LI Jianfeng, ZHANG Jingyi, LI Likang, LIU Yingxin, LI Guowei. Approach to Handling Missing Data in Clinical Trials[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(5): 1165-1172. DOI: 10.12290/xhyxzz.2023-0415
Citation: LI Jianfeng, ZHANG Jingyi, LI Likang, LIU Yingxin, LI Guowei. Approach to Handling Missing Data in Clinical Trials[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(5): 1165-1172. DOI: 10.12290/xhyxzz.2023-0415

Approach to Handling Missing Data in Clinical Trials

Funds: 

Science and Technology Projects in Guangdong Province, Guangzhou 202002030252

More Information
  • Corresponding author:

    LIU Yingxin, E-mail: liuyingxin0630@126.com

    LI Guowei, E-mail: ligw@gd2h.org.cn

  • Received Date: September 03, 2023
  • Accepted Date: December 05, 2023
  • Available Online: December 27, 2023
  • Publish Date: December 27, 2023
  • Issue Publish Date: September 29, 2024
  • Missing data, occurring in clinical trials due to various reasons, will cause information loss of the original data and reduce the robustness and validity of the research results. Therefore, missing data should be dealt with caution in clinical trials. This article introduces the causes and types of missing data, as well as several common methodological approaches to addressing the problem, in order to promote researchers' understanding and improve the quality of handling missing data in trials. Nevertheless, the best way to deal with missing data is to prevent or reduce data loss in clinical trials, rather than relying on post hoc statistical analyses.

  • [1]
    National Research Council. The prevention and treatment of missing data in clinical trials[M]. Washington, D.C. : The National Academies Press, 2010.
    [2]
    Häckl S, Koch A, Lasch F. Empirical evaluation of the implementation of the EMA guideline on missing data in confirmatory clinical trials: specification of mixed models for longitudinal data in study protocols[J]. Pharm Stat, 2019, 18(6): 636-644. DOI: 10.1002/pst.1964
    [3]
    Austin P C, White I R, Lee D S, et al. Missing data in clinical research: a tutorial on multiple imputation[J]. Can J Cardiol, 2021, 37(9): 1322-1331. DOI: 10.1016/j.cjca.2020.11.010
    [4]
    Marino M, Lucas J, Latour E, et al. Missing data in primary care research: importance, implications and approaches[J]. Fam Pract, 2021, 38(2): 200-203.
    [5]
    Altman D G. Missing outcomes in randomized trials: addressing the dilemma[J]. Open Med, 2009, 3(2): e51-e53.
    [6]
    Groenwold R H H, Moons K G M, Vandenbroucke J P. Randomized trials with missing outcome data: how to analyze and what to report[J]. CMAJ, 2014, 186(15): 1153-1157. DOI: 10.1503/cmaj.131353
    [7]
    Bell M L, Fiero M, Horton N J, et al. Handling missing data in RCTs; a review of the top medical journals[J]. BMC Med Res Methodol, 2014, 14: 118. DOI: 10.1186/1471-2288-14-118
    [8]
    何丽云, 刘保延, 梁志伟, 等. 临床研究中数据管理及其质量评价[J]. 中国新药与临床杂志, 2005, 24(11): 916-919. DOI: 10.3969/j.issn.1007-7669.2005.11.020

    He L Y, Liu B Y, Liang Z W, et al. Data administration and quality evaluation in clinical research[J]. Chin J New Drugs Clin Remedies, 2005, 24(11): 916-919. DOI: 10.3969/j.issn.1007-7669.2005.11.020
    [9]
    Lazar N A. Statistical analysis with missing data[J]. Technometrics, 2003, 45(4): 364-365.
    [10]
    Heymans M W, Twisk J W R. Handling missing data in clinical research[J]. J Clin Epidemiol, 2022, 151: 185-188. DOI: 10.1016/j.jclinepi.2022.08.016
    [11]
    Rautenberg T A, Ng S K, George G, et al. Seemingly unrelated regression analysis of the cost and health-related quality of life outcomes of the REVAMP randomized clinical trial[J]. Value Health Reg Issues, 2023, 35: 42-47. DOI: 10.1016/j.vhri.2022.12.006
    [12]
    Sayasone S, Keiser J, Meister I, et al. Efficacy and safety of tribendimidine versus praziquantel against Opisthorchis viverrini in Laos: an open-label, randomised, non-inferiority, phase 2 trial[J]. Lancet Infect Dis, 2018, 18(2): 155-161. DOI: 10.1016/S1473-3099(17)30624-2
    [13]
    Menendez M E, Thornton E, Kent S, et al. A prospective randomized clinical trial of prescription of full-time versus as-desired splint wear for de Quervain tendinopathy[J]. Int Orthop, 2015, 39(8): 1563-1569. DOI: 10.1007/s00264-015-2779-6
    [14]
    Witkiewitz K, Falk D E, Kranzler H R, et al. Methods to analyze treatment effects in the presence of missing data for a continuous heavy drinking outcome measure when partici-pants drop out from treatment in alcohol clinical trials[J]. Alcohol Clin Exp Res, 2014, 38(11): 2826-2834. DOI: 10.1111/acer.12543
    [15]
    Ratitch B, O'Kelly M, Tosiello R. Missing data in clinical trials: from clinical assumptions to statistical analysis using pattern mixture models[J]. Pharm Stat, 2013, 12(6): 337-347. DOI: 10.1002/pst.1549
    [16]
    Mongin D, Lauper K, Finckh A, et al. Accounting for missing data caused by drug cessation in observational compara-tive effectiveness research: a simulation study[J]. Ann Rheum Dis, 2022, 81(5): 729-736. DOI: 10.1136/annrheumdis-2021-221477
    [17]
    Tsikriktsis N. A review of techniques for treating missing data in OM survey research[J]. J Oper Manag, 2005, 24(1): 53-62. DOI: 10.1016/j.jom.2005.03.001
    [18]
    Lachin J M. Fallacies of last observation carried forward analyses[J]. Clin Trials, 2016, 13(2): 161-168. DOI: 10.1177/1740774515602688
    [19]
    衡明莉, 陈丽嫦, 王骏. 临床试验中缺失数据处理方法研究[J]. 中国临床药理学杂志, 2019, 35(22): 2948-2952.

    Heng M L, Chen L C, Wang J. Introduction to missing data processing methods in clinical trials[J]. Chin J Clin Pharmacol, 2019, 35(22): 2948-2952.
    [20]
    Rubin D B. A method for formalizing subjective notions about the effect of non-respondents in sample surveys[J]. ETS Res Bull Ser, 1975, 1975(2): i-24.
    [21]
    Rubin D B. Multiple imputation for nonresponse in surveys[M]. New York: John Wiley & Sons, Inc., 1987.
    [22]
    Schafer J L. Multiple imputation: a primer[J]. Stat Methods Med Res, 1999, 8(1): 3-15. DOI: 10.1177/096228029900800102
    [23]
    De Goeij M C M, Van Diepen M, Jager K J, et al. Multiple imputation: dealing with missing data[J]. Nephrol Dial Transplant, 2013, 28(10): 2415-2420. DOI: 10.1093/ndt/gft221
    [24]
    Fairclough D L, Peterson H F, Cella D, et al. Comparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials[J]. Stat Med, 1998, 17(5/7): 781-796.
    [25]
    Enders C K, Du H, Keller B T. A model-based imputation procedure for multilevel regression models with random coefficients, interaction effects, and nonlinear terms[J]. Psychol Methods, 2020, 25(1): 88-112. DOI: 10.1037/met0000228
    [26]
    Kim S, Sugar C A, Belin T R. Evaluating model-based imputation methods for missing covariates in regression models with interactions[J]. Stat Med, 2015, 34(11): 1876-1888. DOI: 10.1002/sim.6435
    [27]
    Tseng C H, Chen Y H. Regularized approach for data missing not at random[J]. Stat Methods Med Res, 2019, 28(1): 134-150. DOI: 10.1177/0962280217717760
    [28]
    Cole B F, Bonetti M, Zaslavsky A M, et al. A multistate Markov chain model for longitudinal, categorical quality-of-life data subject to non-ignorable missingness[J]. Stat Med, 2005, 24(15): 2317-2334. DOI: 10.1002/sim.2122
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