Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients. (NCT03220230), a registered phase not stated study. The primary outcome is Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker.

2. Clinical Question

3. Trial Design

This was a completed, non-interventional, multicenter diagnostic study of molecular testing in participants with non-small cell lung cancer. The registry lists a total enrollment of 4240 and identifies Chile and Brasil as locations with investigational sites. The recorded study start date is 2015-07-06, and the primary completion date is 2018-10-30. The registry status is COMPLETED.

The study’s stated purpose was to validate novel diagnostic technologies, including next-generation sequencing from tissue and blood, in relation to the current diagnostic standard. Its primary outcome focused on ALK biomarker prevalence. The description names NGS-Oncomine Focus Assay and Ventana immunohistochemistry as the procedures used to measure ALK status. ROS1 is discussed in the study background, but the primary outcome described in the record concerns ALK.

Because the study was non-interventional, it did not assign treatment. Participants were to receive treatment indicated by their doctor regardless of participation. The registry does not describe a randomized allocation, and the record does not establish treatment arms for a like-for-like treatment comparison. The diagnostic testing comparison should therefore be understood as an assessment of paired test classifications, not as evidence from a randomized treatment trial.

The primary outcome timeframe is 40 months. The registry lists 7 outcome measures, including secondary measures concerning ALK prevalence or association with participant characteristics, but reports 0 analyses. Outcome counts and estimates are not reported in the registry record. The record also does not report the number of participants who had valid paired test results or explain how many enrolled participants contributed to each outcome.

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

Analysis population for the primary outcome, as defined in the registry: Per protocol analysis set included all participants with valid IHC-Ventana and NGS-OFA results.

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: Full analysis set included all NSCLC participants who satisfied all inclusion and exclusion criteria.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker, measured over 40 months.

The primary endpoint is the number of participants with an ALK biomarker, measured using NGS-Oncomine Focus Assay and Ventana immunohistochemistry. It is a count outcome: it describes how many participants in the defined analysis population had a particular classification, rather than a time-to-event outcome or a comparison of treatment effects. The stated timeframe is 40 months.

The registry defines the per-protocol analysis set as participants with valid results from both IHC-Ventana and NGS-OFA. It classifies a specimen as a true positive when both procedures are positive, and as a true negative when both are negative. A false negative is an NGS-OFA negative result paired with an IHC-Ventana positive result; a false positive is an NGS-OFA positive result paired with an IHC-Ventana negative result.

These categories allow the study to describe both the number of participants classified as ALK positive and the pattern of agreement or disagreement between procedures. A prevalence count alone does not fully characterize diagnostic performance: the paired positive and negative classifications are also needed to assess agreement and errors relative to the stated comparator procedure. The registry record does not report these counts, nor does it report sensitivity, specificity, predictive values, or another diagnostic accuracy estimate. The purpose of the endpoint is therefore clear, but its observed value and precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a count endpoint and a per-protocol analysis population, but does not report a statistical analysis plan or outcome estimates. The statistical points below explain how this type of endpoint is generally interpreted; they do not describe analyses confirmed in the registry record unless specifically stated.

What does a count endpoint represent?

General: a count records the number of participants meeting a defined outcome. To interpret a count as a prevalence, the analysis denominator is also needed. A count without its denominator does not show the proportion of participants with the finding. In this study, the primary outcome is the number of participants with an ALK biomarker, and the stated per-protocol population includes participants with valid IHC-Ventana and NGS-OFA results. The outcome count and the size of that analysis population are not reported in the registry record.

The endpoint description also defines four categories for paired results. A true positive means NGS-OFA and Ventana are both positive; a true negative means both are negative. A false negative means NGS-OFA is negative and IHC-Ventana is positive; a false positive means NGS-OFA is positive and IHC-Ventana is negative. Those labels describe concordance and discordance relative to the registry’s specified test classifications. They are operational definitions in the record, not reported counts.

How should paired diagnostic tests be understood?

General: paired testing means that results from two procedures can be compared for the same participant or specimen. The comparison can describe agreement, but agreement is not identical to diagnostic accuracy. Accuracy depends on how the comparator is treated as a reference and on the observed distribution of positive and negative results. The registry refers to a current gold standard in its general description and uses IHC-Ventana in defining the paired classifications. It does not report the classification counts or estimates such as sensitivity and specificity. Consequently, the names of the categories alone cannot establish how the tests performed.

General: sensitivity describes the proportion of reference-positive cases identified as positive by the test under evaluation, while specificity describes the proportion of reference-negative cases identified as negative. These quantities require the underlying paired counts. Predictive values also depend on the observed case mix and prevalence. None of these estimates is reported in the registry record, and none can be reconstructed from the endpoint definitions alone.

What does uncertainty add?

General: statistical uncertainty describes how much an estimate may vary because it is based on a sample rather than every possible participant in the target population. A confidence interval is one way to present that uncertainty around an estimate. Narrower intervals generally indicate greater precision under the selected model and assumptions; wider intervals indicate less precision. No confidence intervals or other measures of uncertainty are reported for the primary endpoint.

Without an analyzed denominator and outcome counts, neither a prevalence estimate nor its precision can be assessed. Even if a count were available, interpretation would require knowing which participants were included and how missing or invalid test results were handled. The registry identifies valid paired test results as a condition for inclusion in the per-protocol analysis set, but does not give the number excluded or the reasons for invalid or unavailable results.

What role do statistical tests and models have?

The registry reports 0 analyses. It does not report a statistical test, model, adjusted estimate, or confidence interval for the primary endpoint. The secondary outcomes list participant characteristics for which ALK rearrangement associations were to be examined, including smoking history, stage, biopsy classification, location, gender, and age. The record does not report the methods or findings for those analyses.

General: when several outcomes or subgroup comparisons are examined, estimates can be affected by multiplicity. Multiplicity refers to the increased chance of finding apparently notable results when many statistical questions are tested. Strategies such as prespecifying a primary comparison or adjusting inference can address this issue, but the registry record does not report whether any strategy was planned or used. The listed outcomes do not, by themselves, reveal the analysis plan.

How should the sample-size illustrations be read?

The planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration varies the effect as a stated fraction of the observed effect. These are planning assumptions, not a report of the original study’s design. The record describes a non-interventional diagnostic study and does not state that participants were randomized to two arms. The actual sample-size illustration values are not reported in the registry record. Such illustrations are not observed power and should not be interpreted as evidence that a study was adequately powered for its own design.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, with the primary outcome addressing the number of participants with an ALK biomarker and secondary outcomes describing prevalence or associations with participant characteristics. It reports 0 analyses. The record does not report whether outcomes were tested formally, whether any hierarchy among outcomes was prespecified, or whether a multiplicity adjustment was used. The presence of several outcome topics is not enough to infer how statistical error across analyses was managed.

The analysis population is described as the per-protocol set of participants with valid IHC-Ventana and NGS-OFA results. This establishes a validity requirement, but not how unavailable, invalid, or incomplete results were handled. The number of participants in the per-protocol set, the number missing either test, and reasons for missing or invalid results are not reported in the registry record. It is therefore not possible to assess whether exclusions affected the composition of the analyzed group or the interpretation of prevalence.

The record also does not report imputation, sensitivity analyses, or an intention-to-diagnose approach. These methods should not be assumed. General: missing data can matter when the likelihood of an unavailable test result is related to participant characteristics or biomarker status. Without counts and reasons, readers cannot determine whether missingness was limited or whether it could have influenced the reported outcome.

The registry does not report interim analyses, a statistical analysis plan, or a justification for the target enrollment. No conclusions about those design features can be drawn from the listed enrollment or the planning assumptions. The planning illustration is described separately from the trial’s own design and should not be treated as evidence of a prespecified sample-size calculation for this diagnostic study.

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 0% reporting threshold.

The registry’s safety listing names a group of non-small cell lung cancer participants, with 4240 participants at risk for the serious adverse event measure and 4240 at risk for the other adverse event measure. It records 0 participants affected in each category and 0 deaths. No serious adverse event terms are listed.

These are the figures recorded for the safety outcomes, not a full account of how events were collected or reviewed. The registry record does not report additional detail about the event definitions, observation period for safety collection, completeness of reporting, or whether all participants had the same duration of follow-up. The study is described as non-interventional, and treatment was selected by participants’ doctors independently of study participation. The safety figures should therefore be read as the posted counts for this study group, not as a comparison between randomized treatments.

General: a zero recorded count means that no affected participants were entered for that listed measure in the record. It does not, by itself, establish that an event could not occur or that the risk is absent. Interpretation depends on the data collection procedures, follow-up, and completeness, details that are not reported in the registry record. The safety listing also does not identify which treatments participants received, so it cannot be used to compare treatment-related safety.

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

The record shows that a completed, multicenter, non-interventional diagnostic study was conducted, with enrollment of 4240 participants. Its stated objective was validation of molecular diagnostic technologies for non-small cell lung cancer, and its primary outcome concerned ALK status using NGS-OFA and Ventana IHC. It also explains how paired results were categorized as true positive, true negative, false positive, or false negative.

Those descriptions clarify the study question and the intended interpretation of paired test results. However, the primary count, the number of valid paired results, and the counts in the diagnostic categories are not reported in the registry record. The posted results therefore do not quantify the prevalence of ALK positivity or the agreement and discordance between the procedures. No precision estimates or secondary analysis findings are reported either.

The study does not assess whether treatment improves health outcomes. It was non-interventional, and the participant’s doctor selected treatment independently of study participation. The diagnostic endpoint also cannot, by itself, establish that test use changed management or outcomes; such findings are not reported in the registry record.

General: diagnostic validation involves more than naming the tests and defining result categories. Interpretation ordinarily considers the relevant population, the comparator, the underlying counts, the accuracy measures, and uncertainty around estimates. Here, the population definition and classification rules are described, but the result quantities needed for that evaluation are absent. The record thus documents the intended assessment, but does not allow the magnitude or precision of its diagnostic findings to be judged.

The listed safety figures report 0 participants affected by serious events, 0 affected by other events, and 0 deaths in the recorded group. These counts should be interpreted within the limits of the safety reporting details available, rather than as proof that adverse events are impossible or as a comparison of treatments. Overall, the study’s registry description is informative about design and definitions, while the posted outcome information is not sufficient to support conclusions about diagnostic performance or clinical impact.

13. Why This Trial Matters Statistically

This study raises a statistical question that is distinct from the usual treatment-trial comparison: how do molecular diagnostic procedures classify the same clinical specimens, and what can those paired classifications say about biomarker prevalence and test performance? The registry’s definitions of concordant and discordant results make the intended comparison explicit. That clarity is important because a prevalence count and a diagnostic accuracy assessment answer related but different questions.

The distinction between the enrolled group and the valid-pair analysis population is also statistically important. The registry reports enrollment of 4240 participants, but defines the primary per-protocol population by availability of valid results from both procedures. Without the size and characteristics of that population, it is not possible to evaluate the denominator for the primary endpoint or the possible effects of excluding participants without valid paired results.

Another important feature is the difference between a study’s objective and its reported evidence. The stated aim is to validate technologies, but the registry does not report outcome counts or accuracy estimates. A clear endpoint definition supports understanding of what would be measured; it does not substitute for the result data needed to judge performance or precision.

General: diagnostic studies benefit from transparent reporting of test-result distributions, reference definitions, missing results, and uncertainty. Those details allow readers to separate agreement from accuracy and to understand how applicable an estimate may be to other settings. The record identifies the tests and classification rules, but does not include the numerical results needed for these assessments. This makes the study statistically relevant as a diagnostic-validation design while leaving its quantitative findings unassessable from the posted record.

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 most direct limitation of the registry record is that it does not report the primary endpoint count or the paired test-result counts. As a result, the stated ALK prevalence and the degree of agreement between NGS-OFA and IHC-Ventana cannot be evaluated. The record also does not report diagnostic accuracy estimates or their uncertainty.

The per-protocol population requires valid results from both tests, but the number of participants meeting this criterion is not reported. Nor does the record describe how many participants had an invalid or missing result, why results were unavailable, or how those cases were handled. The total enrollment of 4240 should not be mistaken for the primary analysis denominator.

The registry lists secondary topics involving smoking history, stage and biopsy classification, location, gender, and age, but reports 0 analyses. No subgroup results, adjustment methods, or multiplicity strategy are reported. The statistical analysis plan, interim analyses, and sample-size justification for the study are not reported in the registry record.

The study is non-interventional and does not provide a randomized treatment comparison. The record says treatment decisions were made by participants’ doctors independently of study participation, so the results cannot establish comparative treatment effects. Further, the study background mentions testing from tissue and blood, while the primary endpoint description identifies NGS-OFA and Ventana IHC; the record does not report outcome detail that would allow readers to assess performance by specimen type.

Finally, the safety listing gives counts but limited information on event ascertainment and follow-up. These limits do not invalidate the design description, but they constrain what can be concluded from the registry record about diagnostic performance, representativeness, and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients. — NCT03220230.
• Registry record last updated 2019-11-08; status last verified 2019-10.
• Results first posted 2019-11-08.
• 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

This completed, non-interventional multicenter study evaluated molecular diagnostic technologies in participants with non-small cell lung cancer. The registry reports enrollment of 4240 participants, investigational sites in Chile and Brasil, a start date of 2015-07-06, and primary completion on 2018-10-30.

The primary outcome was the number of participants with an ALK biomarker, assessed using NGS-Oncomine Focus Assay and Ventana immunohistochemistry, over a timeframe of 40 months. The per-protocol analysis set required valid results from both procedures. The registry defines categories for concordant and discordant paired results but does not report their counts or the primary outcome value.

The record lists 7 outcome measures and 0 analyses. Safety figures list 0 participants affected by serious events, 0 affected by other events, and 0 deaths among 4240 at risk in the named participant group. The quantitative diagnostic findings, analyzed population size, statistical analysis plan, and missing-result details are not reported in the registry record.