A Retrospective Study to Determine the Incidence of NTRK Fusions. NTRK Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Retrospective Study to Determine the Incidence of NTRK Fusions. NTRK Study (NCT04010240), a registered phase not stated study. The primary outcome is Count of Participants With NRTK Fusions Among Participants Analyzed by NGS (Next-generation Sequencing)..

2. Clinical Question

The primary outcome is a count of participants meeting the molecular definition, not a reported rate or percentage. To interpret incidence, a reader would need both the count with a fusion and the relevant number tested, ideally by histological diagnosis. The registry record gives an overall enrollment figure but does not state the NGS-tested denominator, the primary count, or results by histology. Enrollment therefore cannot be treated as the denominator for the primary endpoint.

The record also lists a secondary outcome counting participants with fusions among participants with positive immunohistochemistry (IHC). That listing identifies an additional question, but no result or analysis detail is reported. The clinical question is consequently an ascertainment and frequency question in a selected, tested cohort, not a treatment-effect question.

3. Trial Design

This is registered as a retrospective cohort study with no intervention. The listed study population comprises subjects with locally advanced, unresectable or metastatic solid tumors. The study’s primary objective is to estimate NTRK gene fusion incidence according to histological diagnosis and to describe related treatment outcomes. The registry names Institut Bergonié as sponsor and gives enrollment as 3820. The recorded status is completed; the start date is 2015-12-23 and the primary completion date is 2022-12-31.

The primary endpoint concerns participants analyzed by NGS at baseline, defined as the time of tumor removal. A participant is classified as having an NTRK fusion when the tumor harbors an NTRK1, NTRK2 or NTRK3 gene fusion, based on NGS. The record describes RNA analysis with Archer or full RNA sequencing to assess rearrangements producing NTRK fusion transcripts. Alternatively, DNA was analyzed using a hybrid-capture-based NGS assay. It says DNA and RNA were extracted from tumor tissue according to standard procedures.

No allocation method or treatment arms are described as a randomized comparison. The sole arm description identifies subjects with locally advanced, unresectable or metastatic solid tumors, and the intervention field explicitly identifies no intervention. Thus, the arm label should not be interpreted as evidence of a control group or a like-for-like treatment comparison. Allocation details beyond the absence of an intervention are not reported in the registry record.

The record lists three outcome measures, but the details available for the primary endpoint do not include a numerical result. It reports zero analysis entries. The number of participants actually tested by NGS, the distribution across histological diagnoses, and the timing or completeness of retrospective data collection are not reported in the registry record. These omissions limit assessment of how the stated cohort objective was implemented.

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: Subjects with locally advanced/unresectable or metastatic solid tumors and for whom NGS (new generation sequencing) was performed

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.

Population: Age and sex were not collected.

6. Primary Endpoint

The registry lists the primary outcome as Count of Participants With NRTK Fusions Among Participants Analyzed by NGS (Next-generation Sequencing)., measured over at baseline (i.e. at the time of tumor removal).

The primary endpoint is the count of participants with an NTRK1, NTRK2 or NTRK3 gene fusion among participants analyzed by NGS. The assessment is specified at baseline, meaning at the time of tumor removal. A positive classification depends on a tumor having an NTRK fusion identified by the stated sequencing methods. The endpoint is a count, not itself an incidence rate.

Counts can answer how many tested participants met a definition, but an incidence estimate also needs a denominator: the number of eligible participants tested in the relevant group. Because the stated objective is to estimate incidence by histological diagnosis, a useful interpretation would also require the tested denominator and positive count for each histological category. Neither the primary count nor the NGS-tested denominator or histology-specific results are reported in the registry record. The enrollment of 3820 cannot substitute for the tested denominator without evidence that all enrolled participants were analyzed.

General statistical context: classifying a molecular finding as present or absent creates a binary outcome for each tested participant. A count of positive classifications can then be related to the number tested to describe frequency. The validity and interpretation of that frequency depend on a clearly defined population, consistent testing and classification, and an appropriate denominator. The registry describes the molecular definition and testing approaches, but the results needed to evaluate the resulting frequency are not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a count of participants classified as having an NTRK fusion by NGS. General statistical context: a count reports the number of observed cases meeting a definition. By itself, it does not show how common the finding was in the population at risk or among those tested. To describe frequency, the count must be interpreted with its denominator. For this study, the endpoint title identifies participants analyzed by NGS as the relevant group, but the number analyzed and the positive count are not reported in the registry record.

What does a binary endpoint mean?

General statistical context: a binary outcome classifies each person into one of two categories, such as meeting or not meeting a defined criterion. Here the stated criterion is a tumor harboring an NTRK1, NTRK2 or NTRK3 fusion based on NGS. A participant-level classification can be counted across a tested group. A clear definition helps readers understand what qualifies as a case, but it does not reveal the observed frequency unless both the count and the tested population are reported.

The registry specifies that the primary assessment is at baseline, described as the time of tumor removal. It describes extraction of DNA and RNA from tumor tissue, RNA analysis with Archer or full RNA sequencing to assess specific novel NTRK rearrangements that produce fusion transcripts, and an alternative hybrid-capture-based NGS assay using DNA. These are descriptions of the testing approaches; the record does not give the number tested with each method, the criteria for choosing between approaches, or method-specific results.

Why is the denominator important?

General statistical context: a frequency estimate is interpretable only when its denominator is defined and matches the population to which the estimate refers. A count among participants tested by NGS is not automatically a count among all enrolled participants. Nor can an overall tested group answer a question about differences by histological diagnosis unless category-specific counts and denominators are available. The record gives enrollment as 3820, but does not identify the NGS-tested denominator or histology-specific endpoint results. No recalculation of incidence is possible from the registry record.

General statistical context: when the number tested is limited, an estimate may be imprecise; a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A confidence interval cannot be described for this endpoint because the record does not report a result, denominator, or interval. No precision estimate by histological diagnosis is reported either. The absence of those quantities should not be mistaken for a precise estimate or a finding of no fusions.

What can be inferred from the planning assumptions?

The record contains planning-illustration assumptions based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. It also says that the illustration is not the study’s own design and distinguishes participant-per-arm quantities from total event quantities for time-to-event settings. These assumptions do not establish that the retrospective cohort had two assigned arms; the intervention field says there was no intervention. They are not observed power, and they do not substitute for the missing endpoint results. Because no observed effect or relevant group results are reported, the planning illustration cannot be interpreted as evidence about the study’s outcome.

General statistical context: a sample-size planning calculation describes the sample size associated with specified assumptions for a future design. It is distinct from an analysis of the data collected, and it does not establish what the study found. For a retrospective frequency question, interpretation primarily requires the number tested and the number meeting the molecular definition, along with a clear account of the population and testing. Those results are not reported in the registry record.

How should the absence of analysis entries be read?

The record lists zero analysis entries. General statistical context: an analysis entry can report an estimate, uncertainty measure, or model result, but the absence of registered analysis entries does not itself show that no analysis occurred. It means that the registry record does not present those analysis details through that field. The endpoint’s numerical result, method of estimating incidence, handling of histological categories, and any adjusted analyses are not reported in the registry record. No particular statistical model or test should be attributed to the study.

Over-dispersion is a general issue in count modeling: observed counts can vary more than a model’s assumptions allow, which can make uncertainty estimates too small if the extra variability is ignored. There is no reported count model, dispersion estimate, or analysis indicating that over-dispersion was assessed in this study. It would therefore be inappropriate to claim that this issue affected the reported results. More broadly, without analysis results and methods, statistical precision and assumptions cannot be checked.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Subjects With Locally Advanced/Unresectable or Met")
n      <- c(2378)
events <- c(11)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Subjects With Locally Advanced/Unresectable or Met  2378  11  0.5  0.2  0.8  0.3  0.8  0.3  0.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and zero analysis entries. It identifies the primary outcome as the count of participants with NTRK fusions among those analyzed by NGS and lists a secondary outcome concerning fusion counts among participants with positive IHC. It does not report the complete results for the outcomes, an analysis hierarchy, or a plan for controlling the chance of false-positive findings across multiple outcomes or histological categories. A multiplicity adjustment, or a decision not to use one, is not reported in the registry record.

The registry does not report how missing tumor specimens, unavailable sequencing results, failed assays, or incomplete clinical records were handled. It also does not give the number excluded from the primary analysis or reasons for exclusion. These details are important because the primary endpoint is defined among those analyzed by NGS, while enrollment is reported separately as 3820. The tested analysis population and its relation to enrollment are not specified.

The population description and the testing method are stated, but the record does not report whether all eligible participants were tested, how histological categories were defined or combined, or how missing histology was treated. It does not identify a statistical analysis population beyond participants analyzed by NGS for the primary outcome. No imputation method, complete-case rule, sensitivity analysis, or missing-data assumption is reported in the registry record.

General statistical context: missingness can affect a frequency estimate when participants with unavailable testing differ from those with observed testing. The direction and extent of any effect depend on the pattern of missingness and the analysis approach. The registry does not provide the information needed to assess those issues. These omissions limit reproducibility and interpretation; they do not establish that missing data or multiplicity altered any result.

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

The record describes a retrospective study intended to estimate NTRK fusion incidence according to histological diagnosis in people with locally advanced, unresectable or metastatic solid tumors. It defines a fusion-positive participant using NGS assessment of tumor tissue and specifies assessment at the time of tumor removal. Those details describe the question and the measurement approach, but they do not state the observed frequency.

The record reports enrollment of 3820, but does not report how many participants underwent NGS or how many had a fusion. Consequently, it does not support a numerical estimate of incidence, an estimate within any histological category, or a statement about the precision of such estimates. The enrollment number alone is not enough to calculate a frequency because it is not identified as the number tested for the primary endpoint.

The listed secondary outcome about IHC-positive participants does not establish how well IHC identifies NTRK fusions. No subgroup counts, comparison results, or diagnostic performance estimates are reported. Similarly, the study’s reference to related treatment outcomes does not establish a treatment effect: no intervention or comparator is described, and no treatment outcome results are reported in the information available.

General statistical context: an observed count can describe the tested cohort, while generalization to a wider clinical population requires evidence that the tested group is relevant to that target population and that selection and measurement are understood. The registry record does not report enough information to evaluate representativeness, testing completeness, or histology-specific precision. The completed status does not fill these gaps. The defensible interpretation is limited to the study’s stated objective, population, endpoint definition, and testing description; conclusions about the magnitude or clinical implications of the outcome are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically distinctive because its central question is about the frequency of a molecular finding across histological diagnoses, rather than the effect of an assigned treatment. That makes the definition of the tested population and the denominator central to interpretation. The registry record describes the molecular case definition and the use of NGS, but does not report the count of fusion-positive participants or the number tested.

The record also illustrates the difference between enrollment and an analysis population. Enrollment is 3820, while the primary endpoint applies to participants analyzed by NGS. Without the number tested, readers cannot determine how much of the enrolled cohort contributed to the endpoint. This distinction is important in retrospective studies, where available records and tissue testing define what can be analyzed.

The description of multiple sequencing approaches is also relevant to reproducibility. The registry identifies RNA-based approaches and an alternative DNA-based assay, but does not report their use across participants or method-specific results. A reader therefore cannot assess whether the incidence estimates were consistent across testing approaches or whether testing availability varied by histology.

Finally, the registry’s lack of numerical outcome and analysis entries demonstrates the limits of interpreting a record based on its objective and methods alone. The intended question may be clear while its answer, uncertainty, and analytical handling remain unreported. This distinction matters for statistical reading: a study’s design description is not a substitute for observed results, and enrollment or planning assumptions cannot stand in for an endpoint estimate.

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 principal limitation for interpretation is that the registry record does not report the primary result. Neither the number of NGS-tested participants nor the count classified as having an NTRK fusion is stated. Without both, the study’s intended incidence estimate cannot be evaluated. Results by histological diagnosis, which are central to the stated objective, are also not reported.

The reported enrollment of 3820 does not establish how many participants contributed to the primary endpoint. The record does not describe the flow from enrollment to NGS testing, assay completion, and analysis. It does not report exclusions, unavailable tissue, failed tests, missing histology, or handling of incomplete records. These gaps prevent evaluation of the endpoint denominator and the potential for selection related to test availability.

Although the registry describes RNA sequencing approaches and an alternative DNA-based hybrid-capture assay, it does not state how participants were assigned to testing methods, the numbers tested by each approach, or how any differing findings were resolved. The record also does not report assay-specific counts or results. Consequently, the consistency of fusion classification across methods cannot be assessed.

The registry lists three outcome measures but provides zero analysis entries. It does not report statistical methods for estimating incidence, precision estimates, treatment-outcome analyses, or handling of multiple histological categories. The secondary IHC-related outcome is listed without subgroup counts or results. These limitations concern what is reported in the registry record; they do not establish that the study did not collect or analyze such information elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Retrospective Study to Determine the Incidence of NTRK Fusions. NTRK Study — NCT04010240.
• Registry record last updated 2025-10-16; status last verified 2025-09.
• Results first posted 2025-10-16.
• 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

NCT04010240 is a completed retrospective cohort study sponsored by Institut Bergonié. Its stated objective is to estimate NTRK fusion incidence according to histological diagnosis among subjects with locally advanced, unresectable or metastatic solid tumors. The registry reports enrollment of 3820, a start date of 2015-12-23, and a primary completion date of 2022-12-31.

There was no intervention. The primary endpoint is the count of participants with NTRK1, NTRK2 or NTRK3 fusions among those analyzed by NGS, assessed at baseline at the time of tumor removal. The record describes RNA-based sequencing and an alternative DNA-based hybrid-capture approach. It also lists a secondary outcome involving fusion counts among participants with positive IHC.

The primary count, NGS-tested denominator, histology-specific results, missing-data handling and analysis details are not reported in the registry record. Therefore, the stated incidence objective cannot be evaluated from the registered information alone.