Clinical trials explained

Nearly 75,000 people in Yorkshire have taken part in clinical trials funded by Yorkshire Cancer Research.

The charity plays an important role in making sure people in our region are among the first to receive access to pioneering treatments and innovative ways to diagnose cancer.

But what are clinical trials? And how do they help?

Clinical trials are research studies performed in people. They are used to test treatments and procedures, like a new drug or diet or medical device, to make sure they are safe and effective. They provide evidence to improve how future patients are treated.

Clinical trials aim to find out if a treatment:

• is safe
• has any side effects
• is more, or less, effective than an existing treatment

Clinical trials rely on the goodwill of people who are prepared to test treatments that may not work, and who may not receive the treatment at all.

Many clinical trials involve a group of patients who don’t receive the treatment and are instead given usual care or a ‘placebo’, which is a substance or treatment that has no therapeutic effect.

Researchers use this group to accurately compare the benefits of the new treatment or procedure against the usual care of those patients.

Those taking part in clinical trials will usually receive a treatment or intervention at random, without the researcher or patient being involved in making the decision. This process is called ‘randomisation’.

Those who don’t receive the new treatment are not always worse off. Not all clinical trials will show that a new treatment is better than existing treatments. They may show that it is not as effective or has more side effects, but this information is still important to be able to give future patients the best possible care.

Clinical trials are not just about testing new drugs.

There are lots of ways they can help, from studying new surgery methods to investigating techniques to change health-related behaviours and new ways to improve the quality of life for people going through cancer.

In ‘Evolution of Clinical Research: A History Before and Beyond James Lind’, published in the journal Perspectives in Clinical Research, Dr Arun Bhatt explains how the world’s first clinical trial is recorded in the “Book of Daniel” in The Bible. During his rule in Babylon, King Nebuchadnezzar – a resourceful military leader – ordered his people to eat and drink only meat and wine. He believed this diet would keep them in sound physical condition.

However, several young men objected to the new rules, preferring to eat vegetables. The king allowed them to follow a diet of legumes and water – but only for 10 days.

When the experiment ended, the vegetarians appeared better nourished than the meat-eaters, so the king permitted them to continue their diet. This was one of the first times a human experiment guided a decision about public health.

James Lind is considered the first physician to have conducted a clinical trial of the modern era. While working as a surgeon on a ship in 1747, Dr Lind decided to carry out a trial to cure scurvy among its sailors.

He selected 12 patients and gave them a common diet. He then split the patients into pairs and prescribed different treatments to each group, including cider, elixir vitriol, vinegar, sea water, a treatment recommended by a hospital surgeon and oranges and lemon.

Those that had been prescribed two oranges and a lemon recovered better and more quickly than the others. Although the results of the experiment were clear, oranges and lemons were too expensive to be recommended. It wasn’t until 50 years later that the British Navy eventually made lemon juice a compulsory part of the seafarer's diet, and this was soon replaced by lime juice because it was cheaper.

To begin a clinical trial, researchers must identify the medical question they would like answers to. They then set about seeing if they can create a clinical trial that will answer this question.

Trials are carried out in a series of steps, called phases. Each phase is designed to answer a separate research question.

1. Phase 1
   In this first phase, the treatment is given to a small group of patients for the first time to evaluate its safety, determine a safe dosage range and identify side effects.
2. Phase 2
   In a Phase 2 trial, the treatment is given to a larger group of patients to look for early signs the treatment might work. and to further evaluate its safety, including safe dosage levels when testing a drug.
3. Phase 3
   These trials are used to confirm the treatment’s effectiveness and monitor side effects – but also compare it to usual care by studying the outcomes of patients who don’t receive the treatment.
4. Phase 4
   These trials involve long term monitoring in routine practice for side effects.

Research trials and studies are strictly regulated to try to make sure they are run ethically, safely and with the full consent of everyone taking part.

All clinical trials go through a lengthy approval process. Independent experts who are not involved in the research must review the science behind the study, and funding must be secured. A recognised research ethics committee, responsible for protecting the rights, safety, dignity and wellbeing of those taking part, must then review and approve the research study and allow it to proceed.

The Health Research Authority ensures studies comply with key laws and guidelines, such as Clinical Trials Regulations, the Human Tissue Act and the Data Protection Act. The Medicines and Healthcare Products Regulatory Agency (MHRA) then inspects where the trial is taking place, to ensure it is being conducted in line with good clinical practice.

There are three rules of consent for clinical trials – those taking part must be legally competent, be provided with all the information about the research study in plain English, and must give consent voluntarily, without pressure from others.

Researchers will carry out regular tests to find out how the treatment is working and look out for any side effects. Being part of a clinical trial often means visiting the hospital or GP more often.

There are lots of reasons to get involved in research.

The National Institute of Health Research’s Be Part of Research campaign suggests that taking part in clinical trials can help people:

• Learn more about their condition
• Make a difference by helping to improve treatments and quality of life, now and for future generations
• Access new treatments
• Take an active role in their own care

People often think of big drug companies carrying out trials for new drugs.

However, charities will also fund new drug and other clinical trials for many reasons. Often charities fund trials where there is no financial gain to be made, such as new surgical or radiotherapy techniques, or testing existing drugs that are ‘off-patent’ - where the drug is cheaply available because marketing rights have expired - to treat different diseases.

Yorkshire Cancer Research funds clinical trials in Yorkshire to test how we can prevent cancer, ensure people get an earlier diagnosis of cancer and how to treat cancer.

The charity’s funding also helps to attract further investment from other organisations, creating a beacon of world-leading research in our region.

Clinical trials funded by Yorkshire Cancer Research include the Leeds Lung Health Check, which aims to test screening in community settings and provide information to improve the effectiveness and benefit of future lung screening programmes.

Another recently announced study will involve testing thousands of women living in Yorkshire for genetic faults to find out if they are at high risk of cancer. If found through testing, women can take measures to prevent breast, bowel, womb and ovarian cancers from developing, as well as get screened regularly so that if they do develop cancer they are diagnosed at the earliest possible stage.

The best place to start is by talking to your doctor and letting them know you’re interested in taking part in research.

You can also visit the Be Part of Research website and search for clinical trials relating to your illness or area of interest. Once you’ve found a trial you’re eligible to take part in, you can contact the study team directly and they will get in touch about the next steps.

It’s important to remember that there may not be a trial for you to enter. However, it’s worth checking regularly in case new ones have started recruiting.

• Bhatt A. Evolution of clinical research: a history before and beyond james lind. Perspect Clin Res. 2010;1(1):6-10.
• National Institute of Health Research - Be Part of Research