Callum Morris: What happens in a clinical trial?

In this explainer episode, we’ve asked Callum Morris,
Pharmaceutical Research and Development Insights Manager at
Genomics England, to explain what happens in a clinical trial.


You can also find a series of short videos explaining some of the
common terms you might encounter about genomics on
our YouTube channel.


If you’ve got any questions, or have any other topics you’d like
us to explain, feel free to contact us
on info@genomicsengland.co.uk.


You can download the transcript or read it below.


Florence: What happens in a clinical trial? I'm joined with
Callum Morris, Pharmaceutical Research and Development Insights
Manager for Genomics England, to find out more. So, Callum, first
things first. What is a clinical trial?  


Callum: So, a clinical trial is a study that looks to people to
answer a specific medical research question. 


So, this involves gathering a group of participants that are
willing to participate in providing evidence on how to improve
clinical care. And so, the main purpose for a clinical trial is
to evaluate health related outcomes between different groups of
participants. If it's an interventional clinical trial, you
change clinical care for one group and not another. 


And evaluate whether the change you made improved health outcomes
for that group, or if it's an observational clinical trial, you
might focus on different groups but not change anything about
their clinical care and collect real world data to understand how
outcomes differ across the groups. 


Florence: Can you briefly explain what we mean by real world
data?  


Callum: Sure. So real world data relates to data collected
routinely as part of standard clinical care. So, it could be
collected from your electronic health records, data from product
or disease registries, or data gathered from other sources such
as digital health technologies. 


And all of this can inform on particular groups from the
population you're interested in. 


Florence: And are there different types of clinical
trials?  


Callum: Yes. Clinical trials can take many forms depending on the
medical research question you're trying to answer. They
could be related to understanding the risk of disease. So,
evaluating a potential risk factor that you may be concerned
with. They might evaluate preventing disease. So, what different
approaches can you take to people who have never had the disease,
and does this prevent its occurrence? You can have a clinical
trial that looks at screening for disease. For cancer, that's
really important. 


Does a new screening approach mean more people with cancer can be
identified earlier? And importantly, does this lead to an
improvement in survival? You can have clinical trials that
evaluate the different approaches to diagnosing a disease and can
you diagnose a patient earlier and better? 


And then the classical clinical trial is revolving therapeutics
or different treatments, and you can have treatments that are
addressing the disease itself. Or you'd have treatments that are
controlling the symptoms of side effects you might get from
another treatment you might be taking.  


So even within a specific medical research question, you can have
different clinical trials depending on how much evidence you
already have regarding that question. For clinical trials
involving the assessment of new treatments and therapies, these
are broken down into three stages and we call these phases. 


So, you have phase one, phase 2, and phase 3. 


Florence: Can you explain a bit more about these
phases?  


Callum: Sure. So, the overarching medical research question might
be, what is the safety profile of this new therapy, and does it
work improving on the current standard of care? So, you'll break
this down depending on the phase, and with each phase you expand
your clinical trial to a larger population. 


Phase ones are typically on a small group of people around, let's
say 20 to 50, and are designed to check the safety of a new drug
that's being entered into humans for the first time. Sometimes,
especially in early phase cancer trials, you're trying to find
the right dose for your patients. 


So, you might take a small group, test them on a low dose, and if
there are no severe reactions to the new drug, you start
incrementally increasing your dose a little bit more. And this
gives you a really good idea of the safety profile of your drug
as you try it for the first time in a human population. 


Next, you'll move on to a phase 2. And these are typically larger
than your phase one, around 50 to 200 people. And, usually you
use the dose recommended by the phase one. So instead of slowly
adjusting your dose and just focusing on the drug safety profile,
the phase 2 will evaluate the safety of the medicine in a large
population, but also have an additional focus on health-related
outcomes. 


Is the medicine causing the effect you want? Whether that's
relief of symptoms or for cancer reduction in the size of your
cancer. If the data is really promising from your phase two, it
will move to a phase 3. And the idea is the same, increasing the
size of the population. typically phase threes can be from 300 to
3000 participants. 


And the key thing here is that you will evaluate the potential
benefit of your new treatment against the current standard of
care. Normally, meaning the treatments that are already available
in the clinic. Health regulators will need to look at all the
data collected from all the trials before they approve it for the
general population. 


And typically, they need a phase 3 to do this. They need a phase
3 to confirm that the benefit provided by the treatment outweighs
the potential risks associated with it, across a fairly large
cohort of participants. And this is to ensure the therapy is
appropriate to be given to the general patient population. 


But also, a phase 3 is needed to see that if the new treatment is
moving clinical care forward in the right direction and in
providing improvements for patients against what is already
available in the clinic. And this is the process by which we call
it evidence-based changes, to make improvements to clinical
care. 


Florence: So then how do people join clinical trials? 


Callum: So firstly, it's about becoming aware of the clinical
trial. You might be referred to a clinical trial by your doctor
who's been aware of it and where it is. Or you might be able to
find a clinical trial using clinical trial databases or finding
about them through patient advocacy groups. 


And they should be able to tell you which hospitals are taking
part in the clinical trial. So, the next step might be your
doctor can contact someone on the research team, and there is
always a principal investigator per research site that is always
a medical professional. 


The study team at the site have all undergone training from the
people organising the trial to run through the protocols
necessary to keep the trial consistent in different sites. 


Once they've been contacted, you'll undergo a screening process,
and what they'll determine is your eligibility for the trial.
They might assess medical history or your health status. And if
you're eligible for the trial, the next step is to provide
informed consent. The healthcare team should provide detailed
information about the trial, its risks and benefits, the aim of
the trial, and who's funding it. 


And what are the treatment options for participating and not
participating in the trial? How long is the follow-up in the
clinical trial? And what will happen if you leave the clinical
trial? And then also what are the safety concerns for the
clinical trials and the possible side effects if it's something
to do with a new treatment. Once you've been informed of all
these details and you agree to be part of the clinical trial,
you'll sign a consent form, and that means you're officially
enrolled in the clinical trial. 


Florence: And what happens once someone is enrolled in a clinical
trial?  


Callum: Once you are in the trial, you'll follow the procedures
outlined in the trial protocol. This can take many forms, but
normally it involves more regular follow-ups and check-ins with
the clinical care team. And this is to establish safety concerns
and to enable lots of data collection. 


There also may be additional checks related to health outcomes
during the trial, and so the study team may want to take
additional samples to understand what is happening
physiologically during the study. There also may be additional
questionnaires for you to fill out, to capture patient reported
health outcomes. 


And this is to understand the patient's quality of life whilst
they're on the trial. So, depending on the protocol, you may be
followed up for a set period of time, and that may get less
frequent as time goes on. And of course, you may pull out of the
trial at any point after which the follow up will stop. 


So, following data collection, there may be a while before you
see anything, but results should be published following analysis
of the data.  


Florence: And finally, why might someone want to be involved in a
clinical trial?  


Callum: Clinical trials are all about providing evidence to
improve clinical care. At any time we want to make a change to
healthcare, we want it to be evidence-based. And so, this
requires lots of people all contributing in a group effort to
generate a data set large enough to determine how to change our
approach to healthcare and move the field forward for improving
people's lives. 


Florence: That was Callum Morris explaining what happens in a
clinical trial. If you'd like to hear more explainer episodes
like this, you can find them on our website
www.genomicsengland.co.uk. Thank you for listening.