F-18 Sodium Fluoride in Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for F-18 Sodium Fluoride in Prostate Cancer (NCT01240551), a non-randomized phase 2 study. The primary outcome is Number of Participants With Present or Not Present Bone Metastasis.

2. Clinical Question

The study's stated objectives were to evaluate imaging measurements of bone tumors, compare those measurements with clinical course, and determine the smallest amount of change that the imaging method can accurately measure. These are measurement and imaging questions, rather than a test of whether a treatment improves a clinical outcome. F-18 NaF is taken up in bone, with greater uptake in areas of more active bone change; the registry's definition classifies uptake greater than normal as present bone metastasis and physiological uptake as not present, excluding traumatic and degenerative foci of increased uptake.

The two groups differ by clinical status before the imaging assessment. Therefore, a contrast between them would not by itself show that imaging caused a difference or establish diagnostic accuracy against an independent reference standard. The registry record does not report a diagnostic accuracy result or the primary endpoint counts by group and time point.

3. Trial Design

This was a phase 2, completed, non-randomized, unmasked, parallel-group study sponsored by the National Cancer Institute (NCI). The registry lists enrollment of 60. The study began on 2010-11-30, with primary completion on 2013-05-31. Participants were assigned to groups according to known bone-metastasis status rather than randomized to different imaging strategies: one group had known bone metastases, and the other had no clinical evidence of bone metastases.

Both groups underwent F-18 NaF PET/CT. The brief description says participants had two separate-day scans at baseline, intended to help assess measurement variability. The primary outcome timeframe describes imaging sessions at baseline, between 4-6 months, and between 10-12 months. The registry record does not report further details about the schedule, adherence, or the number of scans actually completed by participants.

The study is described as a pilot evaluation of metastatic-burden qualification. The stated objectives include measuring bone tumors and change over time, comparing imaging with clinical course, and identifying the smallest reliably measurable change. The registry record does not report the operational protocol for making those comparisons, a prespecified threshold for measurable change, or a sample-size justification.

Because allocation was non-randomized and the arms represent different baseline clinical groups, they should not be read as treatment and control arms in a randomized trial. Any differences in their imaging findings could reflect their differing clinical status as well as other factors. The record does not report adjustment methods intended to address such differences. It lists a secondary outcome for participants with adverse events, but does not provide an inferential analysis for that outcome.

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: Patient with known prostate cancer. One group with known metastatic bone disease, based on prior clinical imaging scan (Tc-99m bone scan or NaF-18 bone scan or CT, and a second group with clinical risk factors for obtaining bony metastatic disease (i.e. pelvic soft tissue mets, high PSA (prostate specific antigen) blood levels).

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 of Participants With Present or Not Present Bone Metastasis, measured over Single imaging sessions will be acquired at baseline, between 4-6 months and between 10-12 months on emolument..

The primary endpoint is the number of participants classified as having present or not present bone metastasis on NaF PET/CT. The registry defines present metastasis as greater than normal bone uptake. Not present metastasis is defined as physiological F-18 NaF uptake, excluding traumatic and degenerative foci of increased uptake. The measure is therefore a participant count based on imaging classification, not a continuous measure of lesion size or a direct measure of clinical benefit.

The endpoint is relevant to the study's imaging objective: it records whether the scan identifies bone-metastasis status at designated imaging sessions. The stated time points are baseline, between 4-6 months, and between 10-12 months. Repeated imaging can support assessment of change over time, while repeat baseline scans are described as a way to examine measurement variability. In general, repeatability matters because a change in a scan measurement is more interpretable when ordinary variation in measurement is understood.

The registry record does not report the number classified in each category at each time point, a formal estimate of sensitivity or specificity, or an estimate of the smallest reliably detectable change. It also does not report a numerical comparison with clinical course. Consequently, the endpoint definition can be described, but the magnitude and precision of the primary findings cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a non-randomized, parallel-group study with no masking. In general, randomization helps balance measured and unmeasured baseline characteristics across groups on average. Without randomization, group differences may reflect the clinical characteristics used to define the groups or other factors. Here, the groups are expressly distinguished by known bone-metastasis status versus no clinical evidence of bone metastases. The registry record does not report a statistical adjustment strategy for group comparisons, so an adjusted interpretation cannot be reconstructed.

What does the primary measure count?

The outcome is a count of participants assigned an imaging classification: present or not present bone metastasis. The record defines present disease as greater than normal uptake and describes not present disease as physiological uptake, excluding traumatic and degenerative uptake foci. This is a categorical classification. In general, categorical endpoints summarize how many people fall into each category; they do not convey lesion size or the degree of uptake unless those are separately measured and reported.

The timeframe names baseline and follow-up imaging between 4-6 months and between 10-12 months. The brief description also says two scans on separate days were planned at baseline. Repeating a measurement can help characterize within-person variation. In general, if repeated scans differ even when biological status has not changed, that variation affects how confidently a later difference can be interpreted as real change. The record does not report the repeatability estimates, the method used to quantify change, or a minimum change threshold.

How should the planning illustration be understood?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a fraction of the observed effect. In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen probability, if the assumptions hold. It is not an analysis of what the enrolled participants actually experienced.

The record's planning description explicitly identifies the illustration as separate from the trial's own design. It should not be read as observed power, nor as evidence that the study was originally sized using those assumptions. The registry record does not report a sample-size justification for the trial. No numerical planning estimates are stated in the registry record summarized for interpretation, so no participant requirement can be inferred from the assumptions alone.

In general, a normal approximation simplifies calculations by treating an estimate's sampling distribution as approximately normal. Whether that is adequate depends on the endpoint and data. Counts or proportions based on small numbers can have discrete and asymmetric uncertainty. The registry record does not report the precise statistical procedure used for the primary endpoint, so it is not possible to determine how uncertainty was calculated or whether an approximation was used in the actual analysis.

What can be concluded from the reported analyses?

The registry lists no analyses. It gives an endpoint definition and describes an imaging schedule, but does not post primary endpoint results by group and time point, an estimate of change, or uncertainty intervals. In general, an estimate describes the observed magnitude, while an interval conveys uncertainty about that estimate under the chosen model. Without either, there is no numerical basis for assessing the precision of the imaging findings from the registry record.

The record also does not report a diagnostic accuracy analysis. In general, evaluating diagnostic accuracy requires a stated reference standard and a comparison of imaging classifications with that standard. The description says prior clinical imaging could identify known metastatic bone disease, but it does not specify an analysis comparing the NaF PET/CT classification with an independent reference standard. No sensitivity, specificity, predictive value, or agreement statistic is reported.

For safety, the record provides numbers at risk and numbers affected by serious and other adverse events, along with a list of top serious terms. These are descriptive counts. In general, a formal comparison would need a defined analysis population, event definitions, follow-up time, and a statistical method. The record does not report an inferential safety comparison, event attribution, or detailed exposure-adjusted rates. Thus the safety counts can be presented as recorded, but should not be stretched into a comparative effect estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and names the primary endpoint as participants with present or not present bone metastasis. A secondary outcome is the number of participants with adverse events. It does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment for testing multiple outcomes or time points. In general, when several hypotheses are tested, the chance of at least one false-positive finding can increase unless the analysis plan accounts for multiplicity. No claim about such adjustment can be made from this record.

The record does not report a missing-data method, the number of participants with missing imaging at any visit, or how incomplete follow-up was handled. Repeated imaging studies can have missing observations when a participant does not complete a planned scan. In general, complete-case analyses and other approaches rely on assumptions about why observations are missing; those assumptions affect interpretation. The registry record does not identify an approach or permit assessment of those assumptions.

The analysis populations are not reported in the registry record. It is therefore unclear which enrolled participants contributed to each outcome or whether all participants were analyzed according to their original group classification. The record also does not report prespecified interim analyses, a statistical analysis plan, or a plan for handling deviations from the imaging schedule. These details should not be inferred from the phase, design label, or stated objectives.

Since the record lists no analyses, it also does not give hypothesis tests, confidence intervals, or a specified model for the primary endpoint. The registry's planning illustration does not fill these gaps: planning calculations are distinct from methods used to analyze collected observations. Interpretation is consequently restricted to the endpoint definitions and descriptive counts that are actually posted.

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: atrial fibrillation (3.3%), renal calculi (3.3%), syncope (3.3%).

The registry lists serious adverse events separately for the two clinical groups. In the group with known bone metastases, 30 participants were at risk and one was affected by a serious adverse event; in the group with no clinical evidence of bone metastases, 30 were at risk and none was affected by a serious adverse event. The record lists zero deaths in both groups. These are counts, not a randomized safety comparison.

The registry lists atrial fibrillation, renal calculi, and syncope as top serious adverse event terms, each at 3.3%. It does not identify those terms by group in the listed summary, so they should not be assigned to a particular arm. Other adverse events are also reported: one participant in each group is listed as affected, with 30 at risk in each group.

In general, an adverse event is not necessarily caused by the study procedure; attribution requires specific information. The registry record does not report the causal relationship, severity details beyond the serious-event classification, timing, duration, or event-level narratives. The counts therefore describe what is posted, but do not establish causation or support a precise comparison of risk. The non-randomized group definitions further limit comparative interpretation.

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

The study addresses a measurement question: whether F-18 NaF PET/CT can classify bone-metastasis status and help characterize bone changes over time in people with prostate cancer. The registry defines how present and not present bone metastasis were classified and describes imaging at baseline and follow-up. It also states an objective of identifying the smallest change that can be measured accurately. Those aims are distinct from testing whether a treatment changes health outcomes.

The registry record does not report the primary endpoint counts by group and time point, a quantified change in imaging findings, or a result for the smallest accurately measurable change. It therefore does not allow a reader to determine the observed imaging performance or its precision. No diagnostic accuracy statistics or confidence intervals are reported. A definition of an endpoint is not itself evidence of how well the measurement performed.

The groups were formed according to clinical evidence of metastasis, not random allocation. Their characteristics and imaging findings should not be treated as a causal treatment contrast. The record does not report adjusted comparisons that would address differences between groups. Likewise, the adverse event counts are descriptive and do not show that the imaging procedure caused or did not cause an event.

In general, a statistically interpretable finding requires both an estimate and a description of uncertainty, together with enough information about the analysis to understand what population and comparison it represents. Here, the registry supplies the design description, outcome definition, and some safety counts, but not the primary analysis results or the analysis methods. The posted information can clarify what the investigators intended to measure; it cannot establish the magnitude, reproducibility, or clinical meaning of the measured changes.

13. Why This Trial Matters Statistically

This study is statistically interesting because it treats imaging as a measurement process, not simply as a way to label disease at one point in time. Its stated objectives include examining bone tumors and change over time and determining the smallest accurately measurable change. Those questions depend on separating genuine change from variation in image acquisition and interpretation. The plan for two separate-day baseline scans reflects the relevance of repeatability, although the registry record does not report repeatability results.

Repeated measurements also raise design and analysis questions. In general, observations from the same person are related, so methods that treat every scan as independent may misrepresent uncertainty. The registry record does not report how repeated observations were analyzed. Nor does it describe how changes in clinical status, incomplete visits, or varying observation intervals were handled. These omissions matter when the objective concerns change over time rather than a single classification.

The non-randomized grouping is another important statistical feature. Known metastasis status and no clinical evidence of metastases define clinically distinct groups; differences between them should not be attributed to the imaging procedure. The distinction can be useful for exploring whether the imaging measure behaves differently across clinical contexts, but the record does not post results that permit that assessment.

Finally, the gap between clearly stated measurement aims and the absence of posted primary analyses illustrates why endpoint definitions alone are insufficient. Counts, estimates, and uncertainty measures are needed to assess performance. The record enables readers to identify the intended questions and important design constraints, while leaving the central quantitative imaging findings unreported.

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 registry record does not report primary endpoint results by group or time point, although it defines the endpoint and names the imaging intervals. It also does not report a numerical estimate of change, a smallest accurately measurable change, or a comparison between imaging findings and clinical course. These omissions prevent assessment of the study's central measurement objectives from the record.

The groups were not randomized and were defined by clinical metastasis status. The registry record does not report baseline characteristics beyond those group descriptions or methods to adjust for differences between groups. Accordingly, any unreported group contrast could not be interpreted as though allocation had created comparable arms.

The record does not report the reference standard or a formal diagnostic accuracy analysis. It does not provide sensitivity, specificity, agreement, or confidence intervals. It also does not describe who interpreted the scans, whether interpretation was independent, or how disagreements were resolved. These details are not reported in the registry record and should not be assumed.

Although repeated scans are described, the record does not report how many participants completed each scan, the amount of missing data, adherence to the schedule, or the methods used to analyze repeated measures. It does not report a statistical analysis plan, multiplicity handling, analysis populations, or sample-size justification. Finally, safety reporting is limited to aggregate counts and listed terms; attribution, timing, and event-level context are not reported. Together, these limits constrain both the statistical and clinical interpretation of the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: F-18 Sodium Fluoride in Prostate Cancer — NCT01240551.
• Registry record last updated 2017-11-06; status last verified 2017-10.
• Results first posted 2014-12-24.
• 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.

18. Record Summary

The registry record describes NCT01240551, “F-18 Sodium Fluoride in Prostate Cancer,” a completed phase 2, non-randomized, unmasked, parallel-group imaging study sponsored by the National Cancer Institute (NCI). Enrollment was 60. The listed groups were patients with known bone metastases and patients with no clinical evidence of bone metastases.

The primary endpoint was the number of participants classified by NaF PET/CT as having present or not present bone metastasis. The stated imaging timeframe included baseline, between 4-6 months, and between 10-12 months. A secondary outcome concerned participants with adverse events. The registry lists serious adverse event counts and zero deaths in both groups.

Primary outcome counts, statistical analyses, confidence intervals, missing-data methods, and a sample-size justification are not reported in the registry record. The posted information therefore supports description of the design, endpoint definitions, and safety counts, but not a quantitative conclusion about imaging performance or change over time.