Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions (NCT01457196), a na na study. The primary outcome is Progression Free Survival.

2. Clinical Question

This is a specimen-correlative study rather than a trial description centered on assignment to different treatments. Its stated objectives combine linking known molecular alterations to clinical outcomes with using genetic profiling to support treatment decisions. These objectives describe the program's purpose; they do not by themselves establish whether a molecular finding changed care or whether any resulting decision improved an outcome.

The registry lists a total enrollment of 2798. That figure describes enrollment in the record and should not be assumed to be the number included in the primary endpoint analysis, the number with active disease, or the number in either molecular subgroup. Those analysis-specific populations and counts are not reported in the registry record.

3. Trial Design

NCT01457196 is recorded as a completed study sponsored by UNC Lineberger Comprehensive Cancer Center. The registry lists a start date of 2011-09 and a primary completion date of 2018-06-06. The study's title is “Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions.” Its listed condition is Neoplasm, and its phase is NA.

The design is described as single group, with masking listed as none and allocation listed as NA. Tumor Genetic Sequencing is the listed diagnostic-test intervention. The record identifies a Sequencing Arm, but does not give a description for that arm. A single-group structure is important when interpreting the primary question: the comparison of patients with and without a reportable genetic variant is not a randomized, like-for-like comparison of assigned treatments. Molecular subgroup membership may coincide with differences in disease or patient characteristics, and the registry record does not explain whether or how such differences were handled.

The brief description calls the work a specimen correlative study. It states that tumor and germline specimens are used to provide rapid genetic profiling of alterations with known clinical utility, alongside an effort to associate known molecular alterations with clinical outcomes. These are stated objectives, not evidence that a particular treatment decision was made or that a clinical benefit followed.

The record lists 4 outcome measures and 0 analyses. It identifies progression-free survival at 2 years as the primary outcome, expressed as a percentage of participants and accompanied by a 95% confidence interval. The registry record does not report the analysis population, subgroup counts for that endpoint, numerical outcome estimates, or a detailed statistical analysis plan. The enrollment figure of 2798 should therefore not be treated as an analysis denominator without further information.

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: Of the 2798 participants screened for eligibility, 2074 were deemed eligible, 459 failed processing/sequencing, 226 had a sample collection failure, 19 were pediatric patients who were excluded from the final cohort, and 20 consents were withdrawn.

Overall Study

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 Progression Free Survival, measured over 2 Year.

The primary endpoint is progression-free survival at 2 years among cancer patients with active disease, described for patients with and without a reportable genetic variant. Progression-free survival generally refers to the time during which a participant remains alive without documented disease progression. In this record, the outcome is specified as a percentage of participants at a fixed time point, rather than as a numerical median or a reported hazard ratio.

In general, a fixed-time survival percentage can give a clinically interpretable description of the proportion estimated to remain free of the event by a specified time. It can be useful when the scientific question concerns prognosis at a defined follow-up point. The estimate depends on how progression and death are defined, how follow-up is managed, and how participants without complete follow-up are handled. Those endpoint details are not reported in the registry record.

The 95% confidence interval is intended to show the statistical uncertainty around an estimated percentage. In general, it describes a range of values reasonably compatible with the data under the method's assumptions; it is not a guarantee that an individual participant's outcome lies in that range. The registry record gives the confidence-interval type but does not report the estimate or its interval. It also does not report a numerical comparison between the genetic subgroups. No conclusion about the size, direction, or precision of a subgroup difference can therefore be drawn from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: a percentage at a fixed follow-up time summarizes the estimated proportion of participants who have not experienced the endpoint by that time. For progression-free survival, the endpoint ordinarily concerns progression or death, but the event definitions and assessment procedures for this study are not reported in the registry record. The record describes the primary result as a percentage of participants and names 2 years as the timeframe. It does not give the percentage itself or specify how it was estimated.

What does a confidence interval express?

General statistical explanation: a confidence interval communicates uncertainty around an estimate. A narrower interval usually indicates greater precision under the statistical method used, while a wider interval indicates more uncertainty. Its width can depend on the amount of usable information, the number of events, follow-up, and the method's assumptions. The registry specifies a 95% confidence interval for the primary endpoint but reports no interval bounds. Without the estimate, interval, and analysis denominator, neither precision nor compatibility with particular values can be assessed.

A confidence interval is not an individual prediction and does not correct for limitations in study design. In particular, an interval around a subgroup percentage would not by itself remove confounding or show that a genetic result caused a difference in outcome. The registry's single-group design and subgroup framing should be kept distinct from a randomized comparison. The approach used to account for prognostic factors is not reported in the registry record.

How should the subgroup comparison be understood?

General statistical explanation: when participants are grouped by a characteristic observed or measured in the study, the groups can differ in other ways as well. An unadjusted contrast describes the observed groups; an adjusted contrast attempts to account for selected measured factors using a specified model. Neither label alone guarantees that all relevant differences have been addressed. Here, the endpoint description names subgroups by reportable genetic variant status, but the registry record does not report the subgroup sizes, a contrast estimate, a model, or adjustment variables.

For time-to-event outcomes, participants may have different lengths of follow-up. General statistical methods can account for incomplete observation through censoring, but the validity of the estimate depends on how follow-up and censoring relate to the outcome and on the method used. The registry record does not report the censoring rules, follow-up distribution, progression assessment schedule, or survival-estimation procedure. These details matter when interpreting a fixed-time survival percentage.

What do the planning assumptions mean?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed or conducted as a two-arm randomized trial. They also do not establish observed power. No planning sample-size values or observed effect estimates are reported in the registry record.

General statistical explanation: a planning calculation asks what information a hypothetical design might require to detect a specified effect under chosen assumptions. It is not a measure of the probability that a completed study has found a true effect. A calculation based on an observed effect can be especially dependent on the estimate used, and it must not be confused with a prespecified design justification. The registry record does not report a sample-size justification for the study itself.

The planning note distinguishes time-to-event illustrations, which give a total number of events using the Schoenfeld approach, from other illustrations, which give participants per arm. That convention describes how the illustrations are expressed. It does not supply a study-specific number of events, a target number of participants, or evidence that the single-group program used equal allocation.

How do multiple outcomes affect interpretation?

General statistical explanation: when several outcomes or comparisons are examined, the chance of finding at least one apparently unusual result can increase if each is evaluated independently without an appropriate strategy. Methods for addressing multiplicity can include prespecifying a primary endpoint, adjusting significance thresholds, or treating secondary findings as exploratory. The registry lists 4 outcome measures, but the multiplicity strategy and the analysis status of the other outcomes are not reported. The count alone does not reveal how many statistical tests were conducted.

The record lists 0 analyses, so it does not provide analysis-level results with which to evaluate a model, test, or estimate. The endpoint label and confidence-interval type identify limited elements of the intended reporting, not a complete reproducible statistical method. Details such as the analysis population, treatment of missing observations, subgroup definitions, covariate adjustment, and methods for estimating uncertainty are not reported in the registry record.

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("Reported", "Not Reported")
n      <- c(1267, 807)
events <- c(393, 500)
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  Reported  1267  393  31.0  28.5  33.6  28.5  33.6  28.5  33.6
ARM  Not Reported  807  500  62.0  58.5  65.3  58.6  65.2  58.6  65.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures and 0 analyses. It identifies progression-free survival at 2 years as the primary endpoint, but does not report numerical results for it or for other measures. The number of listed outcomes does not show how many were analyzed, whether the outcomes were tested, or whether a multiplicity strategy was used. Prespecification details, an ordering of secondary outcomes, and any adjustment for multiple comparisons are not reported in the registry record.

Missing-data handling is also not reported. In general, missing outcome information can affect estimates when the participants with observed data differ from those without observed data. For a time-to-event outcome, incomplete follow-up and censoring require clear definitions and suitable analysis assumptions. The record does not describe how unavailable progression assessments, loss to follow-up, death, or missing genetic results were handled. It would be inappropriate to assume a particular method or that missingness had no effect.

The analysis population is not reported. Enrollment of 2798 is not necessarily the denominator for the primary endpoint or either molecular subgroup. The record does not state how many participants had active disease, a reportable variant, outcome follow-up, or an evaluable result. It also does not report whether analyses were restricted to a particular population or how exclusions were defined.

These omissions limit evaluation of both bias and precision. Without analysis denominators and missing-data methods, the extent to which the endpoint estimate represents the intended population cannot be assessed. Without an analysis plan, it is also not possible to determine how choices about outcomes or subgroups were made. These details are not reported in the registry record.

12. 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 safety figures are listed for the Sequencing Arm. The record reports 2074 participants at risk for serious adverse events and 0 affected, and 2074 at risk for other adverse events and 0 affected. It lists 723 deaths. No top serious adverse-event terms are listed. These are registry counts; they should be read as reported rather than treated as evidence about cause.

The record does not give the timeframe, event-collection rules, severity grading, or attribution criteria for these counts. It does not explain how the number at risk was determined or whether the death count overlaps with other reported categories. The figures do not establish that sequencing caused or prevented any event, and they are not a comparison against a control group. Because the study is listed as single group, there is no randomized comparator in the registry design information with which to estimate a comparative safety effect.

In general, an adverse-event count is most interpretable when its population, observation period, event definitions, and ascertainment procedures are clear. A zero count means that no affected participants are recorded for that category in the listed figure; it does not establish that the event is impossible or that no unrecorded event occurred. No percentage should be inferred from the counts without a justified denominator and method. Further safety definitions and follow-up details are not reported in the registry record.

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

The record describes a program using tumor genetic sequencing, with tumor and germline specimens, to connect molecular alterations with clinical outcomes and support treatment decisions. Its primary outcome is progression-free survival at 2 years in patients with active disease, considered by reportable genetic variant status. This identifies a clinically relevant prognostic question and a molecular subgroup contrast within a single-group study.

What the record does not provide is the numerical outcome estimate. It gives no subgroup percentages, confidence-interval bounds, group-specific analysis counts, or contrast estimate. Thus, the record cannot establish the direction or size of any difference in progression-free survival, or how precisely such a difference was estimated. It also cannot establish whether a result was statistically distinguishable from no difference.

The observational subgroup structure matters. In general, participants with different genetic findings may differ in other ways that relate to outcome. Without details of adjustment or design controls, an association between variant status and progression-free survival would not alone show that the variant caused the outcome difference. Nor does the program's stated goal of supporting decisions establish that those decisions changed treatment or improved outcomes.

The enrollment figure and safety counts provide limited descriptive information, but they do not fill in the missing primary endpoint results. Enrollment is not an analysis denominator, and the safety counts lack reported definitions and a comparative group. The record can therefore be used to understand the study's objectives and broad structure, but not to quantify its primary clinical finding. No medical decision should be based on an unreported estimate or inferred from the study's stated aims.

14. Why This Trial Matters Statistically

This study is statistically notable because it links a molecular profiling program to clinical outcomes rather than describing only a test's laboratory performance. The stated objective combines association of known molecular alterations with outcomes and rapid profiling of alterations with known clinical utility to support treatment decisions. Such a question requires careful separation of prognostic association from the effect of a treatment decision.

The primary outcome makes that distinction important. Progression-free survival at 2 years is described across groups defined by whether a reportable genetic variant was identified. This can address whether outcomes differ by molecular-result status, but it is not automatically a test of whether sequencing-guided care changes outcomes. The single-group design does not create a randomized treatment comparison, and the registry record does not report methods for addressing differences between the subgroups.

The record also illustrates why an endpoint label is not a complete statistical result. A percentage and a 95% confidence interval are specified, but the numerical estimate, interval, analysis population, and subgroup denominators are not reported. Without them, readers cannot assess the magnitude or precision of the primary finding. The listed enrollment alone cannot answer those questions.

More broadly, evaluating programs that connect genomic information to care requires clear reporting of who was tested, how findings were classified, what decisions followed, and how outcomes were analyzed. The registry description establishes the program's stated purpose, but those operational and analytic details are not reported in the registry record. Its statistical importance lies in the distinction between a promising research question and evidence sufficient to quantify an outcome association or decision effect.

15. 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 important trial-specific details unreported. It does not define the criteria for active disease, the meaning of a reportable genetic variant, or the process for classifying participants into the comparison groups. Without these definitions, the target population and subgroup contrast cannot be fully reconstructed.

The primary outcome description gives a 2-year timeframe and a 95% confidence interval but no numerical estimate, interval bounds, subgroup denominators, or comparison statistic. The record does not describe the progression and death definitions, outcome-assessment procedures, follow-up, or censoring. Consequently, neither the calculation nor the precision of the stated endpoint can be evaluated.

The single-group design and lack of masking are recorded, while allocation is NA. The genetic subgroup comparison is therefore not described as randomized. Whether relevant differences between groups were measured or adjusted for is not reported. The record also does not explain whether sequencing results influenced treatment, which treatments were used, or how decisions were incorporated into an outcome analysis.

Although 2798 participants are listed as enrolled, the record does not identify the number eligible for the primary outcome or the number with usable sequencing and follow-up data. Missing-data procedures, analysis-population definitions, and multiplicity handling are not reported. The registry lists 4 outcome measures and 0 analyses, leaving no analysis-level numerical results to evaluate.

Finally, safety event definitions, observation periods, and attribution procedures are not reported. The recorded counts should not be interpreted as comparative evidence about harms. These limitations are specific to the information in the registry record and do not establish that unreported methods or results do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions — NCT01457196.
• Registry record last updated 2019-12-30; status last verified 2019-12.
• Results first posted 2019-12-30.
• 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.

19. Record Summary

NCT01457196 is a completed, single-group study sponsored by UNC Lineberger Comprehensive Cancer Center. The registry lists the study start as 2011-09, primary completion as 2018-06-06, phase as NA, and enrollment as 2798. The listed condition is Neoplasm. Tumor Genetic Sequencing is the diagnostic-test intervention, and the study description refers to tumor and germline specimens.

The stated purpose is to associate known molecular alterations with clinical outcomes and provide rapid profiling of alterations with known clinical utility to support treatment decisions. The primary outcome is progression-free survival at 2 years, expressed as a percentage of participants with a 95% confidence interval, comparing patients with active disease who have a reportable genetic variant with those who do not.

The numerical primary outcome, subgroup denominators, analysis population, and detailed statistical methods are not reported in the registry record. The record lists 4 outcome measures and 0 analyses. Safety counts are listed for the Sequencing Arm, including 0 affected for serious adverse events and 723 deaths; event definitions and follow-up details are not reported.