N-of-1 trials test treatment effectiveness within an individual patient.
To assess (i) the impact of three different N-of-1 trials on both clinical and economic outcomes over 12 months and (ii) whether the use of N-of-1 trials to target patients’ access to high-cost drugs might be cost-effective in Australia.
Descriptive study of management change, persistence, and costs summarizing three N-of-1 trials.
Volunteer patients with osteoarthritis, chronic neuropathic pain or ADHD whose optimal choice of treatment was uncertain.
Double-blind cyclical alternative medications for the three conditions.
Detailed resource use, treatment and health outcomes (response) data collected by postal and telephone surveys immediately before and after the trial and at 3, 6 and 12 months. Estimated costs to the Australian healthcare system for the pre-trial vs. 12 months post-trial.
Participants persisting with the joint patient-doctor decision 12 months after trial completion were 32% for osteoarthritis, 45% for chronic neuropathic pain and 70% for the ADHD trials. Cost-offsets were obtained from reduced usage of non-optimal drugs, and reduced medical consultations. Drug costs increased for the chronic neuropathic pain and ADHD trials due to many patients being on either low-cost or no pharmaceuticals before the trial.
N-of-1 trials are an effective method to identify optimal treatment in patients in whom disease management is uncertain. Using this evidence-based approach, patients and doctors tend to persist with optimal treatment resulting in cost-savings. N-of-1 trials are clinically acceptable and may be an effective way of rationally prescribing some expensive long-term medicines.
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attention-deficit hyperactivity disorder
bias-corrected and accelerated
general practitioner i.e. family physician
pharmaceutical benefits scheme
randomized controlled trial
- 95% CI:
95% confidence interval
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Thanks to, Jonathan Chan, and Fraser Mackenzie from Princess Alexandra Hospital for their help in recruiting participants; Jo Sturtevant from Princess Alexandra Hospital and Nancy Fish from Port Kembla Hospital for estimates of costs and assistance with trials; staff from the Mater Children’s Hospital, Brisbane for their help in implementing ADHD trials in the Mater Hospital; Eric Lee for technical advice and preparation of pharmaceuticals for the ADHD trial; the N-of-1 trial service staff for collecting the data; Virginia Priest for reviewing a previous draft of this manuscript and making valuable comments; and the doctors and participants who took part in the trials.
We did not receive any specific funding to write this article.
The Australian Health Ministers Advisory Council (http://www.ahmac.gov.au) provided funding but had no involvement in any facet of the research. For the celecoxib/acetominophen n-of-1 trial, GlaxoSmithKline Consumer Healthcare (http://www.gsk.com.au) supplied medication, placebos, some funding and invaluable support; participated in initial planning discussions; and viewed the manuscript prior to publication, but had no role in the conduct, collection, management, analysis or interpretation of data; preparation or approval of the manuscript or the decision to submit the final manuscript for publication. The Princess Alexandra Hospital (http://www.health.qld.gov.au/pahospital/) and the Port Kembla Hospital (http://www.sesiahs.health.nsw.gov.au/Hospitals/Port_Kembla_Hospital) contributed funding for the gabapentin N-of-1 trial. Apart from the investigators based at these hospitals, no other personnel had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Paul Scuffham had full access to the economic data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Conflict of interest statement
GlaxoSmithKline Consumer Healthcare provided funding that supported the salaries of Jane Nikles and Norma McNairn on the project. Michael Yelland has been paid by GlaxoSmithKline to present the results of aspects of this research at two conferences.
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Scuffham, P.A., Nikles, J., Mitchell, G.K. et al. Using N-of-1 Trials to Improve Patient Management and Save Costs. J GEN INTERN MED 25, 906–913 (2010). https://doi.org/10.1007/s11606-010-1352-7