A Study Assessing the Safety and Effectiveness of IC2000 and SPY Fluorescence Imaging Systems (SPY-PHI) in the Visualization of Lymphatic Vessels and Identification of Lymph Nodes During Sentinel Lymph Node Biopsy in Subjects With Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Assessing the Safety and Effectiveness of IC2000 and SPY Fluorescence Imaging Systems (SPY-PHI) in the Visualization of Lymphatic Vessels and Identification of Lymph Nodes During Sentinel Lymph Node Biopsy in Subjects With Breast Cancer (NCT03200704), a na phase 3 study. The primary outcome is Proportion of Lymph Nodes Identified by IC2000/SPY-PHI Compared to the Proportion of Lymph Nodes Identified by Tc99m/Gamma Probe.

2. Clinical Question

The study is described as a non-inferiority study. That label indicates the intended question was whether the fluorescence approach could identify lymph nodes without being worse than the comparator by more than a prespecified margin. The margin and the analysis needed to evaluate it are not reported in the registry record. Without the observed comparison, its uncertainty, and the margin, the non-inferiority question cannot be answered from this record.

The clinical context is sentinel lymph node biopsy in subjects with breast cancer. The study assesses visualization during lymphatic mapping and surgery, not a patient-centered outcome such as recurrence or survival. Those outcomes are not reported in the registry record.

3. Trial Design

This is a Phase 3, prospective, open-label, multicenter, single-group study. The registry lists enrollment of 152 and gives the status as completed. The recorded start date is 2019-01-04, and the primary completion date is 2020-08-27. The sponsor is Novadaq Technologies ULC, now a part of Stryker.

The study is described as a non-inferiority within-patient comparison. Participants received Tc99m radioactive colloid as standard of care, and IC2000 was used with SPY-PHI for intraoperative fluorescence visualization. The comparison was with Tc99m and a Gamma Probe, with identification assessed in the same participant rather than through randomized assignment to separate treatment arms. The registry lists allocation as not applicable and masking as none.

This design permits comparison of the two identification approaches within the study setting, but it is not a randomized, parallel-group trial. A within-patient comparison can reduce the influence of differences between participants when assessing the methods, while still depending on how the methods were applied and how the outcome was defined and analyzed. The registry record does not report procedural details sufficient to assess those issues fully.

The primary endpoint is described as the proportion of lymph nodes identified by each method, with the timeframe running from Tc-99m injection to completion of surgery. The listed analysis populations are PP and mITT. Definitions of those populations, the non-inferiority margin, and detailed analysis procedures are not reported in the registry record. Nor does the record report the number of participants contributing data to either population or the number of lymph nodes observed and identified.

Completion status and the enrollment entry do not, by themselves, establish how many participants had usable endpoint data or how many were included in a particular analysis. Those details, along with the primary comparison estimate, 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: PP and mITT populations

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: Total enrollment (N=152) \*PP and mITT population (N=148)

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Lymph Nodes Identified by IC2000/SPY-PHI Compared to the Proportion of Lymph Nodes Identified by Tc99m/Gamma Probe, measured over From Technetium-99 (Tc-99m) injection to the completion of surgery.

The primary outcome compares the proportion of lymph nodes identified by IC2000/SPY-PHI with the proportion identified by Tc99m/Gamma Probe. The unit is lymph nodes, and the listed timeframe extends from Tc-99m injection to completion of surgery. The outcome is specified for the PP and mITT populations.

In general, an identification proportion describes the share of the relevant lymph nodes that a method identifies under the study’s definitions. Comparing such proportions can characterize how frequently each approach detects the nodes considered in the analysis. It is therefore directly related to the study’s stated aim of evaluating intraoperative visualization and lymph-node identification.

The endpoint name alone does not establish how the denominator was constructed, how lymph nodes identified by both methods were handled, or how within-participant clustering among multiple nodes was accounted for. Those details are not reported in the registry record. They matter because the outcome concerns lymph nodes, while measurements may also be grouped within participants; treating correlated observations as independent can misstate uncertainty.

The record does not include the observed proportions, their comparison, a confidence interval, a p-value, or the non-inferiority margin. It therefore does not show the size or precision of any difference between methods or whether the prespecified non-inferiority criterion was met. The endpoint is a measure of identification during surgery, not a direct measure of later clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a non-inferiority, within-patient comparison, but does not report the statistical analysis procedures in enough detail to reproduce or evaluate the primary analysis. The concepts below are general explanations of what such methods address; they are not claims about procedures used in this study unless explicitly stated in the registry record.

What does a within-patient comparison mean?

In general, a within-patient design assesses two methods in the same participant. Because both methods are used in the same clinical setting for that participant, the comparison can account for some participant-level characteristics that would differ between separate groups. The analysis must still respect the paired structure: observations from the same person are related, not independent.

Here, the registry describes Tc99m/Gamma Probe and IC2000/SPY-PHI as the methods being compared during mapping and surgery. The primary outcome is stated in lymph nodes. If a participant contributes multiple nodes, those observations may also be related to one another. A method that treats every node as independent could understate uncertainty when within-participant correlation is present. The statistical model or variance calculation used to account for pairing and clustering is not reported in the registry record.

What does non-inferiority require?

In general, a non-inferiority analysis asks whether the result for a new approach is not unacceptably worse than a comparator. Before examining results, a protocol ordinarily defines a margin that represents the largest difference considered acceptable for the study’s purpose. The analysis then compares the estimate and its uncertainty with that margin. A result that does not show a conventional difference is not, by itself, proof of non-inferiority.

The registry record describes the study as non-inferiority but does not report the margin, the direction in which the comparison was framed, or the decision rule. It also does not report a primary estimate or confidence interval. Those omissions prevent a reader from checking whether the evidence met a non-inferiority criterion.

How should a confidence interval be read?

In general, a confidence interval gives a range of values compatible with the observed data under the analysis assumptions. Its width conveys precision: a narrower interval indicates more precise estimation than a wider interval. For a non-inferiority analysis, the interval must be interpreted in relation to the prespecified margin and the direction of the comparison. No interval for the primary endpoint is reported in the registry record, so the precision and criterion cannot be assessed.

Why do analysis populations matter?

The primary outcome is listed for PP and mITT populations. In general, an mITT population is a modified intention-to-treat set, but its exact membership depends on the protocol’s definition. A PP population typically reflects adherence to specified eligibility and protocol requirements, but that definition also varies by study. The record does not define either population or report their sizes, exclusions, or results.

For non-inferiority questions, choices about inclusion, adherence, and missing observations can influence the comparison. Reviewing both prespecified populations can help readers understand whether conclusions are sensitive to those choices, but the registry record does not provide enough information to do that review.

What can planning calculations tell a reader?

In general, sample-size planning calculations illustrate how an assumed effect, statistical threshold, allocation, and model relate to a planned sample size. They are conditional on those assumptions. They do not measure the probability that the completed study has demonstrated an effect, and they are not a substitute for an observed estimate and its uncertainty.

The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated output is total events; for other calculations, it is participants per arm. These are planning assumptions, not a description of the within-patient study design. The numerical illustration values and the trial’s own sample-size justification are not reported in the registry record.

What information is needed to assess the analysis?

For a complete statistical assessment, readers would need the endpoint definition and denominator, the method used to account for pairing and any clustering of lymph nodes within participants, the non-inferiority margin, the prespecified analysis populations, and handling of missing observations. They would also need the effect estimate with a measure of uncertainty and the analysis result for the stated populations. These details are not reported in the registry record. The record lists one analysis, but does not provide its statistical specification or result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one analysis for the primary endpoint and identifies PP and mITT populations. It also lists secondary outcomes concerning whether subjects had at least one lymph node identified by each method, the route by which lymph nodes were identified, and safety of intradermal IC2000 injection. The detailed results for these outcomes are not reported in the registry record.

Multiplicity arises when several outcomes, comparisons, time points, or analysis populations are examined. In general, testing many questions can increase the chance of a seemingly notable result arising by chance. Researchers may prespecify a hierarchy or use an adjustment procedure, but the registry record does not report a multiplicity strategy. It does not specify how the primary endpoint, the two analysis populations, or secondary outcomes relate to any testing plan.

The record names PP and mITT populations but does not define them, report how participants were included or excluded, or provide the number analyzed in either population. The number with evaluable endpoint data and the endpoint denominators are also not reported in the registry record.

Missing-data methods are not reported in the registry record. It is therefore not possible to determine whether observations were incomplete, how any missing values were handled, or whether sensitivity analyses were conducted. In general, missingness can affect an estimate when the availability of observations is related to the outcome or to the method being assessed. Without participant flow and analysis details, the extent and direction of any such effect cannot be judged.

Definitions of the non-inferiority margin and the statistical analysis plan are also not reported. These omissions limit assessment of whether the analysis followed a prespecified approach and whether the conclusion, if one was made, was robust to reasonable analysis choices.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (100.0%), febrile neutropenia (0.7%), oxygen saturation decreased (0.7%), apnea (0.7%), hypertension (0.7%).

The registry records 4 participants with serious adverse events and 27 with other adverse events in the IC2000/SPY-PHI group. The listed number at risk is 151 for each category, and the recorded number of deaths is 0. These are registry counts; they do not by themselves establish that an event was caused by IC2000 or SPY-PHI.

The record lists pulmonary embolism at 100.0% among the serious-event terms, and febrile neutropenia, oxygen saturation decreased, apnea, and hypertension at 0.7% each. The basis for these percentages and their relationship to event counts or participants is not reported in the registry record. They should not be read as participant-level risks without that denominator and definition.

In general, serious adverse-event counts and other adverse-event counts describe different categories and should not be combined. These figures also do not provide a controlled comparison of safety: the record describes a single-group study and does not report corresponding adverse-event counts for an independent comparator group. The listed counts do not show event timing, severity beyond the serious classification, relatedness assessments, or the duration of follow-up; those details are not reported in the registry record.

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

The registry record establishes that a prospective, open-label, multicenter study assessed IC2000 with SPY-PHI for lymphatic-vessel and lymph-node visualization during lymphatic mapping and sentinel lymph node biopsy in subjects with breast cancer. It describes a within-patient comparison against Tc99m/Gamma Probe and names the proportion of lymph nodes identified by each method as the primary outcome.

It does not report the primary endpoint result. Readers therefore cannot determine from this record how many lymph nodes were identified by either method, how the proportions compared, or how precisely any comparison was estimated. The non-inferiority margin and the statistical criterion are also not reported, so the intended non-inferiority question cannot be evaluated.

The registry’s enrollment entry is 152, but the number contributing endpoint data or included in each analysis population is not reported. The record identifies PP and mITT populations without defining them or giving their results. Consequently, the effect of missing observations, exclusions, or analysis-population choices cannot be assessed.

The adverse-event listing provides counts for the IC2000/SPY-PHI group, including serious events, other events, and deaths. Those counts are descriptive and do not establish causation or a comparative safety difference. The record does not provide a randomized control group or a separate comparator-group safety result.

In general, a registry description can clarify the study question and design, while an assessment of findings requires outcome estimates, uncertainty, analysis details, and context for the prespecified criteria. Those elements are not reported for the primary comparison in this record. No conclusion about the comparative identification performance or non-inferiority can be drawn from the record alone.

13. Why This Trial Matters Statistically

This study raises a statistical question that is not captured by simply comparing two independent groups. The registry describes a within-patient assessment of two lymph-node identification approaches. In general, paired designs can account for participant-level differences, but their analysis must preserve the relationship between measurements collected from the same participant.

The outcome is measured in lymph nodes, while the methods are applied in participants. That distinction matters: several node-level observations may belong to one participant and may not be statistically independent. The record does not report how pairing or within-participant clustering was handled. Understanding that analysis is important for judging whether uncertainty around the comparison is appropriately estimated.

The stated non-inferiority aim also makes the margin central to interpretation. A finding of no statistically significant difference would not, on its own, demonstrate non-inferiority. The margin, the effect estimate, and its uncertainty must be considered together. Because these are not reported in the registry record, the central statistical question remains unresolved in the available record.

The record identifies PP and mITT populations, making analysis-population definitions relevant to interpretation. In general, choices about adherence and incomplete data can influence non-inferiority assessments. The record does not define the populations or report their results, participant flow, or missing-data procedures.

These considerations show why the study’s design description alone cannot establish what the comparison found. A clear report of the endpoint definition, analysis method, margin, population results, and uncertainty would be needed to judge the strength and precision of the evidence.

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 the primary endpoint estimate, the comparison between methods, a confidence interval, or a p-value. It also does not report the non-inferiority margin or the decision rule. These omissions prevent assessment of the study’s main statistical question.

The endpoint is expressed as a proportion of lymph nodes, but the record does not describe the denominator, the handling of nodes detected by both methods, or how multiple nodes within a participant were treated in the analysis. It names PP and mITT populations without defining their membership, reporting their sizes, or giving population-specific results.

Participant flow, endpoint completeness, missing-data procedures, and sensitivity analyses are not reported in the registry record. The enrollment entry of 152 does not indicate how many participants contributed to the primary analysis. The record also does not provide sufficient detail to assess the effects of the open-label design on outcome ascertainment or procedural conduct.

The record describes a single-group, within-patient study, not a randomized comparison between independent groups. It therefore does not provide a separate randomized control arm for interpreting adverse events or other outcomes. The safety listing lacks context about event timing, relatedness, follow-up duration, and the basis for the reported percentages.

The registry does not report the protocol’s statistical analysis plan, sample-size justification, or multiplicity strategy. The listed planning assumptions are described as illustrations based on the observed effect, not as the trial’s own design rationale. Without the primary results and analysis details, neither the precision nor the robustness of the intended comparison can be evaluated.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study Assessing the Safety and Effectiveness of IC2000 and SPY Fluorescence Imaging Systems (SPY-PHI) in the Visualization of Lymphatic Vessels and Identification of Lymph Nodes During Sentinel Lymph Node Biopsy in Subjects With Breast Cancer — NCT03200704.
• Registry record last updated 2023-09-21; status last verified 2023-08.
• Results first posted 2023-09-21.
• 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.

18. Record Summary

The registry describes a completed Phase 3, prospective, open-label, multicenter, single-group study of IC2000 with SPY-PHI for visualization during lymphatic mapping and sentinel lymph node biopsy in subjects with breast cancer. It is characterized as a non-inferiority within-patient comparison against Tc99m radioactive colloid with a Gamma Probe.

The primary outcome is the proportion of lymph nodes identified by each method, assessed in PP and mITT populations from Tc-99m injection to completion of surgery. The registry lists enrollment of 152, a start date of 2019-01-04, and a primary completion date of 2020-08-27.

The primary endpoint result, non-inferiority margin, analysis details, and definitions of the analysis populations are not reported in the registry record. Safety counts are listed for the IC2000/SPY-PHI group, but they do not provide a randomized comparative safety assessment.