Transcutaneous Electrical Nerve Stimulation (TENS) and Head and Neck Cancer Pain (HNC) (TENS & HNC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transcutaneous Electrical Nerve Stimulation (TENS) and Head and Neck Cancer Pain (HNC) (TENS & HNC) (NCT01194466), a randomized na study. The primary outcome is Change in Pain Intensity in Head/Neck Cancer Area: 10cm Visual Analog Scale (VAS).

2. Clinical Question

The registry record describes a study of adults with oropharyngeal or laryngeal cancer and pain in the head and neck cancer area. It asks whether pain ratings changed within a study visit under active transcutaneous electrical nerve stimulation (TENS), low-intensity placebo TENS, or a no-treatment condition.

The primary measure was each participant’s pre-visit pain score minus the post-visit score. The registry’s stated hypothesis was that a single dose of TENS would decrease pain and improve function and quality of life. However, the posted primary result concerns pain change; a primary result for function or quality of life is not reported in the registry record.

3. Trial Design

This was a randomized, crossover study with a reported enrollment of 41. In a crossover design, participants receive or experience more than one condition, so comparisons can be made across conditions within a study population. The primary endpoint description says that pain was assessed during one study visit for each of the three TENS conditions: active, placebo, and no TENS.

The registry lists three conditions: active high-frequency TENS, low-intensity placebo TENS, and no treatment, with the device in place but not turned on. The registry identifies the allocation as randomized and the model as crossover. It records masking as single. The official title calls the study double blind, so those descriptions are not aligned; who was masked is not reported in the registry record.

The outcome listings report 40 participants for each condition. The registry enrollment is 41, but the reason the condition-level result counts are 40 is not reported in the registry record. Those numbers alone do not establish why a participant is absent from a particular result.

The study is listed as completed, with a start date of 2011-05-15 and primary completion date of 2012-08-14. The registry lists the phase as NA. The sequence of conditions, the timing between conditions, and any washout procedure are not reported in the registry record. The original sample-size rationale and detailed analysis plan are also 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.

Before assignment: Study exclusion criteria were (1) TENS use within 5 years, (2) conditions precluding TENS use (pacemaker, nickel allergy), (3) pain intensity less than 1 of 10 with rest or swallowing, (4) sensory impairment (could not identify sharp and dull stimuli on face), and/or (5) inability to read, write, or follow directions.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The sample was adults (18 or greater) years old with oropharyngeal or laryngeal cancer.

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 Pain Intensity in Head/Neck Cancer Area: 10cm Visual Analog Scale (VAS), measured over The change in VAS pain score was assessed within one study visit for each of the 3 study TENS conditions.

The primary endpoint is the mean change in pain intensity in the head and neck cancer area, measured with a 10 cm visual analog scale (VAS). Participants marked pain from 0, meaning no pain, to 10, meaning worst possible pain. A score was recorded at the start and end of a visit for each condition.

The individual change was calculated as the pre-condition VAS score minus the post-condition score. Thus, a positive change represents a lower score at the end than at the start; a negative change represents a higher score at the end. The registry reports the average of participants’ change scores for each condition, along with a standard deviation.

A continuous pain score preserves information about the amount and direction of change, rather than reducing the outcome to a yes-or-no classification. The within-visit measure was intended to capture short-term change associated with each condition. It does not by itself describe longer-term pain, function, or quality of life. The timing and procedures beyond the within-visit assessments are not reported in the registry record.

7. Results Posted in the Registry

• Active TENS: mean -1.40 versus -0.60 on control; difference -0.80 (95% CI -1.33 to -0.27), standardized effect d = -0.66; z-test p = 0.003.
• No TENS: mean 0.10 versus -0.60 on control; difference 0.70 (95% CI 0.26 to 1.14), standardized effect d = 0.70; z-test p = 0.002.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: it is a numerical VAS change score. The registry reports a mean and standard deviation for each condition. The mean describes the average change across the participants included in that condition’s result. The standard deviation describes variation among individual change scores around that average. It is not the standard error of the mean and does not describe uncertainty in the same way as a confidence interval.

What does the change-score direction mean?

The outcome is defined as pre-VAS minus post-VAS. This direction matters when interpreting signs. A positive value corresponds to a lower post-visit score than pre-visit score; a negative value corresponds to a higher post-visit score. The condition averages were -1.4 for active TENS, -0.6 for placebo TENS, and 0.1 for no TENS. A mean is a summary and does not show the distribution of individual changes or how many participants moved in either direction.

What is a mean difference?

A mean difference compares two condition averages. In the listed contrasts, placebo is the reference condition: active TENS is compared with placebo, and no TENS is compared with placebo. The recalculated differences are -0.8 for active TENS versus placebo and 0.7 for no TENS versus placebo. Their signs inherit the pre-minus-post direction of the endpoint. The value is a contrast between averages, not the change for a typical individual and not a percentage.

The registry identifies the trial as crossover, which means measurements from the same participant under different conditions may be related. A paired analysis can use that within-participant relationship. The posted comparisons are unadjusted recalculations from summary statistics, using the listed condition means, standard deviations, and sample sizes. They do not provide a participant-level paired analysis. The within-participant covariance, condition sequence, and any period or carryover analysis are not reported in the registry record. Consequently, these comparisons should be understood as summary-statistic contrasts, not as a reported crossover model.

What do the p-values indicate?

The posted unadjusted p-values are 0.003 for active TENS versus placebo and 0.002 for no TENS versus placebo. A p-value measures how inconsistent the observed contrast is with a specified no-difference model under the assumptions of the calculation. It is not the probability that the no-difference model is true, nor does it measure the size or importance of a difference. The registry does not report a multiplicity adjustment for the two contrasts, so these values are unadjusted.

What does a confidence interval add?

A confidence interval gives a range of values compatible with the observed data and the method’s assumptions. It helps communicate uncertainty in an estimated mean difference, rather than treating the point estimate as exact. The active-versus-placebo interval is entirely below zero; the no-TENS-versus-placebo interval is entirely above zero. Both are recalculated unadjusted intervals based on the posted summaries. They do not address possible crossover-specific effects that are not represented in those summaries.

The registry record lists no posted analysis count, despite presenting outcome summaries and the comparisons. A full statistical analysis plan, including handling of missing observations and analysis populations, is not reported in the registry record. No adjusted treatment effect, model diagnostics, or participant-level distributions are posted in the registry record described by this record.

Over-dispersion is a concern in models for count outcomes when variability exceeds what the model expects. General statistical context: this outcome is continuous rather than a count, so count-model over-dispersion is not the central issue for these results. More relevant considerations are variability in continuous change scores, dependence between repeated condition measurements, and uncertainty in the mean contrasts. The record gives standard deviations but not the subject-level data needed to examine those patterns directly.

10. Confidence Intervals and Precision

The active-TENS versus placebo contrast is -0.8 change units, with a 95% confidence interval from -1.328 to -0.272. The no-TENS versus placebo contrast is 0.7, with a 95% confidence interval from 0.260 to 1.14. Each interval excludes zero under the stated unadjusted calculation. This indicates that the estimated contrasts are not especially close to zero relative to their calculated uncertainty, but it does not establish that the estimates are free of bias or that the analysis reflects the crossover structure.

In general, a confidence interval represents uncertainty about an estimated quantity under the assumptions of the calculation. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. An interval does not show the range of individual participant outcomes, and it is not a guarantee that the true effect lies within its limits.

The precision of these comparisons is limited by the reported condition sample sizes of 40 and the standard deviations of the change scores. The registry enrollment is 41, and the reason for the difference between enrollment and condition-level counts is not reported in the registry record. The interval calculations are unadjusted recalculations from summary statistics. In particular, they do not show whether a paired crossover method would yield different uncertainty estimates. Participant-level paired data and the covariance between conditions are not reported in the registry record.

The confidence intervals also do not account for uncertainty about unreported features such as condition sequence, carryover, missing data handling, or multiplicity adjustment. Their precision should therefore be interpreted as conditional on the summary-statistic calculation, rather than as a complete account of all uncertainty in the trial.

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 participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: this is a continuous outcome, and the planning values are participant counts per arm. The planning assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses a stated fraction of the observed effect as the effect to detect.

For the active-TENS-versus-placebo comparison, planning for 100% of the observed effect gives 36 participants per arm for 80% power and 48 participants per arm for 90% power. Planning for 75% of the observed effect gives 64 participants per arm for 80% power and 85 participants per arm for 90% power. Planning for 50% of the observed effect gives 143 participants per arm for 80% power and 191 participants per arm for 90% power.

For the no-TENS-versus-placebo comparison, planning for 100% of the observed effect gives 33 participants per arm for 80% power and 44 participants per arm for 90% power. Planning for 75% gives 58 participants per arm for 80% power and 78 participants per arm for 90% power. Planning for 50% gives 130 participants per arm for 80% power and 174 participants per arm for 90% power.

In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting the chosen effect at the specified significance level if that effect were the true effect; 90% power describes a higher chance under the same kind of assumptions. Smaller effects require more participants to detect with the same power. These are planning illustrations based on observed effects, not observed power. The trial’s original sample-size assumptions are not reported in the registry record.

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 = -0.800; pooled standard deviation σ = 1.204.
2. n = 2 × (1.96 + 0.842)² × 1.204² / -0.800² = 35.6, rounded up to 36 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 <- -0.8                      # observed difference in means
sigma <- 1.20415945787923                     # 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(1194466)
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 = 36 (80% power), 48 (90% power)
 75% of observed effect: n per arm = 64 (80% power), 85 (90% power)
 50% of observed effect: n per arm = 143 (80% power), 191 (90% power)
power.t.test: 36.6 
Simulated power at n = 36 per arm: 0.792 (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 two comparisons against placebo: active TENS versus placebo TENS, and no TENS versus placebo TENS. Their recalculated p-values are unadjusted. The record does not report whether the original analysis used a multiplicity procedure or how it would have handled multiple comparisons. When several hypotheses are tested, the chance of at least one false positive can increase; adjustment methods are one way to address that issue. Without a reported plan, the posted p-values should be treated as unadjusted rather than as family-wise adjusted evidence.

The trial is described as randomized and crossover, but the posted results do not give a full account of participant flow or analysis populations. The enrollment is 41, while each condition result lists 40 participants. Why those counts differ, whether any observations were missing, and how missing measurements were handled are not reported in the registry record. The record also does not specify whether the analysis included every randomized participant or only participants with complete outcome measurements.

For a crossover study, important analysis details can include treatment sequence, period effects, carryover, and the correlation of measurements from the same participant across conditions. These details are not reported in the registry record. The posted summary-statistic comparisons do not present an adjusted crossover model or a paired estimate. It is therefore not possible to tell from the record whether these issues were evaluated in the sponsor’s analysis.

The registry does not report a prespecified analysis plan, a missing-data method, or an approach for defining analysis populations. It also does not post secondary outcome results, although the study summary refers to function and quality of life as interests. These reporting gaps constrain interpretation of the primary outcome and preclude conclusions about the unposted outcomes.

14. 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.

The adverse-event results list 41 participants at risk in each of the active TENS, low-intensity TENS, and no-treatment groups. For each listed group, zero participants were affected by serious adverse events, and zero were affected by other adverse events. These are the registry’s reported affected-participant counts for the listed groups.

The registry record does not list serious adverse-event terms. Death counts are recorded as null, so the number of deaths is not reported in the registry record; null should not be interpreted as a reported zero. The record does not explain how adverse events were collected, how long participants were followed for safety, or how events were attributed across conditions in this crossover study.

These entries describe what was recorded in the registry and are not a guarantee that no event occurred outside the recorded definitions or reporting period. The adverse-event counts should be read separately from the pain outcome: they do not establish a treatment effect on pain, and the pain comparisons do not determine safety.

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

The posted primary outcome describes average within-visit pain-score changes for three conditions in a randomized crossover study. The active and placebo condition means were both negative on the pre-minus-post scale, while the no-TENS mean was positive. The unadjusted active-versus-placebo contrast was -0.8, and the no-TENS-versus-placebo contrast was 0.7. Their calculated confidence intervals exclude zero, but the estimates are based on summary statistics and do not report a crossover-adjusted analysis.

The result does not establish what happened to every participant. Means can conceal varied responses, and the registry does not provide the individual-level distributions. The short-term, within-visit outcome also does not establish longer-term pain change. Although the study summary mentions function and quality of life, results for those outcomes are not reported in the registry record.

The posted data do not establish that condition order, carryover, or within-person correlation was handled in the comparisons. They also do not report a multiplicity adjustment or explain why the condition results include 40 participants when enrollment was 41. Those omissions limit interpretation and the scope of claims that can be drawn from the displayed contrasts.

The outcome scale and its direction are essential: positive values mean lower post-visit pain ratings than pre-visit ratings, while negative values mean higher post-visit ratings. The active-versus-placebo difference is negative, so it must not be paraphrased as a greater reduction in pain. These data describe the observed means and unadjusted contrasts; they do not, on their own, answer broader questions about sustained effects or all aspects of care.

16. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and sign conventions matter. The primary measure is pre-score minus post-score, rather than the more familiar post-score minus pre-score. Under this definition, negative values correspond to higher post-visit ratings. Interpreting a contrast without checking that direction could reverse its meaning.

The crossover design also highlights an important distinction between the trial structure and the available summary analysis. Repeated condition measurements from the same participants may be correlated, and a paired analysis can use that relationship. The registry identifies a crossover model, but the posted comparisons are unadjusted summary-statistic recalculations and do not report a paired analysis. The design alone does not show how the analysis accounted for repeated measurements.

Finally, the record separates observed estimates from planning illustrations. The sample-size illustrations use fractions of the observed effect and specified planning assumptions, while the original trial design rationale is not reported in the registry record. Treating these calculations as the trial’s original plan, or as observed power, would confuse planning scenarios with evidence from the completed study. Together, these points show how design, endpoint coding, uncertainty, and reporting determine what can reasonably be inferred from trial results.

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 primary endpoint is a within-visit pain change, so it reflects a short-term assessment rather than a longer-term trajectory. The registry does not report follow-up pain results beyond the condition assessments described for the study visit. Function and quality-of-life results are also not reported in the registry record, despite being mentioned in the study summary.

The crossover description makes condition order and carryover relevant, but the sequence of conditions, washout details, and analyses of period or carryover effects are not reported in the registry record. The posted mean differences are unadjusted recalculations from condition summaries and do not show a paired crossover analysis. The participant-level relationship between measurements across conditions is not available in the registry record.

The record lists an enrollment of 41 and condition result counts of 40, without explaining the difference. Missing-data handling and analysis population definitions are not reported in the registry record. The masking entry is single, while the official title describes a double-blind study; the people masked are not identified in the registry record.

The registry reports no multiplicity adjustment for the two listed contrasts. The posted results also do not include individual-level distributions or a detailed statistical analysis plan. These limitations do not change the recorded means, but they restrict what can be inferred about uncertainty, robustness, and the broader effects of the conditions.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Transcutaneous Electrical Nerve Stimulation (TENS) and Head and Neck Cancer Pain (HNC) (TENS & HNC) — NCT01194466.
• Registry record last updated 2019-09-17; status last verified 2019-08.
• Results first posted 2019-09-17.
• 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

NCT01194466 is a completed randomized crossover study of TENS for mucositis pain and function in adults with oropharyngeal or laryngeal cancer. The registry reports enrollment of 41 and three conditions: active TENS, placebo TENS, and no TENS. The primary outcome is mean change in head and neck cancer-area pain on a 10 cm VAS, calculated as pre-visit minus post-visit score.

Condition results list 40 participants each. Mean changes were -1.4 for active TENS, -0.6 for placebo TENS, and 0.1 for no TENS. Unadjusted recalculated contrasts against placebo were -0.8 for active TENS and 0.7 for no TENS, with both reported confidence intervals excluding zero. A paired crossover analysis, original sample-size rationale, missing-data approach, and multiplicity procedure are not reported in the registry record.

The safety listings report zero affected participants for serious and other adverse events in each group; deaths are not reported as a number.