This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for PCORI Urea Cycle Disorder Study (NCT02740153), a registered phase not stated study. The primary outcome is Mortality.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02740153 |
| Phase | Phase not stated |
| Condition | Urea Cycle Disorders |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 187 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Children's National Research Institute |
| Results posted | Yes |
2. Clinical Question
Population
Children aged 18 and under with neonatal-type urea cycle disorders: CPSD, OTCD, ASD or ALD. The registry describes eligibility by age, diagnosis and transplant history; it does not report additional eligibility details in this record.
Intervention
Liver transplantation, with the transplant group defined by a history of liver transplant. The registry lists no intervention as given for the study itself, so this is an observational comparison by treatment exposure rather than a trial assigning the transplant.
Comparator
Participants without a history of liver transplant, managed medically. The brief summary describes conservative management as a low-in-protein diet, drugs and amino acid supplements; specific regimens used by participants are not reported in the registry record.
Primary question
How does mortality compare between the liver-transplant and no-transplant groups? The primary outcome is expressed as a number of deaths per 1000 person-years, with a 95% confidence interval. The registry record does not include the resulting mortality estimates or intervals, so the size and precision of the comparison cannot be read from the record.
3. Trial Design
The study, NCT02740153, is titled PCORI Urea Cycle Disorder Study. Its official title describes a comparison of liver transplantation with conservative management for urea cycle disorders. Children's National Research Institute is the sponsor. The registry lists the study as completed, with a start date of 2016-03-04, primary completion on 2019-06-10 and enrollment of 187.
The design description says that participants were selected according to exposure: liver transplant or medical management. The groups are defined by transplant history, rather than by random assignment. Allocation is not stated, and the registry explicitly identifies the comparison as nonrandomized. Consequently, the groups are not a like-for-like control comparison by design. The record does not report how treatment decisions were made or whether the groups were balanced on characteristics that could relate to mortality.
The transplant group is described as participants aged 18 and under with one of the listed neonatal-type disorders and a history of liver transplant. The comparison group has the same stated age and diagnosis criteria, no transplant history, and medical management. The registry's intervention entry is No Intervention Given, consistent with observing existing exposure rather than assigning a treatment within the study.
The listed primary outcome is mortality, with exposure time of 436 person years in the Liver Transplant Group and 386 person-years in the Without Transplant Group. The brief summary says Aim 1 compares survival, neurocognitive function and patient-reported quality of life. The registry lists 3 outcome measures, but the record does not provide their result estimates in the information. The number of analyses reported is 0.
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.
Before assignment: No pre-assignment details, this was not an intervention study.
Overall Study
| Stage | Urea Cycle Disorder With Liver Transplant | Urea Cycle Disorder Without Transplant |
|---|---|---|
| STARTED | 101 | 86 |
| COMPLETED | 101 | 86 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Treatment-related effects on mortality
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.
| Characteristic | Unit | Urea Cycle Disorder With Liver Transplant | Urea Cycle Disorder Without Transplant | Total |
|---|---|---|---|---|
| Participants analysed | 101 | 86 | 187 | |
| Age, Customized: <6 Months | Participants | 20 | 28 | 48 |
| Age, Customized: 6-12 Months | Participants | 29 | 10 | 39 |
| Age, Customized: 1-5 Years | Participants | 38 | 35 | 73 |
| Age, Customized: 5-10 Years | Participants | 10 | 10 | 20 |
| Age, Customized: >10 Years | Participants | 4 | 3 | 7 |
| Sex: Female, Male: Female | Participants | 34 | 33 | 67 |
| Sex: Female, Male: Male | Participants | 67 | 53 | 120 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 17 | 11 | 28 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 77 | 62 | 139 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 7 | 13 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Mortality, measured over 436 person years in the Liver Transplant Group and 386 person-years in the Without Transplant Group.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | participant per 1000 person-years |
| Endpoint classification | Event-Rate Endpoint |
The primary endpoint is mortality, described as a number of participants per 1000 person-years. It is a rate: deaths are considered in relation to the time participants contribute to follow-up. Person-time offers a way to describe event frequency when participants may contribute different amounts of observation time. The registry specifies 436 person years for the Liver Transplant Group and 386 person-years for the Without Transplant Group.
A mortality rate is useful for a comparison framed around follow-up because it accounts for the amount of observed time, rather than describing deaths only as a share of group membership. The registry specifies a 95% confidence interval as the measure of dispersion. In general, a confidence interval communicates the uncertainty and precision of an estimate under the assumptions of the analysis. It does not by itself remove bias from differences between groups.
The record names the endpoint and its unit but does not report the mortality rates or confidence limits. Therefore, the direction, magnitude and statistical precision of the primary comparison cannot be assessed from the endpoint information in the registry record. The zero deaths listed in the adverse-event entries are safety-record figures and should not be treated as a substitute for the primary endpoint analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies mortality as the primary outcome and specifies a rate per 1000 person-years, with a 95% confidence interval. It gives the exposure time for each group, but does not report the mortality rate estimates or their confidence limits. It therefore does not establish, in the available record, how the mortality rates compare or how precisely any difference was estimated. No p-value or other numerical result for the primary comparison is reported.
The group definitions matter to interpretation. Participants were grouped according to history of liver transplant or medical management; allocation is not stated, and the registry describes the study as nonrandomized. A difference between observed groups, if estimated, would not automatically represent an effect caused by transplantation. General statistical reasoning: treatment selection can be related to participant characteristics, disease history or other factors that also relate to outcome. Without information about adjustment and group comparability, the extent to which such factors were addressed is not reported in the registry record.
The registry describes the mortality aim as prospective by design, based on selection by exposure. This description identifies the exposure-based comparison, but does not supply details about follow-up procedures, outcome ascertainment or analysis methods. Those details are not reported in the registry record. The person-year denominators indicate that follow-up time is relevant to the intended rate comparison; they do not, on their own, supply the event counts or rates needed to interpret the outcome.
The adverse-event entries list 0 deaths in the transplant group and 0 in the group without transplant. Those entries also list 0 participants with serious or other adverse events in each group. These figures describe the registry's adverse-event reporting, not a reported mortality rate analysis. In particular, the record does not explain how those entries relate to the primary endpoint population, follow-up window or endpoint calculations. They cannot fill in the missing rate estimates or confidence intervals.
The study's brief summary names survival, neurocognitive function and patient-reported quality of life as aims of Aim 1. The record lists 3 outcome measures but does not report results for those outcomes in the information available. As a result, conclusions about the size, precision or clinical meaning of any outcome comparison are not supported by the registry results.
9. Statistical Methods Explained
The registry gives a rate-type primary endpoint and a confidence interval, but it does not report the numerical mortality estimates, the confidence limits or the specific analysis method. The explanations below describe general statistical ideas relevant to this kind of outcome; they do not identify methods that the registry confirms were used.
What a person-time rate describes
In general, a rate relates the number of observed events to the time participants are observed and at risk of those events. Here, the stated unit is participant per 1000 person-years, and the registry gives separate exposure times for the transplant and no-transplant groups. Person-time can accommodate differences in follow-up duration: a participant observed for less time contributes less time to the denominator than a participant observed for longer. The rate is not the same quantity as the proportion of participants who experience an event.
Interpreting a rate still requires clarity about the event definition, observation period, censoring and how person-time was accumulated. The registry identifies mortality and reports group exposure time, but details of these procedures are not reported in the registry record. Without an event count and the rate estimate, the person-time figures alone do not indicate the observed mortality frequency.
What a confidence interval contributes
In general, a confidence interval expresses statistical uncertainty around an estimate under a specified model and its assumptions. A relatively narrow interval would indicate greater precision than a wide interval, though precision is not the same as freedom from bias. A confidence interval also does not establish that a group difference is causal. Because the record supplies only the stated 95% confidence interval format and not its endpoints, the precision of the mortality comparison cannot be assessed.
For rate comparisons, the analysis must account for event counts and the amount of time at risk. The approach also depends on assumptions about how events arise and how the observations relate to one another. These modeling choices are not reported in the registry record. In general, over-dispersion means that observed variation is greater than a model expects. If it is present but not accounted for, uncertainty estimates can be too small; whether it is relevant or addressed in this study is not reported.
Why the group structure matters
The study compares groups defined by exposure history rather than by stated random allocation. In general, randomization can help balance measured and unmeasured prognostic factors across groups, while an observational comparison can retain differences associated with treatment selection. Adjustment can address measured factors when specified and appropriately analyzed, but it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjustment set or model, so the extent of adjustment is unknown.
The record describes the mortality aim as prospective by design and based on selection by exposure. Prospective data collection does not itself make an exposure-based comparison randomized. It is still necessary to know how groups were formed, how follow-up and outcomes were determined, and how baseline differences were considered. The registry does not report these details.
What the planning illustration means
The registry describes sample-size planning illustrations as calculations based on the observed effect, not as the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation; the effect to detect is a stated share of the observed effect. For time-to-event tables, the illustration refers to the total number of events using Schoenfeld; other illustrations refer to participants per arm.
These assumptions describe planning illustrations only. They do not establish that the study was designed or conducted using those assumptions, and they are not observed power. The numerical planning values and any original sample-size justification are not reported in the registry record. General statistical reasoning: a planning calculation depends on its assumed effect and design conditions, so it should not be read as evidence that an observed result is reliable or that the study had a particular probability of detecting an effect.
Finally, the record reports 0 analyses. It does not identify a fitted model, a statistical test, a method for handling missing observations, or an approach to multiple outcomes. Those analytic choices cannot be inferred from the endpoint format or the planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and describes Aim 1 as comparing survival, neurocognitive function and patient-reported quality of life. Mortality is identified as the primary outcome. The record reports 0 analyses, and does not provide a multiplicity strategy, such as whether or how inference across outcomes was adjusted. It is therefore not possible to determine how the study handled the chance of false-positive findings across multiple comparisons. This is a reporting gap, not evidence that a particular method was or was not used.
Missing-data procedures are not reported in the registry record. There is no description of the extent of missing outcome or covariate data, how missingness was assessed, or whether any imputation or sensitivity analysis was used. The registry also does not report an analysis population definition, such as inclusion rules for participants who began follow-up or contributed outcome data. The enrollment and group descriptions alone do not establish which participants were included in an analysis.
Without reported analyses, estimates or analysis-population details, the handling of incomplete follow-up and outcome data cannot be evaluated. General statistical reasoning: missingness can affect both the amount of information and the interpretation of a comparison, especially if the reasons for missing data differ between groups or relate to outcomes. Whether that concern arose or was addressed in this study is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Urea Cycle Disorder With Liver Transplant | 0 | 101 | 0.0% |
| Urea Cycle Disorder Without Transplant | 0 | 86 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Urea Cycle Disorder With Liver Transplant | 0 of 101 |
| Urea Cycle Disorder Without Transplant | 0 of 86 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Urea Cycle Disorder With Liver Transplant | 0 of 101 |
| Urea Cycle Disorder Without Transplant | 0 of 86 |
The registry's adverse-event entries list the transplant group as having 101 participants at risk, with 0 affected by serious adverse events, 0 affected by other adverse events and 0 deaths. The group without transplant is listed as having 86 participants at risk, with 0 affected by serious adverse events, 0 affected by other adverse events and 0 deaths. No top serious adverse-event terms are listed.
These are adverse-event reporting figures, not a complete description of safety surveillance. The registry record does not report event definitions, collection procedures, follow-up windows or an explanation of how these counts relate to the primary mortality analysis. A count of 0 in an adverse-event entry does not establish that no events occurred outside the recorded categories or observation period.
The zero deaths in these entries should not be used to reconstruct a mortality rate. Although the primary endpoint includes group exposure time, the record does not give the endpoint event counts, calculated rates or confidence intervals. The adverse-event entries do not explain whether they use the same outcome definition, analysis population or follow-up as the primary endpoint. Interpretation should therefore remain specific to what the registry records in these safety fields.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to compare mortality across groups defined by liver-transplant history in children with specified urea cycle disorders. It also records the primary endpoint's unit, confidence interval format and group exposure times. The available result information does not include the mortality estimates or confidence limits, however, so it does not show the magnitude or precision of the primary comparison.
The adverse-event entries report 0 deaths and 0 affected participants in the serious and other adverse-event categories for each group. Those counts should be read as the entries in the registry, not as a replacement for the primary mortality analysis or as proof that no events occurred under every possible definition or follow-up period. The record does not provide the detail needed to reconcile those safety entries with the endpoint.
The study is observational as described: participants were selected according to transplant exposure, and allocation is not stated. General statistical reasoning: an association between exposure and outcome in such groups can reflect treatment effects, differences in participant characteristics, or both. Since adjustment methods and group comparability are not reported, the registry information does not support a causal interpretation.
The brief summary identifies survival, neurocognitive function and patient-reported quality of life as study aims, but results for those outcomes are not reported in the record described. The registry also does not provide a reported analysis, missing-data method or multiplicity approach. Accordingly, the information supports describing the study question and its recorded design, but not drawing conclusions about whether one management strategy has better outcomes or about the clinical importance of any comparison.
13. Why This Trial Matters Statistically
This study addresses a difficult statistical setting: a rare disorder, an exposure-based comparison and outcomes that include mortality. The registry's stated approach relates mortality to person-time, which is useful when the amount of observed follow-up may vary across participants. Reporting group exposure time makes the intended rate framework clearer than a bare count would, although rates and their confidence intervals are needed to interpret the comparison.
The nonrandomized design is central to how the question should be read. Participants are classified by transplant history rather than by stated random allocation. This makes confounding and differences between groups important considerations for interpretation. The registry does not report adjustment methods or enough information to assess whether those differences were addressed.
The record also illustrates the distinction between a clearly named endpoint and a fully interpretable result. It specifies mortality, the rate unit, the confidence-interval format and exposure time, yet does not report the rate estimates or intervals. The adverse-event counts do not supply those missing results. Nor does the record give analyses for the other outcomes named in the study aims.
Statistically, these omissions limit assessment of effect size, precision, analysis choices and the relationship between the stated aims and reported results. The planning assumptions describe illustrations rather than the study's own design, so they cannot stand in for a reported analysis or a sample-size justification. The record is informative about the comparison's structure, but the absence of outcome estimates places a firm boundary on what can be concluded from it.
14. 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 interpretation is that the registry record does not report the mortality rates or their 95% confidence limits. It gives group exposure time but not the numerical endpoint results, so neither the magnitude nor precision of the primary comparison can be assessed. The record also reports 0 analyses.
The design is described as a prospective comparison based on selection by exposure, with allocation not stated. It is explicitly not a randomized comparison, and the groups are not a like-for-like control comparison. The registry does not report how treatment selection occurred, whether baseline characteristics differed, or whether analyses adjusted for potential confounders. Causal interpretation is therefore not supported by the design description alone.
Details of follow-up, outcome ascertainment and person-time calculation are not reported in the registry record. The relationship between the adverse-event deaths and the primary mortality endpoint is also not described. The event entries list no affected participants or deaths, but do not give enough context to establish the scope of that reporting.
The record names survival, neurocognitive function and patient-reported quality of life as aims, but does not give results for these outcomes. It does not report methods for multiplicity, missing data, analysis populations or a statistical model. The sample-size material is described as planning illustration based on the observed effect, rather than the study's own design; the original sample-size justification is not reported in the registry record. These limitations concern what can be evaluated from the registry information and do not establish what analyses may have been conducted elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: PCORI Urea Cycle Disorder Study — NCT02740153.
- Registry record last updated 2021-01-26; status last verified 2021-01.
- Results first posted 2021-01-26.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02740153, PCORI Urea Cycle Disorder Study, is listed as completed and sponsored by Children's National Research Institute. Enrollment was 187. The study dates are 2016-03-04 to primary completion on 2019-06-10.
The study compares participants aged 18 and under with specified neonatal-type urea cycle disorders according to history of liver transplant or medical management. The registry describes the mortality comparison as prospective by design and based on selection by exposure; allocation is not stated, and the comparison is nonrandomized.
Mortality is the primary endpoint, expressed per 1000 person-years with a 95% confidence interval. Group exposure times are reported, but endpoint estimates and confidence limits are not. The record lists 3 outcome measures and 0 analyses. Adverse-event entries report 0 deaths and 0 affected participants for serious and other adverse events in each group. Further analysis, missing-data, multiplicity and follow-up details are not reported in the registry record.