Evaluation of 18 F-FP-DTBZ Pancreatic PET Scanning as a Tool to Measure Beta Cell Mass: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of 18 F-FP-DTBZ Pancreatic PET Scanning as a Tool to Measure Beta Cell Mass (NCT02236754), a non-randomized early/phase 1 study. The primary outcome is Mean VMAT2 Functional Binding Capacity in the β Cells to 18 F-FP-DTBZ.

2. Clinical Question

3. Trial Design

This is an early-phase, nonrandomized, unmasked, parallel study sponsored by Columbia University. Its title describes evaluation of 18 F-FP-DTBZ pancreatic PET scanning as a tool to measure beta cell mass. The registry lists an enrollment of 23 and a completed status. The study start date is 2013-07-02, and primary completion is dated 2014-04-23. The recorded phase is EARLY PHASE1.

The two described groups are healthy controls and patients with longstanding type 1 diabetes. The control group is characterized as having predicted normal beta cell mass, while the patient group is characterized as having predicted reduced beta cell mass. These are not randomized assignments. The registry record explicitly cautions that the arms are not a like-for-like control comparison, so the group structure should not be interpreted as a randomized treatment contrast.

The study description says that two PET measurements will be taken in each subject and compared for reproducibility. The primary outcome timeframe is up to 2 months from enrollment. Biochemical testing is also mentioned in the brief summary, but the registry record does not report detailed results or a complete description of how those measurements were analyzed.

The record identifies no masking. It does not report a protocol for allocation, a sample-size justification, an interim-analysis plan, or a prespecified statistical analysis plan. It also does not report participant flow, exclusions, or the number included in the primary outcome analysis. Those details should not be inferred from the enrollment figure or from the group counts in the safety 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:

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 Mean VMAT2 Functional Binding Capacity in the β Cells to 18 F-FP-DTBZ, measured over Up to 2 months from enrollment.

The primary endpoint is mean VMAT2 functional binding capacity in the beta cells to 18 F-FP-DTBZ. The registry defines the measure for the body and tail of the pancreas as BPND, or VMAT2 binding potential, multiplied by PET region-of-interest volume. BPND is unitless and region-of-interest volume is measured in mL; the reported endpoint is described as unitless in the outcome listing. The registry states that higher functional binding capacity indicates greater beta cell mass.

This endpoint is used as an imaging-based measure related to pancreatic beta cell mass. The study rationale describes beta cell mass as imperfectly correlated with insulin production and proposes PET imaging as a noninvasive way to quantify insulin-producing cells. The listed primary outcome is a mean, with standard error as its dispersion measure. A mean summarizes the central value of a continuous measure, while a standard error describes uncertainty in estimating that mean; it is not a description of the spread of individual participant values.

The endpoint definition does not itself establish that the imaging measure is accurate or reproducible. To assess repeatability, the scan measurements would need to be compared within participants using an appropriate analysis. No numerical endpoint results, repeatability statistic, or uncertainty estimate are reported in the registry record. The registry also does not report a direct validation of this imaging measure against an independent measure of beta cell mass.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure summarized as a mean. In general, a mean gives the center of a set of measurements by averaging their values. The standard error attached to a mean describes how precisely that sample mean estimates the underlying mean under the analysis assumptions. It does not describe how widely participant values vary. A standard deviation is commonly used to describe participant-level spread, but the registry lists standard error and does not report a standard deviation for this outcome.

The study's repeatability question is inherently about measurements made more than once in the same person. In general, repeated measurements should be analyzed in a way that preserves their pairing: a person's scans are related observations, not independent observations from unrelated people. An analysis could examine within-person differences, agreement, or another repeatability measure. The registry record does not report which repeatability statistic or model was used, and it gives no numerical repeatability result. It would therefore be inappropriate to attribute a particular method to the investigators.

Agreement and association are not interchangeable. In general, two scans can track participants in a similar rank order while still differing systematically in their measured values. A correlation alone would not necessarily demonstrate close agreement between repeat scans. Methods that assess agreement consider how measurements differ within a person and whether the differences are small or systematic. This is general statistical context, not a claim about an analysis performed in this study.

The group comparison is also distinct from the repeatability analysis. The healthy controls and longstanding type 1 diabetes participants were not randomized, and the record warns that the arms are not a like-for-like control comparison. In general, a comparison of nonrandomized groups can be affected by differences in participant characteristics, selection, or measurement conditions. Adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjusted comparison or describe covariates used in an analysis.

Uncertainty matters for both purposes. In general, an estimate without an uncertainty measure gives limited information about how compatible the observed data are with a range of underlying values. A confidence interval expresses uncertainty around an estimate under specified assumptions, while a p-value assesses data compatibility with a null model under those assumptions. The registry record reports neither a confidence interval nor a p-value for the primary outcome. It does not state a statistical test or model for the endpoint, so none can be assumed.

The registry lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It describes planning to detect a stated fraction of the observed effect. Such calculations, in general, are design illustrations rather than observed power: they indicate the participant count that would be needed under stated assumptions, not the probability that a completed study has detected an effect. Numerical planning results and the fractions used are not reported in the registry record. The record also does not state that these assumptions were the trial's own design basis.

Over-dispersion is a general concern when variation in data is greater than the assumed statistical model allows. If ignored, standard errors can be too small and uncertainty can be understated. For a continuous PET measure, the relevant variance structure and any repeated-measure correlation should be assessed in the chosen model. The registry record does not report a model, a variance assessment, or any adjustment for repeated observations. This is a general methodological consideration, not evidence that over-dispersion occurred.

The record identifies one primary outcome measure and zero analyses. It does not specify whether additional endpoints were planned, whether exploratory analyses were conducted, how missing measurements were handled, or whether any analysis populations were defined. These omissions prevent evaluation of the analysis choices and of how much the reported findings, if available elsewhere, might depend on those choices. The endpoint definition and the proposed repeat-scan design alone are not enough to reconstruct the statistical analysis.

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("Study Controls", "Longstanding T1D")
n   <- c(14, 8)
m   <- c(103, 38)
sp  <- c(12, 5)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Study Controls  14  103.000  44.900  77.076  128.924
CARM  Longstanding T1D  8  38.000  14.142  26.177  49.823

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and zero analyses. It does not report outcome estimates or describe a multiplicity-control strategy. The number of listed primary outcomes does not establish whether other planned or exploratory comparisons were made. The registry record does not report a complete hierarchy of endpoints, a family of hypotheses, or a plan for adjusting significance thresholds across multiple tests. As a result, the handling of multiplicity cannot be assessed.

The record says that two PET measurements are taken in each subject, but does not report how missing scans or incomplete pairs were handled. It does not state whether participants with only one scan could contribute to an analysis, whether imputation was considered, or whether reasons for missingness were recorded. No missing-data counts or analysis methods are reported in the registry record.

The registry also does not define analysis populations for the primary endpoint. It does not say whether all enrolled participants, only participants with evaluable scans, or another group was intended for analysis. The enrollment figure does not by itself identify the population used for an endpoint analysis, and the safety group counts should not be taken as the analysis denominators for the primary outcome.

These omissions matter because the estimate and its precision can depend on which measurements and participants are included. Without a stated analysis population, missing-data approach, and multiplicity plan, the robustness of any unreported analysis cannot be evaluated.

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 5% reporting threshold.

The safety record lists Study Controls with 14 at risk and zero serious adverse events, zero other adverse events, and zero deaths. It lists Longstanding T1D with 8 at risk and zero serious adverse events, zero other adverse events, and zero deaths. No serious adverse event terms are listed.

These are descriptive counts for the safety groups as recorded. They do not provide an estimate of risk beyond the listed observation, and the record does not describe event ascertainment details or exposure time. The safety counts should not be interpreted as proof that the imaging procedure or radiopharmaceutical cannot be associated with adverse events. Nor should the group counts be treated as a randomized comparison: the study is nonrandomized and the populations differ by design.

The safety record and the primary endpoint address different questions. Zero events in the listed categories do not provide information about measurement reproducibility or the accuracy of the imaging measure. Conversely, the registry's endpoint definition does not determine safety. The record does not provide further safety analysis or a narrative of event monitoring.

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

The study addresses an important measurement question: whether repeat PET imaging with 18 F-FP-DTBZ can produce reproducible estimates of pancreatic VMAT2 functional binding capacity. The registry describes an approach in which each subject has two PET measurements and defines an outcome intended to reflect beta cell mass. Those design features explain the question being investigated, but they do not establish that the measure is reproducible or valid.

The registry record does not report primary outcome values, a repeatability statistic, a group contrast, or uncertainty estimates. It therefore does not allow a reader to judge whether scan measurements were similar within participants, whether the groups differed, or how precise any estimate was. The absence of reported results is not evidence that there was no effect; it means the result cannot be determined from this record.

The endpoint is a proxy-based imaging measure. The registry rationale links VMAT2 binding capacity to beta cell mass and states that higher values indicate greater beta cell mass. That stated interpretation does not, by itself, demonstrate a one-to-one relationship with beta cell mass or establish validity against an independent reference. The record does not report such a validation result.

The comparison between healthy controls and people with longstanding type 1 diabetes is nonrandomized. Any observed difference would describe these selected groups, not necessarily an effect caused by group membership or a treatment. The registry cautions that the groups are not like-for-like controls. The record also does not report an adjusted analysis that might address measured differences.

Accordingly, this record supports understanding the study's aim, design, and endpoint definition, but not a conclusion about the performance of the imaging method. It does not establish a clinical benefit, a treatment effect, or the suitability of the measure for use in other settings. Those questions require results and analyses that are not reported in the registry record.

14. Why This Trial Matters Statistically

Clinical measurement studies often need to establish whether a proposed measure can be repeated consistently before it can serve as an informative outcome. This study's stated focus on repeated PET scans makes within-subject reproducibility central. If a measure varies substantially between scans for reasons unrelated to the underlying biology, it may be difficult to distinguish biological differences from measurement variation. This is general measurement reasoning; the registry record does not report how much variation occurred in this study.

The study also raises a statistical distinction between repeatability and group separation. A measure could be consistent across repeated scans yet fail to distinguish the selected groups; conversely, a difference between groups would not by itself establish good repeatability. Each question requires its own estimate and uncertainty assessment. The registry defines the endpoint and groups but reports no corresponding results, so neither question can be answered from the record.

The nonrandomized design is important for interpretation. The groups were selected for different expected beta cell mass and clinical characteristics, rather than assigned randomly to a condition. Statistical comparisons in such designs are descriptive unless assumptions and adjustment strategies support broader interpretation. The registry explicitly cautions against treating the arms as a like-for-like control comparison.

This record also illustrates why an endpoint's biological rationale and statistical evidence are separate. The endpoint is described as an imaging measure related to beta cell mass, but its performance must be evaluated through the observed measurements, repeatability, and uncertainty. Without reported analyses, the proposed measurement cannot be judged from its definition alone. The study question is statistically meaningful, but the registry record does not include the results needed to assess its answer.

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 consequential limitation of the registry record is that it does not report numerical results for the primary outcome. The endpoint is defined, but no mean, standard error, repeatability estimate, confidence interval, or group comparison is reported. The registry lists zero analyses, so the statistical evidence for the stated aims cannot be assessed from this record.

The study is nonrandomized and unmasked. The healthy-control and longstanding type 1 diabetes groups are selected populations and are explicitly not described as a like-for-like control comparison. The registry does not report adjustment for differences between groups, so a group contrast, if available elsewhere, would require cautious interpretation.

The record does not report a detailed statistical plan, sample-size justification, interim-analysis plan, missing-data methods, or analysis populations. It does not explain how repeat-scan agreement was quantified. The planning assumptions listed in the record are described as an illustration based on an observed effect, not as the trial's design, and numerical planning results are not reported in the registry record.

The outcome timeframe is up to 2 months from enrollment, but the registry does not provide scan timing or participant-level completion information. The brief summary mentions biochemical testing, but does not report those results. The record also does not provide an independent validation result for the imaging measure. These limitations restrict assessment of measurement performance, group comparability, and the completeness of the reported evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of 18 F-FP-DTBZ Pancreatic PET Scanning as a Tool to Measure Beta Cell Mass — NCT02236754.
• Registry record last updated 2024-07-23; status last verified 2024-07.
• Results first posted 2024-07-23.
• 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

NCT02236754 is a completed, early-phase, nonrandomized, unmasked, parallel study sponsored by Columbia University. It evaluates 18 F-FP-DTBZ PET imaging as a proposed measure of pancreatic beta cell mass, with healthy controls and patients with longstanding type 1 diabetes. The registry lists enrollment of 23, a start date of 2013-07-02, and primary completion on 2014-04-23.

The primary endpoint is mean VMAT2 functional binding capacity in the body and tail of the pancreas, defined using VMAT2 binding potential and PET region-of-interest volume. The stated study question includes reproducibility of repeat PET measurements. The registry record lists zero analyses and does not report primary outcome results, repeatability estimates, or a group comparison. Safety listings report zero serious adverse events, zero other adverse events, and zero deaths in each recorded group.