BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes (NCT03432897), a na phase 2 study. The primary outcome is Number of Participants With Prostate Specific Antigen (PSA) Response.

2. Clinical Question

The trial was intended to evaluate olaparib before radical prostatectomy in patients whose prostate cancer had DNA repair gene defects. The clinical question is therefore about a preoperative treatment period and a PSA-based response measure, not a comparison of olaparib with another treatment. The registry describes approximately 3 months of olaparib and planned surgery after treatment, but enrollment was 1 and the record does not report how much treatment that participant received or whether surgery occurred.

Repeated PSA assessments were planned from baseline through follow-up. According to the outcome description, measurements were to be made at baseline, approximately 8 weeks later, and 2 weeks after olaparib, approximately 10-14 weeks after baseline; follow-up was then described as approximately every 6 months for 2 years. The registry record does not report the resulting PSA measurements, the number meeting the response definition, or an estimate of response frequency. Thus, the clinical question is identifiable from the protocol description, but its answer is not available in the posted results.

3. Trial Design

BrUOG 337, registered as NCT03432897, was a phase 2, single-group study sponsored by Brown University. The registry lists allocation as NA, masking as none, and enrollment as 1. There was no randomized comparator. Olaparib was the drug intervention, and prostatectomy was the procedure planned after the treatment period.

The treatment description specifies olaparib 300 mg BID q 4 weeks for up to 3 cycles, with the third cycle omitted if progression was found after cycle 2. The plan was for participants to undergo prostatectomy between 22-42 days after olaparib. The brief description characterizes treatment as approximately 3 months before surgery. These are descriptions of the planned regimen; the registry record does not document the participant’s actual treatment exposure, whether the progression rule applied, or whether prostatectomy was performed.

The study start date was 2018-05-25, and the primary completion date was 2020-12-15. Its status is listed as TERMINATED. The reason for termination is not reported in the registry record. A completion date in the record should not be read as evidence that the planned enrollment or follow-up was completed, particularly given the enrollment of 1 and the terminated status.

The primary outcome was the number of participants with a PSA response, with a response defined as a reduction of at least 50% from baseline. PSA progression was defined as a 25% increase from baseline. The stated assessment period was throughout the trial for approximately 2 years. Secondary outcomes concerned PSA progression-free survival and safety. The record lists 3 outcome measures, but reports no analyses. It also does not report a statistical analysis plan, sample-size justification, interim analysis plan, or analysis population.

Because this was a single-group study, the design can describe observations in the enrolled participant but cannot provide a randomized estimate of how outcomes would differ under a comparator regimen. Enrollment of 1 also makes any group-level summary dependent on a single person’s experience. No inference about a broader population follows from the design alone.

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 Number of Participants With Prostate Specific Antigen (PSA) Response, measured over Throughout the trial for approximately 2 years.

The primary endpoint is the number of participants with a prostate-specific antigen response. The registry defines response as a reduction of at least 50% in PSA from baseline. It separately defines progression as a 25% increase in PSA from baseline. These are distinct definitions: the response threshold should not be treated as the progression threshold, and the record does not report how the definitions were applied to an observed participant result.

As a general statistical concept, a binary endpoint classifies each participant according to whether a specified event or threshold is met. Counting participants meeting that rule gives a direct description of the endpoint in the study population. PSA is a biological marker used to track changes in prostate cancer over time; a prespecified threshold makes the response classification interpretable and repeatable. The registry record does not state the rationale for selecting this particular response threshold.

The planned assessments began at baseline and continued at approximately 8 weeks, 2 weeks after olaparib (approximately 10-14 weeks after baseline), and then approximately every 6 months for 2 years in follow-up. Repeated measurements can describe the timing and persistence of changes, but the primary endpoint is stated as a participant count, not as a continuous average change in PSA. The record does not give an endpoint result, the observed PSA values, or the number of participants with evaluable measurements. It therefore does not establish whether the response criterion was met.

As a general matter, a biomarker response is not identical to a patient-centered outcome or a measure of long-term disease control. The registry also lists PSA progression-free survival and safety as secondary outcomes, but does not report their results. No conclusions about those outcomes can be drawn from the primary endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is mainly descriptive. The study is listed as a single-group phase 2 trial with enrollment of 1, and the primary outcome is a count of participants meeting a binary PSA response definition. The record lists no analyses. It does not report a model, an analysis estimate, a confidence interval, or a hypothesis test for the primary outcome. As a result, there is no reported inferential result to interpret.

What does a count endpoint represent?

As a general statistical concept, a count endpoint records how many participants meet a defined criterion. For this study, the criterion is a reduction of at least 50% in PSA from baseline. A count is not the same as a response rate: a rate also requires a specified denominator of participants assessed for the endpoint. The registry records enrollment of 1 but does not report the primary response count or the number with evaluable PSA data. It is therefore not possible to summarize the observed primary outcome from this record.

For a binary endpoint, analysis also depends on how the event is defined and when it is assessed. Here, the registry defines PSA progression separately as a 25% increase from baseline, and describes repeated assessments from baseline into follow-up. It does not report how changes between assessment times were handled, how a participant with incomplete measurements would be classified, or whether a sustained response was required. Those details are not reported in the registry record.

What can a confidence interval tell readers?

In general, a confidence interval describes the statistical uncertainty around an estimate under specified assumptions. It does not guarantee that the true value lies within a particular interval, and it cannot address sources of bias created by design or missing data. No confidence interval for PSA response is reported. With enrollment of 1 and no reported endpoint result, there is no posted estimate around which to interpret precision. The registry also gives no method for interval estimation.

What does the design allow?

A single-group study describes observations among participants receiving the study regimen. General causal inference requires a credible comparison that helps distinguish treatment-related change from other explanations. This registry record describes no control arm and no randomization. The outcome therefore cannot be compared with a concurrent alternative group. The absence of masking is also recorded, though the record does not describe how outcome assessment was conducted or whether PSA measurements were handled without knowledge of treatment.

These design features do not invalidate the description of an individual observation. They do limit what can be concluded about a treatment effect. A before-and-after change in a biomarker, even if it had been reported, would not by itself show what would have happened over the same period without the intervention. In this case, the primary before-and-after result is not reported at all.

What do the planning illustrations mean?

As a general concept, a sample-size calculation estimates how many participants may be needed to detect a specified effect under stated assumptions. It is a planning exercise, not a result from participants. The planning description associated with the statistical material uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes effects to detect as stated fractions of the observed effect. Those are planning assumptions, not the registered single-group design, and they are not evidence that the trial had the planned power or achieved an effect.

The planning description distinguishes between total events for time-to-event illustrations and participants per arm for other illustrations. It also states that the calculations are illustrations based on the observed effect, rather than the trial’s own design. Such illustrations must not be interpreted as observed power. Observed power is not a substitute for an effect estimate and its uncertainty; the registry record does not report the primary effect estimate needed to evaluate the result. It also does not report a protocol sample-size justification. The numerical planning results are not available in the registry record.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variation exceeds what a particular statistical model assumes. If a model does not account for that extra variation, its uncertainty estimates can be too small. Over-dispersion is relevant to some count-data analyses, but the registry reports no count model or analysis of this kind. The primary outcome is a count of participants meeting a binary criterion, and no model-based estimate is presented. Thus, over-dispersion is a general consideration, not a reported feature of this trial’s analysis.

More broadly, the record does not report how missing observations were handled, which participants were included in each analysis, whether any adjustment was planned, or how secondary outcomes were analyzed. Without an analysis plan and outcome results, readers cannot assess whether the analysis followed a prespecified method or how robust any estimate would be. In this study record, the central methodological point is the gap between a clearly described endpoint and the absence of a reported analysis of that endpoint.

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("Treatment")
n      <- c(1)
events <- c(0)
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  Treatment  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary PSA response outcome and secondary outcomes concerning PSA progression-free survival and safety. It does not report analyses for any outcome. The number of analyses listed is 0. No multiplicity strategy is reported in the registry record, including whether testing across multiple outcomes was planned or whether any adjustment to control false-positive findings was intended.

As a general statistical concept, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. The more opportunities there are to identify a result, the more important it is to understand which analyses were planned and how results are interpreted together. The registry describes repeated PSA assessment over follow-up, but it does not report a testing strategy across those time points. No claim about adjustment or selective reporting can be made from the record alone.

Missing-data handling is also not reported in the registry record. The outcome description gives a schedule of PSA assessments, but does not say how missed visits, unavailable PSA values, withdrawal, or incomplete follow-up would affect the primary outcome. It does not state whether a participant with no post-baseline measurement would be excluded, counted as not having a response, or treated in another way. Those choices can affect an endpoint summary, particularly when the sample is very small.

The analysis populations are not reported. The record does not identify whether analyses were to include all enrolled participants, only those who received treatment, or only those with endpoint measurements. It also does not report participant disposition or the number assessed at each time point. Because enrollment was 1 and no primary result is posted, neither missingness nor the population used for analysis can be evaluated. These are reporting gaps, not grounds to infer a particular analysis choice.

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 non-serious adverse event terms

The registry reports 0 participants with serious adverse events among 1 at risk, 1 participant with other adverse events among 1 at risk, and 0 deaths. These are counts, not estimates of risk in a broader patient population. The record lists no serious adverse event terms.

As a general statistical concept, an at-risk count gives the number of participants included in the relevant safety summary. The counts should be read separately: serious adverse events, other adverse events, and deaths are distinct categories in the record. The presence of 1 participant with an other adverse event does not reveal the event’s nature, severity, duration, or relationship to olaparib. None of those details is reported in the registry record.

With only 1 participant at risk, the safety observations are limited to that participant’s recorded experience. The absence of a serious adverse event or death in this record does not establish that such events cannot occur, while the other adverse event count does not describe how often similar events might occur in a larger group. The record does not give event timing, grades, a list of non-serious events, or an attribution assessment. These safety counts should not be interpreted as a complete characterization of the regimen’s safety.

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

The result available from this registry record is primarily a description of the study, not an estimate of the primary clinical outcome. It establishes that BrUOG 337 was a phase 2, single-group study of olaparib before prostatectomy, with enrollment of 1 and a planned PSA response definition. It does not report whether the response criterion was met. The central endpoint result is therefore unknown from the posted results.

The record does not show that olaparib reduced PSA, nor does it show that it failed to do so. A planned endpoint is not an observed outcome, and missing outcome reporting cannot be interpreted as a zero response. The record likewise does not provide a PSA response rate, a confidence interval, or a formal test. No quantitative conclusion about the primary outcome can be drawn.

Even a reported response in this single-group study would require careful interpretation. Without a randomized comparator, a change during treatment cannot isolate the contribution of olaparib from other explanations. With enrollment of 1, the observation would also provide very limited information about variability between patients. Those considerations concern what the design can establish; they do not establish a particular outcome.

The registry lists secondary outcomes for PSA progression-free survival and safety, but does not report analyses for them. The safety counts describe 0 serious adverse events, 1 participant with other adverse events, and 0 deaths among 1 at risk. They are not sufficient to characterize event frequency or types in a wider population. The record does not report the reason for termination, the participant’s treatment completion, or whether prostatectomy occurred.

Accordingly, the trial record supports a narrow conclusion: the study was registered to examine PSA response and safety around a preoperative olaparib regimen, but the posted information does not answer the primary response question. It should not be taken as evidence that treatment works or does not work. It also cannot establish how findings would apply to other patients or compare the regimen with another approach.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design and reporting sharply limit the scope of possible conclusions. The registered question concerns a specific treatment period before prostatectomy and a defined PSA threshold, but the study had enrollment of 1 and the registry reports no primary outcome analysis. The distinction between a clearly stated endpoint and a reported result is fundamental when interpreting clinical trial records.

A single-group design can be useful for describing treatment delivery and observations, but it cannot provide a randomized comparison. The absence of a control arm means that any change over time, if reported, would need cautious interpretation. With one participant, the study also cannot characterize how outcomes vary among people with the condition. A count from one participant cannot serve as a dependable estimate for a broader population.

The case also illustrates why outcome definitions, assessment schedules, and analysis reporting matter together. The registry specifies a PSA response threshold and a follow-up schedule, but does not report the observed PSA values, endpoint count, missing-data handling, or analysis population. Without those details and results, readers cannot assess the response, its precision, or the influence of incomplete follow-up.

The listed safety counts are similarly bounded by the small number at risk. They describe the posted observations but do not estimate the frequency of adverse events in a larger group. The terminated status and absence of a reported termination reason add uncertainty about study conduct and disposition, without explaining why the study stopped.

Statistically, the most important lesson is not a treatment comparison but the need to separate registration details from analyzed outcomes. A protocol can define an important question, while an incomplete or absent results record leaves that question unanswered. The registry information permits a precise description of the study’s limits, but not a conclusion about the primary PSA response.

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.

Several limitations specific to this trial constrain interpretation. Enrollment was 1, and the study was single-group, with allocation listed as NA and no masking. There was no randomized comparator to support a comparative estimate. The small enrollment also means the record cannot describe outcome variation across participants. The registry record does not report why enrollment was 1 or whether the study stopped for a particular operational or scientific reason.

The study status is TERMINATED, but the reason for termination is not reported in the registry record. Although a primary completion date of 2020-12-15 is listed, the record does not state whether the participant completed the planned treatment, underwent prostatectomy, or completed the approximately 2 years of follow-up. The planned regimen should not be treated as a confirmed account of treatment received.

The primary endpoint result is absent. The record gives the PSA response and progression definitions and a planned assessment schedule, but not observed PSA values, a response count, or an analysis. It does not report the number of participants with evaluable measurements at each time point. Missing-data procedures, analysis populations, and the treatment of incomplete follow-up are also not reported in the registry record.

The registry lists secondary outcomes but no analyses. It does not provide a statistical analysis plan, a protocol sample-size justification, or an interim analysis plan. The reason for termination, participant disposition, and any departures from the intended regimen are not reported. Safety data consist of counts for one participant at risk, without event descriptions or timing. These omissions prevent assessment of endpoint precision, robustness, and the completeness of outcome ascertainment.

These limitations do not establish that an unreported event occurred or that the planned procedures were not followed. They identify information that the record does not report and explain why the registered study question cannot be answered from the posted results alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes — NCT03432897.
• Registry record last updated 2025-07-08; status last verified 2025-07.
• Results first posted 2022-02-03.
• 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.

19. Record Summary

NCT03432897, BrUOG 337, was a phase 2 single-group study sponsored by Brown University. It evaluated planned olaparib treatment before prostatectomy for patients with locally advanced prostate cancer and DNA repair gene defects. The registry lists enrollment of 1, no masking, and status TERMINATED.

The primary endpoint was the number of participants with a PSA reduction of at least 50% from baseline. The record does not report the primary response count or any analyses. It lists secondary outcomes for PSA progression-free survival and safety. Safety counts were 0 participants with serious adverse events, 1 with other adverse events, and 0 deaths among 1 at risk. The reason for termination, participant treatment completion, and surgery status are not reported in the registry record.