Kinematic-guided BoNT-A Treatment for ET and PD Tremor: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Kinematic-guided BoNT-A Treatment for ET and PD Tremor (NCT02427646), a non-randomized phase 2 study. The primary outcome is Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale).

2. Clinical Question

3. Trial Design

The registry classifies this as a phase 2, non-randomized study with no masking and a single-group model. It records enrollment of 54 and lists tremor as the condition. The sponsor is Western University, Canada. The recorded start is 2011-10, and primary completion is 2015-04; the overall status is listed as unknown.

The arm descriptions distinguish ET participants receiving kinematic-guided BoNT-A injections from participants receiving the same treatment for Parkinson disease tremor. Both descriptions specify 6 injection cycles. The record therefore presents diagnostic cohorts receiving treatment, rather than a randomized treatment arm and a control arm. It states that the primary outcome was considered from baseline to each time point, and that baseline and final-visit scores per group were to be stated. Numerical group scores are not reported in the registry record.

Non-randomized allocation means treatment assignment was not described as random. Without a randomized untreated or alternative-treatment comparator, changes over time cannot be separated from other explanations such as natural variation, changes in assessment, or other concurrent influences. These are general limitations of within-group comparisons, not findings about what occurred in this study. The record does not report a protocol, recruitment procedures, allocation procedures beyond the non-randomized classification, or details of follow-up beyond the stated outcome timeframe of 0 to 96 weeks.

The record identifies Kinematic Tremor Severity as a secondary outcome and lists two outcome measures and two analyses. Further descriptions of the analysis populations and statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Protocol enrollment identifies participants who agreed to participate and sign the consent form (total N=54). However, in the total started participant flow, two participants did not have a high enough tremor severity or consistent tremor severity during the scripted tasks held during the kinematic technology assessment, leaving N=52 in the study

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Mean total FTM score was compared from baseline to each time-point. Here we state the baseline and final visit scores per group

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale), measured over 0 to 96 weeks.

The primary endpoint is the Clinical Tremor Rating Scale, identified more specifically as the Fahn-Tolosa-Marin Tremor Rating Scale (FTM). It is a continuous measure reported as a total score, with means and standard deviations specified as the summary form. The stated scale range is 0 to 92 FTM points, and lower scores indicate a better outcome.

The registry describes the outcome as improvement in hand tremor, assessed by comparing the mean total FTM score at baseline with scores at subsequent time points. It also defines improvement as a reduction of >8 points on the standardized assessment. This criterion communicates the change the record regards as improvement; it does not establish that such a reduction was observed. No group means, standard deviations, or change estimates are reported in the registry record, so the criterion cannot be evaluated from the available numerical results.

As a general statistical matter, a standardized clinical rating scale allows observations to be expressed using a common scoring framework. A continuous score can describe the degree of measured change, while its mean summarizes the group and its standard deviation describes how dispersed individual scores are around that mean. Neither summary alone establishes why a change occurred. In this non-randomized treatment record, within-group score changes would describe change during follow-up, not a causal treatment effect relative to a control.

The stated timeframe is 0 to 96 weeks. The record does not report the exact timing of the final visit for each participant or the numerical scores at the assessed time points.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: the FTM total score takes values on a numeric scale, and the registry specifies means and standard deviations. The general purpose of a mean is to summarize a group’s scores with a central value. A standard deviation describes spread around that mean. Together they can show both average symptom-rating level and variation among the scores, but they do not show the full distribution or explain the reasons for individual differences.

What does a within-group comparison estimate?

The registry describes comparing mean FTM scores from baseline to later time points for each diagnostic group. In general, a within-group comparison describes how the measured score changes over time among participants included in the analysis. It does not by itself estimate what would have happened to those same participants without treatment. A control group helps address that counterfactual question; this record is classified as non-randomized and single-group, and its listed groups are both treatment cohorts. Thus, a change from baseline should not be interpreted as a controlled causal treatment effect.

The ET and Parkinson disease tremor groups have different diagnoses. Comparing their scores with each other would not automatically create a valid treatment contrast: diagnosis and other group characteristics may differ, and the record does not describe random assignment or a control condition. The reported design supports describing the cohorts separately, subject to the absence of numerical results and analysis details.

How should the score threshold be read?

The outcome description defines improvement as a reduction of >8 points on the FTM scale. This is a threshold stated by the registry, while the primary outcome is also described using mean scores. A threshold can be used to classify whether a change meets a chosen criterion; a mean change instead describes average score movement. Those summaries answer different questions. The registry record does not report whether the threshold was reached by the group or by individual participants, nor does it provide numerical score changes to evaluate it.

As a general concept, statistical uncertainty describes how much an estimate might vary across comparable samples under a stated analysis. A confidence interval is one way to express uncertainty around an estimate; its width is affected by factors such as sample information and score variability. No confidence interval for the primary outcome is reported in the registry record. Without an estimate and uncertainty interval, the magnitude and precision of any FTM change cannot be judged from the reported information.

What do planning calculations mean?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the target effect is a stated fraction of the observed effect. The illustration is not the trial’s original design justification, and its numerical results are not reported in the registry record. No sample-size justification for the trial is reported.

In general, a planning calculation asks how many participants per arm might be needed to detect a specified effect under stated assumptions. It depends on the assumed effect, variability, significance level, allocation, and analysis method. An illustration based on an observed effect is a planning exercise, not observed power and not proof that the study was adequately powered. Because the reported record does not include the effect values or the resulting sample-size values, those quantities cannot be assessed. The record also does not report an original power calculation, a prespecified target effect, or the reasoning behind the chosen enrollment.

What does over-dispersion mean in general?

Over-dispersion is relevant when a statistical model assumes a particular amount of variation but the data show more variation than that assumption allows. If present and not addressed, uncertainty can be understated and statistical tests may be misleading. This is a general explanation, not a claim about this study: the primary endpoint is continuous, and the registry record does not report an over-dispersion assessment or a model for the primary outcome.

The record identifies means and standard deviations but does not describe whether the analysis used paired observations, a repeated-measures model, or another method to account for measurements from the same participant over time. Repeated measurements are generally related within a person, so an analysis that accounts for that relationship can differ from one treating observations as independent. The specific method, assumptions, and any adjusted estimates are not reported in the registry record.

Likewise, the record does not report adjustment for baseline score, covariates, or other potential differences between participants. These omissions matter for interpreting an observational within-group change because score trajectories may also reflect differences in participant composition or follow-up. The stated design and endpoint information alone do not identify which statistical model was used or whether model assumptions were checked.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, and identifies FTM as the primary outcome and Kinematic Tremor Severity as a secondary outcome. A multiplicity plan describing how the analyses relate to one another, or whether any adjustment was made for multiple testing, is not reported in the registry record. As a general statistical matter, considering multiple outcomes, time points, or subgroup comparisons can increase the chance of a seemingly notable result arising by chance. Adjustment or a prespecified hierarchy can address that issue, but the record does not state whether either was used.

The primary outcome description refers to comparison of baseline scores with each time point, within each group. The number of comparisons included in the analysis, how they were selected, and how any repeated testing was handled are not reported in the registry record. This limits interpretation of any isolated result, although numerical primary outcome results are also absent.

The registry records enrollment of 54, but does not report the numbers included in each primary outcome analysis or the amount and pattern of missing FTM data. A definition of the analysis population—such as which participants were included in each comparison—is not reported. Missing-data methods, imputation, and sensitivity analyses are also not reported in the registry record.

Generally, missing observations can affect an estimate when the availability of follow-up measurements is related to participant characteristics or outcomes. Whether missingness occurred, why it might have occurred, and whether it could affect these results cannot be determined from the information reported. The registry record also does not report an interim-analysis plan or stopping rules.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The serious adverse-event figures list the ET treatment group with 24 at risk and 0 affected, and the Parkinson disease tremor treatment group with 28 at risk and 0 affected. Deaths are recorded as 0 in each group. The record also lists 0 other events in each group, with at-risk counts of 24 and 28 respectively. These are the event counts as recorded, not evidence that every possible adverse experience was assessed or absent.

The figures describe the listed groups and should not be treated as a randomized safety comparison. There is no control group described, and the record does not provide an event definition, collection method, observation duration for safety, or detailed event narratives. The record also does not explain how the at-risk counts relate to the enrollment or to the population analyzed for the primary outcome.

In general, a zero count means no event of the specified recorded category was listed for that group. It does not establish zero underlying risk, especially when the size and duration of observation are limited or incompletely described. No risk estimate or uncertainty interval for adverse events is reported in the registry record. The event counts should therefore be read narrowly as registry entries, without drawing broader conclusions about safety.

12. What the Result Does, and Does Not, Mean

The record documents a phase 2 investigation of kinematic-guided BoNT-A injections for hand tremor in ET and Parkinson disease tremor. It identifies the FTM total score as the primary outcome, states that lower scores indicate a better outcome, and defines improvement as a reduction of >8 points. It also describes treatment over 6 injection cycles and an outcome timeframe of 0 to 96 weeks. These details clarify the intended clinical question and how the primary measure was framed.

They do not establish that scores improved. The numerical baseline and final-visit means and standard deviations, changes, and uncertainty estimates are not reported in the registry record. The threshold in the outcome definition is not a reported result. The registry information therefore does not show the degree of change, whether change varied by diagnosis, or how consistently participants’ scores moved.

The design also constrains causal interpretation. The registry classifies allocation as non-randomized and the model as single-group. The ET and Parkinson disease tremor cohorts are treatment groups, not randomized controls. Even if within-group score changes were available, they would describe change over time rather than isolate the effect of treatment from other possible influences. This is a general interpretation of the design, not a claim that any particular alternative explanation occurred.

The safety record lists zero serious adverse events, zero other events, and zero deaths for both groups. These recorded counts do not establish that all adverse experiences were captured or that the treatment has no safety risk. Definitions and ascertainment details are not reported in the registry record.

The most defensible reading is therefore about what was planned and how the outcome was defined, rather than about treatment benefit or harm. The posted information does not permit an estimate of the magnitude or precision of the primary outcome, a reliable comparison between diagnostic cohorts, or a controlled treatment-effect conclusion.

13. Why This Trial Matters Statistically

This study raises a useful statistical question about how an objective measurement approach might be paired with a clinical rating scale. The brief summary describes use of multi-sensor kinematic information to guide BoNT-A injections, while the primary endpoint is the clinician-oriented FTM total score. In principle, assessing both movement features and a clinical scale can address different aspects of tremor measurement. The registry also lists Kinematic Tremor Severity as a secondary outcome.

Statistically, the record illustrates why the design and the reporting of numerical results matter as much as the choice of endpoint. A baseline-to-follow-up change can be clinically interpretable only when the measured values, variability, analysis population, and uncertainty are available. Without those results, readers cannot judge the size, precision, or consistency of the measured change, even though the scale and an improvement criterion are described.

The record also distinguishes an intervention study from a controlled treatment comparison. The diagnostic cohorts offer context for assessing the intervention in different clinical populations, but non-randomized, single-group classification means they do not function as untreated controls. This design feature limits causal interpretation independently of the measurement approach.

Finally, the stated sample-size illustration is explicitly based on an observed effect and planning assumptions. General statistical practice treats such calculations as planning aids rather than evidence of observed power. The absence of the calculation results and the trial’s own sample-size justification makes it important not to infer adequacy from enrollment alone. The record is informative about the intended measurement and design, while its missing numerical outcome details sharply limit what can be concluded from the posted results.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record classifies the study as non-randomized, unmasked, and single-group. The arm descriptions refer to ET and Parkinson disease tremor treatment cohorts, but neither is described as a control group. Consequently, any change from baseline would not by itself isolate treatment effects from time-related changes or other influences. The record does not describe procedures for controlling confounding.

Numerical FTM outcome values are not reported in the registry record. There are no reported group means or standard deviations for baseline and final visits, numerical changes, or uncertainty estimates. Although the record states an improvement criterion of >8 points, it does not report whether the criterion was met. This prevents evaluation of the primary outcome’s magnitude and precision.

The registry does not report participant characteristics beyond the diagnostic groups, detailed eligibility criteria, group-specific primary-outcome analysis populations, or the amount and handling of missing data. It also does not report the statistical model, adjustment for repeated measurements, covariates, multiplicity procedures, or sensitivity analyses. These omissions prevent assessment of how the outcome analyses were conducted and how robust any estimates might be.

The outcome timeframe is 0 to 96 weeks, but the exact final assessment timing for participants and visit-specific results are not reported. Treatment is described over 6 injection cycles, without doses or further administration details. Safety counts are listed, but event definitions and ascertainment methods are not reported. The overall study status is unknown. These limitations concern the information available in the registry record and do not establish what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Kinematic-guided BoNT-A Treatment for ET and PD Tremor — NCT02427646.
• Registry record last updated 2019-08-20; status last verified 2019-08.
• Results first posted 2019-08-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The record describes a phase 2, non-randomized, unmasked study classified as single-group, with enrollment of 54. It concerns hand tremor in essential tremor and Parkinson disease and evaluates kinematic-guided BoNT-A treatment, identified in the brief summary as incobotulinumtoxinA (Xeomin®). Treatment descriptions specify 6 injection cycles for each diagnostic cohort.

The primary outcome is the Fahn-Tolosa-Marin Tremor Rating Scale total score, assessed from baseline to later visits over a stated timeframe of 0 to 96 weeks. Lower scores indicate a better outcome, and the outcome description defines improvement as a reduction of >8 points. The record lists Kinematic Tremor Severity as a secondary outcome.

Numerical primary outcome results and uncertainty estimates are not reported in the registry record. The safety entries list zero serious events, zero other events, and zero deaths in each treatment group. The registry’s non-randomized, single-group classification and absence of a control group limit causal interpretation of any within-group change.