What is clinical trial and how does it work?

Question 1

What are 4 phases of clinical trials?

Answer 1

pre clinical
phase 1 
phase 2
phase 3
phase 4

Question 2

What are controlled clinical trials?

Answer 2

MHRA- medical and healthcare regulatory agents

FDA- food and drug administration of USA

Question 3

Phase 1

Answer 3

-safety of drug
20-30 healthy volunteers
=>months

Question 4

phase 2

Answer 4

-safety study
-identify side effects
-measure effectiveness
-100-300 patients
=> 6 months to 2years
Early phase: 20-200 patients with disease:
-therapeutic benefits
Late phase 50-500
-double blind
-compared with placebo or standard drug
Outcomes :
- assess efficacy against a defined therapeutic endpoint
- establishes a dose

Question 5

Phase 3

Answer 5

• measure effectiveness
  Method:
  -multicentric : ensures geographic and ethnic variations
  -Randomised allocation of test drug/placebo/standard drug
  -Double blinded:
  -vigilant recording of all adverse drug reactions
  -rigorous stastical evaluation of all clinical data
• monitor side effect
  -1000 -3000 ppl
  =>years to decade

Question 6

phase 4

Answer 6

• long term side effects monitored
  -post marketing surveillance
  -helps to detect:
  rare ADRs, Drug interactions, new uses of drugs.
  => ongoing

Question 7

Which parties participate in clinical trial?

Answer 7

1. patient/health volunteer
2. clinical pharmacologist , clinical investigator
3. institution where trials are held
4. research ethics committee (REC) or institutional ethical committee
   =>supervise and onitor every step
   =>safeguard the welfare and rights of participants
5. Sponsor
   =>pays all expenses
   =>appoints competent investigators
   =>ship all drugs for trial
   =>files all papers to legal
6. regulatory authorities
   =>legal authority
   MHRA, HPA

Question 8

What is the structure of clinical trial protocol?

Answer 8

1. Title and abstract
2. Introduction
   - general statements of purpose
   - complete preclinical results on animal study
   - clinical data available
3. Goals: primary and secondary objectives
4. Study design:
   - type of study
   - recruitment criteria : exclusion and inclusion criteria
   - randomisation criteria and sample size
   - duration of study
5. Data analysis
   - case reports forms , statistical analysis

Question 9

Types of observational studies

Answer 9

cohort studies

• group of subjects followed over time
• purpose: defining the incidence and ivestigatiing potential ccauses of a condition.
• can be prospective
• can be retrospective

Question 10

Experimental/intervention studies

Answer 10

- these studies evaluate the effects of an intervention
types of intervention: 
-Behaviour modification 
-drug 
-device 
strength : can demonstrate causality

Question 11

What is parallel design?

Answer 11

-simple treatment versus placebo

Question 12

What is crossover designs?

Answer 12

-comparison of treatment and placebo made in each subject

Question 13

What are advantages of crossover?

Answer 13

• allows each subject to be a control such that treatments can be assessed in each subject
• smaller study sample required for power

Question 14

What are disadvantage of crossover?

Answer 14

• period effects, carry over effects , sequence effects all need to be considered
• longer duration and more complex stats

Question 15

what are steps in running a trial?

Answer 15

1. recruitment
2. screening
3. informed consent after patient information sheet
4. Randomisation/double blinded
5. protocol visits step by step procedures
6. reports of adverse events
7. store investigatory product
8. subject compensation
9. electronic data collection
10. study closure

Question 16

What should informed consent be?

Answer 16

• voluntary
• explained in simple nontechnical language
• comprehensive information regarding the trials
• all possible adverse reactions
• freedom to withdraw from the trial

Question 17

Ethical considerations

Answer 17

• treated with respect
• not harmed in any way
• fully informed about what is being done

Question 18

Syphilis study

Answer 18

• originally designed to make treatment available to african -American men with syphilis
  issues:
  1. Men were recruited without their consent
  2. Misinformation about procedures, ie. 6 month duration and free health care
  3. After penicillin was proven an effective treatment, men were denied antibiotics and prevented treatment from military and local physician.

Question 19

Nuremberg (1947)

Answer 19

• rials of Nazi doctors and scientist from WWII
• Did NOT follow these guidelines:
  1. need for informed consent
  2. Research should be based on prior animal work
  3. Risks should be justified
  4. only qualified scientists must conduct research
  5. physical and mental suffering must be avoided
  6. no research where death/serious injury is expected.

Question 20

What are good clinical practices?

Answer 20

• kown GCPs
• Misnomer- they are rules/regulations for the conduct of research
• standard for design, conduct, performance, monitoring, analyses and reporting of research
• even though established for drug studies, they dictate appropriate conduct for all research

Question 21

What are key principles of good clinical practice?

Answer 21

1. anonymity
2. confidentiality
3. Data protection
4. consent