Ethics

Question 1

What is a clinical trial?

Answer 1

A research study in which one or
more human subjects
are prospectively assigned to one
or more interventions to evaluate
the effects of those interventions
on health-related biomedical or
behavioural outcomes

Question 2

Compare and contrast clinical trials and studies

Answer 2

Clinical trials are a type of clinical studies. They both involve human participants. Clinical trials have the following features, whereas clinical studies could maybe have them: subjects are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioural outcomes.

Question 3

First recorded clinical trial

Answer 3

• 562 BCE, King Nebochandnezzar. Two diets were presented to soldiers: legumes & water as well as meat & wine. Legumes and water = more well nourished soldiers

Question 4

First recorded clinical trial of 2 medical treatments

Answer 4

-1537, Ambroise Pair, contrasted 2 treatments re cauterisation of wounds. Boiling oil (usual method) and creating a digestive containing yolk (from egg) oil (from roses) and turpentine. Latter was better at cauterisation (less painful)

Question 5

First controlled trial

Answer 5

-1747, Scurvy. Patients were very similar, provided different diets. Most successful diet became mandate in the British Navy.

Question 6

First double blind trial

Answer 6

-1940s, first blind trial (including giving a placebo) as well as the medication

Question 7

First randomised clinical trial

Answer 7

Streptomycin. Patients didn’t know they were part of a trial, some patients had usual care, some had usual + streptomycin.(Pulmonary TB)

Question 8

Randomised control trials

Answer 8

Gold standard. Testing effectiveness of a treatment while eliminating as many biases as possible. Patients split into two groups - control (comparison) group and experimental group. Groups are followed up. Outcomes are measured at specific times and any differences are tested statistically.

Question 9

nRCT

Answer 9

Allocations are not random. Purely observational studies, non-randomised interventional studies and single-arm trials (no control group, everyone is given the treatment)

Question 10

Cohort studies

Answer 10

Observing/following a group of people for an extended period of time. Similar characteristics.

Question 11

Prospective cohort studies vs retrospective cohort studies
SIMPLE ANSWER

Answer 11

Prospective: watch people over time
Retrospective: look back at people with disease.

Question 12

Case-control studies

Answer 12

• observational study
• aim: find out the cause of disease
• how its carried out: comparing cases (patients w disease) to control (patients w/o disease) the disease should be the only thing that differs between case and ctrl.

Question 13

Cross-sectional studies

Answer 13

A ‘snapshot’ of observations across a population at 1 time. Like observing number of people with diabetes in an area.

Question 14

Ecological studies

Answer 14

observational study that is used to understand the relationship between outcome and exposure level at a population level

Question 15

Phases of a clinical trial

Answer 15

Pre-clinical and then 4 clinical stages

Question 16

Pre-clinical research

Answer 16

can be in-vitro or in-vivo, understanding drug mechanism and predict efficacy (treatment outcomes) and safety (identify & characterise all toxicities associated w a rug to predict adverse events in ppl) for informed RA

Question 17

Phase 1: how many people?

Answer 17

20-80

Question 18

Phase 1: aim?

Answer 18

Safety and identifying side effect

Question 19

Phase 1: timeline?

Answer 19

Several months

Question 20

Phase 1: success rate?

Answer 20

52%

Question 21

Phase 2: how many people?

Answer 21

100-300

Question 22

Phase 2: aim?

Answer 22

effectiveness & gathering preliminary data whether the drug works.P

Question 23

Phase 2: timeline?

Answer 23

1-4 years

Question 24

Phase 2: success rate?

Answer 24

30%

Question 25

Phase 3: people?

Answer 25

1000-3000

Question 26

Phase 3: Aim?

Answer 26

Safety and effectiveness, and DOSAGE. (combining w other durgs?

Question 27

Phase 3: success?

Answer 27

58%

Question 28

FDA approval

Answer 28

NDA submitted to FDA. FDA reviews results and determines approval of drug.

Question 29

Phase 4: people?

Answer 29

Made available to the public!

Question 30

Phase 4: aim?

Answer 30

monitoring safetry and effectiveness w large, diverse pop. more information about benefits and optimal use of treatmennt/drug

Question 31

Special case: COVID-19

Answer 31

COVID-19 vaccine development was done very quickly.

Question 32

COVID-19: pre-clinical

Answer 32

Within 3 months, an already tested vaccine technology platform (AdVac) was being tailored o COVID-19. (Viral vector, Adenovirus is modified and the antigen gene is inserted into the adenovirus

Question 33

COVID-19: pre-clinical. Timeline

Answer 33

3 months (Jan - March 2020)

Question 34

COVID-19: phases 1/2a and 2b

Answer 34

Phase 1-2 were combined (refresh: phase 1 is where safety is being monitored, phase 2 is where effectiveness is being monitored). In 2b, more people were tested, more diverse groups, trying to find optimal doses etc

Question 35

COVID-19: phase 1-2, timeline

Answer 35

4 months (March-July 2020)

Question 36

COVID-19 Phase 3

Answer 36

Vaccine administered to thousands of people. Volunteers: 1/2 vaccinated, 1/2 placebo. Waiting for results.