A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1 (NCT02855125), a randomized phase 2 study. The primary outcome is Progression-free Survival (PFS) Based on Central Independent Review.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group phase 2 study of TAS-114 plus S-1 versus S-1 alone in advanced or metastatic non-small cell lung cancer. The registry record describes an international study in Asian, specifically Japan, and Western regions, specifically Europe and the United States. Randomization was described as 1:1. The recorded enrollment was 128, with 64 participants listed in each group for the primary endpoint.

Because masking was absent, participants and study personnel were not blinded to assigned treatment. The primary endpoint, however, was based on central independent review. That review provides a specified assessment source for the primary disease-progression outcome, but the registry record does not report whether reviewers were blinded to treatment assignment or provide further review procedures.

The combination regimen consisted of TAS-114 and S-1, while the control regimen consisted of S-1 monotherapy. Both were administered in a 2-week treatment period followed by a 1-week recovery period in each 21-day cycle. The combination description states that treatment continued until progressive disease or another stopping condition, but its text is truncated. The S-1 description lists intolerable side effects, investigator removal, and withdrawal of consent among stopping conditions, as well as progressive disease.

The recorded study status is completed. The study start was 2016-08-29, and primary completion was 2017-09-30. These dates describe the registry record; they do not establish the duration of follow-up for every participant. Details of the original sample-size justification, randomization implementation, stratification, and prespecified interim analyses are not reported in the registry record.

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: A total of 128 participants were randomized.1 participant in S-1 (Monotherapy) arm was randomized but not treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) population included all participants randomized in the study, regardless of whether they actually received any study treatment (TAS-114 or S-1) or not.

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: Baseline population included all participants randomized in the study, regardless of whether they actually received any study treatment (TAS-114 or S-1) or not.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS) Based on Central Independent Review, measured over From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months).

The primary endpoint was median progression-free survival based on central independent review. It measures the time from randomization until the first occurrence of radiologic disease progression or death from any cause. Participants without a recorded progression or death were censored at the last known time they were progression free. The registry describes an approximate assessment timeframe of up to 13 months.

Progression was assessed using Response Evaluation Criteria in Solid Tumors Version 1.1. The record defines progressive disease as at least a 20% increase in the sum of target-lesion diameters from the smallest sum observed on study, with an absolute increase of at least 5 millimeters. The appearance of one or more new lesions also counted as progression. These rules turn changes in imaging findings into a defined time-to-event outcome.

Progression-free survival is used in trials because it captures disease progression as well as death, rather than requiring death to occur before an event is counted. The median is the time by which the estimated proportion remaining progression free has reached the midpoint of the survival distribution. It is not an average participant’s observed duration, and it does not describe every participant’s experience. The registry record does not report further details of the survival estimation procedure or the handling of assessment timing beyond the stated censoring rule.

7. Results Posted in the Registry

• TAS-114 + S-1 vs S-1 (Monotherapy): hazard ratio 1.16 (95% CI 0.71–1.88), reported p = 0.274 (as reported in the registry).

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.

Overall Survival (OS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • TAS-114 + S-1 vs S-1 (Monotherapy): hazard ratio 1.31 (95% CI 0.80–2.14), reported p = 0.143 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between TAS-114 + S-1 vs S-1 (Monotherapy) and the control. The interval gives the range of effects that remain compatible with the data.

Overall Response Rate (ORR) Based on Central Independent Review

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • S-1 (Monotherapy): 10.3% (6/58) versus 19.7% (12/61) on control; risk difference -9.3 percentage points (95% CI -22.0 to 3.4), risk ratio 0.53 (0.21–1.31); unadjusted two-proportion z-test p = 0.156.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between S-1 (Monotherapy) and the control. The interval gives the range of effects that remain compatible with the data.

Disease Control Rate (DCR) Based on Central Independent Review

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • S-1 (Monotherapy): 75.9% (44/58) versus 80.3% (49/61) on control; risk difference -4.5 percentage points (95% CI -19.3 to 10.4), risk ratio 0.94 (0.78–1.14); unadjusted two-proportion z-test p = 0.556.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between S-1 (Monotherapy) and the control. The interval gives the range of effects that remain compatible with the data.

Across the secondary outcomes, the posted point estimates do not form a uniform pattern suggesting a consistent advantage for one group across every endpoint. Overall survival and response-related outcomes describe different aspects of the disease course, and their confidence intervals reflect substantial uncertainty. The secondary results add context to the primary progression-free survival finding but do not replace it.

Overall survival concerns time until death, whereas response rate and disease control rate classify tumor response under central independent review. These outcomes need not move in parallel: an imaging response measure and a time-to-death measure capture distinct events and can be influenced by different features of follow-up and subsequent care. Thus, a different point-estimate direction across outcomes does not by itself contradict the primary result.

The registry lists five secondary outcomes, including duration of response and treatment-emergent adverse events, but not every secondary outcome has a posted numerical result in the record described. The available response and survival estimates should be read with their own confidence intervals and analysis populations. The reasons that outcome counts vary are not reported in the registry record.

Unadjusted secondary findings carry less weight because evaluating multiple outcomes creates more opportunities for apparently notable results by chance. The registry does not report a multiplicity strategy, such as a prespecified sequence of testing or an adjustment to control the overall false-positive risk. The binary endpoint comparisons are unadjusted recalculations rather than sponsor-reported inferential analyses. Consequently, secondary estimates are best treated as descriptive and hypothesis-generating, not as independent confirmation of the primary comparison.

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

• Overall Survival (OS)
• Overall Response Rate (ORR) Based on Central Independent Review
• Disease Control Rate (DCR) Based on Central Independent Review
• Duration of Response (DR) Based on Central Independent Review
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is a time-to-event outcome. Each participant contributes information from randomization until progression or death, or until the last known progression-free time if neither event has occurred. A participant whose follow-up ends without an event is censored rather than treated as though an event occurred at that time. The registry record explicitly states this censoring rule for progression-free survival.

What does the median represent?

As a general statistical explanation, the median survival time is the time at which the estimated survival curve reaches its midpoint. For progression-free survival, the curve represents the estimated probability of remaining alive without documented progression over time. The median is a distribution summary, not a mean and not a claim that every participant experienced the event at that time. The registry lists the median in months and gives a 95% confidence interval for each group.

The reported primary comparison uses a log-rank method and a hazard ratio. As a general statistical explanation, the log-rank test compares the timing of events across groups over follow-up, rather than comparing only the medians. A hazard ratio summarizes the relative event rates over time under the assumptions of the analysis. A value of 1 corresponds to equal hazards; values on either side indicate different directions of the estimated contrast. The registry does not report the assumptions or detailed implementation for this analysis, including whether proportional hazards were assessed.

How should the hazard ratio be read?

The registry reports the hazard ratio as TAS-114 plus S-1 versus S-1 monotherapy. The estimate is 1.16, with a 95% confidence interval from 0.71 to 1.88. The interval includes 1, so the result does not provide a statistically clear distinction from equal hazards at the conventional two-sided significance level used in the planning illustration. The p-value reported for the log-rank analysis is 0.274. That p-value is not a measure of the size or clinical importance of a difference.

The primary endpoint definition follows RECIST 1.1. The registry specifies that progression can be based on a relative and absolute increase in the sum of target-lesion diameters, or on the appearance of new lesions. Central independent review was used for the endpoint. The record does not describe the review process, the schedule of scans, or how disagreements were resolved.

What do the secondary endpoint methods add?

Overall survival is also a time-to-event endpoint, measured from randomization until death. The registry reports medians and a log-rank hazard ratio for this outcome. Overall response rate and disease control rate are percentages based on central independent review. For these binary outcomes, a participant is classified according to whether the specified response or disease-control condition was met. Their confidence intervals describe uncertainty around the estimated percentages.

Unadjusted comparisons for the binary outcomes are recalculations from the posted summary counts, not sponsor-reported analyses. Such recalculations do not incorporate any covariates or additional analysis details that may have been used in a full clinical study report. The registry record does not report inferential analyses for those secondary outcomes.

As a general statistical point, time-to-event analyses use event timing and account for censoring, while binary analyses reduce outcome information to a classification over the stated assessment period. These methods answer related but not identical questions. Differences in endpoint definitions, follow-up, assessment, and analysis population can affect how estimates compare. The registry record does not provide a complete statistical analysis plan, further modeling details, or enough information to reconstruct all endpoint analyses independently.

11. Confidence Intervals and Precision

Confidence intervals show the range of values reasonably compatible with the data under the statistical method used. They reflect uncertainty in an estimate; they are not guarantees that the true value lies within the interval. The primary median estimate for TAS-114 plus S-1 is 3.65 months, with a 95% confidence interval of 2.69 to 5.16 months. The S-1 monotherapy median is 4.17 months, with a 95% confidence interval of 2.6 to 6.6 months. The reported hazard ratio is 1.16, with a 95% confidence interval of 0.71 to 1.88.

The hazard-ratio interval includes 1, leaving uncertainty about the direction and magnitude of the comparative effect. Its breadth also indicates that the posted data are compatible with more than a narrow range of relative hazards. The p-value of 0.274 is consistent with the absence of a statistically clear difference by the reported log-rank analysis, but it does not measure precision on its own.

Confidence intervals also accompany the secondary estimates. For example, the overall survival medians and the response percentages have intervals that convey uncertainty in those estimates. They should be interpreted within their endpoint definitions and analysis populations, not as proof of an effect when point estimates differ. The record’s participant counts differ across outcomes, and the reasons for those differences are not reported in the registry record.

Precision depends on such features as the amount of outcome information and the analysis method. As a general statistical point, more events can improve precision for time-to-event comparisons, while binary estimates depend on the number of participants with usable outcome information and the event frequency. The posted intervals are the appropriate guide to uncertainty in the reported estimates; small differences between point estimates should not be treated as established differences.

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 estimates are illustrations based on the observed effects, not the trial’s original design calculations. The planning assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

For the time-to-event endpoints, the planning figures are total events, not participants per arm. For progression-free survival, the estimates range from 1,426 total events for 80% power at 100% of the observed effect to 5,701 total events for 80% power at 50% of the observed effect. The corresponding 90% power figures range from 1,908 to 7,632 total events. For overall survival, the figures likewise represent total events: 431 to 1,723 for 80% power and 577 to 2,306 for 90% power across the stated effect fractions.

For the binary outcomes, the figures are participants per arm. For overall response rate, the estimates range from 229 participants per arm for 80% power at 100% of the observed effect to 1,034 at 50% of the observed effect; for 90% power, they range from 307 to 1,383. Disease-control planning estimates also rise as the assumed effect becomes smaller.

In plain language, the 80% power column represents the planned chance of detecting the specified effect under the stated assumptions if that effect is present; the 90% column uses a higher target chance and generally requires more outcome information. Smaller effects need more participants or events to detect. These are planning illustrations, not observed power.

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

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.160, so ln(HR) = 0.1484.
2. d = 4 × (1.96 + 0.842)² / [ln(1.160)]² = 1,425.2, rounded up to 1,426 events in total 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
hr <- 1.16                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(2855125)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 1,426 (80% power), 1,908 (90% power)
 75% of observed effect: events = 2,534 (80% power), 3,392 (90% power)
 50% of observed effect: events = 5,701 (80% power), 7,632 (90% power)
Simulated power with 1,426 events: 0.797 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

For the primary progression-free survival comparison, the registry reports the sponsor’s log-rank hazard ratio as 1.16, with a 95% confidence interval of 0.71 to 1.88 and p = 0.274. The posted comparison uses those same reported values. There is no discrepancy between the primary comparison and the reported analysis in the registry record.

The sponsor-reported method is important because a time-to-event comparison can depend on analysis choices and details not recoverable from group medians alone. The hazard ratio and log-rank result, rather than a new calculation from the median values, are the relevant comparative results for the primary endpoint. The confidence interval includes 1, and the reported p-value does not indicate a statistically clear difference.

The binary endpoint comparisons are different: their unadjusted risk-difference calculations are based on posted group counts, while the registry does not list sponsor-reported inferential analyses for those endpoints. Those recalculations should be treated as simple summaries, not as substitutes for a sponsor’s analysis or a full statistical analysis plan. Where a sponsor-reported analysis is available, it takes precedence over a simple recalculation if the two disagree. The registry record does not provide enough detail to determine whether additional adjusted analyses were conducted outside the posted results.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as progression-free survival based on central independent review, and the record also lists secondary endpoints that include overall survival, response rate, disease control rate, duration of response, and treatment-emergent adverse events. Considering several outcomes can increase the chance of finding at least one apparently unusual result even when no true treatment difference exists. A prespecified multiplicity strategy can address that concern by controlling how statistical evidence is interpreted across endpoints or comparisons. Such a strategy is not reported in the registry record.

The registry gives an intent-to-treat definition for the primary population: all randomized participants, whether or not they received treatment. It does not provide equivalent population definitions for every secondary endpoint. The numbers with outcome data vary across the posted endpoints, and the reasons for those differences are not reported in the registry record. The record also does not describe a general missing-data strategy, the extent of missing assessments, or sensitivity analyses for missing outcomes.

For progression-free survival, participants without progression or death were censored at their last known progression-free time. That is the stated handling of participants who had no observed event; it does not explain how missed assessments or withdrawal may have affected the timing of censoring. Censoring can matter if the chance of remaining under observation is related to prognosis. The record does not report diagnostic checks or sensitivity analyses addressing that possibility.

The primary analysis method is listed as log-rank, but additional details of the statistical plan are not reported in the registry record. The record does not state whether analyses were stratified, whether proportional hazards were assessed, or whether interim analyses were planned or performed. These omissions limit assessment of the full analysis strategy; they do not change the values reported for the primary comparison.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (6.2%), pulmonary embolism (6.2%), bronchitis (4.7%), rash maculo-papular (4.7%), pleural effusion (3.2%).

The registry lists 30 participants with serious adverse events among 64 at risk in the TAS-114 plus S-1 group, and 19 among 63 at risk in the S-1 monotherapy group. It also records other treatment-emergent adverse events for 64 of 64 participants and 61 of 63 participants, respectively. Deaths are listed as 36 in the combination group and 29 in the monotherapy group. These counts are descriptive; the record does not establish that deaths or adverse events were caused by study treatment.

The serious-event terms listed include dyspnoea and pulmonary embolism at 6.2% each, bronchitis and rash maculo-papular at 4.7% each, pleural effusion at 3.2%, and anaemia at 3.1%. The registry’s posted details do not clearly assign these listed term percentages to a specific treatment group, so they should not be attributed to one arm on that basis.

Counts of participants with at least one serious event are not necessarily counts of all serious-event occurrences; a participant may have more than one event. The registry record does not provide enough detail in these figures to assess severity patterns, timing, exposure-adjusted rates, or causality. The safety counts should therefore be read as reported event summaries rather than as a causal comparison.

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

The primary result estimates progression-free survival in this randomized phase 2 study of TAS-114 plus S-1 versus S-1 alone. The reported hazard ratio is 1.16, with a 95% confidence interval of 0.71 to 1.88 and p = 0.274. The interval includes 1, and the log-rank analysis does not show a statistically clear difference between the groups. The data do not establish that the regimens have the same effect, nor do they prove that one is better.

A confidence interval spanning values on either side of 1 leaves uncertainty about both direction and magnitude for the hazard-ratio comparison. The medians are descriptive summaries of the group distributions, not direct estimates of individual benefit. The trial’s open-label design, the available follow-up, outcome assessment, and the analysis details all matter when interpreting the estimates. Central independent review was used for the primary endpoint, but further review procedures are not reported.

The posted secondary endpoints provide complementary information, but they do not offer a definitive resolution of the primary result. They involve different outcomes and, for some comparisons, unadjusted recalculations rather than sponsor-reported analyses. No multiplicity strategy is reported, so apparent patterns among several secondary measures should not be treated as confirmatory evidence.

These findings apply to the participants and procedures represented in this trial record. They do not establish what would happen in other populations, under different treatment schedules, or in a trial with a different design. They are statistical evidence about outcomes recorded in this study, not medical advice or a recommendation for an individual.

18. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison should be interpreted through its prespecified primary endpoint and the uncertainty around the comparative estimate, rather than through isolated point estimates. The primary median values differ, but the comparative result is the reported log-rank hazard ratio of 1.16 with a 95% confidence interval of 0.71 to 1.88. The interval’s span is central to understanding how much the trial can say about the relative progression-or-death hazard.

It also shows the distinction between a sponsor-reported analysis and a simple calculation from posted summary counts. The primary hazard ratio and p-value are reported by the registry, whereas the binary comparisons are unadjusted recalculations. Those are not interchangeable sources of evidence. Knowing which estimates come from a reported analysis helps prevent summary-data calculations from being mistaken for a full analysis plan.

The planning illustrations make another statistical point: the information required to detect an effect depends on the effect size one aims to detect and on the target power. Smaller effects require more information. These planning estimates are not evidence about the probability that this completed trial detected an effect, and they do not reveal the study’s original design justification.

Finally, secondary endpoints and safety counts need careful framing. Multiple outcomes can produce chance findings, differing endpoints can tell different parts of the clinical story, and adverse-event counts do not establish causation. Reading the result with these distinctions in view supports a more measured account of what the trial does and does not show.

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 does not report the original sample-size justification, a complete statistical analysis plan, or details of randomization implementation and stratification. It also does not report whether interim analyses were planned or conducted. These omissions prevent a full assessment of how the study’s design and analysis decisions were set before outcomes were known.

The study was open-label. Central independent review was used for the primary progression-free survival endpoint, but the registry does not describe whether reviewers were blinded, how assessments were scheduled, or how disagreements were handled. It also does not provide detailed information on scan timing, missing assessments, or sensitivity analyses for censoring. The primary population is defined as intent-to-treat, but analysis-population definitions for all secondary outcomes are not stated.

The registry reports a completed phase 2 study with approximate endpoint timeframes, not a complete account of each participant’s follow-up. The reasons for differences in outcome denominators are not reported in the registry record. The record also does not report adjustment for testing multiple secondary outcomes. Binary endpoint comparisons are simple unadjusted recalculations from posted summaries, rather than sponsor-reported inferential results.

Safety summaries are limited to the posted counts and selected serious-event terms. The record does not provide sufficient detail in these figures about event timing, exposure, causality, or the arm attribution of the listed term percentages. These limitations constrain interpretation of both efficacy and safety patterns without changing the reported primary estimate.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1 — NCT02855125.
• Registry record last updated 2024-09-19; status last verified 2024-08.
• Results first posted 2021-12-23.
• 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

The registry record describes a randomized, open-label, parallel-group phase 2 study of TAS-114 plus S-1 versus S-1 monotherapy in advanced or metastatic non-small cell lung cancer. Recorded enrollment was 128, and the primary endpoint was progression-free survival assessed by central independent review in the intent-to-treat population.

Median progression-free survival was 3.65 months for the combination and 4.17 months for S-1 monotherapy. The registry-reported hazard ratio was 1.16, with a 95% confidence interval of 0.71 to 1.88 and p = 0.274. The result does not establish a statistically clear difference between groups. Secondary outcomes and safety counts add context but have limitations, including unreported multiplicity handling and incomplete details for some analyses.