Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis (NCT02097303), a na phase 2 study. The primary outcome is Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria.

2. Clinical Question

3. Trial Design

This was an open-label phase two study with a single group. The registry lists Carolina Research Professionals, LLC as sponsor, an enrollment of 36, and a completed status. The recorded start was 2014-03 and primary completion was 2015-12. These dates describe the registry record; they do not by themselves provide information about the timing or completeness of individual follow-up.

All participants in the single arm received concurrent radium Ra 223 dichloride and abiraterone acetate plus prednisone. Allocation is listed as not applicable, consistent with the absence of multiple randomized groups. Masking was listed as none. With no separate comparator arm, the study can describe the experience of participants receiving the combination and changes measured during the study, but it cannot estimate a between-group treatment contrast from this design.

The primary outcome concerned the number and percentage of participants meeting specified quality-of-life improvement criteria between baseline and end of treatment. The registry describes assessments at screening, monthly during the study, and 30 days after the last dose of radium Ra 223 dichloride. It states that the latter assessment was expected to be approximately 32 weeks after screening for evaluable subjects. The primary outcome result and the number of participants evaluable for that endpoint are not reported in the registry record.

Secondary outcomes included safety data among subjects who received at least one infusion, changes in alkaline phosphatase and prostate-specific antigen levels, and radiologic assessment of mean bone-lesion counts before and after treatment. The record lists 7 outcome measures and 2 analyses, but does not report the detailed statistical plan, analysis populations for all outcomes, or outcome-specific numerical findings in the posted information. The design is therefore most informative as a single-group description, not as a controlled estimate of comparative effect.

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

Analysis population for the primary outcome, as defined in the registry: Improvement at the EOT visit was defined as increase from baseline of \>= 10 points for FACT-P Total Scale. \>9 points for FACT-G Total and FACT-TOI scales, and \>=3 points for the remaining scales.

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 and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria, measured over Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects..

The primary endpoint was the number and percentage of participants with a clinically meaningful improvement in quality of life between baseline and end of treatment. It used several patient-reported scales: FACT-P, FACT-G, FACT-TOI, and the prostate cancer subscale, or PCS. The registry states that higher scores indicate better scores for these instruments. FACT-P combines the FACT-General and prostate cancer subscale; FACT-TOI combines physical well-being, functional well-being, and the prostate cancer subscale.

The registry defined improvement at the end-of-treatment visit as an increase from baseline of >= 10 points for FACT-P Total Scale, >9 points for FACT-G Total and FACT-TOI scales, and >=3 points for the remaining scales. These criteria turn a score change into a responder classification: a participant either meets a scale-specific improvement threshold or does not. Reporting the number and percentage meeting the criteria can make the endpoint easier to interpret than a score change alone, although the registry does not report the primary result or the number assessed.

Quality-of-life measures are used to capture symptoms and aspects of functioning reported by participants, complementing clinical and laboratory outcomes. The record says FACT-P assesses symptoms and problems related to prostate carcinoma and its treatment, while FACT-G measures physical, functional, social, and emotional well-being. The posted information does not explain why these thresholds were selected or report scale-level results. It therefore permits a description of the intended endpoint, but not an assessment of how many participants experienced the defined improvement.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome: each participant either meets a scale-specific definition of clinically meaningful quality-of-life improvement or does not. The endpoint title calls for the number and percentage of participants meeting that definition. A count describes the observed number of responders; a percentage expresses that count relative to an analysis denominator. The registry record does not report either primary endpoint result or the denominator used for it, so no response rate can be interpreted from the posted information.

What does a responder threshold do?

A threshold converts a continuous score change into a classification. This can be useful when the scientific question concerns whether a change reaches a prespecified level considered meaningful, rather than whether the average score moved by any amount. Here, the registry lists different point-increase criteria for FACT-P, FACT-G, FACT-TOI, and the remaining scales. These criteria should be treated as the recorded definitions; the rationale for selecting them is not reported in the registry record.

Thresholds also simplify a complex experience. Two participants with changes on opposite sides of a cutoff may be classified differently even if their score changes are close. Conversely, participants classified as responders may have different score changes. A binary outcome therefore answers a focused question about meeting a criterion, but it does not convey the full distribution of score changes or the extent of change among participants. The registry describes the scales and their score ranges, but does not report the scale-level score distributions or primary responder counts.

How should a before-and-after comparison be read?

The primary outcome compares baseline with end of treatment within the study group. In general, paired measurements can show how participants’ recorded scores changed over time. A within-participant comparison is not the same as a comparison of separate randomized groups. Without a concurrent control group, a change cannot be attributed uniquely to the treatment combination: time trends, other care, natural variation, and the availability of follow-up measurements may also matter. This is a general limitation of uncontrolled before-and-after designs.

Open-label status means masking was absent according to the registry. For a participant-reported outcome, expectations and knowledge of treatment can be relevant considerations in general, although the record does not establish whether or how such influences affected responses in this study. Standardized instruments and specified thresholds can make outcome definitions explicit, but do not remove the design’s lack of a control group.

What does uncertainty mean for a binary outcome?

In general, an estimate of a response proportion has sampling uncertainty because the observed participants are only one possible set of participants who could have been studied. A confidence interval expresses a range of values compatible with the observed data under the chosen statistical method and its assumptions. A wider interval indicates less precision; a narrower one indicates greater precision. No primary response estimate or confidence interval is reported in the registry record, so the uncertainty of the primary endpoint cannot be assessed from the posted information.

For event counts, interpretation also depends on the time period and population under observation. Different follow-up durations or incomplete assessment can affect how many events are recorded. The registry gives a safety population defined as subjects who received at least one infusion for its safety outcome description, but does not give detailed follow-up time or event-specific exposure time in the posted information. The reported counts should therefore be read as registry summaries, not as exposure-adjusted rates.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variation in count data exceeds what a chosen model assumes. If a count model underestimates variability, standard errors and confidence intervals may be too small, making results appear more precise than they are. A suitable analysis may use a model that allows extra variation or otherwise accounts for the data structure. The registry record does not report a count-model specification or a method for assessing over-dispersion; this concept is relevant generally to count outcomes, not evidence that over-dispersion occurred in this study.

What can planning calculations say?

Any sample-size figures associated with a planning illustration are not observed power and are not the trial’s enrollment or observed result. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The illustration is not the design of this single-group study, which had no two-arm allocation. The registry record does not report that these assumptions were used to plan the trial. Sample-size planning is generally conditional on its assumptions; it does not demonstrate that an observed result is reliable or that a study had a particular probability of detecting an effect.

The registry records 7 outcome measures and 2 analyses, but does not report a detailed statistical analysis plan, model specifications, inferential procedures, or the handling of multiple outcomes. Those omissions limit assessment of how estimates were generated and how uncertainty was quantified. They do not change the basic interpretation: the primary endpoint was defined, but its numerical result and precision are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, scales, time points, or statistical comparisons are assessed. In general, examining more results creates more opportunities for chance findings, so a statistical plan may specify a primary outcome, a hierarchy of tests, or an adjustment strategy. The registry identifies a primary quality-of-life endpoint and lists secondary safety, laboratory, and radiologic outcomes. It also records 7 outcome measures and 2 analyses. The detailed analysis plan, any multiplicity adjustment, and the relationships among those analyses are not reported in the registry record. It is therefore not possible to determine how the study handled the chance of false-positive findings across its outcomes.

Missing data matter particularly for a before-and-after endpoint because a participant needs the measurements required to classify change. The registry describes visits at screening, monthly during the study, and 30 days after the last radium Ra 223 dichloride dose, expected to be approximately 32 weeks after screening for evaluable subjects. It does not report the number with baseline and end-of-treatment assessments, reasons for missing measurements, or any imputation or sensitivity analysis. The primary analysis population is not reported in the registry record.

The safety outcome description specifies subjects who received at least one infusion. That is a stated population for safety summaries; it does not establish the analysis population for quality of life or other secondary outcomes. The record does not describe how withdrawals, incomplete questionnaires, or unavailable follow-up measurements were handled. Because missingness can affect who contributes to an endpoint, readers should not assume that the enrollment count is the denominator for every outcome.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (2.8%), cardiopulmonary arrest (2.8%), urinary tract infection (2.8%), syncope (2.8%), small bowel obstruction (2.8%).

The safety summary describes 5 participants with serious adverse events among 36 at risk, 30 participants with other adverse events among 36 at risk, and 1 death. These are counts for the study group, not comparisons against another treatment group. The registry’s safety outcome description refers to subjects who received at least one infusion of radium Ra 223 dichloride.

The listed serious adverse-event terms are abdominal pain, cardiopulmonary arrest, urinary tract infection, syncope, small bowel obstruction, and congestive heart failure. Each is listed with a frequency of 2.8%. These term-level figures should not be added together: the registry does not report whether an individual participant experienced more than one term, and the list is not a participant-level total. Nor does the record establish that any listed event was caused by the treatment combination.

General safety interpretation depends on event definitions, observation time, severity, relatedness assessments, and how events were collected. The posted information does not give all of those details or a control-group rate. The figures describe what the registry records for this study and cannot establish comparative safety or the likelihood of an event in other populations.

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

This study’s registry entry describes a completed, open-label, single-group phase two evaluation of concurrent radium Ra 223 dichloride, abiraterone acetate, and prednisone in people with symptomatic castration-resistant prostate cancer and bone metastases. Its primary question concerned clinically meaningful quality-of-life improvement from baseline to end of treatment. The record provides the scales and thresholds used to define that improvement, but the primary outcome result is not reported in the registry record.

Accordingly, the posted information does not show how many participants met the improvement criteria, what percentage they represented, or how precise an estimated response proportion would be. It also does not provide primary endpoint score changes or a confidence interval. The absence of a reported result is not evidence that improvement did or did not occur; it means the registry entry does not permit that conclusion.

The single-group design supports descriptive reporting of outcomes among participants who received the combination. It does not provide a randomized or concurrent control comparison. A baseline-to-end-of-treatment change, even if numerical results were available, would not by itself isolate the contribution of the combination from time, other care, expectations, or selective availability of follow-up. The design therefore cannot establish a comparative treatment effect from the posted information.

The safety summaries report adverse-event counts, including serious events and a death, but do not establish causation or comparative safety. The secondary outcome descriptions identify laboratory and radiologic measures, without numerical results in the registry record. The study’s enrollment and completion status provide useful context, but do not replace outcome-specific denominators, follow-up completeness, and uncertainty estimates.

Overall, the registry record supports a clear account of the intended population, intervention, design, assessment schedule, endpoint definition, and selected safety counts. It does not support a conclusion about the primary quality-of-life result or the magnitude and precision of benefit or harm. Those boundaries are important when interpreting a trial record that specifies what was measured but does not report the primary outcome estimate.

13. Why This Trial Matters Statistically

Statistically, this trial illustrates the distinction between specifying an endpoint and reporting its result. The registry gives a detailed definition of clinically meaningful quality-of-life improvement, including several instruments and scale-specific thresholds. That definition makes the intended responder question understandable. However, without the responder count, denominator, and an estimate of uncertainty, the primary endpoint cannot be evaluated quantitatively from the registry record.

The study also illustrates what a single-group design can and cannot address. Repeated measurements can describe participants’ changes over time, while a separate concurrent group would be needed for a direct between-group comparison. In an open-label study using participant-reported outcomes, the absence of masking is relevant context, though the registry record does not show whether it affected responses. These design features shape interpretation independently of whether the endpoint is clinically meaningful.

The safety summaries show why event counts need context. A count is not a comparative risk estimate, and terms listed for serious events do not necessarily correspond to unique participants. Without a control group, follow-up detail, and event-relatedness information, the counts remain descriptive. This distinction helps prevent a numerical safety summary from being read as a causal conclusion.

Finally, the record’s missing statistical details matter for reproducibility and precision. It does not report the primary analysis population, missing-data approach, detailed multiplicity strategy, or primary endpoint estimate. The stated sample-size illustration assumptions are separate from the actual single-group design and should not be mistaken for evidence about observed power. Together, these features make this trial useful for understanding endpoint construction and design limits, while also showing how incomplete numerical reporting restricts statistical interpretation.

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 primary limitation for interpreting the main question is that the primary quality-of-life result is not reported in the registry record. The count and percentage meeting the improvement criteria, the denominator assessed, and any estimate of uncertainty are absent from the posted information. Although the registry defines scale-specific thresholds and describes an assessment schedule, those details cannot substitute for the observed endpoint data.

The single-group, open-label design has no concurrent control arm. Changes from baseline to end of treatment can be described, but cannot be attributed uniquely to the study combination. The registry does not report a randomized comparison, and the record’s allocation and masking entries are consistent with a nonrandomized, unmasked design.

Assessment was planned at screening, monthly during the study, and 30 days after the last radium Ra 223 dichloride dose, expected to be approximately 32 weeks after screening for evaluable subjects. The record does not report endpoint-specific follow-up completeness, missing-data reasons, or methods for handling incomplete assessments. It also does not report the primary analysis population or justify the improvement thresholds.

Several secondary outcome areas are named, including safety, laboratory measurements, and radiologic assessment, but their numerical results are not reported in the registry record. The record does not provide a detailed statistical analysis plan, multiplicity handling, or outcome-specific model details. Safety summaries lack a comparison group and do not establish event causation. These limitations restrict conclusions to the design and reported descriptive counts rather than comparative effectiveness or causal safety claims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis — NCT02097303.
• Registry record last updated 2018-02-01; status last verified 2018-01.
• Results first posted 2018-02-01.
• 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 NCT02097303 as a completed, open-label phase two study with a single group and enrollment of 36. The study evaluated concurrent radium Ra 223 dichloride, abiraterone acetate, and prednisone in people with symptomatic castration-resistant prostate cancer and bone metastases, including pre- and post-chemotherapy settings. The primary endpoint was the number and percentage meeting defined quality-of-life improvement criteria between baseline and end of treatment.

The registry lists 7 outcome measures and 2 analyses. Safety summaries report 5 participants with serious adverse events, 30 with other adverse events, and 1 death. The primary quality-of-life outcome result, its analysis denominator, and its precision are not reported in the registry record. The single-group design supports descriptive interpretation but not a controlled treatment comparison.