L11 PHRM20001 - How do we know it works?

Question 1

Phase 1 – Clinical Pharmacology

Answer 1

• 20-50 subjects
• Usually 1/10th of maximum tolerated dose in animals
• Healthy volunteers
• Is the drug safe?

Question 2

Phase 2 – Clinical Investigation

Answer 2

A) Small group given max therapeutic dose
B) Small group given a range of doses
- 50-300 patients
-Healthy individuals or small number of patients with disease
-What is the appropriate does?

Question 3

Phase 3- Formal therapeutic trials

Answer 3

• 250-1000+ subjects (randomised and controlled)

- Patients with disease

Question 4

Phase 4 – Post-marketing studies

Answer 4

• 2000-10,000+ subjects
• Drug now licensed for use
• Surveillance for safety and efficacy
• Subsequent reporting of adverse events in individual patients – monitor side effects including rare, and long-term

Question 5

How to eliminate bias?

Answer 5

Single or double blind

Question 6

How to eliminate variability?

Answer 6

Random controlled trials and allocation to treatment is random. Stratified randomisation

Question 7

How to eliminate confounding issues?

Answer 7

Controls – compare new treatment with no treatment/current treatment

Question 8

Placebo (“to please” in Latin)

Answer 8

• Need to match the entire process for each treatment group
• Unless have a matching treatment – experiment no longer blind
• Therefore – need a dummy medicine containing no active ingredient (can also be a sham surgery or intervention)
• Participant believes the dummy medicine is or could be the experimental treatment

Question 9

Nocebo

Answer 9

Opposite of placebo, harmful effects instead

Question 10

Explanations for the Placebo effect

Answer 10

Decreased anxiety (can have adrenal effect) and patient expectations (disregard -ve events and beneficial behavioural changes)

Question 11

Nuremberg Code

Answer 11

The Nuremberg Code is a set of research ethics principles for human experimentation set as a result of the Subsequent Nuremberg Trials at the end of the Second World War.

Question 12

Intra-articular and topical placebo treatments lesser or greater responses than oral ones?

Answer 12

Greater

Question 13

Factors influencing the placebo effect (3)

Answer 13

1) Features of disease
2) Patient factors
3) Provider factors

Question 14

Homeopathy (placebo effect in play?)

Answer 14

Like cures like. Using the poison causing the disease to treat it in small doses. Activate the vital energy of diluted sample by vigorous shaking and 10 hard strikes against an elastic body. Theory of “water memory”, dilutions > 12C so no original substance left.