Precision Medicine for Patients With Identified Actionable Mutations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Precision Medicine for Patients With Identified Actionable Mutations (NCT04111107), a na phase 2 study. The primary outcome is Progression Free Survival Ratio.

2. Clinical Question

3. Trial Design

This was a Phase 2, single-group, unmasked trial with allocation listed as not applicable. Its title describes precision medicine for participants with identified actionable mutations, and the intervention strategy used a Next Generation Sequencing report to select treatment. The listed sponsor was Wake Forest University Health Sciences. The registry record gives a start date of 2020-04-22, a primary completion date of 2022-12-09, enrollment of 45, and status of terminated.

The treatment rule was to choose the first drug listed in the tumor analysis report for the first mutation listed. The arm description notes that a medical contraindication to that drug or inability to obtain it could affect treatment selection. The record available for this trial ends mid-sentence while describing those exceptions, so the full fallback rule is not reported in the registry record. Investigational agents, supportive care regimens, and the sequencing report are listed as interventions.

The primary outcome was a progression-free survival ratio comparing treatment under the trial strategy with the participant’s last treatment before the trial. This makes the prior treatment a historical reference, rather than a concurrently randomized control. The study also intended to collect information about barriers investigators encountered when prescribing options based on sequencing reports and to measure quality of life during the treatment period. Overall survival, adverse events, and response rate are listed as secondary outcomes. Participants were to be followed until death for survival endpoints, according to the brief summary.

The registry record does not report why the trial was terminated, whether the intended follow-up was completed, or whether treatment assignment or assessment procedures changed during conduct. It also does not report a detailed statistical analysis plan or the rationale for the enrollment target.

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: For various reasons, 27 patients were not evaluable for the primary outcome. Five patients had no prior treatment but did have an actionable mutation to qualify them for inclusion in the study. Another ten patients were enrolled but never started treatment under this protocol. Nine patients started treatment but died prior to testing for best response and for progression. Two patients died with stable disease and one patient is alive with stable disease and no sign of progression .

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 Ratio, measured over From the start of treatment to the time of progression, death, or date of last contact, assessed up to 2 years.

The primary endpoint, called the progression-free survival ratio, relates the duration of progression-free time on trial treatment to the corresponding duration on the last treatment received before the trial. The numerator begins at the start of trial treatment and ends at progression, death, or last contact, according to the stated timeframe. The denominator is defined as the duration from the last pre-trial treatment to progression on that treatment. The endpoint is therefore a relative, within-participant measure rather than a direct comparison of group-level survival times.

A ratio of 1.0 is the stated null value, representing no difference under the endpoint’s definition. The record says that a ratio larger than 1.3 was hypothesized to suggest that targeted therapy was doing better than the previous, non-targeted treatment. This is a hypothesis about how to interpret the measure, not an observed result. The registry record does not report the median ratio, its range, or the test result.

General: A ratio can put two time periods on a common relative scale, which may be useful when each participant has a relevant prior-treatment history. It also depends on having usable information for both periods. Because the periods occur at different times, the ratio alone cannot separate a treatment effect from other changes between treatment episodes. Progression-free survival is used to describe time until a defined disease-related event, while allowing follow-up to end at last contact when an event has not been observed. The record does not provide further endpoint-adjudication details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a ratio of two progression-free durations for the same participant: time on trial treatment and time on the last treatment received before the trial. The numerator’s stated timeframe runs from trial treatment start to progression, death, or last contact. The denominator is the duration from the last pre-trial treatment to progression on that treatment. The registry record describes estimation of the median ratio and its range, followed by a two-sided Wilcoxon Signed Rank test against 1.0.

What does the ratio represent?

General: A ratio expresses one quantity relative to another. A value of 1.0 is the stated null value here, so it represents equal durations under the endpoint definition. The trial description treats a ratio larger than 1.3 as the hypothesized level that would suggest better performance relative to the prior treatment. That threshold is part of the stated hypothesis, not a reported estimate or a guarantee of clinical benefit. A ratio can be affected by either duration in its calculation, and interpreting it requires understanding how the prior-treatment period was defined and measured.

Using a participant’s prior treatment creates a historical comparison. General: observing the same person under different treatment periods may reduce the influence of characteristics that remain stable over time. It does not make the treatment periods interchangeable. Changes in disease status, available therapies, supportive care, follow-up, or other circumstances may coincide with the treatment change. The registry record does not describe an adjustment strategy for such differences. There is no randomized comparison group in this trial design.

Why use a median and range?

The median is the middle value after individual ratios are ordered. General: it can describe a typical value without being pulled as strongly by extreme observations as the mean can be. The range describes the span from the lowest to the highest observed value, but it can be sensitive to unusual observations and does not by itself show how precisely the median is estimated. The registry record says the median and range would be estimated, but neither is reported as a result. It does not report a confidence interval for the median ratio.

What does the Wilcoxon Signed Rank test assess?

The stated test is a paired, rank-based method for assessing whether the distribution of within-participant differences is centered on a hypothesized value; in this trial, the ratio is assessed against 1.0. General: rank-based procedures use the ordering and signs of paired observations rather than relying directly on a normal model for the raw measurements. The test still depends on having paired, evaluable information and on assumptions appropriate to its application. The registry record does not give the test statistic, p-value, exact analysis population, or further assumptions. It therefore does not allow readers to assess the test’s result or implementation.

The record specifies a two-sided test. General: a two-sided test considers departures in either direction from the null value, rather than only a departure in one prespecified direction. A p-value, if reported, would describe how compatible the data are with the test’s null model; it would not measure the probability that the null hypothesis is true or the size of a treatment effect. No primary p-value is reported in the registry record.

How should planning illustrations be read?

General: sample-size calculations ask how much information a future study might need under stated assumptions. They are not a measure of the power actually achieved by a completed trial. The planning assumptions associated with the posted calculations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Those assumptions describe planning illustrations, not this single-group design. The record does not report a trial-specific sample-size justification, and the numerical planning outputs are not repeated.

The planning note distinguishes time-to-event calculations, which report total events, from other calculations, which report participants per arm. General: event-driven calculations focus on the number of observed events because event information contributes to precision for time-to-event comparisons. This trial’s primary analysis is a within-participant ratio, however, and the equal-allocation, two-arm assumptions do not describe its design. Any planning illustration must therefore be interpreted in light of its assumptions rather than as a reconstruction of the trial’s design or observed power.

Finally, progression-free outcomes can involve participants whose event status is not observed during follow-up. General: methods for handling censoring and incomplete follow-up can affect estimates, especially when follow-up ends before progression or death is recorded. The stated timeframe includes last contact, but the registry record does not report the censoring rules, missing-data methods, sensitivity analyses, or details of outcome assessment. These omissions limit evaluation of how the endpoint was analyzed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and secondary outcomes of overall survival, number of participants with adverse events, and response rate. It also describes intended collection of information about barriers to using sequencing reports and quality-of-life measurement. The record lists four outcome measures and two analyses, but it does not report how the analyses correspond to the outcome measures or how the multiple questions were handled statistically. A multiplicity adjustment or a hierarchy for interpreting secondary outcomes is not reported in the registry record.

The primary outcome description says that a two-sided Wilcoxon Signed Rank test would assess whether the progression-free survival ratio differed from 1.0. The result of that test is not reported. The registry record also does not report whether there were interim analyses, whether any analysis was changed, or how the final analysis population was defined. The reason for termination is not reported.

For missingness and evaluability, the primary outcome population description states that 27 patients were not evaluable. It identifies five patients with no prior treatment who nevertheless had an actionable mutation, ten enrolled patients who never started treatment under the protocol, and begins a further explanation involving nine patients who started treatment. The text is incomplete, so the full reasons and accounting are not reported in the registry record. It is not reported how missing primary outcome data were handled, whether any values were imputed, or whether the analysis included all enrolled participants who could be evaluated.

General: excluding participants with incomplete endpoint information can change the group represented by an analysis, particularly if evaluability is related to prognosis or treatment experience. Imputation and sensitivity analyses are possible approaches in some studies, but their use cannot be assumed. The registry record does not report those methods, the handling of incomplete secondary outcomes, or an analysis of how missing information might affect conclusions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (11.8%), generalized muscle weakness (8.8%), dysphagia (5.9%), vomiting (5.9%), disease progression (5.9%).

The registry record lists a single group titled Drug Administration Based on Next Gen Sequencing Report. It reports 34 at risk for serious adverse events, with 18 affected; for other adverse events, it reports 34 at risk, with 34 affected. It also lists 32 deaths. These are posted safety figures, not a randomized comparison. The record does not provide a concurrent control group against which to judge whether the counts differ from another treatment approach.

The serious-event terms listed include dehydration at 11.8%, generalized muscle weakness at 8.8%, and dysphagia, vomiting, disease progression, and cerebral edema at 5.9% each. The denominator and event-specific counting rules for those percentages are not reported in the registry record. The terms should therefore be read as registry-listed descriptions, not as evidence that the intervention caused those events. The list does not establish that all serious events are represented in the displayed terms.

General: safety counts describe reported events or participants meeting an event definition within a stated observation context. They do not by themselves establish causation, compare risks across treatments, or show how long participants were observed. The registry record does not report further detail on attribution, severity grading, timing, recurrence, or exposure duration. The death count should not be interpreted as a treatment-related death count, because that relationship is not reported.

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

The registry record establishes that investigators studied a treatment-selection strategy based on Next Generation Sequencing reports and defined a within-participant progression-free survival ratio as the primary outcome. It states a null value of 1.0, describes a two-sided Wilcoxon Signed Rank test, and gives a hypothesized ratio larger than 1.3 as a level that would suggest better performance relative to the previous treatment. These are descriptions of the planned question and interpretation, not evidence of what the study found.

The primary result is not reported in the registry record. There is no reported median ratio, range, test statistic, or p-value. As a result, the posted record cannot establish whether the primary endpoint was above, below, or different from the null value, or how precise any estimate was. The secondary outcome results are also not reported. The safety figures and listed event terms provide descriptive information, but without a concurrent control group or further context they do not establish comparative risk or causation.

General: statistical significance and clinical importance are different questions. A test result, when available, addresses compatibility with a statistical model and null hypothesis; the size and precision of an estimate help characterize the magnitude and uncertainty. Neither a planned test nor a hypothesized threshold substitutes for an observed estimate. Here, the missing primary estimate prevents assessment of both its magnitude and precision from the registry record.

The single-group design also limits causal interpretation. Comparing current treatment with a participant’s prior treatment can be informative, but treatment periods may differ in ways that are not caused by the selected therapy. The design does not include random assignment to a concurrent comparator that could balance such differences by design. The record does not report an adjustment strategy that would resolve this limitation.

The registry status is terminated, and the record does not give the reason. It reports 45 enrolled and states that 27 patients were not evaluable for the primary outcome; the explanation of that group is incomplete. These registry entries matter when considering how much of the enrolled population contributed to the primary endpoint, but the complete analysis population and missing-data handling are not reported. The record therefore supports describing the study question, design, and some safety information, but not a conclusion about the primary outcome or comparative effectiveness.

13. Why This Trial Matters Statistically

This trial raises a statistical question that arises when molecular testing is used to guide treatment: how should outcomes on a selected treatment be compared with outcomes on a participant’s previous treatment? A within-participant ratio places the two progression-free durations on a relative scale. It can be attractive when participants have different treatment histories, but it also makes the quality and comparability of each participant’s prior-treatment information central to interpretation.

The design illustrates the difference between a historical comparison and a randomized comparison. A prior treatment is not assigned at the same time as the trial treatment, and the circumstances around the two treatment periods may differ. General: randomization helps balance measured and unmeasured factors on average across concurrent groups; a historical comparison does not provide that same design-based protection. Statistical adjustment can address some measured differences, but the registry record does not report such an approach.

The endpoint also highlights why a point estimate and its uncertainty are both important. The trial description specifies a median ratio and range, and a test against 1.0, but the registry record does not report those primary results. Without them, the central statistical question remains unanswered in the posted record. The stated hypothesis of a ratio larger than 1.3 cannot stand in for an observed result.

Finally, the record’s statement that 27 patients were not evaluable for the primary outcome makes analysis-population reporting particularly important. The available reasons are incomplete, and the handling of missing outcomes is not reported. This limits assessment of whether the primary analysis represents the enrolled population. The trial is therefore statistically informative as an example of a biomarker-directed, single-group design and a historical within-participant endpoint, while its posted results do not permit evaluation of the primary 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 main trial-specific limitation is the lack of a concurrent randomized comparator. The primary endpoint compares trial treatment with the last pre-trial treatment, so differences between treatment periods may reflect changes other than the selected treatment. The registry record does not report methods to address time-related differences, changes in disease status, or selection of the prior treatment used for comparison.

Primary outcome availability is also a concern. The record states that 27 patients were not evaluable and gives an incomplete account of the reasons. It mentions five patients with no prior treatment, ten who enrolled but never started protocol treatment, and a further description involving nine who started treatment that is cut off. The full accounting, reasons for non-evaluability, and analysis population are not reported in the registry record. The approach to missing data is also not reported.

The available results do not include the primary median ratio, range, or test result, and secondary outcome findings are not reported. Thus, the registry record does not permit assessment of the primary estimate’s size or precision. Although safety counts and serious-event terms are posted, the record does not report event attribution, exposure duration, or a control group for comparison. The reason for termination and the completeness of outcome follow-up are not reported.

The arm description is incomplete where it begins to explain what happens when the first listed drug is contraindicated or unavailable. The record does not report a detailed statistical plan, a trial-specific sample-size justification, multiplicity handling, interim analyses, endpoint-adjudication details, or sensitivity analyses. These omissions limit assessment of implementation and robustness beyond the design features that are explicitly described.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Precision Medicine for Patients With Identified Actionable Mutations — NCT04111107.
• Registry record last updated 2024-07-03; status last verified 2024-06.
• Results first posted 2024-07-03.
• 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

The registry record describes NCT04111107, a Phase 2, unmasked, single-group trial sponsored by Wake Forest University Health Sciences. It reports enrollment of 45, a start date of 2020-04-22, a primary completion date of 2022-12-09, and terminated status. Treatment selection was based on the first drug listed for the first mutation listed in a tumor analysis report, subject to the exceptions described incompletely in the arm description.

The primary outcome was the median progression-free survival ratio, comparing trial treatment with the last pre-trial treatment. A two-sided Wilcoxon Signed Rank test against 1.0 was described. The primary result and secondary outcome results are not reported in the registry record. The record states that 27 patients were not evaluable for the primary outcome, but its explanation is incomplete. Safety figures include 18 affected by serious adverse events among 34 at risk, 34 affected by other adverse events among 34 at risk, and 32 deaths. The reason for termination, missing-data methods, and the full analysis plan are not reported.