This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer (NCT01620593), a randomized phase 2 study. The primary outcome is Metabolic Syndrome.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01620593 |
| Phase | Phase 2 |
| Condition | Prostate Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 41 |
| Arms in the primary outcome | 2 |
| Lead sponsor | The University of Texas Health Science Center at San Antonio |
| Results posted | Yes |
2. Clinical Question
Population
Men with advanced prostate cancer receiving castration therapy. The registry record lists prostate cancer as the condition and reports enrollment of 41 participants. The primary analysis was limited to subjects who completed the study.
Intervention
Metformin alongside castration therapy. The registry record describes a possible reduction to 500 mg twice a day if a participant could not tolerate 500 mg three times a day; further dosing details are not reported in the registry record.
Comparator
Placebo alongside castration therapy. Both groups therefore received castration therapy; the planned contrast was the addition of metformin rather than castration versus no castration.
Primary question
Does adding metformin change weight from 0 weeks to 28 weeks, in the context of the metabolic consequences of castration therapy? The primary endpoint is listed as mean change in weight, measured in kilograms. A usable between-group estimate is not reported in the registry record.
The trial was designed to examine a metabolic question in men receiving castration therapy. The registry rationale describes concerns about metabolic changes associated with that therapy and notes interest in metformin’s potential metabolic effects. Those points explain the research question; they are not findings from this trial.
PSA response, treatment failure, and adverse events were also listed as secondary outcomes. The posted PSA result is a secondary measure, not a substitute for the primary weight-change result. The distinction matters: a reported secondary comparison cannot establish what happened on the primary endpoint when that endpoint’s between-group values are not estimable in the record.
3. Trial Design
The registry describes a randomized, placebo-controlled, prospective phase II study with a parallel-group model. The official title also describes the study as double blind, while the registry masking field says quadruple. The record does not explain which roles were masked, so the masking label should not be expanded into assumptions about participants, clinicians, assessors, or analysts.
Participants were assigned to placebo plus castration or metformin plus castration. This design targets the incremental contrast between metformin and placebo while castration therapy is present in both groups. It does not compare castration with no castration, and the record does not provide a separate untreated group.
The registry reports enrollment of 41, a start in 2011-04, primary completion in 2016-07, and a completed status. The primary outcome description specifies analysis of subjects who completed the study. The posted group counts for that primary analysis are 17 for placebo and 19 for metformin. The record does not explain why these counts differ from the enrollment figure or report the reasons for non-completion.
The primary endpoint was change in weight from 0 weeks to 28 weeks. The registry lists PSA response, treatment failure, and participants with adverse events as secondary outcomes. Only the PSA outcome has a posted continuous comparison in the available results. A treatment-failure estimate is not reported in the registry record. Details such as the allocation procedure, concealment, exact castration regimen, full metformin dosing schedule, and the analysis plan are not reported in the registry record.
This is a small phase II trial record with a narrow comparison and incomplete outcome reporting. Randomization and placebo control describe the design; they do not by themselves resolve uncertainty caused by missing endpoint results or limited detail about analysis and follow-up.
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
| Stage | Placebo and Castration | Metformin and Castration |
|---|---|---|
| STARTED | 21 | 20 |
| COMPLETED | 17 | 19 |
| NOT COMPLETED | 4 | 1 |
Analysis population for the primary outcome, as defined in the registry: Only subjects that completed the study were analyzed
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.
| Characteristic | Unit | Placebo and Castration | Metformin and Castration | Total |
|---|---|---|---|---|
| Participants analysed | 17 | 19 | 36 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 | 19 | 36 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 17 | 19 | 36 |
| Region of Enrollment: United States | Participants | 17 | 19 | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Metabolic Syndrome, measured over Change from 0 weeks to 28 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | kilograms |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the change in weight, in kilograms, from 0 weeks to 28 weeks. Weight is a direct measure of body mass and was selected in this trial as one indicator of the metabolic consequences associated with castration therapy. The registry’s outcome description frames the comparison as metformin versus placebo among castrated men.
Weight is useful for describing change in body mass, but it does not by itself identify the underlying body-composition or metabolic mechanism. A weight measure cannot establish whether any change reflects fat mass, lean mass, fluid, or another component. Nor does weight alone measure insulin resistance, glucose, lipids, or other metabolic features discussed in the registry rationale.
The primary endpoint is reported as a mean, and the analysis population is described as subjects who completed the study. However, the posted group entries are 0.0 with no reported spread, and the record identifies the two-arm comparison as missing or not estimable. Those entries therefore should not be interpreted as evidence that average weight change was exactly zero in either group. A usable estimate of the primary between-group difference, together with its uncertainty, is not reported in the registry record.
As a result, the endpoint’s clinical purpose can be described, but the posted record does not permit a numerical conclusion about the primary weight comparison. Its absence also limits how secondary findings can be related back to the trial’s principal question.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary question concerns whether weight changed differently between men receiving metformin and castration and men receiving placebo and castration. The registry lists mean change in weight over 0 weeks to 28 weeks as the primary endpoint. Yet the two group entries are recorded as 0.0, with no spread, and the primary comparison is flagged as missing or not estimable. These values do not support an interpretation of no weight change. The record does not provide an estimable primary effect or a measure of its precision.
The secondary PSA summaries report means of 58.2 ng/ml for placebo and 8.36 ng/ml for metformin at 28 weeks, with standard deviations of 193.4 and 18.35, respectively. The unadjusted recalculation gives a mean difference of -49.84 ng/ml for metformin compared with placebo, with an interval from -142.2 to 42.48 and p = 0.29. The interval includes values on either side of no difference, and its breadth indicates substantial uncertainty in this unadjusted summary. The result is not a definitive estimate of a treatment effect.
The PSA groups also show markedly different reported standard deviations, with the placebo group’s spread much larger than its mean. In general, a large spread relative to a mean can make a group average sensitive to unusually high or low observations. The registry record does not provide the underlying participant-level values or a reported analysis that would clarify the influence of such observations. The posted unadjusted comparison should therefore be read as a summary with notable uncertainty, not as a precise characterization of every participant’s response.
The PSA finding is secondary and cannot repair the missing primary result. It addresses a different endpoint, measured in ng/ml rather than kilograms, and the record does not report a prespecified hierarchy or adjustment for multiple outcomes. A secondary comparison may be informative as an exploratory result, but it carries less evidential weight than a complete, interpretable analysis of the primary endpoint.
Planning illustrations based on the observed PSA comparison are not observed power and do not indicate how well the completed trial was powered for its actual primary question. They illustrate sample sizes under stated assumptions and effect-size scenarios. The actual primary effect is unavailable, so the PSA-based planning exercise should not be treated as a design justification for weight change or as evidence about the trial’s ability to detect that endpoint.
Overall, the registry record supports a description of the randomized comparison and some secondary summaries, but not a conclusion about the primary weight outcome. The PSA comparison is imprecise and unadjusted. The posted figures should be interpreted with these reporting and precision limitations in view, without turning them into a claim that metformin did or did not change either endpoint.
9. Statistical Methods Explained
Several statistical distinctions help interpret the posted results. The central one is between an endpoint value, a between-group effect estimate, and the uncertainty around that estimate. A group mean describes an average in that group. A mean difference compares averages across groups. An interval around a difference describes a range of values compatible with the data and analysis assumptions; a wider interval indicates less precision. A p-value is another summary of compatibility with a null model, not a measure of clinical importance or the probability that a treatment works.
For PSA, the registry posts group means and standard deviations at 28 weeks. The unadjusted recalculation reports the mean difference for metformin relative to placebo as -49.84 ng/ml, an interval from -142.2 to 42.48, and p = 0.29. The interval crosses zero, so the estimate is compatible with both a lower and a higher mean under this calculation. Its width matters: the data do not pin down the direction or size of a between-group difference precisely. The recalculated comparison is a simple unadjusted analysis of posted summary statistics; it should not be confused with an adjusted analysis or an analysis reported by the trial investigators.
The PSA standard deviations are highly unequal in the posted summaries: 193.4 for placebo and 18.35 for metformin. In general, standard deviation describes how dispersed measurements are around a group mean. When dispersion is large, the mean may be influenced by observations far from the center. Unequal dispersion can also make methods based on a shared-variance assumption less suitable. These general cautions are relevant to the summaries, but the registry record does not report participant-level data, distribution plots, a robust analysis, or a sponsor-reported comparison that would resolve their impact. The posted recalculation should therefore be treated as a limited summary rather than a definitive model of the PSA data.
The primary endpoint presents a different issue: not merely imprecision, but the absence of an estimable comparison. The record identifies weight change over 0 weeks to 28 weeks as the primary measure and says only study completers were analyzed. It records 0.0 for both groups without a spread, while the comparison status indicates that values are missing or not estimable for a two-arm comparison. A displayed zero in this context cannot be taken as a measured null effect. Without group-level change estimates and an uncertainty measure, readers cannot assess the magnitude, direction, or precision of the primary contrast.
Randomization is intended, in general, to make treatment groups comparable in expectation, but it cannot guarantee balance in a small realized sample. Placebo control helps distinguish the added intervention from the experience shared by both groups, and masking can reduce some forms of bias. Those general design principles do not replace reporting of the outcome estimates, analysis population, or methods. The registry’s masking field is quadruple, but which groups were masked is not reported in the registry record.
The planning illustrations use the observed PSA effect and state assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. They show participants per arm for 80% power and 90% power under scenarios based on the stated fractions of the observed effect. Such calculations are planning illustrations, not observed power. They are conditional on the observed effect being a sensible value for planning, which can be uncertain when the estimate is imprecise. They also concern the PSA comparison, not the missing primary weight outcome. The registry record does not report the trial’s own sample-size justification or design assumptions.
Over-dispersion is a general concern when observed variability is larger than an analysis model expects. It can make standard errors too small if the model fails to account for that extra variability, leading to intervals that are too narrow and p-values that appear more decisive than warranted. The PSA summaries alone do not establish that a particular model was used or that over-dispersion occurred under that model. They do make caution about a simple mean-based recalculation reasonable, especially given the large difference in reported group variability.
Finally, statistical significance and practical importance are separate questions. A p-value does not quantify the size of an effect, while an estimate without adequate precision may leave a broad range of possible effects. The primary estimate is unavailable, and the secondary PSA estimate is uncertain. Neither the design label nor a planning scenario fills that evidential gap. The most defensible reading is to distinguish what was measured, what was numerically posted, and what remains unknown in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study assesses more than one outcome or makes more than one statistical comparison. In general, repeated testing can increase the chance of finding a result that appears noteworthy by chance. Researchers may address this through a prespecified primary outcome, a testing hierarchy, or an adjustment to the significance threshold. The registry identifies a primary endpoint and lists secondary outcomes, but any multiplicity procedure, hierarchy, or adjustment is not reported in the registry record. The PSA p-value is therefore described as unadjusted and should not be treated as a multiplicity-controlled confirmatory result.
Missing-data reporting is also limited. The primary analysis population is described as subjects who completed the study, with posted group counts of 17 and 19. The record does not report the reasons participants were not included in that analysis, how missing endpoint measurements were handled, or whether sensitivity analyses were conducted. A completer-only analysis can differ from an analysis that includes all randomized participants, particularly if completion is related to outcome or treatment. This is a general concern, not evidence that such bias occurred in this trial.
The registry record does not report an intention-to-treat analysis, a missing-data model, imputation procedures, or sensitivity analyses. It also does not explain whether the PSA summaries use the same analysis population as the primary endpoint. Readers should not assume that the treatment groups’ posted analysis counts represent all randomized participants or that missing observations had no effect.
Analysis populations and missingness methods are important because they define who contributes to an estimate and how incomplete outcomes influence it. For the primary endpoint, the record’s missing or not-estimable status prevents evaluation of the group contrast regardless of the displayed 0.0 entries. For secondary findings, the absence of detailed population and missing-data information adds uncertainty to interpretation. These omissions make it difficult to assess whether the posted results reflect the randomized comparison as a whole.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo and Castration | 0 | 17 | 0.0% |
| Metformin and Castration | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo and Castration | 0 of 17 |
| Metformin and Castration | 0 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo and Castration | 2 of 17 |
| Metformin and Castration | 8 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo and Castration | Metformin and Castration |
|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 1 of 17 | 3 of 19 |
| Nausea | Gastrointestinal disorders | 0 of 17 | 3 of 19 |
| Increased Creatinine | Renal and urinary disorders | 1 of 17 | 1 of 19 |
| Muscle Pain | Musculoskeletal and connective tissue disorders | 0 of 17 | 1 of 19 |
The registry reports no serious adverse events in either group: 0 of 17 participants in the placebo-and-castration group and 0 of 19 in the metformin-and-castration group. No deaths are reported in either group. These are counts within the reported groups, not proof that serious events could not occur. With no reported serious events in these groups, the record offers little information for estimating or comparing the frequency of uncommon serious harms.
Other adverse events are reported for 2 participants in the placebo group and 8 participants in the metformin group. The record does not identify those events in the posted summary, describe their severity, or provide event-level detail. These counts should not be treated as a complete account of tolerability or as evidence that an event was caused by the assigned treatment. Differences in counts alone do not establish a treatment-related safety effect.
In general, adverse-event interpretation depends on definitions, observation time, completeness of collection, and whether events are counted by participant or by event. The registry presents participants affected, but further details about collection and adjudication are not reported in the registry record. The safety figures are therefore descriptive and limited; they should be read separately from the efficacy endpoints.
12. What the Result Does, and Does Not, Mean
The posted record describes a randomized comparison of metformin plus castration with placebo plus castration in men with advanced prostate cancer. Its primary question concerns weight change from 0 weeks to 28 weeks. The crucial limitation is that the registry does not provide an estimable primary between-group result. The 0.0 entries, without a spread and alongside the missing-or-not-estimable status, do not show that weight was unchanged or that the groups had identical outcomes.
The secondary PSA summaries show a mean difference estimate with an interval that spans zero and a p-value of 0.29. This unadjusted result is imprecise and secondary; it does not establish a clear direction or size of difference. It also cannot stand in for the missing weight result. The posted safety counts describe reported serious events, deaths, and other adverse events, but they do not establish causation or provide a complete assessment of risk.
These results do not establish whether metformin altered weight, PSA, or the broader metabolic consequences of castration therapy. They also do not establish that the groups were equivalent. Equivalence or non-inferiority requires a suitable design and prespecified margins, neither of which is reported in the registry record. A non-significant p-value is not evidence that two treatments have the same effect.
The registry record is informative about the study’s population, comparison, endpoints, and some secondary summaries. It is less informative about the principal outcome because the primary values are not estimable, and it does not report several analysis details needed to assess bias and precision. The sound conclusion is therefore bounded: the design can be described, the posted secondary summaries can be interpreted cautiously, and the primary weight question remains unanswered by the reported results.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates how a clearly stated primary question can remain unanswered when the corresponding result is not estimable in the registry record. The primary endpoint is defined, timed, and linked to the comparison of interest, yet the posted entries do not provide interpretable group changes or a between-group estimate. Statistical interpretation depends not only on design but also on complete outcome reporting.
It also demonstrates why secondary results should be kept in their proper role. The PSA comparison is numerically available, but it is unadjusted, imprecise, and measures a different outcome from weight change. It can inform description of the posted record without resolving the primary metabolic question. Treating a secondary result as a replacement for a missing primary result would change the question after seeing the available data.
The study’s small reported analysis groups and the disparity in PSA variability make precision and analysis assumptions especially important. In general, limited information and high dispersion can leave effect estimates unstable. Planning scenarios based on the observed PSA effect can illustrate assumptions for future planning, but they do not retrospectively tell readers the trial’s observed power or validate its design.
Finally, this record highlights the value of reporting analysis populations, missing-data handling, multiplicity procedures, and treatment-effect uncertainty. Without those details, readers have fewer tools to distinguish a true absence of effect from incomplete reporting or imprecise estimation. The lesson is methodological rather than a treatment conclusion: trial design labels and posted p-values cannot substitute for interpretable primary estimates and transparent analysis methods.
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.
Several limitations are specific to the available record. Most importantly, the primary endpoint’s group values are recorded as 0.0 without a spread, while the comparison is identified as missing or not estimable. The record does not explain whether those entries reflect a data-processing convention, a reporting problem, or another cause. They should not be interpreted as observed zero change, and the primary effect cannot be quantified from these entries.
The primary analysis was limited to study completers, but reasons for non-completion and the handling of missing measurements are not reported in the registry record. The reported analysis counts are smaller than the enrollment figure, and the record does not explain the disposition of participants. It also does not report whether an all-randomized analysis or sensitivity analyses were conducted.
The PSA comparison is based on posted summary statistics and a simple unadjusted recalculation, not a reported trial analysis. Its group standard deviations differ substantially, and participant-level data or alternative analyses are not reported. This limits assessment of skew, influential values, and the suitability of assumptions behind the summary comparison. Treatment-failure results are not reported as an estimable comparison, and the secondary testing strategy is not reported.
Other trial details relevant to interpretation are also absent, including allocation concealment, exact castration and metformin schedules, the identities of masked roles, and a sample-size justification. The record reports adverse-event counts but not the event details needed to assess their nature or attribution. These gaps restrict evaluation of precision, bias, and completeness; they do not themselves demonstrate that the trial was conducted improperly.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer — NCT01620593.
- Registry record last updated 2018-05-23; status last verified 2016-09.
- Results first posted 2018-05-22.
- 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.
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18. Record Summary
The registry describes a completed, randomized, placebo-controlled, parallel-group phase II trial of metformin plus castration versus placebo plus castration in men with advanced prostate cancer. Enrollment was 41. The study started in 2011-04, and primary completion was 2016-07.
The primary endpoint was mean weight change from 0 weeks to 28 weeks, among subjects who completed the study. The registry does not report an estimable two-arm result for that endpoint. PSA response, treatment failure, and adverse events were listed as secondary outcomes. A PSA mean comparison is posted, along with limited adverse-event counts; an estimable treatment-failure comparison is not reported in the registry record.
The posted PSA comparison is an unadjusted recalculation and is imprecise. The record does not report the trial’s sample-size justification, multiplicity procedure, or detailed missing-data methods. Accordingly, the study design and some secondary results can be described, but the primary weight question cannot be answered from the reported result.