1.1.1 Clinical Trials I

Question 1

What is a clinical trial?

Answer 1

Any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition

Question 2

What must be used in a clinical trial?

Answer 2

Must have a placebo or comparative to remove placebo bias

Question 3

What is the purpose of a clinical trial?

Answer 3

To provide reliable evidence of treatment efficacy and safety

Question 4

What is efficacy and safety in a clinical trial?

Answer 4

Efficacy- ability of a health care intervention to imrpove the health of a defined group under specific conditions

Safety- ability of health care intervention not to harm defined group under specific conditions

Question 5

What are the 5 stages of drug development?

Answer 5

Pre-Clinical phase -Lab stage pharmacology and animal toxicology (test on cell cultures and animals)

Phase I -
Volunteer stages
Pharmacodynamics
Pharmacokinetics
Major side-effects, less than 100 healthy volunteers

Phase II -
Treatment studies
Effects and dosages
Common side-effects
Less than 1000 patients

Phase III-
Clinical trials
Comparison with standard treatments
Less than 10,000 patients

Phase IV
Post-marketing surveillance
Monitoring for adverse reactions
Potential new uses
Whole population

Question 6

What is the yellow card system?

Answer 6

Reporting system for post-marketing adverse symptoms

Question 7

What are the most important ethical considerations
for any trial to go ahead?

Answer 7

Trials of new drugs may do harm

Only conduct a trial if you are genuinely in clinical equipose (uncertain if it will work or not) and don’t know what is best treatment for patients

Participants must understand the risks

Question 8

What is a non-randomised trial?

Answer 8

Patients given new treatment compared with a group receiving standard treatment

Allocation by geographical location, historical controls, alternate allocation

Comparison with historial controls

Question 9

What is a historical control?

Answer 9

Group given old drug compared to new treatment group

Selection less well defined
Treated differently from new group
Less information about bias/confounders
Unable to control for confounders

Question 10

What are some issues with non-randomised

Answer 10

Allocation bias- by patient, clinician or investigator

Confounding- known and unknown

Question 11

What does random allocation (randomisation) do?

Answer 11

Eliminates allocation bias- each participant gets equal chance of being allocated to each treatment

Minimal confounding- randomisation leads to treatment groups likely to be similar in size and characteristics by chance

Question 12

What is a confounder?

Answer 12

Factor that gets in the way of measuring the effect of the study

“associated with exposure and is independently a risk factor for the disease”

Question 13

What is concealed allocation?

Answer 13

Used in randomisation, no possiblity of predicting allocation of next patient

Prepared by someone who is NOT entering patients and allocation should be at a distance

Now done with 3rd party computerised randomisation

Question 14

What are some examples of how we do randomisation?

Answer 14

Coin toss

Random number tables, if even new treatment, odd standard treatment

Most trials now use 3rd party computer generated random allocation

Question 15

What 3 things does a clinical trial need to be able to give a fair comparison of effect and safety?

Answer 15

Reproducible in experimental conditions

Controlled comparison of interventions

Fair unbiased without confounding

Question 16

What can happen if clinicians or patients know what treatment they are getting?

Answer 16

Patient may change behaviour, or have expectation of outcome behaviour effect

Clinician may change treatment, care and interest in the patient non-treatment effect

Investigator may alter their approach when making measurements and assessing outcomes measurement bias

Clinicians tend to favour new drug over the old one

Patients inherently biased if receiving new drug

Question 17

What is blinding?

Answer 17

Patient or assessor or clinician don’t know treatment allocation

Single blind-one of patient, clinician or assessory does not know treatment allocation (normally patient)

Double blind- two of patient, clinician, assesor does not know treatment allocation (normally patient + clinician/assessor)

Triple blind- all 3, rarely used as double blind implies all do not know allocation

Question 18

What is an example of blinding?

Answer 18

Aim to make treatments appear identical in every way, apperance, taste, texture, dosage, warnings, smell

Use designated pharmacy to label identical containers for treatments with code numbers and to have a code sheet detailing which code number corresponds to which treatment

Question 19

When is blinding difficult?

Answer 19

Surgical procedures
Pyschotherapy vs anti-depressant
Alternative medicine e.g. acupuncture vs western medicine
Lifestyle interventions
Prevention programmes

Question 20

What is bias?

Answer 20

Systematic distortion in allocation/measurement

Can effect selection, outcome measurement by patient, doctor/researcher

Question 21

What eliminates confounding?

Answer 21

Randomisation

Question 22

What eliminates bias?

Answer 22

Good randomisation- eliminates selection bias

Blinding- reduces outcome measurement bias

Question 23

What two things should be determines before the study begins?

Answer 23

Inclusion criteria
Exclusion criteria e.g. sifnificant co-morbidities