Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Using a 22 vs 25-Gauge Needle: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Using a 22 vs 25-Gauge Needle (NCT03004586), a randomized na study. The primary outcome is Percentage of Lymph Nodes With Adequate Samples.

2. Clinical Question

This is a comparison of needle sampling within a crossover design, with participants assigned to different needle sequences. The registry’s stated goal was to compare the effectiveness of the smaller, 25-gauge needle with the standard 22-gauge needle and also study needle safety. The posted primary results are 79.0 for the sequence beginning with the 25-gauge needle and 78.5 for the sequence beginning with the 22-gauge needle. Those are reported as group-level percentages; the record does not provide confidence intervals, a test of the difference, or a participant-level account of the paired data. The question is therefore clinically framed as a comparison of adequacy, but the posted summary does not establish the precision or statistical evidence for a needle-to-needle contrast.

3. Trial Design

The registry record describes a randomized, double-masked, crossover trial. Enrollment was 61. Participants underwent sampling with both the 22-gauge and 25-gauge needles, with the randomized sequences differing in which needle was used first. One sequence began with the 25-gauge needle and then used the 22-gauge needle; the other began with the 22-gauge needle and then used the 25-gauge needle. The arm records list 31 participants in the first sequence and 30 in the second.

A crossover design differs from a parallel-group comparison because participants receive both interventions or procedures being compared, rather than being assigned to only one. Here, the sequence groups describe the order of needle use. Consequently, the sequence-level percentages are not necessarily equivalent to a direct analysis of paired needle results within each participant. A paired analysis would generally use information about each participant’s results under both needles, while also considering the order in which the needles were used. The registry record does not report the statistical model or analysis details needed to determine how these features were handled.

The registry lists the study as completed, with a start date of 2016-12-16 and a primary completion date of 2020-06-25. The listed phase is NA. The sponsor is M.D. Anderson Cancer Center. The primary outcome timeframe is described as one to two hours. The record also lists concordance with the final diagnosis and needle usability as secondary outcomes, but it does not include posted results for them in the information available. Details of the randomization procedure, the masking procedures, and the conduct of the crossover beyond the sequence descriptions 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: A total of 61 patients were enrolled with a total of 200 lymph node stations evaluated. We randomized the "needle size order" on a per-patient basis with first three needle passes performed with one needle and the remaining 4th and 5th needle passes performed with the other needle. All participants completed the studies and there were no dropouts. Since the randomization was done at the lymph node level, both arms had equal number of participants.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants underwent sampling with both needles.

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 Percentage of Lymph Nodes With Adequate Samples, measured over One to two hours..

The primary outcome is titled “Percentage of Lymph Nodes With Adequate Samples.” Its description says sample adequacy was assessed after two passes using each needle in all participants and recorded. The description also characterizes the primary outcome as the proportion of concordance between the 22-gauge and 25-gauge needles in sample adequacy. Thus, the intended measurement concerns whether needle sampling yields an adequate specimen, with the comparison framed around agreement or performance across the two needles.

Sample adequacy is used as a procedural outcome because it captures whether material obtained by sampling meets an adequacy criterion. In general, this kind of endpoint can reflect the technical result of a sampling procedure, but its interpretation depends on the operational definition of adequacy, who assessed the samples, and whether assessment was blinded. Those details are not reported in the registry record. Nor does the record state a threshold for adequacy or clarify how the concordance description relates to the percentages posted for the two randomized sequence groups.

The registry reports 79.0 for the group that started with the 25-gauge needle and 78.5 for the group that started with the 22-gauge needle. These values are listed as percentages of lymph nodes. The record does not supply uncertainty estimates or a formal paired comparison, so the percentages alone do not show how precisely adequacy differed between needles. The stated timeframe is one to two hours.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to a treatment or procedure sequence by chance, helping prevent systematic differences between groups at allocation. The registry identifies this trial as randomized, but the method used to generate the sequence and conceal assignments is not reported in the registry record. It also identifies the study as double-masked, without specifying who was masked or how masking was maintained. These labels describe features of the trial design; they do not by themselves establish how the primary outcome was analyzed.

What does a crossover design imply?

In a crossover design, each participant receives the interventions or procedures being compared, and randomization determines the order. Here, participants underwent EBUS-TBNA with both needle gauges, with one randomized sequence beginning with the 25-gauge needle and the other beginning with the 22-gauge needle. This makes within-participant comparisons possible. In general, paired observations can be more informative than separate group summaries because each participant can serve as their own reference. However, a valid analysis must use the paired structure rather than treating all measurements as unrelated.

Order may also matter in a crossover study. For example, sampling with the first needle could affect what is available for sampling with the second, or results could vary with procedure period. These are general design considerations, not findings about this trial. The registry record does not report whether period or sequence effects were evaluated, how such effects were modeled, or whether any carryover issue was considered. It also does not provide enough analysis detail to determine whether the primary result was based on individual paired needle outcomes or on summaries by sequence.

Why does the outcome definition matter?

The primary outcome is called the percentage of lymph nodes with adequate samples. Its description also calls the outcome the proportion of concordance between needles in sample adequacy after two passes. Adequacy and concordance are related but distinct concepts: adequacy concerns whether a sample meets a criterion, whereas concordance concerns whether results from two methods agree. A clear analysis needs to define the unit being assessed, the adequacy threshold, and how agreement is summarized. Those details are not reported in the registry record. The record states that adequacy was assessed after two passes with each needle in all participants, but does not explain how the percentage was constructed.

The outcome is based on lymph nodes, while randomization is reported by participant sequence. When a participant contributes multiple observations, those observations may be correlated. General statistical methods for clustered data account for such dependence when estimating uncertainty. If dependence is ignored, a nominal amount of information can appear larger than the truly independent information in the data. The record does not report the number of nodes contributing to each posted percentage, the handling of multiple nodes per participant, or whether clustering was accounted for.

What can the posted estimates tell us?

The registry reports percentages of 79.0 and 78.5 for the two sequence groups. A point estimate is a summary of the observed data, not a complete account of uncertainty. General inferential reporting commonly pairs an estimate with a confidence interval, which communicates the range of values consistent with the data and the model’s assumptions. A hypothesis test may also be reported, but its interpretation depends on the question, the null hypothesis, and the analysis plan. No confidence interval, p-value, or other primary comparative estimate is reported in the registry record.

For a crossover question, a direct comparison could be based on each participant’s paired outcomes. The analysis might also need to account for sequence, period, and repeated observations, depending on the design and data structure. This is general statistical context, not a claim about the method used in the trial. The registry record does not report the model, covariates, estimand, handling of missing outcomes, or other analysis specifications. It records zero analyses in the posted analysis information.

What is the role of planning illustrations?

Any sample-size planning illustration based on the observed effect is a hypothetical design calculation, not evidence that the trial had a particular probability of detecting an effect. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These assumptions are not reported as the trial’s original design plan. The record does not report a trial-specific sample-size justification. Planning illustrations should therefore not be described as observed power, and they do not replace the trial’s unreported precision estimates.

Over-dispersion is a general issue in count or proportion data when variability exceeds what a simple model assumes. If present, it can make standard errors too small unless the model accommodates it. The registry record does not report an over-dispersion assessment, and the posted outcome is not accompanied by an analysis model or variance estimate from which to assess it. No conclusion about over-dispersion in this trial can be drawn.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as percentage of lymph nodes with adequate samples and lists concordance with the final diagnosis and usability of the needle as secondary outcomes. It reports three outcome measures overall, but the results for the secondary outcomes are not reported in the registry record. The registry information records zero analyses. No statistical plan for controlling multiplicity across outcomes or comparisons is reported in the registry record.

Multiplicity arises when several outcomes or statistical comparisons are examined. In general, conducting multiple tests can increase the chance of a nominally unusual result, so an analysis plan may specify which outcome is primary and how secondary analyses will be interpreted. The designation of a primary outcome helps clarify priority, but without the analysis plan and posted results, it is not possible to determine whether or how multiplicity was addressed in this trial.

Missing-data details are not reported in the registry record. The record does not describe the amount or pattern of missing outcome information, the approach to incomplete observations, or whether all randomized participants were included in the primary analysis. It states that all participants underwent sampling with both needles, but this does not establish that every relevant outcome was available or analyzed. The analysis population, including whether it followed randomization assignment or required a particular level of completion, is also not reported in the registry record.

These omissions constrain interpretation: the percentages can be read as posted descriptive results, but the record does not establish the completeness of the analysis set, the handling of missing observations, or the inferential framework used for the primary question.

11. 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 5% reporting threshold.

The safety results list 31 participants at risk in the sequence that began with the 25-gauge needle and 30 participants at risk in the sequence that began with the 22-gauge needle. The registry reports zero serious adverse events in each group, zero other adverse events in each group, and zero deaths in each group. These are the posted counts for the reported groups.

A reported count of zero means that no event in that category was recorded among the participants listed as at risk in the registry results. It does not demonstrate that the true risk is zero, nor does it establish that the two needles have identical safety profiles. Rare events can be difficult to characterize from a trial of this size, and the registry does not give uncertainty intervals for the safety counts. This is a general limitation of interpreting event counts.

The record does not provide definitions for serious or other adverse events, event-specific descriptions, severity grades, relatedness assessments, or the duration and completeness of safety follow-up. It also does not clarify how safety events were attributed when every participant underwent sampling with both needles. No serious adverse event terms are listed. Accordingly, the zero counts should be interpreted narrowly as the events posted for the two sequence groups, not as proof that the procedures carry no risk.

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

The registry reports sample-adequacy percentages of 79.0 in the group that used the 25-gauge needle first and 78.5 in the group that used the 22-gauge needle first. These are descriptive summaries by randomized sequence. The record also states that all participants underwent sampling with both needles, making the study a crossover comparison in which the order of use differed between groups.

The main limitation for interpretation is that the record does not report a direct paired estimate comparing the needles, its precision, or an inferential test. The primary outcome description combines the idea of adequate samples with concordance between needle results, but the record does not specify how that relationship was translated into the posted percentages. It also does not state the denominator for the percentages or how multiple lymph nodes from the same participant were handled. This leaves uncertainty about the precise meaning of the group-level values.

The reported values do not establish equivalence or noninferiority. Such conclusions require a specified margin and an analysis designed to evaluate whether uncertainty excludes differences considered important. Neither a margin nor an analysis of that kind is reported in the registry record. Likewise, the values do not establish superiority for either gauge. Without uncertainty estimates, readers cannot judge how compatible the results are with a range of possible comparative effects.

The record lists concordance with final diagnosis and needle usability as secondary outcomes, but their results are not reported in the registry record. Safety results report zero serious adverse events, zero other adverse events, and zero deaths in both sequence groups; these counts do not establish the absence of risk. Overall, the posted information offers a limited descriptive account of the trial’s primary outcome and safety counts, rather than a complete statistical evaluation of the needle comparison.

13. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to analyze procedural comparisons when participants receive both methods. A randomized crossover design can support paired comparisons, but the analysis must preserve the relationship between measurements from the same participant. Reporting only group-level percentages by randomized sequence may not communicate the within-participant contrast that the design makes possible. The registry does not report whether the posted summaries are based on paired outcomes or how the order of needle use was handled.

The unit of outcome is also important. The primary outcome refers to lymph nodes, whereas the randomized groups are described by participant sequence. When several nodes can be sampled in a participant, observations may be correlated. A complete statistical report would clarify the unit of analysis, the number of observations contributing to each summary, and the approach to dependence among observations. The registry record does not report those details.

Another important issue is the distinction between adequacy and concordance. Adequacy is a property of a sample; concordance describes agreement between the results from the two needles. The primary outcome description invokes both, while the registry’s outcome title refers to the percentage of nodes with adequate samples. Clear definitions and a direct comparative estimate would help readers understand what the reported percentages mean and how they address the trial question.

Finally, statistical interpretation depends on uncertainty, not just point estimates. No confidence interval or primary test is reported in the registry record, and the secondary outcome results are absent. The record’s sample-size illustration assumptions are not a substitute for the trial’s own design justification or for an uncertainty analysis. These features make the trial a useful example of how design labels and outcome summaries alone may not provide enough information to assess a comparative result.

14. 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 questions unresolved. Although the primary outcome is titled as a percentage of lymph nodes with adequate samples, its description defines the primary outcome in terms of concordance between the 22-gauge and 25-gauge needles. The record does not explain whether the posted sequence-group percentages represent adequacy for each needle, a concordance measure, or another summary. It also does not state the adequacy criterion or identify who assessed adequacy.

The outcome is measured at the lymph-node level, but assignment to sequence is reported at the participant level. The registry does not provide the number of lymph nodes contributing to each percentage or describe how multiple nodes per participant were handled. This matters because observations within a participant may be statistically related. The outcome description refers to two passes with each needle and mentions 200 lymph nodes in the control-group wording, but the record does not reconcile that wording with its participant enrollment and group sizes.

There are no posted analysis estimates, confidence intervals, p-values, or model details for the primary outcome. The registry does not report whether the paired structure, sequence, period, or potential carryover was considered. Nor does it report a prespecified equivalence or noninferiority margin. The randomization and masking labels are present, but the methods used to implement them are not reported in the registry record.

The record lists secondary outcomes but does not report their results. Missing-data handling, analysis populations, and the completeness of outcome assessment are not reported in the registry record. Safety event definitions, attribution, and follow-up details are also not reported. These limitations mean the posted percentages and event counts should be treated as limited descriptive information, not as a complete account of comparative effectiveness or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Using a 22 vs 25-Gauge Needle — NCT03004586.
• Registry record last updated 2022-06-22; status last verified 2022-05.
• Results first posted 2022-06-22.
• 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.

18. Record Summary

NCT03004586 is a completed randomized, double-masked crossover trial titled “Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Using a 22 vs 25-Gauge Needle.” The record lists M.D. Anderson Cancer Center as sponsor, enrollment of 61, a start date of 2016-12-16, and a primary completion date of 2020-06-25. The study compared sequences in which EBUS-TBNA began with either the 25-gauge or 22-gauge needle; all participants underwent sampling with both.

The primary outcome concerns lymph-node sample adequacy, with the description also referring to concordance between needles. The posted percentages are 79.0 for the sequence beginning with the 25-gauge needle and 78.5 for the sequence beginning with the 22-gauge needle. The record lists concordance with final diagnosis and needle usability as secondary outcomes, but their results are not reported in the registry record. It reports zero serious adverse events, zero other adverse events, and zero deaths in both groups. A comparative analysis estimate, its uncertainty, and the detailed statistical plan are not reported in the registry record.