Background

What is a clinical trial?

 A study which evaluates the safety and efficacy of a new treatment (medical drug or device)

How do clinical trials work?

 The researchers monitor and evaluate the effects of the new drug or device 

Why are they used?

 To establish if the new treatment is safe and effective or if it is more safe and effective than the current standard treatment 

Phases of Clinical trial research

Pre-clinical phase:

 This phase is designed to prove the safety of the treatment in a controlled laboratory environment

 This involves testing the new treatment on cells and animals to see if an immune response is produced

 Safety, toxicity, pharmacokinetic, and pharmacodynamic information are all assessed

 If pre-clinical phases are given approval, the trial moves onto phase 1

 Usually lasts 1 to 2 years

COVID-19:

 A research phase in which a natural or synthetic antigen is identified which will trigger the same immune response in your body, as if you were infected with the SARS-COV-2 virus

 Testing of this antigen is then carried out on cells and animals

Phase 1:

 The treatment is administered to a small group of adults (normally between 20 and 80 people)

 The safety is evaluated, looking at the dosage range and any side effects that arise

 The level of immune response generated in the adults is also evaluated

COVID-19:

 The vaccine is given to a small group of healthy individuals to confirm its safety and efficacy at stimulating an immune response

Phase 2:

 The treatment is given to larger group of people (normally between 100 and 500 people)

 The treatment is evaluated further 

 Safety and optimal dosage are assessed

 It is also given to different groups of people to see how its safety and efficacy vary amongst them

COVID-19:

 The safety of a COVID-19 vaccine is further tested on a larger and broader group of people

Phase 3:

 A much larger group of adults receive the treatment (normally thousands of people)

 The researchers then wait to see how effective the treatment is compared to a placebo group

 The safety and efficacy on a larger group of people is evaluated

 As there are more people, relatively rare side effects may be identified in this phase

COVID-19:

 The researchers administer the vaccine to thousands of people and then monitor them to see how many become infected in comparison to a placebo group

 The efficacy rate is also established here, for example, the Pfizer vaccine was established to be over 94% effective

Regulatory Approval:

 Following success in phase 3, the manufacturer of the new treatment will submit it for approval to regulatory boards

 E.g. the Food and Drug Administration in the US or the European Commission

 The regulatory bodies review the data collected from the trials to decide whether it can be deemed safe and effective

COVID-19:

 Due to the emergency situation, many countries including the UK are giving vaccines emergency authorisation based on preliminary evidence of safety and efficacy

 China and Russia have approved COVID-19 vaccines based on the Phase 1 and 2 trials alone

Phase 4:

 Studies continue after the treatment is available on the market

 Regulatory bodies remain involved in the new treatment, monitoring its production, safety, potency etc.

 These studies gather additional information about the risk, benefits and optimal use of the treatment

COVID-19:

 As vaccines are being given to the public, they will continue to be monitored so that any adverse effects, or optimal usage information, is identified as rapidly as possible 

Combined phases:

 Sometimes different phases are combined in clinical trials in order to speed up the process

COVID-19:

 Some manufacturers combined Phase 1 and 2 trials due to the emergency situation

Paused/Abandoned Clinical Trials:

 If the researchers identify concerning signs/symptoms in volunteers, a trial can be paused while they are investigated (before being resumed or abandoned)

COVID-19:

 A number of vaccine trials were temporarily paused during their development

 E.g. the AstraZeneca Oxford vaccine was voluntarily paused in September 2020 due to a potentially unexplained illness in a participant in the phase 3 trials

Summary:

1. Clinical trials are studies which assess the safety and efficacy of new medical treatments
2. They involve pre-clinical research in which a new treatment is identified and then tested on cells and animals to prove its safety and efficacy
3. The new treatment must then undergo 3 phases of human trials on an increasing number of people each time
4. Finally, the treatment can then be approved by regulators who look at the evidence collected
5. Once approved, the treatment will be available on the market but phase 4 research continues, meaning the safety and efficacy is still being assessed
6. Clinical trial phases can be combined to speed up the process, or paused if unexpected results occur