In the clinical research landscape, researchers can use many different types of trials to test a new drug or treatment. Each has its own benefits and drawbacks, which are heavily assessed and considered before a trial type is decided. One type of clinical trial is a non-inferiority trial.
While most standard clinical trials seek to show that a new treatment is better than an existing one, non-inferiority trials aim to show that the new treatment is not inferior to the existing one. Essentially, it is either equally effective or better.
Looking to participate in a clinical trial? Don't know where to start?
Our clinical trial platform can connect you with trials that match your needs and eligibility. Take the first step towards accessing cutting-edge treatments and start your search today to discover the potential benefits of participating in clinical trials.
The purpose of non-inferiority trials
In non-inferiority trials, researchers aim to demonstrate that the test treatment is not worse than a comparator by more than a predefined amount. The predefined amount is typically known as the non-inferiority margin, or delta, while the comparator is usually an already established and active treatment.
This type of clinical trial is commonly used when it is not ethical or feasible to use a placebo or standard care as a control group. Non-inferiority trials have an important role in the clinical research landscape, supporting researchers in developing and evaluating new medical treatments. With the data collected, clinical researchers can provide valuable information for clinicians and patients when making treatment decisions.
What is the non-inferiority principle?
The non-inferiority principle refers to the concept used in this type of clinical trial to determine whether a new treatment is as effective as one already in existence. The principle is based on the belief that a new treatment should not be considered inferior to an established one unless otherwise proven.
Researchers use this principle to compare two treatments without requiring one to be significantly better than the alternative. Instead, it allows clinicians to focus on ensuring the new treatment is not significantly worse than the existing one.
What treatments are tested in non-inferiority trials?
Many different treatments are tested in non-inferiority trials, including new medications like generics and biosimilars. Researchers test new drugs with this method to ensure they match the efficacy of branded drugs, but also to find out if they could be more affordable. Reformulated drugs, including extended-release versions of existing medications, can also be tested to confirm they are not less effective while potentially improving patient adherence.
Non-inferiority trials can also assess dosage forms and administration methods. For example, researchers may test oral medications versus injectables or topical treatments versus systemic treatments. Researchers will compare these methods to establish whether they have similar efficacy with potentially better patient compliance or fewer side effects.
New surgical methods or medical devices could also be evaluated to confirm they are not inferior to traditional methods. Clinicians will seek to determine outcomes of different types, to see if benefits like less invasiveness or quicker recovery times could be established.
Another common focus in non-inferiority trials is vaccines, with new vaccines tested to ensure they provide comparable immune responses to active ones. Fewer side effects or broader protection could be key areas of consideration for researchers testing vaccines with this type of trial.
Finally, non-inferiority trials can be used for new therapeutic regimens. For example, shorter treatment durations or different dosing schedules could be tested to determine whether they are as effective as standard regimens, while offering greater convenience or cost-efficiency.
Key features of a non-inferiority trial
Non-inferiority trials have several key features that set them apart from other types of clinical trials.
- Objective: The primary objective of a non-inferiority trial is to show that the new treatment's effectiveness is not significantly worse than the standard or existing treatment.
- Non-inferiority margin: The non-inferiority margin is a pre-specified threshold set out by researchers at the beginning of the trial. It defines the maximum allowable difference in efficacy between the new treatment and the existing one. The margin needs to be small enough to make sure the new treatment's efficacy is clinically acceptable.
- Control group: Most clinical trial types have a control group, as is the case in non-inferiority trials. The control group in these trials receives the standard treatment to provide a benchmark for comparison.
- Statistical considerations: In non-inferiority trials, the analysis is concerned with whether the new treatment's efficacy falls within the non-inferiority margin. Typically, researchers use confidence intervals to determine if the outcome difference is within the acceptable range.
- Sample size: Typically, smaller sample sizes are required in non-inferiority trials. However, researchers will often need to compare against superiority trials to ensure they can detect that the new treatment is not worse by more than the non-inferiority margin. Therefore, the sample size will be dependent on the specific trial.
The benefits and challenges of non-inferiority trials
Like all types of clinical trials, non-inferiority trials have several advantages and disadvantages. Each of these should be carefully considered before a research team decides to use this method as part of their clinical research.
The advantages of non-inferiority trials
Non-inferiority trials offer a number of advantages over traditional trial methodologies. Firstly, they enable researchers to evaluate new treatments to establish whether they have different mechanisms of action or can be used for different indications. This allows for a more comprehensive assessment of the treatment landscape, benefitting researchers, patients, and the wider research community.
Another advantage of non-inferiority trials is that they can often be more cost-effective. Since they usually require smaller sample sizes, they take up fewer resources and can be more efficient to complete.
Non-inferiority trials also have the potential to provide evidence for several treatment options, offering more choices for patients and healthcare professionals. This can be beneficial both in terms of treatment outcomes and cost.
Finally, non-inferiority trials are able to uncover valuable information about the safety and tolerability of a new treatment. This is vital for patient wellbeing and ensuring patients are receiving the best care and most relevant treatment for their condition.
The limitations of non-inferiority trials
Like any clinical trial type, non-inferiority trials can also pose challenges and limitations. While they offer valuable information about the effectiveness of a new treatment, researchers will need to consider the limitations of the methodology before proceeding.
A key limitation of non-inferiority trials is the choice of non-inferiority margin. This predetermined threshold establishes how much worse the new treatment can be compared to the comparable existing treatment. However, the margin is often subjective and can have a large impact on the interpretation of the trial results.
Another challenge is the ability to detect small differences in effectiveness between new and existing treatments. As non-inferiority trials cannot always detect these small differences due to the margins, it can be difficult to establish whether the new treatment is truly as good as what is already available.
Like other clinical trials, non-inferiority trials can also be subject to potential bias, lack of blinding, and difficulty in recruiting and retaining participants.
The difference between non-inferiority trials and other trials
We’ve already mentioned that non-inferiority trials have many differences when compared to other types of clinical trials. Understanding these differences is crucial for researchers to make informed decisions on the type of trial they should use. The differences between trials can also help clinical research teams establish clear evaluations on whether a new treatment is effective enough to be used in place of an existing one.
Placebo-controlled trials vs non-inferiority trials
The key difference between placebo-controlled trials and non-inferiority trials is the objective and control used in the trial.
Placebo-controlled trials have an objective to prove that a new treatment is effective when compared to no treatment. This makes them vital for determining the baseline efficacy of a new treatment. Non-inferiority trials, however, seek to show that a new treatment is comparably effective to an existing treatment while having the potential to offer other benefits.
Another difference in these trials is when they are used. Placebo-controlled trials are typically used in the earlier stages of research or when there isn’t another standard treatment available. Non-inferiority trials are commonly used when a proven treatment is already in existence and being used but researchers seek to establish whether the new treatment offers more advantages.
Both types of clinical trials are valuable and can be used effectively in clinical research. While placebo-controlled trials are critical for determining the efficacy of new treatments against no intervention, non-inferiority trials are important for testing new treatments that may offer more benefits over what’s already available.
Equivalence trials vs non-inferiority trials
Objectives and margins for comparison are the key differences between equivalence trials and non-inferiority trials.
Equivalence trials aim to show that two treatments have no meaningful differences in their efficacy, while non-inferiority trials only require researchers to show that the new treatment is not significantly worse than the standard treatment available. This means that equivalence trials need to show that the new treatment’s effect falls within a narrow range on both sides of the standard treatment’s effect. For non-inferiority trials, researchers only focus on one side of the margin.
Superiority trials vs non-inferiority trials
Once again, superiority trials and non-inferiority trials place their differences in their objectives and outcomes.
Superiority trials seek to prove that a new treatment is better than an existing one or a placebo. This is in contrast to non-inferiority trials which aim to establish that a new treatment is not unacceptably worse than the existing one. Superiority trials require a demonstration of a statistically significant improvement, while non-inferiority trials have a pre-defined, clinically acceptable range of inferiority which is often a much smaller margin.
The outcome of a superiority trial is to show that a new treatment is more effective in terms of efficacy, making them crucial in establishing clear clinical benefits. However, non-inferiority trials seek to demonstrate that a new treatment could be a viable alternative, potentially offering different benefits outside the efficacy factor.
Can you claim superiority in a non-inferiority trial?
As non-inferiority trials aim to demonstrate that a new treatment is simply not inferior to the standard treatment, superiority is not the key focus. However, despite this, it is possible for researchers to observe a superior outcome in the new treatment. In some cases, this is an added benefit of a non-inferiority trial, even though it is not the primary focus.
How to get involved in a non-inferiority clinical trial
If you’re interested in volunteering in a clinical trial, it’s possible to get involved in a non-inferiority trial in many different ways. The first step is to look for a clinical trial that is relevant to you and currently recruiting participants. You can do this by searching online databases or speaking with your healthcare professional.
If you have a specific illness or condition, you may also be able to speak to local groups about any clinical trials they are aware of. Many group organizers have access to this information and can pass on the recruitment details to you.
Once you’ve found a trial taking on participants, you should research the clinical trial and its purpose to ensure it is suitable for you. You can do online research or speak directly with the trial coordinator to ask any questions you may have about the trial.
The benefits of taking part in a non-inferiority trial
Taking part in a non-inferiority trial can be hugely beneficial for everyone, including participants, patients and the wider medical community. As this type of trial is designed to establish that a new treatment is not worse than the existing option available, it can be considered safer.
For patients, you could gain access to new therapies that could offer similar efficacy to what you’re already using, with potential added benefits such as fewer side effects, greater convenience, or lower costs. You may even find that the new treatment works better for you in terms of efficacy.
For healthcare professionals and researchers, non-inferiority trials are beneficial for introducing alternative treatments that could enhance patient care and provide solutions when standard treatments are either unsuitable or unavailable.
Conclusion
Non-inferiority trials are a crucial methodology in clinical research, enabling researchers to validate new treatments and determine whether there are additional benefits when compared to existing treatments, without compromising on efficacy. They enhance the patient care journey and ensure that patients are continually offered the best and most suitable care for their condition, while potentially delivering improved convenience, safety and cost-efficiency.