A Novel Approach for Brain Stimulation in Severe Stroke: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Novel Approach for Brain Stimulation in Severe Stroke (NCT03868410), a randomized early/phase 1 study. The primary outcome is Change in Upper Extremity Fugyl-Meyer Score (UEFM).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, single-masked, parallel-group study. It is classified as early phase 1 and lists an enrollment of 16. The study is marked completed. The record lists The Cleveland Clinic as sponsor. The start date is 2019-04-01 and the primary completion date is 2023-04-21.

Participants were assigned to one of two stimulation-and-training approaches. The cPMD arm used the new approach, while the iM1 arm used the conventional approach. The registry describes both as repetitive transcranial magnetic stimulation paired with upper-limb training. The planned intervention consisted of 12 visits over 6 weeks. The record does not identify which party or parties were masked.

The described study visits included eligibility screening and informed consent, an MRI visit, two testing visits involving motor function and neurophysiology, the intervention visits, repeat testing, repeat MRI testing, and a follow-up visit completed 3 months after the interventions. The primary outcome timeframe was change from baseline to post-test, described as an average of 6 weeks. This should be distinguished from the later follow-up visit: the posted primary outcome is not described as the 3-month follow-up result.

The registry enrollment and the outcome-specific arm counts are not identical in the posted record: the primary outcome lists 8 participants in the cPMD arm and 7 in the iM1 arm. The record does not explain the difference. The adverse-event entries list 8 participants at risk in each arm. These counts refer to different posted record entries and should not be treated as interchangeable.

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:

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.

Population: Adults with chronic (\>6 months) unilateral upper limb motor deficits post-stroke.

6. Primary Endpoint

The registry lists the primary outcome as Change in Upper Extremity Fugyl-Meyer Score (UEFM), measured over Change between Baseline and Post-Test (average 6 weeks).

The primary endpoint is change in Upper Extremity Fugl-Meyer (UEFM) score from baseline to post-test, with post-test described as occurring on average 6 weeks after baseline. The UEFM is an assessment of impairment after stroke. The registry describes a score range from 0-66: 0 means no movement of the paretic arm, and 66 means no functional limitation of the paretic arm. The posted endpoint is a change score, not a post-test score alone.

The registry record says the UEFM was selected as the primary outcome because it is widely used in stroke and was considered sensitive to effects of repetitive transcranial magnetic stimulation and rehabilitation. It also reports reliability, consistency, and validity information: ICC= 0.97 and Cronbach's α= 0.84, alongside the statement that the measure has excellent validity. These are properties of the assessment described in the record, not estimates of treatment effects from this trial.

The posted arm results give mean change scores and standard errors. Both arms have a mean change of 2.625. The standard errors are 0.498 for cPMD and 0.68 for iM1. These summaries describe the reported change scores and their precision; they do not, on their own, provide a formal estimate of the difference between arms.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The primary outcome is a continuous measure, and the registry reports the mean change from baseline to post-test for each arm. A mean summarizes the central level of the observed change scores within an arm. It does not show how every participant changed, whether changes were similar across participants, or how the scores were distributed. Here, both arm means are 2.625. That is a descriptive equality of the posted means, not a reported estimate of the treatment contrast with uncertainty.

General statistical explanation: a change score is calculated for each participant by comparing a later measurement with a baseline measurement, and a group mean summarizes those individual changes. The details of how the registry calculated or analyzed each participant’s score beyond its stated baseline-to-post-test timeframe are not reported in the registry record.

What does the standard error tell the reader?

The standard errors reported are 0.498 for cPMD and 0.68 for iM1. A standard error describes the precision of an estimated mean under the analysis assumptions; it is not the standard deviation of participant-level scores and does not describe the range of individual outcomes. A smaller standard error generally indicates a more precise estimate, but interpretation also depends on the analysis and sample size. The record does not provide confidence intervals or a detailed statistical model for these estimates.

General statistical explanation: a confidence interval combines an estimate with a measure of its uncertainty to give a range of values compatible with the data under stated assumptions. It is not the probability that a particular treatment effect is true. Since the registry record does not report confidence intervals for this primary outcome, no interval-based conclusion about the difference between arms can be drawn from the posted summaries alone.

How should the two arms be compared?

The main design question is whether average change differs between the cPMD and iM1 approaches. The registry presents each arm’s mean and standard error, but does not report the estimated between-arm difference, its standard error, a confidence interval, or a hypothesis-test result. Although the posted means are both 2.625, a formal comparison cannot be reconstructed from those values and arm-specific standard errors alone without additional information about the data and analysis. No recalculated comparison is reported for this continuous endpoint.

General statistical explanation: a randomized comparison is usually interpreted through an estimate of the contrast between assigned groups, together with uncertainty around that contrast. The estimate addresses the size and direction of the observed difference, while its uncertainty indicates how compatible the data are with a range of possible population differences. A p-value, if reported, would address a specific null hypothesis under specified assumptions; it would not measure clinical importance. None of these between-arm inferential results is reported in the registry record.

What is the role of over-dispersion?

General statistical explanation: over-dispersion refers to variability greater than a statistical model expects. It is especially relevant to count outcomes analyzed with models that assume a particular relationship between their mean and variance. The primary endpoint in this trial is a continuous change score, and the registry provides no model details that would establish whether over-dispersion was assessed or relevant. It is therefore not possible to say that an over-dispersion adjustment was used or needed.

What do the planning calculations represent?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It considers effects expressed as fractions of the observed effect and reports planning quantities as participants per arm for continuous outcomes. Those calculations are hypothetical design illustrations, not results observed in this trial and not observed power. Observed power is not an appropriate substitute for interpreting the estimated effect and its uncertainty.

General statistical explanation: a sample-size calculation depends on assumptions about the effect worth detecting, variability, allocation, and the chosen statistical error rate. If an assumed effect is based on a small study’s observed estimate, that estimate may be imprecise; planning values should therefore be read as conditional illustrations rather than as guarantees about a later study. The registry record does not report the trial’s own sample-size justification, so the planning illustration should not be mistaken for the original design rationale.

What analytical details are absent?

The registry record does not report the primary-outcome analysis model, any covariate adjustment, handling of missing values, the analysis population, or an inferential comparison of the arms. It also does not report whether interim analyses were conducted. These omissions limit reproducibility and make it difficult to assess how the summaries relate to the randomized groups. The record’s randomization and masking labels describe design features, but do not supply these missing analysis details.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("cPMD Repetitive Transcranial Magnetic Stimulation ", "iM1 Repetitive Transcranial Magnetic Stimulation (")
n   <- c(8, 7)
m   <- c(2.625, 2.625)
sp  <- c(0.498, 0.68)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  cPMD Repetitive Transcranial Magnetic Stimulation   8  2.625  1.409  1.447  3.803
CARM  iM1 Repetitive Transcranial Magnetic Stimulation (  7  2.625  1.799  0.961  4.289

11. Multiplicity, Missing Data and Analysis Populations

The study record lists secondary outcomes covering additional motor-function measures, stroke impact, functional imaging, motor evoked potentials, and diffusion tensor imaging. Results for those outcomes are not reported in the registry record summarized for this trial. The record reports no analyses (n analyses 0), so it does not establish which outcomes were analyzed, whether multiple comparisons were considered, or whether any multiplicity adjustment was used. The plan for handling multiplicity is not reported in the registry record.

When a study evaluates several outcomes or several comparisons, the chance of at least one apparently unusual result can increase if each is interpreted separately. General statistical explanation: multiplicity procedures can control a chosen error rate across a defined family of tests, but they require knowing which tests belong to that family and what procedure was planned. Neither the family of analyses nor an adjustment strategy is reported in the registry record. No claim about adjusted or unadjusted secondary-outcome findings can therefore be made.

The record does not describe missing-data methods, reasons for missing measurements, or whether participants without post-test measurements were included in any analysis. The primary outcome counts are 8 and 7, while overall enrollment is 16; the record does not explain this accounting. It also does not identify an intention-to-treat, per-protocol, or other analysis population. Those details are not reported in the registry record.

General statistical explanation: missing outcomes can affect both precision and the interpretation of a comparison, especially if the likelihood of missingness is related to outcomes or group assignment. A clear analysis-population definition and a transparent account of missing measurements help readers judge this risk. The posted summaries alone do not establish how missingness affected the results.

12. 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 registry adverse-event entries list 8 participants at risk in each arm. In the cPMD group, 0 participants are recorded as affected by serious adverse events, 2 as affected by other adverse events, and 0 deaths. In the iM1 group, the corresponding counts are also 0, 2, and 0. No serious adverse-event terms are listed.

These are counts in the registry record, not estimates of comparative risk. The entries do not describe the type, timing, duration, severity, or relationship of the other adverse events to the intervention. Definitions and collection procedures for the adverse-event categories are not reported in the registry record. The recorded denominator for each group is 8, which differs from the primary outcome count of 7 in the iM1 arm; the record does not explain that difference.

General statistical explanation: zero recorded serious events does not establish that an event cannot occur, particularly in a small study. Event counts are most informative when read alongside the number followed, the duration of follow-up, the event definitions, and the completeness of reporting. Those details are not all available in the registry record, so the entries should be read narrowly as the posted counts.

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

The posted primary result describes change in a stroke-related upper-limb impairment measure from baseline to post-test. The cPMD and iM1 arms each have a mean change of 2.625. Their reported standard errors are 0.498 and 0.68, respectively. These are the registry’s descriptive arm summaries for the primary endpoint.

The result does not establish that the two approaches have the same effect. Identical rounded arm means are not a formal equivalence or non-inferiority result, and the registry record reports no prespecified margin or inferential comparison. It also does not establish that one approach is better than the other. No between-arm effect estimate, confidence interval, or p-value is reported.

The posted result also cannot establish whether either approach is effective relative to no stimulation, training alone, or another treatment. Both trial arms included stimulation with upper-limb training, and the comparison was between stimulation targets and approaches. No untreated or training-only comparator is listed.

The record does not provide results for the listed secondary outcome domains, nor does it describe how missing measurements or the analysis population were handled. The small outcome-specific arm counts and absent inferential details make it important to distinguish the descriptive summaries from broader claims. The trial’s classification and enrollment appear in the registry, but the record does not supply the protocol rationale or analysis details needed to assess all design choices.

General statistical explanation: statistical uncertainty and clinical importance are different questions. A result may be estimated imprecisely or precisely, while its importance depends on context and an interpretable threshold. The registry describes the UEFM scale and its measurement properties but does not state a threshold for clinically meaningful change. No judgment about clinical importance can be made from the arm means alone.

14. Why This Trial Matters Statistically

This trial addresses a comparison that can be framed statistically with a randomized, parallel-group design: two different stimulation targets are paired with upper-limb training, and change in UEFM score is the primary outcome. Random assignment is a design feature intended to support a fair comparison between groups, while the parallel structure means participants are assigned to one approach rather than crossing between approaches.

The posted endpoint summaries are useful because they identify the measure, timeframe, arm-specific means, and standard errors. They also make clear what is not available for interpretation: a direct estimate of the difference between arms and its uncertainty. Reporting the contrast with an interval would allow readers to assess both the possible direction and precision of the comparison. The registry record does not report those results.

The trial also illustrates why outcome counts, enrollment, and adverse-event denominators should be read in context. Overall enrollment is 16, primary outcome counts are 8 and 7, and adverse-event entries list 8 at risk in each arm. These figures are not reconciled in the record. Transparent reporting of participant flow and analysis populations would help readers understand which participants contributed to each result.

Finally, the outcome program extends beyond the primary impairment measure to motor function, stroke impact, imaging, and neurophysiology. Those domains may describe different aspects of recovery or mechanism, but their results and multiplicity handling are not reported in the record. Statistically, the key distinction is between a clearly stated research question and the evidence needed to answer it: the posted means summarize observed arm changes, while the missing comparative analyses limit conclusions about the randomized contrast.

15. 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 outcome result is incomplete for evaluating the randomized comparison. The record provides a mean change and standard error in each arm, but no between-arm estimate, confidence interval, p-value, or analysis model. The reported means are both 2.625, but the registry record does not identify a formal test of whether the groups differ.

The outcome counts are 8 for cPMD and 7 for iM1, whereas overall enrollment is 16. The record does not explain the discrepancy or specify the analysis population. The adverse-event entries instead list 8 participants at risk in each arm. It is not possible to determine from the registry record whether these differences reflect missing endpoint data, record conventions, or another reason.

Details needed to assess the analysis are not reported in the registry record, including missing-data handling, covariate adjustment, interim analyses, multiplicity procedures, and the sample-size justification. The record also does not state who was masked. These gaps constrain assessment of potential bias and the reproducibility of the analysis.

The registry describes a study in stroke survivors with severe limitations in use of the affected upper limb, but further eligibility details are not reported in the record summarized for this trial. Generalizability beyond the described population cannot be evaluated from this information. Secondary outcome results are not reported, so the primary endpoint summaries do not describe the full set of measured domains.

Finally, the adverse-event entries give counts but little context about event definitions, types, timing, or follow-up completeness. The recorded counts are therefore a limited account of safety reporting, not a comprehensive characterization of adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Novel Approach for Brain Stimulation in Severe Stroke — NCT03868410.
• Registry record last updated 2025-06-05; status last verified 2025-05.
• Results first posted 2025-06-05.
• 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.

19. Record Summary

NCT03868410 is a completed, randomized, single-masked, parallel-group early phase 1 study sponsored by The Cleveland Clinic. It enrolled 16 participants and compared cPMD repetitive transcranial magnetic stimulation plus training, described as the new approach, with iM1 repetitive transcranial magnetic stimulation plus training, described as conventional.

The primary endpoint was change in UEFM score from baseline to post-test, with the timeframe described as an average of 6 weeks. The posted mean change was 2.625 in both arms; standard errors were 0.498 for cPMD and 0.68 for iM1. Outcome counts were 8 and 7. The registry record does not report a direct inferential comparison or explain the outcome-count difference.

Adverse-event entries list 0 serious events, 2 other adverse events, and 0 deaths in each arm. Further analysis details, including missing-data methods, analysis populations, and multiplicity procedures, are not reported in the registry record.