A Study of A-101 Topical Solution in Subjects With Dermatosis Papulosa Nigra: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of A-101 Topical Solution in Subjects With Dermatosis Papulosa Nigra (NCT03224598), a randomized phase 2 study. The primary outcome is Physician's DPN Lesions Assessment.

2. Clinical Question

3. Trial Design

The registry identifies NCT03224598 as a Phase 2, randomized, open-label, parallel-group study of A-101 topical solution in subjects with dermatosis papulosa nigra. The listed enrollment is 39. The study began on 2017-06-26, had primary completion on 2019-01-08, and is marked completed. These dates describe the registry record and do not, by themselves, describe how long each participant was followed.

Three groups appear in the posted primary outcome results: No Medical Abrading, Medically Abrading, and Initial Cohort - no Medical Abrading. The first group received A-101 40% without medical abrasion of identified lesions; the second received A-101 40% with identified lesions medically abraded before treatment. The initial cohort is also described as receiving A-101 40% without medical abrasion. The registry does not explain how the initial cohort relates to the other group, or whether its results are intended for a direct comparison with either group.

Although the registry labels the study randomized, the sequence generation, allocation concealment, and allocation procedures are not reported in the registry record. Masking is listed as none, making this an open-label study. The registry does not specify which participants or assessors, if any, were unaware of treatment assignment. The model is listed as parallel, meaning the registry presents separate groups rather than a crossover design.

The record names a single primary outcome measure and lists no posted secondary outcome measures. The primary results are identified as per-protocol. The planned sample size and its justification, eligibility details beyond the stated population, treatment schedule, and full visit schedule are not reported in the registry record. Randomization can support comparisons when properly conducted, but open-label assessment and the absence of a posted comparative analysis limit what can be concluded from the posted results alone.

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: per-protocol

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 Physician's DPN Lesions Assessment, measured over Day 106.

The primary endpoint is Physician's DPN Lesions Assessment, reported as a score on a scale (PLA), with Day 106 as the stated timeframe. The scale grades each treated lesion from 0 to 3. Grade 0 means Clear, with no visible DPN lesion; grade 1 means Near Clear, with a slightly visible lesion that may be macular; grade 2 means Small, a visible lesion with a diameter less than 3 mm; and grade 3 means Large, a visible elevated lesion with a diameter of at least 3 mm.

This ordinal scale captures clinicians' assessments of lesion visibility and size. It can describe the distribution of lesion grades and, when summarized numerically, their mean and standard deviation. Lower grades correspond to descriptions of less visible or smaller lesions. The registry describes planned efficacy summaries that include means, medians, frequency distributions, proportions, and standard deviations, as appropriate. It also mentions subject responders and changes from baseline treated-lesion diameter as efficacy endpoints, but those are not the primary result reported in the posted outcome.

The posted primary results are means with standard deviations for the three groups. The registry does not clarify whether the values represent a change from baseline or another score summary. Therefore, the negative values should not be interpreted as a particular amount of improvement without that definition. A mean also does not show how many lesions or participants fell into each grade, and the standard deviation describes spread rather than uncertainty in a treatment comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous in the registry's statistical classification, and the reported statistic is a mean. A mean is the arithmetic average of observations on a numeric scale. It provides a compact description of the center of the observed scores, but it does not describe every participant or lesion. On an ordinal grading scale such as PLA, the numerical average can be useful for summary, while the grade definitions and the full distribution remain important for understanding what observations the average represents.

What does the standard deviation describe?

The standard deviation describes how spread out individual observations are around their group mean. A larger standard deviation indicates more variability in the observations; it is not a measure of how certain the mean is, and it is not a treatment-effect estimate. The posted standard deviations are 0.52 for No Medical Abrading, 0.9 for Medically Abrading, and 0.95 for Initial Cohort - no Medical Abrading. Without the individual observations or confidence intervals, the precision of each group mean and of any contrast cannot be established from these summaries alone.

Why is a group comparison different from separate means?

A randomized comparison generally focuses on a contrast between groups, such as the difference in an outcome under two assigned approaches. That contrast needs an estimate and a measure of uncertainty, such as a confidence interval, or a test result. Separate group means do not report that contrast. The registry has no posted analyses for the continuous endpoint and indicates that values are missing or not estimable for a two-arm comparison. Consequently, it is not appropriate to infer statistical significance, precision, or a treatment effect from visual or informal comparison of the group means.

How should confidence intervals be understood?

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a mean or a difference between means. Its width reflects precision under the assumptions of the analysis: narrower intervals indicate greater precision, while wider intervals indicate less. The registry does not report confidence intervals for these primary outcome results. No interval should be inferred from the standard deviations alone, because the group sizes, analysis population, and estimand also matter, and because a group-level interval would not answer the between-group question by itself.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It matters when the chosen model assumes less variability than the data contain, since uncertainty estimates and tests can then be too optimistic. The endpoint is listed as continuous and summarized by means and standard deviations; the registry does not report a model, a test for over-dispersion, or a model-based analysis. Over-dispersion should not be asserted as a feature of these results. More generally, the choice of analysis should reflect the outcome scale and its observed distribution, but the specific method used is not reported in the registry record.

What can be said about planning calculations?

General sample-size planning calculations estimate how many participants per arm might be needed to detect a specified effect under stated assumptions. They are planning illustrations, not observed power and not evidence that a study was adequately powered. The registry record does not report the trial's sample-size justification or its own planning assumptions. Any planning illustration based on the observed effect is distinct from the original design decision and should not be treated as a retrospective test of whether the study was successful. The posted information does not provide an analysis result for the primary comparison.

How does the scale affect interpretation?

The PLA categories are ordered, from Clear through Near Clear and Small to Large. General statistical practice distinguishes an ordinal outcome, where categories have a rank order, from a continuous measure with equal intervals between every possible value. The registry classifies the posted measure as continuous and reports means and standard deviations. The category definitions help explain the scale, but the record does not describe how the numeric means were formed or whether the analysis accounted for the ordered categories. This is another reason to avoid reading a mean as a complete account of the participants' lesion grades.

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("No Medical Abrading", "Medically Abrading", "Initial Cohort - no Medical Abrading")
n   <- c(9, 14, 13)
m   <- c(-0.75, -1.38, -0.92)
sp  <- c(0.52, 0.9, 0.95)
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  No Medical Abrading  9  -0.750  0.520  -1.150  -0.350
CARM  Medically Abrading  14  -1.380  0.900  -1.900  -0.860
CARM  Initial Cohort - no Medical Abrading  13  -0.920  0.950  -1.494  -0.346

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcome measures. It reports zero analyses. A multiplicity adjustment controls the increased chance of false-positive findings that can arise when many hypotheses are tested. The planned number of hypotheses, any testing hierarchy, and any multiplicity adjustment are not reported in the registry record. With no posted inferential analysis, there is no reported p-value family or adjustment to interpret.

The primary outcome population is described as per-protocol. In general, a per-protocol analysis includes participants who meet specified adherence or protocol criteria; the exact criteria used in this study are not reported in the registry record. A per-protocol estimate may differ from an estimate based on all randomized participants, especially if inclusion depends on events after randomization. The record does not report an intention-to-treat analysis or a comparison between analysis populations.

Missing data methods, the amount and pattern of missing primary outcome observations, and any imputation or sensitivity analyses are not reported in the registry record. The reported outcome group sizes are 9.0, 14.0, and 13.0, while the listed enrollment is 39. These figures do not establish why outcome data are absent for some enrolled participants or whether everyone in the per-protocol population had an observed measurement. The registry record also does not describe how incomplete lesion assessments were handled. These omissions limit assessment of possible attrition bias and of how robust the reported summaries are to missing observations.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event record lists 0 serious events among 9 participants at risk in No Medical Abrading, 0 among 17 in Medically Abrading, and 0 among 13 in Initial Cohort - no Medical Abrading. Deaths are listed as 0 for each group. These figures describe the recorded safety data; zero events in the registry does not establish that an event is impossible or that a treatment is free of risk.

The record also lists other adverse events affecting 1 participant in No Medical Abrading, 2 in Medically Abrading, and 1 in Initial Cohort - no Medical Abrading. The registry distinguishes these from serious adverse events, but the details of the other events are not given in the listed results. No serious adverse-event terms are listed. The period and methods used to collect these events are not reported in the registry record, so the figures should be interpreted as registry counts rather than as a complete description of safety over a specified duration.

The safety denominators differ from the primary outcome group sizes for the Medically Abrading group. The reason is not reported in the registry record. Comparisons of these small descriptive counts should not be treated as formal tests of safety differences.

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

The posted results describe mean Physician's DPN Lesions Assessment values at Day 106 for three groups receiving A-101 topical solution 40%, with and without medical abrasion. The scale's categories range from no visible lesion to a visible elevated lesion. The registry reports group means and standard deviations, but does not report a comparative estimate, confidence interval, or statistical test for the primary outcome.

Accordingly, the record does not establish whether medical abrasion changes the outcome relative to A-101 without abrasion. It also does not establish a causal contrast between the separate no-abrading groups. The randomization label describes the study design, but the posted results do not include the analysis needed to quantify a randomized between-group difference. The initial cohort is listed separately, and its relationship to the other groups is not explained.

The negative mean values require particular caution. Although the scale grades lesions from 0 to 3, the registry does not clearly state whether the reported means are changes from baseline or another summary, so the sign cannot be translated into a specific amount of change. Means and standard deviations also cannot show the distribution of individual lesion grades or the proportion of participants meeting a responder definition. Such additional outcome details are not posted as results.

These findings should not be generalized beyond the population and assessments described in the record. The study summary concerns subjects with Fitzpatrick Skin Type 5 or 6, and the primary analysis population is per-protocol. The record does not provide enough information to assess how participants were selected into that population or how missing outcome data were handled. In general, a registry result is most informative when its endpoint definition, analysis population, and comparative estimate are fully specified. Those details are incomplete for this primary comparison.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a randomized design and a reported randomized treatment comparison. The registry labels the study randomized and parallel, but the primary result available is a set of group-level descriptive summaries. Without an estimated contrast and uncertainty interval, readers cannot determine how precisely the groups differ or whether the observed means are compatible with a range of possible comparative effects.

The three-group presentation also raises an interpretation issue. Two groups are described as A-101 with and without medical abrasion, while a separate initial cohort also received A-101 without abrasion. The registry does not explain the initial cohort's role or how the groups should be compared. Keeping that group distinct avoids assuming that it is interchangeable with the other no-abrading group or that it forms part of a planned contrast.

The endpoint demonstrates why scale definition matters. PLA categories have an ordered clinical description, while the registry reports means and standard deviations. A clear account of whether the values are raw scores or changes, how the scale was summarized, and which lesions or participants contributed would make interpretation more transparent. The missing comparative analysis and incomplete information about analysis populations and missing data further limit what readers can learn from the reported estimates.

Statistically, the record is useful for identifying the study design, intended population, outcome, and the descriptive results that were posted. It also shows why raw summaries should not be treated as proof of a treatment difference. Reporting the analysis methods, a prespecified contrast, its uncertainty, and the handling of missing observations would be needed for a fuller assessment.

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 trial-specific details needed to interpret the primary outcome are not reported in the registry record. In particular, the record does not define whether the negative PLA values are changes from baseline, give a confidence interval, or report a test or estimate for the comparison between medical abrasion and no medical abrasion. It also does not provide the distribution of the lesion grades or the responder results mentioned in the outcome description.

The three outcome groups include two groups described as receiving A-101 without medical abrasion, one identified as an initial cohort. The relationship among these groups, and whether they were intended for direct comparison, is not explained. The randomization process is not described, and masking is listed as none. The record does not clarify who assessed lesions or whether assessment procedures were standardized across groups.

The primary results are identified as per-protocol, but the criteria for that population are not reported. Missing outcome counts, reasons for missingness, and the methods used to address missing observations are also not reported in the registry record. The primary outcome denominators differ from the safety denominators for the Medically Abrading group, without an explanation in the record.

The registry does not report a sample-size justification, statistical analysis plan, or multiplicity approach. It lists no posted secondary outcome measures and zero analyses. These omissions prevent a fuller assessment of the intended analysis and the robustness of the primary result. The safety record gives event counts but does not state the safety observation period or provide detailed terms for the other adverse events. These limitations concern the available registry information; they do not establish why particular details or analyses are absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of A-101 Topical Solution in Subjects With Dermatosis Papulosa Nigra — NCT03224598.
• Registry record last updated 2020-03-30; status last verified 2020-02.
• Results first posted 2020-03-17.
• 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.

19. Record Summary

NCT03224598 is a completed Phase 2, randomized, open-label, parallel-group study of A-101 topical solution 40% for dermatosis papulosa nigra. The registry lists enrollment of 39, a start date of 2017-06-26, and primary completion on 2019-01-08. Its primary measure is Physician's DPN Lesions Assessment at Day 106, reported for a per-protocol population.

Three groups have posted mean PLA values and standard deviations: No Medical Abrading, Medically Abrading, and Initial Cohort - no Medical Abrading. The registry does not report a two-group analysis, confidence interval, or test for the primary outcome. It also does not clarify whether the negative values are change scores. Serious adverse events and deaths are listed as 0 in each safety group, with other adverse events also recorded. Important analysis details, including missing-data methods and the sample-size justification, are not reported in the registry record.