High Frequency Impulse Therapy for Neuropathic Pain in NMOSD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High Frequency Impulse Therapy for Neuropathic Pain in NMOSD (NCT04614454), a randomized phase 2 study. The primary outcome is Change in Pain Score on the Numerical Rating Score (NRS).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 trial of high frequency impulse therapy for neuropathic pain in neuromyelitis optica spectrum disorder. The registry lists 46 participants enrolled. The study status is completed; its recorded start date is 2021-06-07 and its primary completion date is 2022-04-13. Massachusetts General Hospital is listed as the sponsor.

The two arms were an experimental device and a sham device. The registry describes the sham unit as visually identical to the experimental unit and says it may produce a sensation without delivering electric current. Devices were programmed by a study coordinator. The arm descriptions also refer to assistance with electrode placement, but the full descriptions are not reported in the registry record. The study is listed as randomized and quadruple masked. Who was masked, how masking was implemented, and how allocation was generated are not reported in the registry record.

The primary outcome was change in pain score on the numerical rating scale, assessed from baseline to week 4. The analysis population was not all 46 enrolled participants: it comprised those with both baseline and week 4 assessments, analyzed according to randomized arm regardless of actual device use or further participation. This included 19 experimental-arm participants and 21 sham-arm participants. The registry does not report the reasons participants were absent from this endpoint analysis.

Three secondary outcomes are listed: worst pain score on the numerical rating scale, withdrawal from trial, and a quality-of-life survey. The posted continuous comparisons cover worst pain score and quality of life; a numerical comparison for withdrawal is not reported in the registry record. Further details of the trial's design and analysis procedures 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.

Before assignment: Inclusion criteria included age 18+ years, diagnosis of NMOSD, presence of aquaporin-4 immunoglobulin (AQP4 IgG) serum antibodies, pain lasting ≥ 3 months attributable to a previous inflammatory spinal cord lesion, and pain rated at a level of ≥ 4 on an 11-point Numeric Rating Scale (NRS).12 Exclusion criteria included spinal cord relapses or surgery to treat a pain-related condition within 6 months of enrollment, presence of neuropathic pain due to non-NMOSD-related identified causes.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All individuals who completed their baseline and week 4 assessment were included in the analysis as randomized, regardless of actual device usage or further participation in the trial. Twenty-one participants in the sham arm and 19 in the TENS arm met these criteria.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: There is no difference.

6. Primary Endpoint

The registry lists the primary outcome as Change in Pain Score on the Numerical Rating Score (NRS), measured over 4 weeks from baseline to completion of the experimental phase..

The primary endpoint is change in pain score on the numerical rating scale from baseline to week 4. The scale runs from 0, meaning no pain, to 10, meaning worst pain. The outcome is a continuous measure, and the registry reports arm means and standard deviations. A change score expresses how an individual's recorded pain score differed between the two assessment times; comparing average change between randomized groups addresses whether the observed change differed between the device and sham arms over that period.

Pain is a patient-reported experience, so a numeric rating offers a straightforward way to record and compare reported intensity at specified times. It also retains more gradation than a simple yes-or-no measure. As a general statistical point, the endpoint's clinical interpretation depends not only on the size of a group difference but also on the scale's meaning, the direction used to calculate change, and the precision of the estimate. The registry record says the posted result is the difference between baseline and week 4 scores, but does not state explicitly which time point is subtracted from the other.

The outcome is limited to the recorded pain score at the two stated assessment times. It does not, by itself, describe device use, changes between assessments, or longer-term experience. The registry gives a four-week assessment timeframe; other follow-up information for this outcome is not reported in the registry record.

7. Results Posted in the Registry

• Experimental Arm: mean 2.20 versus 1.30 on control; difference 0.90 (95% CI -0.50 to 2.30), standardized effect d = 0.40; z-test p = 0.206.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

"Worst" Pain Score on the NRS Scale

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Experimental Arm: mean 1.00 versus 1.40 on control; difference -0.40 (95% CI -1.67 to 0.87), standardized effect d = -0.20; z-test p = 0.538.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Experimental Arm and the control. The interval gives the range of effects that remain compatible with the data.

Quality of Life Survey

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Experimental Arm: mean 14.70 versus 10.20 on control; difference 4.50 (95% CI -4.18 to 13.18), standardized effect d = 0.32; z-test p = 0.309.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Experimental Arm and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add information about other reported dimensions, but they do not make the primary estimate more precise. The posted secondary results include worst pain score and quality of life, with mean differences that point in different directions. Their confidence intervals also span values on both sides of zero. Overall, the secondary pattern is not a consistent set of precise differences that independently resolves the uncertainty in the primary comparison.

Worst pain score is closely related to the primary pain outcome, but it is a distinct reported measure. Quality of life addresses a broader outcome than pain intensity. Agreement across related outcomes can sometimes make a pattern easier to interpret, while disagreement can reflect differences in the constructs measured, variability, or chance. These are general possibilities; the registry record does not report an explanation for the observed pattern or evidence identifying its cause.

The registry lists withdrawal from trial as a secondary outcome, but a numerical result for it is not reported in the registry record. Consequently, the posted secondary comparisons do not provide a complete numerical account of all listed secondary outcomes.

The secondary comparisons are unadjusted recalculations, and the registry record reports no analyses for them. When several outcomes are examined, the chance of at least one apparently unusual result can increase. As a general statistical principle, this is why unadjusted secondary findings carry less weight than a prespecified primary analysis, particularly when the multiplicity plan and analysis hierarchy are not reported in the registry record. The secondary estimates are useful as descriptive context and as indications of uncertainty, not as independent proof that the primary finding should be interpreted differently.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• "Worst" Pain Score on the NRS Scale
• Withdrawal From Trial
• Quality of Life Survey

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference represent?

The primary outcome is continuous, so the registry reports the mean change in each arm and the standard deviation around each mean. The mean is the arithmetic average of participants' recorded changes. The standard deviation describes how spread out those individual changes are around the average; it is not the uncertainty in the arm mean itself. The experimental-arm mean was 2.2 units and the sham-arm mean was 1.3 units. The posted experimental-minus-sham comparison is 0.9 units.

The interpretation of a change score depends on its sign convention. The registry states that the result is the difference between baseline and week 4, but the subtraction order is not reported in the registry record. The comparison is therefore best read using the posted labels and estimates, without assuming a direction for the underlying subtraction beyond what the record states.

What does a confidence interval add?

As a general explanation, a confidence interval gives a range of values compatible with the data under the method used to construct it. It represents uncertainty around an estimate, rather than a range that contains a fixed proportion of individual participants' outcomes. For the primary comparison, the posted interval reaches from below zero to above zero. Zero corresponds to no difference between the arm means. Because the interval includes values on both sides of zero, the data do not precisely distinguish the direction of the difference. Its breadth also indicates uncertainty about the magnitude.

How should the p-value be read?

The posted unadjusted p-value for the primary comparison is 0.206. As a general explanation, a p-value describes the compatibility of the observed data with a null hypothesis within a statistical model; it does not measure the probability that the null hypothesis is true, nor the probability that a treatment effect exists. It also does not describe the size or clinical importance of a difference. No adjusted analysis is reported in the registry record. The unadjusted value should be read alongside the estimate and confidence interval, not on its own.

What does randomization contribute?

Random assignment is intended, in general, to make treatment groups comparable on average at the point of allocation, including for characteristics that may not be measured. It supports a between-arm comparison when analysis and follow-up preserve the randomized groups. The registry lists randomized allocation and says the endpoint participants were analyzed as randomized. However, eligibility for the posted endpoint analysis required completion of both baseline and week 4 assessments. The record does not report whether missing endpoint data could have affected comparability, nor does it describe an imputation or missing-data analysis.

The registry lists quadruple masking, but the identities of the masked parties, procedures for maintaining masking, and assessment of whether masking was successful are not reported in the registry record. The sham description gives some information about device appearance and sensation; it does not establish that participants or study personnel could not distinguish assignments.

Why does variation matter?

As a general explanation, greater variability makes it harder to estimate a group mean difference precisely when other factors are similar. The primary standard deviations, 2.2 and 2.3 units, are large relative to the observed difference of 0.9 units. This is consistent with the confidence interval allowing a range of differences. Variation can reflect genuine differences among participants and measurement variability; the registry does not partition these sources.

Clinical outcomes may also show more variability than a simple statistical model assumes. In general, over-dispersion means that data vary more than the model expects. When that occurs, standard errors may be too small if the extra variability is ignored, producing intervals that are too narrow and tests that overstate precision. The primary outcome is a continuous change score, and the record reports its standard deviations. The registry does not describe an over-dispersion assessment or an alternative model; this is a general consideration, not a claim that over-dispersion occurred in this trial.

What is recalculated and what is not?

The posted comparison is an unadjusted recalculation from the reported arm summary statistics. Such a calculation describes the difference between the observed arm means and its uncertainty under a simple two-group comparison. It does not adjust for baseline covariates, account for unreported analysis features, or replace a sponsor's prespecified analysis. The registry record does not list reported analyses for this comparison. The discrepancy indicator does not flag a disagreement between the recalculation and posted information.

The registry's detailed statistical analysis plan, including the model, covariate adjustment, handling of multiplicity, and any interim analyses, is not reported in the registry record. Those omissions limit what can be concluded about whether the simple recalculation matches the trial's intended inferential procedure. This limitation is distinct from the arithmetic meaning of the posted means and comparison.

11. Confidence Intervals and Precision

The primary mean difference is 0.9 units, and the confidence interval runs from a negative lower bound to a positive upper bound. Because zero lies within the interval, the estimate is not precise enough to rule out either direction of an arm difference under the interval's method. The interval also permits differences larger than the point estimate in either direction, so the observed 0.9-unit estimate should not be treated as a sharply determined effect.

As a general explanation, a confidence interval combines the estimated difference with its sampling uncertainty. A wider interval indicates less precision; a narrower interval indicates greater precision, assuming the method is appropriate. The interval does not say that every value inside it is equally plausible, and it does not show the distribution of individual outcomes. The reported standard deviations of 2.2 and 2.3 units show appreciable spread in the observed changes, while the endpoint comparison includes 19 experimental-arm and 21 sham-arm participants.

The unadjusted p-value of 0.206 is consistent with the interval's inclusion of zero, but the p-value does not communicate the full range of compatible differences. Nor does either statistic establish whether a difference is important to patients. A clinical importance threshold for this outcome is not reported in the registry record.

The confidence interval is based on a simple unadjusted comparison from the posted summary statistics. The registry record does not report the trial's own detailed statistical model or whether another prespecified analysis was used. The interval therefore describes the precision of this recalculated comparison, not necessarily every uncertainty addressed by a full trial analysis. The endpoint population also excludes participants without both required assessments, and the effect of their missing data on precision or bias is not reported in the registry record.

12. 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 describe participants per arm for a two-group comparison, not total events. They are illustrations based on the observed primary effect, rather than the trial's original design justification. The registry's planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. The original trial sample-size assumptions are not reported in the registry record.

For planning for 100% of the observed effect, the illustration gives 99 participants per arm for 80% power and 132 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 175 participants per arm for 80% power and 235 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 394 participants per arm for 80% power and 527 participants per arm for 90% power.

In plain terms, 80% power is the probability, under the planning assumptions and if the chosen effect is the true effect, of obtaining a statistically significant result using the stated significance level. The 90% column uses a higher target probability under those same assumptions. Smaller effects are harder to distinguish from random variation, so the planning illustration requires more participants per arm when the target effect is a smaller fraction of the observed effect. These figures are not observed power: they are hypothetical planning calculations, not a measure of the trial's achieved ability to detect an effect.

13. 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 = 2.253.
2. n = 2 × (1.96 + 0.842)² × 2.253² / 0.900² = 98.4, rounded up to 99 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 <- 0.9                      # observed difference in means
sigma <- 2.2531848804                     # 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(4614454)
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 = 99 (80% power), 132 (90% power)
 75% of observed effect: n per arm = 175 (80% power), 235 (90% power)
 50% of observed effect: n per arm = 394 (80% power), 527 (90% power)
power.t.test: 99.4 
Simulated power at n = 99 per arm: 0.800 (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.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, comparison, time point, or analysis. As a general statistical principle, examining multiple results without an adjustment or a prespecified hierarchy can increase the chance that one result appears noteworthy because of random variation. This trial lists a primary pain-change outcome and three secondary outcomes: worst pain score, withdrawal from trial, and quality of life. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a plan describing how the secondary outcomes were to be interpreted. The posted secondary comparisons are unadjusted, so they should be treated as exploratory context rather than as a set of confirmatory tests.

The analysis population for the primary endpoint required both baseline and week 4 assessments. The registry states that included participants were analyzed as randomized regardless of device use or further participation, but it does not report reasons for missing assessments, the amount or pattern of missing data, or any imputation method. It also does not report sensitivity analyses examining alternative assumptions about missing outcomes. Complete-case inclusion can affect both the number of participants contributing information and how representative the analysis population is of everyone randomized.

The record lists 46 enrolled participants, while 19 experimental-arm and 21 sham-arm participants met the stated primary analysis criteria. Safety reporting uses 23 participants at risk in each arm. These are different analysis denominators for different reported information; the registry does not explain the flow between enrollment, endpoint completion, and safety populations in detail.

The registry record does not report the trial's detailed statistical analysis plan, covariate adjustment, interim analyses, or the original sample-size justification. It also does not report a numerical result for the listed withdrawal outcome. These gaps do not alter the arithmetic of the posted summaries, but they limit assessment of prespecification, missing-data handling, and the intended control of false-positive findings across outcomes.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

For serious adverse events, 0 affected participants were reported among 23 at risk in the experimental arm, and 0 among 23 at risk in the sham arm. The record also reports 0 deaths in each arm. These figures describe the recorded safety counts and denominators; they do not establish that no serious event could occur or that the two devices have identical safety profiles.

For other adverse events, 16 participants were affected among 23 at risk in the experimental arm and 14 among 23 at risk in the sham arm. These are counts of participants affected, not a measure of severity, duration, or the total number of event episodes. The registry record does not provide serious adverse event terms, since none are listed, or a fuller breakdown of other adverse events in the information reported.

As a general statistical point, small safety groups give limited precision for uncommon outcomes. A zero count in a group does not show that the underlying risk is exactly zero. These counts should be read as descriptive registry reporting rather than as a precise comparative safety analysis. The record does not report a formal statistical comparison of adverse events.

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

The main result is a comparison of average pain-score change over four weeks among participants who completed both baseline and week 4 assessments. The experimental-arm mean was 2.2 units and the sham-arm mean was 1.3 units, with a posted mean difference of 0.9 units. The confidence interval crosses zero and the unadjusted p-value is 0.206. Together, these statistics show that the observed difference is uncertain and that the data do not precisely establish its direction or magnitude.

This is not evidence that the two arms are equivalent. Equivalence requires a prespecified margin and an analysis designed to determine whether differences are sufficiently small to fall within that margin. Such a margin or analysis is not reported in the registry record. Likewise, the result does not prove that there is no difference. A nonsignificant result can arise when an estimate is imprecise, and the interval allows a range of possible differences.

The result also does not by itself establish how participants would fare outside this trial, over a longer period, or with different patterns of device use. The primary endpoint covers baseline to week 4, and the analysis is limited to people with both assessments. The registry says participants were analyzed in their randomized arms regardless of actual device usage, but it does not report how much devices were used or why some participants were not included in the endpoint analysis.

Nor do the posted values establish whether the size of a score change matters to participants. A threshold for clinical importance is not reported in the registry record. Statistical uncertainty and clinical importance are related but distinct questions: the confidence interval describes uncertainty in a group comparison, whereas a clinical threshold would help interpret whether a difference is meaningful in practice.

The appropriate reading is therefore narrow: the posted summaries describe an uncertain four-week difference between randomized arms among assessment completers. They do not provide a definitive conclusion about benefit, equivalence, long-term outcomes, or individual response. The secondary findings and safety counts offer context, but do not remove the uncertainty in the primary comparison.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate should not be read in isolation. The primary mean difference is 0.9 units, but the confidence interval crosses zero and extends across a broad range of possible differences. The point estimate alone can give a false impression of certainty; pairing it with its interval makes the uncertainty visible.

It also highlights the distinction between randomization and analysis population. Randomized assignment supports a fair comparison in principle, but the primary summary includes only participants with both baseline and week 4 assessments. Knowing how many participants contributed to an outcome, and what is not known about missing observations, is necessary for judging how directly the result represents the full randomized group.

The record also demonstrates why statistical significance, effect size, and clinical importance are separate. The unadjusted p-value does not express the probability that the treatment works, and the registry does not give a threshold for a meaningful change. Readers need the estimate, uncertainty, outcome scale, and population together to interpret a clinical comparison.

Finally, the planning illustration makes clear that sample-size requirements depend strongly on the effect one aims to detect. Smaller target effects require more participants per arm under the stated assumptions. These calculations are distinct from the trial's original design rationale, which is not reported in the registry record. Taken together, the study offers a useful example of reading a randomized clinical result with attention to precision, analysis population, multiplicity, and the limits of registry reporting.

18. 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 trial affect interpretation. The primary endpoint analysis included 19 experimental-arm participants and 21 sham-arm participants, whereas the registry lists 46 enrolled overall. The record specifies that both baseline and week 4 assessments were required for inclusion but does not report why other enrolled participants were not included in that endpoint analysis. Missingness could influence the representativeness of the observed comparison, and its effect cannot be assessed from the reported information.

The assessment period for the primary and posted continuous secondary outcomes was four weeks. The record therefore supports interpretation of short-term measurements only; later outcomes for these measures are not reported in the registry record. The trial's practical question involves self-administered at-home use, yet actual device use is not quantified in the posted primary result. Participants were analyzed regardless of actual usage, and adherence information is not reported in the registry record.

The registry identifies the study as quadruple masked but does not identify the masked groups or report whether masking was assessed. The sham description indicates that a sensation may occur without electric current, but whether that experience could reveal assignment is not reported. The complete intervention and sham procedures are also not reported in the registry record.

The primary confidence interval is broad and crosses zero, and the endpoint analysis is small. No clinical importance threshold, detailed statistical analysis plan, missing-data sensitivity analysis, or multiplicity procedure is reported. The registry lists withdrawal as a secondary outcome but provides no numerical result for it. These limitations make the posted findings informative as estimates with uncertainty, while restricting conclusions about durability, adherence, missing data, and confirmatory inference.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: High Frequency Impulse Therapy for Neuropathic Pain in NMOSD — NCT04614454.
• Registry record last updated 2025-04-30; status last verified 2025-04.
• Results first posted 2025-04-30.
• 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.

22. Record Summary

NCT04614454 is a completed randomized, parallel-group phase 2 trial sponsored by Massachusetts General Hospital. It compared high frequency impulse therapy with a sham device for neuropathic pain in neuromyelitis optica spectrum disorder. The registry lists 46 participants enrolled and identifies the study as quadruple masked.

The primary outcome was change in numerical rating score from baseline to week 4. The primary analysis included participants with both assessments: 19 in the experimental arm and 21 in the sham arm. Mean change was 2.2 units in the experimental arm and 1.3 units in the sham arm; the posted difference was 0.9 units, with an unadjusted p-value of 0.206 and a confidence interval spanning zero.

Secondary outcomes listed include worst pain score, withdrawal from trial, and quality of life. The registry also reports adverse-event counts, including no serious adverse events or deaths in either arm. Important details—including the full analysis plan, missing-data handling, and original sample-size justification—are not reported in the registry record.