Topical NVN1000 for the Treatment of External Genital and Perianal Warts: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical NVN1000 for the Treatment of External Genital and Perianal Warts (NCT02462187), a randomized phase 2 study. The primary outcome is Efficacy: Complete Clearance of Baseline External Genital and Perianal Warts at or Before Week 12.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, vehicle-controlled, parallel-group study of topical NVN1000. The registry lists an enrollment of 108 and identifies external genital warts and perianal warts as the conditions under study. The study began on 2015-06-12, had primary completion in 2016-10, and is listed as completed. The sponsor was Novan, Inc.

Four active regimens were studied: NVN1000 8% gel twice daily, NVN1000 8% gel once daily, NVN1000 16% once daily, and NVN1000 24% once daily. Vehicle gel was administered once daily or twice daily, with the vehicle frequency intended to match active treatment. The endpoint counts list 12 participants in the 8% twice-daily group, 24 in the 8% once-daily group, 14 in the 16% once-daily group, 30 in the 24% once-daily group, 23 in the once-daily vehicle group, and 4 in the twice-daily vehicle group.

Randomization and double masking can reduce some sources of allocation and assessment bias, although the registry record does not describe the randomization procedure, masking procedures, or allocation concealment in detail. It describes the primary assessment as physical examination by the investigator. The record identifies the primary population as ITT, but notes that one randomized subject in the 8% twice-daily group did not receive treatment and was excluded from that population. Further population definitions and details of participant flow are not reported in the registry record.

The study assessed tolerability, safety, and efficacy. Listed secondary outcomes include tolerability scores, changes in laboratory assessments, complete clearance of total warts, and complete or partial clearance of baseline warts. The registry record does not report the original sample-size justification or the full prespecified statistical analysis plan.

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

Analysis population for the primary outcome, as defined in the registry: ITT population. One subject in the NVN1000 8% Gel BID group was randomized but not dispensed treatment and thus was excluded from the ITT population..

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: Intent to Treat Population (ITT)--the ITT includes all study subjects who were randomized and dispensed study medication.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Efficacy: Complete Clearance of Baseline External Genital and Perianal Warts at or Before Week 12, measured over 12 weeks.

The primary endpoint was the count of participants with complete clearance of baseline external genital and perianal warts at or before Week 12. Clearance was determined by physical examination by the investigator. The endpoint focuses on whether all baseline warts met the study's clearance criterion by the specified time, rather than on partial improvement or change in the total wart count. The registry record does not provide a more detailed operational definition of complete clearance.

A binary endpoint of this kind can be summarized by counting participants who meet the criterion and comparing that count with the number assessed in each group. The posted groups have counts of 2 of 12 for 8% twice daily, 5 of 24 for 8% once daily, 2 of 14 for 16% once daily, and 10 of 30 for 24% once daily. In the once-daily vehicle group, 1 of 23 participants met the endpoint. The twice-daily vehicle group is listed separately, with 2 of 4 meeting the endpoint, but it is not the comparator used in the posted primary comparisons.

Complete clearance is a clinically interpretable outcome because it describes an all-or-none status at a defined assessment time. That simplicity does not capture partial clearance, duration of response, or later recurrence. Those are different questions, and the registry record does not report recurrence as part of this primary endpoint. The primary measure also does not, by itself, summarize tolerability or safety, which are addressed separately in the listed outcomes.

7. Results Posted in the Registry

• Cohort 1: NVN1000 8% Gel Twice Daily: 16.7% (2/12) versus 4.3% (1/23) on control; risk difference 12.3 percentage points (95% CI -10.4 to 35.0), risk ratio 3.83 (0.39–38.11); unadjusted two-proportion z-test p = 0.217.
• Cohort 2: NVN1000 8% Gel Once Daily: 20.8% (5/24) versus 4.3% (1/23) on control; risk difference 16.5 percentage points (95% CI -1.8 to 34.7), risk ratio 4.79 (0.60–37.95); unadjusted two-proportion z-test p = 0.090.
• Cohort 3: NVN1000 16% Once Daily: 14.3% (2/14) versus 4.3% (1/23) on control; risk difference 9.9 percentage points (95% CI -10.2 to 30.1), risk ratio 3.29 (0.33–32.99); unadjusted two-proportion z-test p = 0.283.
• Cohort 4: NVN1000 24% Once Daily: 33.3% (10/30) versus 4.3% (1/23) on control; risk difference 29.0 percentage points (95% CI 10.2 to 47.8), risk ratio 7.67 (1.06–55.67); unadjusted two-proportion z-test p = 0.010.

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.

Percentage of Subjects With Complete Clearance of Total EGW/PAW at or Before Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cohort 1: NVN1000 8% Gel Twice Daily: 16.7% (2/12) versus 4.3% (1/23) on control; risk difference 12.3 percentage points (95% CI -10.4 to 35.0), risk ratio 3.83 (0.39–38.11); unadjusted two-proportion z-test p = 0.217.
  • Cohort 2: NVN1000 8% Gel Once Daily: 20.8% (5/24) versus 4.3% (1/23) on control; risk difference 16.5 percentage points (95% CI -1.8 to 34.7), risk ratio 4.79 (0.60–37.95); unadjusted two-proportion z-test p = 0.090.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort 1: NVN1000 8% Gel Twice Daily and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort 2: NVN1000 8% Gel Once Daily and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects With Complete or Partial Clearance of Baseline Warts at or Before Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cohort 1: NVN1000 8% Gel Twice Daily: 66.7% (8/12) versus 47.8% (11/23) on control; risk difference 18.8 percentage points (95% CI -14.7 to 52.4), risk ratio 1.39 (0.78–2.50); unadjusted two-proportion z-test p = 0.288.
  • Cohort 2: NVN1000 8% Gel Once Daily: 79.2% (19/24) versus 47.8% (11/23) on control; risk difference 31.3 percentage points (95% CI 5.2 to 57.4), risk ratio 1.66 (1.03–2.66); unadjusted two-proportion z-test p = 0.025.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort 1: NVN1000 8% Gel Twice Daily and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Cohort 2: NVN1000 8% Gel Once Daily than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes address related but distinct aspects of the study. Complete clearance of total external genital and perianal warts is a separate clearance definition from complete clearance of baseline warts. Complete or partial clearance of baseline warts uses a broader outcome than the primary endpoint because partial improvement can qualify. The registry also lists tolerability scores and changes in laboratory assessments, but numerical results for those outcomes are not included in the posted outcome data.

For complete clearance of total warts, the posted counts were 2 of 12 for 8% twice daily, 5 of 24 for 8% once daily, 2 of 14 for 16% once daily, 9 of 30 for 24% once daily, and 1 of 23 for once-daily vehicle. For complete or partial clearance of baseline warts, the respective counts were 8 of 12, 19 of 24, 10 of 14, 17 of 30, and 11 of 23. These outcomes give context for the primary endpoint, but they should not be treated as interchangeable measurements. Broader partial-clearance criteria can yield a different pattern from the all-or-none primary measure.

The posted secondary comparisons do not cover every active regimen for every endpoint, and the registry lists no reported analyses for these outcomes. The comparisons are unadjusted, and the record does not report a correction for testing multiple endpoints and regimens. When many comparisons are considered, some apparently notable findings can arise by chance even if no real differences exist. Secondary results are therefore useful for describing the pattern and informing future study questions, but they carry less weight than a clearly prespecified, appropriately analyzed primary result. The registry record does not describe a hierarchy or testing strategy that would establish confirmatory status for these secondary findings.

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

• Tolerability of Topical NVN1000 Gel as Determined by Scores on a 4 Point Grading Scale for Erythema, Edema, Erosions/Ulcers, and Itch
• Safety as Determined by Changes in Laboratory Assessments
• Percentage of Subjects With Complete Clearance of Total EGW/PAW at or Before Week 12
• Percentage of Subjects With Complete or Partial Clearance of Baseline Warts at or Before Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant either met the complete-clearance criterion by Week 12 or did not. A count and denominator describe how often the event occurred in each group. The posted comparisons use the risk difference, which expresses the active-group event proportion minus the event proportion in the once-daily vehicle group. A positive risk difference means the event was more frequent in the active group in these observed data. This is a comparison of proportions, not a measure of the number of warts cleared or the time until clearance.

What does a confidence interval add?

A confidence interval describes uncertainty around an estimated effect under the statistical method used. It is not a range containing the true value with certainty, nor does it measure the probability that a treatment works. For the primary comparisons, intervals that extend below zero and above zero include no difference as a possibility under the interval method. The 24% once-daily comparison has an interval from 0.102 to 0.478, which does not include zero. The width of an interval matters as well as whether it crosses zero: a wide interval indicates less precision and leaves a broader range of effects compatible with the data.

How should the p-values be read?

The posted p-values are unadjusted. A p-value describes how unusual data at least as incompatible with a specified no-difference model would be, if that model and the test assumptions held. It is not the probability that the no-difference model is true, and it does not quantify clinical importance. The registry record does not report the sponsor's test specification or state a multiplicity adjustment. Consequently, the p-values should be interpreted alongside the effect estimates, confidence intervals, group sizes, and the number of comparisons rather than as stand-alone decisions.

What is a risk ratio or odds ratio?

A risk ratio compares event proportions by division, while an odds ratio compares the odds of the event. These measures use different scales from the risk difference, so their numerical values are not interchangeable. The posted primary comparison data include risk-ratio and odds-ratio estimates and intervals, but the main interpretation uses risk differences because they express the absolute difference in observed event proportions. In small groups and with few events, ratio estimates can be especially uncertain; the registry's intervals should be read as part of the result rather than relying only on the point estimate.

Why does the comparison group matter?

The primary comparisons use once-daily vehicle, which has 1 of 23 participants meeting the endpoint. Although the registry also reports a twice-daily vehicle group, it contains 2 of 4 participants meeting the endpoint and is not the control used for the posted active-regimen comparisons. The active groups and their vehicle comparator have different group sizes. A randomized study is intended to support fair comparisons, but randomization does not guarantee that every characteristic is balanced in a small sample. Baseline characteristics and adjusted estimates are not reported in the registry record, so the posted comparisons do not allow assessment of how covariate adjustment might affect results.

What does the analysis population mean?

The primary outcome is labeled as being for the ITT population. The registry's description says one subject randomized to 8% twice daily was not dispensed treatment and was excluded from that population. This is a specific departure from retaining every randomized subject in the stated population. The record does not explain whether other missing endpoint data occurred, how missing outcomes were handled, or whether sensitivity analyses were conducted. The endpoint denominators are the group sizes reported with the posted counts; they should not be mistaken for a full account of missing-data handling.

In general, a binary-outcome analysis can use methods with different assumptions, especially when event counts are small. The posted comparison statistics include unadjusted estimates and p-values, but the statistical test and interval construction are not reported in the registry record. The record also does not describe stratification, covariate adjustment, interim analyses, or a hierarchy for testing outcomes. Those details should not be inferred from the numerical output. General statistical interpretation is therefore limited to what the reported group counts and comparison estimates support.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate a difference, not whether that difference is important in practice. For the primary endpoint, the risk-difference confidence intervals are -0.103 to 0.350 for NVN1000 8% twice daily, -0.018 to 0.347 for 8% once daily, -0.102 to 0.301 for 16% once daily, and 0.102 to 0.478 for 24% once daily. The first three intervals include zero; the last does not. Their widths indicate that the estimates are not exact, and the intervals leave substantial uncertainty about the size of the difference.

Small event counts are relevant to that uncertainty. The once-daily vehicle group had 1 participant with complete clearance, and the active-group counts ranged from 2 to 10. With few events and modest groups, changing the outcome status of a participant can have a noticeable influence on an observed proportion. The confidence intervals make uncertainty visible, but they do not remove limitations from sparse data or from the study design.

The registry record does not report adjusted confidence intervals or a sponsor analysis for these comparisons. The posted intervals accompany unadjusted risk differences. They also do not account, as presented, for the fact that several active regimens and additional outcomes were assessed. The methods used to calculate the intervals are not reported in the registry record, so their precise coverage properties cannot be independently interpreted from the record alone.

The interval for 24% once daily is entirely above zero, but its range still includes effects of notably different magnitudes. A point estimate should therefore not be treated as a precise forecast. For the other regimens, the intervals are compatible with both no difference and positive differences. None of these intervals establishes the likely effect in a new setting; they describe uncertainty around the posted comparisons for the trial groups.

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 sample-size figures are planning illustrations based on the observed effects, not the trial's original design calculations. For these binary outcomes, the figures refer to participants per arm, not total events. The assumptions listed for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The original trial's sample-size assumptions and justification are not reported in the registry record.

The 80% power column means the illustrated number of participants per arm for a future comparison to have an 80% chance of detecting the specified effect under the listed assumptions, if that effect and the statistical model are correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are design concepts: power is the probability of rejecting the no-difference model under a specified alternative, not a measure of how likely the observed result is to be true.

The planning rows also consider effects smaller than the observed effect. For example, planning for 75% of the observed effect or 50% of the observed effect requires more participants per arm than planning for 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so more information is generally needed to detect them under otherwise similar assumptions. The exact figures vary by comparison because the observed event rates and estimated effects differ.

These values are not observed power. They should not be read as a statement about the chance that this completed trial detected a real effect, and they do not indicate that the trial was designed using those assumptions. They are conditional illustrations for planning, based on the observed comparison estimates, which themselves are uncertain.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.043; treatment proportion p₁ = 0.167; average p̄ = 0.105.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4337 = 0.8500.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4248 = 0.3575.
4. n = (0.8500 + 0.3575)² / (0.1232)² = 96.1, rounded up to 97 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
p0 <- 0.0434782608695652                          # control proportion
p1 <- 0.166666666666667                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2462187)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 97 (80% power), 129 (90% power)
 75% of observed effect: n per arm = 149 (80% power), 199 (90% power)
 50% of observed effect: n per arm = 284 (80% power), 379 (90% power)
power.prop.test: 96.1 
Simulated power at n = 97 per arm: 0.833 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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

The study includes multiple active regimens, a once-daily vehicle comparator, a separate twice-daily vehicle group, and several outcomes. Testing several comparisons creates a multiplicity concern: the more statistical tests considered, the greater the chance that at least one result appears notable by chance. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for controlling that risk. The posted primary p-values are unadjusted, and the secondary comparisons are also unadjusted.

The registry describes the primary analysis population as ITT but notes that one randomized subject in the 8% twice-daily group was not dispensed treatment and was excluded. The rationale for this population definition is stated, but further details about participant disposition are not reported in the registry record. It does not report how missing Week 12 assessments, if any, were handled, whether outcomes were imputed, or whether sensitivity analyses were performed. The denominators attached to outcome counts identify the groups used for those summaries; they do not by themselves reveal every aspect of missing-data handling.

The record lists zero reported analyses and does not provide a sponsor statistical analysis plan or a sponsor-reported primary comparison. The inferential method, interval construction, covariate adjustment, and handling of any protocol deviations are not reported in the registry record. It would therefore be inappropriate to assume that an unadjusted calculation reproduces the sponsor's intended analysis or that the listed endpoint summaries reflect all planned analyses. General limitations from multiple testing and incomplete reporting remain relevant when interpreting the posted findings.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal adhesions (8.3%), cellulitis (8.3%), prostate cancer (8.3%), affective disorder (7.1%).

The serious adverse event summaries report affected participants and participants at risk by group. Serious events were reported for 2 of 12 participants in the 8% twice-daily group, 0 of 23 in the 8% once-daily group, 1 of 14 in the 16% once-daily group, and 0 of 30 in the 24% once-daily group. The once-daily vehicle group had 0 of 20 participants with serious events in the safety summary, and the twice-daily vehicle group had 0 of 4. Deaths were reported as 0 in every group.

The safety denominators differ from some efficacy denominators; for example, the primary endpoint lists 23 participants for once-daily vehicle, while the serious-event summary lists 20 at risk. These summaries should be read using their stated denominators rather than combined. The record lists abdominal adhesions, cellulitis, and prostate cancer at 8.3%, and affective disorder at 7.1%, among the top serious event terms. The record does not establish from these listings whether an event was caused by study treatment.

Event counts alone do not describe timing, duration, severity beyond the serious-event classification, or clinical context. The registry also lists other adverse-event counts by group, but no causal interpretation follows from those counts alone.

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

The posted primary results describe the proportion of participants in each trial group who had complete clearance of baseline warts by Week 12. More participants met that endpoint in each NVN1000 group than in the once-daily vehicle group in the observed data. The largest posted primary risk difference is for NVN1000 24% once daily, with an estimate of 0.290 and a confidence interval from 0.102 to 0.478. For the other active regimens, the confidence intervals include zero. These are findings from the groups enrolled in this Phase 2 study, not a guarantee of outcomes for other people or settings.

The results do not establish that NVN1000 caused the observed differences. Randomization and masking are strengths of the design, but the registry record does not report enough detail to assess the full analysis procedure, multiplicity handling, or missing-data approach. The groups are modest in size, and the posted event counts are small. The estimates and intervals should be considered together rather than focusing on a single p-value or point estimate.

The primary endpoint measures complete clearance at or before Week 12. It does not answer how quickly clearance occurred, whether clearance persisted, whether warts later recurred, or how partial improvement affected participants. Secondary clearance outcomes add different perspectives, but their unadjusted comparisons do not replace the primary result. The listed tolerability and laboratory outcomes are not fully quantified in the posted data.

The safety summaries report serious adverse events and deaths by group, but they do not determine whether an event was treatment-related or provide a comprehensive clinical assessment. Accordingly, these data support a statistical description of observed outcomes and uncertainty, not medical advice or a definitive judgment about benefit or harm. Further interpretation depends on analyses and details that are not reported in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically informative as an example of a randomized, vehicle-controlled study with several active dosing regimens and a binary primary endpoint. The results show why counts, denominators, effect estimates, and uncertainty need to be considered together. A positive point estimate describes the direction of the observed difference, while a confidence interval shows how imprecisely that difference is estimated. In this study, the event counts are small enough that uncertainty is central to interpretation.

The ascending-dose structure can generate questions about whether observed outcomes vary across regimens, but the posted comparisons are each against once-daily vehicle. They do not directly test differences between active doses. A pattern across point estimates should not be mistaken for a formal dose-response analysis. Such an analysis and its assumptions are not reported in the registry record.

The trial also illustrates the importance of transparent reporting. The record provides a primary endpoint and group counts, yet does not report a sponsor analysis, the detailed statistical plan, multiplicity procedures, or missing-data handling. Those omissions limit how confidently a reader can connect the posted unadjusted comparisons to the study's prespecified inferential aims. Planning illustrations based on observed effects can help show how sample-size needs change as target effects become smaller, but they do not reveal the original design rationale.

For biostatisticians and clinical researchers, the central lesson is to distinguish an observed contrast from a definitive conclusion. The estimated differences are useful descriptions, but their precision, the multiple comparisons, endpoint definitions, and incomplete methods reporting all shape what can be inferred.

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 trial-specific limitations affect interpretation. The study is described as Phase 2 and includes four active regimens, with modest group sizes and relatively few primary endpoint events. The once-daily vehicle comparison group had 1 of 23 participants meeting the primary endpoint, so the estimates may be sensitive to a small number of outcomes. The confidence intervals are broad for several comparisons, and only the 24% once-daily interval excludes zero.

The primary endpoint is complete clearance of baseline warts by Week 12, based on investigator physical examination. The registry does not provide a detailed clearance definition, information about assessor training, or an account of repeatability of assessments. This endpoint does not measure persistence of clearance or recurrence. The secondary outcomes use different clearance criteria and should not be treated as interchangeable with the primary measure.

The record reports an ITT population but states that one randomized subject in the 8% twice-daily group was excluded because treatment was not dispensed. It does not provide fuller missing-data details, participant flow, or sensitivity analyses. Safety group denominators differ from efficacy denominators, and the record does not explain the difference. It also does not report the statistical analysis plan, adjusted analyses, multiplicity control, or detailed randomization and masking procedures.

Finally, the posted primary comparisons are unadjusted and the registry reports no analyses. The listed study enrollment does not itself explain the size or composition of each analysis group. These reporting gaps mean that the findings are best treated as limited descriptive evidence rather than as a complete account of the trial's intended statistical analysis.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Topical NVN1000 for the Treatment of External Genital and Perianal Warts — NCT02462187.
• Registry record last updated 2023-04-06; status last verified 2023-04.
• Results first posted 2023-04-05.
• 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

NCT02462187 is a completed, randomized, double-blind, parallel, vehicle-controlled Phase 2 study of topical NVN1000 for external genital and perianal warts. The registry lists enrollment of 108, a start date of 2015-06-12, and primary completion in 2016-10. It studied 8% gel twice daily, 8% once daily, 16% once daily, and 24% once daily, with vehicle gel administered once or twice daily.

The primary endpoint was complete clearance of baseline warts at or before Week 12. Posted counts were higher in each active group than in the once-daily vehicle group, with the largest risk-difference estimate for 24% once daily. The unadjusted confidence intervals include zero for three active-regimen comparisons and exclude zero for the 24% once-daily comparison. The registry record does not report a sponsor analysis, the original sample-size justification, or details of multiplicity and missing-data procedures.