The Effect of Lanthanum Carbonate on Fibroblast Growth Factor 23 ( FGF23) in Chronic Kidney Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Lanthanum Carbonate on Fibroblast Growth Factor 23 ( FGF23) in Chronic Kidney Disease (NCT01002872), a randomized na study. The primary outcome is Fibroblast Growth Factor (FGF) 23 Mean Change From Baseline.

2. Clinical Question

The study description identifies FGF23 as relevant to chronic kidney disease and states that targeting its measurement may affect understanding of disease progression and mortality. Those statements describe the motivation for studying the biomarker; they are not outcomes tested by the reported primary comparison. The registry record does not describe a target treatment effect or a minimum clinically important difference.

3. Trial Design

The registry identifies this as a randomized, double-masked, parallel-group study comparing lanthanum carbonate (Fosrenol) with placebo. It lists an enrollment of 19 and a completed status. The study start is recorded as 2009-10, and primary completion as 2012-05. The phase is listed as NA. Endeavor Health is named as sponsor.

The primary outcome was continuous: mean change in FGF23 from baseline to 60 days, measured in RU/mL. The primary analysis population was restricted to participants with readings at both timepoints. The reported arm summaries include 7 participants in the lanthanum carbonate arm and 6 in the placebo arm. These outcome counts are distinct from the adverse-event risk denominators, which are reported separately.

The registry lists eight secondary outcomes, covering calcium, serum phosphate, parathyroid hormone, vitamin D measures, alkaline phosphatase, osteocalcin, and 24-hour urine phosphate. It does not provide a dose, treatment schedule, detailed eligibility criteria, recruitment setting, or allocation ratio. The record also does not describe the randomization procedure or how double masking was implemented. These omissions limit what can be said about conduct and design beyond the stated randomized, double-masked, parallel structure.

Enrollment describes the study overall, while the primary endpoint summaries are based on participants with measurements at both specified timepoints. The registry does not explain why the numbers contributing to those endpoint summaries differ from overall enrollment. No additional assumptions about participant flow or analysis populations should be made from the counts alone.

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: Subjects who were naive to phosphate binders were enrolled

Overall Study

Analysis population for the primary outcome, as defined in the registry: Only patients with readings at both timepoints (baseline and 60 days) were included.

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 Fibroblast Growth Factor (FGF) 23 Mean Change From Baseline, measured over Baseline, 60 days.

The primary endpoint is mean change from baseline in fibroblast growth factor 23 (FGF23) at 60 days, with measurements expressed in RU/mL. Change scores describe how a measured value differs from a participant’s baseline value over the stated follow-up period. The record specifies that only people with readings at both baseline and 60 days were included in this outcome analysis.

FGF23 is a biomarker relevant to the study’s focus on chronic kidney disease. Measuring its change provides a way to compare the biomarker response between the randomized arms over the trial period. The registry description refers to c-terminal and FGF23 levels, while the named primary endpoint is mean change in FGF23. It does not give further assay details or explain how the c-terminal measurement relates to the primary endpoint.

This endpoint is a laboratory measure, not a direct measure of symptoms, kidney function, disease progression, or survival. A difference in the biomarker’s mean change therefore addresses the stated measurement question but, by itself, does not establish what that difference means for clinical outcomes. The record does not state a threshold that would make a particular change clinically important.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported t-test compare?

The registry reports a two-sided t-test for the primary comparison. In general, a two-sample t-test assesses whether the means in two groups differ, relative to the variation in the observations and the number of observations. A two-sided test considers departures in either direction rather than testing only whether one arm has a larger mean. Here, the measurements being compared are participant-level changes in FGF23 from baseline to 60 days.

The arm means and standard deviations summarize those changes: the mean is the average change within an arm, and the standard deviation describes the spread of individual changes around that average. A test of the difference between arms uses both the group means and information about variability and sample size. The reported p-value is 0.037. The registry does not report the test statistic, degrees of freedom, or a confidence interval, so those details cannot be reconstructed from the record.

Why use change from baseline?

In general, analyzing change can focus the comparison on how measurements move over follow-up rather than only on their final values. The interpretation depends on the baseline and follow-up measurements being collected comparably and on the analysis handling missing readings appropriately. The registry states that only participants with both baseline and 60-day readings were included. It does not state whether the analysis adjusted for baseline values in another way, or describe further checks of the change-score analysis.

What assumptions matter?

As a general statistical explanation, a t-test relies on a model for the distribution of observations and the variability used to estimate the mean difference. In small groups, unusual observations or skewed change scores can affect the means and test result. Whether those conditions were examined is not reported in the registry record. The posted standard deviations describe the amount of observed spread but cannot establish that the test assumptions hold.

Another general consideration is whether the two groups can be treated as independent for the comparison. A parallel randomized design assigns participants to one arm, so the usual two-group analysis compares independent groups. The record does not give extra detail on the test implementation, such as whether equal variances were assumed. The posted description is simply a two-sided t-test.

What does the p-value tell readers?

In general, a p-value measures how unusual a result at least as extreme as the observed one would be under a specified null model and its assumptions. It does not tell readers the probability that the null model is true, the probability that the result will replicate, or the clinical importance of the observed difference. Its interpretation is also affected by which outcome and analysis were selected and by whether other analyses were performed.

The registry reports p = 0.037 for the primary comparison. No confidence interval is reported. In general, an interval estimate complements a test by communicating the range of effect values compatible with the data and analysis assumptions. Without such an interval, the reported p-value should not be mistaken for a measure of precision or for an estimate of the likely range of the between-arm effect.

How should the outcome counts be read?

The primary summaries include 7 participants in the lanthanum carbonate arm and 6 in the placebo arm. The primary population is defined by having readings at both timepoints. The overall enrollment is 19, and the safety risk denominators are 10 and 9. These figures refer to different descriptions in the record; the registry does not reconcile them or explain the participant flow. They should not be combined into a single analysis count or used to infer why measurements were unavailable.

The record gives no confidence limits for the arm means and no participant-level data. It also does not report an alternative model, an analysis of all randomized participants, or sensitivity analyses addressing missing readings. As a result, independent verification of the test and assessment of the effect of missing observations are not possible from the registry summaries alone.

What is the role of over-dispersion?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It is especially relevant to count outcomes or models that assume a particular variance structure; additional variability can make standard errors too small if the model does not account for it. The primary endpoint is continuous and the reported method is a t-test, so the main visible dispersion information is the arm-specific standard deviation. The record does not report an over-dispersion assessment or a model that would allow one to be evaluated. This general concept should not be read as evidence that over-dispersion occurred in this trial.

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("Lanthanum Carbonate (Fosrenol)", "Placebo")
n   <- c(7, 6)
m   <- c(-62.96, 9.08)
sp  <- c(55.17, 53.84)
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  Lanthanum Carbonate (Fosrenol)  7  -62.960  55.170  -113.984  -11.936
CARM  Placebo  6  9.080  53.840  -47.422  65.582

11. Analyses Reported by the Sponsor

The registry’s formal primary comparison is a sponsor-reported two-sided t-test with p = 0.037. The arm-level means and standard deviations are also posted: -62.96 RU/mL with a standard deviation of 55.17 in the lanthanum carbonate group, and 9.08 RU/mL with a standard deviation of 53.84 in the placebo group. The comparison is based on 7 and 6 participants, respectively, who had readings at both timepoints.

No separate recalculated between-arm estimate or confidence interval is reported in the registry record. The sponsor’s test is therefore the available formal inferential result; the arm summaries alone should not be presented as a substitute test. The record does not flag a discrepancy between a sponsor result and a recalculation. There is no basis in the posted information for attributing a different result to a different calculation or analysis method.

The test result should be read alongside the limited endpoint counts and the absence of an interval estimate. The p-value does not show how precise the estimated comparison is, and the record does not report enough analytic detail to independently reproduce the sponsor’s test.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and eight secondary outcomes, and lists 9 analyses. Multiple outcomes can create a multiplicity issue: when several hypotheses are tested, the chance of at least one apparently unusual result can rise if each test is interpreted separately. General approaches include prespecifying a hierarchy or adjusting the interpretation of tests. The registry record does not report whether any multiplicity adjustment, hierarchy, or other strategy was planned. The primary p-value should therefore be understood as the reported result for that outcome, without assuming an adjustment was or was not used.

The primary analysis included only participants with FGF23 readings at both baseline and 60 days. This is a complete-measurement analysis for the stated timepoints. The registry does not report how many participants lacked one or both readings, why any measurements were missing, or whether missingness differed between arms. It also does not describe imputation or another method for handling missing outcome data. The posted arm counts alone cannot explain the reasons for inclusion or exclusion.

Overall enrollment is 19, while the primary summaries include 7 participants in the lanthanum carbonate arm and 6 in the placebo arm. Safety risk denominators are 10 and 9. The registry does not reconcile these counts, and the different figures should not be assumed to represent identical analysis populations. The record does not report an intention-to-treat analysis, a per-protocol definition, or a participant flow accounting for these numbers.

Interim analyses, stopping rules, and a detailed statistical analysis plan are not reported in the registry record. Nor is a sample-size justification reported. These omissions do not establish that such plans or procedures were absent; they mean that the record does not describe them. For the same reason, the reported p-value cannot be interpreted with assumptions about unreported interim monitoring or missing-data procedures.

13. 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 non-serious adverse event terms

The adverse-event record reports serious adverse events in 0 of 10 participants at risk in the lanthanum carbonate arm and 0 of 9 at risk in the placebo arm. No deaths were reported in either arm. These are the posted counts and denominators; they do not establish that the risk of a rare event was absent.

For other, non-serious adverse events, the record reports 1 of 10 participants affected in the lanthanum carbonate arm and 0 of 9 in the placebo arm. The record does not provide a list of event terms for those other events. The serious-event terms list is empty, consistent with no serious events being reported in either group, but the record does not provide additional event narratives.

These safety counts use risk denominators of 10 and 9, which differ from the primary endpoint analysis counts of 7 and 6. The registry does not explain the difference. The safety data are descriptive counts from a small study and do not provide a precise comparative estimate of event risk. They should not be interpreted as a complete characterization of safety beyond the events and denominators reported in the record.

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

The posted primary results describe a mean change in FGF23 over 60 days that was negative in the lanthanum carbonate arm and positive in the placebo arm. The reported two-sided t-test has p = 0.037. This provides evidence of a difference in the measured changes under the test’s assumptions, but does not quantify the precision of the estimated between-arm difference. No confidence interval is reported.

The endpoint is a biomarker measurement. The record does not report the effect of the comparison on kidney disease progression, mortality, symptoms, or other clinical outcomes. Although the study description gives a rationale connecting FGF23 measurement with chronic kidney disease, that rationale should not be confused with evidence that those broader outcomes changed in this trial.

Several limits shape the interpretation. The primary summaries include 7 and 6 participants, and the standard deviations indicate variation in observed change scores. The record does not explain the relationship between overall enrollment, the endpoint counts, and the safety denominators. It does not provide a confidence interval, participant-level measurements, or details of missing-data handling. It also does not report whether the multiple outcomes were addressed through a prespecified multiplicity strategy.

Accordingly, the result is best read as a small-trial comparison of mean FGF23 change among participants with readings at both timepoints. It is not a complete account of the uncertainty around the effect, and it does not establish clinical importance or broader health effects. The posted information supports describing the observed biomarker pattern and reported test, while leaving those wider questions unanswered.

15. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and analysis population matter when reading a clinical result. The primary outcome is not simply an FGF23 value at follow-up; it is mean change from baseline to 60 days, and only participants with measurements at both timepoints contributed to the reported summaries. That distinction affects what population the result describes.

It also shows why a p-value is not enough to characterize a result. The reported two-sided t-test gives p = 0.037, while the record does not provide a confidence interval for the between-arm comparison. Readers can see the arm means and standard deviations, but those summaries do not by themselves communicate a precise range of plausible comparative effects. The test result and descriptive statistics answer related but different questions.

The record also gives a practical example of why denominators should be tied to their specific outcomes. The primary analysis counts and safety risk counts are not the same, and the registry does not explain the relationship. Treating all counts as interchangeable would obscure which participants contributed to which analysis.

Finally, a biomarker result and a clinical outcome are not equivalent. FGF23 is the focus of the primary comparison, while progression and mortality appear in the study rationale rather than as reported trial outcomes. Separating the measured endpoint from the broader motivation helps prevent claims that exceed what the record reports. The trial is therefore useful as an example in statistical interpretation: understand the outcome, population, test, uncertainty, and limits before drawing broader conclusions.

16. 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 comparison is based on small endpoint groups: 7 participants in the lanthanum carbonate arm and 6 in the placebo arm. The registry reports means and standard deviations but no confidence interval for the between-arm result. It does not report participant-level data, making it impossible to examine the distribution of change scores, identify influential observations, or independently verify the test from the posted summaries.

The primary population requires readings at baseline and 60 days. Reasons for missing readings, the number of participants with incomplete measurements, and any missing-data procedures are not reported in the registry record. The record also does not reconcile the overall enrollment of 19 with primary endpoint counts or adverse-event risk denominators of 10 and 9. This limits assessment of participant flow and whether the analyzed groups differed from the enrolled groups.

The registry describes a randomized, double-masked, parallel study but does not report the allocation ratio, randomization procedure, masking procedures, dose, or treatment schedule. It does not provide eligibility details or the setting. A detailed statistical analysis plan, sample-size justification, interim-analysis procedures, and multiplicity strategy are also not reported.

The primary outcome is a biomarker change over 60 days. The registry does not report longer-term FGF23 results or clinical outcomes such as kidney disease progression or mortality. It lists eight secondary outcomes, but their results are not included in the posted information. These limits mean that the result describes a short-term biomarker comparison, with uncertainty about precision, missingness, analytic choices, and broader clinical relevance.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: The Effect of Lanthanum Carbonate on Fibroblast Growth Factor 23 ( FGF23) in Chronic Kidney Disease — NCT01002872.
• Registry record last updated 2023-09-21; status last verified 2023-09.
• Results first posted 2023-09-21.
• 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.

20. Record Summary

This completed randomized, double-masked, parallel study compared lanthanum carbonate (Fosrenol) with placebo in chronic kidney disease. The registry lists an enrollment of 19, a study start of 2009-10, primary completion in 2012-05, and Endeavor Health as sponsor.

The primary outcome was mean FGF23 change from baseline to 60 days among participants with readings at both timepoints. The reported means were -62.96 RU/mL for lanthanum carbonate and 9.08 RU/mL for placebo, with endpoint counts of 7 and 6. The registry reports a two-sided t-test with p = 0.037 and does not report a confidence interval for the comparison.

The record lists eight secondary outcomes and describes safety counts separately. It does not report a sample-size justification, detailed missing-data methods, or a multiplicity strategy. The primary result concerns a short-term biomarker change, not a reported clinical outcome.