What is a clinical trial?

Learn about clinical trials, from their early origins to how they're run today

What is a clinical trial?

A clinical trial (also known as a clinical study) is a type of medical research that human volunteers take part in. Clinical trials help us answer questions about a drug, device, or diagnostic test, such as:

Thousands of people take part in clinical trials, globally, every year. Without them, medical progress would simply not be possible. 

Helping you understand clinical trials

Watch the video for an explanation of clinical trials.

Clinical research brochure

You can also download our brochure for any additional information about clinical trials

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The history of clinical trials

What many people don’t realize is that clinical research has been around for many years – centuries in fact! So, where did it all begin?

500 BC

The first scientific experiments

The first documented experiment in people was conducted by King Nebuchadnezzar. He prescribed a diet of meat and wine for his subjects. But the vegetarians objected and ate their normal diet for ten days, while the others ate the investigational diet. The vegetarians looked healthier to the king, so he allowed them to continue their diet.

1537

Ambroise Paré

When Ambroise Paré – a surgeon responsible for looking after soldiers – ran out of boiling oil solution (commonly used as a treatment for wounds) he had to think of a new treatment option. He experimented with a combination of egg yolks, rose oil, and turpentine, which – to his surprise – worked better than oil on its own!

1747

James Lind

In the 18th century, scurvy – caused by Vitamin C deficiency during long sea voyages – was very serious. When his crew became ill, naval surgeon James Lind trialed potential treatments, from seawater to oranges and lemons. He found that patients who ate citrus fruits recovered. This still informs our dietary guidelines today.

1785

Placebo

The word placebo first appeared in medical literature in the early 19th century, used to describe ‘any medicine more to please than benefit the patient.’ In 1863, U.S. doctor Austin Flint carried out the first medical experiment comparing a placebo (a 'dummy' treatment) with an active one. Placebos are still used in clinical trials today to see whether any improvements in those taking part are the result of the investigational drug or something else.

1943

First double-blind, controlled clinical trial

During World War II, an investigational drug – patulin – was tested for treating the common cold and compared with placebo. Unfortunately, patulin didn’t work, but the research project still goes down in history as the first well-controlled trial.

1947 - 1964

Informed consent

Human experimentation, both in the form of the Tuskegee Study and under the Nazi regime, horrified the world and called for new medical research laws. In 1947, the Nuremberg code was created to ensure participants gave consent before taking part in any medical research. This was further regulated in 1962 with the Kaefavuver-Harris amendments in the United States and the Helsinki Declaration in 1964.

NOW

Where are we now?

Clinical trials provide valuable information to improve our understanding of different conditions. Safety measures and regulations have been put in place to make sure unethical historical injustices are never repeated in today's clinical trials. What's more, the way a drug works in the body can vary for different groups of people. So today, we focus on trying to represent everyone in clinical trials.

Where are we going?

We’ve come a long way in terms of improving the design and safety of clinical trials, but there's still much to be done. For many communities of color, lack of participation in clinical trials runs deeper than lack of awareness. Mistrust in the medical system is rooted in historic injustices like the Tuskegee Study, as well as health disparities that persist today.

You have the opportunity to contribute to the health of your community

Diversity in clinical trials not only helps fight health inequalities, it can lead to more knowledge about diseases and potential treatments for all. That’s why, when you take part in a clinical trial, you’re supporting your family, friends, and entire community. Your participation provides unique and important information that can help researchers learn more about diseases and potential treatment options.

Accurate representation of people in clinical trials – across age, gender, race, ethnicity, and socio-economic level – not only helps fight health inequalities and rebuild trust, it can lead to more knowledge about diseases, and potential treatments for all.

What happens in a clinical trial?

Clinical trial phases

Preclinical trials

Before we can test an investigational drug in people, we first test it in animals, in what are called preclinical trials. Preclinical trials investigate which (if any) doses may be generally safe. This can take several years. We can only progress a drug to clinical trials involving people if it meets strict safety standards.

Clinical trials

If a drug passes preclinical trials, it may be tested in humans in interventional trials. Interventional trials are conducted to determine whether an investigational drug, or a new way of using an approved treatment, is generally safe and effective. It can take 10-15 years before regulators approve a drug for use by the general public. In some circumstances, the process can be accelerated, for example, during a pandemic. Each phase provides important information about the drug. If a drug does not pass a particular phase, it cannot progress to the next phase.

Phase 0 and Early Phase 1

How does it behave in the body?

10-15 participants Several months

Phase 0 trials aren’t always part of testing a new drug, but they may help researchers find out if the drug works in the way it’s expected to. Where early phase 1 trials are used, it’s the first time the drug is tested in humans. A small group of participants (10-15) are given a low dose of the investigational drug to confirm what was learned in pre-clinical trials and to better understand how it behaves in the human body.

Phase 1

What can we learn about the safety of the investigational drug?

20-100 participants Several months

The investigational drug is tested in about 20-100 people over the course of a few weeks to see how the body processes it, what effect it has on the body, and information about dosing. Phase 1 trials are normally conducted in a clinic so that participants can monitored.

Phase 2

What are the potential risks and benefits?

100-300 participants Several months to 2 years

The purpose of this phase is to see if the investigational drug works in people who have a certain condition. It also continues to study safety, including short-term side effects.

Phase 3

What are the potential risks and benefits compared to no treatment or existing treatment?

300-3,000 participants 1 to 4 years

An investigational drug is given to 300-3,000 (or more) people with the relevant condition. Typically, phase 3 trials are comparator-controlled (the investigational drug is given to some participants and a placebo or approved treatment is given to others) and continue to investigate if a drug is generally safe and if it works in a larger group of people.

Phase 4

What is the drug’s effectiveness and safety in the real world?

Several thousand participants Years

Phase 4 trials typically take place after a drug has been approved. Phase 4 trials monitor how the drug affects different people in the real world.

What happens before a clinical trial begins?

Before we can run a clinical trial, we must first develop a plan, called a protocol. The protocol includes information about the design of the trial,
such as:

Before a trial can begin, the protocol must be approved by the:

  • Clinical trial sponsor – this may be a pharmaceutical company, a national health institute, or individuals, such as doctors
  • Regulatory authority – they make sure the rights of people who take part are protected. In the United States, the authority is the Food and Drug Administration (FDA), and in Europe it is the European Medicines Agency (EMA). Every part of the world has its own regulatory authority
  • Institutional review boards (IRBs) or ethics committees (ECs) – members of an IRB include healthcare professionals, researchers, and members of the public. Their role is to protect the rights and welfare of people who take part in trials. In an EC, none of the members are involved in the trial in any way. Members of the public are included. An EC looks after the rights, safety, dignity and wellbeing of people who take part in clinical trials

Careful and thoughtful planning goes into the design of a clinical trial. It may include input from doctors, advocacy organizations and patients to help make sure the questions being asked have meaning for people living with the disease. The length and size of a clinical trial is also carefully considered to ensure that it will answer specific research questions.

What does a clinical trial involve?

Each trial design is unique to that trial, and participating can vary in length from days to years. A trial typically includes the following steps: informed consent, screening, treatment, and follow-up. A person can decide to stop their participation at any of these stages, without impact on their usual healthcare.

Informed consent

The purpose of the trial is explained to people who are interested in taking part, in terms that they can understand, and they will get the opportunity to ask any questions they may have about the trial. Before anyone takes part, they’ll first sign an informed consent form.

Screening period

All participants are screened to ensure they meet the trial criteria and that there are no medical reasons why they should not take part.

Treatment period

Participants may receive the investigational drug, a placebo, or approved treatment.

Follow-up period

Participants will continue to have their health monitored at one or more follow-up visits to see the effects of the investigational drug and if they are having any side effects.

Open-label extension

Some trials may offer participants the opportunity to receive the investigational drug after the treatment period has ended regardless of whether they received the investigational drug, a placebo or an approved treatment during the treatment period.

Who's involved in a clinical trial?

When learning about a clinical trial, you might hear about the many people involved. But who exactly are these people, and what do they do?

Sponsor

The sponsor funds, initiates and manages a trial. They can be a company (such as pharmaceutical or biotech), non-profit institution, doctor, or government organization. We (Biogen, a biotech company) are a clinical trial sponsor.

Regulator/regulatory authority

Every country has a regulatory authority with its own laws for running a trial. Each authority must review and approve the protocol before a trial can begin. They must also make sure that the trial follows national regulations.

Institutional Review Board/Ethics Committee

An independent team of people who review trials to protect the rights and welfare of the people who take part.

Data Monitoring Committee

Also known as a Data and Safety Monitoring Board (DSMB), the Data Monitoring Committee (DMC) monitors the reliability of data collected in trials to protect participant safety. This small group of experts (such as statisticians and disease experts) are independent of the trial sponsor and review this data without bias.

Investigators

The principal investigator supervises all aspects of a clinical trial. They’re usually helped by other doctors, nurses, and data managers who are part of the trial team.

Coordinators

A clinical trial coordinator ensures trials are conducted in a way that follows good clinical practice. They conduct the trial under the supervision of the principal investigator.

Participants

If you’re a volunteer who takes part in a trial, you’re a participant. Some trials are looking for patient volunteers (participants with a particular condition) and others are looking for healthy volunteers. You’ll need to be eligible (meet specific criteria) and sign an informed consent form before you can join.

Caregivers

Some trials require a caregiver to take part alongside the person they care for. We call those people ‘trial partners.’ Trial partners may be asked to sign an informed consent form before they take part in a clinical trial. Find out more about the role of a caregiver.

Where do clinical trials take place?

Nowadays, trial visits may take place in many different locations. Technology has also made it possible for some visits to take place virtually. Example of locations include: