Clinical trials

Question 1

the phases of clinical drug trials

Answer 1

1. pre-clinical animal studies
   Phase 0
2. Phase 1 safety phase
3. Phase 2 safety and efficacy
4. Phase 3 safety and efficacy
5. FDA Approval and review
6. Phase 4 Marketing and more safety and efficacy

Question 2

the intention of each phase

Answer 2

Pre-clinical studies: Determines pharmacological profile, administration route, Drug interactions

Phase 1: determine whether the drug is not toxic and lacks side effects, dose escalation

Phase 2: Whether it works against the disease in a small group comparatively

Phase 3: A bigger test of the efficacy of the drug in comparison to BAT or placebo

Phase 0: Designed to achieve early pharmacokinetic profile in a few participants at very low doses

Phase 4: Marketing, safety and efficacy, observational study

Question 3

what groups are recruited into them

Answer 3

Phase 1: Volunteers Healthy people, 20-100

Phase 2: Larger group, 100-300, have the disease

Phase 3: 1,000-3,000 people with the disease, wide range of recruitment

Phase 4: population observation

Question 4

Important characteristics that distinguish each phase of drug trailing

Answer 4

Phase 1: to find a safe dose, under tight supervision, with careful dose escalation until first signs of toxicity

Phase 2: Patients with the condition, strict selection criteria, homogenous sample, carefully monitored, very good measures of treatment outcome

Phase 3: Randomly allocated participants, double-blind, statistically powerful

Phase 4: Collect adverse events on all who are prescribed the drug, observational

Question 5

difference between observational and controlled trials

Answer 5

Observational: “Observational” Collect reports of “adverse events” in very big groups (measure incidence, particularly events too rare to pick up in Phases 1 – 3)

Controlled: Recipients of the drug are selected for and compared against non-recipients of the drug under the same conditions to determine efficacy

Question 6

how is power and bias managed in clinical trials

Answer 6

• Controlling bias
  o use a comparator (often placebo or existing medication)
  o allocate participants randomly to groups
  o blind investigator and patient

Question 7

important ethical considerations surrounding human drug trials

Answer 7

Best practice/comparative treatment
* Tests if medical treatments are better than current best practice
* unethical to use placebo

Question 8

the function of a Human Research Ethics Committee

Answer 8

Assesses clinical trials, from application to closure for:

Research merit and integrity: Soundly designed experiment
Justice: All participants have an equal chance of benefit and harm
Beneficence: participant well-being has priority over all other considerations
Respect: participant’s wishes govern involvement

Question 9

purposes of the Trial Protocol

Answer 9

Protocol
* Describes in detail an experiment meeting standards for:
o Ethical human research (NHMRC statement)
o Good Clinical Practice (ICH135/95)

Question 10

The Investigator’s Brochure

Answer 10

Investigator’s Brochure
* All relevant pharmacology, as known at the time

Question 11

The Patient Information and Consent documents

Answer 11

Patient information and consent documents
* what will be required of the participant
* risks and benefits
* safe-guards for participant’s wellbeing, privacy, etc
* participant’s rights (withdrawal, etc)