A Randomised, Controlled Comparison of Vitamin D Strategies is Acute Hip Fracture Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomised, Controlled Comparison of Vitamin D Strategies is Acute Hip Fracture Patients (NCT00424619), a randomized phase 4 study. The primary outcome is 25-hydroxyvitamin D3 (25-OHD).

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, controlled, single-masked, parallel-group study sponsored by McMaster University. It lists hip fracture as the condition and an enrollment of 64. The recorded start was 2007-10, primary completion was 2009-07, and the status is completed. The record does not say which people were masked, how randomization was generated or concealed, or how participants were assigned to groups.

The three arm descriptions are 50 000 IU Vitamin D2, 100 000 IU Vitamin D2 and placebo. The study summary says its purpose was to determine the best dose of Vitamin D to achieve an optimal therapeutic level in hip fracture patients. The precise administration schedule, treatment duration, adherence procedures and criteria for defining an optimal therapeutic level are not reported in the registry record. The registry also does not specify whether additional care differed between groups.

The primary outcome was serum 25-OHD, measured at baseline, at hospital discharge (approximately 4-weeks) and at a follow-up visit (approximately 3-months). Baseline and 4-week samples were drawn in hospital. At 3-months, samples were drawn in hospital for patients remaining in acute care or rehabilitation, or at an outpatient clinic visit. The assay was the DiaSorin 25-hydroxyvitamin D radioimmunoassay at a central laboratory, except for 3 patients whose data were analyzed at other laboratories.

Secondary outcomes named in the registry were the Timed Up and Go (TUG) Test and the Two Minute Walk Test (2MWT), each assessed after 3 months. The record lists 9 outcome measures overall but no analysis entries. It does not describe the allocation proportions, follow-up procedures beyond those noted for blood sampling, or the planned statistical methods.

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.

Baseline

4 Week

3 Month

Analysis population for the primary outcome, as defined in the registry: Baseline data (n=59) was missing for two participants, and four outliers with 25-OHD taken at 6, 10 or 12 days were not included. 4-week data (n=50) was missing for 13 participants, and two outliers with 25-OHD taken at \<13 days were not included. 3-month data (n=47) was missing for 18 participants.

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 25-hydroxyvitamin D3 (25-OHD), measured over Baseline, 4 weeks and 3 months.

The primary endpoint is serum 25-hydroxyvitamin D3 (25-OHD), a continuous measurement reported in nmol/L. The registry specifies the mean and a 95% confidence interval as the outcome summary. Measurements were scheduled at baseline, 4 weeks and 3 months. The description identifies a radioimmunoassay method and explains where samples were obtained at each assessment, giving context for how the laboratory outcome was collected.

In general, a measured biological level can be used to compare groups’ laboratory values over follow-up, while repeated assessment can describe how levels vary over time. A confidence interval communicates uncertainty around an estimated quantity; it is not a guarantee that the true value lies within that particular interval. For a randomized comparison, the clinically relevant interpretation would depend on the group values and on an appropriate between-group contrast, not on isolated means alone.

The registry record does not report the mean 25-OHD values, confidence intervals, group contrasts or significance tests. It also does not define the “optimal therapeutic level” named in the study purpose. Consequently, the endpoint’s measurement approach is described, but the degree of separation between groups and the precision of any estimated dose effect cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measurement summarized by a mean and 95% confidence interval. General statistical interpretation of a mean is straightforward: it describes the center of the measured values in a group. A confidence interval describes the uncertainty around an estimated quantity under the assumptions of the analysis. Its width reflects precision; narrower intervals generally indicate more precise estimates. The registry names the interval but does not report its endpoints, so no precision assessment is possible for the primary outcome.

What would a group comparison require?

For a randomized trial, the central comparison is usually an estimate of how outcomes differ between assigned groups, with an uncertainty interval. A comparison of separate group means is not a substitute for the estimated contrast and its uncertainty. Because this study has two active-dose arms and a placebo arm, interpretation would depend on which contrasts were planned and how the measurements over time were handled. The registry record does not report contrasts, their estimates or their confidence intervals. It also does not report p-values or a statistical analysis plan.

The outcome was assessed at baseline, 4 weeks and 3 months. In general, repeated measurements can be analyzed in ways that account for within-participant correlation, or assessments can be compared at individual time points. Those approaches answer related but not identical questions and rely on different assumptions. Which approach was used, whether baseline values were incorporated into the analysis, and how time was represented are not reported in the registry record. No single time-point comparison can be reconstructed from the available record.

How should the confidence interval be read?

In general, a 95% confidence interval is produced by a procedure that, under its assumptions and repeated use, covers the target value at the stated rate. It does not mean that there is a 95% probability that a fixed target value lies inside the particular calculated interval. For a group contrast, the interval can help show which effects are compatible with the data and how uncertain the estimate is. Here, the interval is named as the dispersion measure, but no interval values are reported. Its width, location and relation to any clinically meaningful threshold cannot be assessed.

What role does randomization play?

In general, random allocation helps balance known and unknown participant characteristics across groups in expectation. It does not guarantee exact balance in a particular trial, and it does not prevent missing data, measurement error or problems with analysis. The registry labels the study randomized, but the method of sequence generation, concealment and implementation is not reported in the registry record. The record also labels the study single-masked without identifying who was masked. These omissions limit assessment of how allocation and outcome measurement may have been protected from bias.

What can the sample-size assumptions say?

General sample-size calculations are planning tools: they describe the amount of information a future study might need under stated assumptions. The record describes a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such illustrations are not observed power and do not establish the probability that this completed study detected an effect. The record does not give the illustration’s numerical outputs, the observed effect used, or a trial-specific sample-size justification. The registry record does not report the protocol’s sample-size rationale, and that rationale should not be inferred from a planning illustration.

For continuous outcomes, a normal approximation is a general method that can be used in planning or inference when its assumptions are suitable. The record does not report the distribution of 25-OHD, the variability used in any calculation, or diagnostic checks. Over-dispersion is a general concern when variation exceeds what a chosen model expects: standard errors can be too small and intervals too narrow if that extra variation is ignored. The registry record does not state whether over-dispersion was considered or whether a particular model was fitted, so it is not possible to assess its relevance to the analyses.

Finally, a registry record can describe intended outcomes and design features without presenting a full statistical report. In this record, the outcome’s name, unit, time points and summary type are available, but the inferential results are not. No recalculated effect estimate can be obtained from the registry record because the group-level outcome summaries are not reported. The sponsor’s own analysis cannot be compared with a recalculation on the basis of the numerical information recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome with measurements at baseline, 4 weeks and 3 months, and it names the TUG and 2MWT after 3 months as secondary outcomes. It also records 9 outcome measures overall. Considering several outcomes or time points raises a general multiplicity issue: the more comparisons examined, the greater the chance that at least one result appears notable by chance if each is treated as a separate test. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or which comparisons were prespecified for formal inference.

The primary outcome description reports missing observations and exclusions at each assessment. Baseline data were listed as n=59, with missing data for two participants and four outliers excluded because 25-OHD was taken at 6, 10 or 12 days. At 4 weeks, data were listed as n=50, with missing data for 13 participants and two outliers excluded because 25-OHD was taken at <13 days. At 3 months, data were listed as n=47, with missing data for 18 participants. These details are reported as written; they do not explain why each value was missing or how the analysis handled missingness and excluded observations.

In general, missing-data methods rely on assumptions about why measurements are unavailable. The registry record does not report those assumptions, imputation procedures, sensitivity analyses, or the analysis population used for the primary outcome. It also does not state whether participants were analyzed according to randomized assignment. The record lists no analysis entries; this does not establish that no analyses were performed, only that analysis results are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fractured hip (5.0%), pulmonary edmea and myocardial infarction (4.5%), gangrenous left foot requiring amputation (4.5%), death (4.5%).

The adverse-event record gives group-level counts for serious and other adverse events. For the 50 000 IU Vitamin D2 group, 1 of 22 was recorded as affected by a serious adverse event and 2 of 22 by another adverse event. For the 100 000 IU Vitamin D2 group, 3 of 22 were recorded as affected by a serious adverse event and 0 of 22 by another adverse event. For placebo, 1 of 20 was recorded as affected by a serious adverse event and 2 of 20 by another adverse event. These are descriptive counts, not evidence by themselves that an event was caused by the assigned treatment.

The registry lists serious-event terms including “fractured hip” at 5.0%, “Pulmonary edmea and Myocardial infarction” at 4.5%, “gangrenous left foot requiring amputation” at 4.5%, and “Death” at 4.5%. The denominator and the method used to form these percentages are not reported in the registry record. The listed percentages should not be treated as group-specific risks without that information. Group-specific death counts are not reported in the registry record.

In general, adverse-event counts are most useful when their definitions, observation period, attribution rules and denominators are clear. Those details are not reported in the registry record. The figures should therefore be read as registry entries describing events, not as a complete comparison of safety or a causal assessment.

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

This record is useful for identifying a randomized, controlled comparison of 50 000 IU Vitamin D2, 100 000 IU Vitamin D2 and placebo in acute hip fracture patients. It documents a continuous laboratory endpoint, the intended measurement times, the assay approach and two functional secondary outcomes. It also records enrollment, trial status and some adverse-event counts. These are design and reporting details, not evidence of the direction or size of a treatment effect.

The registry record does not report numerical results for the primary endpoint or the secondary outcomes. It gives no group means, between-group estimates, confidence intervals or p-values. Therefore, it does not show whether serum 25-OHD differed among the groups, how precisely any differences were estimated, or whether any group reached an optimal therapeutic level. The registry does not define that level either. No claim that one strategy was better or worse can be supported from the recorded outcome information.

In general, a statistically detectable difference and a clinically important difference are distinct concepts. Statistical evidence depends on the estimated contrast and its uncertainty, while clinical importance requires an interpretable threshold or context. Neither can be assessed without the relevant results and a defined target. The study purpose alone cannot fill that gap.

The record also does not provide enough information to evaluate the analysis choices, handling of missing data, multiplicity, or the details of masking and randomization. The available missing-data notes show that the number of recorded observations varied across assessment times and that some measurements were excluded based on collection timing. How those features affected the estimates is unknown. Likewise, adverse-event counts and terms do not establish causation, and the percentage denominators are not reported.

Accordingly, the registry record supports a description of what was intended and some aspects of what was recorded, but not an efficacy conclusion, a dose recommendation or a complete safety comparison. Those judgments require outcome estimates, uncertainty measures, analysis details and clinical context that are not reported in the registry record.

13. Why This Trial Matters Statistically

Statistically, this trial raises a familiar challenge: a clear randomized comparison can still be difficult to interpret when its numerical outcome results and analysis details are absent from the registry record. The three groups and repeated measurement schedule define an informative research question, but the actual estimates are needed to understand the size and precision of any differences. Without them, the study’s stated purpose cannot be translated into a statistical conclusion.

The record also illustrates why outcome timing and data availability matter. Serum 25-OHD was measured at baseline, 4 weeks and 3 months, with different missing-data notes and timing-based exclusions at those assessments. A transparent analysis would explain how these observations were handled and how comparisons across time were defined. Such decisions can affect both the estimate and its uncertainty, especially when follow-up data are incomplete. The registry record does not report the methods used.

Multiplicity is relevant because the record lists several outcome measures and more than one primary measurement time. General statistical practice distinguishes prespecified primary comparisons from exploratory analyses and describes any adjustment or interpretation strategy. That information is not reported in the registry record, so the status of any potential comparisons cannot be judged.

Finally, the trial highlights the difference between planning information and observed evidence. Sample-size planning illustrations depend on assumptions and are not a substitute for outcome estimates or observed power. The record describes assumptions for an illustration but does not report its numerical outputs or a trial-specific sample-size justification. For readers assessing the evidence, the missing results and analysis plan are more consequential than the presence of a design label alone.

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 important limitation for interpreting this record is that numerical results for the primary endpoint are not reported in the registry record. There are no group means, confidence intervals, treatment contrasts or p-values for serum 25-OHD. The named secondary outcomes, TUG and 2MWT after 3 months, also have no numerical findings recorded. As a result, neither effect size nor precision can be evaluated.

The registry does not define the optimal therapeutic level mentioned in the study purpose, nor does it report how an optimal level would be assessed. Details of the dosing schedule, treatment duration and adherence are not reported in the registry record. The record identifies the study as single-masked but does not say who was masked; random sequence generation and allocation concealment are also not described.

Outcome availability varied by assessment time. The primary outcome notes missing data and exclusions related to blood-sampling timing, but the reasons for missingness, analysis population and handling methods are not reported. The record lists 9 outcome measures and no analysis entries, but does not explain which analyses were conducted or how multiplicity was addressed. The absence of analysis entries should not be taken to mean that no analyses occurred.

Safety interpretation is also limited: the adverse-event percentage denominators and event-attribution procedures are not reported, and group-specific death counts are absent. The registry describes a planning illustration but does not report its numerical results or a trial-specific sample-size justification. These limitations concern what can be concluded from the registry record; they do not establish that the trial itself lacked analyses or other procedures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Randomised, Controlled Comparison of Vitamin D Strategies is Acute Hip Fracture Patients — NCT00424619.
• Registry record last updated 2025-07-16; status last verified 2012-05.
• Results first posted 2012-06-14.
• 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 registry describes a completed Phase 4, randomized, controlled, single-masked, parallel-group study sponsored by McMaster University, with an enrollment of 64 and hip fracture as the condition. The three arms were 50 000 IU Vitamin D2, 100 000 IU Vitamin D2 and placebo. The recorded study start was 2007-10 and primary completion was 2009-07.

The primary outcome was mean serum 25-OHD in nmol/L, measured at baseline, 4 weeks and 3 months, with a 95% confidence interval specified as the dispersion measure. TUG and 2MWT after 3 months were listed as secondary outcomes. The record includes missing-data and exclusion notes and adverse-event counts, but it does not report numerical outcome comparisons, confidence intervals or p-values. Statistical analysis details, multiplicity methods and the definition of an optimal therapeutic level are not reported in the registry record.