Role Of Phosphorus And FGF 23 In Patients With Dent Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Role Of Phosphorus And FGF 23 In Patients With Dent Disease (NCT02016235), a non-randomized phase 1, phase 2 study. The primary outcome is Change in Urine Total Protein.

2. Clinical Question

The rationale in the record concerns phosphorus, FGF 23 and hypercalciuria in Dent disease. It states that suppressed FGF 23 contributes to hypercalciuria, kidney stones, nephrocalcinosis and renal failure, and that phosphorus supplementation may reduce hypercalciuria. These statements describe the study rationale, not findings from the posted outcome data. The record lists urine total protein as the primary measure; it does not list a reported FGF 23 outcome or a hypercalciuria outcome. The clinical question as recorded is therefore narrower than the full biological rationale, and the results needed to answer even that primary question are not reported in the registry record.

3. Trial Design

The registry describes a completed phase 1 and phase 2 study with non-randomized allocation, no masking and a single-group model. It lists Mayo Clinic as the sponsor and records the study start as 2014-09 and primary completion as 2019-01. Enrollment is listed as 30. These record details describe the study; they do not establish that all enrolled participants contributed data to the primary outcome.

Three groups are described: Dent Disease Intervention, Kidney Stone Subjects and Dent Disease Observation. The intervention descriptions say that Dent disease subjects and kidney stone subjects received 2 week supplementation with phosphorus, while Dent disease subjects in the observation group did not get phosphorus. The groups differ in their descriptions and were not assigned through randomization. The record specifically warns that the arms are not a like-for-like control comparison. A difference between groups, if one were reported, could therefore reflect group differences as well as any effect associated with supplementation.

The primary outcome is titled “Change in Urine Total Protein,” with a baseline and day 7 timeframe. However, the record states that data were not collected for the Dent Disease Observation Group. No primary outcome values or analyses are reported. Consequently, the design description alone cannot show the magnitude or direction of a change, or support a comparison of supplementation with observation.

Although the registry marks the study completed, completion status is not itself evidence that results were posted. The record lists one outcome measure and no analyses. It does not report the allocation procedure beyond non-randomization, further details of how participants entered each group, or a statistical analysis plan. Those details should not be inferred from the arm labels or the completed status.

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

Analysis population for the primary outcome, as defined in the registry: Data were not collected for the Disease Dent Observation Group

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 Change in Urine Total Protein, measured over baseline, day 7.

Urine total protein measures the amount of protein released into urine, expressed in mg/day. The registry describes urine protein tests as detecting and/or measuring protein in urine and notes that normal urine protein elimination is less than 150 mg/day. The primary measure is a continuous outcome: its stated parameter is the mean, and its stated measure of dispersion is the standard deviation.

The listed timeframe is baseline and day 7, so the intended endpoint concerns change between those measurements. A change measure can describe whether the observed mean moved over the stated period, while the standard deviation describes variation among measurements. The registry does not define the exact calculation for change, such as whether it was calculated for each participant before summarizing; this is not reported in the registry record.

Urine protein is the primary endpoint named in the record, but the rationale focuses on phosphorus, FGF 23 and hypercalciuria. The registry does not explain why urine total protein was selected as the primary outcome or how it was expected to reflect the proposed biological pathway. It also does not report the mean, standard deviation, change estimate or uncertainty interval. The endpoint’s stated role can therefore be described, but its observed behavior in this study cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as continuous and specifies a mean with standard deviation. These summaries answer different descriptive questions. A mean locates the center of a set of measurements, while a standard deviation describes how spread out measurements are around that mean. Neither summary alone shows the full distribution of observations, and neither indicates how precisely a group mean or change has been estimated. Precision for an estimate is usually conveyed with an uncertainty measure such as a confidence interval, but no such result is reported in the registry record.

What does a change outcome require?

The listed outcome is change in urine total protein, with measurements at baseline and day 7. In general, a change analysis uses measurements from both time points to describe movement over time. The exact method can differ: investigators might calculate each participant’s change and summarize those changes, or model repeated measurements. Those approaches rely on different details about the data and analysis. The registry record does not report which approach was used, how change was calculated, or how missing measurements were handled. No change estimate is posted, so the direction and magnitude cannot be interpreted.

What does non-randomized allocation imply?

Random allocation, when used, can help balance measured and unmeasured characteristics between groups on average. This study is recorded as non-randomized, so that protection against systematic group differences is not present. General statistical interpretation therefore requires caution: an observed difference between groups could reflect differences in who entered each group, differences in care or measurement, or other factors, as well as a treatment-related effect. The registry itself emphasizes that the arms are not a like-for-like control comparison. It does not report adjustment methods that might address measured differences.

The study is also listed as a single-group model, while its arm descriptions include intervention and observation groups. The record does not explain this design labeling or give further detail about how the groups were formed. The label should not be taken as evidence that a particular comparative analysis was conducted. The record lists no analyses.

Why do variation and precision matter?

For a continuous measure, a mean can conceal substantial variation among participants. Standard deviation describes observed spread, but it is not the same as the standard error or a confidence interval. A confidence interval expresses uncertainty around an estimate, conditional on the data and statistical assumptions. It helps readers distinguish an estimate that is relatively precise from one that is compatible with a wide range of values. No estimates or uncertainty intervals for the primary outcome appear in the record.

Some continuous outcomes can have a skewed distribution or unusually variable measurements. In general, those features may make a simple mean-based model less suitable, or may call for robust methods or a different model. Over-dispersion is a related general concern in count data, where observed variability exceeds what a simple model assumes; it is not a reported feature of this study’s continuous primary endpoint. The registry record does not describe distribution checks, transformations, robust methods or model assumptions. None should be presumed.

What can planning calculations tell readers?

Sample-size planning illustrations are conditional calculations, not observed trial findings. 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 set as a stated fraction of the observed effect. Such calculations, in general, illustrate the number of participants per arm for 80% power under specified assumptions; they do not show that a study had that power or that a result was observed. The record does not report the observed primary-outcome effect needed to assess an illustration based on that effect. Planning calculations cannot substitute for the missing outcome estimate, and they are not observed power.

More broadly, a statistical test and a confidence interval would address different aspects of the evidence: a test evaluates data against a null hypothesis under a specified model, while an interval conveys a range of estimates compatible with the data and model. Neither can be reconstructed from the information in the registry record without inventing results. Since no analysis or outcome values are listed, no test, interval, or model-based conclusion can be attributed to this study.

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("Dent Disease Intervention", "Kidney Stone Subjects")
n   <- c(10, 10)
m   <- c(1681, 59)
sp  <- c(979, 38)
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  Dent Disease Intervention  10  1681.000  979.000  980.666  2381.334
CARM  Kidney Stone Subjects  10  59.000  38.000  31.816  86.184

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report whether investigators prespecified multiple outcomes, multiple time points, subgroup analyses or multiple statistical tests beyond the listed primary measure. A multiplicity strategy—such as prioritizing hypotheses or adjusting interpretation for multiple testing—is not reported in the registry record. With no posted analysis results, there is also no basis for assessing whether multiplicity affected the reported evidence.

Missing-data handling is likewise not described. The record says that primary-outcome data were not collected for the Dent Disease Observation Group. This is a design and data-availability limitation for the primary endpoint, not a result that can be repaired through an assumed statistical method. The record does not state whether measurements were missing for any participants in the intervention groups, whether any participants were excluded from analyses, or how incomplete baseline or day 7 measurements were treated. These details are not reported in the registry record.

The record does not identify an analysis population, such as all enrolled participants or only those with measurements at both time points. It therefore does not establish which participants contributed to any primary-outcome analysis. Although enrollment is listed as 30 and the adverse-event entries list group-specific numbers at risk, those entries do not define the analysis population for urine total protein. They should not be used to infer an outcome denominator.

In general, missingness can affect an estimate when the availability of measurements is related to participant characteristics or outcomes. Different assumptions and methods can lead to different interpretations, so transparency about missing data is important. No missingness assumptions or sensitivity analyses are reported. Given the absence of primary-outcome results, the extent and effect of missing data on the endpoint cannot be evaluated.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse events for three listed groups: Dent Disease Intervention, Kidney Stone Subjects and Dent Disease Observation. For each group, the entry shows 10 at risk and 0 affected by serious adverse events. The entries also show 10 at risk and 0 affected by other adverse events for each group, and 0 deaths for each group. These figures are the safety information reported in the registry record.

Zero recorded events should be read as zero events reported in these entries, not as proof that no harms occurred. The figures do not describe the types of surveillance used, the completeness of reporting, or whether events outside the listed categories were collected. The record does not report further safety detail, and the serious-event terms list is empty.

These safety counts do not answer the primary efficacy question about change in urine total protein. They also do not establish a causal safety comparison between phosphorus supplementation and observation: the study was non-randomized, and the registry cautions that the groups are not a like-for-like control comparison. The adverse-event entries should be interpreted as registry-reported counts, with those design and reporting limitations in mind.

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

The registry record establishes that a study of phosphorus supplementation and observation in people with Dent disease and kidney stone subjects was marked completed. It describes a primary endpoint of change in urine total protein at baseline and day 7, and records safety counts for three groups. It also provides a rationale concerning phosphorus, FGF 23 and hypercalciuria. These design and rationale details identify what the study set out to examine; they are not outcome findings.

The record does not report values for the primary endpoint or any statistical analysis. It therefore cannot show whether urine total protein increased, decreased or remained similar over the stated timeframe, nor how precise an estimate might be. No result for FGF 23 or hypercalciuria is reported either. The rationale’s statement that phosphorus may reduce hypercalciuria should not be interpreted as evidence that it did so in this study.

The study’s non-randomized design and the absence of primary-outcome data for the Dent Disease Observation Group further constrain interpretation. Even if group results were available, the registry warns that the arms are not a like-for-like comparison. The posted record does not provide an analysis that addresses potential group differences, and none should be assumed.

The safety entries report zero affected by serious adverse events, zero affected by other adverse events and zero deaths in each listed group. Those entries describe what was reported, not proof of an absence of risk. The record does not provide enough detail to assess the completeness of safety ascertainment.

Thus, the record supports a description of the study’s design, endpoint and reported safety counts, but not a conclusion about the effect of supplementation on the primary outcome or the proposed biological pathway. The missing results are central, not a minor qualification: without them, the study’s outcome magnitude and statistical precision cannot be evaluated.

14. Why This Trial Matters Statistically

This study is statistically instructive because its title and rationale may prompt readers to look for findings about phosphorus, FGF 23 and hypercalciuria, while the registry names change in urine total protein as the primary endpoint. Keeping the stated endpoint distinct from the biological rationale is essential. A rationale explains why a question might be studied; it is not evidence that the proposed effect occurred.

The record also illustrates why design labels and comparison groups require careful reading. Allocation was non-randomized, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The Dent Disease Observation Group lacks primary-outcome data in the record. These details limit what any comparative estimate could mean, even before considering statistical uncertainty.

Finally, a completed study record is not necessarily a results record. Here, the primary outcome is described but no values or analyses are posted. Readers cannot infer a result from the enrollment entry, study status, group descriptions or safety counts. Nor can planning assumptions replace observed data. Clear distinction among study rationale, design, outcome reporting and inference helps prevent unsupported conclusions.

For clinical researchers and biostatisticians, the record emphasizes the value of reporting outcome estimates, uncertainty, analysis populations, missing-data handling and the methods used. Without those elements, readers can identify important limitations but cannot assess the magnitude or precision of the primary outcome.

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.

A central limitation specific to this record is the absence of primary outcome results. Although change in urine total protein is named and its timeframe is stated, no observed values, estimates, uncertainty measures or analyses are reported. The record therefore does not permit evaluation of the endpoint’s direction, magnitude or precision.

The registry states that primary-outcome data were not collected for the Dent Disease Observation Group. This removes that group as a source of primary-outcome comparison in the posted record. The study is non-randomized, and the registry warns that the arms are not a like-for-like control comparison. The intervention groups also have different descriptions: Dent disease subjects and kidney stone subjects. These features limit direct interpretation across groups.

The study rationale discusses FGF 23 and hypercalciuria, but the primary outcome listed is urine total protein. The record does not report an FGF 23 or hypercalciuria outcome. It also does not explain the relationship between the primary endpoint and the rationale. The results therefore cannot be used to assess the proposed pathway from the information recorded.

Further limitations are the lack of reported detail about the statistical analysis, outcome-change calculation, missing-data methods, analysis populations and multiplicity. The record lists no analyses. It also does not describe safety ascertainment beyond the adverse-event counts. These omissions prevent assessment of the methods and completeness of outcome reporting; they do not justify filling in unreported choices or findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Role Of Phosphorus And FGF 23 In Patients With Dent Disease — NCT02016235.
• Registry record last updated 2020-03-23; status last verified 2020-03.
• Results first posted 2020-03-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed phase 1 and phase 2, non-randomized study sponsored by Mayo Clinic, with no masking and a single-group model. It lists an enrollment of 30 and three group descriptions: Dent Disease Intervention, Kidney Stone Subjects and Dent Disease Observation. The supplemented groups were described as receiving phosphorus for 2 weeks; the observation group did not receive phosphorus.

The primary outcome is change in urine total protein, measured at baseline and day 7, with the mean and standard deviation specified. The record states that primary-outcome data were not collected for the Dent Disease Observation Group. It lists one outcome measure and no analyses, and does not report primary-outcome results.

Safety entries report zero serious adverse events, zero other adverse events and zero deaths for each listed group. The registry cautions that the non-randomized arms are not a like-for-like control comparison. The record describes the study question and design but does not provide the results needed to assess the primary outcome.