Trial of Rad-223 Activity in Asymptomatic Patients With mCRPC While on Abiraterone or Enzalutamide Besides AR-V7 Status: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Rad-223 Activity in Asymptomatic Patients With mCRPC While on Abiraterone or Enzalutamide Besides AR-V7 Status (NCT03002220), a na phase 2 study. The primary outcome is Assess the Efficacy of Radium-223 in Terms of Radiological rPFS.

2. Clinical Question

The study addresses a clinical setting that the registry summary characterizes as having limited prior data: patients with mCRPC who are asymptomatic or mildly symptomatic. Its focus is not only the activity of radium-223 in this population, but also whether that activity is associated with AR-V7 status. The registry record does not report the results of either question, so it cannot establish what the observed rPFS was or what association, if any, was found.

The trial title and description concern patients progressing while on abiraterone or enzalutamide. The record does not describe a separate study group for each background therapy, nor does it give an untreated or active-control group. Consequently, the primary question is descriptive within the treated group, rather than a randomized estimate of the difference between radium-223 and another treatment.

3. Trial Design

This was a phase II, single-group study with open-label treatment. The registry lists planned enrollment of 52 and records the study as completed. It gives a start date of 2016-12-21 and a primary completion date of 2020-05-06. These registry entries describe study status and design; they do not by themselves establish how many participants received treatment or contributed data to each analysis.

The intervention was radium-223. The open-label arm description specifies a dose of 55 kilobecquerel (kBq) per kilogram of body weight, given at four-week intervals for six intravenous injections. The record notes that the dose description is after the 2015 National Institute of Standards and Technology implementation. It does not report adherence, dose modifications, treatment discontinuations, or the extent to which participants completed the intended regimen.

Because allocation is listed as not applicable and the model is single-group, there is no randomized comparison in the registry record. The treatment was also not masked. A single-group design can describe outcomes occurring during treatment, but it cannot separate treatment effects from the natural course of disease, participant selection, or other care received during the study. Open-label status can also affect outcome assessment or reporting, depending on the endpoint and procedures; the registry record does not describe blinding of outcome assessors.

The record lists secondary outcomes concerning adverse events, radiographic progression-free survival by AR-V7 status, overall survival, time to first symptomatic skeletal event, PSA progression, alkaline phosphatase response, and AR-V7 mutation evolution. It lists 10 outcome measures but no analyses. Detailed eligibility criteria, recruitment procedures, analysis populations, and the statistical analysis plan 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: Men ≥ 18 years. Signed ICF. mCRPC with bone metastases and asymptomatic progression. Serum testosterone levels ≤ 1.7 nmol/L at screening. Minimum of 24 weeks of treatment with abiraterone acetate or enzalutamide. Ongoing androgen deprivation with luteinizing releasing hormone (LHRH) analogue therapy or bilateral orchiectomy. ECOG score ≤ 1. Life expectancy ≥ 12w. Subject with female partner who is of childbearing potential must use two acceptable methods of birth control.

Overall Study

Reasons for not completing this period:

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 Assess the Efficacy of Radium-223 in Terms of Radiological rPFS, measured over From date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.

The primary endpoint is median radiographic progression-free survival (rPFS), evaluated using RECIST v1.1. The registry defines the observation period as beginning at the date of first drug administration and ending at the first documented progression or death from any cause, whichever came first, with assessment up to 20 months. The endpoint therefore combines radiographic progression and death into a time-to-event outcome.

A median time-to-event outcome describes the point by which half of the outcome distribution has experienced the event, subject to the analysis method and available follow-up. It is useful when follow-up duration varies or when some participants have not experienced the event by the time observation ends. Those participants may be censored: their follow-up contributes information up to the last time they are known to be event-free, without treating them as if the event had occurred then. This is general statistical context; the registry record does not report the censoring rules or the specific estimation method used.

The endpoint is relevant to the study’s stated efficacy question because it tracks documented radiographic progression or death over time. However, a median alone does not describe the full event-time distribution or the precision of the estimate. The registry specifies a 95% confidence interval as the dispersion measure, but does not report the median or its interval. Thus, the endpoint definition is available, while its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Time-to-event outcomes record how long it takes for a defined event to occur. For this study, the primary event was the first documented radiographic progression or death from any cause, whichever came first. Follow-up began at first drug administration, and the endpoint was assessed up to 20 months. This definition determines what counts as an event and the time origin for the analysis; it does not supply an observed result.

What does a median time-to-event estimate describe?

In general, the median is a summary of the event-time distribution: it marks the time by which half of that distribution has experienced the event. It differs from an average because it does not require adding event times and dividing by the number observed, and it can be more suitable when follow-up is incomplete or event times are skewed. The registry record specifies a median for rPFS, but does not report its value.

Time-to-event analyses commonly account for participants whose event has not been observed by the end of their available follow-up. Such an observation is censored at the last known event-free time. Censoring allows partial follow-up to contribute information, but interpretation depends on how censoring is handled and on assumptions about why follow-up ends. This is general statistical explanation. The censoring rules, numbers censored, and method used for the primary analysis are not reported in the registry record.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimated quantity under the statistical method used. For a median rPFS estimate, the registry identifies a 95% confidence interval as the measure of dispersion. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The interval does not guarantee that the true value lies within its bounds, and it does not remove limitations arising from study design or measurement. Because neither the median nor its confidence interval is reported, the precision of the primary endpoint cannot be assessed from this record.

What can a single-group design estimate?

A single-group study can describe outcomes observed among participants who received the intervention. It has no concurrent randomized control group in this record, so it cannot estimate a treatment contrast through random allocation. General statistical context: randomization helps balance measured and unmeasured prognostic factors between groups on average, while a single-group design leaves outcomes open to alternative explanations, including disease course, selection, and other care. This is not a judgment about the observed efficacy of radium-223; the primary result is not reported.

The study is open-label, meaning the treatment assignment was not masked. For a radiographic endpoint, standardized assessment criteria can help define progression, and this record names RECIST v1.1. The registry does not say whether image assessors were blinded, how scans were reviewed, or how disagreements were handled. These details can matter because knowledge of treatment or clinical status may influence some aspects of assessment. They should not be assumed from the endpoint name alone.

How should AR-V7 analyses be interpreted?

The stated study aim includes assessing an association between AR-V7 status and radium-223 activity, and a secondary outcome concerns rPFS depending on AR-V7 status. An association analysis would describe how outcome patterns differ across status categories, if such categories and estimates were reported. It would not by itself show that AR-V7 status causes a difference in treatment activity. The registry record does not report subgroup sizes, subgroup estimates, a prespecified statistical test, or an interaction result. No conclusion about the association can therefore be drawn from the listed aims alone.

Multiple outcomes and subgroup questions can create multiplicity: the more statistical questions examined, the greater the chance that some apparent findings arise by chance if each is assessed separately. General methods for addressing this include prespecifying a hierarchy of outcomes or adjusting inference for multiple testing. The registry record does not report a multiplicity strategy, so it is not possible to determine how the listed secondary outcomes or AR-V7 analyses were handled.

The registry record lists 0 analyses. It does not report an analysis population, missing-data methods, a sample-size justification, or an interim-analysis plan. A sample-size planning illustration may be useful for designing a future study, but it is not observed power and does not establish that a study was adequately powered for a particular endpoint. The design assumptions stated for planning include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions are not evidence that the trial itself used that design: the study is recorded as single-group, and no planning results or trial-specific sample-size justification are reported.

The registry’s endpoint and design details allow a reader to understand what was intended to be measured and the broad type of evidence the study could provide. They do not replace a full statistical analysis plan or reported estimates. In particular, the method for estimating the median, handling censoring, assessing AR-V7, and analyzing secondary outcomes is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures, including the primary rPFS endpoint and secondary measures covering safety, survival, skeletal events, PSA, alkaline phosphatase, and AR-V7. It lists 0 analyses. The presence of multiple planned outcomes raises a general multiplicity concern: when many questions are tested, separate tests can increase the chance of at least one apparently notable result occurring by chance. Statistical approaches can control or contextualize this issue, but the record does not report a multiplicity adjustment, testing hierarchy, or other strategy.

The record does not report how missing outcome data were handled, how participants with incomplete follow-up were treated, or which analysis populations were used. For time-to-event outcomes, incomplete follow-up is often handled through censoring, but the exact rules and assumptions are important and are not reported. The record also does not give a flow of participants through screening, treatment, follow-up, and analysis, so the relationship between planned enrollment and endpoint-specific data cannot be assessed.

It is also not reported in the registry record whether interim analyses were planned or conducted, or what sample-size justification guided the trial. The planning assumptions associated with a sample-size illustration do not establish the trial’s own statistical plan, particularly because the registered design is single-group and the illustration’s assumptions describe equal allocation between two arms. No specific planning result is reported. These gaps limit assessment of analysis choices and precision; they do not establish that a particular method was or was not used.

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: anaemia (5.8%), fever (3.8%), fracture (3.8%), hematuria (3.8%), thrombocytopenia (1.9%).

For the open-label group, the registry reports 52 participants at risk for serious adverse events and 11 affected; it reports 52 at risk for other adverse events and 30 affected. It also records 3 deaths. These are counts reported for the study group, not comparisons with another treatment. The record does not explain whether deaths were judged treatment-related or provide circumstances for the deaths.

The registry lists selected serious adverse-event terms with percentages: Anaemia, 5.8%; Fever, 3.8%; Fracture, 3.8%; Hematuria, 3.8%; Thrombocytopenia, 1.9%; and Acute kidney injury, 1.9%. These entries indicate that the terms were reported in the serious-event listing. The record does not give event-specific counts, timing, severity details beyond the serious classification, or attribution to treatment for each term. The percentages should not be treated as comparative risks or as a complete account of all adverse events.

Safety figures describe what was recorded among participants under observation. They do not, without a suitable comparison and fuller event information, establish how the observed events relate to treatment. The registry record does not report a control group, exposure-adjusted rates, or detailed participant-level safety data.

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

The record establishes that a completed phase II study was designed to examine radium-223 in patients with asymptomatic mCRPC progressing while on abiraterone acetate or enzalutamide. It specifies an open-label, single-group regimen and identifies median rPFS as the primary efficacy endpoint. It also describes an aim to assess the association between AR-V7 status and activity. These are design and research questions, not efficacy findings.

The posted results do not report the primary median rPFS or its 95% confidence interval. They also do not report the results of the AR-V7 analyses or the listed secondary outcomes. The record therefore does not show the observed rPFS, the precision of an efficacy estimate, or whether outcome patterns varied by AR-V7 status. It would be inappropriate to infer a favorable or unfavorable treatment effect from study completion, outcome definitions, or listed aims.

Even if a within-group outcome estimate were available, the absence of a concurrent control group would limit causal interpretation. A single-group result cannot directly compare radium-223 with another treatment or with no treatment. Likewise, the adverse-event counts describe reported events in the treated group; they do not establish comparative safety or treatment attribution.

The appropriate reading is therefore bounded: the registry describes the population of interest, intervention, endpoint, selected safety figures, and intended questions, but does not provide the efficacy analyses needed to answer those questions. This does not mean the trial had no results outside the registry record; it means those results are not reported in the registry record.

13. Why This Trial Matters Statistically

Statistically, this study focuses on a population described as asymptomatic despite progression of mCRPC while receiving abiraterone acetate or enzalutamide. That population raises a clear endpoint question: how long participants remain free of documented radiographic progression or death while receiving radium-223. Naming the event definition, time origin, and RECIST v1.1 provides a framework for interpreting the intended primary measure.

The design also makes a useful distinction between describing activity and estimating comparative treatment effects. A single-group study can characterize outcomes observed during treatment, but it cannot produce a randomized contrast. Recognizing that distinction prevents a within-group result, if reported elsewhere, from being interpreted as though it came from a controlled comparison.

The AR-V7 objective illustrates another statistical challenge: a biomarker association question requires reported group definitions, subgroup information, estimates, uncertainty, and analysis methods. The registry identifies the question but does not give those results. This makes the record useful for understanding the intended biomarker focus while leaving the statistical evidence for that focus unresolved.

Finally, the gap between listed outcomes and reported analyses is itself relevant. The record names multiple outcomes and gives selected safety counts, yet reports no analyses and no primary efficacy estimate. Readers can distinguish what the study set out to measure from what the registry record allows them to evaluate. That distinction is central to careful interpretation of clinical-trial evidence.

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 limitation for interpreting efficacy from the registry record is that it does not report the primary rPFS estimate or its 95% confidence interval. It also does not report event counts, censoring details, or the method used to estimate the median. Without these, neither the magnitude nor the precision of the primary result can be assessed.

The single-group design has no concurrent randomized control, and treatment was open-label. This limits comparative and causal interpretation. The record does not describe whether outcome assessors were blinded, how radiographic assessments were conducted, or whether scans were independently reviewed. It also does not report participant flow, eligibility details, treatment completion, dose modifications, or endpoint-specific analysis populations.

Although the study aimed to examine AR-V7 status, the registry record does not report subgroup definitions, subgroup estimates, or results of an association analysis. It also does not report results for the listed secondary outcomes. The record lists 10 outcome measures and 0 analyses, and does not state how multiplicity or missing data were handled.

The safety information is limited to group-level counts and selected serious-event terms with percentages. Event-specific counts, timing, attribution, and a comparison group are not reported. Finally, a trial-specific sample-size justification, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record. These limitations describe what can be evaluated from the record, not necessarily what was done outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial of Rad-223 Activity in Asymptomatic Patients With mCRPC While on Abiraterone or Enzalutamide Besides AR-V7 Status — NCT03002220.
• Registry record last updated 2024-12-11; status last verified 2024-10.
• Results first posted 2024-12-11.
• 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 describes a completed phase II, open-label, single-group study of radium-223 in asymptomatic patients with mCRPC progressing while on abiraterone or enzalutamide. Planned enrollment was 52. The primary endpoint was median rPFS, defined from first drug administration to documented progression or death from any cause, assessed up to 20 months.

The stated aims included evaluating rPFS and assessing the association between AR-V7 status and radium-223 activity. The record lists 10 outcome measures and 0 analyses. It does not report the primary rPFS estimate, its confidence interval, or AR-V7 analysis results. Safety listings include 11 participants affected by serious adverse events, 30 affected by other adverse events, and 3 deaths; selected serious-event terms and percentages are also recorded.

Because the study has no concurrent control group, its design does not provide a randomized treatment comparison. The efficacy questions remain unanswered by the results reported in the registry record.