rTMS for the Treatment of Chronic Pain in GW1 Veterans: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for rTMS for the Treatment of Chronic Pain in GW1 Veterans (NCT01608321), a randomized phase 3 study. The primary outcome is Change in the Brief Pain Inventory (Short Form) Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, triple-masked, parallel-group trial sponsored by the VA Office of Research and Development. It compared the device intervention rTMS with a sham device intervention. The registry describes 20 sessions in each arm, delivered by trained medical personnel. It does not report the details of sequence generation, allocation concealment, the masking procedures, or how the sham experience was matched to active treatment.

The trial concerned chronic pain in Veterans from the first Gulf War. Enrollment was 17. The registry lists a primary completion date of 2015-06 and a study start date of 2012-09. Its status is terminated; the reason for termination is not reported in the registry record. The record does not explain whether termination affected recruitment, follow-up, or the planned analyses.

The primary outcome was change in the BPI Short Form score, comparing baseline with end-of-treatment assessment at 3-4 weeks. The registry lists 11 participants in the rTMS outcome group and 4 in the sham rTMS outcome group. It also notes that a patient whose baseline pain scale score was 0 did not meet entry criteria and was excluded from the analysis. The record does not describe the outcome status or analysis handling of any other participants who may not appear in the group summaries.

The registry lists one outcome measure and no posted secondary outcomes. It lists no analyses. Descriptive group summaries are nevertheless available for the primary outcome, while a formal between-group analysis is not. Details such as a statistical analysis plan, the intended handling of missing observations, and a sample-size justification 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One patient did not meet study entry criteria at baseline (pain scale score = 0), so was not included in the analysis

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 in the Brief Pain Inventory (Short Form) Score, measured over Comparison of baseline BPI and end-of-treatment BPI (time 3-4 weeks).

The primary endpoint was change in the Brief Pain Inventory Short Form score, expressed as a mean and standard deviation in units on a scale. The registry describes the BPI as a widely used measure of clinical pain. It asks patients to rate pain severity and the degree to which pain interferes with common dimensions of feeling and function. Its basic pain scale ranges from 0, no pain, to 10, the worst pain imaginable.

Using change from baseline focuses the outcome on how a participant’s reported score differs between the starting assessment and the end-of-treatment assessment. A mean summarizes the group’s average change, while a standard deviation describes how dispersed individual changes are around that average. These summaries answer different questions: the mean describes the group’s central tendency, and the standard deviation describes variability among the observed scores.

The stated timeframe was comparison of baseline BPI with end-of-treatment BPI at 3-4 weeks. The registry does not report additional follow-up outcomes for this measure. The posted group means are -1.2 for rTMS and -0.9 for sham rTMS. Because lower BPI pain scores represent less reported pain on the stated scale, a negative change indicates a decrease in the score from baseline on average. These group summaries alone do not give the uncertainty around a difference between groups or establish whether any such difference is compatible with chance variation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the group summaries describe?

The primary outcome is continuous: it is a score measured on a scale, and the registry reports mean change with standard deviation. A mean gives the average change among the participants included in a group summary. A standard deviation describes how spread out individual observations are around that group mean. Neither statistic, on its own, measures how precisely the mean or a between-group contrast is estimated.

The rTMS group’s posted mean change is -1.2 with a standard deviation of 1.5. The sham rTMS group’s posted mean change is -0.9 with a standard deviation of 1.6. These figures describe changes within each group. The question of comparative effect concerns the difference between those group changes. The registry says that values are missing or not estimable for a two-arm comparison of this continuous endpoint, and it lists no analyses. No inferential comparison is reported.

Why is a between-group estimate needed?

In a randomized parallel-group trial, the treatment comparison is generally expressed as a contrast between outcomes in the randomized groups. For a change-score endpoint, that contrast concerns the groups’ changes, rather than interpreting either group’s change as the treatment effect by itself. A group can improve on average for reasons that are not uniquely attributable to the assigned intervention; the sham group provides a concurrent reference for interpreting change. This is a general explanation of comparative trial analysis, not a claim about why either group changed in this study.

A contrast is usually interpreted together with an uncertainty interval and, where reported, a test statistic or p value. A confidence interval gives a range of values compatible with the data and the analysis assumptions at its stated confidence level. Its width conveys precision: a wider interval indicates less precise estimation than a narrower one. A p value, when reported, describes how compatible the data are with a specified null model; it is not a measure of the probability that a treatment works. No comparative confidence interval or p value is reported in the registry record.

What does the standard deviation not tell us?

The standard deviation describes dispersion of participant-level observations within a group. It is not the standard error of the group mean, and it is not a confidence interval for a treatment effect. The standard error depends on both variability and the amount of information available. A comparison also depends on the group sizes and the chosen analysis. Although the record lists group sizes and standard deviations, a comparative estimate is not reported as estimable. The posted record does not supply enough documented analysis detail to explain that status or reproduce a sponsor analysis.

Normal-theory methods for means often rely on assumptions about the distribution of observations or the sampling distribution of the estimate. With small groups, these assumptions and the influence of individual observations can be consequential. This is a general caution about continuous-outcome analysis, not evidence that the assumptions were violated in this trial. The registry does not report diagnostic checks, an alternative distributional method, or participant-level scores.

How should the planning illustration be understood?

A sample-size calculation is a planning exercise: it describes how much information a hypothetical study might need under stated assumptions to detect a chosen effect with a chosen error rate and power. It is not an estimate of what happened in the completed trial and is not “observed power.” The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as a stated fraction of the observed effect. The record does not give a sample-size justification from the trial’s own design. The numerical planning results are not reported in the registry record, so no participant target for a planning scenario can be stated from the registry information.

In general, planning for a fraction of an observed effect asks what hypothetical sample size would be needed if the effect of interest were smaller than the observed estimate. Such illustrations depend on the effect used, variability, allocation, and statistical assumptions. They should not be mistaken for a formal power analysis conducted before this trial. When an observed effect is uncertain, planning directly from it can also carry uncertainty into the illustration. These are general statistical considerations; the registry does not describe whether or how these considerations informed the trial design.

What does the lack of a reported analysis mean?

The record has descriptive endpoint summaries but lists no analyses. It does not report an analysis model, covariate adjustment, method for comparing changes, or standard error for a treatment contrast. It also does not say whether the analysis was prespecified, whether any interim analysis occurred, or how the reported summaries relate to an intended statistical plan. Those details are not reported in the registry record and should not be inferred from the trial’s randomized design or from the descriptive results alone.

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("rTMS", "Sham rTMS")
n   <- c(11, 4)
m   <- c(-1.2, -0.9)
sp  <- c(1.5, 1.6)
sd  <- sp      # posted standard deviations
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  rTMS  11  -1.200  1.500  -2.208  -0.192
CARM  Sham rTMS  4  -0.900  1.600  -3.446  1.646

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted secondary outcomes. That limits the number of registered outcome summaries available for interpretation, but it does not by itself establish how many analyses were planned or conducted. No analysis is listed in the registry, and the record does not describe an adjustment for multiple comparisons, a testing hierarchy, or a statistical analysis plan. Whether multiplicity was considered is not reported in the registry record.

The endpoint population note says a patient with a baseline pain scale score of 0 did not meet study entry criteria and was not included in the analysis. The endpoint summaries list 11 participants for rTMS and 4 for sham rTMS. The record does not explain whether other participants lacked an end-of-treatment assessment, were excluded for another reason, or were otherwise absent from these summaries. It also does not report how missing outcome data were handled.

For a continuous endpoint, missing observations can affect both the estimated group means and the precision of a comparison. Common approaches make different assumptions about why data are missing and how missing values relate to observed scores. This is a general statistical point; the registry does not identify an approach used in this trial. It does not report a sensitivity analysis or an assessment of the robustness of results to missingness.

The registry does not provide a complete description of the analysis population, such as whether the reported summaries include all randomized participants who met entry criteria or another defined set. The distinction between enrolled participants, eligible participants, and participants contributing endpoint data is important for interpreting randomized trials. The available record does not fully account for those populations.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyperglycemia (7.7%).

The registry reports serious adverse event figures for 13 participants at risk in the rTMS group, with 1 affected, and 4 at risk in the sham rTMS group, with 0 affected. It reports other adverse event figures for 13 at risk in the rTMS group, with 2 affected, and 4 at risk in the sham rTMS group, with 0 affected. These are registry counts, not a comparative statistical analysis. The record does not provide confidence intervals or a test of between-group safety differences.

Hyperglycemia is listed among the top serious adverse event terms, at 7.7%. The registry information does not establish from that listing alone whether the event was caused by treatment. The record does not report deaths for these groups. A blank or null death entry should not be interpreted as confirmation that no deaths occurred; death data are not reported in the registry record.

Safety figures require attention to the group at risk, the event definition, and the period during which events were collected. The registry does not provide further detail about event collection, severity grading beyond the serious-event category, relatedness assessment, or follow-up duration for adverse events. The counts therefore describe what is posted but do not establish comparative safety or causal attribution.

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

The posted results show descriptive mean decreases in BPI score in both the rTMS and sham rTMS groups over the stated baseline-to-end-of-treatment period. The mean change was -1.2 for rTMS and -0.9 for sham rTMS. The standard deviations were 1.5 and 1.6, respectively. These figures characterize the observed group summaries; they do not establish the size, direction, or precision of a formal between-group treatment effect.

The results do not show whether the group contrast is statistically distinguishable from no difference. No comparative confidence interval, p value, or analysis estimate is reported in the registry record. Without those, the precision of a comparative result cannot be evaluated. The record explicitly identifies the two-arm continuous-outcome comparison as missing or not estimable, and it lists no analyses.

The mean changes also do not establish how individual participants experienced pain or interference. Group averages can conceal variation among participants, and standard deviations do not reveal the distribution of individual responses. Participant-level results and further distributional summaries are not reported in the registry record.

The record describes a randomized, triple-masked design, but design features do not substitute for a reported analysis. The registry does not provide enough information to establish how the endpoint was analyzed, which participants were included in each analysis, or how missing observations were handled. Nor does the terminated status explain why the study ended or what effect termination had on the results. Those matters are not reported in the registry record.

Accordingly, these data are best read as limited descriptive outcome and adverse-event information from a small trial record, not as a definitive estimate of the comparative effect of rTMS versus sham rTMS. This interpretation does not imply that either intervention is effective or ineffective. It describes the scope and precision of the results available in the registry.

14. Why This Trial Matters Statistically

This trial illustrates the difference between a randomized design and a fully reported statistical comparison. Randomization is intended to support fair comparisons between assigned groups, while masking can reduce some forms of bias. But readers still need a clearly reported treatment-effect estimate and its uncertainty to interpret the primary outcome comparatively. The registry identifies the design as randomized and triple-masked, yet lists no analysis and no estimable two-arm comparison for the continuous endpoint.

The posted results also show why group means alone are not enough. Each mean describes average change within a group, but the scientific comparison concerns the difference between those changes. Without a reported contrast and uncertainty interval, readers cannot judge how precisely the groups differ or whether the data are compatible with a range of possible comparative effects.

The outcome population is another central statistical issue. Enrollment is 17, while the outcome groups are listed as 11 and 4, and the registry notes an exclusion for failure to meet entry criteria because the baseline pain score was 0. The record does not fully explain how the enrolled population relates to the endpoint summaries. Clear accounting of eligibility, randomization, follow-up, and analysis populations is essential for evaluating what the results represent.

Finally, a terminated study with no posted analysis demonstrates the limits of registry summaries. The descriptive outcome and safety counts remain informative about what was recorded, but they cannot fill gaps in the statistical plan, missing-data handling, or comparative inference. These are general lessons in reading trial results; they do not establish why this trial was terminated or how its investigators approached analysis.

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 main limitation for statistical interpretation is the absence of a reported between-group analysis for the primary continuous endpoint. The registry provides group means and standard deviations but no contrast, confidence interval, or p value. It states that values are missing or not estimable for the two-arm comparison and lists no analyses. As a result, the comparative effect and its precision cannot be evaluated from the registry record.

The endpoint summaries represent 11 participants in the rTMS group and 4 in the sham rTMS group. Such limited group sizes can make descriptive estimates sensitive to individual observations and can leave substantial uncertainty. This is a general statistical concern; the record does not provide participant-level data to assess the influence of individual values or the distribution of changes.

The registry’s population accounting is incomplete. It reports enrollment of 17 and states that a patient with a baseline pain score of 0 did not meet entry criteria and was excluded from the analysis, but it does not explain the full relationship between enrollment and the endpoint group sizes. The reasons for any other absence from the outcome summaries, the analysis population definition, and the handling of missing outcomes are not reported in the registry record.

The study is marked terminated, but the reason, timing in relation to recruitment, and consequences for the planned analysis are not reported in the registry record. The record also does not give the trial’s own sample-size justification, a statistical analysis plan, details of interim analyses, or methods for handling multiple comparisons. The design is described as randomized and triple-masked, but implementation details are not reported.

For safety, the posted adverse-event counts do not include uncertainty estimates or details of event collection and attribution. These gaps limit comparative interpretation of both benefit and harm. They should be treated as reporting limitations, not as evidence for or against either intervention.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: rTMS for the Treatment of Chronic Pain in GW1 Veterans — NCT01608321.
• Registry record last updated 2017-04-11; status last verified 2017-04.
• Results first posted 2017-04-11.
• 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

The registry record describes a Phase 3 randomized, triple-masked, parallel-group study of rTMS versus sham rTMS for chronic pain in Veterans from the first Gulf War. The sponsor was the VA Office of Research and Development. The study began in 2012-09, had a primary completion date of 2015-06, and is listed as terminated. Enrollment was 17; the reason for termination is not reported in the registry record.

The primary endpoint was mean change in BPI Short Form score from baseline to end of treatment at 3-4 weeks. The registry lists 11 participants in the rTMS outcome group and 4 in the sham rTMS group. It reports mean changes of -1.2 and -0.9, with standard deviations of 1.5 and 1.6, respectively. It does not report a comparative estimate, confidence interval, or p value and lists no analyses. The registry also posts serious and other adverse-event counts, but no comparative safety analysis.