FGF-23 (Fibroblast Growth Factor 23) Regulation in Chronic Kidney Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for FGF-23 (Fibroblast Growth Factor 23) Regulation in Chronic Kidney Disease (NCT00999037), a randomized na study. The primary outcome is Change in FGF-23 Level.

2. Clinical Question

The study rationale in the registry concerns phosphorus regulation in chronic kidney disease. FGF-23 is described as a protein involved in regulating phosphorus, with levels reported to increase in people with kidney disease. The study was designed to observe FGF-23 levels after use of medication intended to prevent phosphorus absorption. This is a biomarker question; the primary outcome is not itself a measure of clinical events or patient symptoms.

3. Trial Design

This was a randomized, single-masked, parallel-group study. The registry records an enrollment of 18 participants and reports 9 participants in each outcome arm. Random allocation is intended to make the comparison between assigned groups less prone to systematic differences at the start of a study, although it cannot guarantee balance in a small sample. The record does not describe the randomization sequence or how allocation was concealed.

The intervention arm received Renvela, identified as Sevelamer Carbonate, daily with meals for 12 weeks. The other arm received placebo. The record identifies masking as single, but does not state which people were masked. Further details about the placebo regimen are not reported in the registry record. The trial is listed as completed, with a start date of 2009-10 and a primary completion date of 2015-06.

The registry lists the study phase as NA. It gives the primary outcome timeframe as 12 weeks and describes the outcome as mean change in FGF-23, expressed as percentage change from baseline. The reported group summaries are based on 9 participants per arm. The registry does not report whether every randomized participant contributed an endpoint measurement, how analysis populations were defined, or whether participants who stopped or missed visits were included in the outcome summaries.

The record lists two secondary outcomes: 1,25(OH)2vitamin D Value and Serum Phosphate Concentration. No analysis is listed for these outcomes in the posted results. A sample-size justification, detailed protocol, and fuller statistical analysis plan are not reported in the registry record. Accordingly, design features beyond the recorded randomization, masking, parallel structure, enrollment, interventions, and outcome timeframe cannot be assumed.

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 Change in FGF-23 Level, measured over 12 weeks.

The primary endpoint is titled Change in FGF-23 Level. It measures the percentage change in FGF-23 from baseline at 12 weeks, with the registry specifying a mean and standard deviation for each arm. FGF-23 is the biomarker of interest because the study rationale describes it as a regulator of phosphorus and notes that levels increase in people with kidney disease. The endpoint therefore addresses a physiological question about the biomarker during the study period.

A change-from-baseline measure relates the follow-up value to a participant’s starting value, expressed in this trial as a percentage. The reported arm means are 16.0 for Renvela and 41.0 for placebo; the reported standard deviations are 41.0 and 46.0, respectively. These are group summaries, not a reported estimate of the difference between groups. The registry specifies the timeframe as 12 weeks, but does not report the precise calculation procedure for each participant’s percentage change, including how any baseline values that might affect that calculation were handled.

FGF-23 is a biomarker rather than a direct clinical outcome. A change in this measure does not by itself establish a change in symptoms, complications, or other health outcomes. The posted primary outcome can describe the trial’s biomarker measurements, but the registry record does not provide an estimable comparative analysis or a clinical outcome assessment tied to this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what the registry reports from what it does not. The primary outcome is continuous: each participant’s outcome is represented by a numerical percentage change in FGF-23. A mean summarizes the center of a group’s observed values. A standard deviation describes their spread around that mean. The posted means and standard deviations are descriptive summaries for the two assigned arms, not estimates of the uncertainty in a between-arm comparison.

What does randomization contribute?

In general, randomization assigns participants to study arms using a chance-based process. Its purpose is to reduce systematic selection differences between groups, supporting a fair comparison of outcomes after assignment. It does not ensure that every relevant characteristic is balanced in a small trial, and it does not replace reporting the comparison itself. The registry identifies the trial as randomized, but details of sequence generation, allocation concealment, and baseline comparability are not reported in the registry record.

With a parallel-group design, participants are assigned to one arm and the groups are followed over the stated study period. The primary question is about the contrast between the groups’ changes, not simply whether either group’s mean differs from baseline. The registry posts arm-level means and standard deviations, but marks the two-arm continuous comparison as missing or not estimable. It therefore does not give a comparative effect estimate that can be paired with an uncertainty interval or test result.

How should means and standard deviations be read?

The mean is useful as a compact summary, but it can conceal the distribution of individual outcomes. The standard deviation helps describe how dispersed those outcomes are. It is not a confidence interval, and it does not show the range containing a particular proportion of participants unless additional distributional assumptions are made. In this trial, the standard deviations are 41.0 for Renvela and 46.0 for placebo. The registry does not provide participant-level values, medians, ranges, or a distribution plot in the registry record for interpreting the outcome.

A confidence interval is a general statistical way to express uncertainty around an estimated quantity, such as a mean or the contrast between two means. It conveys both the estimated value and the precision supported by the data and analysis. A narrow interval indicates greater precision than a wide interval, while the interval’s location indicates which values remain compatible with the analysis. No confidence interval for the primary between-arm contrast is reported in the registry record. A p-value, also a general inferential measure, addresses compatibility between observed data and a specified null model; it does not measure the probability that a treatment works. No p-value for the primary comparison is reported.

Why might a comparison be not estimable?

For a continuous outcome, a two-arm comparison ordinarily needs the relevant group summaries and an analysis definition sufficient to calculate a contrast and its uncertainty. The registry explicitly indicates that values were missing or not estimable for this comparison. It does not explain the reason in further detail. It would be inappropriate to infer whether the issue arose from missing observations, an unavailable analysis, a reporting limitation, or another cause. The record also does not report an adjusted model, the exact analysis population, or how missing outcome observations were handled.

General statistical methods may account for features of a distribution that is more variable than a simple model expects. Over-dispersion means that observed variability exceeds what a chosen model assumes; if ignored, uncertainty may be understated. That concept is relevant when a model’s variance assumptions are inadequate, but the registry does not report that over-dispersion was assessed or that a particular model was used for this continuous outcome. No model details should be inferred from the posted mean and standard deviation alone.

What do the planning assumptions mean?

The registry describes a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. Such calculations are general design scenarios: they show what participant counts might be needed under chosen assumptions. They are not observed power, do not change the evidence in the completed trial, and are not a record of the trial’s original sample-size justification. The trial’s own sample-size rationale is not reported in the registry record. The registry’s assumptions also distinguish participant counts per arm for continuous outcomes from total event counts for time-to-event outcomes; the primary outcome in this study is continuous.

None of these general concepts supplies the missing comparative result. The reported means and standard deviations can be interpreted as descriptive summaries, while the absence of an estimable contrast and associated precision measures remains central to the statistical reading of the primary endpoint.

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("Renvela", "Placebo")
n   <- c(9, 9)
m   <- c(16, 41)
sp  <- c(41, 46)
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  Renvela  9  16.000  41.000  -15.515  47.515
CARM  Placebo  9  41.000  46.000  5.641  76.359

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: 1,25(OH)2vitamin D Value and Serum Phosphate Concentration. It records three outcome measures in total, but lists no analyses. The posted results therefore do not give inferential results for the secondary outcomes, and the primary two-arm continuous comparison is marked as missing or not estimable.

Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. In general, testing multiple questions can increase the chance of finding an apparently notable result by chance. Prespecified priorities and methods for accounting for multiple comparisons can help readers interpret a set of analyses. The registry record does not report a multiplicity adjustment, a hierarchy for testing the secondary outcomes, or a plan for handling multiple analyses. It is not possible to determine from the listed outcome names alone whether any adjustment was planned or appropriate.

Missing-data methods are also important because incomplete outcome measurements can affect both the estimate and its precision. The record does not report the number of participants with observed baseline and 12-week FGF-23 values, reasons for missing measurements, or a method for handling missing data. Nor does it define an intention-to-treat, per-protocol, or other analysis population. The arm-level outcome summaries each list 9 participants, but the registry does not clarify how those counts relate to all randomized participants or whether any missingness occurred before analysis.

These gaps prevent assessment of whether missing observations, exclusions, or multiple testing influenced the reported results. They are limits of the registry record, not grounds for assuming that any particular method was or was not used in analyses outside the record.

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 safety figures list 9 participants at risk in each arm. In the Renvela arm, 0 participants are reported with a serious adverse event, 0 with another adverse event, and 0 deaths. In the placebo arm, the corresponding counts are also 0, 0, and 0. The record lists no serious adverse-event terms.

These are counts as recorded, not proof that no adverse events of any kind occurred. The registry does not report definitions, event-collection procedures, follow-up completeness, severity classifications beyond the listed categories, or whether events were assessed as related to the intervention. The figures therefore describe what was posted in those categories and should not be interpreted as a complete account of all possible safety observations.

With 9 participants at risk per arm, the safety summaries are limited in their ability to characterize uncommon events or differences between groups. A zero count in a small study does not establish that an event cannot occur, and no comparative safety estimate or uncertainty interval is reported. The record also lists zero deaths in each arm; this is a count during the recorded study period, not a broader conclusion about mortality.

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

The record establishes that a randomized, single-masked, parallel-group study compared Renvela with placebo and posted mean FGF-23 percentage changes at 12 weeks. The reported means were 16.0 and 41.0, respectively, with standard deviations of 41.0 and 46.0, and 9 participants listed in each arm. These numbers describe the observed arm summaries. The primary comparative analysis was not estimable in the registry record, so the posted results do not quantify the difference between assigned groups or the precision of that difference.

This distinction is important because the primary question is comparative. A numerical difference between two group means is not, by itself, a test of a treatment effect. An inferential comparison requires an estimate defined by the analysis and an assessment of uncertainty. Neither a confidence interval nor a p-value for the primary comparison is reported. The record also does not report enough detail to establish the analysis population, account for missing outcomes, or assess adjustment for baseline characteristics.

The outcome is a biomarker related to phosphorus regulation, not a direct measure of symptoms, quality of life, cardiovascular events, kidney outcomes, or survival. Even an interpretable difference in a biomarker would not on its own demonstrate a change in those clinical outcomes. The study rationale notes the interest in FGF-23 in kidney disease, but the posted primary result cannot establish whether changing FGF-23 would alter future health outcomes.

The record also cannot support a clear interpretation of the listed secondary outcomes because no analyses are posted for them. Likewise, the zero adverse-event and death counts are limited descriptions of the recorded categories and sample, not proof of absence of risk. The registry entry is useful for identifying the study question, design, and available arm summaries, while leaving the comparative effectiveness and broader clinical implications unresolved in the posted results.

14. Why This Trial Matters Statistically

This study illustrates why arm-level summaries and comparative inference are different kinds of evidence. The mean and standard deviation in each arm give a first description of the observed FGF-23 changes. The research question, however, concerns how the groups compare. Without an estimable contrast and a measure of its uncertainty, readers cannot assess the size or precision of the comparison from the registry results.

The issue is especially visible in a small randomized study. Randomization is an important design feature, but it does not guarantee balance or precise estimates when only a limited number of participants are enrolled. The registry reports 18 participants overall and 9 in each outcome arm. Statistical interpretation must therefore attend to the amount of information available as well as to the point summaries. No confidence interval is reported for the primary comparison, and the posted data do not support a recalculated comparison.

The endpoint also highlights the distinction between a biomarker and a clinical outcome. FGF-23 is central to the stated biological rationale, but a biomarker result is not equivalent to evidence about symptoms or clinical events. Interpretation depends on a well-defined endpoint, a suitable comparison, uncertainty estimates, and an understanding of how the measure relates to outcomes that matter to patients. The registry record does not establish those broader links.

Finally, the absence of posted analyses for the secondary outcomes and the lack of detail about missing data, multiplicity, and analysis populations show how reporting completeness shapes statistical interpretation. A transparent record of methods and results helps distinguish a descriptive observation from a supported comparative conclusion. In this case, the primary summaries are available, while the crucial comparative analysis is not estimable in the registry record.

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 trial-specific limitation is that the registry marks the primary two-arm continuous comparison as having values missing or not estimable. Although each arm has a mean and standard deviation, the record does not provide an estimated between-arm contrast, confidence interval, or p-value. The reason for the non-estimability is not reported in the registry record, so its source cannot be identified.

The enrolled sample was 18, with 9 participants listed in each outcome arm. This limits the amount of information available for characterizing outcome variability and safety. The record does not provide participant characteristics, baseline FGF-23 summaries, individual measurements, or an explanation of whether all randomized participants contributed to the endpoint summaries. These omissions make it difficult to judge baseline comparability, representativeness, and the effects of any missing measurements.

Masking is listed as single, but the masked parties are not reported. Randomization procedures, allocation concealment, adherence, discontinuations, concomitant care, and placebo regimen details are also not reported in the registry record. The record does not state a detailed analysis plan, a sample-size justification, missing-data methods, or the analysis population. The planning assumptions in the registry are described as illustrative rather than as the trial’s original design rationale.

The primary endpoint is a biomarker measured at 12 weeks. The registry does not report a clinical endpoint assessment, and the secondary outcomes have no analyses listed. Safety counts are posted, but event definitions and ascertainment details are not reported. These limitations restrict both the interpretation of the observed biomarker summaries and the conclusions that can be drawn about clinical outcomes or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: FGF-23 (Fibroblast Growth Factor 23) Regulation in Chronic Kidney Disease — NCT00999037.
• Registry record last updated 2023-05-31; status last verified 2023-05.
• Results first posted 2017-03-31.
• 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

NCT00999037 is a completed randomized, single-masked, parallel-group study titled FGF-23 (Fibroblast Growth Factor 23) Regulation in Chronic Kidney Disease, sponsored by the University of California, Los Angeles. The registry lists an enrollment of 18 and identifies secondary hyperparathyroidism as a condition. The recorded start date is 2009-10 and the primary completion date is 2015-06; the phase is listed as NA.

The study compared Sevelamer Carbonate, identified as Renvela taken daily with meals for 12 weeks, with placebo. The primary outcome was mean percentage change in FGF-23 from baseline at 12 weeks. The arm summaries list 9 participants per group, with means of 16.0 and 41.0 and standard deviations of 41.0 and 46.0. The registry marks the continuous two-arm comparison as missing or not estimable. It lists two secondary outcomes but no analyses. Safety summaries report zero serious adverse events, zero other adverse events, and zero deaths in each arm.