Cited by 568Statistical Methods and Bayesian InferenceStatistical Methods in Clinical TrialsStatistical Methods in Epidemiology

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Multiple imputation of missing values was not necessary before performing a longitudinal mixed-model analysis

Twisk, Jos, de Boer, Michiel, de Vente, Wieke, Heymans, Martijn·2013·Journal of Clinical Epidemiology

DOI 10.1016/j.jclinepi.2013.03.017

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Abstract

Background and objectives As a result of the development of sophisticated techniques, such as multiple imputation, the interest in handling missing data in longitudinal studies has increased enormously in past years. Within the field of longitudinal data analysis, there is a current debate on whether it is necessary to use multiple imputations before performing a mixed-model analysis to analyze the longitudinal data. In the current study this necessity is evaluated.Study design and setting The results of mixed-model analyses with and without multiple imputation were compared with each other. Four data sets with missing values were created-one data set with missing completely at random, two data sets with missing at random, and one data set with missing not at random). In all data sets, the relationship between a continuous outcome variable and two different covariates were analyzed: a time-independent dichotomous covariate and a time-dependent continuous covariate.Results Although for all types of missing data, the results of the mixed-model analysis with or without multiple imputations were slightly different, they were not in favor of one of the two approaches. In addition, repeating the multiple imputations 100 times showed that the results of the mixed-model analysis with multiple imputation were quite unstable.Conclusion It is not necessary to handle missing data using multiple imputations before performing a mixed-model analysis on longitudinal data.

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Ben, Â. J., van Dongen, J. M., Alili, M. E., Eßer, J., Broulíková, H. M., & Bosmans, J. E. (2023) · PharmacoEconomics · doi:10.1007/s40273-023-01301-7 · Cited by 48
“Moreover, despite MI being shown to be unnecessary when using likelihood-based models for analysing effects [31], for analysing costs MI has been shown to produce more accurate estimates [32].”
Method
Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones
van der Loos, M. A. T. C., Vlot, M. C., Klink, D. T., Hannema, S. E., den Heijer, M., & Wiepjes, C. M. (2023) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2023.4588 · Cited by 48
Enhanced Fuzzy Clustering for Incomplete Instance with Evidence Combination
Liu, Z., & Letchmunan, S. (2023) · ACM Transactions on Knowledge Discovery from Data · doi:10.1145/3638061 · Cited by 47
“Interestingly, the literature [42] argued that multiple imputations are not always superior to single estimation in any case by analyzing a large number of data with mixed-model analyses.”
BackgroundMethod
Improving the Multidisciplinary Treatment of Chronic Pain by Stimulating Body Awareness
van der Maas, L. C. C., Köke, A. J. A., Pont, M., Bosscher, R. J., Twisk, J. W. R., Janssen, T. W. J., & Peters, M. L. (2014) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000138 · Cited by 47
“It has been proven that this method is even better than multiple imputation techniques (65).”
MethodSelf-citation
Blended psychosocial support for partners of patients with ALS and PMA: results of a randomized controlled trial.
De Wit, J., Beelen, A., Drossaert, C. H. C., Kolijn, R., Van Den Berg, L. H., SchrÖder, C. D., & Visser-Meily, J. M. A. (2020) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2020.1757114 · Cited by 46
Association of Education and Intracranial Volume With Cognitive Trajectories and Mortality Rates Across the Alzheimer Disease Continuum
van Loenhoud, A. C., Groot, C., Bocancea, D. I., Barkhof, F., Teunissen, C. E., Scheltens, P., van der Flier, W. M., & Ossenkoppele, R. (2022) · Neurology · doi:10.1212/wnl.0000000000200116 · Cited by 46
“We did not conduct multiple imputation, as the linear mixed models described in our Statistical Analysis are capable of handling these types of variability.(26,27)”
Method
A systematic survey of the methods literature on the reporting quality and optimal methods of handling participants with missing outcome data for continuous outcomes in randomized controlled trials
Zhang, Y., Alyass, A., Vanniyasingam, T., Sadeghirad, B., Flórez, I. D., Pichika, S. C., Kennedy, S. A., Abdulkarimova, U., Zhang, Y., Iljon, T., et al. (2017) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2017.05.016 · Cited by 49
Surgery for Degenerative Cervical Myelopathy: A Nationwide Registry-Based Observational Study With Patient-Reported Outcomes
Gulati, S., Vangen-Lønne, V., Nygaard, O. P., Gulati, A. M., Hammer, T. A., Johansen, T. O., Peul, W. C., Salvesen, Ø. O., & Solberg, T. K. (2021) · Neurosurgery · doi:10.1093/neuros/nyab259 · Cited by 48
Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT-based stress management? - A randomized controlled study
Wiklund, T., Linton, S. J., Alföldi, P., & Gerdle, B. (2018) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-018-2020-z · Cited by 45
“Mixed model analysis handles missing data; no imputation method was applied since there are reports that imputations before a mixed model analysis is not necessary and simulations indicated that imputations before mixed models could result in unstable results [30].”
Method
Telehealth coaching to improve self-management for secondary prevention after stroke: A randomized controlled trial of Stroke Coach
Sakakibara, B. M., Lear, S. A., Barr, S. I., Goldsmith, C. H., Schneeberg, A., Silverberg, N. D., Yao, J. K., & Eng, J. J. (2021) · International Journal of Stroke · doi:10.1177/17474930211017699 · Cited by 48
Effect of tailored antibiotic stewardship programmes on the appropriateness of antibiotic prescribing in nursing homes
van Buul, L. W., van der Steen, J. T., Achterberg, W. P., Schellevis, F., Essink, R. T. G. M., de Greeff, S. C., Natsch, S., Sloane, P. D., Zimmerman, S. I., Twisk, J. W. R., et al. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv051 · Cited by 45
Self-citation
Are People With Whiplash-Associated Neck Pain Different From People With Nonspecific Neck Pain?
Anstey, R., Kongsted, A., Kamper, S. J., & Hancock, M. J. (2016) · Journal of Orthopaedic and Sports Physical Therapy · doi:10.2519/jospt.2016.6588 · Cited by 45
Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People—Results from the European Network for the Investigation of Gender Incongruence
van Dijk, D., Dekker, M. J. H. J., Conemans, E. B., Wiepjes, C. M., de Goeij, E. G. M., Overbeek, K. A., Fisher, A. D., den Heijer, M., & T'Sjoen, G. G. (2019) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2019.05.009 · Cited by 46
Long-term Immune Response to Hepatitis B Virus Vaccination Regimens in Adults With Human Immunodeficiency Virus 1
Launay, O., Rosenberg, A. R., Rey, D., Pouget, N., Michel, M., Reynes, J., Neau, D., Raffi, F., Piroth, L., Carrat, F., et al. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2016.0741 · Cited by 44
“Nadir CD4 count/μL, median (range) 197 (0-800) 272 (3-908) 206 (3-754) 311 (39-779) 180 (0-601) 218 (13-534)”
Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty
van der Loos, M. A. T. C., Hellinga, I., Vlot, M. C., Klink, D. T., den Heijer, M., & Wiepjes, C. M. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4262 · Cited by 44
“However, by analyzing the data with a mixed model, the missing data were randomly imputed.((19)) Therefore, the effect of missing data was minimalized while maintaining the largest study sample.”
Method
Transform-Us! cluster RCT: 18-month and 30-month effects on children’s physical activity, sedentary time and cardiometabolic risk markers
Salmon, J., Arundell, L., Cerin, E., Ridgers, N. D., Hesketh, K. D., Daly, R. M., Dunstan, D. W., Brown, H. L., Gatta, J. D., Gatta, P. A. D., et al. (2022) · British Journal of Sports Medicine · doi:10.1136/bjsports-2022-105825 · Cited by 43
The association between persistent cognitive difficulties and depression and functional outcomes in people with major depressive disorder
Matcham, F., Simblett, S. K., Leightley, D., Dalby, M., Siddi, S., Haro, J. M., Lamers, F., Penninx, B. W. J. H., Bruce, S., Nica, R. I., et al. (2022) · Psychological Medicine · doi:10.1017/s0033291722003671 · Cited by 45
Some data quality issues at ClinicalTrials.gov
Chaturvedi, N., Mehrotra, B., Kumari, S., Gupta, S., Subramanya, H. S., & Saberwal, G. (2019) · Trials · doi:10.1186/s13063-019-3408-2 · Cited by 45
Daily Exercises and Education for Preventing Low Back Pain in Children: Cluster Randomized Controlled Trial
Hill, J. J., & Keating, J. L. (2014) · Physical Therapy · doi:10.2522/ptj.20140273 · Cited by 43
Longitudinal Changes in Muscle Mass, Muscle Strength, and Physical Performance in Acutely Hospitalized Older Adults
Aarden, J. J., Reijnierse, E. M., van der Schaaf, M., van der Esch, M., Reichardt, L. A., van Seben, R., Bosch, J. A., Twisk, J. W. R., Maier, A. B., Engelbert, R. H. H., et al. (2021) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2020.12.006 · Cited by 43
Self-citation
Improvements in Blood Pressure Among Undiagnosed Hypertensive Participants in a Community-Based Lifestyle Intervention, Mississippi, 2010
Zoellner, J., Thomson, J. L., Landry, A. S., Anderson‐Lewis, C., Connell, C. L., Molaison, E. F., & Yadrick, K. (2014) · Preventing Chronic Disease · doi:10.5888/pcd11.130269 · Cited by 42
“Maximum likelihood estimation was used to handle missing data in the repeated measures (20).”
Web-Based Aftercare for Women With Bulimia Nervosa Following Inpatient Treatment: Randomized Controlled Efficacy Trial
Jacobi, C., Beintner, I., Fittig, E., Trockel, M., Braks, K., Schade‐Brittinger, C., & Dempfle, A. (2017) · Journal of Medical Internet Research · doi:10.2196/jmir.7668 · Cited by 42
“Multiple imputation before conducting longitudinal mixed effects modeling does not add value and is not necessary [46,47].”
Effectiveness and cost-effectiveness of proactive and multidisciplinary integrated care for older people with complex problems in general practice: an individual participant data meta-analysis
Blom, J. W., van den Hout, W. B., den Elzen, W. P. J., Drewes, Y. M., Bleijenberg, N., Fabbricotti, I. N., Jansen, A. P. D., Kempen, G. I. J. M., Koopmans, R. T. C. M., Looman, W., et al. (2018) · Age and Ageing · doi:10.1093/ageing/afy091 · Cited by 42
Adherence to a Plant-Based Diet and Consumption of Specific Plant Foods—Associations with 3-Year Weight-Loss Maintenance and Cardiometabolic Risk Factors: A Secondary Analysis of the PREVIEW Intervention Study
Zhu, R., Fogelholm, M., Poppitt, S. D., Silvestre, M. P., Møller, G., Huttunen‐Lenz, M., Stratton, G., Sundvall, J., Råman, L., Jalo, E., et al. (2021) · Nutrients · doi:10.3390/nu13113916 · Cited by 43
“Missing data were not handled with multiple imputation because this method did not increase precision [28,29].”
Method
A scoping review of statistical methods for trial‐based economic evaluations: The current state of play
Alili, M. E., van Dongen, J. M., Eßer, J., Heymans, M. W., van Tulder, M. W., & Bosmans, J. E. (2022) · Health Economics · doi:10.1002/hec.4603 · Cited by 41
“First, studies have shown that multiple imputation is not required when analyzing partly missing, clinical effect data using a longitudinal mixed model analysis (Peters et al., 2012; Twisk et al., 2013).”
BackgroundSelf-citation
Effects of a school-based physical activity intervention on academic performance in 14-year old adolescents: a cluster randomized controlled trial – the School in Motion study
Solberg, R. B., Steene-Johannessen, J., Anderssen, S. A., Ekelund, U., Säfvenbom, R., Haugen, T., Berntsen, S., Åvitsland, A., Lerum, Ø., Resaland, G. K., et al. (2021) · BMC Public Health · doi:10.1186/s12889-021-10901-x · Cited by 37
“Multiple imputation when performing mixed models analyses can lead to unstable results [26], and when the analysis was rerun on the imputed data the estimates were attenuated and some no longer significant.”
Method
Efficacy of Videoconference Group Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD) for Chronic Low Back Pain (CLBP) Plus Comorbid Depressive Symptoms: A Randomized Controlled Trial (IMPACT Study)
Sanabria-Mazo, J. P., Colomer-Carbonell, A., Borràs, X., Castaño-Asins, J. R., McCracken, L. M., Montero-Marin, J., Pérez-Aranda, A., Edo, S., Sanz, A., Feliu-Soler, A., et al. (2023) · The Journal of Pain · doi:10.1016/j.jpain.2023.04.008 · Cited by 40
An Internet-supported Physical Activity Intervention Delivered in Secondary Schools Located in Low Socio-economic Status Communities: Study Protocol for the Activity and Motivation in Physical Education (AMPED) Cluster Randomized Controlled Trial
Lonsdale, C., Lester, A., Owen, K., White, R. L., Moyes, I., Peralta, L. R., Kirwan, M., Maeder, A., Bennie, A., MacMillan, F., et al. (2015) · BMC Public Health · doi:10.1186/s12889-015-2583-7 · Cited by 46
Tic-Related Versus Tic-Free Obsessive-Compulsive Disorder
de Vries, F. E., Cath, D. C., Hoogendoorn, A. W., van Oppen, P., Glas, G. G., Veltman, D. J., van den Heuvel, O. A., & van Balkom, A. J. L. M. (2016) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.14m09736 · Cited by 41
Blood pressure and age-related GFR decline in the general population
Eriksen, B. O., Stefansson, V. T. N., Jenssen, T. G., Mathisen, U. D., Schei, J., Solbu, M. D., Wilsgaard, T., & Melsom, T. (2017) · BMC Nephrology · doi:10.1186/s12882-017-0496-7 · Cited by 41
“All of the subjects included in the baseline RENIS cohort were included in the linear mixed regression analyses regardless of whether they were examined at follow-up because linear mixed models allow for missing observations at one or more points in time [41, 42].”
Method
Effects of telephone-based health coaching on patient-reported outcomes and health behavior change: A randomized controlled trial
Dwinger, S., Rezvani, F., Kriston, L., Herbarth, L., Härter, M. C., & Dirmaier, J. (2020) · PLoS ONE · doi:10.1371/journal.pone.0236861 · Cited by 41
“If there were data missing due to lost to follow-up, there was no imputation done since mixed model analyses provide unbiased estimates under the assumption that data are missing at random conditional on the variables in the model [66].”
Method
Childhood trauma and attachment style predict the four-year course of obsessive compulsive disorder: Findings from the Netherlands obsessive compulsive disorder study
Tibi, L., van Oppen, P., van Balkom, A. J. L. M., Eikelenboom, M., Hendriks, G., & Anholt, G. E. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.12.028 · Cited by 42
Just as Tall on Testosterone; a Neutral to Positive Effect on Adult Height of GnRHa and Testosterone in Trans Boys
Willemsen, L. A., Boogers, L. S., Wiepjes, C. M., Klink, D. T., van Trotsenburg, A. S. P., den Heijer, M., & Hannema, S. E. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac571 · Cited by 39
Negative and positive affect regulation in a transdiagnostic internet-based protocol for emotional disorders: Randomized controlled trial
Díaz-García, A., González-Robles, A., García-Palacios, A., Fernández-Álvarez, J., Castilla, D., Bretón, J. M., Baños, R. M., Quero, S., & Botella, C. (2021) · Journal of Medical Internet Research · doi:10.2196/21335 · Cited by 36
“Therefore, patterns of missingness were not found to be MNAR and the decision to continue the analysis with the available data was made [84,85].”
Background
A compassion-based program to reduce psychological distress in medical students: A pilot randomized clinical trial
Rojas, B., Catalan, E., Diez, G., & Roca, P. (2023) · PLOS ONE · doi:10.1371/journal.pone.0287388 · Cited by 38
“Given that imputation of missing values is not necessary before performing longitudinal mixed-model analysis [48], we did not impute the missing data.”
Method
Effectiveness of Resource Groups for Improving Empowerment, Quality of Life, and Functioning of People With Severe Mental Illness
Tjaden, C. D., Mulder, C. L., den Hollander, W., Castelein, S., Delespaul, P., Keet, R., van Weeghel, J., & Kroon, H. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.2880 · Cited by 37
Protocol for a cluster randomised controlled trial of an intervention to improve the mental health support and training available to secondary school teachers – the WISE (Wellbeing in Secondary Education) study
Kidger, J., Evans, R., Tilling, K. M., Hollingworth, W., Campbell, R. M., Ford, T. J., Murphy, S., Araya, R., Morris, R. W., Kadir, B., et al. (2016) · BMC Public Health · doi:10.1186/s12889-016-3756-8 · Cited by 39
Efficacy of a mindful-eating programme to reduce emotional eating in patients suffering from overweight or obesity in primary care settings: a cluster-randomised trial protocol
Morillo‐Sarto, H., Barceló‐Soler, A., Herrera‐Mercadal, P., Pantilie, B., Navarro‐Gil, M., García‐Campayo, J., & Montero‐Marín, J. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031327 · Cited by 40
Efficacy of an internet-based exposure treatment for flying phobia (NO-FEAR Airlines) with and without therapist guidance: a randomized controlled trial
Campos, D., Bretón-López, J., Botella, C., Mira, A., Castilla, D., Mor, S., Baños, R., & Quero, S. (2019) · BMC Psychiatry · doi:10.1186/s12888-019-2060-4 · Cited by 32
Resistance band training or general exercise in multidisciplinary rehabilitation of low back pain? A randomized trial
Iversen, V. M., Vasseljen, O., Mork, P. J., Gismervik, S., Bertheussen, G. F., Salvesen, Ø. O., & Fimland, M. S. (2018) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.13091 · Cited by 37
Effectiveness of Later-Stage Exercise Programs vs Usual Medical Care on Physical Function and Activity After Total Knee Replacement
Piva, S. R., Schneider, M., Moore, C. G., Catelani, M. B., Gil, A. B., Klatt, B. A., DiGioia, A. M., Almeida, G. J., Khoja, S. S., Sowa, G., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.0018 · Cited by 35
Impact of MyDiabetesPlan, a Web-Based Patient Decision Aid on Decisional Conflict, Diabetes Distress, Quality of Life, and Chronic Illness Care in Patients With Diabetes: Cluster Randomized Controlled Trial
Yu, C. H. Y., Choi, D., Bruno, B. A., Thorpe, K. E., Straus, S. E., Cantarutti, P., Chu, K., Frydrych, P., Hoang‐Kim, A., Ivers, N. M., et al. (2020) · Journal of Medical Internet Research · doi:10.2196/16984 · Cited by 36
“To account for missing data, we conducted a fully adjusted mixed effect model using repeated measurements [40-42].”
Method
Long-Term Effects on Loneliness of a Computer-Tailored Intervention for Older Adults With Chronic Diseases: A Randomized Controlled Trial
Boekhout, J. M., Volders, E., Bolman, C. A. W., de Groot, R. H. M., & Lechner, L. (2021) · Journal of Aging and Health · doi:10.1177/08982643211015027 · Cited by 37
“Analyses were conducted on an intention-to-treat basis without any ad hoc imputation (Twisk et al., 2013).”
Method
Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial
Boevé, L. M. S., Hulshof, M. C. C. M., Verhagen, P. C. M. S., Twisk, J. W. R., Witjes, W. P. J., de Vries, P. W., van Moorselaar, R. J. A., van Andel, G., & Vis, A. N. (2020) · European Urology · doi:10.1016/j.eururo.2020.08.023 · Cited by 34
Self-citation

Authors: Twisk, J., de Boer, M., de Vente, W., & Heymans, M.
Affiliations: Vrije Universiteit Amsterdam (NL)
Corresponding author: Twisk, Jos
ORCID: Twisk, Jos
Heymans, Martijn
Venue: Journal of Clinical Epidemiology
Publisher: Elsevier BV
Published: 2013-09
Volume: 66
Issue: 9
Pages: 1022-1028
ISSN: 0895-4356 (ISSN-L)
DOI: 10.1016/j.jclinepi.2013.03.017
OpenAlex: W1974992958
Cited by: 568
References: 43
Citations by year: 2026: 58 · 2025: 68 · 2024: 74 · 2023: 57 · 2022: 61 · 2021: 52 · 2020: 46 · 2019: 45 · 2018: 27 · 2017: 26 · 2016: 21 · 2015: 19 · 2014: 10 · 2013: 4
FWCI: 15.69
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Clinical Epidemiology (publishedVersion)
PubMed (publishedVersion)
UvA-DARE (University of Amsterdam) (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
VU Research Portal (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords: multiple imputation, missing data, longitudinal analysis, mixed models, missing completely at random, missing at random, missing not at random, time-varying covariates
MeSH terms: Data Interpretation, Statistical, Humans, Longitudinal Studies, Patient Dropouts, Research Design, Models, Statistical

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Multiple imputation of missing values was not necessary before performing a longitudinal mixed-model analysis

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