Clinical Trials Explained

Ever stood waiting in line for your prescription and wondered how the doctor knows these drugs are effective? Been offered a vaccine but thought “how do they know it’s safe?”. The answer is clinical trials. Clinical trials are a crucial step in the drug development process, they aim to find whether a drug is safe and effective, what dose it should be used at, and what side effects it may have. In this article, you’ll find a brief overview of how each stage of clinical trials works.

Preclinical

Preclinical trials aim to find whether it is time to move a drug onto clinical trials in humans. These trials can be done in vitro (outside of a living organism) or in vivo (inside a living organism, in the case of preclinical trials in an animal). Researchers will review their findings and consider the drug’s efficacy, toxicity, and dosing before deciding whether or not to move the drug on to clinical trials.

Phase 1

Phase 1 clinical trials are relatively small, they recruit around 20-100 volunteers to be the first humans to receive the drug. These volunteers are usually healthy but depending on the trial, they may prefer volunteers affected by the target condition or disease. These trials last over the course of a few months and aim to test the safety of the drug, find what dosage the body can tolerate and what side effects may appear when adjusting dosage. This information helps researchers decide whether the drug should move on to phase 2 trials, and influences the design of the trials if they do decide to move forward. Around 70% of drugs are able to pass on to phase 2 trials.

Phase 2

Phase 2 trials can have up to several hundred participants with the disease or condition the drug aims to treat. They last anywhere from a few months to two years and aim to evaluate the efficacy of the drug and find any side effects. At this point, researchers will look over their findings to decide whether the drug is worth continued trials, what methods should be used in those trials and what protocols should be put in place. Only around a third of clinical trials will pass on to phase three.

Phase 3

Phase 3 trials will involve around 300-3000 participants who have the target disease or condition and can last for 1-4 years. These trials will provide a lot of the safety data as the larger sample size and longer duration mean that rarer side effects or effects of long term use will show more than they did in phase 2 trials. The drug will be compared to controls like a placebo or the current standard treatment and researchers will evaluate the benefits of the new drug. Is it more effective than the control? Is it safer than the control? Around 25-30% of drugs will pass on to the next phase.

Phase 4

Phase 4 clinical trials take place after the drug has been approved by the relevant regulatory bodies (eg. the FDA) and is being used by the general population. This phase can involve thousands of people with the target condition or disease as researchers monitor the long term safety, efficacy, and benefits of the drug. 

The Length of the Process

The process of getting a drug through preclinical and clinical trials is a long one. Not only is there the length of time it takes to carry out the trial and get results, but also the preparation, applying for funding, the ethics approval, and finding volunteers. 
The Covid-19 pandemic is an example of an emergency situation in which a drug, in this case, a vaccine, got through trials very quickly. This is no small feat. Developments in genome sequencing technology meant that scientists knew fast what they were working with, they collaborated, they used existing research on other viruses within the coronavirus family, and they weren’t the only ones helping. Money was coming from the government and private sector, helping to fund the development and manufacture of vaccines. While trials were still held to rigorous standards, they came quickly as they didn’t need to spend years looking for volunteers, people were eager to help out and filled more testing sites, allowing more data to be collected concurrently. Truly impressive!

Simply Summarised

• Preclinical trials decide if a drug should be trialled in humans
• Phase 1 clinical trials test the safe dosage in a small sample size of humans
• Phase 2 measures efficacy and side effects with a smaller sample size than phase 3
• Phase 3 determines whether the drug is beneficial and watches for adverse effects in a larger sample size for a longer time
• Phase 4 takes place after the Drug’s approval and monitors safety and efficacy in the general population over a long period of time.
• It generally takes years to get a drug through clinical trials but with global effort in an emergency situation, we can find the people and the funding to do the “impossible”.

Further reading

For more information check out these links

• https://www.fda.gov/patients/drug-development-process/step-3-clinical-research
• https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics
• https://www.medicalnewstoday.com/articles/how-did-we-develop-a-covid-19-vaccine-so-quickly#MNT-takeaways