A Microdose Evaluation Study of ABY-029 in Recurrent Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Microdose Evaluation Study of ABY-029 in Recurrent Glioma (NCT02901925), a non-randomized early/phase 1 study. The primary outcome is Fluorescence Signal Detection.

2. Clinical Question

The study also set secondary objectives: assessing diagnostic accuracy of ABY-029 detection by iFI and an intraoperative probe relative to histopathology and other indicators, and measuring molecular uptake and concentration in resected specimens. The listed secondary outcomes are mean tumor-to-background ratio and ex vivo fluorescence intensity.

These are questions about signal detection, tissue imaging, and agreement with tissue-based assessment. They are not questions about whether ABY-029 improves clinical outcomes. The registry record does not report numerical results for the primary endpoint or the secondary outcomes, so the extent of signal detection and diagnostic accuracy cannot be judged from the posted results.

3. Trial Design

The registry describes a Phase 0, open-label, single-center clinical trial of ABY-029 in recurrent glioma. The official title specifies a single intravenous injection. The intervention descriptions say that ABY-029 was to be administered before surgery at 1X, 3X, or 6X dose levels. During the procedure, a probe was to be used to assess whether signal was detectable in vivo; ex vivo tissue pathology was to assess binding with EGFR-positive tumor tissue.

Enrollment was 14. The registry lists the study as non-randomized and single-group, with no masking. The three dose groups are not randomized comparison arms, and the registry record does not establish that they are comparable with respect to participant or disease characteristics. Differences between dose groups, if any, therefore would not by themselves establish a causal dose effect.

The study began on 2017-02-13, had a primary completion date of 2021-06-29, and is listed as completed. The registry identifies Dartmouth-Hitchcock Medical Center as sponsor. These administrative details describe the record and do not indicate whether the imaging objectives were met.

The primary endpoint is fluorescence signal detection measured by BVR during the procedure, described as a mean of a continuous measure with standard deviation as its dispersion. The record also lists mean tumor-to-background ratio and ex vivo fluorescence intensity as secondary outcomes. Although the study objectives refer to diagnostic accuracy and molecular uptake and concentration, numerical findings for those objectives are not reported in the registry record.

No randomized control comparison is described. Histopathology and other indicators are named as reference standards for the diagnostic objective, but the registry record does not provide an analysis plan, participant flow, or endpoint results. The intended design should therefore be read as an exploratory imaging study across dose levels, not as a controlled test of clinical benefit.

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 Fluorescence Signal Detection, measured over during procedure.

The primary endpoint is fluorescence signal detection during the surgical procedure, measured using Biological Variance Ratio (BVR). The registry describes the endpoint as a mean of a continuous measure, with standard deviation as the dispersion measure, and gives the timeframe as during procedure. The endpoint is intended to assess whether ABY-029 fluorescence can be detected in brain tissue while surgery is taking place.

In general, an imaging signal measure can help characterize whether an imaging agent produces a measurable signal in the tissue of interest. A continuous measure can also retain variation across observations, rather than reducing the outcome to a simple detected/not-detected classification. BVR is the named measure in this record; its calculation, interpretation, and threshold for declaring a signal detectable are not reported in the registry record.

The brief study objective also focuses on detectable signals in sampled tissues with an EGFR pathology score of at least 1 based on histological staining. That objective connects the imaging signal to tissue pathology, but the registry does not report the results by pathology score or specify how the primary endpoint relates analytically to that objective.

The endpoint is relevant to an intraoperative imaging question, but it does not directly measure diagnostic accuracy, clinical outcomes, or patient benefit. Those are distinct concepts. The registry lists diagnostic accuracy and tissue uptake among secondary objectives, but numerical findings for the primary endpoint are not reported in the registry record. Without a posted estimate and its uncertainty, the size and precision of any measured fluorescence signal cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as a mean of a continuous outcome, with standard deviation as its dispersion measure. General explanation: a mean describes the central value of a set of measurements, while a standard deviation describes how spread out individual measurements are around that mean. Neither statistic is reported for BVR in this record, so there is no numerical estimate of the central signal or its variability to interpret.

What does a confidence interval add?

General explanation: a confidence interval expresses uncertainty around an estimated quantity. It helps readers distinguish an estimate that is precise from one that is compatible with a broad range of values. The registry record does not report a confidence interval for the primary endpoint or the listed secondary outcomes. Without one, the precision of any underlying estimate cannot be assessed from this record.

What does signal detection mean statistically?

General explanation: detecting a signal involves comparing a measured signal with some criterion for distinguishing it from background variation. The registry names BVR as the primary measure and describes a probe assessment during surgery, but does not report the BVR formula, a detection threshold, or how a threshold would be selected. It also does not report the observed signal values. The terms detectable and signal therefore describe the study objective, not a posted numerical finding.

How should dose groups be interpreted?

The record describes 1X, 3X, and 6X dose groups. It is non-randomized, open-label, and single-group. General explanation: randomized allocation can help balance participant characteristics across comparison groups; without it, groups may differ for reasons other than the intervention level. A numerical difference across these dose groups, if reported, would be descriptive unless the analysis and design justified a stronger interpretation. No dose-group endpoint estimates or adjusted comparisons are reported in the registry record.

Why does variability matter?

General explanation: variation among measurements affects how precisely a group mean is estimated and how readily differences can be distinguished from measurement noise. A continuous imaging measure may vary across tissue samples or procedures. The registry specifies standard deviation as the dispersion measure, but it does not report that value or describe the distribution of measurements. The record also does not report whether the analysis considered over-dispersion. In general, over-dispersion means that observed variability is greater than a statistical model expects; ignoring it can make uncertainty appear smaller than it is. This is a general methodological point, not a reported feature of this study.

What can planning calculations tell readers?

The registry’s stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. The record emphasizes that planning calculations based on an observed effect are illustrations, not the study’s original design. Such calculations are not observed power. They also do not establish the quality of the study’s endpoint analysis.

The illustration’s equal-allocation, two-arm framework differs from the described non-randomized study with three dose groups. The primary endpoint’s observed effect is not reported in the registry record, nor are numerical planning results. Accordingly, there is no basis in this record to interpret a specific participant requirement or to judge whether a target was achieved. A planning illustration is conditional on its assumptions and should not be read as a result from participants.

What does the diagnostic reference add?

The study’s secondary objective compares detection by iFI and an intraoperative probe with histopathology diagnosis and other indicators, which are described as a gold standard. General explanation: diagnostic accuracy analysis evaluates how an index test corresponds with a reference assessment. The registry does not report the diagnostic results, definitions used to classify test findings, or the statistical measures used. It is therefore not possible to assess agreement or diagnostic performance.

Overall, the available methods description identifies the endpoint type and broad objectives, but leaves important analytical details unreported. The registry record does not report the BVR calculation, endpoint thresholds, confidence intervals, model specifications, covariate adjustments, or handling of repeated measurements.

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("1X Dose Group", "3X Dose Group", "6X Dose Group")
n   <- c(3, 3, 6)
m   <- c(6.2, 5, 8.8)
sp  <- c(2.4, 1.2, 3.7)
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  1X Dose Group  3  6.200  2.400  0.238  12.162
CARM  3X Dose Group  3  5.000  1.200  2.019  7.981
CARM  6X Dose Group  6  8.800  3.700  4.917  12.683

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary endpoint and multiple secondary outcomes and objectives. When a study assesses multiple outcomes or makes repeated statistical comparisons, general statistical practice considers multiplicity: the more opportunities there are to identify a nominally notable result, the more important it is to understand which analyses were planned and how conclusions account for them. No multiplicity procedure or hierarchy of secondary analyses is reported in the registry record. Because numerical outcome analyses are not reported, the effect of multiplicity on any findings cannot be evaluated.

Missing data can affect both the estimated outcome and its precision, particularly if measurements are unavailable for reasons related to participant or tissue characteristics. General explanation: analysis methods should describe which observations were included and how missing measurements were handled. The registry record does not report missing-data counts, reasons for missingness, imputation methods, or endpoint-specific analysis populations. Enrollment was 14, but that figure alone does not establish the number with evaluable BVR or secondary outcome measurements.

The record also does not report whether the primary analysis followed a prespecified population definition, whether all enrolled participants were included, or whether analyses were limited to participants with usable tissue or imaging measurements. The registry’s safety risk sets are not substitutes for endpoint analysis populations.

No statistical analysis plan, model details, or analysis results are reported in the registry record. As a result, readers cannot determine how the investigators handled multiple outcomes, missing measurements, exclusions, or potential dependence among observations.

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.

The adverse-event entries list serious adverse events, other adverse events, and deaths for the 1X, 3X, and 6X dose groups. Each group reports zero affected participants for serious adverse events, zero for other adverse events, and zero deaths. The corresponding numbers at risk are 3 in the 1X group, 3 in the 3X group, and 6 in the 6X group.

These entries describe the registry’s reported counts within the listed risk sets. They do not provide a detailed account of event types, timing, severity beyond the serious-event category, or participant-level follow-up. The registry lists no top serious-event terms. The record does not report additional information on how adverse events were collected or how long participants were monitored.

Zero reported events in these groups should be read as the posted counts, not as proof that an event is impossible or that there was no risk. The study was small and the adverse-event denominators are limited. These safety counts also do not supply evidence about the primary imaging endpoint or diagnostic performance.

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

The registry describes an exploratory study of ABY-029 fluorescence imaging in recurrent glioma. It specifies a primary question about detection of fluorescence in brain tissue during surgery, measured by BVR, and lists secondary objectives involving tumor-to-background ratio, ex vivo fluorescence, diagnostic accuracy, and molecular uptake. Those objectives clarify what the study sought to investigate.

The record does not report numerical results for the primary endpoint or listed secondary outcomes. It therefore does not establish whether fluorescence was detected, how large any signal was, how variable the measurements were, or whether detection corresponded with histopathology. The absence of posted estimates should not be interpreted as a positive or negative finding; it leaves the outcome question unresolved in this registry record.

The design is non-randomized, open-label, single-center, and single-group, with three described dose levels. It is not a randomized comparison of ABY-029 against a control. Even if dose-group results were available, the design would require caution in interpreting differences, because dose groups were not randomly assigned according to the registry description.

The study’s imaging and tissue-assessment objectives are distinct from clinical effectiveness. The registry record does not report a clinical outcome comparison, and no conclusion about clinical benefit follows from the endpoint description alone. Likewise, the listed safety counts are limited event summaries and cannot establish that risk is absent.

The most defensible reading is therefore descriptive: this record documents a completed Phase 0 imaging study and its intended measurements, while leaving the numerical findings unavailable. Assessing signal magnitude, precision, diagnostic performance, or dose-related patterns would require outcome estimates and analytical details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for the kind of question it asks. It evaluates whether an imaging agent produces a measurable fluorescence signal in tissue during surgery, rather than testing a clinical outcome in a randomized comparison. That makes measurement definition and interpretation central: the registry names BVR as the primary measure, but does not report its formula, a detection threshold, or numerical results.

The record also illustrates why design labels matter. A non-randomized, single-group study with three dose levels can describe imaging observations across those levels, but it does not provide the same basis for causal comparison as a randomized trial with a control group. Dose-group differences, if reported, would need to be interpreted in the context of how participants entered each group and how measurements were analyzed; those details are not reported in the registry record.

Another important statistical distinction is between an objective and a result. The registry specifies primary and secondary questions, but numerical findings and analysis details are absent. Without estimates and measures of uncertainty, readers cannot assess the magnitude, variability, or precision of the imaging signal. This distinction is especially relevant for exploratory studies, where establishing what was measured and how uncertainty was handled is essential to interpreting early evidence.

Finally, planning calculations should not be confused with observed evidence. The record describes an illustrative framework based on an observed effect, but does not report the effect or numerical planning results. Such calculations cannot substitute for endpoint findings or be read as observed power. The study therefore matters statistically as an example of the need to align design, measurement, analysis, and interpretation—and to make numerical results available for readers to evaluate.

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 primary limitation of the registry record for statistical interpretation is that it does not report numerical primary or secondary outcome findings. There is no reported BVR mean or standard deviation, and no numerical result for mean tumor-to-background ratio or ex vivo fluorescence intensity. The diagnostic-accuracy and tissue-uptake objectives likewise have no reported numerical findings.

The record gives limited detail about endpoint construction. It does not report the BVR formula, the criterion for detectable signal, how tissue measurements were linked to histological findings, or how many observations contributed to each analysis. Although the primary endpoint is described as a mean continuous measure, the underlying measurement process and analysis details are not given.

The design is non-randomized, open-label, single-center, and single-group. The three dose groups are not described as randomized comparisons, and there is no control arm. These features limit the strength of causal comparisons across dose levels. The registry record does not report participant characteristics by dose group or methods for addressing potential differences between groups.

Enrollment was 14, but the registry does not report endpoint-specific analysis populations or missing-data information. It also does not report multiplicity handling, a statistical analysis plan, model specifications, covariate adjustment, or whether repeated measurements were accounted for. The safety entries give event counts and risk sets, but not detailed event descriptions or follow-up information.

Finally, the planning illustration is not a substitute for trial-specific design information or observed outcomes. Its assumptions describe a two-arm framework, while the study is described as three non-randomized dose groups. The record does not report numerical planning results or an observed effect. These gaps constrain what can be concluded from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Microdose Evaluation Study of ABY-029 in Recurrent Glioma — NCT02901925.
• Registry record last updated 2024-12-13; status last verified 2024-08.
• Results first posted 2024-12-13.
• 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

NCT02901925 is a completed, open-label, single-center Phase 0 study of ABY-029 in recurrent glioma. The registry describes a non-randomized, single-group design and enrollment of 14. ABY-029 was described as a single intravenous injection before surgery, with 1X, 3X, and 6X dose groups.

The primary endpoint was fluorescence signal detection during the procedure, measured by BVR as a continuous outcome. Secondary outcomes include mean tumor-to-background ratio and ex vivo fluorescence intensity. The objectives also include diagnostic accuracy relative to histopathology and measurement of molecular uptake and concentration.

The registry record does not report numerical primary or secondary outcome results, endpoint-specific analysis populations, or detailed statistical methods. Safety entries report zero serious adverse events, other adverse events, and deaths in each listed dose group. Those counts are limited summaries and do not establish the absence of risk.