Fluorine F 18 Sodium Fluoride Positron Emission Tomography in Evaluating Response to Dasatinib in Patients With Prostate Cancer and Bone Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fluorine F 18 Sodium Fluoride Positron Emission Tomography in Evaluating Response to Dasatinib in Patients With Prostate Cancer and Bone Metastases (NCT00936975), a na phase 2 study. The primary outcome is Changes in 18F-fluoride PET (SUV) - Tumor Bone.

2. Clinical Question

3. Trial Design

NCT00936975 is a completed phase 2 study sponsored by the National Cancer Institute. The registry record lists a start date of 2009-09 and a primary completion date of 2014-06. Enrollment was 18. The study is described as a multicenter evaluation of 18F-fluoride PET as a pharmacodynamic biomarker for dasatinib in men with castration-resistant prostate cancer and bone metastases.

The design is single group, allocation is listed as not applicable, and masking is listed as none. There is no randomized control arm in this protocol, so the study does not directly compare PET changes between groups assigned to different treatments. Its primary endpoint instead concerns change over time in the PET measure.

Fluorine F 18 sodium fluoride was the listed intervention. Participants underwent PET at baseline and at 12 weeks after initiation of dasatinib. The registry record specifies that dasatinib was delivered under a concurrent protocol and was not considered part of the intervention for this protocol. This distinction matters when describing what the study itself evaluated: it assessed PET measurements around treatment with dasatinib, rather than testing a treatment assignment within this study.

The primary analysis population comprised 37 bone locations in 12 eligible participants with interpretable pre- and post-treatment scans. These are different units: multiple bone locations could contribute data from a participant. The registry record does not state how correlation among locations from the same participant was handled in an analysis. It also does not report the full eligibility criteria, details of the concurrent dasatinib protocol, or the planned sample-size justification.

The registry lists 6 outcome measures and 10 analyses. Secondary outcomes include changes in 18F-fluoride transport, measured by Patlak flux, in tumor and normal tissue. The numerical findings for the primary and secondary outcomes 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis population consists of 37 bone locations in 12 participants who were eligible for the study and had interpretable Pre- and Post-Treatment PET scans

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.

Population: 18 participants meeting the eligibility criteria were accrued to the trial and received the baseline PET scan

6. Primary Endpoint

The registry lists the primary outcome as Changes in 18F-fluoride PET (SUV) - Tumor Bone, measured over Baseline and 12 weeks.

The primary endpoint is change in 18F-fluoride PET SUVmax in tumor bone between baseline and 12 weeks. SUVmax is the maximum standardized uptake value measured within the specified region. In this study, the registry describes the measure as an indicator of regional fluoride incorporation in tumor bone. The endpoint therefore concerns a PET imaging measurement, not a clinical outcome such as symptoms, disease progression, or survival.

A pharmacodynamic biomarker is a measurement used to assess a biological response associated with an intervention. In general, imaging biomarkers can provide a way to examine changes in a target tissue over time. Comparing a participant’s scan at baseline with a later scan can describe whether the measured imaging value changed during that interval. Such a change, on its own, does not establish why it occurred or whether it predicts a clinical outcome.

The endpoint is specified as a mean of a continuous measure, with standard deviation as the dispersion measure. In general, a mean describes the average measured value or change in an analysis population, while a standard deviation describes the spread of individual observations around that average. The record does not report the mean change, standard deviation, confidence interval, or a test result for this endpoint. Consequently, the size, direction, and precision of the primary endpoint result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is described as a mean of a continuous measurement, with standard deviation used to describe dispersion. In general, a continuous measure can take values across a scale rather than being limited to categories. A mean provides a summary of the average value or average change in the analyzed observations. It does not show whether individual participants or bone locations had similar changes, and it can be influenced by unusually high or low values. The standard deviation describes the spread of observations around the mean; it is not the same as the uncertainty in the estimated mean.

A confidence interval, in general, expresses a range of values compatible with the data and the chosen statistical procedure. It helps communicate precision: a narrower interval indicates greater precision than a wider interval under the same method. A p-value, in general, describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the statistical model were correct. Neither quantity is reported for the primary result in the registry record. The mean change and standard deviation are also not reported, so the endpoint’s magnitude and precision cannot be assessed.

The two scans are taken at baseline and 12 weeks after initiation of dasatinib. A paired analysis is a general approach for repeated measurements because it focuses on within-unit change and accounts for the fact that measurements from the same unit are related. The registry record describes the timing and endpoint but does not state the statistical test or model used. It is therefore not possible to say whether the sponsor analyzed changes with a paired test, a repeated-measures model, or another method.

The analysis population includes 37 bone locations in 12 participants. In general, observations from several locations in one participant are clustered: measurements from the same participant may share characteristics and may not be statistically independent. Treating clustered observations as independent can make standard errors and confidence intervals misleading. Methods such as participant-level summaries or models that account for clustering can address this dependence, depending on the question and design. The registry record does not report which approach was used, so the adequacy of the uncertainty calculation cannot be evaluated from the record.

The study is single group, and allocation is listed as not applicable. It therefore does not have a randomized between-group contrast in this protocol. A within-participant comparison can describe change between scans, but a change alone is not a controlled estimate of what would have happened without the concurrent treatment context. General causal interpretation is more limited in an uncontrolled design than in a randomized comparison. This does not determine what the observed imaging result was; that result is not reported.

Sample-size calculations listed with the results are planning illustrations based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. These assumptions describe hypothetical planning calculations; they do not establish that this single-group trial was designed with those assumptions. Such calculations are not observed power, and the registry record does not report the trial’s sample-size justification. The numerical planning illustrations are not reported in the registry record.

For a continuous outcome, general planning calculations depend on the effect size being targeted and the assumed variability, as well as the chosen error rate and allocation. When the effect is expressed as a fraction of an observed effect, the illustration is conditional on that observed estimate. It should not be interpreted as a guarantee that a future study will achieve a particular result. No independent estimate of variability or planning target is reported in the registry record.

Over-dispersion is a general concern when observed variability is greater than assumed by a statistical model. If it is not accounted for, uncertainty can be understated. This concept may be relevant to clustered or variable measurements, but the registry record does not identify over-dispersion or state that a correction was used. It is not possible to infer the statistical model or its diagnostics from the endpoint description alone.

There are 6 outcome measures and 10 analyses listed. Multiple analyses can increase the chance of at least one apparently notable finding when many hypotheses are tested. General methods for addressing this include prespecifying a primary analysis or adjusting inference across a family of tests. The registry record identifies the primary endpoint but does not report a multiplicity strategy, a complete statistical analysis plan, or the results needed to assess how the listed analyses were interpreted.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("18F-Fluoride PET")
n   <- c(12)
m   <- c(-6.67)
sp  <- c(8.98)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  18F-Fluoride PET  12  -6.670  8.980  -12.376  -0.964

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 10 analyses. It identifies changes in tumor-bone SUVmax as the primary endpoint and lists changes in 18F-fluoride transport by Patlak flux in tumor and normal tissue among the secondary outcomes. With several outcomes or analyses, multiplicity is a general concern: the chance of at least one apparently unusual result can increase as more hypotheses are examined. The registry record does not report whether analyses were prespecified in a statistical analysis plan, whether testing was hierarchical, or whether any adjustment for multiple testing was used.

The primary analysis population is described as 37 bone locations in 12 eligible participants with interpretable pre- and post-treatment PET scans. Enrollment was 18. These figures describe enrollment and the population analyzed for the primary endpoint, but they do not explain why some enrolled participants were not included in that analysis. Reasons for unavailable or uninterpretable scans, the amount and pattern of missing data, and any imputation or sensitivity analysis are not reported in the registry record.

Restricting analysis to participants with interpretable scans at both occasions can affect interpretation if inclusion is related to the measurement or participant characteristics. This is a general missing-data concern; the registry record does not provide enough information to determine whether it applied or how it was handled.

The record does not report whether analyses used all available observations, participant-level summaries, or a model accounting for multiple bone locations per participant. It also does not report a separate analysis population for the secondary endpoints. These details are needed to judge how the analysis population, missing observations, and repeated or clustered measurements contributed to the results.

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 0% reporting threshold.

The registry lists an overall group of 18 participants at risk for serious adverse events and 0 participants affected. It also lists 18 at risk for other adverse events and 0 affected. These are the posted counts for the registry’s adverse-event categories; they do not describe the primary PET endpoint.

A count of zero affected means that no participants are recorded as having an event in that category in this registry record. It should not be read as proof that no adverse events occurred in any setting or under the concurrent protocol. The registry record does not provide serious adverse-event terms, and no top serious terms are listed. The deaths figure is not reported in the registry record.

These counts do not provide detail about event timing, duration, severity within the categories, or attribution to a particular treatment. Dasatinib was administered under a concurrent protocol and was not considered an intervention in this protocol. The adverse-event figures should therefore be interpreted as registry counts for this study record, not as a complete account of safety across treatment protocols.

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

The record establishes that the study assessed tumor-bone 18F-fluoride PET SUVmax at baseline and 12 weeks, and that the primary analysis population included 37 bone locations in 12 participants with interpretable paired scans. It also identifies the endpoint as a mean continuous measure and names standard deviation as the dispersion measure. These details clarify the measurement and the population contributing to the primary analysis.

The numerical primary result is not reported in the registry record. There is no reported estimate of mean change, standard deviation, confidence interval, or test result. It is therefore not possible to state whether SUVmax increased or decreased, how large any change was, or how precise the estimate was. The same lack of outcome results prevents interpretation of the listed secondary transport outcomes.

Even if a within-participant change were reported, the single-group design would describe change over time rather than provide a randomized comparison against a control group. It would not, by itself, establish that a change was caused by dasatinib. Dasatinib was administered under a concurrent protocol, rather than being the intervention in this protocol. The record also does not report whether the PET measure was associated with clinical outcomes.

Thus, the registry record supports a description of the study question, design, and analysis population, but not a conclusion about the direction or magnitude of the imaging result. A pharmacodynamic PET endpoint is not interchangeable with a clinical outcome. No statement about treatment effectiveness or lack of effectiveness follows from the information reported for this endpoint.

14. Why This Trial Matters Statistically

This study raises statistical questions that are important when imaging measurements are collected repeatedly and at multiple locations. The primary analysis uses observations from 37 bone locations in 12 participants. Since several locations may belong to the same participant, the analysis must distinguish the number of measured locations from the number of people contributing those measurements. In general, accounting for within-participant dependence is important for valid uncertainty estimates.

The before-and-after structure also calls for careful interpretation. A paired comparison can summarize how measurements changed within the analyzed units, but a single-group design does not create a randomized control comparison. Separating temporal change from treatment-associated change requires a design or assumptions beyond the observation of change alone.

The endpoint is an imaging biomarker rather than a clinical outcome. This distinction matters statistically as well as clinically: a measurable shift in an imaging value does not automatically establish that the biomarker predicts or reflects a patient-centered outcome. The registry record does not report an analysis linking SUVmax change to clinical outcomes.

Finally, the record lists multiple outcomes and analyses but does not report how multiplicity was handled or provide the endpoint estimates. Those omissions limit assessment of both statistical evidence and precision. The study’s design and analysis population are identifiable, but its main numerical finding cannot be evaluated from the registry record.

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 main limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The mean change, standard deviation, confidence interval, and statistical test result are absent. Consequently, the endpoint’s direction, magnitude, and precision cannot be judged.

The study has a single-group design, with no randomized comparator in this protocol. A change from baseline to 12 weeks would not by itself distinguish a treatment-associated change from other changes over time. Dasatinib was administered under a concurrent protocol and was not considered part of this protocol’s intervention.

The analysis population is smaller than the enrollment count: 37 bone locations in 12 eligible participants with interpretable pre- and post-treatment scans, compared with enrollment of 18. The registry record does not explain why participants or scans were not represented in the primary analysis, describe missing-data handling, or report sensitivity analyses. It also does not say how the dependence of multiple locations within a participant was handled.

The record lists 6 outcome measures and 10 analyses, but does not report a full statistical analysis plan or a multiplicity approach. The sample-size justification for the trial is not reported in the registry record. The listed planning illustrations are based on the observed effect and are not the trial’s own design. Finally, the record does not report whether the imaging endpoint was linked to clinical outcomes, limiting interpretation to the PET measurement itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fluorine F 18 Sodium Fluoride Positron Emission Tomography in Evaluating Response to Dasatinib in Patients With Prostate Cancer and Bone Metastases — NCT00936975.
• Registry record last updated 2015-07-16; status last verified 2014-12.
• Results first posted 2015-07-16.
• 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

NCT00936975 is a completed phase 2, single-group study sponsored by the National Cancer Institute. Enrollment was 18. The study evaluated fluorine F 18 sodium fluoride PET in men with castration-resistant prostate cancer and bone metastases. Participants had scans at baseline and 12 weeks after initiation of dasatinib, which was administered under a concurrent protocol and was not an intervention in this protocol.

The primary endpoint was change in tumor-bone 18F-fluoride PET SUVmax. Its analysis population comprised 37 bone locations in 12 eligible participants with interpretable pre- and post-treatment scans. Secondary outcomes included changes in 18F-fluoride transport by Patlak flux in tumor and normal tissue. The registry lists 6 outcome measures and 10 analyses.

The primary and secondary numerical results, missing-data procedures, multiplicity approach, and specific statistical analysis methods are not reported in the registry record. The serious adverse-event count lists 0 affected among 18 at risk; the deaths figure is not reported.