N of 1 trials are becoming a crucial tool for personalising patient care and conducting clinical research across a range of healthcare disciplines. Unlike traditional randomised controlled trials, which average data from many patients to identify group treatment effects, N of 1 trials focus on individual treatment responses. This makes them particularly valuable in areas where treatment outcomes can vary widely between patients. In this article, we will explore specific fields where N of 1 trials are making a significant impact for improving clinical decision-making and patient care, while also driving efficiency and fostering innovation in clinical research.
A key feature of an N of 1 trial is the use of randomisation, which ensures that the order of treatment and comparator phases is unpredictable. This helps minimise bias and ensures rigorous, reliable results. Blinding is used whenever possible, meaning that neither the patient nor the clinician/researcher knows when the patient is receiving the treatment or the comparator during the trial. This further reduces bias and increases the reliability of the results. The systematic observation of the patient's response to an intervention, allowing the most effective course of action to be determined based on direct evidence from the individual’s data,
Consider a patient dealing with insomnia. In an N of 1 trial, the patient might alternate between two different sleep aids - perhaps a commonly prescribed medication like zolpidem and a more natural remedy, such as melatonin. These medications would be randomly assigned in alternating periods over several weeks, with the patient's sleep quality and any side effects carefully monitored and recorded. The data would then be analysed to determine which sleep aid delivers the best improvement in sleep with the least adverse effects for that particular patient. This personalised approach moves away from a one-size-fits-all model of treatment, offering the patient a tailored solution that’s more likely to be effective and safe for them.
N of 1 trials are particularly useful when treatment outcomes vary greatly between individuals. Whether it’s determining the effectiveness of sleep aids, mental health therapies, or allergy medications, the trial’s results focus entirely on the individual, keeping them at the heart of the process. The beauty of this method lies in its flexibility, making it valuable in almost any clinical context where individual variation in treatment response exists.
Now, let’s take a closer look at how N of 1 trials have been successfully applied across various fields, transforming the way we approach treatment and care.
Cardiovascular Conditions
Recognising individual variability is essential when it comes to managing conditions like high cholesterol, high blood pressure and other cardiovascular conditions. A great example is the N of 1 trial conducted in 2020 that assessed the side effects associated with taking statins, a drug used to lower cholesterol. Many patients discontinue statins due to perceived side effects such as muscle pain. In this N of 1 trial, the patients alternated between taking a statin, a placebo tablet, and no treatment. Over time, it became clear that muscle pain wasn’t linked to taking the statin for most patients. The results of individual N of 1 trials were shared with patient participants. In many cases, the results encouraged them to continue the medication knowing that the side effects they were experiencing were not due to the statin, because they experienced them when they were taking placebo. This study underscores the pivotal role N of 1 trials can play in resolving uncertainty about the causes of side effects, enabling patients to confidently continue essential treatments.
Managing muscle symptoms associated with statin use is a common concern for many patients who are prescribed cholesterol-lowering medications. The StatinWISE project, published in 2021, expanded on the concept of using N of 1 trials byUnlike earlier studies, which primarily focused on individual cases, StatinWISE demonstrated the potential for scaling N of 1 trials to generate insights not only for individual patients but also for broader clinical practices. For example, while some patients found their symptoms were unrelated to statin use, others identified a clear connection and were guided toward alternative treatments. This large scale implementation of N of 1 trials underscores their utility in addressing patient concerns while reducing unnecessary discontinuation of effective therapies. The findings also highlight the role of personalised medicine in empowering clinicians to base decisions on both individual responses and population-level data.
Palliative Care
In palliative care, where quality of life is the top priority, N of 1 trials can help patients manage symptoms like fatigue, pain, and nausea. A 2015 study used this approach to assess the effectiveness of methylphenidate in reducing cancer-related fatigue. Patients alternated between the medication and a placebo, with results showing that for some patients, the drug significantly improved their energy levels, while for others, the effect was minimal or even harmful. This focus on the individual is crucial in palliative care, where treatment needs to be as tailored and flexible as possible to maximise comfort and quality of
Furthermore, using aggregated N of 1 trials (where data from multiple N of 1 trials with the same/similar protocol are aggregated) in palliative care settings enables researchers to uncover broader insights while maintaining a patient-centered approach. This powerful fusion of individualised care and collective data analysis showcases the unique strength of N of 1 trials, particularly in situations where traditional clinical trials are challenging due to recruitment difficulties - an issue often encountered in palliative care. By addressing these limitations, N of 1 trials pave the way for advancing research and care in even the most complex and sensitive healthcare contexts
Rare Genetic Conditions
N of 1 trials are perfectly suited for testing interventions in rare genetic conditions, where the limited number of patients makes large-scale clinical trials impractical. This approach ensures that valuable insights can still be gained, even in the context of small patient populations. An example is the (aggregated) N of 1 trial conducted in 2018 on a rare muscle condition called nondystrophic myotonia. Patients alternated between taking the drug mexiletine and a placebo tablet to see if the drug helped with muscle stiffness. The aggregated results from multiple N of 1 trials gave clear evidence that mexiletine was effective overall, offering a valuable treatment alternative for responders, for a condition that otherwise has limited options. A comparable level of statistical support for similar efficacy was achieved with aggregated data from just 11 N of 1 trials, compared to the sample size of 60 required in a similar previous RCT. This shows just how powerful pooled N of 1 trials can be. People with rare genetic conditions, who are often left without clear answers on effective treatments or the cause of their symptoms, can benefit immensely from N of 1 trials as they generate data to inform treatment plans that are tailored to their unique needs.
Musculoskeletal Conditions
Individualised care plays a vital role in the management of musculoskeletal conditions like osteoarthritis. A compelling example is an N of 1 trial designed to evaluate the effectiveness of different pain relief medications for osteoarthritis. The trial compared the efficacy of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and paracetamol by having patients alternate between treatments while closely tracking their pain levels and side effects over time. One notable result from the trial involved a participant with chronic knee pain, who found that NSAIDs provided more consistent relief than paracetamol, leading to an adjustment in their treatment plan. This highlights how N of 1 trials can optimise therapies, ensuring that patients receive the most effective treatments based on their individual responses.
Neurodevelopmental Conditions
N of 1 Trials are particularly well-suited for Neurodevelopmental conditions like Attention Deficit Hyperactivity Disorder (ADHD), where treatment responses can vary widely between individuals. A study explored the effectiveness of using N of 1 trials in routine clinical practice to assess stimulant medications for children with ADHD. In this trial, each child alternated between active stimulant treatment and a placebo over multiple cycles, while both the children and their families monitored changes in ADHD symptoms. The trial revealed that for some children, stimulant medication significantly improved attention and behaviour, while others showed less marked improvement or experienced significant side effects. By using the N of 1 trial design, doctors were able to identify the best course of action for each child, adjusting treatment plans based on individual responses rather than relying on aggregated outcomes from larger randomised controlled trials (RCTs).
The N of 1 trial design allows for truly individualised treatment, addressing the unique needs of each child rather than assuming that results from large RCTs will apply equally to all. Children are often underrepresented in clinical trials due to ethical concerns, recruitment challenges, and the need for parental consent, which can limit the generalisability of RCT findings to pediatric populations. While ADHD trials tend to include children more frequently, challenges remain, such as variability in how children respond to medications, the influence of environmental factors like school and family dynamics, and difficulties in accurately assessing behavioural outcomes. N of 1 trials help overcome these challenges by providing personalised data for each child, enabling clinicians to tailor treatments to their unique circumstances and avoid the trial-and-error approach commonly seen in ADHD management.
Gastrointestinal Conditions
Inflammatory Bowel Disease (IBD), which includes Crohn's disease and ulcerative colitis, is highly unpredictable, with treatment responses varying significantly among patients. N of 1 trials offer a structured approach to identify the most effective therapy for an individual, optimizing treatment based on their unique response and needs. A study published in 2022 in the American Journal of Gastroenterology explored the application of N of 1 trials in IBD management, where patients alternated between therapy, anti-inflammatory medications, and dietary interventions. One patient with Crohn’s disease alternated between different therapies, systematically evaluating both symptom relief and side effects. This approach allowed the patient to pinpoint the most effective treatment for long-term management, ensuring better symptom control while maintaining quality of life. This example highlights how N of 1 trials can yield valuable, patient-specific insights for managing chronic and unpredictable conditions like IBD, facilitating well-informed treatment decisions in the face of varying patient responses.
Metabolic Conditions
Managing highly unstable type 1 diabetes presents significant challenges, particularly when it comes to maintaining consistent blood glucose levels. A study published in 2021 explored the use of a closed-loop insulin delivery system for patients eligible for islet transplantation through a series of N of 1 trials. This innovative system automatically adjusts insulin delivery based on real-time glucose readings, offering a potential solution for those struggling with fluctuating blood sugar levels.
In one of the N of 1 trials, a patient with a history of severe hypoglycaemic episodes participated in the closed-loop system for several weeks. During this period, the patient experienced improved glycaemic control, with fewer extreme fluctuations compared to their previous insulin regimen. This direct comparison allowed better management of their condition, highlighting how N of 1 trials can lead to tailored interventions for individuals with complex metabolic conditions like type 1 diabetes.
Neurological Conditions
Neurological conditions often present complex challenges due to the intricate interplay between the nervous system and motor function. Stroke-related paresis, for example, poses significant difficulties in movement and strength in affected limbs. A 2022 study examined the use of a neuromotor prosthetic for stroke patients, employing a series of N of 1 trials to evaluate its effectiveness. The prosthetic was designed to stimulate neural pathways and support muscle activation, offering a novel approach for managing prolonged paresis. One participant with chronic paresis incorporated the neuromotor prosthetic into their rehabilitation regimen over several weeks and demonstrated significant improvements in mobility and limb strength, achieving better control compared to previous therapy routines. By enabling direct, personalised evaluation, N of 1 trials underscore the potential of tailored interventions to address the complex needs of individuals with stroke-related paresis
Allergy-Related Conditions
Diagnosing food allergies can be complex, often requiring a careful approach to differentiate between true allergies and intolerances and to identify foods triggering allergic responses. N of 1 trials present an innovative solution in this area. A 2018 study highlighted the use of randomised, double-blind N of 1 trials for food challenges, providing a robust framework for both diagnosis and treatment evaluation. One example involved a patient with suspected allergies to multiple food items. Over several weeks, the patient underwent a series of challenges where they alternated between consuming the suspected allergens one at a time and a placebo. By meticulously tracking symptoms, the clinician and patient could ascertain whether or not each food truly triggered an allergic reaction. This method not only clarified the patient’s specific allergens but also evaluated the effectiveness of avoidance strategies. Such trials can significantly enhance diagnostic accuracy and guide effective management plans.
Chronic Pain Conditions
Chronic pain is a multifaceted condition that affects millions worldwide, often requiring a tailored approach to treatment due to significant variability in how individuals respond to pain management strategies. Conventional clinical trials frequently struggle to address this variability, as they rely on aggregated outcomes that may not reflect the needs of individual patients. N-of-1 trials offer a unique solution, enabling clinicians to assess the effectiveness of specific treatments for individual patients by directly comparing interventions, such as active medications and placebos, within the same person. This approach ensures that treatment decisions are guided by the patient’s unique experience, paving the way for more targeted and effective pain management strategies
A previous study utilised an N of 1 trial design to assess the effectiveness of gabapentin, a medication widely prescribed for neuropathic pain. Participants in the trial alternated between gabapentin and a placebo over a series of cycles, tracking their pain levels and any side effects experienced. One notable case involved a patient who reported a marked reduction in pain intensity while taking gabapentin compared to when they received the placebo, highlighting the potential benefits of this medication for certain individuals. The findings from this study demonstrate how N of 1 trials can personalise pain management, offering insights that can help refine treatment strategies and improve patient outcomes in managing chronic neuropathic pain.
The Promise of N of 1 Trials in Health
N of 1 trials are paving the way for a more tailored approach in many diverse clinical contexts, offering the potential to revolutionize how treatments are developed and delivered. These trials provide actionable insights that address individual variability, surpassing the limitations of conventional, population-based methods. By focusing on the patient as their own control, N-of-1 trials allow clinicians to determine the most effective treatments for specific individuals. However, to ensure their reliability and validity, N of 1 trials must be meticulously designed, rigorously conducted, and appropriately analysed. Careful attention to methodology is critical to harness the full potential of these trials and translate their findings into meaningful clinical outcomes
Take the next step with us
At N-of-1 Hub, we provide expert guidance and training to help you navigate the full potential of N of 1 trials. Whether you’re a university researcher, clinician, or part of an organisation conducting clinical trials, we have the expertise to design, conduct, and analyse these powerful personalised clinical studies.
Our training is ideal for health professionals, including medical practitioners, naturopaths, psychologists, and dieticians, who are looking to enhance patient care through evidence-based, individualised treatment strategies. With our support, you can refine treatment approaches, improve patient outcomes, and bring the benefits of tailored interventions to those who need them most