Polidocanol Endovenous Microfoam (PEM) Versus Vehicle for the Treatment of Saphenofemoral Junction (SFJ) Incompetence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Polidocanol Endovenous Microfoam (PEM) Versus Vehicle for the Treatment of Saphenofemoral Junction (SFJ) Incompetence (NCT01231373), a randomized phase 3 study. The primary outcome is Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score).

2. Clinical Question

The trial’s title identifies saphenofemoral junction incompetence as its focus, while its primary outcome is a patient-reported symptom score. The registry record also lists appearance assessments as secondary outcomes. These outcomes address different aspects of the condition: the primary measure records reported symptoms, while the secondary measures concern appearance ratings by patients and photographic review by physicians. The results summarized in the registry therefore concern both symptom change and appearance measures, with the primary statistical interpretation centered on VVSymQ change at 8 weeks.

3. Trial Design

The registry identifies NCT01231373 as a Phase 3, randomized, double-blind, parallel-group study. The listed interventions were polidocanol injectable foam at 0.125%, 0.5%, and 1.0%, and vehicle. The brief description says the study evaluated safety and effectiveness of the concentrations compared with vehicle in treating symptoms and appearance of varicose veins. Arm descriptions beyond the intervention names are not reported in the registry record.

Enrollment was 235. The study status is completed. The registry lists the start as 2010-11 and primary completion as 2011-09. These are registry dates; they do not by themselves describe the follow-up schedule beyond the outcome timeframes specified in the record. The primary outcome timeframe was 8 weeks, and both listed secondary outcomes also use an 8 week timeframe.

The primary endpoint analysis population is described as subjects with a baseline VVSymQ value and a value at the 8 week visit. The reported arm counts for that endpoint are 54 for vehicle, 54 for 0.125%, 60 for 0.5%, and 57 for 1.0%. These are endpoint-specific counts, not a restatement of overall enrollment. The record reports ANCOVA comparisons of vehicle with each foam group. It does not report the trial’s original sample-size justification, detailed allocation procedures, or the full statistical analysis plan. Further information about eligibility criteria, treatment administration, or protocol conduct is 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: Three (3) patients were randomized but never treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Number of subjects with a baseline value (VVSymQ) and value at the 8 week visit.

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: Patients receiving blinded treatment

6. Primary Endpoint

The registry lists the primary outcome as Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score), measured over 8 weeks.

The primary endpoint is change from baseline in the VVSymQ score at 8 weeks. VVSymQ is described as a subset of 5 items from the VEINES-QOL/Sym instrument, selected in earlier studies as important to patients. The daily score sums the duration scores for those 5 symptoms, with scores ranging from 0 to 25. The registry description says symptoms were assessed and graded using duration and intensity scales and that activity level was also assessed; it then describes the VVSymQ score as the sum of the duration scores for the 5 items.

This measure is used to capture symptoms as reported by the patient, rather than relying only on clinician assessment or an appearance rating. A change score compares the recorded value at baseline with the value at the stated follow-up. The posted arm results are least-squares mean changes, accompanied by standard errors. Negative changes indicate decreases in the score from baseline; the registry record does not state a minimum clinically important difference for interpreting the size of a change.

The endpoint is relevant to the stated study purpose because the study brief concerns symptoms as well as appearance. It should nevertheless be interpreted within its defined measurement period and population: the primary comparison concerns the 8 week visit and subjects with both baseline and visit values. The registry record does not report a longer-term symptom result in the primary outcome information.

7. Results Posted in the Registry

• Polidocanol Injectable Foam, 0.125%: mean -5.34 versus -2.00 on control; difference -3.34 (95% CI -4.66 to -2.02), standardized effect d = -0.96; z-test p = <0.001.
• Polidocanol Injectable Foam, 0.5%: mean -6.01 versus -2.00 on control; difference -4.01 (95% CI -5.30 to -2.72), standardized effect d = -1.15; z-test p = <0.001.
• Polidocanol Injectable Foam, 1.0%: mean -5.06 versus -2.00 on control; difference -3.06 (95% CI -4.36 to -1.76), standardized effect d = -0.88; z-test p = <0.001.

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.

Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3)

• 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 errors.
• Result:
  • Polidocanol Injectable Foam, 0.125%: mean -0.74 versus -0.07 on control; difference -0.67 (95% CI -0.89 to -0.45), standardized effect d = -1.11; z-test p = <0.001.
  • Polidocanol Injectable Foam, 0.5%: mean -0.89 versus -0.07 on control; difference -0.82 (95% CI -1.04 to -0.60), standardized effect d = -1.36; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Polidocanol Injectable Foam, 0.125% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Polidocanol Injectable Foam, 0.5% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance

• 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 errors.
• Result:
  • Polidocanol Injectable Foam, 0.125%: mean -1.55 versus -0.32 on control; difference -1.23 (95% CI -1.60 to -0.86), standardized effect d = -1.24; z-test p = <0.001.
  • Polidocanol Injectable Foam, 0.5%: mean -1.86 versus -0.32 on control; difference -1.54 (95% CI -1.90 to -1.18), standardized effect d = -1.54; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Polidocanol Injectable Foam, 0.125% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Polidocanol Injectable Foam, 0.5% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Both listed secondary outcomes concern appearance at 8 weeks: a patient rating and a physician photographic review. Their posted arm means generally show more negative change values in the foam groups than in vehicle, and the reported comparisons for the patient-rated outcome and photographic review are also negative for the listed foam-versus-vehicle contrasts. This overall direction is consistent with the primary endpoint’s pattern of larger decreases in VVSymQ scores in the foam groups than in vehicle. Symptom scores and appearance ratings are different measures, however, so agreement in direction does not make them interchangeable or prove that one outcome explains another.

The registry reports some secondary comparisons with ANCOVA estimates and p-values. Those findings are secondary to the prespecified primary question in the hierarchy of interpretation, particularly because the record does not state whether multiplicity adjustments or a testing sequence were used. When several outcomes and treatment comparisons are examined, unadjusted p-values can overstate the strength of evidence across the full set of questions. A statistically small p-value for an individual secondary comparison does not by itself resolve that broader issue.

The patient-rated appearance outcome includes comparisons with vehicle for 0.125% and 0.5% in the reported analysis list; a corresponding reported comparison for 1.0% is not present in the registry record. For photographic review, the listed comparisons likewise include 0.125% and 0.5%. This description concerns what analyses are posted and should not be read as evidence that an unlisted comparison was negative or not conducted. The registry record does not report a complete account of secondary-outcome analysis decisions or multiplicity handling.

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

• Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3)
• Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score measured on a numeric scale, and the posted group summaries are means. A mean gives a central summary of the scores, but it does not show the distribution of individual values. In this record, the arm estimates are least-squares means and their accompanying dispersion values are standard errors. A standard error describes uncertainty in an estimated mean; it is not the same quantity as the variability of individual observations.

What does the ANCOVA comparison represent?

The registry reports ANCOVA comparisons of vehicle with each foam concentration. In general, analysis of covariance compares groups while accounting for one or more covariates. The registry record labels the reported parameter as a mean difference in final values. It does not identify the covariates used, the model details, or all assumptions checked. Those details are not reported in the registry record, so the analysis should be described at the level the registry states rather than by inferring a specific adjustment model.

The reported mean differences are negative under the comparison ordering of vehicle and foam. For example, the sponsor’s result for the 0.125% group is -3.34. A negative contrast indicates a lower value in the foam group than in vehicle under this direction of subtraction. The registry also gives a confidence interval and p-value for each reported contrast. The values are evidence about the group comparison, not a probability that a particular participant’s result is due to chance.

How do the recalculated estimates differ?

The recalculated comparisons are unadjusted calculations based on posted summary statistics. They use the posted arm means and standard errors to estimate differences and uncertainty. For the primary endpoint, the pooled standard deviations are marked as approximate in the calculation information. This matters because the reported dispersion for the arms is a standard error, not a directly reported standard deviation. Converting or inferring variability from summary information involves assumptions, so these recalculated confidence intervals and p-values should be viewed as approximate and secondary to the sponsor’s own ANCOVA analysis.

In general, an unadjusted comparison does not account for covariates in the way an adjusted model may. The distinction can affect estimates and uncertainty. The recalculated results are useful as a transparent check of the broad pattern in the posted summaries, but they do not reproduce every aspect of the trial’s analysis. The registry record does not report enough model detail to reconstruct the ANCOVA.

What does a p-value say?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The sponsor-reported primary comparisons each have p < 0.001. The recalculated unadjusted comparisons each have p < 0.001. These values should be kept tied to their respective analyses; the two reporting formats are not interchangeable.

Multiple comparisons are relevant because the primary outcome was compared across three foam concentrations against vehicle, and the record also lists secondary outcomes. In general, when many hypotheses are tested, the chance of at least one apparently unusual result can rise unless the analysis accounts for multiplicity. Whether the original trial used a multiplicity adjustment or a prespecified testing order is not reported in the registry record. Therefore, the posted p-values should not be described as multiplicity-adjusted unless that information is available.

Why does over-dispersion matter?

For count outcomes, over-dispersion means that the observed variation exceeds what a simple model assumes; accounting for it can change standard errors and inferences. The primary endpoint is a continuous score, not a count outcome, so over-dispersion is not the central issue in interpreting these primary comparisons. More generally, choosing a model that reflects the outcome type and variability is important. The registry record does not report diagnostics or a detailed rationale for the analysis method.

The endpoint population is described as participants with baseline and 8 week values. This defines the available observations for the reported measure, but it does not explain how missing values were handled beyond that definition. The original analysis population, imputation procedures, and sensitivity analyses are not reported in the registry record. Consequently, interpretation should stay focused on the reported endpoint estimates and the stated population rather than assuming how unobserved outcomes were treated.

Finally, statistical inference depends on design and analysis choices, including the outcome definition, comparison direction, model specification, and handling of incomplete observations. The registry provides the study’s randomized, double-blind, parallel design and the reported analyses, but not a complete protocol or statistical plan. General explanations of these methods do not supply the missing trial-specific details.

11. Confidence Intervals and Precision

The sponsor’s primary ANCOVA estimates are accompanied by 95% confidence intervals. For the 0.125% comparison, the interval is -4.63 to -2.04; for 0.5%, it is -5.26 to -2.74; and for 1.0%, it is -4.33 to -1.77. Each interval lies below zero, consistent with the negative estimated differences in the reported contrast direction.

In general, a confidence interval gives a range of values reasonably compatible with the data and the assumptions of the method. Its width conveys precision: narrower intervals indicate more precise estimates, while wider intervals leave greater uncertainty about the contrast. A 95% confidence level refers to the long-run performance of the interval procedure under its assumptions; it is not a statement that there is a 95% probability that this particular interval contains the true effect.

The recalculated unadjusted intervals are similar in broad location but are not identical to the sponsor’s intervals. They are -4.657 to -2.023 for 0.125%, -5.296 to -2.724 for 0.5%, and -4.359 to -1.761 for 1.0%. The differences reflect that these are simple unadjusted recalculations from summary statistics, whereas the registry reports ANCOVA. The sponsor’s analysis is the principal reported analysis; the recalculated intervals are a supplementary check.

Confidence intervals quantify statistical uncertainty around average contrasts. They do not show the full spread of individual symptom scores, establish clinical importance, or describe outcomes after the stated 8 week timeframe. The registry record does not provide a clinical-importance threshold for VVSymQ change. Precision of an estimate and clinical meaning are related questions, but they are not the same question.

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. They are participants per arm for 80% power and participants per arm for 90% power. They are not total events: the endpoint is continuous, so the figures describe people planned in each of two comparison arms.

The stated planning assumptions 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 the stated fraction of the observed effect. The rows for 100% of the observed effect use the full observed contrast as the planning target; rows for 75% and 50% use smaller targets. These are illustrations computed from observed results, not a report of the original trial’s assumptions. The trial’s own sample-size justification is not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation associates with an 80% chance of detecting the specified effect, if the assumptions hold. The 90% power column gives the corresponding per-arm number for a 90% chance. In general, greater planned power requires more participants when other assumptions remain the same. Likewise, smaller effects need more participants to detect reliably, which is why planning for 75% or 50% of the observed effect requires larger figures than planning for the full observed effect.

These figures are not observed power. They do not describe the probability that the completed trial “had power” after results were known. Use the curve to understand how the illustrative per-arm requirement changes as the target effect is reduced, rather than as evidence about the study’s original design or a guarantee of future results.

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 = -3.340; pooled standard deviation σ = 3.491.
2. n = 2 × (1.96 + 0.842)² × 3.491² / -3.340² = 17.1, rounded up to 18 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 <- -3.34                      # observed difference in means
sigma <- 3.49053061868822                     # 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(1231373)
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 = 18 (80% power), 23 (90% power)
 75% of observed effect: n per arm = 31 (80% power), 41 (90% power)
 50% of observed effect: n per arm = 69 (80% power), 92 (90% power)
power.t.test: 18.2 
Simulated power at n = 18 per arm: 0.796 (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. Analyses Reported by the Sponsor

The registry’s sponsor-reported primary analyses use ANCOVA and report mean differences in final values. The estimates are -3.34 for 0.125%, -4.00 for 0.5%, and -3.05 for 1.0%, each with a 95% confidence interval and p < 0.001. These are the trial’s own posted analyses and should be the main reference for interpreting the primary comparisons.

The recalculated comparisons use the posted arm summaries to form unadjusted mean differences. They are -3.34, -4.01, and -3.06, with corresponding unadjusted p-values of < 0.001. The small differences in estimates and interval limits are consistent with the fact that these calculations do not reproduce the ANCOVA model. The recalculations are useful for checking the direction and approximate scale of the posted results, not for replacing the sponsor’s model-based analysis.

The record identifies no discrepancy between the sponsor’s analysis and the recalculation. The recalculated estimates should nevertheless be understood as supplementary because they use a different, simpler method and rely on summary statistics. The registry does not report sufficient details to reproduce the covariate adjustment or every analytical choice in the sponsor’s model. Any interpretation of the formal trial results should therefore retain the distinction between the sponsor-reported ANCOVA and the unadjusted recalculation.

15. Multiplicity, Missing Data and Analysis Populations

The primary results include three comparisons: each of the three foam concentrations against vehicle. The registry also lists two secondary appearance outcomes, with reported analyses for some treatment contrasts. Testing several hypotheses raises a multiplicity question because, in general, the chance of at least one apparently significant result increases as the number of tests increases. Approaches such as prespecifying an order of testing or adjusting significance criteria can address this, but the registry record does not report whether either approach was used.

The sponsor-reported primary p-values are each < 0.001, and the registry reports 95% confidence intervals for those contrasts. The record does not identify whether those intervals or p-values are adjusted for multiple comparisons. The recalculated p-values are explicitly unadjusted calculations from summary statistics. They should not be interpreted as a multiplicity-controlled family of tests. For the secondary outcomes, the same caution applies: the record does not report a multiplicity procedure, so their p-values carry less weight as confirmatory evidence than a result from a clearly prespecified and controlled testing plan would.

The primary endpoint population is defined as subjects with a baseline VVSymQ value and a value at the 8 week visit. This provides a criterion for inclusion in the reported measure, but the registry record does not explain how participants without one of those values were handled. Imputation, missing-data assumptions, sensitivity analyses, and reasons for missing visits are not reported in the registry record.

The registry also does not give a complete account of the analysis population for every endpoint, such as whether all randomized participants were included under a particular intention-to-treat definition. The listed endpoint counts should therefore be treated as the counts attached to those reported measures, not as proof of a specific population strategy. Without the missing-data and population details, the posted estimates can be described, but the robustness of conclusions to alternative handling of incomplete observations cannot be assessed from the registry record alone.

16. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures report 0 affected participants in each listed group. The corresponding numbers at risk were 59 for vehicle, 58 for polidocanol injectable foam 0.125%, 60 for 0.5%, and 58 for 1.0%. The registry lists no serious adverse event terms in the top serious terms information.

These figures concern participants reported as affected by serious adverse events, not all adverse events. The record separately lists other adverse event counts, but those should not be conflated with serious events. Death counts are not reported in the registry record. The numbers at risk in this safety listing differ from the endpoint-specific counts for the primary symptom outcome, because the listings concern different reported measures and populations.

A zero count in the posted serious-event fields means that no affected participants were recorded there; it does not establish that risk is absent or rule out events not captured in the record. The safety figures also do not, by themselves, determine comparative safety. Interpretation depends on the definitions, observation period, completeness of reporting, and event details, which are not fully described in the registry record.

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

The posted results show that the mean VVSymQ score decreased from baseline in all four groups by the 8 week assessment, with larger negative mean changes in each foam group than in vehicle. The sponsor’s ANCOVA comparisons estimate lower final values in the foam groups than in vehicle, and all three reported primary confidence intervals lie below zero. These are statistical descriptions of group averages under the registry’s reported analysis.

The result does not establish that every participant experienced a decrease, that the same pattern applies to every person with varicose veins, or that the differences are clinically important. The registry record does not state a threshold for a meaningful VVSymQ change. It also does not establish persistence beyond the 8 week timeframe reported for the primary endpoint.

Nor do the findings, by themselves, answer every question about the treatment. The listed primary endpoint measures patient-reported symptoms, while secondary outcomes measure appearance. The posted group estimates do not replace information about individual experiences, broader safety interpretation, or outcomes not included in the registry results. The serious adverse event listing records zero affected participants in each group, but a registry count is not proof of no possible risk.

Statistical evidence and practical importance are distinct. Confidence intervals and p-values summarize uncertainty under particular methods; they do not determine whether a difference matters to patients or support medical advice. The registry record does not report all protocol and analysis details needed to assess every source of uncertainty. The most defensible reading is therefore limited to the reported comparisons, endpoint definition, analysis population, and follow-up timeframe.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares three concentrations of an intervention against a vehicle group in a randomized, double-blind, parallel design. The primary endpoint is a patient-reported continuous symptom score, which permits estimation of group mean changes and contrasts. The registry reports both the group-level changes and ANCOVA comparisons, allowing readers to distinguish the observed arm summaries from the adjusted comparison reported by the sponsor.

It also illustrates why estimates should be read alongside uncertainty. The confidence intervals show ranges around the primary contrasts, while the p-values address compatibility with a null comparison under the analysis assumptions. Neither alone gives a measure of clinical importance. The absence of a reported clinical-importance threshold makes that distinction especially relevant when interpreting score changes.

The record also provides a basis for methodological scrutiny. The sponsor’s ANCOVA results and the unadjusted recalculations are similar in direction and approximate magnitude, but they are not the same analysis. The trial has multiple primary treatment comparisons and secondary outcomes, while the registry does not report multiplicity procedures or a full analysis plan. That makes it important to separate confirmatory conclusions from secondary or exploratory interpretation.

Finally, the primary endpoint’s 8 week timeframe and stated analysis population define the reach of the results. Readers can interpret the comparisons at that visit, but should not infer longer-term effects, missing-data robustness, or original planning rationale from information not reported in the registry record. The case demonstrates how design, estimand, precision, and reporting completeness jointly shape statistical interpretation.

19. 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 registry record does not provide the full protocol or statistical analysis plan. Details such as the covariates in the ANCOVA, the sample-size justification, any interim analyses, and any prespecified approach to multiplicity are not reported in the registry record. These omissions limit the ability to assess how closely the posted analyses follow the original plan.

The primary endpoint is reported at 8 weeks, and the primary analysis population requires both baseline and 8 week values. The registry does not describe missing-value handling, reasons for missing observations, or sensitivity analyses. It also does not provide enough information to establish how the analysis population relates to all randomized participants. These gaps matter when considering whether the available measurements fully represent the randomized groups.

The clinical meaning of the score contrasts is not established by the reported statistics alone. A minimum important difference is not reported in the registry record, and the results concern group averages rather than the distribution of individual changes. The record also does not report a longer-term primary symptom outcome, so durability cannot be assessed from these primary results.

The safety summary lists serious-event counts but does not provide serious event terms or death counts. The registry record’s absence of serious-event terms and its zero affected counts should be interpreted as a limitation of the posted summary rather than a comprehensive account of all possible harms. Finally, the recalculated unadjusted comparisons depend on summary information and approximate variability estimates; they cannot reproduce the sponsor’s ANCOVA model. The sponsor-reported analysis remains the main formal comparison.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Polidocanol Endovenous Microfoam (PEM) Versus Vehicle for the Treatment of Saphenofemoral Junction (SFJ) Incompetence — NCT01231373.
• Registry record last updated 2021-04-21; status last verified 2021-04.
• Results first posted 2014-04-02.
• 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.

23. Record Summary

NCT01231373 is a completed Phase 3, randomized, double-blind, parallel-group study of polidocanol injectable foam concentrations 0.125%, 0.5%, and 1.0% compared with vehicle in people with varicose veins. Enrollment was 235, and the registry lists the study start as 2010-11 and primary completion as 2011-09.

The primary outcome was change in patient-reported VVSymQ symptoms at 8 weeks. The posted group mean changes were -2.0 for vehicle, -5.34 for 0.125%, -6.01 for 0.5%, and -5.06 for 1.0%. Sponsor-reported ANCOVA comparisons found negative differences for each foam group versus vehicle, with p < 0.001 for each.

Secondary outcomes assessed appearance at 8 weeks. The safety listing records 0 serious adverse event-affected participants in each group; deaths are not reported in the registry record. Details about multiplicity, missing-data methods, the trial’s original sample-size justification, and the complete statistical analysis plan are not reported in the registry record.