Clinical trials are vital for determining the safety and efficacy of new drugs and interventions for a variety of different medical conditions, diseases, and illnesses. In clinical research, there are a variety of different trial and study types that can be used. From interventional and observational trials to cohort and cross-sectional studies, researchers have a plethora of options to choose from.
Depending on the objectives of the trial, researchers may also use a single arm methodology as part of an interventional trial to test new interventions.
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What is a single arm study?
A single arm study is a method of data collection used by researchers in interventional trials. In single arm studies, all participants receive the same treatment or intervention. Trial investigators will only observe this group of participants, meaning there is no control group to compare against. Single arm clinical trials can also be open label, which means both the participants and researchers know who is receiving the experimental treatment.
While this type of study can be beneficial in clinical research, it has been critiqued for some time due to the lack of a comparison group. Without a control group, researchers can find it more difficult to establish the effectiveness of a treatment.
Characteristics of single arm studies
Single arm studies can be distinguished by their characteristics which typically differ from other types of clinical studies.
Control group - All participants in a single arm study receive the same intervention, so there is no control group receiving a standard treatment or placebo for comparison. The intervention could be a new drug or other type of treatment.
Sample size - Single arm studies often use a smaller sample size than more commonly used clinical trial types like randomized controlled trials (RCTs). This could be due to limited population numbers for a specific study or to gather more detailed information on a limited number of participants.
Objective - While many clinical trials seek to compare an intervention with placebos or other standard treatments, single arm studies aim to establish the effects of an intervention in more detail.
Design - Compared with other types of trials, like RCTs, single arm studies typically have a much more simple design. They can also be cheaper and quicker to design and run as they involve less participants and are less complex in terms of logistics.
Ethical considerations - In some trials, it is deemed unethical to withhold information from participants, such as by using a placebo in trials studying life-threatening conditions with no effective existing treatments. Single arm clinical trials can be viewed as more ethical as participants all receive the same treatment. In an open label single arm study, participants are aware of what they are receiving which can be viewed as more ethical.
Context - With the ability to offer successful results with a small sample size, single arm studies are regularly used in studies for rare conditions, oncology, or personalized medicine where urgency for treatment is high.
Trial phase - Single arm studies are frequently used by researchers in the early phases of clinical trials, often phase I or II. This is because in these phases, the study can be used to evaluate the potential of the intervention and gather initial safety and efficacy data.
The purpose of single arm studies
Single arm studies are primarily designed to evaluate the safety, efficacy, pharmacokinetics, and other characteristics of a new intervention or treatment in a specific population. Researchers use these studies to obtain preliminary data that can determine whether the treatment shows promise in achieving the desired outcomes. This could be anything from disease stabilization to symptom improvement.
In phase I and II clinical trials, researchers seek to assess the potential of a treatment which is where single arm studies are crucial. They are not designed to provide definitive evidence of efficacy but instead gather data on the safety and tolerability of the intervention.
In a single arm study, researchers monitor participants for adverse effects or other safety concerns. This data can help them establish whether the treatment is safe enough for further testing in more rigorous or larger trials. Single arm studies can also help to determine how the treatment can be administered and its appropriate dosage for future studies. This includes figuring out the maximum tolerated dose or optimal dosing regimen.
With more detailed and close monitoring, single arm studies can provide data on how an intervention or treatment behaves in the body, such as how it’s absorbed, distributed, metabolized, and excreted. The data can also be used to establish the treatment’s biological effects.
Another key purpose of single arm studies is to provide a “proof of concept”. For studies researching a rare disease or condition that has no established standard of care, these studies can provide evidence that the treatment is effective. Researchers can use this evidence to further justify research and investment.
The benefits and challenges of single arm trials trials
Like any type of clinical trial or trial methodology, single arm studies offer a number of advantages and disadvantages for researchers and participants alike.
The advantages of single arm trials
Single arm studies offer several unique advantages that are not always available in other types of clinical trials. A key benefit is the ability to provide preliminary evidence of the safety and effectiveness of a new intervention or treatment. Researchers can gain valuable insights into the potential mechanisms of action of a treatment, supporting the guidance of future research.
Cost and time efficiencies are also prominent benefits of single arm trials. Compared to RCTs, single arm studies require fewer participants and are therefore cheaper to run and can be completed more quickly.
In a single arm clinical trial, researchers are able to evaluate the data from a treatment more quickly too. This makes them particularly beneficial for trials researching rare conditions or diseases with limited treatment options.
The disadvantages of a single arm study
The main disadvantage of single arm studies is that they don’t involve a comparison group. Without this element, it can be difficult to establish whether any of the observed effects are due to the intervention or other factors. With no control group to rule out placebo effects or natural disease progression, there is the potential that single arm studies can be seen as less reliable. A lack of control group also makes it difficult for researchers to draw definitive efficacy conclusions, leading to potential bias and less meaningful conclusions.
In most cases, single arm studies have a small sample size which can make it harder for researchers to generalize the findings for a larger population, therefore limiting the overall impact and applicability of the trial.
What trial phases are single arm studies used in?
While they are most commonly used in early phases of clinical trials, specifically phase I and II, single arm studies can be used in all four phases of clinical research.
Phase I single arm studies
With a primary focus on assessing the safety profile of a new intervention, single arm studies are most commonly used in phase I of a clinical trial where researchers give the experimental treatment to all participants. They are then monitored for adverse effects and pharmacological data. At this stage, they can also help to establish the appropriate dosage levels for a treatment should it be continued into further phases or trials.
Phase II single arm studies
In phase II of a clinical trial, single arm studies can be used to determine whether the intervention has a biological effect and what side effects could be experienced in a larger group of participants. Single arm studies are particularly useful in exploratory or preliminary studies where the goal is to establish treatment efficacy.
Phase III and IV single arm studies
Although they are not as commonly used in phase III and IV trials, single arm studies can still be used in certain situations. In studies targeting rare diseases where participant recruitment can be difficult, or in studies where it’s unethical to withhold a potentially beneficial treatment, single arm studies can be used in phase III.
Phase IV trials are known as post-marketing studies, and on occasions, single arm studies can be used to gather additional information about the effectiveness or safety of a drug in specific populations or in real-world conditions.
The differences between single arm studies and other types of clinical research
All types of clinical studies are different, including single arm studies. From design and purpose to data collection and evidence gathered, each has its own distinct characteristics.
Single arm studies vs. randomized controlled trials (RCTs)
There are several distinct differences between single arm studies and RCTs, which are often considered the ‘gold standard’ of clinical research.
Design - In single arm studies, all participants receive the same experimental intervention and there is no control group for comparison. RCTs, however, randomly assign participants to different groups. There is typically a group receiving the treatment, and a group receiving either the standard treatment or a placebo.
Objective - Single arm studies are typically used to establish safety and efficacy in early phases of clinical trials, particularly those studying rare diseases or where control groups are impractical or unethical. In RCTs, researchers can provide more high-quality evidence regarding the safety and efficacy of a treatment, reducing bias.
Evidence - With no control group, single arm studies generally provide lower levels of evidence than RCTs. This is because the results can be influenced by placebo effects, natural disease progression, or other factors. RCTs can provide much higher-quality evidence due to the control group enabling direct comparisons and establishment of casualty between the intervention and observed outcomes.
Interested in learning more about randomization in clinical trials? Read about its purpose, various methods, and the important role it plays in ensuring accurate and reliable research outcomes in our guide What is Randomization in Clinical Trials?
Single arm studies vs. cohort studies
Single arm studies also have distinct elements that differentiate them from cohort studies, typically used in observational trials.
Design - Single arm studies deliver the experimental treatment to one group of participants, while cohort studies follow two or more groups over time. In cohort studies, one group is exposed to the intervention or risk factor while the other is not.
Objective - While single arm studies mostly focus on the treatment’s effects in the treated group, cohort studies can investigate the natural history of a condition, disease risk factors, and the effects of exposures on outcomes.
Evidence - In single arm studies, researchers seek to provide preliminary or supporting evidence about an intervention. Cohort studies can deliver strong observational evidence, especially in prospective trials. However, they may be more susceptible to confounding variables.
Single arm studies vs. case-control studies
Several features distinguish single arm studies from case-control studies too, including the design and objectives of each.
Design - In a single arm study, one group receives the intervention, while case-control studies compare individuals with a specific condition or outcome to those without the condition or outcome. In case-control studies, researchers can identify factors that may contribute to the condition.
Objective - Single arm studies are designed to establish the effects of the intervention. Case-control studies, on the other hand, are mostly used to identify associations between exposures and outcomes, particularly when researching rare diseases or conditions.
Evidence - While single arm studies aim to establish preliminary evidence, they can be limited by the lack of a comparison group. In case-control studies, researchers can generate hypotheses and establish potential risk factors. However, they can be limited by recall bias and challenges in establishing causality.
Why take part in a single arm study
There are many reasons why someone should consider taking part in a single arm study, but the biggest benefit for participants is the access to new and innovative treatments that are not yet available in the wider population. This is particularly beneficial for individuals with conditions that have limited treatment options or who have not responded well to standard therapies.
Another benefit of being involved in a single arm study is that close monitoring and high-quality care will be provided. This might be more detailed than standard care which could help to identify adverse effects, additional symptoms or disease progression more quickly. Some participants may also experience personal health benefits from the experimental treatment, such as greater stabilization or symptom relief.
Clinical research is important for the wider medical community, improving understanding of conditions and enabling researchers to improve treatments. Participation in a single arm study means individuals will be contributing to the advancement of medical knowledge and the development of new treatments.
How to get involved in a single arm study
If you’re interested in participating in a single arm study, there are several ways you can get involved. The first step is to find a clinical trial that is actively recruiting participants. You can do this by searching online clinical trial databases, seeking out local groups, or speaking with your healthcare team who may know about upcoming trials.
Once you’ve found a clinical trial that is suitable for you and your condition, it’s important to educate yourself about the trial and its purpose. You can do this by reading online resources, or reaching out to the trial organizers to gather more information.
Conclusion
Although they have been critiqued by the medical community and can come with some uncertainties, there are several instances where single arm trials can be a beneficial method of clinical research. With guaranteed access to new treatments, enhanced medical care, and the potential for personal health benefits, as well as a contribution to medical research, single arm studies offer an effective way to study certain conditions.