Effect of Simultaneous Dual Stimulation on Freezing of Gait in Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Simultaneous Dual Stimulation on Freezing of Gait in Parkinson's Disease (NCT02850159), a randomized na study. The primary outcome is Change of Freezing of Gait Questionnaire (FOG-Q).

2. Clinical Question

The registry describes a five-consecutive-day course and identifies the assessment points as T0, pre-NIBS at day 1, and T1, immediately after NIBS at day 5. The clinical question is therefore about the measured questionnaire outcome at the end of that course, not about longer-term outcomes. Follow-up beyond the day-5 assessment is not reported in the registry record.

The posted group means are 12.0 for the dual-mode group and 13.9 for the rTMS group. However, the endpoint description defines the outcome as a difference with a minimum score of -5 and a maximum score of 0. Those stated bounds do not align with the posted means. The record does not explain this inconsistency, so interpretation of the score scale and its direction requires caution.

3. Trial Design

The registry describes a randomized, double-masked, parallel-group trial. Participants were assigned to one of two groups: simultaneous high-frequency rTMS and active tDCS, or high-frequency rTMS with sham tDCS. The listed enrollment is 32, and the posted outcome data include 16 participants per group. The sponsor is Samsung Medical Center, and the study status is completed.

The study started in 2013-09, with primary completion in 2015-09. The phase is listed as NA. The registry does not report the randomization sequence method, allocation concealment procedures, which people were masked, how masking was maintained, or whether masking was assessed. The label “double” establishes the registry's masking classification but does not identify the masked roles.

The groups differ in whether tDCS was active or sham, while both received rTMS. The brief description specifies stimulation sites and modalities, but further implementation details, including device settings beyond the stated high frequency, session duration, and treatment adherence, are not reported in the registry record. The record also does not describe participant flow, withdrawals, exclusions, or the number analyzed for the primary outcome separately from enrollment.

One primary outcome measure is posted: change in FOG-Q score, assessed before stimulation at day 1 and immediately after stimulation at day 5. No secondary outcomes are posted, and the number of posted analyses is zero. Although group-level summary values and a comparison are available, the registry record does not describe a statistical analysis plan or identify an analysis population. The study's original sample-size justification and design assumptions 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.

Overall Study

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: 32 patients with Parkinson's disease

6. Primary Endpoint

The registry lists the primary outcome as Change of Freezing of Gait Questionnaire (FOG-Q), measured over Assessed at T0, pre-NIBS at day 1 and T1, immediately after NIBS at day 5.

The primary endpoint is titled “Change of Freezing of Gait Questionnaire (FOG-Q).” FOG-Q is described as a self-assessment scale for evaluating freezing-of-gait symptoms. The measure is intended to reflect how participants reported their symptoms after non-invasive brain stimulation (NIBS), compared with before stimulation. The assessments were at T0, pre-NIBS at day 1, and T1, immediately after NIBS at day 5, following five consecutive days of stimulation.

The record defines change as the FOG-Q after NIBS minus the FOG-Q before NIBS. It states a minimum score of -5 and a maximum score of 0, and says lower values represent a better outcome. In general, a change score can make the before-to-after contrast the outcome of interest; its meaning depends on the scale definition and direction.

There is an unresolved inconsistency in this record: the posted group means are 12.0 and 13.9, which do not fall within the stated -5 to 0 range for the defined change score. The record does not clarify whether the reported values refer to another score or reflect a difference in endpoint reporting. As a result, the numerical comparison can be described, but its clinical interpretation against the stated change-score scale is uncertain.

7. Results Posted in the Registry

• rTMS Group: mean 13.90 versus 12.00 on control; difference 1.90 (95% CI -1.53 to 5.33), standardized effect d = 0.38; z-test p = 0.278.

8. Statistical Interpretation

9. Statistical Methods Explained

For a continuous outcome, a group mean describes the average recorded value in that group. The standard deviation (SD) describes the spread of individual observations around that mean. The record reports means and SDs for each group: 12.0 with SD 5.0 in the dual-mode group, and 13.9 with SD 4.9 in the rTMS group. These summaries describe the posted values; they do not show the distribution of individual scores or establish how the analysis handled any missing observations.

What does the mean difference represent?

The reported mean difference is 1.9, calculated as the rTMS group mean minus the dual-mode group mean. A difference of zero would mean equal group means on the analyzed scale. Positive and negative differences indicate opposite directions of contrast, but what those directions mean clinically depends on the endpoint's scoring rules. The endpoint description says lower change values represent a better outcome, but the reported group means do not fit the stated minimum and maximum for the change score. The record does not clarify that inconsistency, so the numerical contrast should not be translated into a firm clinical direction.

What does the p-value say?

The unadjusted p-value is 0.278. In general, a p-value describes how unusual results at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The record does not give a detailed statistical plan or model for the comparison. The unadjusted value should therefore be interpreted as a limited summary, not as a complete account of the trial's analysis.

Why is the confidence interval useful?

The 95% confidence interval for the mean difference is -1.53 to 5.33. In general, a confidence interval presents a range of estimates compatible with the data under the calculation's assumptions. Its width conveys precision: wider intervals leave more uncertainty about the underlying contrast. Here, the interval includes zero and extends in both directions. That means the summary data do not pinpoint a single direction or a narrow range of possible differences.

What does the standard deviation add?

The SDs, 5.0 and 4.9, describe variability among the reported participant values within each group. Variation matters because the mean difference is estimated from groups whose individual values are not all identical. A relatively variable outcome can make a between-group estimate less precise, particularly when group sizes are limited. The record gives equal group sizes of 16, but does not supply individual observations, so the distributions, outliers, and shape of the data cannot be assessed from the summaries alone.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When a model underestimates variability, its standard errors can be too small and its intervals too narrow. This trial's primary endpoint is treated as continuous and summarized using means and SDs; the registry record does not report a model check or a finding of over-dispersion. It would not be appropriate to claim that over-dispersion occurred. The general issue is relevant because uncertainty estimates depend on assumptions about the data and analysis.

What is and is not documented?

The posted summaries permit a basic unadjusted comparison of the two group means. The registry record does not report the analysis population, any covariate adjustment, the treatment of missing observations, the distributional assumptions used for the primary analysis, or whether an analysis was prespecified. The count of posted analyses is zero. Without those details, readers cannot determine from the registry record whether the displayed contrast matches a prespecified sponsor analysis or how robust it is to alternative methods.

The calculations associated with the reported comparison are simple, unadjusted recalculations from the posted summary statistics. The discrepancy indicator is false, so there is no stated disagreement that would require a sponsor analysis to take precedence. This does not replace a missing statistical plan or supply details about the analysis actually conducted by the investigators.

10. Confidence Intervals and Precision

The estimated mean difference is 1.9, with a 95% confidence interval from -1.53 to 5.33. In general, a confidence interval communicates the uncertainty around an estimated contrast under the assumptions used to calculate it. It does not guarantee that the true value lies in the interval, nor does it describe the range of individual participant outcomes.

This interval includes zero, so the data are compatible with no difference in group means as well as with differences on either side of zero. The interval is wide enough that the point estimate should not be read as a precise account of the underlying contrast. The unadjusted p-value, 0.278, is consistent with the interval not isolating a single direction at the conventional two-sided 0.05 level stated for the planning illustration. A p-value does not replace consideration of the size and precision of the estimate.

Each group has 16 participants in the posted outcome summaries. Limited group sizes can contribute to uncertainty, although the registry record does not report a sample-size justification or the precision anticipated during trial planning. The SDs are 5.0 in the dual-mode group and 4.9 in the rTMS group, indicating variation in the recorded scores within both groups.

Precision is also difficult to interpret because the endpoint description defines change values from -5 to 0, whereas the posted means are 12.0 and 13.9. The record does not explain which scale these means represent. The confidence interval can be reported as a numerical contrast, but its interpretation against the stated endpoint scale remains uncertain.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial's original design justification. For this continuous-outcome comparison, the figures are participants per arm. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning effect is set to the stated fraction of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrated number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. These percentages describe design targets, not the probability that the observed result is true or that a treatment is effective.

For 100% of the observed effect, the illustration gives 107 participants per arm for 80% power and 143 for 90% power. For 75% of the observed effect, it gives 190 participants per arm for 80% power and 254 for 90% power. For 50% of the observed effect, it gives 427 participants per arm for 80% power and 571 for 90% power. The pattern reflects a general statistical principle: smaller effects are harder to distinguish from random variation and therefore require more participants under otherwise unchanged assumptions.

These are planning calculations, not observed power. They do not describe the chance that this completed trial's result is correct. They are also not evidence that the original investigators planned for these sample sizes or assumptions.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1.900; pooled standard deviation σ = 4.950.
2. n = 2 × (1.96 + 0.842)² × 4.950² / 1.900² = 106.6, rounded up to 107 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 1.9                      # observed difference in means
sigma <- 4.95025251881154                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2850159)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 107 (80% power), 143 (90% power)
 75% of observed effect: n per arm = 190 (80% power), 254 (90% power)
 50% of observed effect: n per arm = 427 (80% power), 571 (90% power)
power.t.test: 107.5 
Simulated power at n = 107 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcomes. It reports zero posted analyses. That means the registry record does not provide a set of analysis results from which to assess whether multiple comparisons were conducted or how any multiplicity was handled. The absence of posted secondary outcomes is not evidence that no other outcomes were collected or considered.

Multiplicity arises in general when several hypotheses or outcomes are tested; the more tests performed, the greater the chance of at least one apparently notable result by chance if all are interpreted without adjustment. The record does not report whether the investigators adjusted for multiple testing, identified one primary comparison in a protocol, or used a testing hierarchy. No adjustment should be inferred from the available entry.

Missing-data handling is also not reported in the registry record. Although enrollment and posted group sizes are 32 and 16 per group, respectively, the record does not explain whether every randomized participant contributed a primary outcome, how missing measurements were treated, or whether any participants were excluded from analysis. It also does not report withdrawals or reasons for missing values. The displayed group sizes alone do not establish an intention-to-treat analysis or another analysis population.

The analysis population is not reported in the registry record. There is no description of whether the comparison included all randomized participants, only participants who completed the intervention, or another defined subset. The record does not report covariate adjustment, a primary statistical model, sensitivity analyses, or methods for addressing protocol deviations. These omissions limit the ability to assess whether the comparison was prespecified and how sensitive it might be to analytic choices.

In general, a transparent analysis record helps readers distinguish planned tests from exploratory ones and understand how incomplete observations affect estimates. Those details are not available in the registry entry, so the posted mean comparison should be treated as an incomplete statistical record rather than a fully documented analysis pathway.

14. 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 registry reports zero serious adverse events among 16 participants at risk in the dual-mode group and zero among 16 at risk in the rTMS group. It also reports zero other adverse events among 16 at risk in each group, and zero deaths in both groups. No serious adverse-event terms are listed.

These figures are counts recorded for the study groups. A zero count in a registry entry means no events are reported in that category for the listed group; it does not establish that an event could not occur or that the intervention is free of risk. The record does not provide details about how adverse events were defined, how actively they were collected, the observation period for safety, or whether all participants had complete safety follow-up.

The figures should be read separately from the primary FOG-Q comparison. They do not clarify the inconsistency between the endpoint's stated score range and the posted means, and they do not resolve uncertainty about the analysis methods. The registry record provides no further safety narrative or listed serious-event descriptions.

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

The posted results describe a small, randomized comparison of simultaneous rTMS and tDCS against rTMS with sham tDCS, with 16 participants in each group. For the primary reported outcome, the means are 12.0 and 13.9, and the mean difference is 1.9. The 95% confidence interval, -1.53 to 5.33, includes zero, and the unadjusted p-value is 0.278. These summaries do not establish a clear between-group difference, but they also do not demonstrate that the groups are equivalent.

The result does not by itself show whether adding active tDCS improves or worsens the measured outcome. The endpoint description says lower change values are better, but the posted means do not fit the stated change-score range of -5 to 0. Without clarification, the score values cannot be confidently mapped to the described endpoint. The estimate and interval remain interpretable as reported numerical summaries, but their clinical direction is uncertain.

The result also does not answer questions about outcomes beyond the immediate day-5 assessment. The registry does not post secondary outcomes, longer-term follow-up, or a detailed analysis plan. The posted adverse-event counts are zero in the listed categories, but the safety collection and observation details are not reported. Those counts should not be taken as proof that no risks exist.

In general, a nonsignificant result is not evidence that an effect is exactly absent. The confidence interval conveys uncertainty about the range of compatible group differences, and the limited posted sample leaves room for meaningful differences in either direction. The trial record supports a cautious description of the reported comparison, not a definitive conclusion about efficacy, equivalence, or clinical benefit.

16. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to interpret an add-on intervention when both groups receive a shared treatment. Because both groups received high-frequency rTMS, while the dual-mode group also received active tDCS and the comparison group received sham tDCS, the intended contrast isolates the difference between those assigned stimulation strategies more closely than a comparison against no stimulation would. The interpretation still depends on adequate randomization, masking, adherence, and analysis; the registry record does not provide detailed information on those procedures.

The posted result also illustrates why the estimate, confidence interval, and p-value should be considered together. The mean difference is 1.9, but its 95% confidence interval extends from -1.53 to 5.33 and the unadjusted p-value is 0.278. The interval communicates substantial uncertainty about the direction and size of the contrast. A single p-value cannot convey that range or determine whether any difference would be important to participants.

Another statistical issue is the consistency of endpoint definitions and reported summaries. The record describes a change score bounded from -5 to 0, yet reports group means of 12.0 and 13.9. This mismatch makes it difficult to connect the numerical comparison to the intended meaning of the outcome. Clear outcome definitions and aligned reporting are essential for reproducible interpretation.

Finally, the record shows how planning illustrations differ from the design choices of a completed trial. The planning figures use the observed effect and stated assumptions, while the original sample-size rationale is not reported. These planning calculations can illustrate how detectable effects relate to sample size, but they cannot establish what the investigators expected or planned before enrollment.

17. 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 most direct limitation in the registry record is the mismatch between the endpoint definition and the posted means. The outcome is described as a change score with minimum -5 and maximum 0, while the group means are 12.0 and 13.9. No explanation is given, so it is unclear how the reported values correspond to the stated measure or its direction. This limits clinical interpretation of the numerical contrast.

The trial enrolled 32 participants, with 16 in each group. The registry does not report an original sample-size justification, so the adequacy of the planned enrollment for a clinically meaningful difference cannot be assessed from the record. The confidence interval for the mean difference extends from -1.53 to 5.33, reflecting uncertainty in the group contrast.

The record does not report participant characteristics beyond the condition, detailed eligibility criteria, withdrawals, adherence, missing-data handling, or the analysis population. It also does not describe the randomization method, allocation concealment, who was masked, or whether masking was maintained. These omissions make it harder to evaluate the conduct of the trial and the possible influence of missing observations or deviations.

Only one outcome is posted, with zero analyses reported and no secondary outcomes. A detailed statistical plan, covariate adjustment, sensitivity analyses, and multiplicity approach are not reported. The primary assessment is immediately after the day-5 intervention; longer-term outcomes are not listed. Safety figures are limited to counts, without definitions or collection details. Together, these features constrain what can be concluded from the registry entry.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effect of Simultaneous Dual Stimulation on Freezing of Gait in Parkinson's Disease — NCT02850159.
• Registry record last updated 2024-05-07; status last verified 2024-04.
• Results first posted 2017-07-02.
• 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.

21. Record Summary

NCT02850159 is a completed, randomized, double-masked, parallel-group study sponsored by Samsung Medical Center. It enrolled 32 participants with Parkinson's disease and freezing of gait. The comparison was simultaneous high-frequency rTMS and anodal tDCS versus high-frequency rTMS with sham tDCS. The study started in 2013-09 and reached primary completion in 2015-09.

The primary outcome was change in FOG-Q score, measured before stimulation at day 1 and immediately after five consecutive days of stimulation at day 5. The posted means are 12.0 in the dual-mode group and 13.9 in the rTMS group, with a mean difference of 1.9, a 95% confidence interval of -1.53 to 5.33, and an unadjusted p-value of 0.278. The means do not align with the endpoint description's stated range of -5 to 0, and the record does not explain why.

No secondary outcomes or analyses are posted. The registry reports zero serious adverse events, zero other adverse events, and zero deaths in each group. Further statistical-plan, missing-data, analysis-population, and safety-collection details are not reported in the registry record.