Clinical Trials = What can go wrong?

Question 1

Outline the risks of clinical trials.

Answer 1

Patients = Physical and Psychological injury - DEATH.
Investigational Medicinal Product = Efficacious treatment not progressed due to risk mitigation strategies.
Population = Trust in regulation of clinical trials alongside participation in clinical trials.
There is also trust in new medicines.

Question 2

What is the definition of Adverse Event (AE)?

Answer 2

Any desirable event occurring to a subject during a clinical study whether or not related to the investigational product.

Question 3

List the different categories of Adverse Event.

Answer 3

Mild Events = Easily tolerated with no disruption of normal daily activity.
Moderate Events = Sufficient discomfort to interfere with daily activity.
Severe Events = Incapacitate and prevent usual activity or require complex medication or hospitalisation.

Question 4

What is the definition of Adverse Drug Reaction (ADR)?

Answer 4

Any unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug.

Question 5

List the different categories of Adverse Drug Reaction.

Answer 5

There are 6 types. Type A - F.
Type A = Related to pharmacological actions and occur within therapeutic dosage range. (DOSE DEPENDENT).
Type B = Idiosyncratic = Not related to pharmacological actions and is unpredictable.
Type C = Associated with chronic dosing (IE: Steroids)
Type D = Delayed reactions (EG: Teratogens)
Type E = Drug withdrawal.
Type F = Unexpected failure of treatment (Drug Interactions).

Question 6

What about on target drug effects?

Answer 6

Predictable from known primary / secondary pharmacology of the drug. (Aspirin and COX).
Adverse Events represent an exaggeration of the pharmacological effect of the drug.
Dose dependence within the individual.

Question 7

What about off target drug effects?

Answer 7

Not predictable from the primary pharmacology of the drug.

Question 8

What is a Serious Adverse Event? (SAE).

Answer 8

Any untoward adverse even which participant suffers during the course of the study :
- Results in death.
- Life threatening.
- Congenital anomaly // birth defect.
- Medically important event.

Question 9

What is a Serious Unexpected Serious Adverse reactions? (SUSAR).

Answer 9

A serious adverse reactions where the nature or severity of which is not consistent with the applicable product information (unexpected).

Question 10

What is the adverse events reporting system?

Answer 10

This is a pre defined trial specific reporting system.
The investigators assign a severity to the event ( mild / moderate / severe ) and then determine relationship with investigation medicinal product for each adverse event.

Question 11

What is the reporting protocol for a SAE or SUSAR occurring?

Answer 11

SAE = Reported to sponsor of the clinical trials within “LESS THAN 24HRS” of awareness.
SUSAR = Reported to MHRA.