Synchronized Transcranial Magnetic Stimulation for PTSD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Synchronized Transcranial Magnetic Stimulation for PTSD (NCT02981381), a randomized na study. The primary outcome is PCL-5 Total Score Change.

2. Clinical Question

This is a question about a between-group difference in symptom-score change, not simply whether scores changed within either group. A randomized sham-controlled comparison is intended to distinguish the outcomes observed under assignment to active treatment from those observed under assignment to a sham procedure. The registry describes the study as a pilot and states that investigators hypothesized sTMS would be effective for PTSD and mood symptoms. That statement is the study rationale, not evidence about the results. The posted primary result is imprecise: its confidence interval includes both negative and positive values, so it is compatible with effects in either direction under the reported comparison. The registry record does not report a separate result for mood symptoms among the posted outcome measures.

3. Trial Design

NCT02981381 is recorded as a completed, randomized, parallel-group study with quadruple masking. The registry lists Providence VA Medical Center as sponsor and describes the study as a small, two-site, sham-controlled pilot. Enrollment is recorded as 23. The recorded start date is 2016-10-13, primary completion date is 2018-10-26, and study status is COMPLETED. The registry lists phase as NA.

The posted primary outcome results include 10 participants in the active sTMS arm and 13 in the sham sTMS arm. These are the arm-level counts attached to the reported outcome and should not be treated as a description of all safety denominators or of every analysis population. The arm descriptions specify 20 treatments of 30 minutes over 40 calendar days for both active and sham assignment. They also describe treatment windows and serial assessments every 5 sessions. The active-arm description is truncated in the registry record after the start of its serial-assessment wording, so further details are not available there.

The intervention list includes NEST-1, SHAM, and NEST-2, while the posted arm descriptions and primary comparison concern active sTMS (NEST-1) and sham sTMS (SHAM). The registry record does not explain the role of NEST-2 in the posted results. Although the masking level is recorded as quadruple, the identities of the masked parties and the procedures used to maintain masking are not reported in the registry record. Detailed eligibility criteria, recruitment methods, allocation procedures, and the original statistical design assumptions are also not reported in the registry record.

The primary endpoint is described as occurring 1 month after the final treatment, approximately 70 days total. Participants without a completed PT1 assessment were to have their last observation carried forward, according to the outcome description. The registry records one outcome measure and no analyses. This means the posted summary offers a limited account of the trial’s analysis, rather than a full report of all protocol procedures or statistical decisions.

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.

Double Blind Phase

Optional Unblinded sTMS

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 PCL-5 Total Score Change, measured over 1 month after final treatment (approximately 70 days total).

The primary endpoint is PCL-5 total score change from baseline to endpoint, compared between active sTMS and sham. The PCL-5 is a 20-item self-report measure of the presence and severity of PTSD symptoms. Its total score ranges from 0 to 80, and higher scores indicate greater symptom severity. The registry notes that a score greater than 33 is typically used to indicate severity sufficient for a PTSD diagnosis. The endpoint is reported in units on the PCL-5 scale.

A symptom scale provides a quantitative way to compare participants’ reported symptom severity over time. In this study, the intended comparison is the difference in change between the randomized groups. That is distinct from asking whether one group’s score changed from baseline by itself: the sham group provides the comparison for the active group. The registry’s outcome description also defines a 50% reduction from baseline to PT1 as a clinical response and defines remission as a post-treatment score below the threshold score published for the PCL-5. However, the posted results contain no separate response or remission results.

The stated assessment point is 1 month after the final treatment, approximately 70 days total. If a participant did not complete PT1, last observation carried forward (LOCF) was specified. The registry record does not report additional details about how the change score was calculated or how the outcome was handled in analyses beyond that description.

7. Results Posted in the Registry

• Active sTMS (NEST-1): mean 50.10 versus 49.20 on control; difference 0.90 (95% CI -5.93 to 7.73), standardized effect d = 0.11; z-test p = 0.796.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the posted comparison is expressed as a difference between group means. General statistical context helps explain what that estimate, its uncertainty, and the accompanying p-value convey. The registry record does not report a complete statistical analysis plan, so the explanations below distinguish general interpretation from methods specifically documented for this study.

What does a mean difference represent?

For a continuous outcome, a group mean is the arithmetic average of participants’ scores in that group. A mean difference compares the averages between groups. The registry reports the active-versus-sham difference as 0.9. The corresponding arm means are 50.1 for active sTMS and 49.2 for sham. The posted comparison is therefore a contrast between group summaries, rather than a count of participants who improved. Because the outcome is change in score, its sign depends on the change-score convention; that convention is not reported in the registry record.

General explanation: a mean difference is useful because it remains in the outcome’s original units, making it possible to relate the estimate to the PCL-5 scale. A standardized difference expresses a contrast relative to variability and is unitless. The posted standardized difference is 0.105, alongside a pooled standard deviation of 8.538. Standardization can help describe relative magnitude, but it does not establish clinical importance. The registry record does not report a threshold for a meaningful between-group difference.

What do standard deviations describe?

The standard deviation summarizes how dispersed participant scores are around a group mean. The posted standard deviations are 7.4 in the active group and 9.3 in the sham group. A larger standard deviation indicates more spread around that group’s mean; it does not show whether the spread is caused by distinct subgroups or by any particular pattern. Standard deviations are not confidence intervals, and they do not show the precision of the estimated mean difference on their own.

General explanation: continuous measures can have distributions that are asymmetric or contain unusually extreme values. A mean and standard deviation are most informative when considered alongside the underlying distribution, which is not described in the registry record. No participant-level outcome data or distributional diagnostics are reported.

How should the p-value be read?

The registry reports an unadjusted p-value of 0.796. General explanation: a p-value measures how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of an effect. The registry record does not identify the test used to obtain this p-value, the exact null hypothesis formulation, or whether any model adjustments were considered. The label unadjusted indicates that the posted value is not described as adjusted for multiple comparisons.

A large p-value does not prove that groups are equivalent. When the amount of information is limited, estimates can remain uncertain even if the observed difference is near zero. That is why the confidence interval is important alongside the p-value: it shows a range of values compatible with the estimate under the method used. The interval for this comparison includes values below and above zero.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when data vary more than a statistical model expects. It is especially relevant to count outcomes, where assuming too little variability can make standard errors too small and confidence intervals too narrow. The primary endpoint is continuous rather than a count, and the registry does not report an over-dispersion analysis. More generally, statistical models should represent the variability and distribution of the outcome appropriately; the registry record does not provide enough detail to evaluate model diagnostics or assumptions.

What analysis details are documented?

The registry describes the outcome as a comparison of change from baseline to endpoint between active treatment and sham. It specifies LOCF if a participant does not complete PT1. The posted result includes group means, standard deviations, a mean difference, a confidence interval, and an unadjusted p-value. The record lists zero analyses and does not report the statistical test or model, covariates, analysis population, handling of other missing observations, or prespecified multiplicity procedure. Those details should not be inferred from the summary statistics. The posted numbers support a descriptive reading of the reported contrast, but they do not reveal all analytic decisions behind it.

10. Confidence Intervals and Precision

The 95% confidence interval for the active-versus-sham mean difference extends from -5.926 to 7.726, around the reported estimate of 0.9. General explanation: a confidence interval describes the uncertainty in an estimated effect under a specified statistical method. It is not a range that contains 95% of individual participant scores, and it is not a probability statement about the particular true value after the data have been observed.

The interval includes zero, as well as values on either side of zero. This means the posted results are compatible with no mean difference and with nonzero differences in both directions, subject to the analysis assumptions. Since the registry does not specify the direction used to calculate change scores, the negative and positive sides should not be translated into improvement or worsening. The interval’s breadth indicates that the estimate is not highly precise. It does not support a firm conclusion that the groups are equivalent or that meaningful differences are ruled out.

The reported standard deviations are 7.4 for active sTMS and 9.3 for sham, and the pooled standard deviation is 8.538. These values provide context about variability in the outcome, but they do not replace the confidence interval for the between-group estimate. The primary result includes 10 active-arm participants and 13 sham-arm participants. With a limited amount of outcome information, uncertainty can remain substantial; the posted interval is the direct summary of that uncertainty.

General explanation: confidence intervals depend on the method used and the assumptions behind it. The registry record does not identify the interval calculation method or report model diagnostics. The interval should therefore be interpreted as the uncertainty measure posted for the comparison, not as a complete account of every possible source of uncertainty, including missing data, selection, or measurement issues.

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 planning figures are illustrative, not a record of the study’s original design target. They are expressed as participants per arm, not as total events. The calculation assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The registry record does not report the trial’s original sample-size assumptions or justification.

For planning at 100% of the observed effect, the figures are 1,413 participants per arm for 80% power and 1,892 participants per arm for 90% power. At 75% of the observed effect, they are 2,512 participants per arm for 80% power and 3,362 participants per arm for 90% power. At 50% of the observed effect, they are 5,651 participants per arm for 80% power and 7,565 participants per arm for 90% power.

In plain terms, 80% power means that, under the planning assumptions and if the chosen effect were the true effect, the design would have an 80% chance of detecting a difference at the specified significance level. The 90% column describes the corresponding chance under that planning scenario. Higher power requires more information, and smaller effects require more participants to distinguish them from random variation. These figures are not observed power; they are prospective planning illustrations based on the observed effect, not measurements of the study’s success or a substitute for its confidence interval.

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 = 0.900; pooled standard deviation σ = 8.538.
2. n = 2 × (1.96 + 0.842)² × 8.538² / 0.900² = 1,412.6, rounded up to 1,413 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 <- 0.899999999999999                      # observed difference in means
sigma <- 8.53764771886429                     # 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(2981381)
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 = 1,413 (80% power), 1,892 (90% power)
 75% of observed effect: n per arm = 2,512 (80% power), 3,362 (90% power)
 50% of observed effect: n per arm = 5,651 (80% power), 7,565 (90% power)
power.t.test: 1413.6 
Simulated power at n = 1,413 per arm: 0.790 (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 outcome measure and zero analyses, with the PCL-5 total score change identified as the primary outcome. It does not report posted secondary outcome results. The outcome description mentions clinical response and remission definitions, but no corresponding response or remission results appear in the record. The registry also lists depression as a condition and refers to comorbid depressive symptoms in the official title, yet a separate depression outcome result is not reported.

Multiplicity arises when investigators make several statistical comparisons or test multiple outcomes. General explanation: as the number of tests grows, the chance of at least one apparently unusual result can increase if each test is judged separately. A prespecified strategy can address this issue, for example by defining a primary comparison or adjusting inference across tests. The registry record does not report a multiplicity strategy. The posted p-value is labelled unadjusted, so it should not be read as a value corrected for a family of comparisons.

The outcome description specifies LOCF for a participant who does not complete PT1. General explanation: LOCF replaces a missing endpoint with that participant’s last recorded observation. This approach can be problematic if symptoms would have changed after the last observed measurement, because the carried-forward value may not represent the missing endpoint. The record does not report how many participants had missing PT1 assessments, whether LOCF was used, or any sensitivity analysis testing alternative missing-data assumptions. It also does not report other missing-data procedures.

The registry record does not identify the analysis population, such as whether the primary analysis included all randomized participants or only participants with observed outcomes. It does not report whether results were adjusted for baseline score or other variables. These gaps limit the ability to assess how missingness, exclusions, or analytic choices may have affected the posted estimate. They do not change the numerical result that is recorded, but they leave important aspects of its interpretation unresolved.

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 5% reporting threshold.

The registry reports serious adverse events for 0 of 7 participants at risk in the active sTMS group and 0 of 12 participants at risk in the sham group. Deaths are reported as 0 in both groups. These are the serious-adverse-event figures posted for the listed at-risk groups; their denominators differ from the participant counts attached to the primary outcome results.

General explanation: a report of zero events means no events of that category were recorded in the stated group and risk set. It does not establish that the event is impossible or that risk is absent. With limited observations, an event may not occur even if it could occur in a larger group or with longer follow-up. The figures also do not describe non-serious adverse events: the registry lists 0 other adverse events among 7 at risk in the active group and 0 among 12 at risk in the sham group, but details about event collection and follow-up are not reported in the registry record.

No serious adverse-event terms are listed. The record does not explain the difference between the safety denominators and the outcome counts, nor does it provide further timing or severity details. These figures describe the registry’s posted safety counts and should not be treated as a complete assessment of safety.

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

The result does not establish a clear difference in mean PCL-5 score change between active sTMS and sham. The estimate is 0.9, the 95% confidence interval runs from -5.926 to 7.726, and the unadjusted p-value is 0.796. The interval includes zero and allows for differences in either direction. The result is therefore uncertain rather than evidence of equivalence or proof that there is no effect.

The registry record describes a randomized, sham-controlled pilot study involving people with PTSD and comorbid depression. The posted primary outcome concerns PCL-5 change from baseline to an endpoint approximately 1 month after final treatment. It does not provide a separate posted result for depressive symptoms, nor does it report response or remission counts. The primary comparison alone cannot answer broader questions about mood outcomes, longer-term outcomes, or effects in populations not described in the record.

The positive mean difference should not be called an improvement or worsening because the record does not state the subtraction order used to calculate score change. The PCL-5 itself has higher scores indicating greater symptom severity, but that fact does not resolve the direction of a difference in change scores. The reported group means and standard deviations likewise do not reveal how individual participants’ scores changed.

Interpretation is constrained by the small pilot context, the limited outcome counts, the broad confidence interval, and missing detail about the statistical test, analysis population, missing data, and multiplicity. These limitations do not invalidate the posted estimate, but they affect how much can be concluded from it. The result is best understood as an imprecise estimate from the reported primary comparison, not as a definitive answer about treatment effects or clinical benefit.

16. Why This Trial Matters Statistically

This trial illustrates why effect estimates and uncertainty should be read together. The mean difference of 0.9 is only one part of the result; its confidence interval from -5.926 to 7.726 shows that the estimate is not precise enough to rule out differences in either direction. The unadjusted p-value of 0.796 does not make the interval or the size of the estimate irrelevant, and it does not demonstrate equivalence.

The randomized, sham-controlled design creates a direct group comparison, but the pilot scale limits the amount of information available for that comparison. The distinction between a pilot result and a definitive estimate matters: a broad interval can reflect limited precision even when a point estimate is near zero. The posted figures also show why a planning calculation based on an observed effect should be treated cautiously. The planning illustrations change substantially when the target is a smaller fraction of that effect, emphasizing the information demands of detecting modest differences.

Missing analysis details are statistically important as well. The registry specifies LOCF for incomplete PT1 assessments but does not report whether it was used, how many assessments were missing, the analysis population, the test or model, or a multiplicity plan. These details affect how readers evaluate the estimate and its uncertainty. Their absence should prompt restraint rather than assumptions about the methods.

Finally, safety counts and outcome counts refer to different recorded denominators. Treating them as interchangeable would obscure what each result describes. Reading denominators, endpoint definitions, effect estimates, and uncertainty together is essential for a sound interpretation of this pilot record.

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.

Several limitations specific to this record constrain interpretation. The study is described as a small, two-site pilot, and the primary outcome comparison includes 10 active-arm participants and 13 sham-arm participants. The confidence interval is broad, leaving uncertainty about the size and direction of the difference. The registry provides no participant-level data or outcome distributions, so the group means cannot show individual response patterns or reveal whether a few observations strongly influenced the averages.

The primary outcome is described as change in PCL-5 total score, but the direction used to calculate change is not stated. As a result, the positive estimate cannot be translated into improvement or worsening. The record defines response and remission but posts no results for either. It also does not report a separate outcome result for depressive symptoms, despite the comorbid depression focus in the study title and summary.

The record specifies LOCF for incomplete PT1 assessments but does not state whether any participants needed it, how many endpoint assessments were missing, or whether alternative missing-data analyses were conducted. The test or model, analysis population, covariate adjustment, and multiplicity procedures are not reported. Safety denominators differ from the primary outcome counts, and the record does not explain that difference. The active-arm description is truncated, and the role of the listed NEST-2 intervention in the posted results is not explained.

These limitations concern the scope and interpretability of the registry record. They do not support assumptions about unreported procedures or results. The posted estimate should be read as the available primary comparison, with these uncertainties kept in view.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Synchronized Transcranial Magnetic Stimulation for PTSD — NCT02981381.
• Registry record last updated 2025-06-17; status last verified 2025-05.
• Results first posted 2025-06-17.
• 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

NCT02981381 is a completed randomized, quadruple-masked, parallel-group pilot study sponsored by Providence VA Medical Center. The registry describes a two-site, sham-controlled study of synchronized TMS for PTSD with comorbid depression. The primary endpoint is PCL-5 total score change from baseline to approximately 1 month after final treatment.

The posted active-versus-sham mean difference is 0.9, with a 95% confidence interval from -5.926 to 7.726 and an unadjusted p-value of 0.796. The interval includes zero and is broad, so the result is imprecise and does not establish a clear between-group difference. The registry specifies LOCF for incomplete endpoint assessments but does not report whether it was used or provide further analysis details. Serious adverse events and deaths are recorded as zero in the listed safety groups.