Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease (NCT02937350), a na phase 1 study. The primary outcome is Metabolic Clearance of D6-25(OH)D3.

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 1, completed, single-group study of D6-25-hydroxyvitamin D3 in chronic kidney disease. Allocation is listed as not applicable, and masking is listed as none. These features distinguish the study from a randomized, masked comparison: the record does not describe assignment to competing treatments or a control group. The registry lists enrollment as 88. It records a start date of 2017-03-01 and primary completion on 2019-07-08.

The brief summary states that the goal was to better understand vitamin D catabolism and how it is affected by chronic kidney disease and race. That is a broad scientific aim; it does not by itself establish that the study included a comparison between racial groups or between people with and without chronic kidney disease. Details of the racial categories, any comparison groups, and any subgroup analysis are not reported in the registry record. The intervention and study population are described in one arm entry, but no further arm-level results are reported.

The primary outcome is metabolic clearance of D6-25(OH)D3, expressed in milliliters per day, with a timeframe of 8 weeks. The record describes calculation from the administered dose and the area under the plasma concentration-time curve. It also lists secondary outcomes for area under the curve, terminal half-life, and volume of distribution. These outcomes characterize different aspects of the compound’s measured concentration and disposition; their numerical findings are not reported in the registry record.

The record lists 9 outcome measures and 0 analyses. It does not report a statistical analysis plan, sample-size justification for the study itself, interim analyses, or a detailed account of how participants were included in each outcome analysis. The planning assumptions associated with illustrative sample-size calculations should not be mistaken for the trial’s design: the actual study is listed as single-group, not as an equally allocated two-arm comparison. No control comparison or causal treatment contrast can be inferred from the design information.

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 Metabolic Clearance of D6-25(OH)D3, measured over 8 weeks.

The primary endpoint is metabolic clearance of D6-25(OH)D3, reported in milliliters per day. Clearance is a measure of how quickly a substance is removed from the body, expressed relative to its concentration in the measured plasma profile. In this study’s registry description, clearance is calculated by dividing the administered dose of 25(OH)D3 by the area under the plasma concentration-time curve. The record refers to D6-25(OH)D3 as the measured compound and describes the AUC-based calculation. It does not report the administered dose or the resulting clearance estimate.

The AUC represents the accumulated measured concentration across the observation period. The registry says it is calculated with the linear trapezoidal method, which estimates the area between observed concentration measurements by connecting successive observations with straight-line segments. Concentrations were measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The primary outcome timeframe is 8 weeks.

Clearance is used as a pharmacokinetic summary: it condenses information from the concentration-time profile into a measure of removal. It is not itself a direct measure of a clinical benefit or harm. The registry specifies that the primary outcome is summarized as a mean with standard deviation, but neither the observed mean nor the standard deviation is reported in the registry record. Without those results, the posted record cannot indicate the observed level of clearance or its variability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The following statistical explanations are general, and distinguish concepts from what the registry record actually reports. The record identifies a continuous primary outcome summarized as a mean and standard deviation. It describes how clearance is derived from a dose and an AUC, but reports no numerical outcome estimates or analysis results. No statistical model for the primary endpoint is reported in the registry record.

What does the mean describe?

For a continuous measure, the mean is a measure of the center of the observed values. It can provide a concise summary of a group’s measured clearance, but it does not show the full distribution. A mean may be affected by unusually high or low observations, and two groups with the same mean could have different patterns of variability. In this record, the primary outcome is specified as a mean, but the actual mean is not reported in the registry record. Thus, the measure’s observed center cannot be read from the posted results.

What does the standard deviation describe?

In general, the standard deviation describes the spread of individual observations around their mean. It is expressed in the same units as the measured outcome, so it describes variability in clearance rather than uncertainty in the mean itself. A standard deviation is not a confidence interval. A confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the analysis. Neither the primary outcome standard deviation nor a confidence interval is reported in the registry record, so neither individual-level spread nor estimate precision can be assessed from this entry.

How does the AUC-based calculation work?

The registry defines metabolic clearance as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve. The AUC aggregates concentration over time, allowing a profile with multiple measurements to be represented by an area. The record says that AUC is calculated with the linear trapezoidal method. In general, this method joins adjacent observed concentrations with straight lines and estimates the area under each segment, then combines those segment areas into an overall AUC. The resulting value depends on the measurements and the time points used. The record lists measurements at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The values at those times, the AUC, and the administered dose are not reported in the registry record.

In general, an AUC-based clearance estimate is sensitive to the quality and coverage of the concentration-time profile. If measurements are sparse during a period of rapid change, the straight-line approximation may not fully represent the curve’s shape. Missing measurements, assay error, or departures from the assumed interpolation can also affect the calculated area and therefore the clearance estimate. These are general methodological considerations; whether any occurred in this study is not reported in the registry record.

What does a single-group design allow?

A single-group design can describe measurements collected in the study population after the intervention. It does not provide a concurrent control group for estimating how outcomes would have differed without the intervention. In general, that distinction matters because time, participant characteristics, measurement conditions, and other influences may affect observed values. The registry lists the model as single-group, allocation as not applicable, and masking as none. It does not report a control group or a randomized contrast. The posted record consequently does not support a between-group estimate of an intervention effect.

The study aim mentions chronic kidney disease and race, but the registry does not describe a comparison population without chronic kidney disease or provide race-specific results. A broad aim does not supply the details needed to identify a statistical contrast. The definitions of the comparison groups, the estimates for those groups, and any adjustment for participant characteristics are not reported in the registry record.

What do planning calculations mean?

In general, sample-size planning asks how many observations a future study might need for a prespecified design, outcome, effect size, and statistical procedure. Such calculations depend on assumptions, including the variability of the outcome and the effect that the study aims to detect. A planning illustration based on an observed effect is not the same as a prospectively justified sample size, and it is not observed power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of an observed effect. Those are assumptions for an illustration, not a description of this single-group study’s actual allocation. The study-specific sample-size justification and the observed effect needed to interpret such an illustration are not reported in the registry record.

In general, power is the probability that a specified analysis will detect an effect of a chosen size under its assumptions. It is not a measure of how likely a result is to be true, and calculating power after results are observed does not establish the precision of the estimate. The registry record does not report a study-specific power calculation, the effect size targeted during planning, or a sample-size justification. No conclusion about the adequacy of the study size can be drawn from the planning assumptions alone.

Why can variability matter?

In general, a statistical model needs to represent the distribution of the outcome and its variability. If observations vary more than a model assumes, standard errors and confidence intervals may be too small, and statistical tests may be poorly calibrated. Over-dispersion is one term for variability greater than a model’s assumed level. The registry does not report a model, a dispersion assessment, or enough outcome data to determine whether over-dispersion is relevant to this continuous endpoint. It would therefore be inappropriate to assert that a particular variance model or correction was used.

For pharmacokinetic measures, individual concentration profiles can differ, and the calculated clearance may inherit variability from both measured concentrations and the AUC calculation. In general, researchers may examine the distribution, influential observations, and sensitivity to modeling choices. Whether such diagnostics or sensitivity analyses were performed is not reported in the registry record. The record also does not describe transformations, covariate adjustment, or treatment of outlying values.

What is the status of the reported analyses?

The registry lists 9 outcome measures and 0 analyses. The outcome descriptions identify a primary clearance measure and secondary measures of AUC, terminal half-life, and volume of distribution, but numerical findings are not reported in the registry record. No p-values, confidence intervals, model coefficients, adjusted estimates, or participant-level distributions are available in the entry. As a result, statistical significance, precision, and consistency across outcomes cannot be assessed from the posted record. The absence of listed analyses should be described as a limitation of the registry record, rather than taken as proof about analyses conducted elsewhere.

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("Healthy Controls", "CKD Group", "Kidney Failure Group")
n   <- c(43, 24, 20)
m   <- c(360, 313, 263)
sp  <- c(108, 86, 163)
sd  <- sp      # posted standard deviations
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  Healthy Controls  43  360.000  108.000  326.763  393.237
CARM  CKD Group  24  313.000  86.000  276.685  349.315
CARM  Kidney Failure Group  20  263.000  163.000  186.714  339.286

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary metabolic clearance outcome and secondary outcomes for AUC, terminal half-life, and volume of distribution. It reports 0 analyses. A statistical plan describing how the primary and secondary outcomes were prioritized, tested, or interpreted is not reported in the registry record. Details of any adjustment for multiple comparisons, prespecified hierarchy, or control of false-positive findings are also not reported.

In general, evaluating many outcomes can increase the chance of observing an apparently notable result by chance if each is considered separately. A multiplicity strategy may define which outcome is primary, adjust inference across outcomes, or clearly distinguish confirmatory from exploratory analyses. The registry identifies a primary outcome, but it does not report how the additional outcomes were handled analytically. No conclusion about multiplicity control can therefore be made.

Missing-data methods are not reported in the registry record. The entry does not state whether any concentration measurements or outcome values were missing, how incomplete profiles were handled in calculating AUC, or whether any participants were excluded from particular analyses. Analysis populations, including the criteria for inclusion in each outcome analysis, are not reported. The registry lists enrollment as 88, while the safety entry uses denominators of 87; the record does not explain this difference. These details limit interpretation of completeness and of the relationship between the recorded enrollment and the safety summaries.

In general, missing observations can affect estimates when their absence is related to participant characteristics or measured values. The consequences depend on the extent and pattern of missingness and on the analysis approach. Because the registry does not describe missingness or its handling, it is not possible to assess whether the reported methods, if any, addressed it appropriately.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: deep vein thrombosis (1.1%).

The registry’s safety entry is labeled All Participants. It reports 1 serious adverse event among 87 participants at risk, 16 other adverse events among 87 at risk, and 0 deaths. Deep vein thrombosis appears among the top serious terms at 1.1%. These are registry-reported counts and a term-level percentage; they do not establish that the events were caused by D6-25-hydroxyvitamin D3.

The at-risk denominators are shown separately for serious and other adverse events. The record does not explain why those denominators are 87 when enrollment is listed as 88, nor does it report the event-collection period, the definitions used for the categories, or further details about event severity and timing. The listed serious term should not be treated as a complete description of all clinical circumstances around the event.

Because the study is single-group and the registry does not report a control group, these figures cannot be used to compare event rates with an alternative treatment or with no intervention. In general, adverse-event counts describe events recorded under a study’s reporting procedures; interpretation also depends on how events were collected and classified. Those additional procedures are not reported in the registry record. The figures should therefore be read as descriptive safety information, not as a causal or comparative estimate.

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

The registry record documents a completed phase 1, single-group study whose stated aim was to better understand vitamin D catabolism and how it is affected by chronic kidney disease and race. It specifies a primary pharmacokinetic measure, metabolic clearance of D6-25(OH)D3, and describes an AUC-based calculation. It also identifies secondary measures of AUC, terminal half-life, and volume of distribution. These details explain what the study set out to measure and how the primary measure was defined.

The posted record does not report the primary outcome’s mean or standard deviation, any confidence interval or statistical test, or numerical results for the secondary outcomes. It therefore does not show the observed clearance value, how variable that value was, or the precision of an estimate. No outcome analyses are listed. The record also does not present results by race or a comparison with people without chronic kidney disease. The study aim cannot substitute for those missing results.

The study’s single-group design is important for interpretation. A measured value after administration can describe the participants and measurements in the study, but there is no reported control group against which to estimate a comparative effect. In general, a comparison group can help distinguish an intervention-related difference from changes or influences that would also occur without the intervention. The registry record does not provide such a contrast, so it cannot support a causal comparison.

The safety entry reports serious and other adverse-event counts and a death count. Those figures are descriptive and do not establish attribution to the intervention. The record does not explain the difference between the listed enrollment and safety denominators or provide fuller information about adverse-event ascertainment.

These limits concern what can be concluded from the registry record. They do not show that the study’s underlying measurements or analyses do not exist elsewhere. A fuller report containing outcome estimates, uncertainty measures, participant characteristics, analysis methods, missing-data handling, and any subgroup results would be needed to assess the findings in greater detail.

14. Why This Trial Matters Statistically

This study raises a statistical question about how to summarize a concentration-time profile as a clearance measure. The registry defines clearance using the administered dose and AUC, and specifies a linear trapezoidal calculation for the AUC. That definition makes the measurement pathway explicit: concentrations over time are reduced to an area, which is then used in a pharmacokinetic summary. Interpreting the final estimate depends on both the measurements and the calculation procedure, rather than on a single concentration alone.

The study is also a useful example of the distinction between a scientific aim and a statistical comparison. Its brief summary says the aim was to understand vitamin D catabolism and how it is affected by chronic kidney disease and race. Yet the listed design is single-group, and the registry does not report comparative results by disease status or race. A research question may motivate measurement without the registry entry documenting a design or analysis that can answer every part of that question.

Precisely describing uncertainty is central to interpreting a continuous outcome. The registry specifies a mean and standard deviation for the primary outcome but does not report their values, a confidence interval, or an analysis estimate. Without these, readers cannot assess either observed variability or the precision of an estimate. This illustrates why a stated endpoint definition and a complete set of results are both important for statistical interpretation.

The record also lists multiple outcomes but no analyses. When several outcomes are measured, the analysis plan and interpretation strategy matter for distinguishing a primary question from exploratory findings. The absence of those details in the record limits assessment of how the outcomes relate to one another and whether multiplicity was addressed. Likewise, unclear reporting of analysis populations and missing-data handling makes it difficult to understand exactly which measurements contribute to each summary.

Finally, a single-group study and a comparative trial answer different kinds of questions. Descriptive pharmacokinetic measurement can characterize values in a study population, while causal claims require a design and analysis that support a credible counterfactual comparison. Keeping those aims distinct prevents a measurement result from being interpreted as evidence of comparative clinical benefit or harm.

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 main limitation for interpreting this trial from its registry record is that the primary outcome result is not reported. Although the record defines metabolic clearance and specifies a mean and standard deviation, it gives neither numerical summary. It also does not report confidence intervals, test results, or analysis estimates. The record therefore cannot support assessment of the observed value, variability, or precision.

The single-group design limits comparative interpretation. Allocation is listed as not applicable, masking as none, and no comparator is described. The record cannot provide a between-group estimate or distinguish an observed measurement from what might have occurred without the intervention. The stated interest in chronic kidney disease and race does not establish that disease-status or racial comparisons were conducted; group definitions and subgroup findings are not reported in the registry record.

The registry does not report the administered dose, route, or full administration procedure, although the clearance definition refers to dose. It lists concentration-measurement times and the linear trapezoidal AUC method but does not provide the concentration values, assay details, or resulting AUC. These omissions prevent readers from checking the calculation or judging the measurement process.

Analysis details are limited. The record lists 9 outcome measures and 0 analyses but does not provide a statistical analysis plan, multiplicity approach, missing-data methods, analysis populations, or sensitivity analyses. The study-specific sample-size justification is not reported in the registry record. The record also does not explain why the safety denominators are 87 when enrollment is listed as 88. Safety counts lack comparative context and do not establish causation.

These are limitations of the information available in the registry entry. They do not establish that the study lacked further documentation or analyses outside the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease — NCT02937350.
• Registry record last updated 2021-09-01; status last verified 2021-08.
• Results first posted 2021-09-01.
• 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 a completed phase 1, single-group study of D6-25-hydroxyvitamin D3 in chronic kidney disease. Enrollment is listed as 88. The stated primary outcome is metabolic clearance of D6-25(OH)D3 in milliliters per day over 8 weeks, defined using dose and AUC. Concentrations were scheduled at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The AUC method is listed as linear trapezoidal.

Secondary outcomes include AUC, terminal half-life, and volume of distribution. The record lists 9 outcome measures and 0 analyses, and does not report numerical primary or secondary outcome results. The safety entry reports 1 serious adverse event among 87 at risk, 16 other adverse events among 87 at risk, and 0 deaths. The registry does not report a comparator, detailed analysis methods, missing-data handling, or an explanation of the safety denominators.