Adjunct Low Frequency Repetitive Transcranial Magnetic Stimulation With Physiotherapy Enhance Upper Extremity Function Restoration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjunct Low Frequency Repetitive Transcranial Magnetic Stimulation With Physiotherapy Enhance Upper Extremity Function Restoration (NCT02490371), a randomized na study. The primary outcome is Change of Cortical Excitability From Baseline to at 4th Weeksand 12th Weeks Training in Motor Evoked Potential at 120% Resting MotorThreshold at Affected Hand.

2. Clinical Question

The clinical comparison is therefore an add-on question: the intervention differs by whether active low frequency rTMS accompanies physiotherapy, while placebo stimulation is used in the comparison group. The stated hypothesis was that the rTMS combination would provide an additional effect on upper limb motor function compared with motor training alone. The primary outcome is a physiological measure rather than a direct functional performance score, while several functional and impairment measures are listed as secondary outcomes.

The record describes a randomized, double-masked, parallel trial. These design labels identify the intended structure of the comparison, but details such as the method of sequence generation, concealment, and which people were masked are not reported in the registry record. Without posted group outcome values or an analysis, the clinical question can be described, but its answer cannot be inferred from the registry information.

3. Trial Design

The registry record describes a randomized, double-masked, parallel-group trial with 24 participants and a completed status. The sponsor was Queen Elizabeth Hospital, Hong Kong. The recorded study start was 2015-12, and primary completion was 2017-05. The condition listed was stroke. The record lists phase as NA, which is consistent with a non-drug intervention record, but does not provide a further phase description.

One group received low frequency rTMS over the contra-lesional M1 region followed by structured physiotherapy upper limb training. The intervention description specifies 1 Hz stimulation, 1200 pulses, 20 minutes at 90% resting motor threshold, for 10 consecutive sessions over 2 weeks, followed immediately by 30 minutes of training. The other group received placebo stimulation over the same region for 10 consecutive sessions, followed immediately by 30 minutes of structured physiotherapy training. Details of the training continuation are incomplete in the registry record and should not be inferred.

Randomization supports a planned comparison between allocated groups, while a parallel design means participants are assigned to a group rather than crossing between interventions. The record labels the study double-masked, but does not identify which roles were masked or describe how masking was maintained. It also does not report the randomization method, allocation concealment, recruitment flow, adherence, withdrawals, or the number included in each outcome analysis.

The registry lists a primary measure of change in cortical excitability at baseline and at the 4th and 12th weeks, with upper limb impairment, grip strength, upper limb function, reaction time, and health status among the secondary outcomes. It lists 6 outcome measures and no analyses. Although the trial status is completed, numerical outcome estimates, uncertainty measures, and hypothesis-test results are not reported in the registry record. Completion alone does not establish that all planned assessments were collected or analyzed.

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: Exclusion criteria: 1. Mini Mental State Test score ≤ 24; 2. Mental illness; 3. Contra-indications to rTMS according to guidelines formulated by Wassermann (e.g., intracranial implants, epilepsy, cardiac pacemaker, implanted medication pumps); 4 Unstable cardio-pulmonary condition.

Overall Study

Reasons for not completing this period:

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 of Cortical Excitability From Baseline to at 4th Weeksand 12th Weeks Training in Motor Evoked Potential at 120% Resting MotorThreshold at Affected Hand, measured over Baseline and at 4th weeks and at 12th weeks.

The primary endpoint is described as change in cortical excitability, assessed with motor evoked potential amplitude at the affected hand at baseline and at the 4th and 12th weeks. The record specifies electromyographic activity in the first dorsal interossei, measured at 120% resting motor threshold. Amplitude is measured peak to peak in millivolts, and the record states that a higher value means better control.

A motor evoked potential is a physiological response elicited by stimulation of the motor system and recorded from muscle activity. In general, this type of measure can be used to characterize the excitability of pathways involved in motor output. It is not itself a direct test of how well a participant performs everyday tasks. The study's stated rationale connects modulation of cortical excitability with possible changes in motor recovery, which is why a physiological measure is relevant to the proposed mechanism.

The endpoint is measured at multiple time points, so interpretation depends on both the measurement occasion and how change is defined and compared between groups. The registry title describes change from baseline, but the analysis definition, summary estimates, and results at each time point are not reported in the registry record. No baseline or follow-up mean, standard deviation, between-group estimate, or confidence interval is available. The recorded endpoint description therefore establishes what was intended to be measured, but does not show the magnitude or precision of any observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives a randomized, double-masked, parallel design and identifies continuous outcomes summarized as means with standard deviations. It does not report a statistical analysis plan, model specification, or outcome estimates. The concepts below explain how such methods are generally read; they should not be taken as descriptions of unreported procedures in this trial.

What does a mean summarize?

General: A mean is a measure of the central location of a set of numeric observations. For a continuous measure such as motor evoked potential amplitude, it gives a group-level summary, but it does not describe every participant's value or the shape of the full distribution. The standard deviation describes how dispersed individual observations are around the mean. A mean and standard deviation can be useful descriptive summaries, but they do not by themselves show the uncertainty in a between-group treatment estimate. That uncertainty depends on the sample size, variability, design, and statistical analysis.

The endpoint is measured at baseline and at follow-up occasions. A comparison may focus on follow-up values, change from baseline, or differences in change between groups. These approaches are not interchangeable in every setting. The registry title identifies change from baseline, but the precise definition of change and the planned method for comparing groups are not reported in the registry record. It would therefore be inappropriate to assign a specific analysis model to this study.

How should a confidence interval be understood?

General: A confidence interval accompanies an estimate to express its statistical precision under the assumptions of the analysis. A relatively narrow interval indicates more precision than a wide interval, while either interval may include values that would lead to different substantive interpretations. The interval should be read alongside the point estimate, measurement scale, and outcome context. It does not repair bias from missing data, poor measurement, or design problems. No confidence interval for the primary endpoint is reported in the registry record.

A p-value is another summary commonly used in trial reports. General: It describes how unusual the observed data, or more extreme data, would be under a specified null model and its assumptions. It does not give the probability that the null hypothesis is true, nor does it measure the size or practical importance of an effect. A p-value alone also does not show precision. No primary endpoint p-value is reported in the registry record.

Why does the outcome have several time points?

The primary outcome description includes baseline, the 4th week, and the 12th week. Repeated measurements can describe the course of an outcome, but they create choices about which time point or contrast is most important. An analysis might estimate change at each follow-up, compare trajectories across time, or designate a particular time point as primary. The registry record does not report how these repeated measures were modeled or which contrast was selected for inference. Its note that the primary outcome has several categories or time points and was not reduced to one comparison means there is no single posted primary comparison to interpret.

General: When the same endpoint is examined at multiple times, or multiple outcomes are tested, the chance of at least one apparently notable result can increase if the comparisons are treated as independent opportunities for discovery. Statistical methods can address this multiplicity, for example by prioritizing a prespecified comparison or adjusting inference. The specific approach matters, and no multiplicity strategy is reported in the registry record.

What does the planning illustration mean?

The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation. They say that the effect to detect is a stated fraction of an observed effect. These are planning assumptions, not a report of the trial's design justification or a statement about the result. The registry record does not report the effect estimate used for planning or numerical planning outputs. Any sample-size illustration is a planning aid rather than observed power. It cannot establish the probability that the trial detected an effect, and it cannot substitute for an estimated treatment effect with uncertainty.

General: Power is a design-stage probability defined under particular assumptions about an effect, variability, significance level, and analysis. Once data have been collected, the more informative focus is usually the estimated effect and its uncertainty, rather than a retrospective power calculation. The registry record does not report a sample-size justification or say whether the stated planning assumptions were used by the investigators when designing the trial.

Why can variability and distribution matter?

General: Standard statistical procedures often rely on assumptions about the distribution of observations or model errors. If observations are highly skewed, contain influential extreme values, or show variability that differs across groups, a simple mean-based analysis may not fully represent the data. Over-dispersion means that observed variability is greater than a model expects; if ignored, uncertainty can be understated. These are general considerations only. The registry record does not provide the participant-level data, distribution summaries, or diagnostics needed to assess them for this trial.

Randomization is intended to support a fair comparison by making group assignment independent of participant characteristics in expectation. It does not guarantee that groups will be identical in a small trial, and interpretation still benefits from baseline summaries, clear handling of missing observations, and a prespecified analysis. The randomization procedure and baseline outcome summaries are not reported in the registry record. In the absence of a posted analysis and results, statistical concepts can clarify what would be needed for interpretation but cannot supply the missing trial findings.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 6 outcome measures, including the primary motor evoked potential outcome and secondary measures of upper limb impairment, grip strength, arm function, reaction time, and health status. The primary description includes baseline and follow-up assessments at the 4th and 12th weeks. Examining multiple outcomes or time points can create multiplicity: the more comparisons considered, the greater the opportunity for a result to appear noteworthy by chance. General statistical practice may address this by prespecifying a main contrast, controlling error across comparisons, or clearly labeling analyses as exploratory. The registry record does not report a multiplicity strategy or a hierarchy among secondary outcomes.

The record lists no analyses and does not provide participant flow or the number with available measurements at each time point. It does not report how missing outcomes were handled, whether withdrawals occurred, or whether the analysis followed randomized assignment. Those omissions prevent assessment of missing-data risk and of whether the analyzed participants represent the randomized groups.

General: Missingness can affect an estimate when the chance that an outcome is absent is related to the outcome itself or to participant characteristics. Complete-case analysis, imputation, and model-based methods rely on different assumptions; no method can be attributed to this trial from the registry information. The record also does not report an intention-to-treat or per-protocol analysis population, or any sensitivity analyses. These are reporting gaps, not evidence that a particular method was or was not used.

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.

Most frequent non-serious adverse event terms

The adverse-event record lists 0 serious adverse events among 12 participants at risk in the rTMS plus physiotherapy group, and 0 among 12 at risk in the placebo stimulation plus physiotherapy group. It also lists 0 other adverse events among 12 at risk in each group and 0 deaths in each group. No serious adverse-event terms are listed.

These figures describe the counts recorded in the registry. A zero count does not establish that an intervention has no risk. It indicates that no events of the specified category were recorded among the listed participants at risk in this record. The counts do not show event timing, duration of observation, severity criteria, relatedness assessment, or whether participants experienced symptoms that were not classified as adverse events.

The registry record does not report detailed safety-monitoring procedures, event definitions, or the completeness of adverse-event collection. The safety denominators also should not be assumed to represent the number with complete outcome assessments. The trial's listed enrollment was 24, but the safety figures alone cannot establish how broadly the findings apply. These data allow a narrow description of recorded events, not a general safety conclusion.

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

The record identifies a focused experimental question: whether low frequency rTMS added to structured physiotherapy is associated with a different course of cortical excitability and upper limb outcomes than placebo stimulation plus physiotherapy. It also documents a randomized, double-masked, parallel design and the intended measurement schedule. That information helps readers understand what comparison the investigators planned.

What the record does not establish is the result of that comparison. No means, standard deviations, changes, between-group estimates, confidence intervals, or p-values are reported for the primary endpoint. No secondary outcome results are reported either. Therefore, the direction and size of any difference, and how precisely it was estimated, cannot be judged. The completed status does not fill this gap.

The primary endpoint is a physiological measure of motor evoked potential amplitude. Even if numerical results were available, this measure would need to be interpreted in relation to the functional outcomes and the clinical context. A difference in a physiological measure would not by itself establish a corresponding difference in daily function. Conversely, a registry entry without an observed difference cannot be inferred from the absence of numerical results.

General: A trial result is best understood through the estimated contrast between groups and its uncertainty, alongside the design, outcome definition, missing-data handling, and multiplicity plan. A sample-size planning calculation is not an outcome and does not show that an effect was detected. In this record, the stated planning framework does not provide the missing observed effect estimate. The most defensible conclusion is that the registry describes the intended study and recorded safety counts, while the trial's comparative efficacy results are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a well-defined research question and an interpretable reported result. The registry specifies the active and placebo stimulation groups, a shared physiotherapy component, a continuous physiological endpoint, and repeated assessments. Those details identify the intended contrast and the kind of evidence needed to answer it.

The endpoint's multiple assessment occasions make the analysis question important. A reader needs to know which time point or change contrast was emphasized, how repeated measurements were handled, and whether other outcomes were treated as secondary or exploratory. Without these details, it is difficult to understand what a single reported result would represent. In this record, the primary outcome is not reduced to one comparison and no analyses are listed.

The trial also illustrates why reporting estimates matters more than relying on completion status or a planning label. A completed study may have collected data, but inference requires transparent group summaries, effect estimates, uncertainty, and information about missing observations. The stated planning assumptions describe a framework for sample-size illustration; they do not establish the observed effect or its precision.

For biostatisticians and clinical researchers, the record emphasizes the value of linking a registry protocol to a complete results report. Clear outcome definitions, a prespecified analysis, participant flow, multiplicity handling, and safety details help readers distinguish confirmatory evidence from descriptive or exploratory findings. Here, the design and outcome intentions can be described, but the available registry information does not support a comparative statistical conclusion.

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.

A central limitation of interpretation is that numerical results are not reported in the registry record. There are no group-level primary outcome summaries, between-group estimates, uncertainty intervals, or hypothesis-test results. The same absence applies to the listed secondary outcomes. As a result, neither effect magnitude nor precision can be evaluated.

The record does not report the randomization procedure, allocation concealment, or the identities of the people masked. It gives the design labels but not enough detail to assess how those procedures were implemented. Baseline characteristics, participant flow, adherence, withdrawals, and the number analyzed at each time point are also not reported in the registry record.

The primary outcome spans baseline and follow-up assessments at the 4th and 12th weeks, but the specific analysis contrast is not reported. The record does not describe a multiplicity approach, missing-data method, or analysis population. Those gaps matter because they affect how repeated measures and incomplete follow-up should be interpreted.

Intervention descriptions are incomplete regarding the continuation of physiotherapy, and the record does not provide further details about treatment fidelity or whether the planned sessions were completed. The safety record reports no adverse events in the listed categories, but does not provide event definitions or detailed observation procedures. These limitations concern what can be evaluated from the registry entry; they do not establish that the trial lacked procedures or that unreported events occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Adjunct Low Frequency Repetitive Transcranial Magnetic Stimulation With Physiotherapy Enhance Upper Extremity Function Restoration — NCT02490371.
• Registry record last updated 2019-09-26; status last verified 2019-06.
• Results first posted 2019-09-26.
• 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 registry record describes a completed, randomized, double-masked, parallel trial enrolling 24 participants with stroke. It compared low frequency rTMS followed by structured physiotherapy upper limb training with placebo stimulation followed by the same described training. The primary outcome was motor evoked potential amplitude at the affected hand, assessed at baseline and at the 4th and 12th weeks. Several functional, impairment, and health-status outcomes were also listed.

The record reports 0 serious adverse events, 0 other adverse events, and 0 deaths in each group, with 12 participants at risk per group. It lists 6 outcome measures and 0 analyses. Numerical efficacy results and analysis details are not reported in the registry record, so the comparative effect and its precision cannot be assessed from the available information.