Application of 3D Printing Technique in Small Pulmonary Nodule Localization: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Application of 3D Printing Technique in Small Pulmonary Nodule Localization (NCT02952261), a randomized na study. The primary outcome is Accuracy of Lung Nodule Localization.

2. Clinical Question

3. Trial Design

This was a prospective, randomized, controlled, non-inferiority trial with a parallel-group design. The registry lists no masking. The planned enrollment was 200 participants, and the record lists the study as completed. The listed study start was 2016-10-24 and primary completion was 2017-10-01. The phase is recorded as not applicable.

Participants were allocated to either template-guided localization or conventional CT-guided localization. For the template approach, a three-dimensional printed template was customized from the participant’s CT information. The comparator group received conventional CT-guided localization. The registry lists the sponsor as Chang Chen.

The primary outcome population is described as modified intention-to-treat. The registry states that participants who did not receive lung nodule localization were excluded, noting 10 participants in this group. The posted outcome summaries include 95 participants in each arm. The record does not give a fuller account of the randomization procedure, allocation concealment, or the timing and reasons for individual exclusions, so those details are not reported in the registry record.

Localization accuracy was assessed from completion of the final CT scan, up to 2 days. The secondary outcomes were procedural duration, radiation dose, and complication rate. Duration and radiation dose were assessed from completion of the final CT scan, up to 1 hour; complication rate was assessed up to 2 days. A detailed protocol, the original sample-size justification, and a formal statistical analysis plan 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intention-to-treat analysis (patients who did not receive lung nodule localization were excluded.(n=10))

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 Accuracy of Lung Nodule Localization, measured over From the time of completing final CT scan, assessed up to 2 days..

The primary endpoint, accuracy of lung nodule localization, is a continuous measurement expressed in millimeters. It is defined as the localizer deviation between the hookwire and the center of the target nodule. The record says this deviation was measured using CAD software after CT images were downloaded from the Picture Archiving and Communications Systems. The endpoint was assessed from completion of the final CT scan, up to 2 days.

In general, a distance-based endpoint is used to quantify how closely the localization marker is positioned relative to the intended target. A smaller deviation represents a closer measured position; this describes the measurement’s direction, not a conclusion about clinical benefit. Reporting the mean and standard deviation gives information about the average deviation and the spread of individual measurements in each group.

The registry identifies the study as a non-inferiority trial, but does not report the non-inferiority margin or a prespecified decision rule. Without that information, the average difference and its confidence interval can be described, but they cannot establish whether a formal non-inferiority criterion was met. The endpoint is a measure of localization accuracy, not a direct measure of surgical success or long-term health outcomes.

7. Results Posted in the Registry

• Template-guided Localization: mean 8.70 versus 9.60 on control; difference -0.90 (95% CI -2.71 to 0.91), standardized effect d = -0.14; z-test p = 0.330.

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.

Procedural Duration of the Nodule Localization

• 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 deviations.
• Result:
  • Template-guided Localization: mean 7.40 versus 9.50 on control; difference -2.10 (95% CI -3.07 to -1.13), standardized effect d = -0.62; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Template-guided Localization than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Radiation Dose

• 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 deviations.
• Result:
  • Template-guided Localization: mean 229.00 versus 313.00 on control; difference -84.00 (95% CI -105.36 to -62.64), standardized effect d = -1.12; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Template-guided Localization than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Complication Rate

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Template-guided Localization: 10.5% (10/95) versus 17.9% (17/95) on control; risk difference -7.4 percentage points (95% CI -17.2 to 2.5), risk ratio 0.59 (0.28–1.22); unadjusted two-proportion z-test p = 0.146.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Template-guided Localization and the control. The interval gives the range of effects that remain compatible with the data.

Across the three posted secondary outcomes, the point estimates are directionally consistent with lower recorded values in the template-guided group. This broad pattern is also consistent in direction with the primary accuracy point estimate. The endpoints address different aspects of the procedure, however, and consistency in direction does not make them interchangeable or establish that the groups differ reliably.

Secondary outcomes can add context to the primary comparison. They may describe procedural burden and complications alongside localization accuracy, but they do not replace the primary endpoint or answer the formal non-inferiority question. Each outcome has its own measurement scale, variability, and uncertainty. The complication comparison is binary, whereas duration and radiation dose are continuous; evidence from one type of outcome cannot simply be transferred to another.

The secondary comparisons are unadjusted. In general, testing several outcomes increases the chance that at least one result will appear notable by chance, especially when no prespecified hierarchy or multiplicity adjustment is used. The registry record does not report an adjustment strategy, a hierarchy, or separate reported analyses for the secondary outcomes. Their p-values and intervals should therefore be treated as descriptive, exploratory evidence, not as a set of confirmatory findings.

The observed pattern can motivate further evaluation, but it does not resolve questions about the original trial design, missing outcomes, or the clinical importance of each measurement. Nor does it establish that a lower value on every endpoint necessarily represents a meaningful improvement. The registry provides outcome definitions and summaries but does not report thresholds for clinically important differences. The appropriate interpretation is a set of additional procedural observations that remain subject to uncertainty and multiplicity.

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

• Procedural Duration of the Nodule Localization
• Radiation Dose
• Complication Rate

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant has a localization deviation measured in millimeters. The registry reports the group mean and standard deviation. In general, the mean describes the arithmetic average, while the standard deviation describes how dispersed individual observations are around that average. A standard deviation is not the uncertainty in the group mean and is not a confidence interval for the treatment difference.

The comparison is expressed as a mean difference, template-guided minus CT-guided. A negative estimate means the posted average measurement is lower in the template-guided group. The recalculated unadjusted estimate is -0.9 mm. “Recalculated” means it is a simple unadjusted comparison derived from the posted group summaries, not a reported adjusted model. The registry does not list a sponsor-reported analysis for this outcome.

In general, a confidence interval gives a range of values compatible with the data under the assumptions of the analysis. It helps show the precision of an estimate: a wider interval indicates more uncertainty. For this comparison the interval includes zero, so the posted summaries do not rule out no mean difference. A confidence interval is not a probability statement that the true value lies within the particular interval, and it does not resolve whether a result meets a non-inferiority criterion.

The reported p-value for the primary comparison is unadjusted. In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The unadjusted p-value is 0.33. The record does not provide a formal non-inferiority test or specify a non-inferiority margin.

For a non-inferiority question, the interpretation depends on the chosen margin: the largest difference considered acceptable for the trial’s purpose. In general, the confidence interval for the treatment difference is compared with that margin in the direction relevant to the endpoint. The margin should be selected before results are known and justified in the protocol. The registry record does not report the margin, its rationale, or the formal decision rule, so the posted mean difference and p-value cannot independently establish non-inferiority.

The primary population is called modified intention-to-treat, with participants who did not receive localization excluded. In general, intention-to-treat analysis seeks to preserve the groups created by randomization by analyzing participants according to their assigned group. Modified versions may omit participants under specified conditions. The record notes 10 participants who did not receive localization but does not provide enough information to evaluate the reasons, arm allocation, or outcome information for those exclusions. The consequences for the comparison are therefore uncertain.

The three secondary outcomes use different statistical summaries. Procedural duration and radiation dose are continuous measures reported as means and standard deviations. Complication rate is a participant count, compared as a risk difference. In general, a risk difference subtracts the event proportion in one group from the proportion in the other; a negative difference in the stated comparison direction indicates fewer recorded events in the template-guided group. The binary comparison also has an unadjusted p-value and confidence interval.

Multiple outcomes create a multiplicity issue. In general, when many hypotheses are tested, the chance of at least one apparently notable result can rise unless the analysis plan accounts for this. Adjustment approaches and a prespecified hierarchy can help manage that issue. The registry lists three secondary outcomes but does not report a multiplicity strategy, a hierarchy, or secondary analyses. The secondary p-values should not be interpreted as though they were adjusted confirmatory tests.

The registry records no reported analyses for the outcomes. Consequently, the comparisons discussed are unadjusted recalculations from the posted summary statistics, rather than estimates from a documented covariate-adjusted model. The record does not report the original sample-size calculation, model specification, handling of missing data, or interim analyses. Those omissions limit assessment of how closely these calculations reflect the trial’s prespecified analysis plan.

11. Confidence Intervals and Precision

For the primary endpoint, the mean difference is -0.9 mm, with a confidence interval that extends from a negative value to a positive value. This interval includes zero, so the summaries are compatible with no average difference as well as with differences in either direction. The interval’s span is important: the point estimate alone does not convey the uncertainty in the comparison. The unadjusted p-value is 0.33, which likewise does not provide evidence that the groups have identical outcomes.

The group standard deviations, 5.8 mm for CT-guided localization and 6.9 mm for template-guided localization, describe variation among observed participants. They are not confidence intervals and do not show the full range of individual measurements. The mean difference and its confidence interval address uncertainty in the contrast between group averages, while the standard deviations describe within-group spread.

In general, precision depends on the amount of information in the data and the variability of the outcome. An interval that includes both negative and positive differences does not establish equivalence: equivalence requires prespecified bounds and an appropriate analysis. Similarly, non-inferiority requires a prespecified margin and a confidence interval assessed against that margin. Neither criterion can be evaluated from the registry record because the margin and formal decision rule are not reported.

The complication comparison also has uncertainty across both sides of zero. Its unadjusted p-value is 0.146. The registry summaries therefore do not support a confident distinction in the risk difference, and the point estimate should not be read in isolation. Precision describes how much the posted data constrain possible values; it does not determine the clinical importance of any value.

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 planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total participant counts or total event counts. The 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 figures are planning illustrations based on the observed effect, not the original trial design; the original design assumptions are not reported in the registry record.

The 80% power column describes an illustrative design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the assumptions were correct. The 90% column uses a higher target probability of detecting that effect. These are prospective planning quantities, not a measure of what happened in the completed trial. This is not observed power.

Rows planning for 100%, 75%, and 50% of the observed effect use progressively smaller assumed effects. Smaller effects are harder to distinguish from random variation, so they require more participants per arm to reach the same target power under the same assumptions. The numerical requirements differ by endpoint because the observed effects and outcome variability differ. In particular, the complication endpoint is a participant count, while the primary outcome, duration, and radiation dose are continuous measures.

These illustrations do not establish what sample size the trial should have used. They rely on effects estimated from the observed trial data, which may not represent the effect in a future study, and they do not incorporate an unreported non-inferiority margin or original design rationale. The registry reports 200 planned participants and 95 participants per arm in the primary outcome summaries, but does not report the trial’s own sample-size justification.

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 = -0.900; pooled standard deviation σ = 6.374.
2. n = 2 × (1.96 + 0.842)² × 6.374² / -0.900² = 787.3, rounded up to 788 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 <- -0.9                      # observed difference in means
sigma <- 6.37377439199098                     # 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(2952261)
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 = 788 (80% power), 1,054 (90% power)
 75% of observed effect: n per arm = 1,400 (80% power), 1,874 (90% power)
 50% of observed effect: n per arm = 3,150 (80% power), 4,216 (90% power)
power.t.test: 788.3 
Simulated power at n = 788 per arm: 0.795 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes. It does not report a prespecified testing hierarchy, a multiplicity adjustment, or a statistical analysis plan describing how conclusions would be drawn across outcomes. Without such information, the secondary p-values should be regarded as unadjusted. In general, the more outcomes tested, the greater the opportunity for chance findings unless the analysis plan accounts for multiple comparisons.

The primary population is described as modified intention-to-treat, excluding participants who did not receive localization; the record notes 10 such participants. The posted primary outcome summaries include 95 participants per arm. The registry does not report the distribution of the excluded participants by randomized group, reasons in more detail, or their outcome data. It also does not specify how any other missing measurements were handled. The possibility and consequences of missing data cannot therefore be assessed from the summaries alone.

The record does not report whether analyses were adjusted for baseline characteristics, whether any protocol deviations occurred, or how deviations were handled. It lists no reported analyses for the primary or secondary outcomes. The comparisons described from the summaries are unadjusted recalculations, and the registry does not document a sponsor-reported model or its assumptions.

For a trial labeled non-inferiority, important missing details include the prespecified margin, its justification, the planned analysis populations, and the formal criteria for concluding non-inferiority. These are not reported in the registry record. The original sample-size justification and interim analysis plans are also not reported. These omissions mean that the registry summaries can describe group outcomes but cannot fully establish whether the intended confirmatory analysis was carried out as planned.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 95 participants at risk in the CT-guided localization group and zero among 95 participants at risk in the template-guided localization group. It also reports zero deaths in each group. These figures describe the recorded serious events in the listed groups and follow-up record; they do not prove that the risk of a serious event is absent. With no serious events recorded, the summaries cannot precisely distinguish between low risks in the groups.

The registry separately lists other adverse events affecting 28 participants in the CT-guided group and 16 in the template-guided group, each with 95 participants at risk. These are not the serious-event counts. The record does not provide serious adverse event terms, and the list of top serious terms is empty. It also does not provide a detailed account of event severity, relatedness, or duration. The reported counts should therefore be read as registry summaries rather than as a complete characterization of safety.

In general, safety counts depend on the event definitions, surveillance, and duration of follow-up. The registry lists safety follow-up in the context of outcomes assessed up to 2 days after completion of the final CT scan; longer-term safety information is not reported in the registry record.

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

The posted primary outcome means are 9.6 mm for CT-guided localization and 8.7 mm for template-guided localization. The unadjusted recalculated mean difference is -0.9 mm, with an interval spanning zero and an unadjusted p-value of 0.33. This describes the observed group averages and the uncertainty in their difference. It does not demonstrate that the approaches are identical, nor does it establish a clinically important difference.

The study’s official title identifies it as a non-inferiority trial, but a formal non-inferiority conclusion cannot be recovered from the posted summaries alone. Such a conclusion requires a prespecified margin and a decision rule. The margin and formal analysis are not reported in the registry record. A nonsignificant difference is not, by itself, evidence of equivalence or non-inferiority.

The results also do not establish what would happen in other settings or over longer periods. The listed primary assessment is limited to up to 2 days after completion of the final CT scan, and the registry does not report long-term outcomes. The record does not provide the original sample-size justification, details of missing outcome handling, or the full analysis plan. Those gaps limit assessment of how representative and robust the summaries are.

In general, statistical results and clinical importance answer different questions. A confidence interval describes uncertainty around an estimated contrast; clinical importance depends on context and prespecified thresholds. The registry does not report a clinically important difference threshold for localization accuracy. Accordingly, the posted data can be described as showing a modest negative point estimate with substantial uncertainty, but not as showing that one method is clinically superior or that the methods meet a non-inferiority standard.

The secondary measures and safety counts add procedural context but do not change those limits. Their interpretation is affected by unadjusted comparisons, potential multiplicity, and the lack of a reported analysis plan. The appropriate conclusion is bounded by the registry’s posted summaries, not a recommendation about which localization approach to use.

17. Why This Trial Matters Statistically

This trial illustrates why the label attached to a study question matters for statistical interpretation. A non-inferiority design asks whether a new approach is not worse than a comparator by more than a prespecified amount. That is not the same as asking whether a conventional test detects any difference. The primary comparison has an unadjusted p-value of 0.33, but that value alone cannot answer the non-inferiority question. The non-inferiority margin and formal decision rule are not reported in the registry record.

It also shows the importance of distinguishing a point estimate from its precision. The mean difference is -0.9 mm, but the confidence interval extends across zero. Looking only at the direction of the point estimate would omit uncertainty; looking only at a p-value would omit the range of differences compatible with the data. The means and standard deviations provide useful descriptive information, but they do not replace a prespecified confirmatory analysis.

The modified intention-to-treat population raises another core issue: how participants excluded after randomization can affect interpretation. The record notes 10 participants who did not receive localization and reports 95 participants per arm in the primary outcome summaries. Without group-specific exclusion details and missing-outcome information, it is not possible to assess the impact of those exclusions.

Finally, the multiple secondary outcomes illustrate why a consistent direction across measures should not automatically be treated as confirmation. The registry does not report multiplicity control or a testing hierarchy. Separating descriptive patterns from confirmatory evidence is essential when readers evaluate registry results.

18. Limitations

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

The registry record leaves several trial-specific details unresolved. It identifies the study as non-inferiority but does not report the margin, its rationale, the original sample-size calculation, or the formal decision rule. It also lists no reported outcome analyses. As a result, the posted summary comparisons cannot be checked against a documented analysis plan or interpreted as a confirmed non-inferiority test.

The primary analysis population excludes participants who did not receive localization, with 10 participants noted. Although the primary outcome summaries contain 95 participants per arm, the registry does not provide the excluded participants’ group allocation, outcome information, or fuller reasons for exclusion. Handling of any other missing measurements is not reported. The effect of exclusions or missingness on the estimates is therefore unknown.

The record reports no masking and does not describe allocation concealment or the detailed randomization method. It does not report whether assessors were masked when measuring the CT images. The endpoint description does identify CAD software and image sources, but does not give further measurement reliability information. These details limit assessment of potential procedural or measurement biases.

The follow-up windows listed for the outcomes are short: up to 1 hour for duration and radiation dose, and up to 2 days for accuracy and complications. Long-term outcomes are not reported in the registry record. The registry also does not report a multiplicity strategy for the secondary outcomes, or detailed adverse-event definitions, severity, or relatedness. These limitations constrain interpretation of the results to the posted measurements and summaries.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Application of 3D Printing Technique in Small Pulmonary Nodule Localization — NCT02952261.
• Registry record last updated 2018-12-19; status last verified 2018-12.
• Results first posted 2018-10-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT02952261 is a completed, randomized, parallel-group trial comparing three-dimensional printed template-guided localization with conventional CT-guided localization of small pulmonary nodules. The official title identifies it as a prospective, controlled, non-inferiority trial, and no masking is listed. Planned enrollment was 200.

The primary outcome was localization accuracy, defined as the deviation between the hookwire and the center of the target nodule. The posted means were 9.6 mm in the CT-guided group and 8.7 mm in the template-guided group, with an unadjusted recalculated mean difference of -0.9 mm and p = 0.33. The registry also posts procedural duration, radiation dose, complication counts, and adverse-event counts.

The primary outcome population excludes participants who did not receive localization; the record notes 10 such participants and reports 95 participants per arm. The non-inferiority margin, original sample-size rationale, formal analysis plan, and multiplicity strategy are not reported in the registry record. The posted summaries describe the observed outcomes but do not establish a formal non-inferiority conclusion.