tDCS to Lower Neuropathic Pain and Fatigue in People With Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for tDCS to Lower Neuropathic Pain and Fatigue in People With Multiple Sclerosis (NCT03870048), a na na study. The primary outcome is Neuropathic Pain Questionnaire (NPQ) Contains 12 Items..

2. Clinical Question

The study also describes fatigue as an outcome of interest and lists the Fatigue Severity Scale as a secondary outcome. Fatigability was to be measured with an isokinetic device, according to the study description, but the registry record does not provide a corresponding result or a detailed analysis plan. The stated hypothesis is that neuropathic pain would be lower and fatigue resistance higher after tDCS sessions. That is a research hypothesis, not an observed finding. Without posted outcome estimates and an account of how the conditions were assigned and analyzed, the registry record does not establish the size, direction, or precision of any change.

3. Trial Design

The registry lists NCT03870048 as a completed study sponsored by the University of Iowa. The recorded enrollment is 6. The study start date is 2019-04-15, and the primary completion date is 2020-03-30. The condition is multiple sclerosis. The intervention is transcranial direct current stimulation, a device-based intervention.

The study description says investigators would conduct tDCS or sham on 5 consecutive days and assess pain and fatigue using questionnaires, as well as measure fatigability with an isokinetic device. The intervention description specifies a tDCS block lasting 20 min at 2 mA. The registry also names groups for tDCS effects and sham effects. These descriptions do not, by themselves, establish how participants were assigned to conditions, whether each participant received both conditions, or how any sequence was determined.

In particular, the registry classifies the model as single group and allocation as NA, and records masking as none. It also flags the arms as not being a like-for-like control comparison. These details mean that the group labels should not be read as evidence of a randomized controlled design. The registry record does not explain the relationship between its single-group design classification and the two named conditions.

The phase is listed as NA. A protocol-level sample-size justification, allocation procedure, treatment sequence, or detailed study schedule is not reported in the registry record. Although the status is completed, completion alone does not show that every planned measurement was collected or that results were analyzed. The registry record lists two outcome measures and zero analyses. It therefore supplies design context but does not provide a statistical comparison of tDCS with sham.

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.

SHAM Effects on Pain and Fatigue

tDCS Effects on Pain and Fatigue

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 Neuropathic Pain Questionnaire (NPQ) Contains 12 Items., measured over 2 Months.

The primary endpoint is the Neuropathic Pain Questionnaire (NPQ), described as containing 12 items. Participants use the items to rate pain as it usually feels. The description gives burning pain as an example: a rating of 0 represents no burning pain, while 100 represents the worst burning pain imaginable. The endpoint is recorded in points, with the registry specifying a mean and standard deviation as the summary format. Its listed timeframe is 2 Months.

As a general statistical explanation, a questionnaire can turn a participant's reports about symptoms into a structured measure that can be summarized across a study group. A mean describes the group's average score; a standard deviation describes how spread out individual scores are around that mean. These summaries address different features of the data and should not be treated as interchangeable. The questionnaire's item-level example does not establish the scoring range or calculation rule for an overall NPQ score, which is not reported in the registry record.

The NPQ is relevant to the stated question because the study focuses on neuropathic pain. The registry record does not report the mean, standard deviation, participant-level scores, baseline values, or a change estimate at the listed timeframe. It also does not explain whether the primary analysis was intended to compare time points, conditions, or another contrast. Consequently, the endpoint definition identifies what was to be measured, but the posted record does not show what the participants' NPQ results were.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a continuous measure summarized by a mean and standard deviation. As a general explanation, a continuous measure can take values along a scale rather than being limited to categories such as yes or no. The mean is an average across measured participants. The standard deviation describes the degree to which individual values vary around that average. A mean alone does not show whether participants' scores were tightly clustered or widely dispersed, while a standard deviation alone does not indicate the average score.

The NPQ is described as a 12-item questionnaire, and the outcome unit is points. The listed summary parameter is a mean, with standard deviation as the dispersion measure. The registry record does not state how item scores are combined, how incomplete questionnaires are scored, or whether the primary quantity was intended to be a final score or a change score. Those distinctions matter because different definitions of the analysis outcome can lead to different interpretations. The item example anchors a response for burning pain, but it does not supply the overall scoring rule.

What would a treatment contrast require?

In general, a treatment contrast compares outcome values under distinct conditions or compares changes over time in a way that accounts for the study design. A sham condition may be included as a comparator in a study, but its mere presence in a description does not establish a valid comparison. Assignment, timing, adherence, measurement, and analysis all affect what contrast can be estimated. Here, allocation is recorded as NA, masking as none, and the model as single group. The registry further cautions that the arms are not a like-for-like control comparison. A planned tDCS and sham condition therefore cannot be interpreted as a randomized comparison on the information recorded.

No specific contrast or inferential method is described in the registry record. In particular, it does not say whether the analysis would compare scores at the 2 Months timeframe, compare changes from baseline, or use another approach. A baseline measurement and a change-from-baseline analysis should not be assumed simply because the study evaluates an intervention. The analysis method, covariate adjustment, and handling of repeated measurements are not reported in the registry record.

How should uncertainty be understood?

As a general statistical concept, an estimate describes the quantity calculated from the observed participants, while a confidence interval communicates uncertainty around that estimate under the assumptions of a method. The interval's width is influenced by features such as the amount of data and variability. A narrow interval indicates greater precision for the specified analysis than a wide interval, but neither width nor location establishes clinical importance by itself. The registry record reports no estimate or confidence interval for the primary outcome, so neither effect size nor precision can be evaluated.

A p-value, when reported, is a measure calculated under a statistical model and a null hypothesis; it is not the probability that the null hypothesis is true. A p-value also does not communicate the size or practical meaning of an effect. No p-value or statistical test result is reported in the registry record. The registry lists zero analyses, so there is no posted inferential analysis to distinguish statistically detectable findings from estimates that remain uncertain.

What do planning illustrations mean?

General sample-size planning estimates ask how many participants might be needed under specified assumptions to detect a target effect with a chosen error rate and power. Any planning illustration based on an observed effect is not an observed-power analysis and does not establish what the completed study could detect. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning convention is participants per arm for 80% power or participants per arm for 90% power. These are planning assumptions, not evidence that the trial enrolled those numbers or had a particular probability of finding an effect.

The registry record does not report a protocol sample-size justification or explain whether those planning assumptions informed the actual design. With enrollment of 6 and no posted outcome estimate, planning illustrations cannot be treated as a description of observed power or as an explanation for the study's enrollment. They are conditional calculations, not trial results.

Why can variability matter?

As a general explanation, greater variability among participant measurements makes a group average less precise when other features of a study are held constant. If continuous outcomes have more variation than an analysis assumes, standard errors and uncertainty estimates may be unreliable; methods that account for over-dispersion can be important for suitable data types. The registry specifies a mean and standard deviation for the primary endpoint but provides no actual variability estimate. It also does not report whether the observed distribution was examined, whether model assumptions were assessed, or whether any alternative method was used. No claim about over-dispersion or model fit can be made.

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("tDCS Effects on Pain and Fatigue", "Sham Effects on Pain and Fatigue")
n   <- c(6, 6)
m   <- c(21.3, 10.3)
sp  <- c(19.5, 13.5)
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  tDCS Effects on Pain and Fatigue  6  21.300  19.500  0.836  41.764
CARM  Sham Effects on Pain and Fatigue  6  10.300  13.500  -3.867  24.467

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the NPQ as primary and the Fatigue Severity Scale as secondary. The study description also mentions measuring fatigability with an isokinetic device. When a study evaluates multiple outcomes, time points, or contrasts, the chance of at least one apparently notable result can be affected by how many analyses are performed and how results are selected. As a general statistical principle, a prespecified hierarchy or multiplicity adjustment can help clarify interpretation. The registry record does not report a multiplicity plan, adjustment method, or analysis hierarchy beyond identifying the NPQ as primary and the FSS as secondary.

The record lists zero analyses and does not report results for either questionnaire or for fatigability. It also does not describe whether other outcomes or time points were assessed. Statistical methods, interim analyses, and a detailed analysis plan are not reported in the registry record. Their absence from the record should not be interpreted as proof that none were used outside the registry; it means the record does not document them.

Missing-data handling is also not reported in the registry record. The enrollment of 6 does not establish how many participants completed the NPQ at 2 Months or contributed to any secondary outcome. The record does not give the number of missing observations, reasons for missingness, rules for excluding measurements, or any imputation method. As a general explanation, missing data can affect both the amount of information available and the interpretation of an estimate, particularly when missingness is related to participants' outcomes or study experience.

The analysis population is not reported in the registry record. It is therefore not possible to determine whether analyses were intended to include all enrolled participants, only those with complete measurements, or another set. Without a documented population, missing-data approach, and analysis plan, the reader cannot assess how those decisions might affect 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 5% reporting threshold.

The registry's adverse-event entries list 6 participants at risk in each of the tDCS and sham groups. For both entries, the number with serious adverse events is 0, the number with other adverse events is 0, and deaths are 0. These are the figures recorded in the registry; they are not a measure of the intervention's efficacy.

The group labels should be read cautiously. The study is classified as single group, allocation is listed as NA, masking as none, and the registry warns that the arms are not a like-for-like control comparison. The record does not explain how the two safety entries relate to the study's participants or whether the same individuals may be represented across conditions. The at-risk counts should not be added together or treated as independent groups without that information.

Zero reported events means that no events are entered in these registry categories. It does not establish that every possible adverse effect was monitored, that all participants had complete safety follow-up, or that the conditions have equivalent safety. The duration and completeness of safety surveillance, event definitions, and whether events were assessed systematically are not reported in the registry record. No serious adverse-event terms are listed. These entries are best understood as the registry's recorded safety counts, with limited information about their context.

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

The registry record describes a completed study with a stated question about tDCS, neuropathic pain, and fatigue in people with multiple sclerosis. It identifies the NPQ as the primary outcome and gives a measurement timeframe. It also describes a sham condition and names fatigue measures. This information explains what investigators intended to study, but it does not supply outcome results.

Without reported NPQ values, there is no basis in the registry record for stating whether pain scores changed, how large any change was, or how variable participants' scores were. Without a reported comparison and its uncertainty, there is also no basis for deciding whether an apparent difference could be attributed to tDCS rather than other features of the study. The stated hypothesis is not a finding, and the completed status does not fill that gap.

The record does not support a conclusion about fatigue or fatigue resistance either. The FSS is named as a secondary outcome, and the study summary mentions an isokinetic measure, but no results or analyses are reported. Likewise, the safety counts do not answer the efficacy question and have limited interpretability because the relationship between the named groups is unclear.

In general, a study's result is interpreted through its estimate, uncertainty, design, and analysis population. A lack of posted estimates is different from an estimate close to no difference or a statistically nonsignificant result. The registry record provides neither an effect estimate nor a test result, so it cannot be classified as evidence of benefit, evidence of no effect, or an inconclusive comparison based on a calculated result.

The defensible reading is narrower: the record documents study aims, a small enrollment, outcome definitions, and selected safety counts, while leaving the actual outcome findings and analysis methods unavailable. Further claims about the size, direction, precision, or clinical meaning of any effect are not supported by the registry record.

14. Why This Trial Matters Statistically

This study raises a statistically important distinction between a research question and an analyzable result. A clearly stated hypothesis about pain and fatigue does not itself provide evidence about the size or precision of an effect. For interpretation, outcome estimates and their uncertainty are essential. The registry record identifies measures and a timeframe but does not report the values needed to evaluate them.

The design classification is also consequential. The record names tDCS and sham conditions, yet classifies the study as single group, lists allocation as NA, and cautions that the arms are not a like-for-like control comparison. This makes it important not to read group labels as proof of a controlled contrast. Understanding how conditions were assigned and how data were compared is central to deciding what an analysis can establish.

Enrollment of 6 highlights why clarity about the analysis population and variability matters. The registry does not state how many participants contributed to each outcome or how missing measurements were handled. In general, the amount and completeness of outcome data affect precision, and a small enrolled group can limit the information available. However, the registry record does not provide the results needed to quantify precision or determine what effects could be distinguished.

The record also illustrates why outcome plans, statistical methods, and posted results need to be considered separately. It identifies a primary measure and a secondary measure, but does not document multiplicity handling or report analyses. The completed status cannot substitute for a transparent account of estimates and methods. Statistically, the most informative conclusion is therefore about the limits of the record: it describes a study designed to investigate a clinical question, but does not allow an effect estimate or inferential conclusion to be assessed.

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.

Several limitations specific to this registry record affect interpretation. First, no primary or secondary outcome results are reported. The NPQ's mean and standard deviation, any change estimate, and any comparison are absent. The record also does not provide outcome-level participant counts, so the number enrolled cannot be equated with the number analyzed.

Second, the design information is difficult to reconcile. The study is classified as single group, while the record names tDCS and sham groups. Allocation is NA and masking is none; the registry explicitly warns that the arms are not a like-for-like control comparison. The record does not clarify assignment, treatment sequence, whether conditions were received by the same participants, or how the conditions were analyzed. Those omissions limit causal interpretation.

Third, important operational and statistical details are not reported in the registry record. These include the sample-size justification, a detailed analysis plan, missing-data procedures, analysis population, multiplicity strategy, interim analyses, and methods for assessing model assumptions. The scoring rule for the overall NPQ result is also not stated, beyond the questionnaire description and summary format.

Fourth, the listed outcome timeframe does not by itself establish when measurements were collected relative to each intervention session or whether there were additional assessments. The registry record does not give participant characteristics, adherence, withdrawals, reasons for missingness, or a detailed account of follow-up. These gaps prevent assessment of representativeness, data completeness, and the context of any potential outcome changes.

Finally, the safety entries provide counts but little information about surveillance or how participants map to the named groups. Taken together, these limitations do not show that the study lacked methods or data; they describe what cannot be established from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: tDCS to Lower Neuropathic Pain and Fatigue in People With Multiple Sclerosis — NCT03870048.
• Registry record last updated 2022-08-25; status last verified 2022-08.
• Results first posted 2022-08-25.
• 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

NCT03870048 is a completed University of Iowa study of tDCS and sham stimulation for neuropathic pain and fatigue in people with multiple sclerosis. The registry lists enrollment of 6, a start date of 2019-04-15, and a primary completion date of 2020-03-30. The primary outcome is the NPQ, described as a 12-item measure summarized by mean and standard deviation at 2 Months. The FSS is listed as a secondary outcome.

The record classifies the study as single group, lists allocation as NA and masking as none, and cautions that the named arms are not a like-for-like control comparison. It lists zero analyses and does not report outcome estimates, confidence intervals, p-values, or a detailed statistical plan. Serious adverse events, other adverse events, and deaths are recorded as 0 in each named safety group, with 6 at risk in each. These counts do not resolve the unclear relationship between groups. The record establishes the study's aims and selected design details, but does not provide results with which to assess effects or their precision.