WP02 Continued Access Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for WP02 Continued Access Study (NCT04862156), a na na study. The primary outcome is Incidence of Early Allograft Dysfunction (EAD).

2. Clinical Question

3. Trial Design

This was a single-group continued access study of normothermic machine perfusion using the OrganOx Metra device in human liver transplantation. The registry describes the intervention as placing the liver on the device after routine retrieval, for normothermic machine perfusion during transport. The study summary states that the continued access phase would collect additional effectiveness and safety data to support the objectives and outcomes of the original IDE pivotal study.

The registry lists enrollment of 19 participants. It records phase as not applicable, allocation as not applicable, and masking as none. The single-group design means that no concurrent comparison arm is reported. The record itself cautions that the arms are not a like-for-like control comparison when allocation is not randomized; in this study, there is only one group. Its observations can describe participants in that group, but cannot provide a randomized estimate of the intervention’s effect relative to another treatment or process.

The recorded study start date is 2021-10-10, and the primary completion date is 2022-07-31. The overall status is terminated. The reason for termination and any consequences for enrollment or follow-up are not reported in the registry record. The record also does not report a detailed protocol, eligibility criteria, recruitment procedures, or how the study team determined that data collection should end.

The registry identifies one primary outcome measure, early allograft dysfunction, with a timeframe of 7 days. It reports no analysis results. Thus, the design and intended outcome can be described, but the available record does not establish what was observed for the primary outcome or whether the planned data collection was completed as intended.

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 Incidence of Early Allograft Dysfunction (EAD), measured over 7 days.

The primary endpoint is the incidence of early allograft dysfunction, expressed as a count of participants. The registry assigns it a timeframe of 7 days and describes it as a measure of the severity of immediate graft injury. In general, an endpoint translates a broad clinical question into an outcome that can be recorded and analyzed. A count of participants with an event is a binary outcome: each participant is classified according to whether the event occurred within the specified timeframe.

Such an outcome can be useful for describing how often a specified complication is observed during an early period after transplantation. A clearly defined timeframe also makes the period of observation explicit. However, the registry record does not give the operational criteria used to classify early allograft dysfunction, the assessment schedule, or procedures for adjudicating uncertain cases. Those details are not reported in the registry record.

Most importantly, no primary endpoint count or analysis is reported. Enrollment of 19 participants does not itself establish how many experienced early allograft dysfunction, nor does it confirm that all enrolled participants contributed evaluable endpoint data. The posted information therefore identifies what the study intended to measure, but does not quantify the observed outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a count of participants with an event, which is a binary outcome at the participant level. In general, analyzing a binary outcome requires knowing how many participants experienced the event and how many were assessed. Those counts allow an event frequency to be described for the group under study. In this registry record, the primary outcome is identified, but its observed count and analysis are not reported. An event frequency or uncertainty interval for early allograft dysfunction therefore cannot be stated.

What a confidence interval would describe

In general, a confidence interval expresses the statistical uncertainty around an estimate. For a binary outcome, it can communicate how imprecisely the event frequency is estimated, given the observed data and the chosen method. An interval does not correct for missing observations, bias in outcome measurement, or the absence of a comparator. Because the registry record does not report the primary endpoint count or an estimate, it also does not report a confidence interval for that endpoint.

What the single-group design can estimate

In general, a single-group study can describe outcomes among the participants observed, if the relevant outcomes and denominators are reported. It cannot use random allocation to balance measured and unmeasured factors between intervention and comparator groups. A comparison with an external or historical benchmark, if one were made, would require additional assumptions and methods; no such comparison is reported in the registry record. Here, there is no comparator arm reported, so a relative effect cannot be estimated from a randomized contrast.

It is also important to distinguish a descriptive result from a causal conclusion. A recorded event after an intervention is an observation in time, but timing alone does not establish that the intervention caused the event. Likewise, an absence of a reported primary result is not evidence that no events occurred. The registry record gives no primary endpoint count, so neither an observed event frequency nor a conclusion about the direction or size of an association is available.

What the planning illustration means

The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes sample sizes for planning based on a fraction of the observed effect. These are planning illustrations, not the design or analysis of this single-group study, and they are not observed power. A planning calculation asks what sample size might be required under stated assumptions; it does not report how much power the completed study had. The assumptions do not turn the single-group study into a two-arm trial or supply a result for the primary outcome.

In general, sample-size planning depends on assumptions about the effect to detect, the outcome variability or event frequency, the significance threshold, and the allocation and analysis method. If those assumptions differ from the study’s actual data or clinical context, a planning figure may not describe the precision achieved. The registry record does not report the study’s own sample-size justification, and the planning illustration should not be interpreted as evidence that the study was designed to detect a particular effect.

Why event definitions and follow-up matter

For a binary endpoint, the outcome definition determines which observations count as events. The timeframe determines when an event qualifies. Consistent assessment and clear rules for participants whose status is uncertain are important for interpretability. The registry identifies early allograft dysfunction and a 7 days timeframe, but detailed diagnostic criteria, assessment procedures, and handling of uncertain or missing outcome data are not reported in the registry record. These gaps limit the ability to evaluate the endpoint’s measurement and completeness.

Over-dispersion is a general concern when data vary more than a simple model assumes, especially for grouped or repeated event data. It can make standard errors too small if the model does not account for the extra variation. The primary outcome is registered as a participant count, and no model or analysis result is reported. The record therefore gives no basis to determine whether over-dispersion was assessed or relevant to the analysis. It should not be inferred that a particular model was used.

What can and cannot be reproduced

A recalculation from posted summary statistics is possible only when the relevant values are available, and would represent a simple unadjusted calculation rather than the sponsor’s full analysis. No primary outcome analysis is reported in the registry record, so there is no reported endpoint estimate to recalculate. The number of analyses recorded is 0. No adjusted model, statistical test, confidence interval, or p-value for the primary endpoint is reported.

In general, a p-value assesses how compatible data are with a specified null hypothesis under the assumptions of a particular test. It does not measure the probability that a treatment works, and it does not describe the size or clinical importance of an effect. Here, no primary-outcome p-value is reported, and the single-group design would in any case not furnish a randomized comparative test. Statistical detail should not be inferred from the study’s stated purpose or from its enrollment count.

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("Normothermic Machine Perfusion (NMP)")
n      <- c(19)
events <- c(9)
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  Normothermic Machine Perfusion (NMP)  19  9  47.4  24.4  71.1  27.3  68.3  27.2  68.5

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure: early allograft dysfunction within 7 days. It does not report a statistical analysis for that outcome, and the number of analyses recorded is 0. The registry record does not report whether additional outcomes were planned, which outcomes were considered secondary, or whether any adjustment for multiple comparisons was planned. Therefore, the approach to multiplicity is not reported in the registry record.

In general, multiplicity arises when several outcomes, timepoints, or statistical comparisons are examined. Repeated testing can increase the chance of at least one apparently notable finding even when no real effect exists. Statistical plans may address this through prespecified outcome hierarchies or adjustments, but the record does not describe such methods. No multiplicity procedure should be presumed.

The record does not report how missing primary outcome data were handled, how many participants had an evaluable outcome, or whether any participants were excluded from an analysis. It also does not describe an intention-to-treat population, a per-protocol population, or another analysis population. Enrollment of 19 participants cannot establish that all participants contributed complete endpoint data. In general, missing observations can affect an estimate when the participants with unavailable outcomes differ from those with observed outcomes, and the direction or size of such an effect depends on the circumstances. Those circumstances are not reported in the registry record.

Without the analysis population, endpoint completeness, and missing-data procedures, the reader cannot determine the denominator used for the primary endpoint or assess whether the analysis represented all enrolled participants. These are reporting gaps, not evidence that particular participants were excluded or that a specific missing-data method was used.

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: hepatic (31.6%), genitourinary (31.6%), cardiovacular (21.1%), respiratory (21.1%), infection (15.8%).

For the normothermic machine perfusion group, the registry reports 19 participants at risk and 19 affected for serious adverse events. For the other adverse-event count, it reports 19 participants at risk and 0 affected. It also reports 2 deaths. The registry lists serious-event categories and percentages: Hepatic, 31.6%; Genitourinary, 31.6%; Cardiovacular, 21.1%; Respiratory, 21.1%; Infection, 15.8%; and Neurology/Psychiatry, 15.8%.

These are safety counts and category percentages as recorded; they are not a comparison between treatment groups. The record does not explain the event definitions, collection period, relationship assessments, or whether category entries can overlap for the same participant. It does not report the timing or causes of the 2 deaths. The category percentages should therefore be read as registry-listed summaries, not as evidence that an event was caused by the device or that categories are mutually exclusive. In general, adverse-event reporting helps describe what occurred during observation, but attribution and comparative risk require additional information and an appropriate comparison.

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

The registry record establishes that a continued access study of normothermic machine perfusion was registered as a single-group study, with enrollment of 19 participants and early allograft dysfunction within 7 days as its primary outcome. It also records selected safety counts, including 19 participants affected in the serious adverse-event count and 2 deaths. These registry entries describe the registered study and its posted information.

The record does not report the primary endpoint count, an endpoint estimate, or an analysis. It therefore does not show how often early allograft dysfunction occurred among participants in this study. The absence of a reported result cannot be interpreted as a zero event count, and the enrollment total cannot be substituted for the number with or without the outcome.

The single-group design also means the record does not offer a randomized comparison with another approach. Even a complete event count would describe outcomes in this group rather than establish what would have happened under a comparator. The safety counts are not, by themselves, evidence that the device or procedure caused an adverse event or death. The registry does not report event attribution, timing, or a comparison group that could help interpret relative safety.

More broadly, a registry entry is a record of study information and posted results, not a complete account of all clinical context. The record does not report detailed eligibility criteria, endpoint ascertainment procedures, missing-data handling, analysis populations, or the reason the study was terminated. Those omissions limit the conclusions available from this entry. It is appropriate to describe the design and recorded figures, while keeping unreported primary results and causal claims unresolved.

14. Why This Trial Matters Statistically

This study is statistically notable because its registry entry combines an explicitly single-group design with an intended primary outcome that is not accompanied by a posted analysis. That distinction matters: a study can identify a clinically relevant question and define a measurement timeframe without supplying the data needed to estimate the outcome. Here, the primary measure is early allograft dysfunction within 7 days, but no participant count or analysis is reported for it.

The design also clarifies what kind of evidence the study could generate. A single group can contribute descriptive information about observed outcomes and safety events, but it does not create a randomized treatment contrast. This is especially important when interpreting adverse events: observed events can be described, but the registry figures alone do not show whether their frequency differs from another approach or whether the intervention caused them.

Reporting detail is central to statistical interpretation. For a binary endpoint, the event count and the number assessed determine the descriptive estimate; the analysis population and handling of unavailable outcomes help explain whom that estimate represents. The registry record does not report these elements for the primary outcome. The resulting limitation is not a subtle modeling issue: the main outcome cannot be quantified from the posted record.

The continued access context is also stated in the registry summary: additional effectiveness and safety data were intended to support the objectives and outcomes of the original IDE pivotal study. That purpose provides context, but does not replace posted results or a documented analysis plan. The record is therefore useful for understanding the study’s scope and design, while also illustrating why transparent reporting of outcome counts, denominators, and analysis methods is necessary for readers to assess evidence.

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 for interpreting this specific study is that the registry record does not report a result for its primary outcome. It names early allograft dysfunction, a count of participants, and a timeframe of 7 days, but does not provide an event count, denominator for the outcome analysis, or statistical analysis. The outcome’s diagnostic criteria and assessment procedures are also not reported in the registry record.

The study is single group, with allocation recorded as not applicable and masking as none. No comparator group is reported, so the registry entry cannot support a randomized comparative estimate. The record does not describe detailed eligibility criteria or participant characteristics, limiting assessment of who the findings would represent even if primary outcome results were available.

Although enrollment is reported as 19, the record does not say how many participants completed follow-up or had an evaluable primary outcome. Missing-data handling, analysis populations, and reasons for any exclusions are not reported. The overall study status is terminated, but the reason for termination and its implications for study conduct are not reported in the registry record.

The safety information includes serious adverse-event counts, category percentages, and 2 deaths, but the record does not report event timing, causes, attribution, or detailed collection methods. It is not possible to infer from the registry entries alone whether categories overlap or whether events were related to the intervention. The record also does not report the study’s own sample-size justification or a statistical analysis plan. These limitations constrain both the descriptive interpretation of outcomes and any broader conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: WP02 Continued Access Study — NCT04862156.
• Registry record last updated 2025-04-15; status last verified 2024-01.
• Results first posted 2023-11-29.
• 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 NCT04862156, WP02 Continued Access Study, sponsored by OrganOx Ltd. It is a single-group study of normothermic machine perfusion using the OrganOx Metra device in human liver transplantation. Enrollment is listed as 19; phase and allocation are recorded as not applicable, and masking as none. The recorded start date is 2021-10-10, the primary completion date is 2022-07-31, and the study status is terminated.

The primary measure is incidence of early allograft dysfunction, recorded as a count of participants over 7 days. No primary outcome analysis is reported. The safety record lists 19 participants at risk and 19 affected for serious adverse events, 19 at risk and 0 affected for the other adverse-event count, and 2 deaths. The reason for termination, detailed outcome methods, missing-data handling, and analysis populations are not reported in the registry record.