Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization (NCT02471313), a na phase 2 study. The primary outcome is Number of Participants for Which Uptake of [18F]-FMISO Was Successful and Hypoxic Tumors Were Observed During PET Scan Imaging Post TACE Procedure.

2. Clinical Question

This is a feasibility question about whether a particular imaging approach can reveal a tumor feature after TACE. It is not a comparison of TACE with another treatment, nor does it test whether imaging changes clinical outcomes. The record describes CT and MRI around the TACE procedure as part of the broader study activities, alongside blood tests and a physical examination. It also says that the [18F] FMISO imaging study was performed at NIH. Those details describe the study context; they do not supply a comparator or a reported result for the primary endpoint.

3. Trial Design

The registry identifies this as a completed Phase 2 pilot study with a single-group model, no allocation, and no masking. Enrollment was 3. Because there was no randomized comparison, the study does not provide a like-for-like control group for evaluating imaging findings or attributing changes to the tracer. Participants were assessed in connection with TACE, which occurred under a separate NCI protocol or at a hospital other than the NIH Clinical Center.

The study intervention was [18F] FMISO, listed as a drug in the registry. In the study description, it functions as an imaging agent: participants received a single dose after TACE, followed by PET imaging to assess whether hypoxic tumor identification was observable. The stated endpoint timeframe was up to 72 hours after injection. The arm description likewise characterizes participants as undergoing [18F] FMISO PET imaging following TACE.

The brief study description includes abdominal CT and MRI before and after TACE, as well as blood tests and a physical examination. It says the PET-CT scans were conducted at NIH and that each scan took about 30 minutes. The description also mentions that some participants would have [18F] FMISO and PET-CT scans before TACE, but the text in the registry record ends before that description is complete. Further detail about the imaging schedule is not reported in the registry record.

The listed study dates are 2015-06-12 for the start and 2018-03-07 for primary completion; the status is COMPLETED. A formal statistical analysis plan, sample-size justification, interim analysis plan, and details of any masking procedures beyond the listed NONE status are not reported in the registry record. The primary outcome description explicitly says power and significance calculations are not applicable to this small sample feasibility study.

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 Number of Participants for Which Uptake of [18F]-FMISO Was Successful and Hypoxic Tumors Were Observed During PET Scan Imaging Post TACE Procedure, measured over up to 72 hours after injection of [18F] FMISO.

The primary endpoint is a count of participants for whom uptake of [18F] FMISO was successful and hypoxic tumors were observed during PET scan imaging after TACE. The registry describes administration of a single dose of the imaging agent after the procedure, with imaging performed to evaluate whether hypoxic tumor identification could be observed. The timeframe is up to 72 hours after injection.

This endpoint is used to address an imaging-feasibility question: whether the tracer and PET imaging can produce an observable signal relevant to hypoxic tumor tissue after TACE. A participant count is a direct way to describe how many participants met the stated endpoint criteria in this small pilot. It does not, by itself, quantify diagnostic accuracy, compare imaging against a reference standard, or establish that the imaging result predicts a later outcome. Those questions would require outcome definitions and analyses that are not reported in the registry record.

The registry record does not report the observed primary endpoint count. It therefore does not show how many participants had successful uptake with observable hypoxic tumors. Enrollment is reported as 3, but that enrollment figure cannot substitute for the endpoint result. No inferential test or confidence interval for the primary endpoint is reported; the outcome description states that power and significance calculations are not applicable to this feasibility study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on the question the study was built to answer. This study asks whether [18F] FMISO uptake and hypoxic tumor observation were achievable after TACE. It is a feasibility question in a single-group pilot, not a comparison between randomized groups. The registry lists 3 participants enrolled and no analyses. The primary outcome is a participant count, but the observed count is not reported in the registry record.

What does a count endpoint describe?

A count endpoint records how many participants meet a defined outcome criterion. Here, the criterion described in the primary endpoint combines successful uptake of the imaging agent with observation of hypoxic tumors on PET imaging after TACE. The count is intended to describe whether the imaging objective was observed among those assessed. It is not automatically a measure of diagnostic accuracy: accuracy requires a suitable reference for determining whether imaging classifications are correct. No reference standard or accuracy analysis is reported in the registry record.

Counts are often accompanied by denominators so readers can understand the number assessed. In this case, enrollment is listed, but the registry does not report the primary endpoint count or make clear in the posted results how many participants contributed an evaluable scan. It would therefore be inappropriate to infer the endpoint result from enrollment or from the separate safety counts. The safety denominator does not establish the denominator used for the imaging endpoint.

Why does the single-group design matter?

In a controlled comparison, results from groups can be contrasted under a specified analysis. This study has no comparator group, and the record explicitly marks it as not a randomized comparison. A single-group feasibility design can describe whether an imaging procedure was carried out and whether the intended observation was made, but it cannot isolate the effect of the tracer by comparing it with a control condition. It also cannot establish comparative performance against another imaging strategy from the information reported.

Masking is listed as NONE. In general, masking can reduce the influence of expectations on measurements or assessments when participants, clinicians, or outcome assessors might otherwise know the intervention. The registry does not give further detail about who assessed the scans or how the endpoint was adjudicated. It is therefore not possible to determine from this record whether image interpretation followed a blinded or standardized review process.

What do power and significance calculations mean?

In general, a significance test evaluates how compatible observed data are with a specified null model, while a confidence interval describes uncertainty around an estimate under the assumptions of the analysis. Power is a design concept concerning the chance that a planned test would detect a specified effect under stated assumptions. These concepts are most useful when an outcome estimate, a comparison, and an analysis plan are clearly defined.

The primary outcome description says power and significance calculations are not applicable to this small sample feasibility study. No analysis is listed, and the registry does not report a p-value, confidence interval, or test result. Consequently, there is no inferential result from this record to interpret. A non-reported significance test should not be described as negative, and the absence of a p-value does not show that the endpoint was or was not achieved.

The registry also includes general sample-size planning assumptions: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the target effect described as a stated fraction of the observed effect. Those assumptions do not match the registered single-group structure as a direct comparison, and no numerical planning outputs are reported in the registry record for this analysis. Planning illustrations are not observed power, and they do not change the interpretation of the pilot’s missing endpoint result.

Why can small feasibility studies be informative but uncertain?

As a general matter, a feasibility study can identify practical issues in carrying out a procedure and can provide an initial description of whether a measurement was obtained. It is usually not designed to provide a precise estimate of performance in a broader population. With limited enrollment, each participant’s outcome can have substantial influence on a descriptive summary. The registry record does not provide enough outcome data to quantify that uncertainty for this study.

Over-dispersion is a general statistical concern when count outcomes vary more than a simple probability model would expect. It is not possible to assess over-dispersion from the registry record because the primary outcome count and analysis are not reported, and the endpoint is described as a participant count rather than a repeated count process. No dispersion parameter or model is listed. Applying a count model or making assumptions about event variability would therefore go beyond the information in the record.

Overall, the methods information supports a narrow interpretation: this was a small, unmasked, single-group feasibility study with a specified post-TACE imaging endpoint. The record does not provide the endpoint estimate or an inferential analysis. The statistical evidence available in the registry record is therefore insufficient to determine how often the primary imaging objective was met or how precisely that frequency was estimated.

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("Uptake of [18F] FMISO With PET Scan Imaging")
n      <- c(3)
events <- c(0)
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  Uptake of [18F] FMISO With PET Scan Imaging  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no analyses. It does not report a multiplicity adjustment, a hierarchy of outcomes, or a plan for handling multiple statistical tests. The primary outcome description says that power and significance calculations are not applicable to this small sample feasibility study. On this record, there is no reported set of inferential tests for which to assess multiplicity adjustment.

Missing-data handling is not reported in the registry record. The posted results do not state whether every enrolled participant completed imaging, whether any scans were unevaluable, or how missing endpoint observations were treated. Without the endpoint count and an evaluable denominator, it is not possible to assess the extent or potential impact of missing primary outcome data.

The analysis population is also not reported in the registry record. Enrollment is listed as 3, but the record does not say whether the primary outcome was analyzed among all enrolled participants, participants who received the imaging agent, or participants with evaluable PET scans. Those populations can differ in a feasibility study, so enrollment should not be assumed to be the endpoint denominator.

In general, a clear analysis-population definition and missing-data approach help readers understand who contributed to an estimate and how incomplete observations were handled. Their absence does not establish that data were missing; it means the registry record does not document whether missingness occurred or what approach was used. No further conclusions about exclusions, protocol deviations, or analysis sets are warranted from the information reported.

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 3 participants at risk for serious adverse events, with 0 affected, and 3 at risk for other adverse events, with 1 affected. Deaths are listed as 0. The record contains no listed serious adverse-event terms. These are counts, not comparative estimates, because the study has no control group.

The serious and other adverse-event categories should be read separately as recorded. The count of 1 for other adverse events does not identify the event or establish its severity, cause, or relationship to [18F] FMISO or TACE. The registry record does not report the term for that event in the registry record. Likewise, 0 serious adverse events and 0 deaths describe what was recorded in this study; they do not demonstrate that the risk of an event is absent.

In general, safety counts from a small study have limited ability to characterize uncommon events or compare risks between interventions. These figures should not be interpreted as evidence about the safety of TACE itself, which was performed under a separate protocol or at another hospital. The registry record does not provide further detail about event timing, attribution, or follow-up procedures.

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

The result that can be described from the registry record is the study structure and the endpoint it intended to assess. This completed Phase 2 pilot enrolled 3 participants in a single-group study of [18F] FMISO PET imaging after TACE. The intended primary measure was a count of participants with successful uptake and observed hypoxic tumors, assessed up to 72 hours after injection. The observed primary endpoint count is not reported in the registry record.

That omission limits the central interpretation. The record cannot establish from the posted results whether the imaging objective was achieved, how many participants had an observable finding, or how often the endpoint was evaluable. It also cannot quantify the precision of an estimated feasibility rate. The enrollment figure alone is not an imaging outcome.

The study does not test whether TACE is effective, whether [18F] FMISO changes care, or whether PET imaging improves clinical outcomes. There is no comparator group and no reported analysis of those questions. The listed safety counts provide a limited description of events recorded in the study, but they do not resolve the missing primary imaging result or establish comparative safety.

In general, pilot studies can inform whether a procedure or measurement merits further evaluation, but conclusions depend on the outcome data and the way those data were collected. Here, the stated endpoint is relevant to imaging feasibility, yet the registry record does not include its observed value. The appropriate conclusion is therefore limited: the study was registered and completed as a small, single-group imaging feasibility study, while the available registry results do not report the primary endpoint result needed to characterize its imaging findings.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is about feasibility rather than comparative efficacy. A count of participants with successful tracer uptake and observable hypoxic tumors is suited to a descriptive question about whether the imaging objective was observed. It should not be interpreted as a treatment-effect estimate or as evidence from a controlled comparison.

The design information helps set the limits of interpretation. The study is listed as single-group, with no allocation and no masking, and the record identifies no randomized comparison. This structure can support an initial description of an imaging procedure, but it cannot separate the contribution of the tracer from other influences through a control-group contrast. The registry’s statement that power and significance calculations are not applicable also signals that conventional hypothesis testing was not the stated purpose.

The most consequential statistical limitation is that the primary outcome count is not reported. Without that result, readers cannot judge whether the feasibility objective was observed or assess its precision. This demonstrates why outcome definitions and study completion status do not substitute for outcome results: the registry describes what was intended to be measured, but not the measured endpoint value.

The safety counts are also descriptive and come from a small study without a comparator. They can be reported as recorded, but they cannot establish relative risk or rule out events that were not observed. More broadly, the record distinguishes a pilot’s operational question from the evidence needed to support broader claims. The distinction is important for biostatistical reading: design, endpoint, observed result, and uncertainty are separate pieces of evidence, and not all are available in this registry record.

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.

Several trial-specific limitations constrain interpretation. Enrollment was 3, and the design was single-group with no allocation or masking. There was no comparator, so the registry record does not support a direct contrast with another imaging method or a control condition. This limits what can be learned about relative imaging performance and prevents a randomized comparison.

The primary endpoint is described, but its observed count is not reported. The record therefore does not permit assessment of how many participants met the endpoint, whether all participants had an evaluable scan, or how much uncertainty surrounds the result. The analysis population, missing-data approach, and handling of unevaluable imaging are not reported in the registry record.

The record does not report details about how PET images were interpreted, whether assessments were standardized, or whether a reference standard was used. Without those details, the endpoint cannot be interpreted as a measure of diagnostic accuracy. The registry also does not report an inferential statistical analysis, confidence interval, or p-value; the outcome description states that power and significance calculations are not applicable to this feasibility study.

The brief study description includes an incomplete sentence about some participants receiving imaging before TACE, so further detail about that schedule is not reported in the registry record. Safety information is limited to aggregate counts, with no listed serious adverse-event terms and no detailed account of the other adverse event. These limitations do not negate the study’s stated feasibility purpose, but they restrict the conclusions that can be drawn from its posted record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization — NCT02471313.
• Registry record last updated 2019-04-23; status last verified 2018-03-07.
• Results first posted 2019-04-23.
• 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

The registry record describes NCT02471313, titled “Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization,” as a completed Phase 2 pilot study sponsored by the National Institutes of Health Clinical Center (CC). The study started on 2015-06-12 and reached primary completion on 2018-03-07. Enrollment was 3.

The study used a single-group, unmasked design and evaluated [18F] FMISO PET imaging after TACE. Its primary endpoint was a participant count for successful uptake and observed hypoxic tumors, with assessment up to 72 hours after injection. The primary endpoint result is not reported in the registry record. The safety record lists 0 serious adverse events, 1 participant with other adverse events, and 0 deaths, with 3 at risk in each adverse-event category.