Extension Study to Evaluate Long Term Safety of Denosumab in Subjects Undergoing ADT for Non-Metastatic Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study to Evaluate Long Term Safety of Denosumab in Subjects Undergoing ADT for Non-Metastatic Prostate Cancer (NCT00838201), a na phase 3 study. The primary outcome is Overall Survival Through Month 24.

2. Clinical Question

The study concerns long-term safety and tolerability of denosumab among people undergoing androgen-deprivation therapy for non-metastatic prostate cancer who had previously received denosumab. The extension was intended to describe safety over up to 5 years of denosumab administration, including 3 years in the earlier Amgen study and 2 years in this extension. Its stated safety focus included adverse events, immunogenicity, and safety laboratory parameters.

The record’s overall-survival outcome and its safety objective address different questions. A count of participants for an overall-survival endpoint would not, by itself, describe the full safety profile, and adverse-event counts do not provide an overall-survival result. The registry describes a completed phase 3 extension, but it does not provide a reported analysis that establishes a causal treatment effect.

3. Trial Design

This was a phase 3, open-label, single-group extension study. The registry lists allocation as not applicable and masking as none. It records enrollment of 384 and a completed status. The study started on 2009-02-01, with primary completion on 2012-05-03.

The extension’s stated purpose was to describe safety and tolerability of denosumab administration for up to 5 years across the earlier study and this extension: 3 years under the 20040138 Amgen study and 2 years on this study. The brief summary identifies adverse events, immunogenicity, and safety laboratory parameters as safety measures. Denosumab is the listed intervention.

The adverse-event record separates participants into groups labelled “Placebo/ Denosumab 60 mg Q6M” and “Denosumab/ Denosumab 60 mg Q6M.” Those labels indicate different treatment histories, but the extension is not described as a randomized comparison, and the record explicitly cautions that the arms are not a like-for-like control comparison. Differences between their event counts therefore cannot be interpreted as randomized treatment effects. The record does not report further details of group assignment or the treatment history needed to assess comparability.

The primary outcome is “Overall Survival Through Month 24,” with a timeframe of 24 months and the Full Analysis Set named as its population. Although the registry identifies this endpoint, it gives no numerical result for it. The record lists one outcome measure and no analyses. It does not report a detailed statistical analysis plan, a sample-size justification, interim analyses, or the definition of the Full Analysis Set.

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: Only recruited those who were participating in the safety follow-up of 20040138 study at the time, were willing to receive Denosumab, and met the inclusion/exclusion criteria. The first portion of the arm label indicates subjects' treatment groups (Placebo or Denosumab) in the parent study 20040138

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set

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 Overall Survival Through Month 24, measured over 24 months.

The primary endpoint is titled “Overall Survival Through Month 24.” Its unit is participants, its parameter is a number, its timeframe is 24 months, and the named population is the Full Analysis Set. As recorded, it is a count-based endpoint rather than a reported survival estimate or a comparative effect measure.

Overall survival is commonly used in clinical research to capture whether participants remain alive over a specified period. As a general statistical point, a count alone does not convey the timing of events or the duration of observation for each participant. Time-to-event analyses can use those details and account for participants whose follow-up ends before an event is observed. The registry record does not report such an analysis for this endpoint.

The endpoint name and measurement description do not include an observed count, an estimate, or a confidence interval. The registry record therefore does not show the numerical overall-survival result through month 24. The death counts in the adverse-event group data are also not reported. Without an outcome result and analysis details, the endpoint cannot support a quantitative assessment of survival in the study.

Overall survival is distinct from the study’s stated long-term safety purpose. The brief summary emphasizes adverse events, immunogenicity, and safety laboratory parameters, while the registered primary outcome is overall survival. Neither type of information substitutes for the other: safety event counts do not establish survival, and a survival count would not describe all safety outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group extension design tell readers?

A single-group extension follows participants receiving a study intervention in an extension setting rather than assigning participants to randomized intervention and control groups for a new comparison. The design can describe outcomes among participants who enter and remain in the extension. By itself, it cannot separate the effect of the intervention from other influences on outcomes. This is particularly important for safety: an event observed during follow-up is not automatically caused by the study drug.

Here, the registry describes an open-label extension with allocation listed as not applicable and masking listed as none. Its adverse-event data use two treatment-history labels, but the record explicitly warns that they are not a like-for-like control comparison. Their counts are therefore descriptive. General principle: a causal comparison requires groups that are sufficiently comparable, along with an analysis appropriate to the design and outcome. The registry record does not report such an analysis.

What does a count-based outcome represent?

The primary outcome is a number of participants for overall survival through month 24. A count describes how many participants meet the recorded outcome definition in the analysis population. It is not automatically a probability, survival curve, or comparison between groups. General statistical practice distinguishes a raw count from an estimate that accounts for follow-up time, censoring, or other features of the data. Those details are not reported for the registered survival outcome, and no outcome count is posted.

A confidence interval is a statistical range used to express uncertainty around an estimate under specified assumptions. It does not guarantee that the true value lies inside the range, nor does it resolve limitations in study design or data collection. No confidence interval for the primary outcome is reported in the registry record. A p-value, if available, would address compatibility of data with a specified statistical hypothesis under a model; it would not describe clinical importance or remove confounding. No p-value or model result is reported.

How should event counts be read?

The adverse-event data list participants at risk and participants affected in each labelled group. These counts provide a descriptive record of events among the listed participants. When group sizes or observation periods differ, raw counts alone do not provide a fair comparison of event frequency. Rates can account for time at risk, but the registry record does not report person-time-based rates. It also does not provide a randomized comparison, and its caution about the groups rules out treating them as equivalent control arms.

Serious adverse events are a category of events distinguished by seriousness criteria; a serious event is not the same as an event proven to be caused by treatment. Causality requires clinical and analytical assessment beyond observing that an event occurred. The registry lists serious-event terms and percentages, but the denominator and calculation basis for those percentages are not reported in the registry record. The listed terms should therefore not be treated as comparative risks or as proof of treatment attribution.

What does over-dispersion mean in general?

General explanation: over-dispersion occurs when observed variation in count data is greater than a statistical model assumes. If a model assumes that counts vary only according to a restrictive distribution, over-dispersion can make uncertainty estimates too small and statistical tests too optimistic. Analysts may use models that allow extra variation, but model choice depends on the outcome structure and study design. The registry record does not report a count model, an over-dispersion assessment, or an analysis of the primary outcome, so no such method can be attributed to this study.

What do planning calculations mean?

General explanation: a sample-size calculation is a planning exercise that estimates the information required to detect a specified effect under chosen assumptions. It is not an observed study result, and it is not “observed power.” The registry record does not report the study’s own sample-size justification or analysis plan. It also does not report a primary outcome estimate from which to assess the precision of an observed survival result. Any planning illustration based on an observed effect would depend on that effect and the stated assumptions; it would not establish that the study was designed or powered in that way.

Interpretation must therefore stay close to what is recorded: a completed extension with descriptive safety counts, a named overall-survival endpoint without a reported numerical result, and no registered analysis details. General statistical methods can explain what would be needed for stronger inference, but cannot fill the gaps in reported results.

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("Placebo/Denosumab 60 mg SC Q6M", "Denosumab/Denosumab 60 mg SC Q6M")
n      <- c(186, 198)
events <- c(174, 184)
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  Placebo/Denosumab 60 mg SC Q6M  186  174  93.5  89.0  96.6  89.1  96.3  89.1  96.2
ARM  Denosumab/Denosumab 60 mg SC Q6M  198  184  92.9  88.4  96.1  88.5  95.7  88.5  95.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no analyses. It does not report a statistical analysis plan, a hierarchy of endpoints, or a method for controlling multiplicity. Multiplicity arises when several outcomes, time points, groups, or hypotheses are tested; repeated testing can increase the chance of a statistically significant finding arising by chance. General approaches include prespecifying a primary hypothesis or adjusting inference across a family of tests. No such approach can be attributed to this study from the registry record.

Missing-data methods are also not reported in the registry record. For an overall-survival outcome, interpretation may depend on whether participants have complete follow-up and how observation ending before an event is handled. For safety outcomes, incomplete observation or differences in time under follow-up can affect counts. General methods can address these problems only when the data structure and assumptions are specified; those details are not reported.

The Full Analysis Set is named as the population for the primary outcome, but its definition, inclusion rules, and handling of missing observations are not reported in the registry record. It is therefore not possible to determine from the record which participants contributed to the endpoint or how incomplete data were treated. The enrollment figure alone does not establish the analysis denominator.

Because no numerical result or analysis is posted for the primary outcome, there is no reported estimate to evaluate for multiplicity or missing-data sensitivity. These omissions limit assessment of both precision and robustness; they do not show that any particular method was or was not used outside what the registry record reports.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: cardiac failure congestive (2.7%), prostate cancer (1.6%), cerebrovascular accident (1.6%), respiratory failure (1.6%), haematuria (1.5%).

The registry lists 45 participants with a serious adverse event among 185 at risk in the “Placebo/ Denosumab 60 mg Q6M” group, and 51 among 199 at risk in the “Denosumab/ Denosumab 60 mg Q6M” group. For other adverse events, it lists 47 among 185 and 46 among 199, respectively. These are participant counts in the registry’s separate treatment-history groups, not randomized comparative estimates.

The record also lists cardiac failure congestive (2.7%), prostate cancer (1.6%), cerebrovascular accident (1.6%), respiratory failure (1.6%), haematuria (1.5%), and anaemia (1.1%) among the serious-event terms. The denominator and calculation basis for these percentages are not reported in the registry record. The list should not be interpreted as a comparison between groups or as evidence that denosumab caused any listed event.

General statistical point: event counts are influenced by the number of participants observed and the duration of observation. The registry does not report person-time rates or sufficient follow-up detail for such an interpretation. The death counts in these adverse-event group data are not reported.

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

The record documents a completed extension study intended to describe long-term denosumab safety and tolerability among people undergoing androgen-deprivation therapy for non-metastatic prostate cancer who had previously received denosumab. It reports adverse-event counts for two treatment-history groups and lists several serious-event terms with percentages. These results provide descriptive information about events recorded in the registry.

The record does not report a numerical result for its primary endpoint, overall survival through month 24. It provides no survival estimate, confidence interval, or inferential analysis. Accordingly, the posted information does not quantify overall survival through the stated timeframe or establish a treatment effect on survival. The registry’s safety counts cannot fill that gap.

The event figures also do not show that denosumab caused or prevented an event. The study is an open-label, single-group extension, and the registry warns that the two adverse-event groups are not a like-for-like control comparison. Raw counts across these groups do not establish comparative risks. The record does not provide an adjusted analysis, person-time rates, or the percentage denominators needed to make broader comparisons.

General interpretation: a study can be useful for documenting outcomes in a defined setting while still being unable to establish causal effects. Design, follow-up, outcome definitions, missing data, and analysis methods all affect what can be inferred. In this record, several of those details are not reported. The findings should therefore be understood as limited registry descriptions, not as proof of benefit, lack of benefit, or treatment-related harm.

14. Why This Trial Matters Statistically

This study illustrates why a registered outcome and a posted result are not the same thing. Overall survival through month 24 is identified as the primary endpoint, with participants as its unit and the Full Analysis Set as its population. Yet the registry record does not report a numerical endpoint result or an analysis. Readers cannot evaluate the observed survival outcome or its precision from the endpoint title alone.

It also shows the distinction between a safety description and a comparative safety analysis. The registry lists serious and other adverse-event counts, but the groups are treatment-history categories in an open-label extension, not randomized comparison arms. Descriptive counts can help convey what was recorded, while still being inadequate for attributing events to treatment or comparing treatment effects.

For biostatistical interpretation, the record highlights the importance of defining the analysis population, reporting follow-up and missing-data handling, and explaining how outcomes were analyzed. Those details matter for interpreting both count outcomes and event data. The Full Analysis Set is named, but its definition is not reported; the analysis plan and multiplicity approach are also not reported.

The distinction between stated study purpose and registered primary endpoint is also important. The brief summary emphasizes long-term safety and tolerability, while the named primary outcome is overall survival. A careful reading keeps those questions separate and avoids treating the available safety summaries as a substitute for an unreported survival result.

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 principal limitation for interpreting efficacy is that no numerical result is reported for overall survival through month 24, despite its designation as the primary outcome. The record lists no analyses, so there is no reported estimate or uncertainty measure to assess. Death counts in the adverse-event data are also not reported.

The study is open-label and single-group, with allocation listed as not applicable and no masking. The two adverse-event groups have different treatment-history labels and are explicitly not a like-for-like control comparison. Their counts cannot establish a causal effect or serve as a randomized contrast. The registry does not report an adjusted comparison or person-time rates.

The registry does not report the definition of the Full Analysis Set, missing-data methods, detailed follow-up information, or a statistical analysis plan. It also does not state the denominator and calculation basis for the percentages attached to serious-event terms. These omissions limit assessment of endpoint completeness, event frequency over time, and the precision of the safety summaries.

The record’s stated purpose includes immunogenicity and safety laboratory parameters, but no numerical results for those measures are included in the information. The study’s own sample-size justification, interim analyses, and multiplicity strategy are not reported in the registry record. These are limits of the available record and do not establish what may have been conducted outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Extension Study to Evaluate Long Term Safety of Denosumab in Subjects Undergoing ADT for Non-Metastatic Prostate Cancer — NCT00838201.
• Registry record last updated 2018-10-18; status last verified 2018-09.
• Results first posted 2013-09-24.
• 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

NCT00838201 is a completed phase 3, open-label, single-group extension study sponsored by Amgen. It enrolled 384 participants and was intended to describe the long-term safety and tolerability of denosumab among people undergoing androgen-deprivation therapy for non-metastatic prostate cancer who had previously received denosumab. The stated safety period was up to 5 years across the earlier study and this extension: 3 years under the 20040138 Amgen study and 2 years on this study.

The registered primary outcome is overall survival through month 24 in the Full Analysis Set. A numerical result and analysis are not reported in the registry record. Adverse-event counts are listed under two treatment-history labels, which are not a like-for-like control comparison. The record does not report a detailed analysis plan, missing-data methods, or the definition of the primary analysis population.