Clinical Trials: What are they? And why do they matter?
By Mark Warburton
In healthcare, every medicine, vaccine, or treatment you might encounter has gone through a rigorous process of investigation and analysis. At the heart of this process are clinical trials – carefully designed research studies which test medical interventions to make sure that they are safe and they work properly.
The field of clinical trials can be difficult to navigate for those who have not taken part in research before. There are often misconceptions about what clinical trials are, and what they might involve. Encephalitis International has a strong history of supporting clinical trials to help improve the lives of those affected by encephalitis. Hence, we would like to share knowledge with our community on this important topic.
What is a clinical trial?
Clinical trials are a type of research study which tests new treatments or therapies on human volunteers, or ‘trial subjects’. The volunteers might be affected by the disease that the treatment is hoping to treat, or they might be people unaffected by the disease, who are assigned to a ‘healthy control group’ (depending on the trial design). Clinical trials are usually initiated and led by the pharmaceutical company which has developed the new treatment. They work with trial sites, such as hospitals, to deliver the new treatment to the trial volunteers. The local delivery of the trial is organised by the hospital’s Research and Development (R&D) department. A clinical trial will typically involve multiple visits to the trial site. It is here where tests and assessments are carried out, data is collected, and the treatment is given to the volunteers.
The term ‘clinical trials’ refers to studies where a medical intervention is given to the subjects. Usually this is a new drug being developed to treat the disease. However, it might be a new combination of or new regime of existing medicines. Clinical trials can also test other ‘interventions’ which don’t involve medicines, such as the use of new medical devices, or new diagnostics.
Other types of clinical research
In clinical research there are other types of studies that you might hear about which do not involve medical interventions. These are called ‘observational studies’, they are intended to ‘observe’ patients in their normal standard care. These studies usually only focus on data collection rather than administering a new treatment. They are designed to find out something new about the disease and improve understanding of it. This could include studies to investigate the natural progression of the disease. Or it might be looking at the different outcomes of patients on different treatments as part of their normal care.
Although no new treatment is being tested, observational studies are still hugely important as they act as a starting point for pharmaceutical companies to research into new medicines. Observational studies collect patient data which researchers then analyse, with the aim of identifying an aspect of the disease which is poorly treated. The researchers can then begin developing new medicines which will better treat disease. Thus, without observational studies there would be no clinical trials, and so it is vital that participants are recruited into both types of research.
What is the purpose of clinical trials?
The overall purpose of every clinical trial is to reduce the burden of the disease on those affected and to advance treatment and/or knowledge of the disease. Each trial however will have a specific rationale or ‘research question’, along with aims for what the investigators are hoping to get out of the research.
In clinical trials, researchers aim to find the best ways to:
- prevent disease and reduce the number of people who become ill
- treat illness to improve survival or increase the number of people cured
- improve the quality of life for people living with illness, by reducing symptoms or the side effects of treatment
- diagnose diseases and illnesses
Clinical trials are also classified into different phases, depending on the design and aim of the study:
Phase I – ‘first in man’: testing of the new treatment in a small number of ‘healthy volunteers’ to see it is safe administer in humans.
Phase II – ‘proof of concept’: testing of the treatment in a larger group, this time with volunteers affected by the disease. This phase aims to determine its effectiveness and further assess its safety.
Phase III – ‘effectiveness’: assessing the treatment in hundreds to thousands of subjects, to confirm its effectiveness, monitor side effects, and compare it with standard approved treatments.
Phase IV – ‘post market surveillance’: monitoring of the drug after it has been licensed for use by the public. Aims to track its safety in the wider population, and to monitor if there are any side effects in different demographics.
Phases I-III are normally ‘placebo-controlled trials’, volunteers will be assigned to one of two groups, one group receives the treatment, and the other receives a placebo (a substance or treatment with no therapeutic benefit). This is to establish any effect observed from the treatment is not due to the ‘placebo effect’. In trials investigating severe disease, such as cancer trials, it is unethical to deny a group of patients the treatment, in which case, a placebo group is not used.
What are the steps involved in carrying out a clinical trial?
Clinical trials are complex, so research teams invest a lot of time, money, and resources into organising them correctly. With so much at stake, it is important that trials are well planned so that money and resources are not wasted later down the line. .
Although each trial might differ slightly, they all follow similar steps in the design, planning, and delivery or the research:
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Define the Objective and Design the Protocol
Investigators will carry out research into a disease to identify an unmet medical need. They will then formulate a research question or hypothesis. A detailed protocol (study procedure) is developed that outlines the trial’s purpose, methodology, and study design, along with outcome measures (how the research team will measure the findings or outcomes of the trial).
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Secure Ethical Approval
The investigators must then submit their protocol to their local ethics committee or Institutional Review Board (IRB) for approval. This is to ensure compliance with ethical guidelines and to meet regulatory requirements.
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Screen and Recruit Participants
Eligible participants are then identified based on defined inclusion and exclusion criteria (factors which determine who does or does not meet the criteria of the study). The trial is then advertised, and those who are interested will attend the trial site for consenting and a screening visit. If they pass screening, they are recruited and can take part in the trial.
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Deliver the Trial
The intervention (e.g., new drug or therapy) will be administered to the participants following the protocol. Important data is collected during the trial visits, and the trial is monitored closely by the leading organisation.
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Analysis of Results
After the volunteers have completed all of their trial visits, the researchers will use statistical methods to assess the trial’s outcomes, comparing the intervention group (who were given the new treatment or intervention) with control or standard treatments, that is treatments that are already used to treat patients affected by that particular illness.
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Report and Disseminate Findings
In the final stage, the results of the study are published in peer-reviewed journals. Findings are reported to stakeholders (the organisations and people involved in the study) and regulatory authorities. If the findings are significant, they can be used to inform clinical practice and guide future research.
References
National Institutes of Health. “The Basics.” National Institutes of Health (NIH), 3 Oct. 2022, www.nih.gov/health-information/nih-clinical-research-trials-you/basics.
NIHR. “Clinical Trials Guide.” Nihr.ac.uk, 2019, www.nihr.ac.uk/clinical-trials-guide.
UKCRC. “Understanding Clinical Trials.” UK Clinical Research Collaboration, UK Clinical Research Collaboration, 2006, www.ukcrc.org/.
World Health Organization. “Clinical Trials.” who.int, 2023, www.who.int/health-topics/clinical-trials#tab=tab_1.
With many thanks to Mark Warburton for writing this blog to share with our community!