Analysis of the application of randomization methods in clinical trials in <i>NEJM</i>_Chinese Journal of Evidence-Based Medicine

Authors：

LIU Yaqi ^1,2 , LIU Man ^1,2 ,  LIU Yuxiu ^1,2,3 , CHEN Wensong ^1,2 , YUAN Yangdan ^2,3

1. Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, P.R.China;
2. Department of Critical Care Medicine, General Hospital of Eastern Theater Command, Nanjing 210002, P.R.China;
3. Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou 510515, P.R.China;

Corresponding author：

LIU Yuxiu, Email: liu_yuxiu@163.com

Keywords：

Randomized controlled trial; Randomization; Allocation concealment; Selection bias; NEJM

DOI：

10.7507/1672-2531.202010080

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To analyze the current status of the application of randomization methods in randomized controlled trials (RCTs) which have been published in New England Journal of Medicine (NEJM).Methods RCTs published by NEJM in 2018 were searched and collected. The characteristics of clinical trial design elements and the application status of randomization methods were comprehensively analyzed to distinguish blind trial and non-blind trial, and characteristics of application of randomization methods and selection of allocation concealment mechanisms of non-blind trials were summarized.Results A total of 151 RCTs were published in NEJM in 2018, in which blinded trials and non-blinded trials accounted for 75 (49.67%) and 76 (50.33%), respectively. 34 (22.52%) RCTs did not report specific randomization methods, and the remaining 117 (77.48%) reported. Among the latter, stratified block randomization accounted for the main body (72.65%), followed by block randomization (11.11%), minimization method (9.40%), simple randomization method (4.27%) and the others. There was no significant difference in the proportion of reporting or using randomization methods between blind and non-blind trials (P>0.05). In 76 non-blind trials, 38 (50.00%) clearly reported the concealment method of random allocation, among which 37 used the central randomization (97.37%) and 1 used envelope method (2.63%).Conclusions The current RCTs published in NEJM still have problems in the selection of randomization methods to be optimized and the transparency of randomization reporting to be improved.

Citation： LIU Yaqi, LIU Man, LIU Yuxiu, CHEN Wensong, YUAN Yangdan. Analysis of the application of randomization methods in clinical trials in NEJM. Chinese Journal of Evidence-Based Medicine, 2021, 21(3): 303-307. doi: 10.7507/1672-2531.202010080 Copy

1.	Cartwright N. Are RCTs the gold standard? BioSocieties, 2007, 2(1): 11-20.
2.	吕燃, 陈能, 刘少南, 等. 单髁置换术治疗膝骨关节炎对术后人工关节遗忘程度影响的Meta分析. 中国循证医学杂志, 2020, 20(8): 956-961.
3.	尤寿江, 仲崇科, 毛学宇, 等. 蚓激酶胶囊治疗急性缺血性卒中有效性和安全性的Meta分析. 中国循证医学杂志, 2020, 20(7): 829-836.
4.	Michael NL. Clinical trial design: the nobility of randomization. Sci Transl Med, 2017, 9(419): 0810-0811.
5.	刘玉秀. 临床试验随机化要领. 医学研究生学报, 2015, 28(2): 113-117.
6.	Rosenberger WF, Lachin JM. Randomization in clinical trials: theory and practice, second edition. New Jersey: John Wiley & Sons, 2016.
7.	Clark L, Schmidt U, Tharmanathan P, et al. Poor reporting quality of key randomization and allocation concealment details is still prevalent among published RCTs in 2011: a review. J Eval Clin Pract, 2013, 19(4): 703-707.
8.	Higham R, Tharmanathan P, Birks Y. Use and reporting of restricted randomization: a review. J Eval Clin Pract, 2015, 21(6): 1205-1211.
9.	Lin Y, Zhu M, Su Z. The pursuit of balance: an overview of covariate-adaptive randomization techniques in clinical trials. Contemp Clin Trials, 2015, 45(Pt A): 21-25.
10.	陈君超, 何迎春, 陈欢, 等. 随机化方法与技术在当前临床试验中的应用. 中国新药杂志, 2019, 28(13): 1582-1586.
11.	Emerson JD, Colditz GA. Use of statistical analysis in the New England Journal of Medicine. N Engl J Med, 1983, 309(12): 709-713.
12.	Horton NJ, Switzer SS. Statistical methods in the journal. N Engl J Med, 2005, 353(18): 1977-1979.
13.	Sato Y, Gosho M, Nagashima K, et al. Statistical methods in the journal - an update. N Engl J Med, 2017, 376(11): 1086-1087.
14.	Berger VW. Do not use blocked randomization. Headache, 2006, 46(2): 343.
15.	Berger VW. Misguided precedent is not a reason to use permuted blocks. Headache, 2006, 46(7): 1210-1212.
16.	Zhao W. A better alternative to the inferior permuted block design is not necessarily complex. Stat Med, 2016, 35(10): 1736-1738.
17.	袁阳丹, 刘甜甜, 刘玉秀, 等. 临床试验随机化方法的优选. 中国卫生统计, 2019, 36(2): 204-208.
18.	Zhao WL, Weng Y. Block urn design-a new randomization algorithm for sequential trials with two or more treatments and balanced or unbalanced allocation. Contemp Clin Trials, 2011, 32(6): 953-961.

1. Cartwright N. Are RCTs the gold standard? BioSocieties, 2007, 2(1): 11-20.
2. 吕燃, 陈能, 刘少南, 等. 单髁置换术治疗膝骨关节炎对术后人工关节遗忘程度影响的Meta分析. 中国循证医学杂志, 2020, 20(8): 956-961.
3. 尤寿江, 仲崇科, 毛学宇, 等. 蚓激酶胶囊治疗急性缺血性卒中有效性和安全性的Meta分析. 中国循证医学杂志, 2020, 20(7): 829-836.
4. Michael NL. Clinical trial design: the nobility of randomization. Sci Transl Med, 2017, 9(419): 0810-0811.
5. 刘玉秀. 临床试验随机化要领. 医学研究生学报, 2015, 28(2): 113-117.
6. Rosenberger WF, Lachin JM. Randomization in clinical trials: theory and practice, second edition. New Jersey: John Wiley & Sons, 2016.
7. Clark L, Schmidt U, Tharmanathan P, et al. Poor reporting quality of key randomization and allocation concealment details is still prevalent among published RCTs in 2011: a review. J Eval Clin Pract, 2013, 19(4): 703-707.
8. Higham R, Tharmanathan P, Birks Y. Use and reporting of restricted randomization: a review. J Eval Clin Pract, 2015, 21(6): 1205-1211.
9. Lin Y, Zhu M, Su Z. The pursuit of balance: an overview of covariate-adaptive randomization techniques in clinical trials. Contemp Clin Trials, 2015, 45(Pt A): 21-25.
10. 陈君超, 何迎春, 陈欢, 等. 随机化方法与技术在当前临床试验中的应用. 中国新药杂志, 2019, 28(13): 1582-1586.
11. Emerson JD, Colditz GA. Use of statistical analysis in the New England Journal of Medicine. N Engl J Med, 1983, 309(12): 709-713.
12. Horton NJ, Switzer SS. Statistical methods in the journal. N Engl J Med, 2005, 353(18): 1977-1979.
13. Sato Y, Gosho M, Nagashima K, et al. Statistical methods in the journal - an update. N Engl J Med, 2017, 376(11): 1086-1087.
14. Berger VW. Do not use blocked randomization. Headache, 2006, 46(2): 343.
15. Berger VW. Misguided precedent is not a reason to use permuted blocks. Headache, 2006, 46(7): 1210-1212.
16. Zhao W. A better alternative to the inferior permuted block design is not necessarily complex. Stat Med, 2016, 35(10): 1736-1738.
17. 袁阳丹, 刘甜甜, 刘玉秀, 等. 临床试验随机化方法的优选. 中国卫生统计, 2019, 36(2): 204-208.
18. Zhao WL, Weng Y. Block urn design-a new randomization algorithm for sequential trials with two or more treatments and balanced or unbalanced allocation. Contemp Clin Trials, 2011, 32(6): 953-961.

Previous Article
Hotspots and frontiers of cirrhosis with portal vein thrombosis: a visual analysis
Next Article
Construction and application of clinical evidence database of traditional Chinese medicine

Chinese Journal of Evidence-Based Medicine

Analysis of the application of randomization methods in clinical trials in NEJM

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content