Suspected Deficient Activation of Vitamin D in Patients With Secondary Hyperparathyroidism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Suspected Deficient Activation of Vitamin D in Patients With Secondary Hyperparathyroidism (NCT00754442), a non-randomized na study. The primary outcome is The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours.

2. Clinical Question

The central statistical question is whether the measured response in activated vitamin D differs between the patient and control groups during the recorded observation period. A difference could be consistent with the study’s hypothesis, but a nonrandomized comparison cannot by itself establish that group status caused any difference. The registry record does not report the numerical outcome results, an estimated group contrast, or its uncertainty. It also lists the number of patients with mutations in CYP27B1 as a secondary outcome, but the mutation findings are not reported in the registry record.

3. Trial Design

This was a completed, parallel-group study with nonrandomized allocation and no masking. The registry lists enrollment of 20 and identifies a control group and a patient group with secondary hyperparathyroidism. The study sponsor was the University of Maryland, Baltimore. The phase is listed as not applicable. The record gives a start date of 2007-02 and a primary completion date of 2008-08.

The study’s stated aim was to characterize whether reduced activity of 1-hydroxylase, the enzyme described as activating vitamin D, might account for parathyroid overactivity in selected young patients with normal kidney function. The main measure was activated vitamin D, collected at baseline and at 4 and 8 hours after parathyroid hormone infusion. The record also lists Teriparatide as an intervention. The relationship between that listed intervention and the infusion procedure is not reported in the registry record.

Because allocation was not randomized, patient and control groups may differ for reasons other than the condition under study. Randomization is a general method for reducing systematic differences between comparison groups; it was not used in this study. The registry itself cautions that the arms are not a like-for-like control comparison. The record does not report a matching strategy, an adjusted analysis, or other methods intended to address baseline differences.

The final analysis population excluded one participant in each group because their GFR was below 70; the registry states that vitamin D production decreases below that threshold. It therefore describes a restricted analysis population rather than all enrolled participants. The number included in the primary outcome analysis beyond these exclusions, and the handling of any other unavailable measurements, are not reported in the registry record. Numerical findings for the primary and secondary outcomes are also not reported.

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: Of 11 "controls" enrolled, 6 completed the study and 5 dropped out because they didn't want to do the parathyroid hormone (PTH) infusion. Of 9 "patients" recruited, 6 completed the study. The others were excluded after their screening labs showed that their renal function was below the inclusion criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The final analysis was made on participants with glomerular filtration rate (GFR) of 70 and above since \<70, 1,25-D production decreases. After study completion, it was noted that one participant in each group (patient and control) had GFR\<70 so these two participants were excluded from final analysis.

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 The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours, measured over baseline, 4 and 8 hours after start of infusion.

The primary endpoint is the level of activated vitamin D, identified as 1,25-dihydroxyvitamin D and measured in pg/ml. The registry describes the outcome as a mean with standard deviation and specifies measurement at baseline and 4 and 8 hours after the start of parathyroid hormone infusion. The endpoint is therefore a continuous measure recorded at multiple times, not a count of events or a time-to-event outcome.

The study’s rationale makes this measure relevant: 1-hydroxylase is described as the enzyme that activates vitamin D, and the stated question concerns whether reduced activity of that enzyme might contribute to secondary hyperparathyroidism. Measuring activated vitamin D around a parathyroid hormone infusion was intended to characterize the response under that stimulation. This describes the endpoint’s role in the study question; it does not establish that the measure identifies the cause of a participant’s condition.

As a general statistical point, a mean describes the central level of a continuous measure, while a standard deviation describes variability among measured values. Measurements at multiple time points can help characterize a response over time, but interpretation depends on the actual values, the analysis used, and the uncertainty around any comparison. Those numerical results and the analysis details are not reported in the registry record. The record also does not state a clinically meaningful threshold for interpreting a difference in this measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: the level of 1,25-dihydroxyvitamin D in pg/ml. The registry describes reporting it as a mean with standard deviation. A mean is a measure of the center of a set of values; a standard deviation describes how spread out those values are around the mean. This is a general explanation of these statistics. The actual group means and standard deviations are not reported in the registry record.

What does the repeated measurement schedule mean?

The outcome was measured at baseline and at 4 and 8 hours after the start of infusion. These observations describe more than one time point for each participant, so measurements from the same person are generally related rather than independent. As a general statistical principle, an analysis of repeated measurements should account for that within-person relationship when estimating changes or comparing patterns over time. The registry record does not report the specific model or method used to analyze the repeated measurements, nor does it report estimates for change over time or a group-by-time comparison.

Baseline measurement can provide a reference for later values, while post-infusion measurements can describe the response during the stated observation window. The precise contrast used in the primary analysis is not reported in the registry record. It is therefore not possible to determine whether the reported analysis, if any, focused on a particular time point, change from baseline, or the overall pattern across time.

Why does the nonrandomized design matter?

In general, random allocation helps reduce systematic differences between groups at the start of a study. This study was nonrandomized, and its registry record warns that the patient and control arms are not a like-for-like comparison. Differences in measured vitamin D levels could be related to group status, but they could also reflect other differences between participants. Statistical adjustment can address measured factors under appropriate assumptions, but it cannot automatically remove bias from unmeasured factors. The registry record does not report a covariate-adjusted model or a strategy for accounting for baseline differences.

There is no masking. In general, masking can reduce the influence of knowledge about group assignment on measurement or assessment. The main endpoint is a laboratory measure, but the registry does not describe laboratory procedures, whether assessors knew group status, or any safeguards against measurement differences. These details are not reported in the registry record.

How should uncertainty be considered?

An estimate describes the result calculated from the study data, while a confidence interval conveys uncertainty around that estimate under the analysis assumptions. A p-value describes how compatible the data are with a specified null hypothesis and statistical model. Neither can substitute for the other, and neither alone establishes the importance of a finding. These are general statistical concepts. The registry record does not report the primary outcome estimate, its confidence interval, or its p-value, so the magnitude and precision of the result cannot be evaluated.

For continuous outcomes, the distribution of values can affect whether a chosen model is suitable. General diagnostics may consider the distribution of residuals, influential observations, and whether the variability is adequately represented by the model. The registry record does not report diagnostic checks, transformations, or model assumptions. It also does not report whether results were adjusted for baseline levels or other participant characteristics.

What do the planning illustrations represent?

The registry describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. These are planning calculations, not the trial’s reported design justification. They are also not observed power: observed power is not a substitute for presenting an effect estimate and its uncertainty. The illustration values are not reported in the registry record. The registry does not report the assumptions or calculations used for the original study’s sample-size planning.

In general, sample-size calculations depend on a target effect, variability, significance level, allocation, and statistical method. Changing the assumed effect changes the planning result. A calculation based on an observed effect should therefore be read as an illustration conditional on that estimate and its assumptions, not as an independent confirmation of the result. No additional planning values or original assumptions are reported in the registry record.

What cannot be reconstructed?

The registry lists three analyses and two outcome measures, but does not report the analysis specifications or numerical results for the outcomes. The record does not identify the statistical software, the handling of repeated observations, the model for the primary comparison, or the approach to missing values. No recalculated estimate is available in the record, and there is no reported discrepancy between a sponsor analysis and a recalculation. Without the outcome data and analysis details, an independent statistical reconstruction is not possible. These omissions limit interpretation; they do not establish that a particular analysis was or was not performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and three analyses. It identifies activated vitamin D level as the primary outcome and the number of patients with mutations in CYP27B1 as a secondary outcome. The numerical results for the secondary outcome are not reported in the registry record. The specific analyses corresponding to the three listed analyses are also not reported.

Multiplicity is a general statistical concern when several outcomes, time points, or comparisons are examined. Each additional statistical test can increase the chance of obtaining at least one apparently notable result by chance if no adjustment or prespecified hierarchy is used. A study may address this through methods such as a defined primary outcome, a testing hierarchy, or an adjustment to significance thresholds. The registry record does not report whether any multiplicity procedure or testing hierarchy was planned or used. The existence of multiple outcome measures or analyses alone does not show that an adjustment was required or omitted; the analysis plan is not reported.

The final primary analysis excluded one participant in each group because GFR was below 70. The registry states that the final analysis was made among participants with GFR of 70 and above. This is an analysis-population restriction based on kidney function. The record does not report whether the restriction was specified before data collection or analysis, or whether other participants lacked outcome measurements.

Handling of missing data is not reported in the registry record. It does not say whether all scheduled measurements were available, how incomplete participant records were handled, or whether any imputation or sensitivity analysis was used. The number analyzed for each outcome beyond the stated GFR exclusions is not reported. These details matter because an analysis limited to participants with complete measurements may differ from one that uses other missing-data methods, particularly if missingness is related to participant characteristics or outcomes. No conclusion about the effect of missing data can be drawn without further information.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events among the listed participants at risk: 0 of 11 controls and 0 of 9 participants in the patient group. It reports one participant with an other, non-serious adverse event in each group: 1 of 11 controls and 1 of 9 participants in the patient group. The record does not give the terms for serious adverse events, and deaths are not reported in the registry record.

These figures are descriptive counts within the groups recorded for safety. They do not establish that an event was caused by an intervention, and the nonrandomized groups should not be treated as directly comparable for causal safety conclusions. A count of zero serious events in the recorded groups does not demonstrate that the risk of such events is absent; rare events may not appear in a study of this size. This is a general interpretation of small safety datasets.

The registry does not report further details about the other adverse events, their timing, severity, duration, or relationship to treatment. It also does not describe how adverse events were collected or whether all participants were followed for the same period. The figures therefore provide a limited account of recorded events, not a comprehensive estimate of safety.

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

The registry record describes a study intended to investigate a proposed biological explanation for secondary hyperparathyroidism in a selected group of young patients. It identifies activated vitamin D as the primary outcome and records measurements at baseline and 4 and 8 hours after parathyroid hormone infusion. It also identifies a secondary outcome concerning mutations in CYP27B1. These details clarify what the investigators aimed to study, but they do not show what the measurements found.

The primary outcome values, group comparison, and uncertainty estimates are not reported in the registry record. The mutation outcome findings are also not reported. As a result, the record does not support a statement about whether the patient group had higher or lower activated vitamin D levels, how large any difference was, or how precisely it was estimated. It likewise does not establish whether mutations were identified.

The design further limits causal interpretation. Allocation was nonrandomized, and the registry warns that the patient and control arms are not a like-for-like comparison. Even a reported difference would need to be interpreted in light of possible differences between groups, the restricted final analysis population, and the unreported analysis methods. A biological association, if observed, would not on its own prove that reduced enzyme activity caused the condition.

These limitations do not make the research question unimportant. They define what can be concluded from this record. The study’s measurement strategy addresses a plausible mechanism, but the posted registry information does not include the numerical outcome evidence needed to assess the findings. It is therefore not possible to claim that the proposed explanation was confirmed or ruled out. Nor can the record establish a treatment benefit or lack of benefit.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring a biological response and demonstrating a causal explanation. Activated vitamin D levels collected at baseline and after infusion can characterize a response over time. Comparing that response across patient and control groups, however, requires attention to the fact that allocation was nonrandomized. The registry explicitly notes that the arms are not a like-for-like control comparison.

The final analysis also applied a GFR threshold: participants with GFR below 70 were excluded because the registry states that vitamin D production decreases below that level. This restriction may make the analysis population more relevant to the stated question about participants with preserved kidney function, while limiting how broadly findings could be applied. The primary outcome results are not reported, so the implications of the restriction for the measured results cannot be assessed.

Statistically, a clear account of estimates and uncertainty is essential for evaluating a mechanistic hypothesis. Means and standard deviations can describe continuous measurements, but a group comparison also needs an explicit contrast and an account of uncertainty. The registry record does not report those primary outcome results or the analysis method. Its description of planning illustrations does not replace the missing outcome estimates and should not be mistaken for observed power.

The record is therefore informative about the study question, group structure, measurement schedule, and analysis-population restriction, while leaving key evidence unavailable. That contrast matters: design information can identify potential sources of bias and clarify what was intended, but only reported outcome estimates and methods can support a statistical assessment of what the study found.

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 most direct limitation for interpretation is that numerical results for the primary outcome are not reported in the registry record. Without means, a comparison estimate, or an uncertainty measure, the direction, magnitude, and precision of the activated vitamin D findings cannot be assessed. The registry also does not report the results for its secondary mutation outcome.

The nonrandomized allocation is a design limitation for comparing the patient and control groups. The registry itself cautions that the arms are not a like-for-like comparison. It does not report baseline characteristics beyond the study’s general description, matching, or adjustment methods that might help assess or address group differences.

The analysis excluded one participant in each group because GFR was below 70. The record gives a biological reason for this restriction, but does not report whether it was prespecified or how it affected the analysis. The number with complete primary outcome measurements is not reported, and missing-data methods are not described.

The primary outcome was measured at multiple times, yet the statistical method for handling repeated measurements is not reported. The record does not state the exact primary contrast, whether baseline values were incorporated analytically, or whether comparisons were adjusted for other factors. It lists three analyses and two outcomes, but does not report the analysis plan or any multiplicity approach.

Finally, the registry lists Teriparatide as the intervention while the primary outcome description refers to parathyroid hormone infusion. Their relationship is not reported in the registry record. The record also lacks detail on measurement procedures and adverse-event collection. These reporting gaps limit evaluation of the study; they should not be mistaken for proof that a particular procedure or analysis was absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Suspected Deficient Activation of Vitamin D in Patients With Secondary Hyperparathyroidism — NCT00754442.
• Registry record last updated 2022-04-01; status last verified 2022-03.
• Results first posted 2014-05-14.
• 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.

18. Record Summary

The completed study was a nonrandomized, unmasked, parallel-group investigation sponsored by the University of Maryland, Baltimore. It enrolled 20 participants and focused on suspected impaired activation of vitamin D in selected patients with secondary hyperparathyroidism. The primary outcome was activated vitamin D level, measured at baseline and 4 and 8 hours after parathyroid hormone infusion.

The final analysis was restricted to participants with GFR of 70 and above, excluding one participant in each group whose GFR was below 70. The registry lists Teriparatide as the intervention, a control subject group, and a secondary outcome concerning CYP27B1 mutations. The relationship between the listed intervention and the infusion procedure is not reported in the registry record.

Numerical outcome findings, detailed analysis methods, and missing-data procedures are not reported in the registry record. The record cautions that the nonrandomized arms are not a like-for-like comparison. Its adverse-event counts list no serious events in either group and one other event in each group; deaths are not reported.