomisation
stratified allocation
minimisation method

Question 10

What is simple randomisation?

Answer 10

assignment of subjects using a sequence of random numbers from a statistical textbook or computer generated sequence

Question 11

What is permuted block randomisation?

Answer 11

blocks having equal numbers of As and Bs (A=intervention, B=control) are used with the order of treatments within the block being randomly permuted
- ABBA, AABB, etc
= a block of four has 6 different possible arrangements of 2 As and 2 Bs.

a random number digit assigns a block of treatment which sets the allocation order for the first four subjects and the process is repeated.

Question 12

What is stratified allocation?

Answer 12

restricts chance imbalances by ensuring treatment groups are as alike as possible

ensures treatment balance on these known prognostic factors

Question 13

What is the minimisation method?

Answer 13

used when you have very large number of data

use a new subject factor status

count the number of subjects with those factors on each treatment

• allocate to balance up scores (so give new patient the treatment which gives the smallest total sum)
• if sums for A and B are equal then one would use simple randomisation to assign the treatment.

Question 14

What is concealment of the randomisation process?

Answer 14

those recruited people into the trial must be unaware of the group the participant will be assigned

Question 15

What are the designs of clinical trials? What is the difference between them?

Answer 15

open trial - patient, doctor, pharmacy and sponsor know what is being used.

blind trial - patient does not know

double blind trial - patient, doctor and sponsor do not know
= minimises potential bias, ensure subjective assessments and decisions

Question 16

Why are double blind trials used? Who is affected?

Answer 16

patient - psychological effect , attendance compliance and cooperation

treatment team - intensity of patient examination, continuance of trial therapy, dose modification

evaluator - need to be objective

Question 17

How is a double blind trial does?

Answer 17

matched placebos
- colour, texture, taste (capsules), shape and size)

coding and randomisation
- allocation concealment

Question 18

How can control groups be classified?

Answer 18

type of treatment used

• placebo
• no treatment
• different dose or regimen of study
• different active treatment

Question 19

What are crossover trials? Why is it used?

Answer 19

patients receive both arms of study at different stages,
- will be in the treatment and control group

allows for the subjects response to treatment A to be contrasted with their response to treatment B

• removes patient variation
• effects can be estimated with greater precision

Question 20

What are the disadvantages of cross trials?

Answer 20

can only be used for chronic diseases/processes not acute
- disease needs to persist long enough for the patient to be exposed to both experimental treatments

effects of one treatment may carry over and alter the response to subsequent treatments
- requires a wash out period

Question 21

What is phase 4 of clinical trials?

Answer 21

looks at therapeutic use
aims to optimise drug use in practice 
- drug-drug interactions 
- dose-response studies 
- safety studies 
- epidemiological studies 

looks at long term side effects, efficacy, dosage

Question 22

What is pharmacovigilance?

Answer 22

science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
- drug safety