Endoscopic Ultrasound Guided Fine Needle Biopsy (EUS-FNB-SC) Using a Novel Fork Needle: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Endoscopic Ultrasound Guided Fine Needle Biopsy (EUS-FNB-SC) Using a Novel Fork Needle (NCT02678442), a randomized na study. The primary outcome is Total DNA Yield of Adenocarcinoma.

2. Clinical Question

3. Trial Design

This completed study was a randomized, single-masked, crossover trial sponsored by Mayo Clinic. It enrolled 50 people with pancreatic cancer. The registry record lists the phase as NA. In the crossover sequences, both needle methods were used: one sequence began with Shark Core Fine Needle Biopsy (FNB) and then used Fine Needle Aspiration (FNA), while the other began with FNA and then used FNB. Randomization therefore concerned the order of the procedures. The registry record does not identify who was masked or describe the masking procedures.

The trial was designed as a pilot-feasibility comparison of tissue acquisition for whole exome sequencing and genomic profiling. Its stated hypothesis was that FNB would yield more tumor DNA and cellular material than conventional FNA, and increase the proportion of cases with sufficient DNA for genomic analysis. That aim provides context for the outcome measures, but the primary result reported is a continuous DNA-yield measure rather than a direct count of successful sequencing or genomic profiling.

The primary outcome was total DNA yield of adenocarcinoma, measured in ng/µL at baseline and described as the quantity obtained from the first needle pass. The registry also lists secondary outcomes concerning the number of passes needed for adequate tissue, core tissue length, DNA concentration, tumor cellularity, and adequacy of first-pass samples for cytologic and histologic interpretation. Results are not reported in the registry record for every listed outcome. Safety information is presented separately for each needle method.

The registry reports a two-sided t-test for the primary comparison and a two-sided t-test for DNA concentration. It does not report the full statistical analysis plan, the handling of the crossover structure, or the original design assumptions. Reasons why the primary outcome lists 37 observations per method while other reported outcomes use 50 are not reported in the registry record. Those counts should not be treated as interchangeable analysis populations.

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.

First Intervention

Second Intervention

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 Total DNA Yield of Adenocarcinoma, measured over Baseline.

The primary endpoint was total DNA yield of adenocarcinoma, expressed in ng/µL. The registry describes it as the total quantity of DNA obtained from the first needle pass, with the timeframe listed as baseline. This endpoint measures the amount of DNA recovered from a sample, rather than whether the sample ultimately produced a successful genomic profile or whole exome sequence.

The endpoint was relevant to the trial’s feasibility aim because the trial summary identified tissue yield as a consideration for genomic profiling and sequencing. A larger yield could be useful for those downstream purposes, but the registry record does not report a threshold defining sufficient DNA, nor does it report a direct primary outcome for successful sequencing. The measured yield should therefore be interpreted as a laboratory quantity, not as proof that downstream testing was completed or successful.

The posted primary results give a mean and standard deviation for each needle method. The FNB mean was 5930.0 ng/µL with a standard deviation of 881.0, and the FNA mean was 3365.0 ng/µL with a standard deviation of 788.0. These group summaries describe the reported outcome; they do not show the distribution of individual values or how each participant’s paired measurements related to each other. The registry record does not provide individual-level data or a detailed definition of the assay procedures.

Using the first pass focuses the comparison on material obtained at the beginning of sampling, but the registry record does not explain why this was selected over total yield from all passes. Nor does it report whether first-pass yield was the only measure used to assess the practical adequacy of tissue for the trial’s genomic aims.

7. Results Posted in the Registry

• Fine Needle Aspiration (FNA): mean 3,365 versus 5,930 on control; difference -2,565 (95% CI -2,946 to -2,184), standardized effect d = -3.07; z-test p = <0.001.

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.

Concentration of DNA Yield of Adenocarcinoma

• 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:
  • Fine Needle Aspiration (FNA): mean 37.21 versus 65.00 on control; difference -27.79 (95% CI -31.64 to -23.94), standardized effect d = -3.29; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Fine Needle Aspiration (FNA) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total Number of Subjects Where First-pass Biopsy Contained Adequate Material for Cytologic Interpretation

• 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:
  • Fine Needle Aspiration (FNA): 36.0% (18/50) versus 6.0% (3/50) on control; risk difference 30.0 percentage points (95% CI 15.2 to 44.8), risk ratio 6.00 (1.89–19.10); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Fine Needle Aspiration (FNA) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total Number of Subjects Where First-pass Biopsy Contained Adequate Material for High Quality Histologic Interpretation

• 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:
  • Fine Needle Aspiration (FNA): 8.0% (4/50) versus 66.0% (33/50) on control; risk difference -58.0 percentage points (95% CI -73.1 to -42.9), risk ratio 0.12 (0.05–0.32); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Fine Needle Aspiration (FNA) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the picture beyond the primary measure of first-pass DNA quantity. The reported results do not point uniformly in the same direction across all dimensions of tissue adequacy. DNA concentration and histologic adequacy follow the direction of the primary DNA-yield result, whereas cytologic adequacy points in the opposite direction. This pattern suggests that adequacy depends on what kind of material is being assessed and how the sample is intended to be interpreted; one secondary endpoint cannot stand in for all the others.

These outcomes relate to the primary result because each addresses a different step or attribute in tissue acquisition. DNA yield and concentration concern DNA quantity, while cytologic and histologic interpretation concern whether a sample contains material judged suitable for particular forms of evaluation. The trial’s stated goal involved genomic profiling and whole exome sequencing, but the reported secondary outcomes do not directly establish successful completion of those downstream procedures. The registry record does not report a direct success endpoint for sequencing or genomic profiling.

The registry lists additional outcomes concerning passes needed for adequate diagnosis, core tissue length, and tumor cellularity. Results for these outcomes are not reported in the registry record. Their absence prevents an overall assessment of all the registered specimen characteristics and means that the available secondary results are not a complete account of every stated outcome.

Secondary comparisons generally carry less weight than the primary result for drawing a focused conclusion. Multiple outcomes create more opportunities for apparently notable findings, particularly when analyses are unadjusted and no multiplicity procedure is reported. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. Their results are therefore best treated as exploratory context that may help characterize the different tissue measures, rather than as independent confirmation of the primary finding.

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

• Total Number of Passes Needed to Obtain Adequate Tissue Sample for Cytology/Histology Diagnosis
• Core Tissue Length
• Concentration of DNA Yield of Adenocarcinoma
• Percentage of Tumor Cellularity
• Total Number of Subjects Where First-pass Biopsy Contained Adequate Material for Cytologic Interpretation
• Total Number of Subjects Where First-pass Biopsy Contained Adequate Material for High Quality Histologic Interpretation

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean describe?

For a continuous outcome such as DNA yield, the mean is the arithmetic average of the recorded measurements in a group. The standard deviation describes how spread out those measurements are around their group mean. In the primary results, the mean and standard deviation are reported separately for FNB and FNA. These summaries help characterize typical yield and variability, but they do not show the full distribution, identify unusual values, or reveal how paired observations from the same participant relate to each other.

As a general statistical point, a mean difference expresses the distance between group averages, with the sign determined by the order of subtraction. The posted recalculation defines the comparison as FNA relative to FNB; consequently, its negative estimate indicates a lower average for FNA. The magnitude is in the endpoint’s units, ng/µL. The estimate is not a percentage, and it should not be interpreted as a change in each individual participant’s yield.

What does the t-test assess?

The registry reports a two-sided t-test for the primary outcome. In general, a t-test evaluates whether the observed difference in means is compatible with a null hypothesis of no mean difference, under the assumptions of the test. A two-sided test allows evidence in either direction rather than testing only for a higher mean in one prespecified direction. A p-value describes how unusual data at least as extreme as those observed would be under the null model and test assumptions. It is not the probability that the null hypothesis is true, nor does it measure the clinical or practical importance of the observed difference.

The registry’s reported primary p-value is 0.01. The unadjusted recalculation from posted summary statistics gives p < 0.001. The recalculation is not a replacement for the trial’s full analysis. It uses summary statistics and does not have the individual-level observations or the full description of the analysis procedure. Although the trial is crossover, the registry record does not say whether the sponsor’s t-test was paired, whether a participant-level correlation was used, or how order was handled. A paired analysis can use the fact that each participant contributes measurements under both methods; an analysis that treats measurements as independent does not use that information in the same way.

Why does crossover structure matter?

As a general statistical point, crossover designs compare interventions within participants, which can reduce the influence of stable differences between participants when the analysis is matched to that design. The order of interventions can also matter if there are period effects, carryover effects, or changes in the measurement process across procedures. The registry record identifies the randomized sequences but does not report whether these possibilities were assessed or how they were incorporated into the primary model. Without that information, a reader cannot reconstruct the sponsor’s treatment contrast or determine how much the reported analysis used the crossover structure.

The displayed recalculated comparison is an unadjusted recalculation from the posted group summaries. It should be read as a summary-statistic comparison, not as a reanalysis of participant-level paired data. No adjustment for sequence, period, or participant effects is reported in the registry record. Those absent details limit how specifically the recalculated uncertainty can be related to the randomized crossover design.

How should the confidence interval be read?

A confidence interval gives a range of estimates compatible with the data under a statistical procedure and its assumptions. It conveys uncertainty about the estimated difference, rather than a range containing a stated proportion of individual DNA-yield measurements. For the primary recalculation, the 95% confidence interval for FNA relative to FNB ranges from -2946.0 to -2184.0 ng/µL. Its position below zero is consistent with the negative mean difference. The registry’s own primary analysis does not include a confidence interval, so this interval belongs to the recalculation rather than the reported sponsor analysis.

As a general statistical point, the width of a confidence interval reflects both the variability of measurements and the amount of information used in the analysis. The interval does not address systematic measurement error, selection into the analysis, missing data, or whether the outcome is the most relevant measure of feasibility. It also does not establish that a downstream genomic application succeeded.

What does “unadjusted” mean in these comparisons?

The recalculated comparisons are unadjusted: they do not incorporate covariates or other model features beyond the posted summary values. This makes them comparatively transparent, but it does not make them equivalent to the full analysis used by the trial investigators. The registry does not report an adjusted model for the primary result, nor does it give enough detail to determine whether covariate adjustment was planned or conducted.

For binary secondary outcomes, a risk difference compares the reported proportions between methods. The displayed comparison uses the direction FNA relative to FNB. Confidence intervals for such differences express uncertainty about the contrast, and the unadjusted p-value tests a null of no difference under the method used for recalculation. These outcomes are distinct from DNA yield, and the number of adequate samples does not serve as a substitute for a continuous yield measurement.

Finally, a p-value below a conventional threshold does not by itself establish that an effect is important, reproducible, or generalizable. Interpretation also depends on the endpoint definition, design, analysis population, missingness, multiplicity, and precision. The registry record leaves several of these analysis details unreported, so the numerical evidence should be read alongside those limitations.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -2565.0 ng/µL for FNA relative to FNB, with a 95% confidence interval from -2946.0 to -2184.0. This interval describes uncertainty in the estimated difference under the recalculation’s assumptions. It does not describe the range of individual participant values. Because the interval is entirely negative, the summary-statistic comparison points consistently toward lower mean yield for FNA than FNB.

The group standard deviations, 881.0 for FNB and 788.0 for FNA, describe variability around the group means. They are not standard errors and do not themselves give the precision of the difference. The recalculation reports standard errors of 144.8 for FNB and 129.5 for FNA. These are measures of uncertainty in the respective group means under the calculation, rather than measures of individual variability.

The registry reports p = 0.01 for its two-sided primary t-test, but does not report a confidence interval for that analysis. The recalculated interval should therefore not be attributed to the registry’s test. The registry record also does not report individual paired data, the correlation between measurements within participants, or the analysis details needed to evaluate uncertainty in light of the crossover structure. Those omissions limit a full assessment of whether the recalculated interval captures the uncertainty of the intended within-participant contrast.

The secondary DNA-concentration comparison also has a recalculated confidence interval, while the reported registry analysis gives a two-sided p-value without an interval. For binary secondary endpoints, the recalculated risk-difference intervals show uncertainty around the between-method contrasts. These intervals belong to the individual secondary comparisons; they do not account for the number of outcomes considered. Precision in any one estimate does not resolve questions about missing data, analysis populations, outcome selection, or multiplicity.

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 illustrations based on observed effects, not the trial’s original design calculations. For continuous outcomes and the binary outcomes shown, the figures are participants per arm, not total sample sizes or total events. The assumptions listed for these illustrations 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 as the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrated participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and model are correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are prospective planning concepts, not descriptions of how likely the completed trial was to find a result after its data were observed.

The rows that plan for 100% of the observed effect use the full observed difference as the target. Rows for 75% and 50% of the observed effect use progressively smaller targets. Smaller effects are harder to distinguish from random variation, so the planning figures rise as the target effect gets smaller. The same pattern applies when choosing the higher power target: a design seeking greater power generally requires more participants per arm for a given effect.

These figures are not observed power. They should not be used to infer that the trial had adequate power, or to explain why its enrolled or analyzed counts took the values reported. The illustrations also do not incorporate the unreported features of the trial’s original design or establish an appropriate sample size for a future study.

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 = -2564.880; pooled standard deviation σ = 835.795.
2. n = 2 × (1.96 + 0.842)² × 835.795² / -2564.880² = 1.7, rounded up to 2 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 <- -2564.88                      # observed difference in means
sigma <- 835.794532166848                     # 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(2678442)
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 = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 50% of observed effect: n per arm = 7 (80% power), 9 (90% power)
power.t.test: 3 
Simulated power at n = 2 per arm: 0.399 (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. Analyses Reported by the Sponsor

The registry reports that the primary comparison used a two-sided t-test and gives p = 0.01. For DNA concentration, it reports a two-sided t-test with p = 0.02. The primary mean difference, confidence interval, and p-value described as recalculated are separate unadjusted calculations from posted summary statistics. The recalculated primary p-value is p < 0.001, and its confidence interval is not a confidence interval reported for the registry’s own analysis.

The sponsor-reported primary p-value and the recalculated p-value differ numerically, but both indicate a result in the same direction as the observed group means. The registry record does not provide the detailed analysis specification, participant-level data, or enough information to determine precisely why the p-values differ. In particular, it does not state whether the sponsor analysis used a paired test or another approach that reflected the crossover structure.

The registry’s analysis is the trial’s reported analysis; the recalculation is a secondary, summary-statistic check and should not be presented as if it were the sponsor’s method. The registry record does not provide a sponsor-reported confidence interval for the primary difference. For questions about the trial’s own inferential result, the reported analysis takes precedence over the recalculation; the latter is useful for showing the direction and scale of the contrast as calculated from the posted group summaries.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists several secondary outcomes. It reports p-values for the primary DNA-yield analysis and the DNA-concentration analysis, and the recalculations give unadjusted p-values for the reported binary outcomes. The registry record does not report whether the investigators adjusted for multiple comparisons, prespecified a hierarchy among secondary endpoints, or treated any secondary results as exploratory. Without that information, the individual p-values should not be read as if they jointly control the chance of false-positive findings across all outcomes.

Missing-data handling is not reported in the registry record. The record does not state how missing measurements were defined, whether any data were excluded, how incomplete outcome observations were handled, or whether an analysis used imputation. It also does not report reasons for the different counts used across outcomes. The primary comparison lists 37 observations for each method, while the adequacy and safety results use 50 as the reported denominator for each method. The reason for this difference is not reported, so it should not be attributed to loss to follow-up, unusable specimens, or any other cause.

The analysis populations are not defined in sufficient detail to establish whether the primary analysis included all randomized participants, only participants with both measurements, or another set. The registry record does not report a participant flow account linking enrollment, sequence assignment, procedures, specimens, and the outcome-specific counts. This limits assessment of potential selection effects if inclusion in an analysis depended on having measurable tissue or complete results.

The crossover design also raises analysis questions that are not answered in the registry record. It does not report how within-participant correlation, treatment order, or possible period and carryover effects were handled. The reported t-test label alone does not establish whether the test was paired or how the randomized sequence was incorporated. These omissions are relevant to both the estimated contrast and its uncertainty, and they make it difficult to reproduce the sponsor analysis from the registry entry.

16. 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.

Most frequent non-serious adverse event terms

The safety record lists serious adverse events for 50 participants at risk under FNB and 50 at risk under FNA, with 0 serious adverse events reported for each method. It also reports 0 deaths for each method. No serious adverse-event terms are listed in the registry record. These are the counts recorded for the trial; they should not be interpreted as establishing that serious harms are impossible or that the methods have identical safety profiles.

For other adverse events, the record lists 2 affected participants under FNB and 0 under FNA, with 50 at risk for each method. The registry does not provide event descriptions, severity details for these other events, or a statistical comparison. It also does not explain how safety attribution was handled in the crossover setting, where participants underwent both procedures. The counts alone therefore do not establish that an event was caused by a particular needle method.

Safety figures should be read alongside the scope and duration of observation, but the registry record does not provide enough detail to characterize those aspects fully. Zero recorded serious events is a descriptive finding in this study, not a guarantee about safety in other populations or settings.

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

The primary data show a higher reported mean first-pass adenocarcinoma DNA yield for FNB than for FNA. The unadjusted recalculation of the mean difference is -2565.0 ng/µL for FNA relative to FNB, with a 95% confidence interval from -2946.0 to -2184.0 and p < 0.001. The registry’s own two-sided t-test reports p = 0.01. These results describe the measured DNA yield in the analysis represented by the registry summaries.

That finding does not by itself show that FNB produces a usable genomic profile or a completed whole exome sequence. Although the trial summary frames tissue yield in relation to genomic profiling, the registry record does not report a threshold for sufficient DNA or a direct outcome measuring the success of those procedures. Nor does a higher mean establish that every participant’s sample contained more DNA under FNB.

The crossover design and the outcome-specific counts require care in interpreting the estimate. The registry does not report the participant-level paired data, the reason for the counts used in each analysis, or the handling of sequence and within-participant effects. The recalculation uses posted group summaries and is not a substitute for a fully specified crossover analysis. The sponsor-reported result and recalculation should be distinguished rather than combined as if they were the same procedure.

Secondary outcomes add context, but their directions are not fully consistent across different forms of sample adequacy, and the registry record does not report results for all listed secondary measures. Unadjusted results across multiple outcomes are less secure as confirmatory evidence when the record does not describe multiplicity handling. The safety counts are also descriptive and do not establish equivalence or rule out uncommon harms.

Overall, the registry supports a difference in the reported first-pass DNA-yield means in this trial. It does not establish broader clinical benefit, the success of downstream genomic testing, generalizability to other settings, or a complete comparison of all relevant diagnostic and safety outcomes.

18. Why This Trial Matters Statistically

This trial illustrates why a statistical comparison needs to be read together with the measurement it uses. DNA yield is relevant to the stated feasibility goal, but it is not identical to successful genomic profiling or sequencing. A clear difference in a laboratory quantity can be informative while still leaving the downstream practical question unanswered. Distinguishing an intermediate measurement from a final intended use is essential when translating a statistical result into a scientific conclusion.

The crossover structure is also statistically important. Because the procedures were given in randomized sequences, the analysis may need to account for the fact that observations from the same participant are related and that procedure order could matter. The registry record identifies the sequences but does not report how the analysis handled those features. This is a useful reminder that a familiar test label, such as a two-sided t-test, may not convey enough detail to evaluate whether the analysis reflects the design.

The contrast between the sponsor-reported p-value and the unadjusted recalculation demonstrates why calculations from group summaries should be labeled and interpreted separately from a trial’s own analysis. Summary-statistic recalculations can make the scale and direction of a comparison easier to inspect, but they cannot recover unavailable individual-level information or fill in missing design details.

Finally, the secondary outcomes reveal that “adequacy” is not a single property. DNA quantity, cytologic interpretation, histologic interpretation, and other tissue characteristics address different questions. Their results should be considered as a set of related but non-interchangeable measures, with due attention to missing results and unreported multiplicity handling.

19. 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 limitations unresolved. Although the study is randomized and crossover, the reported analysis does not specify whether the primary comparison was paired or how treatment order, period effects, or possible carryover were addressed. The summary-statistic recalculation cannot use within-participant correlations. Without the individual-level data and a full analysis description, the uncertainty estimates cannot be independently reconstructed in a way that fully reflects the crossover design.

The outcome counts also differ: the primary yield comparison reports 37 observations per method, while several other results and the safety record report 50 at risk or assessed per method. The registry does not explain why these counts differ, define the analysis populations, or describe missing-data handling. This prevents a clear account of which participants contributed to each outcome and whether the analyzed observations could differ systematically from those not included.

The endpoint is a DNA quantity, not a direct measure of successful genomic profiling or whole exome sequencing. No sufficient-DNA threshold or downstream success result is reported in the registry record. Results for every listed secondary outcome are also not reported, including outcomes related to the number of passes, core length, and tumor cellularity. This restricts evaluation of the wider tissue-acquisition objectives.

The record does not report a multiplicity strategy for the several secondary outcomes. It also provides limited detail on masking and does not identify who was masked. The safety counts are descriptive, with no reported event descriptions for the other adverse events or analysis of attribution in the crossover design. These limitations do not erase the observed difference in the posted primary means, but they constrain the strength, scope, and interpretation of conclusions from the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Endoscopic Ultrasound Guided Fine Needle Biopsy (EUS-FNB-SC) Using a Novel Fork Needle — NCT02678442.
• Registry record last updated 2020-01-06; status last verified 2019-12.
• Results first posted 2020-01-06.
• 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.

23. Record Summary

This completed randomized, single-masked crossover trial compared endoscopic ultrasound-guided FNB and FNA in pancreatic cancer. Enrollment was 50. Its primary endpoint was total DNA yield of adenocarcinoma from the first needle pass, measured in ng/µL. The registry reports means of 5930.0 for FNB and 3365.0 for FNA, with standard deviations of 881.0 and 788.0, respectively.

The registry reports a two-sided primary t-test with p = 0.01. An unadjusted recalculation from the posted summaries estimates an FNA-minus-FNB mean difference of -2565.0 ng/µL, with a 95% confidence interval from -2946.0 to -2184.0 and p < 0.001. The crossover analysis details, reasons for outcome-specific counts, missing-data methods, and multiplicity handling are not reported in the registry record.

Reported secondary results address DNA concentration and first-pass cytologic and histologic adequacy, with directions that are not uniform across all measures. The registry also lists other secondary outcomes without reported results. The primary finding concerns DNA yield and does not itself establish successful genomic profiling or sequencing.