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Using N-of-1 Trials to Improve Patient Management and Save Costs

Journal of General Internal Medicine Aims and scope Submit manuscript

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ABSTRACT

BACKGROUND

N-of-1 trials test treatment effectiveness within an individual patient.

OBJECTIVE

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.

DESIGN

Descriptive study of management change, persistence, and costs summarizing three N-of-1 trials.

PARTICIPANTS

Volunteer patients with osteoarthritis, chronic neuropathic pain or ADHD whose optimal choice of treatment was uncertain.

INTERVENTIONS

Double-blind cyclical alternative medications for the three conditions.

MEASURES

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.

RESULTS

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.

CONCLUSIONS

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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Figure 1
Figure 2

Abbreviations

ADHD:

attention-deficit hyperactivity disorder

BCa:

bias-corrected and accelerated

GP:

general practitioner i.e. family physician

IQR:

inter-quartile range

OA:

osteoarthritis

PBS:

pharmaceutical benefits scheme

RCT:

randomized controlled trial

SD:

standard deviation

SR:

slow-release

95% CI:

95% confidence interval

References

  1. Centre for Disease Control and Prevention. The Burden of Chronic Diseases and their Risk Factors: National and State Perspectives 2004. 2004; www.cdc.gov/NCCDPHP/burdenbook2004/. Accessed March 8, 2010.

  2. Chodick G, Heymann A, Wood F, Kokia E. The direct medical costs of diabetes in Isreal. Eur J Health Econ. 2005;6(2):166–171.

    Article  PubMed  Google Scholar 

  3. Guyatt G, Keller L, Jaeschke R, Rosenbloom D, Adachi J, Newhouse M. The N-of-1 randomized controlled trial: clinical usefulness. Our three-year experience. Ann Intern Med. 1990;112(4):293–299.

    CAS  PubMed  Google Scholar 

  4. Guyatt G, Sackett D, Taylor D. Determining optimal therapy. Randomized trials in individual patients. N Engl J Med. 1986;314(14):889–892.

    Article  CAS  PubMed  Google Scholar 

  5. Kravitz R, Duan N, Niedzinski E, Hay M, Subramanian S, Weisner T. What ever happened to N-of-1 trials? Insiders’ perspectives and a look to the future. Milbank Q. 2008;86(4):533–555.

    Article  PubMed  Google Scholar 

  6. Zucker D, Schmid C, McIntosh M, D’Agostino R, Selker H, Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997;50(4):401–410.

    Article  CAS  PubMed  Google Scholar 

  7. Scuffham P, Yelland M, Nikles C, Pietrzak E, Wilkinson D. Are N-of-1 trials an economically viable option to improve access to selected high cost medications? The Australian experience. Value Health. 2008;11(1):97–109.

    PubMed  Google Scholar 

  8. Nikles C, Mitchell G, del Mar C, McNairn N, Clavarino Z. Long-term changes in management following n-of-1 trials of stimulants in attention-deficit/hyperactivity disorder. Eur J Clin Pharmacol. 2007;63(11):985–989.

    Article  CAS  PubMed  Google Scholar 

  9. Yelland M, Poulos C, Pillans P, et al. N-of-1 randomized trials to assess the efficacy of gabapentin for chronic neuropathic pain. Pain Med. 2009;10(4):754–761.

    Article  PubMed  Google Scholar 

  10. Yelland M, Nikles C, McNairn N, del Mar C, Schluter P, Brown R. Celecoxib compared with sustained-release paracetamol for osteoarthritis: a series of n-of-1 trials. Rheumatology. 2007;46:135–140.

    Article  CAS  PubMed  Google Scholar 

  11. Cramer J, Rosenheck R, Kirk G, Krol W, Krystal J, VA Naltrexone Study Group 425. Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes. Value Health. 2003;6:566–573.

    Article  PubMed  Google Scholar 

  12. Department of Health and Ageing. Medicare Benefits Schedule. 2006; http://www.mbsonline.gov.au/internet/mbsonline/publishing.nsf/Content/MBSOnline-2006. Accessed March 9, 2010.

  13. Department of Health and Ageing. Schedule of Pharmaceutical Benefits for Approved Paharmacists and Medical Practitioners. Canberra: Commonwealth of Australia; 2006.

    Google Scholar 

  14. Efron B, Tibshirani R. The Bootstrap Method for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci. 1986;1(1):1–35.

    Google Scholar 

  15. Efron B, Tibshirani R. An Introduction to the Bootstrap. New York: Chapman Hall; 1993.

    Google Scholar 

  16. Nikles C, Yelland M, Glasziou P, del Mar C. Do individualized medication effectiveness tests (N-of-1 trials) change joint patient-doctor decisions about which drug to use for osteoarthritis and chronic pain? Am J Ther. 2005;12:92–97.

    Article  PubMed  Google Scholar 

  17. Nikles C, Clavarino Z, del Mar C. Using N-of-1 trials as a clinical tool to improve prescribing. Br J Gen Pract. 2005;55(512):175–180.

    PubMed  Google Scholar 

  18. Huser M, Evans T, Berger V. Medication adherence trends with statins. Adv Ther. 2005;22:163–171.

    Article  PubMed  Google Scholar 

  19. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–497.

    Article  CAS  PubMed  Google Scholar 

  20. Tsapas A, Matthews D. Using N-of-1 trials in evidence-based clinical practice. JAMA. 2009;301(10):1022–1023.

    Article  CAS  PubMed  Google Scholar 

  21. Suri R. The use of human deoxyribonuclease (rhDNase) in the management of cystic fibrosis. BioDrugs. 2005;19(3):135–144.

    Article  CAS  PubMed  Google Scholar 

  22. Pocock S. Current issues in the design and interpretation of clinical trials. Br Med J. 1985;290:39–42.

    Article  CAS  Google Scholar 

  23. Sheather-Reid R, Cohen M. Efficacy of analgesics in chronic pain: A series of N-of-one studies. J Pain Symptom Manage. 1998;15:244–252.

    Article  CAS  PubMed  Google Scholar 

  24. Guyatt G. Clinical care and clinical research: A false dichotomy. In: Daly J, ed. Ethical Intersections: Health Research, Methods and Research Responsibility. Sydney: Allen & Unwin; 1996:66–73.

    Google Scholar 

  25. Montori V, Guyatt G. Using N-of-1 trials in evidence-based clinical practice-Reply. JAMA. 2009;301(10):1023.

    Article  CAS  Google Scholar 

  26. Tsapas A, Matthews D. N of 1 trials in diabetes: Making individual therapeutic decisions. Diabetologia. 2008;51(6):921–923.

    Article  CAS  PubMed  Google Scholar 

  27. Nikles C, Mitchell G, del Mar C, Clavarino Z, McNairn N. An N-of-1 trial service in clinical practice: Testing the effectiveness of stimulants for attention deficit hyperactivity disorder. Pediatrics. 2006;117(6):2040–2046.

    Article  PubMed  Google Scholar 

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Acknowledgments

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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Authors and Affiliations

  1. School of Medicine, Griffith University, Brisbane, Queensland, Australia

    Paul A. Scuffham PhD & Michael J. Yelland PhD

  2. School of Medicine, the University of Queensland, Brisbane, Queensland, Australia

    Jane Nikles PhD

  3. Discipline of General Practice, the University of Queensland, Brisbane, Queensland, Australia

    Geoffrey K. Mitchell PhD

  4. Australian Red Cross Blood Service, Brisbane, Queensland, Australia

    Norma Vine BA, Hons

  5. Port Kembla Hospital, Port Kembla, NSW, Australia

    Christopher J. Poulos FAFRM & Guy Bashford FAFRM

  6. Princess Alexandra Hospital, Brisbane, Queensland, Australia

    Peter I. Pillans MD

  7. Faculty of Health Science and Medicine, Bond University, Gold Coast, Queensland, Australia

    Chris del Mar MD

  8. School of Public Health and Psychosocial Studies, Auckland University of Technology, Auckland, New Zealand

    Philip J. Schluter PhD

  9. School of Nursing and Midwifery, The University of Queensland, Brisbane, Queensland, Australia

    Philip J. Schluter PhD

  10. Department of Primary Health Care and Director, Centre for Evidence-Based Practice, Oxford University, Oxford, UK

    Paul Glasziou PhD

  11. Health Economics, School of Medicine, Griffith University, Logan Campus, L03 2.43, Meadowbrook, Queensland, 4131, Australia

    Paul A. Scuffham PhD

Authors
  1. Paul A. Scuffham PhD
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  2. Jane Nikles PhD
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  3. Geoffrey K. Mitchell PhD
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  5. Norma Vine BA, Hons
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  6. Christopher J. Poulos FAFRM
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  7. Peter I. Pillans MD
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  8. Guy Bashford FAFRM
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  9. Chris del Mar MD
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  10. Philip J. Schluter PhD
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  11. Paul Glasziou PhD
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Corresponding author

Correspondence to Paul A. Scuffham PhD.

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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

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  • DOI: https://doi.org/10.1007/s11606-010-1352-7

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