Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study (NCT02967458), a na phase 2 study. The primary outcome is Percentage of Subjects Whose Prostate Cancer Was Detected With Subharmonic Imaging.

2. Clinical Question

The study is titled “Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study.” Its brief summary describes a phase II, single-center investigation using contrast-enhanced ultrasound to identify aggressive forms of prostate cancer. The stated objectives include implementing subharmonic imaging on a transrectal probe suitable for prostate imaging and biopsy, demonstrating visualization of prostatic vascularity, and obtaining a preliminary estimate of diagnostic accuracy for clinically significant prostate cancer.

The biopsy setting supplies the clinical context for evaluating the imaging approach, but the registry record does not specify the diagnostic reference standard or how an imaging result would be compared with biopsy findings. It also does not define “clinically significant” or “high grade” for the primary analysis. The record therefore supports a description of the research question, but not a conclusion about diagnostic accuracy.

3. Trial Design

This is a completed phase II, single-center study with a single-group model. Allocation is listed as not applicable, and masking is listed as none. The registry reports enrollment of 55. Separately, the brief summary says the study will include 50 subjects, and the arm description refers to fifty patients. These entries do not explain the difference between the planned group described in the summary and the recorded enrollment.

Participants were scheduled for a clinically indicated prostate biopsy and were to receive an intravenous infusion of microbubble contrast material immediately before the biopsy procedure. The intervention list names Perflutren Lipid Microsphere Intravenous Suspension. The arm description says participants needed to be able to undergo contrast-enhanced transrectal ultrasound. The available arm-description text ends before completing the intervention details, so further administration or imaging procedures are not reported in the registry record.

The study began on 2017-02-01, reached primary completion on 2018-02-01, and has status “COMPLETED.” The primary outcome timeframe is one week from baseline. The record does not explain the visit schedule, the precise definition of baseline, or whether the one-week timeframe applies to every outcome.

Because there is no separate control arm, the design cannot make a randomized comparison between subharmonic imaging and another imaging strategy. It is suited to describing feasibility and preliminary observations within the enrolled group, subject to the outcome definitions and analysis methods. The registry lists three outcome measures, but the details available for the primary measure do not establish how imaging findings, vascularity visualization, and cancer detection were linked. The eligibility criteria, recruitment approach, and reasons for nonparticipation or withdrawal are not reported in the registry record.

The record gives the sponsor as Thomas Jefferson University. It does not report a sample-size justification, a protocol, or an analysis plan. Enrollment and completion status alone do not show how many participants contributed data to a particular outcome or whether all intended assessments were completed.

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

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 Percentage of Subjects Whose Prostate Cancer Was Detected With Subharmonic Imaging, measured over One week from baseline.

The primary outcome is titled “Percentage of Subjects Whose Prostate Cancer Was Detected With Subharmonic Imaging.” Its unit is participants, and its measurement type is a count of participants. The stated timeframe is one week from baseline. The description, however, says the initial phase will develop and test subharmonic imaging to demonstrate enhanced visualization of prostate vascularity in all study participants, and that the percentage with increased visualization will be reported.

This distinction matters. Cancer detection and increased visualization of vascularity are related concepts in the study rationale, but they are not interchangeable endpoint definitions. The registry record does not report a threshold for increased visualization, a rule for classifying an imaging result as cancer detected, or how the primary outcome title and description were reconciled. It also does not state the reference standard used to confirm cancer for this outcome.

In general, a binary participant-level endpoint classifies each participant according to whether a defined event or finding is present. A percentage can describe how common that classification was in the assessed group, while a count gives the number meeting the definition. The record identifies participants as the unit but does not post the primary outcome count or percentage. It therefore does not permit a numerical estimate of the endpoint or its precision.

Vascularity visualization could be a technical or imaging-performance measure, while cancer detection is a diagnostic-performance question. For interpretation, the distinction between those aims needs a clear operational definition and a stated comparison standard. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-level count represent?

The primary measure identifies participants as its unit and uses a count-of-participants measurement type. In general, a binary outcome assigns each assessed participant to one of two categories, such as meeting or not meeting a prespecified criterion. A count records how many meet the criterion; a percentage expresses that count relative to an appropriate denominator. The denominator should be the participants with the relevant assessment, not automatically everyone enrolled.

For this study, the registry does not report the primary count, percentage, or assessed denominator. It also does not specify the classification rule. The mismatch between the outcome title, which refers to cancer detection, and the description, which refers to increased vascularity visualization, makes that rule especially important. Without it, the intended endpoint cannot be reconstructed from the record.

Why does the outcome definition matter?

In general, a diagnostic study needs a clear definition of what counts as a positive imaging result and an appropriate reference standard for determining whether the condition is present. Measures such as sensitivity, specificity, and predictive values answer different questions and depend on the classification rules and observed data. A broad objective to estimate diagnostic accuracy is not itself an estimate. The registry record does not state the reference standard, thresholds, or diagnostic calculations for this study, and it posts no analysis results.

In general, a vascularity visualization measure may describe whether an imaging technique makes a feature more visible, whereas cancer detection concerns classification of disease. One can be a technical imaging objective without establishing the other. Interpreting a vascularity finding as evidence of cancer would require a prespecified link and validation against an appropriate standard; that link is not reported in the registry record.

What can a confidence interval tell a reader?

In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the statistical method. For a participant-level proportion, its width is influenced by the number of assessed participants and the observed distribution of outcomes. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. An interval does not correct an unclear endpoint definition, selection problems, or bias in measurement.

No primary estimate or confidence interval is reported in the registry record. Consequently, the precision of the study’s diagnostic or vascularity findings cannot be evaluated. A planned enrollment count is not a substitute for the number actually assessed, and the record does not state the analysis denominator.

How should a single-group study be understood?

In general, a single-group study describes outcomes within one group exposed to an intervention or procedure. Without a concurrent comparison group, it does not provide a randomized estimate of how outcomes would differ under another approach. A comparison to an external standard may be useful for a diagnostic question, but the methods and results for such a comparison need to be reported. The registry identifies no separate comparator arm and does not describe a reference-standard analysis.

The study’s stated aims include implementation of a transrectal subharmonic imaging technology, visualization of prostatic vascularity, and a preliminary estimate of diagnostic accuracy. These aims can involve distinct outcomes and methods. The record does not explain whether the primary measure was intended to assess technical visualization, detection, or both, nor how those aims were prioritized analytically.

What is not available about the analysis?

The registry reports three outcome measures and no analysis entries. No statistical analysis plan, model specification, missing-data approach, or interim analysis information is reported in the registry record. The record also does not say whether outcomes were analyzed as counts, proportions, or diagnostic-performance measures beyond the primary measure’s participant unit and count type.

In general, a statistical plan helps establish which outcomes are primary, how observations are classified, which participants enter each analysis, and how uncertainty is quantified. Prespecification can help distinguish planned analyses from exploratory ones. These concepts do not establish what this study actually did. The registry does not provide enough information to identify the methods used or assess whether the posted outcomes correspond to a prespecified plan.

The general sample-size assumptions associated with planning illustrations describe hypothetical planning choices, not the study’s own design justification or observed power. The registry record does not report the trial’s sample-size justification or its own statistical plan. Any planning illustration should therefore be treated as a hypothetical exercise and not as evidence about the trial’s analysis or ability to detect an effect.

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("1Prostate Biopsy Patients")
n      <- c(55)
events <- c(24)
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  1Prostate Biopsy Patients  55  24  43.6  30.3  57.7  31.4  56.7  31.3  56.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but the registry entries describe the primary measure only. The other outcome definitions, their timing, and their role in the analysis are not reported in the registry record. The record reports no analysis entries. It therefore does not show which outcomes were analyzed, whether additional analyses were planned, or how findings across outcomes were handled.

In general, multiplicity arises when several hypotheses or outcomes are examined. Considering many results can increase the chance that an apparently notable finding occurs by chance. A prespecified hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses can help readers understand that risk. None of those methods is reported in the registry record, so it is not possible to assess multiplicity handling for this study.

The registry reports enrollment of 55 and describes 50 subjects in the brief summary, but it does not report outcome-specific denominators, participant flow, or the number of participants with evaluable data. The analysis population for the primary measure is not reported in the registry record. Missing-data methods, reasons for missing observations, and handling of incomplete imaging or biopsy assessments are also not reported.

In general, missing observations can affect estimates when participants with unavailable data differ from those with complete assessments. The extent and direction of any such effect depend on why data are missing and on the analysis method. Since the registry gives no outcome results or missing-data account, this issue cannot be evaluated for the study.

12. 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 non-serious adverse event terms

The registry lists the Prostate Biopsy Patients group as having 55 participants at risk for serious adverse events, with zero affected. For other adverse events, it lists 55 at risk and 2 affected. The recorded number of deaths is zero. These are counts as entered in the registry, not comparative estimates.

The counts do not establish the nature, timing, duration, or severity of the other events. The list of serious-event terms is empty in the available record. The registry also does not describe the event-collection method, completeness of follow-up, or whether every participant was observed for the same period. The primary outcome timeframe is one week from baseline, but the safety follow-up period is not reported in the registry record.

In general, safety counts are most interpretable when readers know the definitions, observation window, denominator, and method of ascertainment. A count of zero serious events in one group does not demonstrate that the risk is absent, and a count of other events does not establish that the intervention caused them. The single-group design supplies no safety comparison group. These figures should therefore be read as limited descriptive reporting rather than as a comparative safety assessment.

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

The registry record describes a pilot investigation of subharmonic contrast-enhanced ultrasound in people scheduled for prostate biopsy. It records a completed phase II, single-center, single-group study and identifies objectives related to imaging implementation, vascularity visualization, and preliminary diagnostic accuracy. It also records limited adverse-event counts.

What the record does not establish is the observed ability of the imaging method to detect prostate cancer. No primary outcome result or diagnostic-accuracy estimate is reported. The primary outcome title and description refer to different concepts, and the registry does not provide enough detail to determine the operational endpoint or its relationship to biopsy findings. Without an outcome definition, numerator, denominator, and analysis, a result cannot be interpreted or assigned a degree of precision.

The study design also limits the claims that could be made from within-group observations. A single group does not provide a randomized comparison with another imaging method or a no-imaging condition. The stated diagnostic objective would require a clearly described reference standard and analysis, which are not reported in the registry record. These are reporting gaps, not evidence that the study did or did not demonstrate a useful imaging signal.

The enrollment entry and the planned group described in the brief summary are not identical, and the record does not explain the difference. Enrollment does not indicate how many participants had usable imaging or complete outcome assessments. Likewise, the safety counts are descriptive and do not establish causation or comparative risk.

In general, a pilot study can inform feasibility and help refine measurement methods, but whether it did so depends on results and methods that must be reported. The registry record identifies relevant questions and records completion, yet does not supply the primary findings needed to answer them. The appropriate interpretation is therefore limited to the study’s design and the information actually recorded, not a conclusion about diagnostic performance.

14. Why This Trial Matters Statistically

This study is statistically notable because its stated aims span technical imaging development, visualization of prostate vascularity, and diagnostic accuracy. Those aims are connected but require clearly distinguished outcomes. A measure of whether vascularity is more visible does not, on its own, quantify whether cancer is detected. The registry’s primary outcome title and description make the distinction especially important for interpreting any eventual estimate.

The study also illustrates why a diagnostic question needs more than a single-group design label and an endpoint title. To interpret performance, readers need an operational definition of a positive imaging finding, a stated reference standard, the number assessed, and results with measures of uncertainty. The record does not report these details or a primary result. Without them, statistical precision and the meaning of any observed finding cannot be evaluated.

At the same time, a single-group pilot can address early questions about implementing an imaging approach in a biopsy setting. The stated objectives include developing subharmonic imaging on a transrectal probe and demonstrating prostatic vascularity visualization. The record captures those aims, but it does not provide results that would establish how successfully they were met.

The discrepancy between the planned group described in the summary and the recorded enrollment is another reminder that enrollment is not necessarily the analysis denominator. Participant flow and outcome-specific data availability are needed to understand who contributed to each estimate. The absence of analysis entries and primary results leaves those questions unresolved.

These issues are consequential because diagnostic findings can influence how a technology is evaluated. Clear definitions and complete reporting let readers distinguish a technical imaging signal from validated detection performance, and distinguish descriptive observations from comparative evidence. The registry record identifies the intended scientific questions but does not contain enough outcome information to resolve them.

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 most important limitation of the available record is the absence of posted primary outcome results. It gives no count or percentage for the primary measure and no diagnostic-accuracy estimate. The analysis population and denominator are not reported, so the recorded enrollment cannot be assumed to represent participants with evaluable outcomes.

The primary measure is not fully clear from its title and description. The title refers to prostate cancer detection; the description refers to increased visualization of prostate vascularity. The record does not report how either finding was defined, whether the two were linked, or how imaging observations were checked against biopsy results. It does not define high-grade or clinically significant cancer for analysis.

The record identifies a single-group design without a comparator and does not describe the diagnostic reference standard. This prevents assessment of any comparative performance and leaves the basis for diagnostic classification unclear. The stated study objectives may include feasibility and imaging visualization, but results for those objectives are not reported either.

The brief summary describes 50 subjects, while enrollment is recorded as 55. The record does not explain the difference. It also does not report participant flow, reasons for withdrawal or missing assessments, outcome-specific sample sizes, or a missing-data approach. Although the study is marked completed, completion status does not resolve these questions.

Further limitations of interpretation include the absence of a reported statistical plan, analysis methods, and analysis entries. The registry’s safety counts lack event terms and detail about ascertainment and follow-up. These limitations concern what can be learned from the registry record; they do not establish whether additional information exists elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study — NCT02967458.
• Registry record last updated 2025-04-30; status last verified 2025-04.
• Results first posted 2019-05-21.
• 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

This completed phase II, single-center, single-group study evaluated subharmonic contrast-enhanced ultrasound in people scheduled for prostate biopsy. The registry lists enrollment of 55 and describes a planned group of 50 in the brief summary. Participants were to receive intravenous microbubble contrast material before biopsy. The primary outcome timeframe is one week from baseline.

The study aimed to implement subharmonic imaging, visualize prostatic vascularity, and obtain a preliminary diagnostic-accuracy estimate. The primary outcome title refers to cancer detection, while its description refers to increased vascularity visualization. Primary results, analysis methods, the analysis population, and the relationship between imaging findings and biopsy results are not reported in the registry record.

Safety entries list zero serious events among 55 at risk, 2 other events among 55 at risk, and zero deaths. The record does not provide further event details. No analysis entries are listed.