The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT)

Simões, Jorge; Schoisswohl, Stefan; Schlee, Winfried; Basso, Laura; Bernal-Robledano, Alberto; Boecking, Benjamin; Cima, Rilana; Denys, Sam; Engelke, Milena; Escalera‐Balsera, Alba; Gallego‐Martinez, Alvaro; Gallus, Silvano; Kikidis, Dimitris; López-Escámez, José A.; Marcrum, Steven C.; Markatos, Nikolaos; Martin-Lagos, Juan; Martínez-Martínez, Marta; Mazurek, Birgit; Vassou, Evgenia; Jarach, Carlotta Micaela; Mueller-Locatelli, Nicolas; Neff, Patrick; Niemann, Uli; Omar, Hafez Kader; Puga, Clara; Schleicher, Miro; Unnikrishnan, Vishnu; Pérez-Carpena, Patricia; Pryss, Rüdiger; Robles-Bolivar, Paula; Rose, Matthias; Schecklmann, Martin; Schiele, Tabea; Schobel, Johannes; Spiliopoulou, Myra; Stark, Sabine; Vogel, Carsten; Wunder, Nina; Zachou, Zoi; Langguth, Berthold

doi:10.1186/s13063-023-07303-2

Cited by 4 publications

(7 citation statements)

References 31 publications

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“…Figure 2 shows least-squares mean changes from baseline to interim visit at week 6, final visit at week 12, and follow-up at week 36 for both the overall and individual single-combination treatment comparison. The results of the remaining objectives (as outlined in the SAP) 15 and time points (interim visit and follow up) are reported in Tables S16 – S18 .…”

Section: Resultsmentioning

confidence: 99%

“…The results of the remaining objectives (as outlined in the SAP) 21 and time points (interim visit and follow up) are reported in Tables S16 – S18 .…”

Section: Resultsmentioning

confidence: 99%

“…Detailed information about the trial rationale, design, methodological approaches, and statistical analysis strategies are published in the study protocol (link: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05835-z) and statistical analysis plan (SAP). 14,15 The study was approved by local ethics committees at every clinical site independently. Further, all authors vouch for the completeness and correctness of the data, adherence of the trial to the study protocol, 14 as well as adherence of data analysis strategies to the SAP.…”

Section: Methodsmentioning

confidence: 99%

“…Further, all authors vouch for the completeness and correctness of the data, adherence of the trial to the study protocol, 20 as well as adherence of data analysis strategies to the SAP. 21 A detailed list of author contributions can be found in the Supplementary Appendix. Written informed consent was obtained from all eligible patients prior to trial participation.…”

Section: Methodsmentioning

confidence: 99%

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Single versus Combination Treatment in Tinnitus: An International, Multicentre, Parallel-arm, Superiority, Randomised Controlled Trial

Schoisswohl,

Basso,

Simoes

et al. 2024

Preprint

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Background: Tinnitus is associated with a variety of etiologies, phenotypes, and underlying pathophysiological mechanisms, and available treatments have limited efficacy. A combination of treatments, addressing various aspects of tinnitus, might provide a viable and superior treatment strategy. Methods: In this multicenter, parallel-arm, randomized controlled clinical trial, patients with chronic subjective tinnitus were randomly assigned to single or combination treatment of 12 weeks each. Cognitive-behavioral therapy, hearing aids, structured counseling and sound therapy were administered either alone or as a combination of two treatments resulting in 10 treatment arms. The primary endpoint was the difference in the change from baseline to week 12 in the total score of the Tinnitus Handicap Inventory between single and combination treatments. Results: Out of 461 enrolled patients 230 were assigned to single and 231 to combination treatment. Least-squares mean changes from baseline to week 12 were -11.7 for single (95% confidence interval [CI], -14.4 to -9.0) and -14.9 for combination treatments (95% CI, -17.7 to -12.1), with a significant between-group difference (p=0.034). Sound therapy alone had the lowest effect size. In contrast, cognitive-behavioral therapy and hearing aids alone had large effect sizes, which could not be further increased by combination treatment. Conclusions: In this trial involving patients with chronic tinnitus, all treatment arms showed improvement in THI scores from baseline to week 12. No clear synergistic effect was observed when combining treatments, but rather a compensatory effect, where a more effective treatment offsets the clinical effects of a less effective treatment.

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Section: Resultsmentioning

confidence: 99%

“…The results of the remaining objectives (as outlined in the SAP) 21 and time points (interim visit and follow up) are reported in Tables S16 – S18 .…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Single versus Combination Treatment in Tinnitus: An International, Multicentre, Parallel-arm, Superiority, Randomised Controlled Trial

Schoisswohl,

Basso,

Simoes

et al. 2024

Preprint

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“…Unification of treatments and Interventions for Tinnitus patients (UNITI) is a European Union-wide project, which overall aim is to deliver a predictive computational model based on existing and longitudinal data 19 . The dataset from the UNITI randomized controlled trial is described by Simoes et al 20 .…”

Section: Methodsmentioning

confidence: 99%

Practical approaches in evaluating validation and biases of machine learning applied to mobile health studies

Allgaier,

Pryss

2024

Commun Med

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Background Machine learning (ML) models are evaluated in a test set to estimate model performance after deployment. The design of the test set is therefore of importance because if the data distribution after deployment differs too much, the model performance decreases. At the same time, the data often contains undetected groups. For example, multiple assessments from one user may constitute a group, which is usually the case in mHealth scenarios. Methods In this work, we evaluate a model’s performance using several cross-validation train-test-split approaches, in some cases deliberately ignoring the groups. By sorting the groups (in our case: Users) by time, we additionally simulate a concept drift scenario for better external validity. For this evaluation, we use 7 longitudinal mHealth datasets, all containing Ecological Momentary Assessments (EMA). Further, we compared the model performance with baseline heuristics, questioning the essential utility of a complex ML model. Results Hidden groups in the dataset leads to overestimation of ML performance after deployment. For prediction, a user’s last completed questionnaire is a reasonable heuristic for the next response, and potentially outperforms a complex ML model. Because we included 7 studies, low variance appears to be a more fundamental phenomenon of mHealth datasets. Conclusions The way mHealth-based data are generated by EMA leads to questions of user and assessment level and appropriate validation of ML models. Our analysis shows that further research needs to follow to obtain robust ML models. In addition, simple heuristics can be considered as an alternative for ML. Domain experts should be consulted to find potentially hidden groups in the data.

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A critical review of established tinnitus patient-reported outcomes as measures of Tinnitus Severity and Tinnitus Distress and exemplar analysis of the Tinnitus Handicap Inventory as a formative or reflective measure

Clarke,

Hoare,

Trigg

2024

Front. Audiol. Otol.

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Tinnitus Severity and Tinnitus Distress are frequently referenced and conflated constructs in research, measured using established tinnitus patient-reported outcome measures (PROs). Confusion regarding these constructs and their relation to fundamental scientific conceptions of tinnitus represents a threat to the validity of PROs as applied in tinnitus research, the conclusions that are reached when applying them, and subsequent progress of theory and clinical interventions for those experiencing tinnitus. Therefore, we critically review relevant literature, providing the Severity of Symptoms (SoS) and Correlates of Complaint (CoC) framework to link tinnitus theory to these constructs. We provide researchers with an overview of latent variable fundamentals (including distinctions between formative and reflective measures, and psychometric and clinimetric measurement traditions). We then provide a synthesis of the relationship between Tinnitus Severity and Tinnitus Distress, the SoS/CoC framework, and latent variable measurement to elucidate their distinctions. Finally, we take the Tinnitus Handicap Inventory (THI) as an exemplar of established tinnitus PROs and use study data (N = 200) to empirically evaluate the appropriateness of the THI as a reflective measure of Tinnitus Distress. Subsequently, conceptual and criterion mediation tests provide evidence that the THI is not a reflective measure of Tinnitus Distress according to the CoC conception and should be considered as a formative measure. Researchers should therefore consider whether established tinnitus PROs, such as the THI, are congruent with the scientific conceptions and subsequent theories that they aim to evaluate.

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The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT)

Cited by 4 publications

References 31 publications

Single versus Combination Treatment in Tinnitus: An International, Multicentre, Parallel-arm, Superiority, Randomised Controlled Trial

Single versus Combination Treatment in Tinnitus: An International, Multicentre, Parallel-arm, Superiority, Randomised Controlled Trial

Practical approaches in evaluating validation and biases of machine learning applied to mobile health studies

A critical review of established tinnitus patient-reported outcomes as measures of Tinnitus Severity and Tinnitus Distress and exemplar analysis of the Tinnitus Handicap Inventory as a formative or reflective measure

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