L5- clinical trials 1

What is a clinical trial according to NIH

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

Clinical study

• involves research using human volunteers that is intended to add to medical knowledge

• Are observational

• Eg cohort studies, case control studies, surveys

Clnical trial

Interventaionl study involving investingational medicinal products (IMP)

Researchers assign participants, stages

When was the last time worlds first clinical trial

562 BCE

What did the first clnical trial invovled

Comparison of 2 diets over 10 days - meat & wine vs legumes & water

When was the first trial of 2 medical treatments

1537

Wen was the first uk double blind trial

1940s

When as the first tri randomised control trial

1948

What happens int he first true randomised trial

Mhc streptomycin trial for treatment of pulmonary TB -tested isual care + streptomycin vs usual care

Types of clnical trials (6)

• mechanistic

• Exploratory/ developemtn

• Pilot/ feasibility

• Other interventional

• Behavioural

• Basic experimental

Types of experimental studies (2)

• randomised control trials

• Non randomised control trials

What are types of observational studies (4)

• cohort studies

• Case control studies

• Cross sectional studies

• Ecological studies

What is teh gold standard trial

Randomised controlled trial

How do randomised controlled trials work

Participants are randomised to one of two or more groups to test a specific drug, treatment or other intervention

• experimental group has intervention being tested

• The comparison/ control group has an alternative intervention, a dummy intervention (placebo) or no intervention at all

How are outcomes of RCTs measured

At specifi times and any difference in response between the groups is assessed statistically - also used to reduce bias

Non randomised control trial

An experimental study in which people are allocated to different interventions using methods that are not random

What can non randomised control trials include

Purely observational studies, non randomised interventional studies and singel arm trials with external control

Cohort study

An observational study in which a defined group of people is followed over time

In cohort studies what does the cohort include

People with similar characteristics

What are cohort studies used to examine

Associations between different interventions received and subsequent outcomes

What does a prospective cohort study do

recruits participants before any international and follows them into the future

What does a retrospective cohort study do

Identifies subjects from past records describing the interventions received and follows them from the time of those records

Case conotrl study

An observational study to find out the possibel cause(s) of a disease or condition

How are case control studies done

By comparing a group of patietns who have the disease or conditions (cases) with a group of people who do not have it (controls) but who are otherwise as similar as possible (in characteristics thought to be unrelated to the cases of the disease or condition)

What do case control studies allow for

Researcher can look for aspects of individuals lives that differ to see if they may have cuased the condition → useful when the outcome is rare

Cross sectional studies

A snapshot observation of a set of people at 1 time

What do cross sectional studies aim to do

Describe a variable not measure it

What are cros sectional studies used for

To assess exposure (cause) and a disease (effect) and compare the rates of diseases and symptoms of an exposed group with an unexposed group

Advantages of cross sectional studies

• simple

• Cheap

• Quick

• Minimal room for error

Disadvantages of cross sectional studies

• Doesnt help determine cause and effect

• report bias is probable

Wwhat are ecological studies ised to understand

The relationship between outcome and exposure at a population level where population represents a group of individuals with a shared characteristic which can include geography, ethnicity, socio economic status and employment

What differentiates ecological studies from others

The unti analysis being studied is the group therefore assumptions cannot be made about individual study participants

Phases of a clinical trial

• laboratory studies

• Pahse 1

• Pahse 2

• Pahse 3

• phase 4

Preclnical research

Basic research, drug discovery and preclinical research

What are the ultimate goals of preclinical studies

To accurately model the desired biological efect of a drug to predict treatment outcomes in patients (efficacy) and to identify and hatcheries all toxicities assocaited with a drug in order to predict adverse events in people for informaed risk assesment

What testing can occur in pre clinical research

• in vitro

• In vivo

• Drug profiling using computer models that show how the durg will interact with the human body

Pahse 1 clinical trial

Researchers test a drug or treatment in a small group of people (20-80) for the first time

What is the purpose of phase 1

To study the drug or treatment to learn about safety and identify side effects

How long do pahse 1 trials last

Usually several months

What is the probability of success of phase 1 trials

52%

Phase. 2 trial

The new drug or treatment is given to a larger group of people (100-300)

Aims of phase 2 trials

• effectiveness

• Aim to obtain preliminary data on whether the drug works in people who have a certain disease or condition

• Continue to study safety including short term side effects

How long is pahse 2

Can last several years usually between 1-4 years

Whta is the probability of success in pahse 2

Aroudn 30%

Phase 3 of a trial

• treatment is given to a larger group of people (1000-3000)

• Gathers more info about safety and effectiveness studying different populations and dosages using teh drug in combination with others

Probability of success in phase 3

Aroudn 58%

What can happen after the first 3 phases of trials

If foudn to be safe and effective, can submit a Marketing AUthorisation Application (MAA), new drug application (NDA USA) for the treatment to an organisation such as medicines and healtchare products regulatory agency (MHRA), the food and drug administration, across EU EUropean medicines agency

What % of drugs make it thourgh approval process

25-30%

Stage 4 og clinical trial

Post marketing monitoring stage one a drug is approved- is made available to the public and its effectiveness and safety are monitored in large, diverse populations

What is monitored during phase 4

Researchers seek more info about a drugs benefits and optimal use of- sife effects may not become clear unitl more people have taken it over a longer period of time

How long does the whole process tkae

Appro 10 years for a new treatment to complete the journey

How did covid vaccine come aroudn so quick

Already had a tested vaccine tech platform that was inn in Ebola vaccine and tested in HIV and RSv