BrUOG 390: Neoadjuvant Treatment With Talazoparib: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BrUOG 390: Neoadjuvant Treatment With Talazoparib (NCT04598321), a na phase 1 study. The primary outcome is Determine the Preliminary Effectiveness of Talazorparib.

2. Clinical Question

The registry frames the study as a preliminary assessment of talazoparib before surgery. The endpoint focuses on completing the planned treatment period without progression, rather than on a comparison between therapies. That makes the question one of observed completion in the study group, not a randomized estimate of comparative benefit.

The record identifies feasibility of the trial design as a secondary outcome. However, it does not report outcome analyses, and it does not give a result for the proportion meeting the primary endpoint. The registered enrollment is 1, and the study status is terminated. Consequently, the registry does not establish an estimate of the endpoint proportion or its precision.

In general, a single-group study can describe what occurred among participants who entered its treatment pathway. Without a concurrent control group, it cannot separate the treatment experience from other explanations for observed outcomes. The question is therefore narrow: whether completion without progression was observed during the planned treatment period, as recorded for this study.

3. Trial Design

NCT04598321, titled BrUOG 390: Neoadjuvant Treatment With Talazoparib, is listed as Phase 1 and sponsored by Brown University. The registry gives a start date of 2021-03-29, a primary completion date of 2022-11-30, and a status of terminated. Enrollment is recorded as 1.

The design is single-group, with allocation listed as NA and masking listed as none. The intervention is talazoparib oral capsule. The planned therapy description specifies talazoparib monotherapy as a 1 mg capsule taken orally daily for three cycles before surgery; each cycle is described as a 21-day period. Volunteers were to continue treatment to complete the cycles unless disease progression or unacceptable toxicity occurred. The remainder of the arm description is incomplete in the registry record and cannot be interpreted from the available text.

Because there is no comparator group, the study is not a randomized treatment comparison. Its primary outcome concerns completion of the planned treatment duration without progression, and the stated timeframe is the first 9 weeks of treatment. Feasibility of the trial design is listed as a secondary outcome.

The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or the criteria used to terminate the study. The termination status alone does not explain why the study ended. The record also does not report a primary endpoint result or an analysis of the feasibility outcome. These omissions limit what can be concluded about how the study was conducted and what it found.

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

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 Determine the Preliminary Effectiveness of Talazorparib, measured over First 9 weeks of treatment.

The primary endpoint is described as the proportion of volunteers who complete the planned 9 weeks of treatment without disease progression. The registry identifies the measure as a count of participants and gives the timeframe as the first 9 weeks of treatment. In substance, this is a binary outcome for each participant: completion without progression either meets the stated endpoint definition or it does not.

Such an endpoint can be useful in an early, single-group study because it captures whether participants can remain on the planned neoadjuvant treatment period without a specified progression event. It connects treatment exposure and disease status over a defined period. It is not, by itself, a direct comparison with another regimen, and the registry does not state a threshold that would define an acceptable or clinically meaningful proportion.

The outcome description refers to a proportion, which requires both a count meeting the definition and an appropriate denominator. The registry record does not report either a primary endpoint result or a denominator for an endpoint analysis. Although enrollment is recorded as 1, that figure alone does not establish whether the participant was evaluable for the endpoint, completed treatment, or experienced progression. Those details are not reported in the registry record.

General statistical interpretation of a binary endpoint depends on the event definition, follow-up completeness, and analysis population. Without these details and an observed outcome, no endpoint estimate or confidence interval can be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study has a single-group design, so its primary endpoint is naturally described as a proportion within the treated group. The endpoint definition is completion of the planned 9 weeks of treatment without disease progression. To estimate that proportion, an analysis would need to identify which participants satisfy the definition and specify who is included in the denominator. The registry record does not report those counts or an analysis population.

In general, a binary outcome records whether a participant meets a defined condition. A count of participants meeting the condition can be divided by a stated denominator to estimate a proportion. The denominator matters: for example, a protocol might define it as everyone enrolled or only those with sufficient follow-up, but the choice must be prespecified and reported. The registry record does not state the denominator rule for this endpoint, so it is not possible to reconstruct an estimate from enrollment alone.

Uncertainty around a proportion is commonly expressed with a confidence interval. In general, the interval describes a range of values that are reasonably compatible with the observed data under the statistical method used. Its width depends on the amount of information and the observed result. A confidence interval for the primary endpoint is not reported in the registry record, nor is a method for calculating one. No result is given from which to evaluate precision.

The design does not include random allocation to competing study arms. Allocation is listed as NA, masking as none, and the model as single-group. Therefore, there is no randomized between-group contrast to estimate. General methods for comparing randomized arms do not create a valid comparator when the trial contains only one group. Comparisons with external or historical groups would require data and methods that are not reported in the registry record.

The registry lists planning assumptions for an illustrative sample-size calculation: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Those assumptions are not a reported protocol justification or a statistical analysis plan. In particular, equal allocation between two arms does not describe the registered single-group design. No numerical planning result or underlying observed effect is reported in the record, so no sample-size quantity can be interpreted as the trial's planned enrollment or as evidence of power.

More generally, sample-size planning asks what amount of information may be needed to detect a specified effect under stated assumptions. An illustrative calculation is conditional on those assumptions; it does not show the probability that a completed study found an effect. The registry record does not report the rationale for enrollment, a target effect, an assumed endpoint rate, or any protocol-based power calculation. The registered enrollment of 1 should not be treated as confirmation of a completed sample-size plan.

The primary endpoint has a time component: it concerns completion without progression during the first 9 weeks of treatment. This is not described as a time-to-event analysis. The outcome is framed as whether the participant meets the completion definition over a stated period. No event-time method, censoring rule, or handling of incomplete follow-up is reported in the registry record. In general, these details affect how participants who do not have complete observation through the period are classified.

The registry reports 0 analyses. It does not specify whether the primary analysis would be descriptive, whether an interval estimate would be included, or which analysis population would be used. It also does not report an interim-analysis plan. These details should not be inferred from the Phase 1 designation or from the endpoint wording. The statistical interpretation is therefore limited to the design and outcome definition actually recorded, rather than an unreported model or decision rule.

Safety counts require their own definitions and denominators. The record gives counts at risk and affected for serious and other adverse events in Planned Therapy, alongside a serious-event term. General interpretation depends on how events were collected, whether counts refer to participants or events, and the observation period. Those operational details are not fully specified in the registry record. The counts can be described as posted, but they do not support a causal estimate or a comparison of risk.

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("Planned Therapy")
n      <- c(1)
events <- c(1)
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  Planned Therapy  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as preliminary effectiveness and gives feasibility of the trial design as a secondary outcome. It also records 2 outcome measures, but the available outcome information does not include an analysis of either measure. The registry reports 0 analyses. Thus, there are no reported estimates, tests, confidence intervals, or analysis-population descriptions for these outcomes.

Multiplicity concerns arise when several outcomes or statistical tests are used to support conclusions. In general, a prespecified hierarchy or adjustment strategy can clarify how evidence across multiple outcomes is interpreted. The registry record does not report a multiplicity strategy, any hierarchy among outcomes, or whether the secondary outcome was intended to support a formal statistical claim. No correction method or decision rule should be assumed.

Missing-data handling is also not reported in the registry record. The primary outcome requires observing treatment completion and progression status during the stated timeframe. The record does not say how incomplete follow-up, early withdrawal, missing progression assessments, or other unavailable outcome information would be treated. These choices can affect both the numerator and denominator of a proportion, so they are relevant to interpretation even when an endpoint appears straightforward.

The analysis populations are not described. The registry does not state whether an analysis would include all enrolled participants, only treated participants, or participants meeting other criteria. With enrollment recorded as 1 and no outcome analysis reported, it is not possible to determine who contributed to an endpoint result or whether anyone was evaluable. These are reporting limitations, not evidence that any particular data were missing or excluded.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small intestinal obstruction (100.0%).

The Planned Therapy safety summary lists 1 at risk and 1 affected for serious adverse events, and 1 at risk and 1 affected for other adverse events. Deaths are recorded as 0. The serious-event term listed is small intestinal obstruction, with 100.0% shown beside that term.

These are registry counts and should be read as descriptive safety entries. The record does not provide enough information to determine event timing, duration, outcome, recurrence, or whether the same participant contributed to both serious and other adverse-event categories. The percentage is reported as 100.0%, but the denominator definition for that term is not reported in the registry record.

A serious adverse event is not automatically caused by the study intervention. The entries do not establish causality, and the registry record does not give an investigator attribution or a detailed clinical narrative. They also do not show a rate comparison against another group, because no comparator arm is registered.

With enrollment recorded as 1, the safety counts are limited descriptive information. They do not, on their own, characterize the frequency or range of potential harms in a broader population. The record does not report an analysis relating these events to dose exposure or treatment duration.

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

The record establishes that BrUOG 390 was registered as a Phase 1, single-group study of neoadjuvant talazoparib for women with newly diagnosed, advanced ovarian cancer associated with a BRCA1 or BRCA2 mutation. It describes a planned treatment schedule and an endpoint focused on completion of the first 9 weeks without disease progression. These are features of the study question and design, not evidence of an observed treatment effect.

The registry does not report the primary endpoint result. There is no reported count meeting the endpoint, no reported denominator for an endpoint calculation, and no statistical analysis. Accordingly, the record does not establish what proportion completed treatment without progression or how precisely such a proportion could be estimated. It also does not report an analysis of the secondary feasibility outcome.

The absence of a comparator means that the design cannot provide a randomized estimate of the difference between talazoparib and another treatment. In general, a single-group observation can describe outcomes in the participants who received the study regimen, but it cannot by itself show what would have happened to those participants under a different treatment. No such comparative outcome is reported in any case.

The safety summary records events, including small intestinal obstruction as a serious-event term. These entries do not establish that talazoparib caused the events. They also do not provide enough information to estimate a comparative safety effect or to characterize the clinical course of the events.

The study's termination status and enrollment are relevant context, but the registry does not state why the study terminated or whether the primary outcome was unavailable, unevaluable, or simply not posted. Those possibilities should not be conflated. The defensible interpretation is limited: the registry documents the study plan and selected safety counts, while leaving its primary outcome and statistical conclusions unreported.

14. Why This Trial Matters Statistically

This study illustrates why a clearly worded endpoint is not the same as a reported result. The primary question specifies a clinical time window and a condition for success: completion of the planned 9 weeks without disease progression. Yet without the observed count, denominator, and analysis population, no endpoint proportion can be evaluated. Statistical interpretation depends on the data and analysis details as well as on the endpoint definition.

The single-group structure also clarifies the scope of inference. It may describe outcomes among participants treated under the protocol, but it does not create a randomized comparison. Recognizing that distinction prevents a within-group observation from being read as a comparative treatment effect. The registry lists no comparator and no analyses.

The enrollment of 1 makes transparent reporting of each outcome especially important. In general, limited information yields substantial uncertainty, and a point estimate without its denominator or precision measure can be misleading. Here, even a point estimate is not reported, so the main statistical issue is the absence of an analyzable endpoint result rather than the choice among competing models.

The safety entries offer another useful lesson: counts and percentages need context. The registry records serious and other adverse-event counts and identifies a serious-event term, but does not report enough information to infer causation or compare risks. Transparent definitions, follow-up details, and attribution are essential for interpreting safety summaries.

Finally, planning assumptions should be kept separate from the study's actual design and analysis. The registry's illustrative sample-size assumptions mention equal allocation between two arms, whereas the registered study is single-group. That contrast shows why planning language should not be mistaken for a protocol justification or evidence that the trial had a particular statistical capability.

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 most consequential limitation of the registry record is the absence of a reported primary endpoint result. No count of participants completing the planned treatment period without progression, endpoint denominator, estimate, or confidence interval is reported. The record also does not report an analysis of the secondary feasibility outcome.

Enrollment is recorded as 1, and the status is terminated, but the reason for termination is not reported in the registry record. The record does not explain whether the planned treatment was started or completed, whether endpoint follow-up was available, or whether any participant was evaluable. These matters cannot be inferred from enrollment or status alone.

The single-group design has no randomized comparator, limiting any potential inference to descriptive experience in the study group. The registry does not report a statistical analysis plan, an analysis population, missing-data rules, an interim-analysis plan, or a protocol-based sample-size justification. The planning assumptions described for an illustration use equal allocation between two arms, which does not match the registered single-group design.

The safety summary is also limited. It gives counts and a serious-event term, but details about event timing, duration, outcomes, attribution, and denominator definitions are not reported in the registry record. The arm description is truncated, so its incomplete text cannot be used to establish any additional treatment procedures or follow-up plan.

These limitations concern what the registry record reports; they do not establish that unreported analyses or data never existed. They do mean that the trial's primary result, precision, and reasons for termination cannot be determined from this record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BrUOG 390: Neoadjuvant Treatment With Talazoparib — NCT04598321.
• Registry record last updated 2023-10-12; status last verified 2022-12.
• Results first posted 2023-10-12.
• 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

NCT04598321 is a Phase 1, single-group study sponsored by Brown University. It evaluated planned neoadjuvant talazoparib monotherapy for women with newly diagnosed, advanced ovarian cancer associated with a BRCA1 or BRCA2 mutation. The registry lists enrollment as 1, status as terminated, and no masking.

The primary endpoint asks whether volunteers complete the planned 9 weeks of treatment without disease progression. Feasibility of the trial design is listed as a secondary outcome. The registry record reports 0 analyses and does not give a result for either outcome.

The safety summary lists serious and other adverse-event counts for Planned Therapy, records 0 deaths, and names small intestinal obstruction as a serious-event term. The record does not report a comparator, endpoint estimate, analysis plan, or reason for termination.