rTMS and Retraining in Focal Hand Dystonia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for rTMS and Retraining in Focal Hand Dystonia (NCT01738581), a randomized phase 1, phase 2 study. The primary outcome is Change From Baseline in Global Rating of Change at Posttest (Day 5).

2. Clinical Question

The study is listed as randomized, single-masked, and crossover, with Phase 1 and Phase 2 status. Its stated purpose was to explore whether rTMS combined with rehabilitation could reduce dystonia symptoms, assessed through motor performance. The posted result is a small-sample description of participant-rated change, not a precise estimate of a treatment effect. The registry record does not report who was masked or how masking was implemented.

3. Trial Design

This completed study enrolled 9 participants and compared two treatment sequences. In one sequence, participants received rTMS with sensorimotor retraining first, followed by rTMS with control therapy. In the other, the order was reversed. The control therapy is described as non-specific therapy including stretching, massage, and range of motion. Both sequences therefore included rTMS; the contrast of interest is the accompanying rehabilitation treatment, interpreted using the first treatment period.

The registry identifies the design as randomized, single-masked, and crossover. Randomization assigns participants to treatment sequences, while a crossover design ordinarily exposes participants to more than one treatment over successive periods. For this record, however, the analysis population description says data were analyzed only in the first intervention period because there was a lack of washout between periods. It further states that the lack of washout made data from the second period unreliable. Thus, the posted primary-outcome comparison does not use the full within-participant sequence that a crossover analysis might otherwise use.

The primary outcome was change from baseline in Global Rating of Change at posttest on Day 5. The record describes six secondary outcomes: changes in Arm Dystonia Disability Scale, sensation, cortical silent period, pressure during handwriting, physician-rated impairment, and physical function. The study is classified as Phase 1 and Phase 2. The registry record does not report the planned duration of each treatment period, a washout interval, the randomization procedure, the masking target, or a protocol rationale for the crossover structure.

The reported primary results are organized by first-period treatment: rTMS with sensorimotor retraining and rTMS with control therapy. This design feature matters when interpreting the arm summaries. They represent first-period groups rather than a full crossover comparison adjusted for participants’ responses in both periods. The record does not report an adjusted treatment estimate, a formal model for period or sequence effects, or a statistical comparison between the groups.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

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 Change From Baseline in Global Rating of Change at Posttest (Day 5), measured over Baseline and Posttest.

The primary endpoint is change from baseline in the Global Rating of Change (GROC) at posttest on Day 5. The measure asks participants to identify one to three functions most affected by focal hand dystonia and then rate perceived change in those functions at posttest relative to baseline. The scale runs from -7, described as a very great deal worse, through 0, no change, to +7, a very great deal better. The registry reports the endpoint in units on a scale.

A participant-reported change measure can capture whether a person notices a difference in activities that are personally important. In this study, identifying affected functions before rating change ties the response to the participant’s own experience rather than to a single fixed task. As a general measurement principle, such a rating is useful for describing perceived change, but it is not the same as an objective measurement of motor performance or a clinician’s assessment. Its meaning also depends on how participants understand the response options and recall their baseline function.

The posted summaries give a mean and a full range for each first-period group. The sensorimotor-retraining group has a mean of 1.3 and a range from 0.0 to 3.0; the control-therapy group has a mean of 1.2 and a range from -4.0 to 3.0. These are descriptive summaries. The registry record does not report a confidence interval, standard deviation, or inferential test for the primary endpoint. The available summaries therefore do not quantify the uncertainty around a between-group effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the primary outcome as a mean with a full range. A mean is a measure of the arithmetic center of observed values; the full range records the lowest and highest values. The mean communicates an overall level of response, while the range gives a limited view of how widely the observations extend. Neither summary shows how responses are distributed between the endpoints of the range. A range is also not a confidence interval: it describes the observed data, whereas a confidence interval is designed to express uncertainty about an estimated quantity.

What does a confidence interval add?

As a general statistical explanation, a confidence interval gives a range of values compatible with a statistical estimation procedure and the observed data, under the assumptions of that procedure. It conveys the precision of an estimate more directly than a mean alone. The registry record does not report a confidence interval for the primary treatment comparison, so the precision of a between-group effect cannot be assessed from an interval. The posted ranges for the two groups should not be substituted for such intervals.

Why does the crossover structure need care?

As a general concept, a crossover study compares treatments received by the same participants in different periods. This can make within-participant comparisons informative when responses in one period do not affect responses in a later period and when period effects are appropriately handled. The registry describes this trial as crossover but says that a lack of washout between periods made second-period data unreliable. It therefore analyzed only the first intervention period. The posted primary summaries should be interpreted as results from separate first-period groups, not as paired within-person treatment contrasts.

A carryover effect occurs, in general, when an earlier treatment influences outcomes measured after a later treatment has begun. A washout period is intended to reduce such influence, although the appropriate approach depends on the intervention and outcome. The registry record does not report the planned washout, the evidence used to identify a lack of washout, or an analysis estimating carryover. It does state the practical consequence: second-period data were not used for the primary analysis.

What does the scale measure?

The GROC is a participant-rated measure of perceived change. In this study, participants selected one to three functions most impacted by focal hand dystonia and rated perceived change at posttest relative to baseline. The stated scale ranges from -7, very great deal worse, to +7, very great deal better, with 0 indicating no change. As a general measurement point, a change rating is a report of perceived difference, not a direct measurement of the size of a motor deficit. The registry record does not report validation details or a clinically meaningful threshold for interpreting a score.

What can be inferred from the posted summaries?

The group means and full ranges support a descriptive account of observed ratings. They do not provide the uncertainty around the group means or a formal estimate of the difference between treatments. A p-value, when reported, addresses how compatible data are with a specified null model under its assumptions; it does not quantify the size or clinical importance of an effect. No p-value for the primary comparison is reported in the registry record. Nor is an effect estimate with a confidence interval reported. Therefore, the numerical summaries alone cannot establish statistical significance or precision.

The record lists six secondary outcomes alongside the primary endpoint. As a general statistical issue, testing multiple outcomes can increase the chance of finding at least one apparently unusual result when there is no true effect. A prespecified analysis plan may address this through a hierarchy of outcomes or multiplicity adjustment. The registry record does not report such a plan or an adjustment method. This does not imply that an adjustment was or was not used; it means the information needed to assess that aspect of the analysis is not reported in the registry record.

How should planning estimates be understood?

As a general distinction, a sample-size calculation is a forward-looking planning exercise. The stated sample-size assumptions for any planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These calculations are planning illustrations, not observed power. They do not show that the enrolled study had a particular probability of detecting an effect, and they do not resolve uncertainty in the actual result. The registry record does not report its own sample-size justification or design calculation.

The posted analysis uses the first-period population described as participants who completed that phase. The group summaries contain 5 and 4 participants. The registry record does not report details of missing outcome data, exclusions beyond the stated first-period restriction, or whether analyses followed an intention-to-treat principle. These omissions limit assessment of the analysis population and of how missingness might affect the results.

10. Multiplicity, Missing Data and Analysis Populations

The primary population is described as all participants who completed the first phase. The record says the outcome data were analyzed only in the first intervention period because a lack of washout made second-period data unreliable. The posted primary groups contain 5 participants receiving rTMS with sensorimotor retraining first and 4 receiving rTMS with control therapy first. The registry record does not report further eligibility rules for the analysis population or whether every randomized participant completed the first phase.

Missing-data details are not reported in the registry record. There is no account of missing outcome measurements, reasons for missingness, imputation, or sensitivity analyses. The record does not state whether the primary analysis was intention-to-treat, per-protocol, or another analysis population beyond its description of first-phase completers. These details matter because an analysis limited to completers can differ from an analysis that retains all randomized participants, particularly if completion is related to treatment or outcome.

One primary outcome and six secondary outcomes are listed. The registry record does not report a multiplicity strategy, such as a testing hierarchy or adjustment for multiple comparisons. As a general statistical principle, assessing several outcomes can make isolated positive findings harder to interpret unless the analysis plan accounts for the number and relationship of tests. No secondary-outcome results or corresponding inferential analyses are reported in the registry record.

The registry record also does not report a prespecified statistical analysis plan, a sample-size justification, interim analyses, or the handling of period and sequence effects beyond the decision to use first-period data. Those omissions do not establish that these procedures were absent; they mean they cannot be evaluated from the registry record.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports serious adverse events separately for the two randomized treatment sequences. The sequence of rTMS with sensorimotor retraining followed by rTMS with control therapy had 5 participants at risk and 0 serious adverse events. The reverse sequence had 4 participants at risk and 0 serious adverse events. The record does not list serious adverse-event terms.

For other, non-serious adverse events, 3 of the 5 participants in the first sequence were affected, and 2 of the 4 participants in the reverse sequence were affected. These are counts of participants affected as recorded, not counts of distinct event episodes or evidence about severity beyond the serious-versus-other categorization. The registry record does not report the specific non-serious event terms in the information.

The safety groups are defined by treatment sequence, with both treatments appearing across the sequence. These figures should not be treated as a clean comparison of adverse events attributable to one component alone. The registry record does not report event timing by period in these figures, exposure-adjusted event rates, or a causal assessment of whether events were related to treatment. Deaths are not reported in the registry record.

Zero reported serious events in these small groups means none were recorded in the registry summaries; it does not establish that serious harms are impossible or rule out uncommon events. Likewise, the other-event counts describe what was recorded among participants at risk and do not establish a comparative safety difference.

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

The posted results establish that the registry contains first-period descriptive GROC summaries for two groups: a mean of 1.3 with a range of 0.0 to 3.0 for rTMS with sensorimotor retraining, and a mean of 1.2 with a range of -4.0 to 3.0 for rTMS with control therapy. These values characterize participant ratings in the small groups included in the primary analysis. The record also establishes why later-period data were excluded: the registry says there was a lack of washout and that those data were considered unreliable.

The summaries do not establish a statistically significant difference, because the registry record does not report a treatment-effect estimate, confidence interval, or p-value for the primary comparison. They do not show how precisely the treatment contrast is estimated. The reported ranges are observed endpoints, not measures of uncertainty about the treatment effect. The results also do not establish that the two combinations are equivalent; a lack of a reported inferential comparison is not evidence of equivalence.

The study’s stated purpose was to explore whether rTMS combined with rehabilitation could reduce symptoms, with motor performance described as the intended indication of improvement. The primary outcome, however, is a participant rating of perceived functional change. That is informative about reported experience but is not interchangeable with an objective performance measure or the listed physician-rated outcome. The registry record does not report a threshold for what amount of GROC change would be clinically meaningful.

Because the second crossover period was not used, the result does not provide the full within-participant comparison that readers might expect from a crossover design. The first-period results can be described by assigned treatment, but the small groups and absence of an uncertainty estimate make the treatment contrast difficult to assess. The record also lists six secondary outcomes without reporting their results in the posted outcome information.

In general, a study result is most informative when its estimate, uncertainty, analysis population, and limitations are considered together. In this record, the available primary values are descriptive and the stated washout problem narrows the analysis to the first period. These findings should not be taken as a definitive estimate of treatment benefit, proof of no effect, or a complete assessment of safety.

13. Why This Trial Matters Statistically

This trial illustrates how the design label and the analysis actually used can differ in practical importance. It is registered as a crossover study, but the registry says the second period was unreliable because there was a lack of washout. The primary analysis consequently uses only first-period observations. For interpretation, it is not enough to know that participants were assigned to sequences; readers also need to know which periods contributed to the reported estimate and why.

It also highlights the distinction between descriptive results and an inferential comparison. Means and ranges can show the observed level and spread of responses, but they do not quantify uncertainty around the treatment contrast. With only 5 and 4 participants in the posted first-period groups, individual responses can have substantial influence on group summaries. The registry does not provide an interval estimate or test to help characterize that uncertainty.

The outcome itself is another statistical consideration. The GROC asks participants to identify functions affected by dystonia and then rate perceived change. This approach can reflect personally relevant experience, while remaining distinct from a direct performance measure. A clear definition of the construct, its scale, and any threshold for meaningful change helps readers understand what an outcome can support; the registry does not report a clinically meaningful threshold.

Finally, the study lists multiple secondary outcomes, but its multiplicity plan and their posted results are not reported in the registry record. This is a reminder that the number of outcomes and the analysis population are part of interpreting evidence, not merely technical details. The record offers a useful account of what was measured and of the decision to omit second-period data, while leaving important questions about precision and analysis methods unresolved.

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 primary analysis is limited to the first intervention period because the registry reports a lack of washout between periods. This means the posted primary comparison does not use the within-participant information expected from a complete crossover analysis. The record does not report how lack of washout was assessed, the intended washout interval, or an analysis of carryover or period effects.

The primary-outcome groups are small, with 5 participants in the rTMS and sensorimotor-retraining group and 4 in the rTMS and control-therapy group. The registry reports means and full ranges, but not standard deviations, confidence intervals, or a formal comparison. The precision of the treatment contrast is therefore not reported. Individual observations may have notable influence in groups of this size, although the record does not provide participant-level data to assess that influence.

The endpoint is a self-reported rating of perceived functional change. The record describes its scale and the process of selecting affected functions, but does not report a clinically meaningful threshold, measurement validation information, or individual scores. The results therefore describe ratings without establishing how large a change would be important to participants or how they relate to objective performance.

The registry lists six secondary outcomes, but their results and any approach to multiplicity are not reported in the registry record. Missing-data handling, exclusions beyond the first-period restriction, the precise analysis population, and the statistical model are also not reported. The registry record does not report the sample-size justification, the detailed randomization method, or who was masked. These limitations constrain assessment of the design, analysis, and generalizability of the posted summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: rTMS and Retraining in Focal Hand Dystonia — NCT01738581.
• Registry record last updated 2019-11-18; status last verified 2019-10.
• Results first posted 2016-06-28.
• 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

NCT01738581 is a completed randomized, single-masked crossover study listed as Phase 1 and Phase 2, with 9 participants enrolled. It evaluated rTMS combined with sensorimotor retraining and rTMS combined with non-specific control therapy, delivered in opposite sequences.

The primary endpoint was change from baseline in Global Rating of Change at posttest on Day 5. The registry reports first-period means of 1.3 for 5 participants receiving rTMS with sensorimotor retraining and 1.2 for 4 participants receiving rTMS with control therapy. The corresponding full ranges were 0.0 to 3.0 and -4.0 to 3.0. The record says second-period data were considered unreliable because there was a lack of washout.

Six secondary outcomes are listed. A formal primary comparison, uncertainty estimates, missing-data methods, and a multiplicity plan are not reported in the registry record. Serious adverse events were recorded for neither sequence group; other adverse events affected 3 participants in one sequence and 2 in the other.