Efficacy of Fibrin Sealant to Reduce the Amount of Post-thyroidectomy Drain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Fibrin Sealant to Reduce the Amount of Post-thyroidectomy Drain (NCT01126060), a randomized phase 3 study. The primary outcome is Postoperative Drainage Amount.

2. Clinical Question

The registry describes the study as a phase 3 randomized trial. Its clinical rationale states that fibrin sealant had been studied in relation to post-thyroidectomy drainage and hospital stay, while strong evidence from well-designed clinical trials was considered lacking. It also describes the harmonic scalpel as a way to cut and coagulate tissues, and frames reduced postoperative drainage as relevant to minimizing hospital stay. These points explain the question motivating the trial; they are not additional outcomes reported for this comparison.

The intervention contrast is specifically the addition of fibrin sealant after surgery versus no fibrin sealant. The primary measure is drainage amount, not hospital stay, complications, or whether patients can be managed without a drain. The registry’s brief summary describes a hypothesis about no-drain postoperative care, but the posted primary outcome is postoperative drainage amount. No result for hospital stay or a no-drain outcome is reported in the registry record.

3. Trial Design

The registry classifies this study as phase 3, randomized, quadruple-masked, and parallel-group. It lists enrollment as 78. The recorded groups are Fibrin Sealant, with 38 participants, and No Fibrin Sealant, with 40 participants. The intervention description says fibrin sealant was used after surgery in the treatment group and not used in the control group. The trial title and official title specify harmonic scalpel-assisted total thyroidectomy with anterior compartment neck dissection.

The registry lists Samsung Medical Center as the sponsor. The recorded start is 2010-02, primary completion is 2011-01, and status is completed. These registry dates describe the recorded study timeline; they do not establish the timing of each participant’s procedures or follow-up. The masking label is quadruple, but which people were masked and how masking was maintained are not reported in the registry record.

The primary outcome is described as a mean continuous measure, with standard deviation as its dispersion. The record gives serial measurement from 1day to 4day after surgery. It describes measurement of drainage fluid from a negative suction system every 8 hr until the daily total amount reduces under 20mL. This description gives the measurement approach, but does not explain how serial measurements were combined into the reported group mean or how observations after the stopping condition were handled.

The registry record does not report the trial’s original sample-size assumptions, detailed randomization procedure, allocation concealment, or a statistical analysis plan. The planning calculations associated with the observed comparison are not evidence of the assumptions used when the trial was designed.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

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 Postoperative Drainage Amount, measured over serial measurement from 1day to 4day after surgery.

The primary endpoint is postoperative drainage amount, measured in mL and summarized as a mean with standard deviation. Drainage was measured serially from 1day to 4day after surgery. The record describes collection from a negative suction system every 8 hr until the daily total amount reduced under 20mL. Thus, the endpoint concerns the amount of fluid recorded through the drain, rather than a patient-reported symptom or a clinical event.

Drainage amount is relevant to the trial’s stated rationale because the brief summary connects postoperative drainage with the aim of minimizing hospital stay and describes a hypothesis about no-drain postoperative care. However, drainage amount is the outcome that was posted as primary; it should not be treated as a direct measure of hospital stay or proof that a drain can be omitted. The registry record does not report results for hospital stay or a no-drain endpoint.

The published group summaries are means and standard deviations. The registry does not specify in the primary outcome description whether the reported value represents a particular day, a cumulative amount, an average across serial measurements, or another summary of the measurement sequence. This matters because those approaches would represent different summaries of repeated drainage observations. The record also does not report the analysis population or handling of incomplete measurements.

7. Results Posted in the Registry

• No Fibrin Sealant: mean 105.70 versus 93.50 on control; difference 12.20 (95% CI -1.54 to 25.94), standardized effect d = 0.39; z-test p = 0.082.

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the observed group summaries from the uncertainty around their comparison. The registry reports a continuous primary outcome as a mean and standard deviation for each group, and gives a mean difference, an interval, and an unadjusted p-value. These quantities address related but different questions: the means describe the observed group averages, the difference describes their contrast, the interval expresses uncertainty about that contrast, and the p-value assesses compatibility with a specified null model under the test’s assumptions.

What does a mean difference describe?

A mean is an arithmetic summary of measured values within a group. The reported mean is 93.5 mL for fibrin sealant and 105.7 mL for no fibrin sealant. The comparison is oriented as no sealant minus fibrin sealant, so its reported estimate of 12.2 mL is positive when the no-sealant mean is larger. That sign convention is useful for reading the result, but it does not itself establish the importance or reliability of the difference.

A mean difference expresses the contrast in the measurement’s own units, here mL. It is not a percentage change, and no percentage comparison is needed to interpret the reported contrast. Because drainage was measured serially, the precise way in which the repeated observations contributed to each participant’s summary is important. The registry gives a serial measurement window and a collection procedure, but does not report the calculation used to produce the group-level endpoint.

Why report standard deviations?

A standard deviation describes how spread out measurements are around a group mean. The reported standard deviations are 30.7 mL for fibrin sealant and 31.2 mL for no fibrin sealant. Standard deviations describe variability among observations; they are not standard errors and are not confidence intervals for the group means. A larger spread can make a group mean less precisely estimated, while the amount of precision also depends on the number of observations and the analysis approach.

For continuous outcomes, a mean comparison can be sensitive to the distribution of the measured values and to unusual observations. General statistical practice considers whether the mean is a suitable summary, whether the analysis assumptions are plausible, and whether the endpoint has a skewed distribution or influential values. The registry record does not report distributional checks, transformations, robust methods, or individual-level data, so those features cannot be assessed from the posted summaries.

What does the p-value say?

The unadjusted p-value is 0.082. In general, a p-value quantifies how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The record also includes a two-sided significance level of 0.05 for its planning illustration. Those planning assumptions do not establish that this exact test or threshold was prespecified for the trial’s primary analysis; the original statistical plan is not reported in the registry record.

Because the p-value is unadjusted, it should not be described as accounting for multiple outcomes or multiple comparisons. The registry lists one outcome measure and no secondary outcomes, but the analysis count is zero. This record does not clarify whether analyses were conducted but not posted, whether the displayed outcome is the only analysis performed, or what multiplicity considerations were used.

What does the interval add?

An interval around a mean difference shows a range of effect estimates compatible with the data under the interval’s method and assumptions. The reported range is -1.539 to 25.94 mL. Since this range crosses zero, it includes no mean difference as well as positive and negative values under the stated comparison direction. Its width conveys that the estimate is not highly precise. The confidence level and construction method for the interval are not reported in the registry record, so they should not be inferred.

In general, an interval is more informative than a point estimate alone because it makes uncertainty visible. It does not show every value as equally plausible, and it does not account for biases or missing information that the analysis did not address. Randomization supports a comparative design, but the record does not provide enough statistical detail to assess the analysis population, the treatment of repeated measurements, or the effect of missing observations.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means that variation exceeds what a simple model assumes; it can lead to standard errors that are too small if ignored. This endpoint is reported as a continuous drainage amount rather than a count, so over-dispersion is not a stated feature of the analysis. More generally, the assumed data distribution should match the outcome and analysis method. The registry does not report enough detail to determine which distributional assumptions were used.

10. Confidence Intervals and Precision

The reported mean difference is 12.2 mL, with an interval from -1.539 to 25.94 mL. Because the comparison is no sealant minus fibrin sealant, the positive point estimate corresponds to a higher observed mean in the no-sealant group. The interval, however, includes zero and also includes values in the opposite direction. It therefore does not isolate a single direction of difference with high precision.

The interval spans values that could represent little or no difference as well as a larger positive difference. This makes it important not to interpret the point estimate alone as the settled effect. The unadjusted p-value of 0.082 is consistent with the uncertainty reflected in an interval that includes zero, although the exact interval construction and confidence level are not reported in the registry record.

Precision depends on the amount of information in the analysis, the variability of the outcome, and the method used to analyze it. The group standard deviations are 30.7 mL and 31.2 mL. The group sizes recorded for the comparison are 38 and 40. The reported results do not explain whether all randomized participants contributed to the endpoint analysis, whether any serial observations were missing, or how such observations were handled. Those details could affect precision and are not reported in the registry record.

The interval communicates sampling uncertainty under its statistical assumptions; it does not address potential bias, endpoint-definition ambiguity, or incomplete reporting. The posted estimate should therefore be read as an uncertain comparison of the recorded drainage summaries, rather than a precise estimate of every effect relevant to the trial’s rationale.

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 events. The planning illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers an effect equal to the observed effect, 75% of the observed effect, and 50% of the observed effect. These are planning scenarios based on the observed comparison; the trial’s own original design assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under its assumptions, if that effect and model were correct. The 90% power column gives the corresponding planning target for a 90% chance. These percentages describe long-run operating characteristics of a planned study under assumptions; they do not describe the probability that the result of this completed trial is correct.

As the target effect gets smaller, distinguishing it from random variation generally requires more information. Accordingly, the rows for planning for 75% and 50% of the observed effect call for more participants per arm than the row using 100% of the observed effect. The illustration does not show that those participant numbers were enrolled or that the trial had a particular achieved power. This is not observed power. The posted planning values are scenario-based calculations, not evidence about the trial’s prespecified design or its actual probability of detecting an effect.

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 = 12.200; pooled standard deviation σ = 30.958.
2. n = 2 × (1.96 + 0.842)² × 30.958² / 12.200² = 101.1, rounded up to 102 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 <- 12.2                      # observed difference in means
sigma <- 30.9575877103192                     # 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(1126060)
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 = 102 (80% power), 136 (90% power)
 75% of observed effect: n per arm = 180 (80% power), 241 (90% power)
 50% of observed effect: n per arm = 405 (80% power), 542 (90% power)
power.t.test: 102 
Simulated power at n = 102 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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and reports no secondary outcomes. It lists zero analyses. This does not establish that only one analysis was performed; it means that the registry record does not contain posted analysis entries beyond the reported outcome result. The statistical analysis plan, including any prespecification of outcomes, contrasts, or multiplicity adjustments, is not reported in the registry record.

Multiplicity arises when several outcomes, comparisons, time points, or analytic choices are examined. In general, repeated testing can increase the chance of a false-positive finding if results are interpreted without accounting for that process. The posted p-value is described as unadjusted, and no multiplicity adjustment is reported. The serial measurement description does not explain whether each day or time point was analyzed separately, whether a single summary was formed, or whether other comparisons were considered.

The record does not state the analysis population, such as whether the primary comparison included all randomized participants or only those with observed endpoint data. It also does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. These omissions matter because the interpretation of a randomized comparison can depend on how participants with incomplete measurements are handled.

The outcome description specifies repeated drainage collection and a stopping condition, but not how the repeated observations were reduced to the reported mean. It is not reported in the registry record whether the analysis used a participant-level summary, a repeated-measures model, or another method. No adjustment variables, model diagnostics, or prespecified subgroup analyses are reported. Consequently, the available comparison can be described, but the broader analytic strategy and the robustness of the result to alternative choices cannot be assessed.

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 2% reporting threshold.

The serious adverse event figures report 0 affected participants among 38 at risk in the fibrin-sealant group and 0 affected participants among 40 at risk in the no-sealant group. The other adverse event figures also report 0 affected participants in each group, with the same recorded at-risk counts. These are the counts posted in the registry record; they should be read as reported event figures, not as proof that no adverse events occurred outside the categories or reporting period captured by the record.

Deaths are not reported in the registry record. The record does not provide serious adverse event terms, event timing, severity details, or a fuller account of how adverse events were collected and classified. With zero affected participants recorded in each category, there is no event-count contrast in these posted figures, but the registry entry alone cannot establish the completeness of safety ascertainment or rule out uncommon harms. The figures do not support conclusions beyond the adverse event information recorded.

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

The posted results describe an observed difference in mean postoperative drainage amount between the two randomized groups. The no-sealant group had a mean of 105.7 mL and the fibrin-sealant group had a mean of 93.5 mL; the reported mean difference is 12.2 mL in the no-sealant-minus-sealant direction. The interval from -1.539 to 25.94 mL includes zero, and the unadjusted p-value is 0.082. These results indicate uncertainty about the size and direction of the underlying difference.

The result does not establish that the groups had identical drainage amounts, nor does it establish a definite difference. An interval that includes zero does not prove absence of an effect. The point estimate alone also does not establish that any difference is important for patients or clinical care. No threshold for a clinically important drainage difference is reported in the registry record.

The primary measure is drainage amount. Although the brief summary discusses hospital stay and a no-drain postoperative-care hypothesis, the registry record does not report results for hospital stay or a direct no-drain outcome. The drainage result cannot by itself answer whether hospital stay changed, whether a drain could be omitted, or whether other clinical outcomes differed.

The result is also limited by missing statistical detail. The registry does not report the analysis population, the treatment of missing measurements, the method for summarizing serial drainage observations, or the confidence level and construction method for the interval. These gaps do not erase the posted comparison, but they constrain how fully its precision and robustness can be evaluated. The findings should be understood as the reported comparison for the recorded endpoint, not as a complete account of all effects or safety outcomes.

16. Why This Trial Matters Statistically

This trial is statistically informative because it presents a randomized comparison of a defined intervention contrast and reports a continuous primary outcome in its measurement units. The group means, standard deviations, mean difference, interval, and unadjusted p-value allow readers to distinguish the observed estimate from its uncertainty. In particular, the interval makes clear that the point estimate does not provide a precise determination of the direction or size of the difference.

The trial also illustrates why the endpoint definition and analysis details matter. Drainage was measured serially, but the registry record does not explain how those observations were combined into the posted mean. Different summaries of repeated observations can address different questions, so a clear endpoint construction and analysis plan are important for reproducibility and interpretation.

The statistical result must also be kept distinct from the broader clinical rationale. The record frames drainage in connection with minimizing hospital stay and a hypothesis about no-drain care, but posts a drainage outcome rather than a hospital-stay or drain-omission result. Separating the measured endpoint from the motivation helps prevent overinterpretation.

Finally, the planning illustrations show how sample-size requirements depend on the target effect under stated assumptions. They are not a substitute for the original design rationale, which is not reported in the registry record. Together, these features make the trial a useful example of reading an effect estimate alongside uncertainty, distinguishing planned-study calculations from observed evidence, and recognizing the limits imposed by incomplete registry reporting.

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 primary outcome description gives a serial measurement window from 1day to 4day after surgery and a collection procedure, but does not state precisely how these repeated measurements were combined into the mean outcome. It is also unclear whether the posted value represents cumulative drainage, a daily summary, or another participant-level quantity. This limits the ability to interpret the endpoint’s exact meaning.

The registry does not report baseline characteristics, the randomization sequence method, allocation concealment, or the people included under the quadruple-masking label. It therefore offers limited detail for assessing how assignment was implemented and how masking operated. The analysis population and handling of missing endpoint observations are also not reported in the registry record.

The record provides a mean difference, interval, and unadjusted p-value, but does not report the interval’s confidence level or construction method, the primary analysis plan, model assumptions, diagnostics, or any covariate-adjusted analysis. The original sample-size justification and trial-specific design assumptions are not reported. The available planning illustration instead uses the observed effect under stated hypothetical assumptions.

The endpoint is drainage amount, while outcomes mentioned in the rationale, including hospital stay and no-drain care, do not have posted results. The record also does not report detailed adverse event terms or deaths. These limitations concern the detail and scope of the registry record; they do not change the numerical results that are posted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy of Fibrin Sealant to Reduce the Amount of Post-thyroidectomy Drain — NCT01126060.
• Registry record last updated 2011-12-19; status last verified 2011-11.
• Results first posted 2011-12-19.
• 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 completed phase 3 study is recorded as randomized, quadruple-masked, and parallel-group, with enrollment of 78. It compares use of fibrin sealant after surgery with no use of fibrin sealant in patients undergoing harmonic scalpel-assisted total thyroidectomy with anterior compartment neck dissection.

The primary outcome is mean postoperative drainage amount in mL, measured serially from 1day to 4day after surgery. The recorded means are 93.5 mL for fibrin sealant and 105.7 mL for no fibrin sealant. The mean difference, no sealant minus fibrin sealant, is 12.2 mL, with an interval from -1.539 to 25.94 mL and an unadjusted p-value of 0.082.

The registry record does not report the original design assumptions, full statistical plan, analysis population, or missing-data methods. It does not post results for hospital stay or a no-drain outcome.