A scoping review of randomized trials assessing the impact of n-of-1 trials on clinical outcomes

• Published in: PloS one Vol. 17; no. 6; p. e0269387
• Main Authors: Samuel, Joyce P., Wootton, Susan H., Holder, Travis, Molony, Donald
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.06.2022; Public Library of Science (PLoS)
• Subjects: Air flow; Atrial Fibrillation; Attention deficit hyperactivity disorder; Bias; Biology and Life Sciences; Biomedical materials; Cardiac arrhythmia; Chronic illnesses; Chronic pain; Clinical outcomes; Clinical trials; Collaboration; Consent; Fibrillation; Health risks; Health services; Human subjects; Humans; Hyperactivity; Hyperlipidemia; Hypertension; Intervention; Intolerance; Medical research; Medicine and Health Sciences; Medicine, Experimental; Osteoarthritis; Pain; Pain management; Patient satisfaction; Patients; Publication Bias; Quality of life; Randomized Controlled Trials as Topic; Registries; Research and Analysis Methods; Risk assessment; Statistical analysis; Treatment outcome; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0269387

The single patient (n-of-1) trial can be used to resolve therapeutic uncertainty for the individual patient. Treatment alternatives are systematically tested against each other, generating patient-specific data used to inform an individualized treatment plan. We hypothesize that clinical decisions informed by n-of-1 trials improve patient outcomes compared to usual care. Our objective was to provide an overview of the clinical trial evidence on the effect of n-of-1 trials on clinical outcomes. A systematic search of medical databases, trial registries, and gray literature was performed to identify trials assessing clinical outcomes in a group of patients undergoing an n-of-1 trial compared to those receiving usual care for any clinical condition. We abstracted elements related to study design and results and assessed risk of bias for both the overall randomized trials and the n-of-1 trials. The review was registered on PROSPERO. (CRD: 42020166490). Twelve randomized trials of the n-of-1 approach were identified in conditions spanning chronic pain, osteoarthritis, chronic irreversible airflow limitation, attention-deficit hyperactivity disorder, hyperlipidemia, atrial fibrillation, statin intolerance, and hypertension. One trial showed a statistically significant benefit in the primary outcome. Only one reached the pre-specified sample size target. Secondary outcomes showed modest benefits, including decreasing medication use, fewer atrial fibrillation episodes, and improved patient satisfaction. Very few trials have been undertaken to assess the effectiveness of n-of-1 trials in improving clinical outcomes, and most trials were underpowered for the primary outcome. Barriers to enrollment and retention in these trials should be explored, as well-powered randomized trials are needed to clarify the clinical impact of n-of-1 trials and assess their utility in clinical practice.