IRB 14-009240, Does CEUS Positively Influence Selection of Biopsy Sites When Evaluating Transplant Kidneys?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IRB 14-009240, Does CEUS Positively Influence Selection of Biopsy Sites When Evaluating Transplant Kidneys? (NCT02625428), a non-randomized phase 4 study. The primary outcome is Abnormal Biopsy.

2. Clinical Question

The stated rationale is that CEUS may evaluate segmental renal perfusion differences better than Doppler ultrasound. If imaging identifies a region that is more abnormal, sampling that region could affect whether a biopsy detects a histopathological abnormality and its grade or severity. The trial is described as a pilot study investigating that possibility, not as a randomized comparison establishing a treatment effect.

The primary outcome is the number of participants with abnormal biopsies in either the primary or secondary biopsy location, based on diagnosis by a clinical pathologist. A secondary outcome concerns the number of patients with a higher degree of renal transplant rejection using multiple biopsies compared with a single biopsy. The registry record does not report the observed counts for either outcome, nor does it report a direct numerical comparison of biopsy-site selection by CEUS and Doppler ultrasound.

3. Trial Design

The registry record describes NCT02625428 as a completed, Phase 4, non-randomized, single-masked, parallel study sponsored by Mayo Clinic. Enrollment was 40. The listed study start was 2015-11, and primary completion was 2018-12. The primary outcome timeframe is 1 year. The record does not describe the masking procedure or state which people were masked.

Two groups are described. For-cause biopsies were performed to evaluate a recent rise in serum creatinine. Surveillance biopsies were performed after transplant, mostly to look for subclinical rejection. These groups reflect different clinical reasons for biopsy; the registry expressly flags that the allocation was non-randomized and that the arms are not a like-for-like control comparison. Differences between the groups therefore cannot be interpreted as if participants had been randomly assigned to comparable conditions.

The interventions listed are Optison, ultrasound (US), and contrast-enhanced ultrasound (CEUS). The summary describes CEUS as a possible way to assess segmental renal perfusion and help direct biopsy to the most abnormal part of the renal cortex. The registry record does not give the sequence or timing of imaging and biopsy procedures, the specific allocation process, or further protocol details.

The registry lists 2 outcome measures and 0 analyses. It identifies abnormal biopsy as the primary outcome and lists a secondary outcome about rejection grade when multiple biopsies are compared with a single biopsy. Although the study status is completed, the registry record does not report outcome results or an inferential analysis. It also does not report a statistical analysis plan or a sample-size justification. Planning illustrations based on an observed effect, if displayed with the registry information, should not be mistaken for the study’s original design rationale or for evidence of observed power.

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 Abnormal Biopsy, measured over 1 year.

The primary endpoint is the number of participants with an abnormal biopsy in either the primary or secondary biopsy location. The registry defines the outcome as a count of participants and specifies that abnormality is determined by diagnosis from a clinical pathologist. Its stated timeframe is 1 year.

This endpoint is relevant to the study question because the proposed role of CEUS is to help select a biopsy site in a transplanted kidney. Comparing findings from primary and secondary biopsy locations can address whether sampling more than one location identifies an abnormality that a single location might not reveal. The endpoint is a participant count, not a continuous measure of renal perfusion or a direct measure of diagnostic accuracy. The registry record does not provide a threshold defining an abnormal biopsy, details of pathology grading, or the actual number of participants with abnormal findings.

As a general statistical point, a count of participants with an outcome can be reported alongside the number assessed in each group. For a comparison, the interpretation depends on clearly defined analysis groups, complete outcome ascertainment, and an appropriate account of how participants were assigned or selected. In this study, the group allocation was non-randomized, and the registry warns that the arms are not comparable as a like-for-like control comparison. The endpoint definition alone therefore cannot establish that CEUS caused any difference in biopsy findings.

The secondary outcome asks whether multiple biopsies identify a higher degree of renal transplant rejection than a single biopsy. The registry record does not report the corresponding result or explain how rejection grade was classified for that comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with matching the method to the outcome and design. The primary outcome is a count of participants with an abnormal biopsy, so a result would ordinarily be presented as the number of participants meeting the endpoint and the number assessed. A comparison would also need a clearly defined contrast, such as a difference in outcome frequency between explicitly described strategies. The registry record identifies the endpoint but does not report those counts, a comparison estimate, or an analysis.

What a confidence interval would add

As a general statistical explanation, a confidence interval expresses uncertainty around an estimated quantity under a specified method and its assumptions. It helps readers distinguish a relatively precise estimate from one compatible with a broad range of effects. A point estimate alone does not convey that uncertainty. No confidence interval for the primary or secondary outcome is reported in the registry record, so the precision of any study finding cannot be evaluated from the posted results.

For a binary outcome, uncertainty depends on how many participants experience the outcome and how many contribute data. A valid interval also depends on the estimand and analysis population being clear. In this study, the registry identifies the primary endpoint as a participant count and gives an enrollment total, but does not report the numbers with abnormal biopsies or the number actually assessed for that outcome. Enrollment is not a substitute for the endpoint denominator.

Why the design affects interpretation

The study is non-randomized and parallel, with for-cause and surveillance groups. General statistical reasoning cautions that non-randomized groups may differ in their reasons for entering the study or in other characteristics. Here, the stated reasons for biopsy differ by group, and the registry explicitly says the arms are not a like-for-like control comparison. An observed difference between groups, if reported, would not on its own isolate an effect of CEUS. The record does not describe an adjustment strategy that might address measured differences, and it does not report an analysis.

The study’s question also concerns selection of biopsy sites and findings from multiple locations. A comparison of locations within a participant would involve paired observations: findings from the same person are related, rather than independent. As a general matter, analyses of paired observations should account for that relationship. The registry record does not specify whether the primary or secondary outcome was analyzed as paired data, how multiple sites were handled, or what statistical method was used.

Planning illustrations are not trial results

The stated assumptions for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are described as being computed from an observed effect, with the effect to detect expressed as a stated fraction of that observed effect. These are planning assumptions, not a report of the study’s own design justification. The registry record does not report a sample-size justification or a numerical observed effect for the endpoint. It therefore does not support interpreting any planning illustration as a pre-specified power calculation for the trial.

In general, sample-size calculations estimate the amount of information a future study might need to detect a chosen effect under specified assumptions. They do not establish that a completed study had that level of power, and they are not a substitute for an outcome estimate with uncertainty. If a planning calculation is based on an observed effect, it should be understood as an illustration conditional on that effect and the stated assumptions. It does not show that the effect is reliable or that the study’s design anticipated it.

Counts, event rates, and over-dispersion

The registry classifies the primary outcome as binary and describes it as a participant count. For a binary endpoint, a participant either meets the endpoint definition or does not, assuming the outcome is assessed. General methods may model such outcomes using counts of events and non-events or a probability model. The registry does not identify a model, link function, or test. No specific method should therefore be attributed to the trial.

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. It matters because uncertainty can then be understated if the model treats observations as less variable or more independent than they are. The registry record does not identify an over-dispersion assessment or a model for the primary endpoint. Given that the primary outcome is a participant-level binary count, over-dispersion should not be presumed; whether any such issue applies depends on the analysis structure and data, which are not reported.

Multiplicity and interpretation

The registry lists 2 outcome measures, including the primary abnormal-biopsy endpoint and a secondary outcome related to rejection grade with multiple versus single biopsies. When several outcomes or comparisons are examined, general statistical practice considers whether multiple testing increases the chance of a nominally unusual result. A pre-specified hierarchy or adjustment may be used, depending on the objectives and analysis plan. The registry record does not report a multiplicity strategy, and it lists 0 analyses. It is not possible to determine from the record whether or how multiplicity was addressed.

Methods must also distinguish the planned question from the result actually reported. The summary describes a hypothesis about CEUS and perfusion assessment, but the primary outcome is abnormal biopsy in either biopsy location. Those concepts are related by the rationale, but they are not identical measures. Because outcome results, analysis details, and uncertainty estimates are not reported in the registry record, statistical conclusions about the magnitude or precision of any CEUS-related effect cannot be drawn from it.

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("For Cause", "Surveillance")
n      <- c(20, 20)
events <- c(10, 7)
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  For Cause  20  10  50.0  27.2  72.8  29.9  70.1  29.8  70.2
ARM  Surveillance  20  7  35.0  15.4  59.2  18.1  56.7  18.1  57.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures: the primary count of participants with abnormal biopsies in either the primary or secondary biopsy location, and a secondary outcome about identifying a higher degree of transplant rejection with multiple biopsies compared with a single biopsy. It lists 0 analyses. No multiplicity strategy, testing hierarchy, or adjustment method is reported in the registry record.

As a general statistical matter, examining several outcomes or comparisons can make nominal significance levels harder to interpret because more opportunities exist to observe an apparently notable result. A planned hierarchy or adjustment can clarify which outcomes are confirmatory and how inferences should be interpreted. The record does not say whether such procedures were planned or used, so it is not possible to characterize the reported analysis on this point.

The record does not report missing-data counts, the number of participants assessed for each endpoint, reasons for missing outcomes, or an approach to handling missing observations. It also does not describe an analysis population, such as whether all enrolled participants were included in each outcome analysis. The enrollment of 40 participants should not be treated as proof that all contributed complete endpoint data.

Without outcome denominators and missing-data information, readers cannot determine whether the endpoint findings were available for all enrolled participants or whether missingness could affect interpretation. The registry record also does not report a statistical analysis plan, so it is unknown whether the outcome definitions or analytical decisions were finalized before results were examined.

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 serious adverse event terms

Serious events with the highest arm-level rate: major bleeding complications (10.0%).

The registry reports serious adverse event figures separately for the for-cause and surveillance groups. In the for-cause group, 2 participants were affected by serious adverse events among 20 at risk; in the surveillance group, 1 participant was affected among 20 at risk. The record lists 0 other adverse events and 0 deaths in each group. It also lists Major Bleeding Complications as a serious adverse event term with 10.0%.

These counts should be read as registry-reported safety information, not as a causal comparison between groups. The study was non-randomized, and the group descriptions reflect different reasons for biopsy. The record does not state which imaging or biopsy procedure was associated with each serious event, provide event-level timing, or explain the context for the 10.0% figure. It also does not report a formal statistical comparison of adverse event rates.

In general, adverse event counts depend on the definitions used, observation period, and completeness of reporting. The listed figures do not establish whether events were related to CEUS, Optison, ultrasound, or biopsy. They should not be used alone to compare interventions or infer causation.

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

The registry record supports a limited description of the study’s purpose and design. It describes a pilot investigation of whether CEUS may help evaluate segmental renal perfusion and direct biopsy toward the most abnormal part of the renal cortex. It identifies abnormal biopsy in either the primary or secondary biopsy location as the primary outcome and reports enrollment of 40 participants.

The record does not report the observed primary endpoint result, the secondary rejection outcome result, an effect estimate, or a confidence interval. It therefore does not show how often abnormal biopsies occurred, whether multiple locations identified more abnormalities than a single location, or how precisely any difference was estimated. Although the study is completed, its registry entry does not provide the outcome findings needed to answer those questions.

The design also limits causal interpretation. For-cause and surveillance participants entered the study for different stated reasons, and allocation was non-randomized. The registry specifically cautions that the arms are not a like-for-like control comparison. Any difference between those groups, if one were reported, could not automatically be attributed to CEUS or to biopsy-site selection.

The endpoint is relevant to abnormal biopsy detection, but it is not equivalent to a direct estimate of CEUS diagnostic accuracy or superiority over Doppler ultrasound. The registry’s rationale proposes a possible advantage in assessing regional perfusion; it does not report a numerical comparison of the imaging methods. No conclusion about the magnitude, direction, or clinical importance of an imaging effect can be drawn from the posted outcome information.

The safety counts are descriptive and do not identify the intervention associated with each event. Overall, the record documents a study question, group descriptions, outcome definitions, and limited adverse-event information. It does not report the results or statistical detail required to determine whether CEUS changed biopsy selection or findings.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it connects an imaging question with a sampling question. The stated rationale is that regional perfusion differences might help identify a more abnormal biopsy location. The primary endpoint then counts participants with an abnormal biopsy in either the primary or secondary location. Understanding that link requires attention to what was measured: abnormal biopsy findings are not the same outcome as image quality, site-selection accuracy, or a direct comparison of imaging tests.

The design also illustrates why the allocation process matters. For-cause and surveillance biopsies arise from different clinical reasons, and the registry describes a non-randomized study. Its warning that the arms are not a like-for-like control comparison is important when interpreting any group contrast. Statistical adjustment cannot be assumed to remove differences, especially when the registry does not report an analysis or adjustment plan.

Finally, this record demonstrates the distinction between a study being completed and results being available in the registry. Enrollment and outcome definitions describe the intended scope, while estimates and uncertainty are needed to understand what the study found. The record lists 0 analyses and does not report the primary or secondary outcome results. That absence prevents assessment of precision, comparison of biopsy strategies, or evaluation of the stated imaging rationale from the registry information alone.

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 central limitation for interpreting the registry entry is that it does not report results for either listed outcome. There are no primary endpoint counts, endpoint denominators, effect estimates, confidence intervals, or statistical tests. The registry lists 0 analyses. Accordingly, the study’s findings and their precision cannot be assessed from this record.

The study is non-randomized, and the two groups represent different biopsy contexts. For-cause biopsies evaluate a recent rise in serum creatinine, while surveillance biopsies are mostly intended to look for subclinical rejection. The registry explicitly states that the arms are not a like-for-like control comparison. This limits interpretation of any potential difference between groups as an effect of imaging or biopsy strategy.

The registry does not describe the allocation process, masking procedure, participant characteristics, imaging sequence, biopsy-site selection rules, pathology grading criteria, or handling of multiple biopsy locations. It does not report the analysis population, missing outcome counts, or methods for missing data. It also does not report a statistical analysis plan, a sample-size justification, or a multiplicity approach.

The primary endpoint concerns abnormal biopsy findings, while the study rationale concerns CEUS assessment of perfusion and selection of a biopsy site. The record does not report a direct measure of diagnostic accuracy or a numerical comparison of CEUS with Doppler ultrasound. The safety information is limited to group-level counts and a listed serious adverse event term; event attribution and further context are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: IRB 14-009240, Does CEUS Positively Influence Selection of Biopsy Sites When Evaluating Transplant Kidneys? — NCT02625428.
• Registry record last updated 2020-03-02; status last verified 2020-02.
• Results first posted 2020-03-02.
• 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

NCT02625428 is a completed, Phase 4, non-randomized, single-masked, parallel pilot study sponsored by Mayo Clinic. Enrollment was 40. The listed study start was 2015-11 and primary completion was 2018-12. The study investigates whether CEUS may help assess segmental renal perfusion and guide biopsy-site selection in kidney transplants.

The primary outcome is the number of participants with an abnormal biopsy in either the primary or secondary location, diagnosed by a clinical pathologist, with a timeframe of 1 year. A secondary outcome concerns higher rejection grade with multiple biopsies compared with a single biopsy. The registry record lists 0 analyses and does not report results for either outcome.

For-cause and surveillance groups are described, but the registry cautions that the non-randomized arms are not a like-for-like control comparison. Serious adverse event counts are reported by group; the record does not attribute them to a specific intervention.