Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy (NCT02115607), a na na study. The primary outcome is Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders.

2. Clinical Question

The study also examines whether subharmonic imaging can depict breast cancer angiogenesis. Imaging is described at baseline, during treatment, and after treatment completion. The brief summary describes measurements around 10% and 60% of treatment in part 1, or 30% in part 2, as well as after completion. The primary outcome description refers to baseline and measurements around 10% and 30% of treatment, with comparison to MRI and pathology. The registry record does not explain the reason for the different part-specific schedules.

This is a diagnostic accuracy and monitoring question, not a randomized test of whether one treatment is better than another. The registry record does not report numerical accuracy measures, associations with pathology, or evidence that SHAPE tracked changes. The question is therefore about what the imaging measure records over treatment and how those measurements relate to the reference assessments, not about a treatment effect against a control group.

3. Trial Design

The study is registered as a completed, single-group study with enrollment of 17. Allocation is listed as not applicable, masking as none, and phase as not applicable. These design features mean that the record does not describe randomized assignment, blinding, or a parallel comparison group. The listed intervention is infusion of Definity, an ultrasound contrast agent.

The brief summary describes women with locally advanced breast cancer undergoing neoadjuvant chemotherapy. SHI and SHAPE were to be used with the contrast agent at baseline, during chemotherapy, and after completion. The schedule is described as around 10% and 60% of treatment in part 1, or around 30% in part 2, with an additional post-treatment assessment. The primary outcome description instead specifies baseline and around 10% and 30% of treatment, and gives an average timeframe of 6 months from baseline to completion. The registry record does not provide further detail explaining the schedules or how the two parts were assigned.

MRI and pathology are named as comparison assessments in the study summary and primary outcome description. No numerical comparison results are reported in the registry record. The record identifies secondary outcomes concerning SHI depiction of angiogenesis for complete and partial responders, but does not give their numerical results.

The study started in 2014-03, had primary completion on 2018-05-23, and is marked completed. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University. Six participants were not counted in the data analysis: 2 because of technical issues, 2 who withdrew due to worsening of underlying disease, and 2 who stopped neoadjuvant chemotherapy unexpectedly. The registry record does not report the full analysis plan, the number included in each outcome analysis, or how incomplete measurements were handled.

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: six participants were not counted in the data analysis. 2 due to technical issues, 2 withdrew due to worsening of underlying disease, and 2 stopped their nedoadjuvant chemotherapy treatment unexpectedly. Data presented below is for those who achieved Complete Response (CR)

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 Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders, measured over from baseline to completion of neoadjuvant chemotherapy, average of 6 months.

The primary endpoint is titled SHAPE After Treatment for Complete Responders. It is a continuous measure in dB, with the outcome parameter described as a mean and dispersion described as a standard deviation. The timeframe is from baseline to completion of neoadjuvant chemotherapy, an average of 6 months. SHAPE is intended to estimate interstitial fluid pressure using ultrasound contrast imaging; the study asks whether the measure can track changes during treatment.

In general, a continuous measure retains gradations in the observed quantity rather than reducing it to categories. A mean describes the central value of measurements for the analysis population, while a standard deviation describes how spread out individual measurements are around that mean. Neither quantity by itself establishes whether measurements correspond closely to MRI or pathology. That requires results from the comparison and an interpretation of the measurement scale.

The outcome title identifies complete responders, and the registry says the presented data are for participants who achieved complete response. The numerical mean, standard deviation, number analyzed for this outcome, and any estimate of change are not reported in the registry record. The direction and precision of any observed change therefore cannot be assessed from the record. The registry also does not define a threshold for a meaningful change or provide numerical validation against MRI or pathology.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help frame the stated outcome, even though the numerical primary result and a detailed analysis plan are not reported in the registry record. These are general explanations, not descriptions of analyses confirmed to have been performed.

What does a mean and standard deviation describe?

The primary outcome is a continuous measure in dB, summarized using a mean and standard deviation. In general, the mean describes the center of a set of measurements. The standard deviation describes the extent to which measurements vary around that center. A mean alone can conceal substantial variation between participants, while a standard deviation alone does not identify the central value. Neither tells the reader whether a change is clinically or diagnostically important unless the scale and the intended interpretation are established.

The record does not report the numerical mean or standard deviation for the primary outcome, nor does it provide individual measurements or a distribution plot description. It is therefore not possible to assess skew, outliers, or whether the mean is a representative summary. In general, extreme observations can affect a mean more than a median. Whether another summary would be useful depends on the observed data and the prespecified analysis plan, which is not reported in the registry record.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the statistical assumptions used to calculate it. It communicates precision as well as a point estimate: a narrower interval indicates greater precision under those assumptions, while a wider interval indicates more uncertainty. A confidence interval does not show that every value in its range is equally plausible, and it does not resolve bias from missing data, selection, or measurement error.

No confidence interval for the primary outcome is reported in the registry record. Consequently, the precision of the estimate cannot be evaluated. The record also does not report a p-value or a formal hypothesis test for this outcome. A p-value, if reported, would address compatibility with a specified null hypothesis under the test assumptions; it would not by itself measure diagnostic accuracy, the size of an effect, or clinical importance.

How should repeated measurements be understood?

The study description includes measurements at baseline, during treatment, and after completion. In general, repeated measurements from the same participant are correlated: observations from one person are not independent observations in the way measurements from different people may be. An analysis of change over time should account for that within-participant structure. Possible approaches in general include modeling repeated measurements or analyzing a defined change from baseline, but the registry record does not report which approach was used.

The primary outcome timeframe describes baseline to completion, while the description also mentions measurements around 10% and 30% of treatment. The brief summary gives a different schedule for part 1 and part 2. The record does not state whether intermediate measurements contributed to the primary analysis, how timing variation was handled, or whether the primary contrast was a single endpoint value or a change from baseline. Those details matter because different choices answer different questions.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. A model that underestimates variability can produce intervals that are too narrow and tests that appear more decisive than the data justify. This concept is especially relevant when a model imposes a particular distributional structure, but the registry record does not describe a model, report a dispersion assessment, or provide data that would establish whether over-dispersion arose. It should not be inferred from the outcome’s use of a standard deviation.

What can a planning illustration tell readers?

Any sample-size planning illustration should be distinguished from the study’s observed outcome and from its original design. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect described as a fraction of the observed effect. The record explicitly frames this as a planning illustration rather than the trial’s own design. The actual study is single-group, so the equal-allocation assumption is not a description of its allocation.

In general, such calculations ask how many participants per arm might be needed under the assumptions and effect size chosen. They do not show that a study had a particular probability of detecting an effect after data collection, and they are not observed power. The numerical planning results are not reported in the registry record, and the numerical observed effect needed to interpret the illustration is also not reported. No sample-size justification for the actual study is reported in the registry record.

The registry lists no analyses. It does not report whether confidence intervals, repeated-measures methods, adjustments for multiple outcomes, or sensitivity analyses were used. Statistical concepts can clarify what would be relevant to judge, but they cannot substitute for results or methods that the record does not report.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome concerning SHAPE after treatment for complete responders and secondary outcomes concerning SHI depiction of angiogenesis for complete and partial responders. It also lists 4 outcome measures, while no analyses are listed. The registry record does not describe how the outcomes were prioritized in statistical testing, whether any multiplicity adjustment was planned or used, or how a family of comparisons was defined. The absence of those details means the risk of chance findings across multiple analyses cannot be assessed from the record.

Multiplicity is a general statistical concern when many outcomes, time points, or subgroup comparisons are examined. If each is tested separately, the chance of at least one apparently notable result can increase. Prespecifying a primary outcome and analysis can help define the main inference, while adjustment methods or a clearly exploratory interpretation can address additional comparisons. These general principles do not establish what was done in this study. The analysis strategy is not reported in the registry record.

For missing data, the registry states that six participants were not counted in the data analysis: 2 due to technical issues, 2 withdrew due to worsening of underlying disease, and 2 stopped neoadjuvant chemotherapy unexpectedly. It does not report the number available for each outcome, whether the exclusions applied uniformly, or whether partial measurements were retained. Imputation, complete-case analysis, and sensitivity analyses are not described.

In general, missingness can affect interpretation when the reasons for missing measurements are related to the outcome or to participant characteristics. Technical problems may affect which measurements are observed, while withdrawal and treatment cessation may select a different analysis population from the enrolled population. The registry does not provide enough information to determine the direction or extent of any such effect. It also does not report a formal analysis population definition beyond the statement that primary outcome data presented are for complete responders.

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.

The registry lists one Definity Infusion group, with 17 participants at risk for serious adverse events and 0 affected. It also reports 17 at risk for other adverse events and 0 affected. The deaths field reports 3. These are distinct reported entries: a count of deaths should not be treated as a count of serious adverse events or other adverse events unless the registry record explicitly connects them.

The record does not identify causes of death, timing, relationship to Definity, or relationship to chemotherapy. It does not report whether the deaths occurred during the safety observation period or after it, and it gives no further narrative about the events. No serious adverse event terms are listed. The zero counts therefore describe the registry’s event entries; they do not establish that no clinically important events occurred in every sense, nor do they explain the reported deaths.

In general, safety counts need context about definitions, follow-up duration, attribution, and completeness of reporting. The registry record does not provide those details. The reported counts should be read as descriptive entries for the listed group, not as a comparison with another group or as evidence that the infusion caused or did not cause any event.

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

The registry record documents a completed study designed to examine SHI and SHAPE with Definity during neoadjuvant chemotherapy. It identifies a continuous SHAPE outcome in dB for complete responders and names MRI and pathology as comparison assessments. Those details establish the study’s question and intended measurements, but they do not establish what the results were.

The numerical primary outcome result, its standard deviation, and any estimate of precision are not reported in the registry record. Numerical results for the secondary outcomes and comparisons with MRI or pathology are also not reported. It is therefore not possible to say from this record whether the imaging measures changed, how large any change was, how consistently participants’ measurements behaved, or how closely the measures corresponded with the comparison assessments.

The study has no randomized control group. In general, a single-group design can describe observed measurements and their change over time, but it does not provide a concurrent control for separating treatment-associated change from other time-related influences. Further, the primary outcome description focuses on complete responders; that result, even if numerically reported, would not automatically describe participants with partial response or the full enrolled group.

The registry reports that six participants were not counted in the data analysis and gives reasons, but does not describe the handling of missing measurements or the exact analysis populations. This limits assessment of whether the analyzed participants represent those enrolled. No conclusion about diagnostic performance, clinical benefit, or treatment effectiveness follows from the design description alone.

The defensible conclusion from the registry record is narrow: it describes a study intended to monitor imaging measures during chemotherapy and lists its endpoint definitions and selected safety counts. Whether the methods achieved the stated monitoring aims cannot be judged without numerical outcome results and further analysis details, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises a useful statistical question: whether imaging measurements can follow biological changes over the course of treatment, and how those measurements relate to MRI and pathology. That question involves more than detecting a difference in an average. It also concerns repeatability, participant-to-participant variation, timing of measurements, and agreement with assessments used for comparison.

The single-group, longitudinal setting makes the analysis structure important. Measurements taken repeatedly from one participant are related, and the timing of an observation can affect its interpretation. A clear definition of the endpoint, analysis population, and method for handling incomplete follow-up is therefore central to understanding any estimate. The registry identifies a primary outcome and reports exclusions, but does not give the analysis details needed to evaluate these choices.

It also matters that the primary outcome is described for complete responders. Restricting attention to a response-defined subgroup can answer a focused descriptive question, but it does not by itself establish performance across the broader population or across response categories. Generalizability depends on who was analyzed and how that subgroup was defined; those details are not fully reported in the registry record.

Finally, a monitoring study should be interpreted through the numerical results and their uncertainty, not only through its stated objective. Means and standard deviations, together with appropriate precision estimates and comparisons to reference assessments, would help readers evaluate the data. The registry record does not report those numerical results. Its statistical importance therefore lies in the questions it frames and in the need for transparent longitudinal and missing-data methods, rather than in evidence of a particular imaging result.

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 main limitation for statistical interpretation is that numerical primary and secondary outcome results are not reported in the registry record. The reader cannot evaluate the size or direction of SHAPE measurements, their variability, or their precision, nor can the relationship to MRI or pathology be assessed from numerical comparisons. The record also does not report numerical diagnostic accuracy measures.

The study is single-group, has no masking, and has no randomized control group. This design can describe observations over time, but it does not provide a control-based estimate of change. The brief summary and primary outcome description give different intermediate measurement schedules: part 1 is described with measurements around 10% and 60%, part 2 around 30%, while the primary outcome description mentions around 10% and 30%. The registry does not explain how those schedules relate or how timing was handled in analysis.

The primary outcome is focused on complete responders, but the number of complete responders analyzed and the numerical result are not reported. Six participants were not counted in the data analysis for technical issues, withdrawal due to worsening underlying disease, or unexpected treatment cessation. The record does not say how missing data were handled, whether exclusions differed by outcome, or whether sensitivity analyses were performed.

The registry lists 4 outcome measures but no analyses. It does not report the statistical analysis plan, a sample-size justification for the actual study, a multiplicity strategy, interim analyses, or model diagnostics. The planning assumptions are illustrative and do not describe the actual single-group design. The record also provides limited context for the safety entries, including no reported event timing, causes, or attribution for the 3 deaths.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy — NCT02115607.
• Registry record last updated 2025-05-06; status last verified 2025-05.
• Results first posted 2019-10-31.
• 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

NCT02115607 is a completed, single-group study of quantitative subharmonic imaging and SHAPE with Definity in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Enrollment was 17. The primary outcome is SHAPE after treatment for complete responders, a mean continuous measure in dB, with standard deviation specified as the dispersion and an average timeframe of 6 months from baseline to treatment completion.

The record names MRI and pathology as comparison assessments and lists secondary outcomes on SHI depiction of angiogenesis for complete and partial responders. Six participants were not counted in the data analysis for technical issues, worsening underlying disease, or unexpected cessation of chemotherapy. Numerical outcome results and detailed analysis methods are not reported in the registry record. Safety entries list 0 serious adverse events, 0 other adverse events, and 3 deaths among the Definity Infusion group.