Design and Data Analysis Methods of N-of-1 Trials_Chinese Journal of Evidence-Based Medicine

Authors：

 CHENXin-lin ¹ , LIHai-wen ² , LIUFeng-bin ² , LIXian-tao ¹ , HOUZheng-kun ² , MOChuan-wei ¹ , XUQian ¹

1. Basic Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, China;
2. The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China;

Corresponding author：

Keywords：

N-of-1 trials; Design; Data analysis method; Mixed-effects model; Meta-analysis

DOI：

10.7507/1672-2531.20160038

Video：

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This paper mainly introduces the design, advantages, disadvantages and its application of single case of randomized controlled trials (N-of-1 trials), and also introduces the commonly used data analysis methods of N-of-1 trials including nonparametric test and parameter test methods (t-test, paired t-test, analysis of variance), mixed-effects model, and meta-analysis. N-of-1 trials are suitable for individualized treatment, and could be expected to be widely used in the research of modern medicine and traditional Chinese medicine.

Citation： CHENXin-lin, LIHai-wen, LIUFeng-bin, LIXian-tao, HOUZheng-kun, MOChuan-wei, XUQian. Design and Data Analysis Methods of N-of-1 Trials. Chinese Journal of Evidence-Based Medicine, 2016, 16(2): 242-245. doi: 10.7507/1672-2531.20160038 Copy

1.	Guyatt G, Sackett D, Taylor DW, et al. Determining optimal therapy——randomized trials in individual patients. N Engl J Med, 1986, 314(14) :889-892.
2.	Nikles J, Mitchell GK, Schluter P, et al. Aggregating single patient (n-of-1) trials in populations where recruitment and retention was difficult:the case of palliative care. J Clin Epidemiol, 2011, 64(5) : 471-480.
3.	Johnston BC, Mills E. n-of-1 randomized controlled trials:an opportunity for complementary and alternative medicine evaluation. J Altern Complement Med, 2004, 10(6) :979-984.
4.	Guyatt GH HR, Jaeschke R, Cook D, et al. Introduction:The philosophy of evidence-based medicine. In:Guyatt G, Rennie D. The Users' Guides to the Medical Literature:A Manual for EvidenceBased Clinical Practice. Chicago:American Medical Association Press, 2002:3-11.
5.	Edgington ES. Statistics and single case analysis. Progress in behavior modification, 1984, 16:83-119.
6.	Edgington ES. Statistical inference from N-1 experiments. J Psychol, 1967, 65(2) :195-199.
7.	陈炜炜, 李宁. 针刺治疗脊髓损伤后下肢痉挛:单病例随机对照试验. 中国针灸, 2010, 30(6) :473-477.
8.	王辉, 陈静, 商洪才. 单病例随机对照试验设计在中医药临床研究的探索与实践. 中华中医药杂志, 2010, 25(11) :1823-1828.
9.	田永明. 十味益元颗粒治疗化疗骨髓抑制的单病例随机对照试验. 中国中医科学院. 2010.
10.	Zucker DR, Schmid CH, McIntosh MW, et al. 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.
11.	Senn S. Cross-over trials in clinical research. Chichester, UK:John Wiley and Sons, 1993.
12.	Yelland MJ, Poulos CJ, Pillans PI, et al. N-of-1 randomized trials to assess the efficacy of gabapentin for chronic neuropathic pain. Pain Med, 2009, 10(4) :754-761.
13.	Nathan PC, Tomlinson G, Dupuis LL, et al. A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy:a Bayesian randomized serial N-of-1 trials design. Support Care Cancer, 2006, 14(3) :268-276.
14.	Gabler NB, Duan N, Vohra S, et al. N-of-1 Trials in the Medical Literature:A Systematic Review. Medical Care, 2011, 49(8) :761-768.
15.	Zucker DR, Ruthazer R, Schmid CH. Individual (N-of-1) trials can be combined to give population comparative treatment effect estimates:methodologic considerations. J Clin Epidemiol, 2010, 63(12) :1312-1323.
16.	Guyatt GH JR, Roberts R. N-of-1 randomized clinical trials in pharmaco epidemiology. In:Strom B, eds. Pharmacoepidemiology, 3rd ed. Chicago:John Wiley & Sons Inc, 2000:615-631.
17.	Blumberg CJ. Comments on "A simplified time-series analysis for evaluating treatment interventions". J Appl Behav Anal, 1984, 17(4) : 539-544.
18.	Deprospero A, Cohen S. Inconsistent visual analyses of intra subject data. J Appl Behav Anal, 1979, 12:573-579.
19.	Guyatt G, Sackett D, Adachi J, et al. A clinician's guide for conducting randomized trials in individual patients. CMAJ, 1988, 139(6) :497.
20.	Huber AM, Tomlinson GA, Koren G, et al. Amitriptyline to relieve pain in juvenile idiopathic arthritis:a pilot study using Bayesian metaanalysis of multiple N-of-1 clinical trials. J Rheumatol, 2007, 34(5) :1125-1132.
21.	Higgins J, Whitehead A, Turner RM, et al. Meta-analysis of continuous outcome data from individual patients. Sta Med, 2001, 20(15) :2219-2241.
22.	Schluter PJ, Ware RS. Single patient (n-of-1) trials with binary treatment preference. Stat Med, 2005, 24(17) :2625-2636.
23.	Chen X, Chen P. A Comparison of Four Methods for the Analysis of N-of-1 Trials. PLOS ONE, 2014, 9(2) :e87752.
24.	陈新林, 陈平雁. N-of-1无残留效应定量数据混合效应模型的模拟研究. 中国卫生统计, 2013, 30(3) :347-350.
25.	刘保延, 胡镜清, 谢雁鸣, 等. 中医药学现代个体诊疗体系建立的构想与研究. 世界科学技术-中医药现代化, 2003, 5(1) :1-6.

1. Guyatt G, Sackett D, Taylor DW, et al. Determining optimal therapy——randomized trials in individual patients. N Engl J Med, 1986, 314(14) :889-892.
2. Nikles J, Mitchell GK, Schluter P, et al. Aggregating single patient (n-of-1) trials in populations where recruitment and retention was difficult:the case of palliative care. J Clin Epidemiol, 2011, 64(5) : 471-480.
3. Johnston BC, Mills E. n-of-1 randomized controlled trials:an opportunity for complementary and alternative medicine evaluation. J Altern Complement Med, 2004, 10(6) :979-984.
4. Guyatt GH HR, Jaeschke R, Cook D, et al. Introduction:The philosophy of evidence-based medicine. In:Guyatt G, Rennie D. The Users' Guides to the Medical Literature:A Manual for EvidenceBased Clinical Practice. Chicago:American Medical Association Press, 2002:3-11.
5. Edgington ES. Statistics and single case analysis. Progress in behavior modification, 1984, 16:83-119.
6. Edgington ES. Statistical inference from N-1 experiments. J Psychol, 1967, 65(2) :195-199.
7. 陈炜炜, 李宁. 针刺治疗脊髓损伤后下肢痉挛:单病例随机对照试验. 中国针灸, 2010, 30(6) :473-477.
8. 王辉, 陈静, 商洪才. 单病例随机对照试验设计在中医药临床研究的探索与实践. 中华中医药杂志, 2010, 25(11) :1823-1828.
9. 田永明. 十味益元颗粒治疗化疗骨髓抑制的单病例随机对照试验. 中国中医科学院. 2010.
10. Zucker DR, Schmid CH, McIntosh MW, et al. 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.
11. Senn S. Cross-over trials in clinical research. Chichester, UK:John Wiley and Sons, 1993.
12. Yelland MJ, Poulos CJ, Pillans PI, et al. N-of-1 randomized trials to assess the efficacy of gabapentin for chronic neuropathic pain. Pain Med, 2009, 10(4) :754-761.
13. Nathan PC, Tomlinson G, Dupuis LL, et al. A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy:a Bayesian randomized serial N-of-1 trials design. Support Care Cancer, 2006, 14(3) :268-276.
14. Gabler NB, Duan N, Vohra S, et al. N-of-1 Trials in the Medical Literature:A Systematic Review. Medical Care, 2011, 49(8) :761-768.
15. Zucker DR, Ruthazer R, Schmid CH. Individual (N-of-1) trials can be combined to give population comparative treatment effect estimates:methodologic considerations. J Clin Epidemiol, 2010, 63(12) :1312-1323.
16. Guyatt GH JR, Roberts R. N-of-1 randomized clinical trials in pharmaco epidemiology. In:Strom B, eds. Pharmacoepidemiology, 3rd ed. Chicago:John Wiley & Sons Inc, 2000:615-631.
17. Blumberg CJ. Comments on "A simplified time-series analysis for evaluating treatment interventions". J Appl Behav Anal, 1984, 17(4) : 539-544.
18. Deprospero A, Cohen S. Inconsistent visual analyses of intra subject data. J Appl Behav Anal, 1979, 12:573-579.
19. Guyatt G, Sackett D, Adachi J, et al. A clinician's guide for conducting randomized trials in individual patients. CMAJ, 1988, 139(6) :497.
20. Huber AM, Tomlinson GA, Koren G, et al. Amitriptyline to relieve pain in juvenile idiopathic arthritis:a pilot study using Bayesian metaanalysis of multiple N-of-1 clinical trials. J Rheumatol, 2007, 34(5) :1125-1132.
21. Higgins J, Whitehead A, Turner RM, et al. Meta-analysis of continuous outcome data from individual patients. Sta Med, 2001, 20(15) :2219-2241.
22. Schluter PJ, Ware RS. Single patient (n-of-1) trials with binary treatment preference. Stat Med, 2005, 24(17) :2625-2636.
23. Chen X, Chen P. A Comparison of Four Methods for the Analysis of N-of-1 Trials. PLOS ONE, 2014, 9(2) :e87752.
24. 陈新林, 陈平雁. N-of-1无残留效应定量数据混合效应模型的模拟研究. 中国卫生统计, 2013, 30(3) :347-350.
25. 刘保延, 胡镜清, 谢雁鸣, 等. 中医药学现代个体诊疗体系建立的构想与研究. 世界科学技术-中医药现代化, 2003, 5(1) :1-6.

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