Volume 33, Issue 2
Research Article

Qualitative interaction trees: a tool to identify qualitative treatment–subgroup interactions

Elise Dusseldorp

Corresponding Author

Statistics Group, Netherlands Organization for Applied Scientific Research (TNO), Wassenaarseweg 56, Leiden, The Netherlands

Department of Psychology, Katholieke Universiteit Leuven, Tiensestraat 102 – bus 3713, Leuven, Belgium

Correspondence to: Elise Dusseldorp, Statistics Group, TNO, PO Box 2215, 2301 CE Leiden, The Netherlands.

E‐mail: elise.dusseldorp@tno.nl

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Iven Van Mechelen

Department of Psychology, Katholieke Universiteit Leuven, Tiensestraat 102 – bus 3713, Leuven, Belgium

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First published: 06 August 2013
Citations: 59

Abstract

When two alternative treatments (A and B) are available, some subgroup of patients may display a better outcome with treatment A than with B, whereas for another subgroup, the reverse may be true. If this is the case, a qualitative (i.e., disordinal) treatment–subgroup interaction is present. Such interactions imply that some subgroups of patients should be treated differently and are therefore most relevant for personalized medicine. In case of data from randomized clinical trials with many patient characteristics that could interact with treatment in a complex way, a suitable statistical approach to detect qualitative treatment–subgroup interactions is not yet available. As a way out, in the present paper, we propose a new method for this purpose, called QUalitative INteraction Trees (QUINT). QUINT results in a binary tree that subdivides the patients into terminal nodes on the basis of patient characteristics; these nodes are further assigned to one of three classes: a first for which A is better than B, a second for which B is better than A, and an optional third for which type of treatment makes no difference. Results of QUINT on simulated data showed satisfactory performance, with regard to optimization and recovery. Results of an application to real data suggested that, compared with other approaches, QUINT provided a more pronounced picture of the qualitative interactions that are present in the data. Copyright © 2013 John Wiley & Sons, Ltd.

Number of times cited according to CrossRef: 59

  • Subgroup Identification for Tailored Therapies: Methods and Consistent Evaluation, Design and Analysis of Subgroups with Biopharmaceutical Applications, 10.1007/978-3-030-40105-4_8, (181-197), (2020).
  • A Novel Method of Subgroup Identification by Combining Virtual Twins with GUIDE (VG) for Development of Precision Medicines, Design and Analysis of Subgroups with Biopharmaceutical Applications, 10.1007/978-3-030-40105-4_7, (167-180), (2020).
  • Subgroup Analysis from Bayesian Perspectives, Design and Analysis of Subgroups with Biopharmaceutical Applications, 10.1007/978-3-030-40105-4_16, (331-345), (2020).
  • Data-Driven and Confirmatory Subgroup Analysis in Clinical Trials, Design and Analysis of Subgroups with Biopharmaceutical Applications, 10.1007/978-3-030-40105-4_3, (33-91), (2020).
  • Identifying treatment effects of an informal caregiver education intervention to increase days in the community and decrease caregiver distress: a machine-learning secondary analysis of subgroup effects in the HI-FIVES randomized clinical trial, Trials, 10.1186/s13063-020-4113-x, 21, 1, (2020).
  • Depth Importance in Precision Medicine (DIPM): A Tree and Forest Based Method, Contemporary Experimental Design, Multivariate Analysis and Data Mining, 10.1007/978-3-030-46161-4, (243-259), (2020).
  • Effects of Exergaming on Cognitive and Social Functioning of People with Dementia: A Randomized Controlled Trial, Journal of the American Medical Directors Association, 10.1016/j.jamda.2020.04.018, (2020).
  • Qualitative treatment-subgroup interactions in the antidepressant treatment of major depression: Application of QUINT to individual participant data from seven placebo-controlled randomized controlled trials, Personalized Medicine in Psychiatry, 10.1016/j.pmip.2019.100054, (100054), (2020).
  • Statistical Data Mining of Clinical Data, Quantitative Methods in Pharmaceutical Research and Development, 10.1007/978-3-030-48555-9, (225-315), (2020).
  • Exploratory identification of predictive biomarkers in randomized trials with normal endpoints, Statistics in Medicine, 10.1002/sim.8452, 39, 7, (923-939), (2019).
  • Comparing internal and external validation in the discovery of qualitative treatment-subgroup effects using two small clinical trials, Contemporary Clinical Trials Communications, 10.1016/j.conctc.2019.100372, (100372), (2019).
  • Added value of Mindfulness-Based Cognitive Therapy for depression: A tree-based qualitative interaction analysis, Behaviour Research and Therapy, 10.1016/j.brat.2019.103467, (103467), (2019).
  • Estimating the quality of optimal treatment regimes, Statistics in Medicine, 10.1002/sim.8342, 38, 25, (4925-4938), (2019).
  • PSICA: Decision trees for probabilistic subgroup identification with categorical treatments, Statistics in Medicine, 10.1002/sim.8308, 38, 22, (4436-4452), (2019).
  • Subgroup identification via homogeneity pursuit for dense longitudinal/spatial data, Statistics in Medicine, 10.1002/sim.8192, 38, 17, (3256-3271), (2019).
  • Composite interaction tree for simultaneous learning of optimal individualized treatment rules and subgroups, Statistics in Medicine, 10.1002/sim.8105, 38, 14, (2632-2651), (2019).
  • Predictive Subgroup/Biomarker Identification and Machine Learning Methods, Statistical Methods in Biomarker and Early Clinical Development, 10.1007/978-3-030-31503-0, (1-22), (2019).
  • undefined, 2019 IEEE International Conference on Data Science and Advanced Analytics (DSAA), 10.1109/DSAA.2019.00054, (392-402), (2019).
  • The (cost-) effectiveness of exergaming in people living with dementia and their informal caregivers: protocol for a randomized controlled trial, BMC Geriatrics, 10.1186/s12877-019-1062-x, 19, 1, (2019).
  • Moderators of the effect of guided online self-help for people with HIV and depressive symptoms, AIDS Care, 10.1080/09540121.2019.1679703, (1-7), (2019).
  • A non-parametric statistical test of null treatment effect in sub-populations, Journal of Biopharmaceutical Statistics, 10.1080/10543406.2019.1636810, (1-17), (2019).
  • Look before you leap: systematic evaluation of tree-based statistical methods in subgroup identification, Journal of Biopharmaceutical Statistics, 10.1080/10543406.2019.1584204, (1-21), (2019).
  • Studying treatment-effect heterogeneity in precision medicine through induced subgroups, Journal of Biopharmaceutical Statistics, 10.1080/10543406.2019.1579220, (1-17), (2019).
  • Subgroups from regression trees with adjustment for prognostic effects and postselection inference, Statistics in Medicine, 10.1002/sim.7677, 38, 4, (545-557), (2018).
  • Random forests of interaction trees for estimating individualized treatment effects in randomized trials, Statistics in Medicine, 10.1002/sim.7660, 37, 17, (2547-2560), (2018).
  • A recursive partitioning approach for subgroup identification in individual patient data meta‐analysis, Statistics in Medicine, 10.1002/sim.7609, 37, 9, (1550-1561), (2018).
  • Subgroup identification in dose‐finding trials via model‐based recursive partitioning, Statistics in Medicine, 10.1002/sim.7594, 37, 10, (1608-1624), (2018).
  • Detecting Safety Signals Among Adverse Events in Clinical Trials, Biopharmaceutical Applied Statistics Symposium, 10.1007/978-981-10-7826-2_7, (107-125), (2018).
  • Development and evaluating multimarker models for guiding treatment decisions, BMC Medical Informatics and Decision Making, 10.1186/s12911-018-0619-5, 18, 1, (2018).
  • Improving treatment for patients with childhood abuse related posttraumatic stress disorder (IMPACT study): protocol for a multicenter randomized trial comparing prolonged exposure with intensified prolonged exposure and phase-based treatment, BMC Psychiatry, 10.1186/s12888-018-1967-5, 18, 1, (2018).
  • A Bayesian Approach to Intervention-Based Clustering, ACM Transactions on Intelligent Systems and Technology, 10.1145/3156683, 9, 4, (1-23), (2018).
  • Subgroup identification by recursive segmentation, Journal of Applied Statistics, 10.1080/02664763.2018.1444152, (1-24), (2018).
  • An Algorithm for Generating Individualized Treatment Decision Trees and Random Forests, Journal of Computational and Graphical Statistics, 10.1080/10618600.2018.1451337, (1-12), (2018).
  • Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees, Behavior Research Methods, 10.3758/s13428-017-0971-x, 50, 5, (2016-2034), (2017).
  • Individual treatment effect prediction for amyotrophic lateral sclerosis patients, Statistical Methods in Medical Research, 10.1177/0962280217693034, 27, 10, (3104-3125), (2017).
  • Sources of Safety Data and Statistical Strategies for Design and Analysis, Therapeutic Innovation & Regulatory Science, 10.1177/2168479017738980, 52, 2, (141-158), (2017).
  • undefined, 2017 16th IEEE International Conference on Machine Learning and Applications (ICMLA), 10.1109/ICMLA.2017.00-68, (755-760), (2017).
  • Comparing Four Methods for Estimating Tree-Based Treatment Regimes, The International Journal of Biostatistics, 10.1515/ijb-2016-0068, 13, 1, (2017).
  • Thou Shalt Not Bear False Witness Against Null Hypothesis Significance Testing, Educational and Psychological Measurement, 10.1177/0013164416668232, 77, 4, (631-662), (2016).
  • Tutorial in biostatistics: data‐driven subgroup identification and analysis in clinical trials, Statistics in Medicine, 10.1002/sim.7064, 36, 1, (136-196), (2016).
  • Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design, Journal of Psychiatric Research, 10.1016/j.jpsychires.2016.03.001, 78, (11-23), (2016).
  • Physical activity and relaxation in the work setting to reduce the need for recovery: what works for whom?, BMC Public Health, 10.1186/s12889-016-3457-3, 16, 1, (2016).
  • Differential efficacy of cognitive behavioral therapy and psychodynamic therapy for major depression: a study of prescriptive factors, Psychological Medicine, 10.1017/S0033291715001853, 46, 4, (731-744), (2016).
  • Identification of subgroups with differential treatment effects for longitudinal and multiresponse variables, Statistics in Medicine, 10.1002/sim.7020, 35, 26, (4837-4855), (2016).
  • Personalized Effective Dose Selection in Dose Ranging Studies, Statistical Applications from Clinical Trials and Personalized Medicine to Finance and Business Analytics, 10.1007/978-3-319-42568-9_8, (91-104), (2016).
  • Qualitative Treatment-Subgroup Interactions in a Randomized Clinical Trial of Treatments for Adolescents with ADHD: Exploring What Cognitive-Behavioral Treatment Works for Whom, PLOS ONE, 10.1371/journal.pone.0150698, 11, 3, (e0150698), (2016).
  • QUINT: A tool to detect qualitative treatment–subgroup interactions in randomized controlled trials, Psychotherapy Research, 10.1080/10503307.2015.1062934, 26, 5, (612-622), (2015).
  • Quint: An R package for the identification of subgroups of clients who differ in which treatment alternative is best for them, Behavior Research Methods, 10.3758/s13428-015-0594-z, 48, 2, (650-663), (2015).
  • Methods for identification and confirmation of targeted subgroups in clinical trials: A systematic review, Journal of Biopharmaceutical Statistics, 10.1080/10543406.2015.1092034, 26, 1, (99-119), (2015).
  • Assessment of Methods to Identify Patient Subgroups with Enhanced Treatment Response in Randomized Clinical Trials, Applied Statistics in Biomedicine and Clinical Trials Design, 10.1007/978-3-319-12694-4_24, (395-410), (2015).
  • Regularized outcome weighted subgroup identification for differential treatment effects, Biometrics, 10.1111/biom.12322, 71, 3, (645-653), (2015).
  • An analysis of moderators in the COMBINE study: Identifying subgroups of patients who benefit from acamprosate, European Neuropsychopharmacology, 10.1016/j.euroneuro.2015.06.006, 25, 10, (1586-1599), (2015).
  • Personalized Medicine: Four Perspectives of Tailored Medicine, Statistics in Biopharmaceutical Research, 10.1080/19466315.2015.1059354, 7, 3, (214-229), (2015).
  • A Framework of Statistical Methods for Identification of Subgroups with Differential Treatment Effects in Randomized Trials, Applied Statistics in Biomedicine and Clinical Trials Design, 10.1007/978-3-319-12694-4_25, (411-425), (2015).
  • Biomarker Evaluation and Subgroup Identification in a Pneumonia Development Program Using SIDES, Applied Statistics in Biomedicine and Clinical Trials Design, 10.1007/978-3-319-12694-4_26, (427-466), (2015).
  • Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some simple themes, Clinical Trials, 10.1177/1740774514557725, 12, 4, (299-308), (2015).
  • A regression tree approach to identifying subgroups with differential treatment effects, Statistics in Medicine, 10.1002/sim.6454, 34, 11, (1818-1833), (2015).
  • Rejoinder, International Statistical Review, 10.1111/insr.12057, 82, 3, (367-370), (2014).
  • A nonparametric method for value function guided subgroup identification via gradient tree boosting for censored survival data, Statistics in Medicine, 10.1002/sim.8714, 0, 0, (undefined).

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