What are the types of Clinical Trials?
Photo by Owen Beard on Unsplash
Article by Simone Richer
Clinical trials are conducted by researchers who recruit volunteers to participate in a study that aims to answer a specific research question. Each clinical trial has a unique research question and study protocol but can be categorized into a broad category based on the study objective and design.
The two main types of clinical trials are interventional and observational. There are also sub-types of trials within interventional and observational and some trial types that do not fit into either of these categories.
Interventional trials aim to investigate the effect of a treatment. Participants are split into groups and each group receives a different treatment. The groups are then compared to determine if the one treatment is better than the other. The ‘treatment’ may be a new drug or vaccine but could also be a new surgical method, medical device, or behavioural change such as a special diet or exercise regime. A new intervention will always be compared to the current standard treatment unless no treatment is currently available in which case the new treatment will be compared to a placebo.
Interventional trials are usually classified into different stages ranging from zero to four. The earlier phases are focused on determining the safety and side effects of the treatment, and the later phases are focused on determining if the new treatment is any better than the existing treatment options. Earlier trial phases are usually conducted with smaller treatment groups and are not typically randomized whereas later stage trials involve larger treatment groups, randomization, and blinding.
What is randomization? This process involves at least two separate treatment groups and participants are assigned to a group at random by a computer program. One group will be given the standard treatment for their condition (this becomes the control group) and the other group is given the new treatment. Randomization is important because it decreases the risk of bias influencing the results.
In addition to being randomized late-stage treatment trials are usually blinded. This means the patient does not know if they are receiving the control or the intervention. A double-blind trial is when neither the patient nor the researcher knows what intervention the patient is receiving.
Multi-arm or multi-stage treatment trials are trials with more than two treatment groups (arms) as well as a control group. The control group remains constant throughout the study but the treatment groups may change. For example, if an intervention is clearly not working researchers will stop recruiting participants to that group, or if a new treatment becomes available a new treatment group may be added.
Observational trials aim to investigate health outcomes in groups of participants who are exposed to different environments. Participants are observed by researchers but researchers do not interfere with treatment and patients may receive treatment as per their normal medical routine. The main sub-types of observational trials include cohort studies, case-control studies, and cross-sectional studies.
Cohort studies observe the same group of people over a period of time. Researchers will often recruit participants and follow them for many years gathering information through qualitative questionnaires, blood tests, and other measurement tools. One common example is for researchers to recruit participants who are ‘at risk’ of developing a certain disease and follow them to observe which individuals go on to develop the disease. Researchers then look back to determine if all the individuals who developed the condition had anything in common. This can help identify risk factors for specific conditions.
Case-control studies observe a group of people who already have a disease (cases) and a group of people who do not have the disease (controls) to look back in time and determine how many people in each group were exposed to certain risk factors. These studies often rely heavily on participants’ memory which can be biased and unreliable.
Cross-sectional studies are conducted at a specific point in time for a short period of time. They look at who has been exposed to a specific risk factor and who has then gone on to develop the disease to determine if there is a link. Results from this type of study are often unreliable and not very useful.
Before conducting a full scale interventional or observational trial, researchers may choose to conduct a feasibility study and/or a pilot trial.
A feasibility study is the earliest stage of a clinical trial (more like a pre-trial) and the researchers’ only aim is to determine if it is possible to conduct a full-scale study. This involves determining if doctors and patients are happy to participate and how best to design and organize the trial. This type of study does not aim to answer the primary research question. A pilot trial is a small scale version of the main study and acts as a ‘trial run’ for the main study. Information collected during a pilot study may be used to help answer the primary research question.
Although interventional and observational trials are most common there are many other types of clinical trials that do not fit into either category. These include prevention trials, screening trials, diagnostic trials, genetic studies, and quality of life research. All of which are equally important to advancing medical knowledge and improving the future of healthcare.
Prevention trials are very important and can be used to determine if a particular intervention can potentially prevent the onset of a disease. Participants are those who do not currently have the disease but may have specific risk factors. Prevention trials are commonly used to prevent ‘at risk’ patients from developing cancer and can be action studies or agent studies.
Action studies are prevention trials focused on ‘doing something’ such as exercising or changing diets to reduce the risk of cancer or heart disease.
Agent studies are prevention trials focused on ‘taking something’ such as medications, vitamins, or supplements that may reduce the risk of future disease.
Screening trials are research studies that test for early signs of disease (ie. cancer) before any symptoms are present. This type of trial is mainly used to determine if a specific test is reliable enough to detect a positive/negative result. This type of study can also help researchers to determine if there is a benefit to early intervention and treatment.
Overall there are many types of clinical trials and it is important to understand that the trial-type will determine the primary research objective and the study design. All trial-types are valuable for medical research, but not all trial types will have a direct benefit on your personal health. For example, observational trials help researchers determine risk-factors and disease-associations to help prevent the condition in future patients, but participating in this type of trial will likely not have a significant impact on your personal health. Even late-stage treatment trials do not always have a direct positive impact on your personal health and so it is important to consider the broader benefits of how participating in medical research can influence care for future generations of patients.
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