Clubfoot Tenotomy Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clubfoot Tenotomy Trial (NCT04766684), a randomized phase 4 study. The primary outcome is FLACC (Face, Legs, Activity, Cry, Consolability) Scale.

2. Clinical Question

3. Trial Design

The registry describes a completed Phase 4, randomized, parallel-group trial. It lists quadruple masking. The record does not explain which study roles were masked or how masking was maintained, so those details are not reported in the registry record.

The trial compares topical 4% liposomal lidocaine cream with a needle-free jet injection of 1% lidocaine. The arm descriptions specify placebo cream plus 0.25 ml of lidocaine for the jet group, and active cream plus 0.25 ml of saline for the topical group. This makes the contrast a comparison of the full listed regimens, rather than simply a comparison of two drugs without their accompanying procedures.

The registry lists enrollment as 107. For the primary outcome, the posted group counts are 49 for topical anesthesia and 45 for jet anesthesia. The record does not explain why those outcome counts differ from the enrollment figure, or describe whether the counts reflect exclusions, unavailable measurements, or another reason.

The registry lists Vanderbilt University Medical Center as sponsor and gives the study dates as 2021-06-01 for start and 2024-08-01 for primary completion. It reports the status as completed. The original design assumptions, including any planned sample-size justification or intended analysis population, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Patients enrolled in the study were treated with the Ponseti method. Weekly serial casting was initiated with above-knee Ponseti clubfoot casts. After the final weekly serial casting visit, the attending surgeon determined if the patient would need either unilateral or bilateral TAL due to residual equinus deformity. If tenotomy was not required, the patient was then transitioned to a foot abduction orthosis and removed from the study.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as FLACC (Face, Legs, Activity, Cry, Consolability) Scale, measured over FLACC Score at the time of tenotomy (poke of the scalpel).

The primary endpoint is the FLACC score at the time of tenotomy, specifically at the scalpel poke. FLACC stands for Face, Legs, Activity, Cry, Consolability. The registry describes it as a measure used to assess pain in children and in people unable to communicate their pain. A Certified Child Life Specialist is identified as the person who will administer the scale.

The score ranges from 0 to 10, with 0 representing no pain; lower values indicate less pain on the measure. The reported endpoint is a continuous score, summarized as a group mean and standard deviation. Comparing group means describes the average observed score in each anesthesia group, while the standard deviations describe how spread out individual scores were within each group.

A score taken at the scalpel poke focuses on pain at a particular procedural moment. It does not, by itself, summarize pain at other times, recovery, or the overall experience of the procedure. The registry record does not report additional details about the timing of any other pain assessments or how multiple measurements, if any, were handled.

7. Results Posted in the Registry

• Intervention Group: JET Anesthesia: mean 8.40 versus 9.50 on control; difference -1.10 (95% CI -1.93 to -0.27), standardized effect d = -0.55; z-test p = 0.009.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary measure summarized by its mean and standard deviation. The mean is the arithmetic average of the observed scores within a group. It gives a concise description of the central score, but does not imply that every participant had a score near that average. The standard deviation describes the spread of scores around the group mean. In these results, the topical group has a standard deviation of 1.2 and the jet group has a standard deviation of 2.6, so the observed scores were more variable in the jet group.

What does the mean difference represent?

The reported mean difference is -1.1, defined for jet anesthesia relative to topical anesthesia. A negative value means the jet-group mean is lower than the topical-group mean in this comparison. Since lower FLACC scores indicate less pain on the scale, the sign of the estimate points toward a lower observed average score in the jet group. It does not mean that each participant's score was lower, and it does not describe a within-person change. The estimate is a difference between group means at the assessment time specified by the registry.

A difference in means is one way to summarize a continuous outcome. It is expressed in the outcome's own units, which are points on the FLACC scale. Whether a difference is meaningful in a practical or clinical sense requires context beyond the statistical estimate. The registry record does not report a threshold for a meaningful difference, so none can be applied from the record.

How should the p-value be understood?

The posted p-value is unadjusted and equals 0.009. In general, a p-value measures how surprising data at least as incompatible with a specified null model would be if that model and the analysis assumptions were true. It is not a measure of effect size, and it does not express the chance that the null model is true. A small p-value does not remove uncertainty about the estimated difference, as the confidence interval remains relevant for showing a range of values compatible with the data and model.

The registry does not identify the exact test used to obtain the posted p-value, the model assumptions for that test, or whether it accounted for any design features beyond the two groups. Those analysis details are not reported in the registry record. Accordingly, the p-value should be treated as the reported unadjusted result, not as evidence that an unreported analysis plan was followed.

Why does variability matter?

When scores are more dispersed, group means may be less precise for a given amount of observed data. The size of the standard deviation is therefore useful context for the mean difference and its confidence interval. In general, an analysis that assumes a particular distribution or common variability can be affected when score distributions do not fit those assumptions. General statistical methods can use approaches that allow unequal variability or non-normal distributions, but the registry record does not say whether such methods were considered or used. No particular assumption should be attributed to the trial beyond what the posted results identify.

Over-dispersion is a general concern when the data vary more than a model expects. If a model understates variability, it can give overly narrow uncertainty estimates and p-values that are too small. This is a general statistical point, not a claim that over-dispersion occurred in this trial. The posted standard deviations reveal differing observed spreads, but they do not alone diagnose the fit of the analysis model.

What does randomization contribute?

Random allocation is intended to make groups comparable in expectation, reducing systematic differences in baseline characteristics as an explanation for outcome contrasts. It does not guarantee identical groups in a particular trial, and it does not address every possible source of bias after allocation. Masking can reduce the influence of knowledge of assignment on care or outcome assessment, but the registry's quadruple-masking label does not specify the masked roles or implementation. The record does not describe allocation concealment, baseline balance, protocol deviations, or the handling of participants who did not contribute an endpoint.

In general, a randomized comparison estimates the contrast between the assigned regimens under the analysis used. Interpretation also depends on follow-up, measurement, missing data, adherence, and the analysis population. The registry record does not report these details sufficiently to reconstruct the full analysis. The posted comparison should therefore be described as the observed result for the reported outcome groups, without assuming an intention-to-treat or per-protocol analysis.

What can be concluded from the reported analysis?

The evidence describes lower mean FLACC scores in the jet group at the specified procedural moment, accompanied by a reported unadjusted p-value and confidence interval. The statistics do not show individual-level responses, explain the reason for the outcome-group counts, or establish whether other planned analyses were performed. Statistical interpretation should keep the scale, the contrast definition, the uncertainty, and the unreported analysis details in view rather than treating a single p-value as a complete account.

10. Confidence Intervals and Precision

The reported mean difference for jet anesthesia relative to topical anesthesia is -1.1 FLACC points. The confidence interval gives a range of values that, under the analysis assumptions, is compatible with the observed data and provides a sense of precision around that estimate. The reported interval lies entirely below zero. That direction aligns with the lower mean score in the jet group, but an interval is not a guarantee that the true difference falls within its limits.

Precision concerns the range of plausible values, not whether the estimate is important in practice. A narrower interval indicates more precise estimation than a wider interval, while an interval that includes values of different practical importance can leave substantial uncertainty about the size of an effect. The registry record does not provide a threshold for interpreting the clinical importance of a FLACC-point difference. The interval should therefore be read as statistical uncertainty around the group contrast, not as a decision rule.

The posted standard deviations also help contextualize precision: scores had a standard deviation of 1.2 in the topical group and 2.6 in the jet group. The group counts for the outcome are 49 and 45, respectively. Precision depends on both the amount of information and variability, as well as the analysis method. The registry does not report enough methodological detail to independently assess those assumptions. The reported interval is the appropriate posted uncertainty summary; its limits should not be interpreted as accounting for unreported missing-data or multiplicity considerations.

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 illustrative participant counts per arm, not total event counts. They are based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect is set as a stated fraction of the observed effect. These are planning assumptions for the illustration; the trial's original sample-size assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the illustration gives 52 participants per arm for 80% power and 70 participants per arm for 90% power. At 75% of the observed effect, the corresponding figures are 92 participants per arm for 80% power and 124 participants per arm for 90% power. At 50% of the observed effect, they are 207 participants per arm for 80% power and 277 participants per arm for 90% power.

Power is the probability, under a specified assumed effect and analysis model, of detecting that effect using the chosen test procedure. The 80% column and the 90% column therefore represent different target probabilities for a future study to detect its assumed effect under the planning assumptions. The higher target generally requires more participants under otherwise similar assumptions. Smaller effects need more participants because they are harder to distinguish from random variation.

These counts are planning illustrations based on the observed effect, not observed power for the completed trial. The observed group counts and the illustration's planning counts serve different purposes: one describes the posted result, while the other explores what a future study might require under stated assumptions. The record does not report whether the original trial used these assumptions or planned for any of these sample sizes.

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 = -1.100; pooled standard deviation σ = 1.996.
2. n = 2 × (1.96 + 0.842)² × 1.996² / -1.100² = 51.7, rounded up to 52 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 <- -1.1                      # observed difference in means
sigma <- 1.99608312103654                     # 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(4766684)
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 = 52 (80% power), 70 (90% power)
 75% of observed effect: n per arm = 92 (80% power), 124 (90% power)
 50% of observed effect: n per arm = 207 (80% power), 277 (90% power)
power.t.test: 52.7 
Simulated power at n = 52 per arm: 0.790 (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 registry posts a primary outcome result and identifies three outcome measures, but no secondary results are posted. It reports no analyses in the record. The posted primary comparison has an unadjusted p-value. Whether the study planned multiple primary comparisons, repeated testing, subgroup analyses, or an adjustment for multiplicity is not reported in the registry record.

In general, multiplicity arises when several hypotheses are tested or when results are examined repeatedly. With more opportunities to find a small p-value, the chance of at least one apparently notable result can increase. Procedures for controlling that issue depend on the planned family of comparisons and the analysis strategy. Because the registry does not describe such a plan, it is not possible to determine whether the posted p-value was selected from several analyses or how any multiplicity was handled. The unadjusted value should be read as reported, without assuming adjustment or asserting that adjustment was required.

The record does not report the number of participants with missing primary outcome data, reasons for missingness, imputation methods, or sensitivity analyses. The posted primary outcome counts are 49 for topical anesthesia and 45 for jet anesthesia, while enrollment is listed as 107. The reason for the difference between the enrollment figure and the group outcome counts is not reported in the registry record. It cannot be inferred from those figures whether any particular participant lacked an outcome or was excluded.

The registry does not specify whether the primary analysis followed intention-to-treat, per-protocol, or another analysis population. It also does not describe protocol deviations, treatment adherence, or how any unavailable measurements were handled. These details matter because analysis populations and missing-data approaches can affect a randomized comparison. Without them, interpretation should remain anchored to the results and counts that are posted, rather than assuming a particular population or missing-data procedure.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The serious adverse-event figures report zero affected participants in each group: 0 among 49 at risk in the topical-anesthesia group and 0 among 45 at risk in the jet-anesthesia group. The registry also reports zero participants with other adverse events in both groups and zero deaths in both groups.

These counts mean that no events of the listed types were recorded in the posted results for the reported at-risk groups. They do not establish that the true risk is zero, nor do they show that the regimens have identical safety. When no events are observed, the data still allow uncertainty about events that might occur in a larger group or over a different observation period.

The registry does not report the adverse-event observation window, event definitions beyond the serious and other categories, or a comparative statistical analysis. No risk difference or confidence interval is posted, and none should be inferred from the zero counts alone. The safety figures are descriptive and should be read alongside the limits of the available follow-up and reporting detail.

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

The posted primary result describes a lower average FLACC score at the scalpel poke in the jet-anesthesia group than in the topical-anesthesia group. The reported mean difference is -1.1, with an unadjusted p-value of 0.009 and a confidence interval that lies below zero. Together, these statistics describe the direction and uncertainty of the measured group contrast at that particular procedural moment.

The result does not establish that every infant experienced less pain with the jet regimen. Group averages can conceal individual variation, and the standard deviation was larger in the jet group than in the topical group. The measure is a behavioral pain scale administered by an assessor, rather than a direct report of pain from an infant. The registry identifies a Certified Child Life Specialist as the assessor, but does not report implementation details for the posted assessment.

The endpoint also does not represent pain throughout the procedure or beyond the scalpel poke. It does not answer questions about recovery, later discomfort, acceptability, or other outcomes unless those are separately measured and reported. Although the registry identifies an adverse-event aim, the posted zero counts are not enough to prove equivalent safety or to rule out uncommon events, particularly without an observation window and a comparative safety analysis.

The comparison concerns the full listed regimens: active topical cream with saline jet injection versus placebo cream with lidocaine jet injection. It should not be interpreted as isolating the effect of lidocaine route alone without considering these accompanying components. Generalization beyond the enrolled clinical context also requires caution; the registry describes infants undergoing in-office percutaneous tendoachilles lengthening for idiopathic clubfoot during Ponseti treatment.

Important details about missing data, analysis populations, the original statistical plan, and multiplicity are not reported in the registry record. The posted numbers therefore support a focused description of the measured comparison, not a comprehensive account of all possible effects or the basis for a treatment decision.

16. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through its endpoint and contrast definition. The main estimate is a difference in mean FLACC scores at a specific moment, rather than a general measure of procedural experience. The negative mean difference is interpretable only alongside the scale direction: lower scores represent less pain on the FLACC measure.

It also shows why averages and variability belong together. The group means differ, but the observed score spread is not the same in both groups. Reporting standard deviations makes that feature visible and reminds readers that an average does not describe the range of individual experiences. Confidence intervals add another layer by expressing uncertainty about the estimated contrast, while the p-value addresses compatibility with a no-difference model under the analysis assumptions.

The design details matter too. Randomization supports a comparative interpretation, and masking may limit some sources of bias, but the registry's labels do not reveal the allocation process or which roles were masked. The arm descriptions include companion cream and injection components, so the estimand is the comparison of those complete regimens. Clear attention to those features prevents an overly simple interpretation of the intervention label.

Finally, the record highlights how incomplete reporting constrains interpretation. Enrollment, outcome counts, missing-data handling, the statistical plan, and adverse-event follow-up answer different questions. When key details are not reported in the registry record, statistical conclusions should stay close to the available outcome and uncertainty summaries. That restraint is part of reading a clinical trial responsibly.

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 posted primary outcome is measured at the scalpel poke, a narrowly specified point in the procedure. It cannot represent pain at other stages or later outcomes. The registry does not report additional timing details for pain measurement, thresholds for a clinically important score difference, or further outcome assessment results.

The arm outcome counts are 49 and 45, while listed enrollment is 107. The reason for this difference is not reported in the registry record. No missing-data accounting or analysis-population definition is posted, so the outcome counts cannot be used to determine which participants were included or why others may not appear in those summaries.

The registry describes quadruple masking but does not identify the masked roles, allocation concealment procedures, or how the masking was maintained. It also does not report baseline characteristics or treatment adherence in the record. These omissions prevent a full appraisal of group comparability and the conduct of the randomized comparison from the posted information alone.

The available primary result is a mean comparison with an unadjusted p-value; the detailed statistical test and model assumptions are not reported. The record does not describe a multiplicity plan, missing-data sensitivity analyses, or a protocol-based sample-size justification. The planning illustration uses the observed effect and should not be mistaken for the trial's original design calculation.

For safety, the registry reports no affected participants for serious or other adverse events, but does not give an observation window or detailed event definitions. Zero recorded events do not establish zero risk. The registry's stated enrollment and completion status do not resolve these outcome-reporting limitations.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Clubfoot Tenotomy Trial — NCT04766684.
• Registry record last updated 2026-05-05; status last verified 2026-05.
• Results first posted 2026-05-05.
• 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.

21. Record Summary

NCT04766684 is a completed, randomized, parallel-group Phase 4 trial sponsored by Vanderbilt University Medical Center. The registry lists quadruple masking and enrollment of 107. The study compared topical 4% liposomal lidocaine cream with a needle-free jet injection of 1% lidocaine for infants undergoing in-office percutaneous tendoachilles lengthening for clubfoot.

The primary outcome was mean FLACC score at the scalpel poke. The posted means were 9.5 for topical anesthesia and 8.4 for jet anesthesia, with a reported mean difference of -1.1 and unadjusted p-value of 0.009. Serious and other adverse-event counts were zero in both groups. The registry does not report the original sample-size assumptions, analysis population, missing-data handling, multiplicity plan, or adverse-event observation window.