Endovenous Ablation With and Without Polidocanol Endovenous Microfoam Treatment for Patients With Great Saphenous Vein Incompetence and Visible Varicosities: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Endovenous Ablation With and Without Polidocanol Endovenous Microfoam Treatment for Patients With Great Saphenous Vein Incompetence and Visible Varicosities (NCT01197833), a randomized phase 3 study. The primary outcome is Absolute Change From Baseline in Independent Photography Review (IPR-V3 Score).

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 3, randomized, double-blinded, parallel-group study. Its official title describes a multicenter study of endovenous thermal ablation with or without Varisolve™ polidocanol endovenous microfoam treatment. The record lists Boston Scientific Corporation as sponsor, an enrollment of 117, a start date of 2010-09, primary completion in 2012-03, and a completed status.

All outcome arms include endovenous ablation. The control arm is labelled endovenous ablation with vehicle placebo. The posted results also include foam arms labelled 0.5% and 1.0%, with 39 and 40 participants respectively; the control arm has 38. These are outcome-arm labels and counts. They do not resolve the differing concentration names elsewhere in the registry record: the intervention list includes 0.125%, 1.0%, and 2.0%, while an arm description names 0.125% and another names 1.0%. The complete correspondence among intervention names, arm descriptions, and outcome labels is not reported in the registry record.

The primary outcome is a continuous score, reported as a least-squares mean with standard error. The assessment timeframe is baseline and 8 weeks. The registry describes the study purpose as evaluating safety and effectiveness of polidocanol endovenous microfoam compared with vehicle after heat treatment. Its brief summary refers to two different doses, but the posted outcome arms contain two foam labels and a vehicle arm. Further details about allocation procedures, the concealment process, the exact blinding arrangements, and the original statistical design assumptions 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.

Overall Study

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: all treated patients

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change From Baseline in Independent Photography Review (IPR-V3 Score), measured over IPR-V3 measured at baseline and then at 8 weeks.

The primary endpoint is absolute change from baseline in the Independent Photography Review—Visible Varicose Veins score, measured at baseline and 8 weeks. It is a continuous appearance measure on a five-point scale: none is scored as 0, and very severe as 4, with mild, moderate, and severe between them. The outcome description says the assessment considers caliber, dilatation, tortuosity, and the extent and number of visible varicosities.

At screening, a site clinician reviewed the visible varicosities in the medial section of each leg and selected a score representing their appearance. Reference photographs were used to assist with assigning that screening score. The registry names the primary measure as an independent photography review, but does not give further details of how the review was conducted or how scores were combined across legs.

A change score expresses how the measured appearance score differs at follow-up from baseline. Because higher scale values represent more severe visible varicosities, negative changes indicate a lower score at follow-up than at baseline. That describes the direction of the scale, not a judgment about clinical importance. The registry record does not report a threshold for a meaningful change, nor does it report additional secondary outcomes in the posted results.

7. Results Posted in the Registry

• Endovenous Ablation, Polidocanol Injectable Foam, 0.5%: mean -1.30 versus -0.80 on control; difference -0.50 (95% CI -0.78 to -0.22), standardized effect d = -0.80; z-test p = <0.001.
• Endovenous Ablation, Polidocanol Injectable Foam 1.0%: mean -1.11 versus -0.80 on control; difference -0.31 (95% CI -0.59 to -0.03), standardized effect d = -0.50; z-test p = 0.028.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a change in a scored measure rather than a count or a time until an event. The registry reports least-squares means and standard errors for the arms. A least-squares mean is a model-based average; the record does not describe the model or the covariates used to obtain these estimates. The standard error describes the statistical uncertainty in an estimated mean. It is not the spread of individual participants’ scores.

What does a mean change represent?

A change score compares a participant’s score at follow-up with the baseline score, and the arm-level result summarizes those changes. The posted estimates are -0.8 for vehicle, -1.3 for the arm labelled 0.5% foam, and -1.11 for the arm labelled 1.0% foam. The score runs from none at 0 to very severe at 4, so a negative average change indicates a lower follow-up score than baseline. The average does not show how much participants’ individual changes varied. The registry does not provide the distribution of individual scores or changes.

How should the comparisons be read?

The comparison estimates are mean differences between each foam arm and the vehicle arm. The recalculated estimate for the 0.5% arm is -0.5; for the 1.0% arm it is -0.31. A negative value indicates that the foam arm’s average change is more negative than the vehicle arm’s average change. These comparisons are unadjusted recalculations from the posted summary statistics. They are not evidence that the registry has reported the trial’s full analysis model, and the registry record lists no analysis entries.

The comparison calculations use standard errors to approximate the underlying standard deviations, as indicated by the approximate standard-deviation flag. A pooled standard deviation is an estimate of common variability across the two groups. General statistical context: pooling can provide a common scale for a comparison when the groups are treated as having similar variability, but the resulting estimate depends on that assumption and on the summary statistics used. The registry does not report raw participant-level data with which to check that approximation.

What does a p-value tell the reader?

The unadjusted p-values are p < 0.001 for the 0.5% comparison and p = 0.028 for the 1.0% comparison. In general, a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure clinical importance. The recalculated p-values do not account for multiplicity. Whether the original trial analysis used a different test or adjustment is not reported in the registry record.

Why do confidence intervals matter?

A confidence interval gives a range of values compatible with the data under the method used. In general, narrower intervals indicate greater precision, while wider intervals indicate more uncertainty about the estimated effect. For the 0.5% comparison, the recalculated 95% interval is -0.78 to -0.22. For the 1.0% comparison, the recalculated interval is entirely below zero and approaches zero more closely. These are unadjusted intervals from summary-statistic calculations; they are not a substitute for an interval from a fully reported, prespecified trial model.

What is not known about the statistical plan?

The registry record does not report the trial’s original sample-size justification, analysis populations, missing-data methods, interim analyses, or a complete statistical analysis plan. It also does not explain how the least-squares means were estimated. General statistical context: model specification, handling of missing outcomes, and multiplicity procedures can affect estimates and their uncertainty. Without those details, the posted summaries can be described, but the original analysis choices cannot be reconstructed from the registry record alone.

10. Confidence Intervals and Precision

The recalculated mean difference for the arm labelled 0.5% foam versus vehicle is -0.5, with a 95% confidence interval from -0.78 to -0.22. The interval does not include zero and is entirely negative. In general, a confidence interval describes a range of effect values compatible with the data and calculation method; it is not a guarantee that the true effect lies within that particular interval. This interval is an unadjusted recalculation from the posted summary statistics.

For the arm labelled 1.0% foam versus vehicle, the recalculated difference is -0.31. Its confidence interval also lies below zero, but approaches zero more closely than the interval for the 0.5% comparison. The associated unadjusted p-value is 0.028. The posted interval limits have more than three decimal places, so they are not reproduced. The interval’s relation to zero and the estimate are sufficient to describe its direction without implying more precision than is useful for this account.

Precision is not the same as clinical importance. A relatively precise estimate can still be too small to matter to patients, while an uncertain estimate may include effects of differing practical importance. The registry does not report a threshold for a clinically meaningful IPR-V3 change, so the clinical interpretation of these intervals cannot be settled from the endpoint results alone.

The comparisons are based on arm-level summary statistics, and the standard deviations used in recalculation are approximate. The registry does not provide participant-level outcomes or further details of the model behind the least-squares means. Those omissions limit independent assessment of the assumptions and methods that produced the estimates. The intervals should therefore be read as precision measures for the posted, unadjusted recalculations, not as a complete account of uncertainty under every possible analysis.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They are illustrations based on the observed comparison effects, not the trial’s original design calculations. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

For the comparison of the arm labelled 0.5% foam with vehicle, planning for 100% of the observed effect gives 25 participants per arm for 80% power and 34 participants per arm for 90% power. Planning for 75% of the observed effect gives 44 participants per arm for 80% power and 59 participants per arm for 90% power. Planning for 50% of the observed effect gives 99 participants per arm for 80% power and 133 participants per arm for 90% power.

For the comparison of the arm labelled 1.0% foam with vehicle, planning for 100% of the observed effect gives 63 participants per arm for 80% power and 85 participants per arm for 90% power. Planning for 75% of the observed effect gives 112 participants per arm for 80% power and 150 participants per arm for 90% power. Planning for 50% of the observed effect gives 252 participants per arm for 80% power and 338 participants per arm for 90% power.

In plain terms, the 80% and 90% columns give the number of participants per arm estimated to detect the selected effect at those target power levels, under the stated assumptions. A smaller effect requires more participants to detect under the same assumptions. These planning calculations are not observed power and do not establish what the original trial was designed to detect.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.500; pooled standard deviation σ = 0.627.
2. n = 2 × (1.96 + 0.842)² × 0.627² / -0.500² = 24.7, rounded up to 25 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 <- -0.5                      # observed difference in means
sigma <- 0.626610181851524                     # 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(1197833)
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 = 25 (80% power), 34 (90% power)
 75% of observed effect: n per arm = 44 (80% power), 59 (90% power)
 50% of observed effect: n per arm = 99 (80% power), 133 (90% power)
power.t.test: 25.7 
Simulated power at n = 25 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The posted results include two recalculated comparisons of foam arms with the vehicle arm for the primary continuous outcome. Their p-values are unadjusted: p < 0.001 for the arm labelled 0.5% foam and p = 0.028 for the arm labelled 1.0% foam. The registry record lists no analysis entries and no secondary outcomes in the posted results. It does not report a multiplicity plan or whether the original trial analysis adjusted for multiple comparisons.

General statistical context: when several comparisons are examined, the chance of at least one apparently unusual result can rise if each is assessed without accounting for the others. Adjustment procedures can change the interpretation of p-values and intervals. Because no adjustment is included in these recalculations, the p-values should be understood as unadjusted rather than as family-wise or otherwise multiplicity-controlled evidence.

The registry record does not report how missing primary outcome measurements were handled, whether participants were analyzed according to assignment, or which analysis population was used. It also does not say whether any participants lacked baseline or 8-week measurements. These details matter because missing outcomes and choices about analysis populations can affect the estimates and their uncertainty. No imputation method, sensitivity analysis, or other missing-data procedure is reported in the registry record.

The arm-level outcome counts are listed, but those counts alone do not establish how analysis populations were defined or whether they correspond to all randomized participants. The record also does not describe the model used to calculate least-squares means. As a result, the registry supports description of the posted arm results and unadjusted recalculations, but not a full reconstruction of the trial’s prespecified analysis strategy.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero participants with serious adverse events in the vehicle group, the arm labelled 0.5% foam, and the arm labelled 1.0% foam. The corresponding numbers at risk are 38, 39, and 40. These are counts as reported, not estimates of comparative safety. The registry lists no serious adverse event terms.

The record also reports other adverse events affecting 20 participants in the vehicle arm, 29 in the 0.5% arm, and 35 in the 1.0% arm. Those counts are distinct from the serious adverse event counts and should not be interpreted as severity rankings. Death counts are not reported in the registry record.

A zero count in a group means the registry reports no participants with a serious adverse event in that group; it does not prove that an event is impossible or that the groups have equivalent safety. The record does not provide further detail about event definitions, timing, duration, attribution, or the method for collecting adverse events. The counts alone cannot support conclusions about comparative risk or events not captured in the registry results.

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

The posted results describe change in an appearance score from baseline to 8 weeks after endovenous ablation with vehicle or foam. All three arm-level least-squares mean changes are negative: -0.8 for vehicle, -1.3 for the arm labelled 0.5% foam, and -1.11 for the arm labelled 1.0% foam. On this scale, a lower score represents less severe visible varicosities. The recalculated differences versus vehicle are also negative, meaning that the average score change was more negative in the foam arms in these summaries.

The unadjusted comparison for the 0.5% arm is -0.5, with a 95% confidence interval from -0.78 to -0.22 and p < 0.001. The unadjusted comparison for the 1.0% arm is -0.31, with p = 0.028. These results concern the specified score and time point only. They do not establish whether the score changes are important to patients, because a threshold for meaningful change is not reported.

The results do not establish durability beyond 8 weeks, effects on outcomes not reported in the registry, or the reason for changes in score. Nor do the adverse-event counts establish that one approach is safer than another. The registry does not report the statistical analysis plan, missing-data handling, or multiplicity adjustment needed for a complete assessment of the original analysis.

There is also a reporting inconsistency in treatment labels: the intervention list includes 0.125%, 1.0%, and 2.0%, while the posted outcome arms are labelled 0.5% and 1.0% and include vehicle. This limits certainty about how the outcome labels correspond to every intervention entry. The estimates should be interpreted using the labels attached to the posted comparisons, without assuming a reconciliation that the registry does not provide.

16. Why This Trial Matters Statistically

This trial illustrates why endpoint definition matters when interpreting a treatment comparison. The primary result is not a direct count of visible veins or a time-to-event measure; it is change in a five-point appearance score. Reading the estimates therefore requires understanding the scale, its direction, the baseline-to-follow-up contrast, and the stated 8-week timeframe.

It also demonstrates the distinction between an arm-level estimate and a comparison between arms. Each least-squares mean describes change in one group, while the mean difference contrasts that change with the vehicle group. The negative differences indicate the direction of the contrast, and confidence intervals help convey its precision. Neither statistical significance nor direction alone determines whether the observed difference is clinically important.

The registry contains two unadjusted recalculated comparisons, but does not report a multiplicity plan, analysis populations, or missing-data methods. Those gaps matter because inference depends not only on the point estimates but also on how the original analysis was planned and conducted. The figures are useful for transparent description of the posted summaries, but they do not replace a complete statistical analysis record.

Finally, the mismatch among concentration labels is an important reporting limitation. Treatment identity must be clear to connect an estimate to the intervention it represents. Where the registry uses different labels in its intervention list and outcome arms, careful description is preferable to an unsupported assumption about which concentration was administered.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry’s treatment labels are inconsistent. Its intervention list names polidocanol concentrations of 0.125%, 1.0%, and 2.0%, while the outcome arms name 0.5% and 1.0% foam plus vehicle. The arm descriptions also include 0.125% and 1.0% wording, and do not provide a complete reconciliation. Consequently, the posted comparisons can be described by their outcome-arm labels, but their exact correspondence to all intervention entries is not reported in the registry record.

The primary endpoint is based on an appearance score, and the registry does not state a threshold for clinically meaningful change. It describes the score’s attributes and the use of reference photographs at screening, but does not give further details of the independent photography review procedure, score aggregation, or how ratings were made at follow-up. The model used to generate the least-squares means is also not reported.

The recalculated comparisons are unadjusted and rely on approximate standard deviations derived from the posted standard errors. Participant-level data are not reported, so these recalculations cannot verify the underlying distributions or model assumptions. The record does not report multiplicity procedures, missing-data methods, analysis populations, or the original sample-size justification. It also does not report whether interim analyses were conducted.

The primary outcome is reported at 8 weeks. Results at other time points and additional secondary outcome results are not reported in the registry record. Serious adverse event counts are posted, but further event details and death counts are not reported. These limits constrain conclusions to the posted score results and the adverse-event counts, rather than supporting broader conclusions about long-term outcomes or comparative safety.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Endovenous Ablation With and Without Polidocanol Endovenous Microfoam Treatment for Patients With Great Saphenous Vein Incompetence and Visible Varicosities — NCT01197833.
• Registry record last updated 2021-04-21; status last verified 2021-04.
• Results first posted 2014-09-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry describes a completed, randomized, double-blinded, parallel-group Phase 3 trial of endovenous ablation followed by polidocanol foam or vehicle for great saphenous vein incompetence with visible varicosities. Enrollment was 117; the start date was 2010-09 and primary completion was 2012-03. Boston Scientific Corporation is listed as sponsor.

The primary outcome was change in the IPR-V3 visible varicose vein score from baseline to 8 weeks. Posted arm estimates were -0.8 for vehicle, -1.3 for the arm labelled 0.5% foam, and -1.11 for the arm labelled 1.0% foam. Recalculated unadjusted mean differences versus vehicle were -0.5 and -0.31, respectively. The registry’s concentration labels do not fully agree across intervention and outcome listings. Details of the original statistical plan, missing-data handling, and analysis populations are not reported in the registry record.