A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors (NCT00186901), a randomized phase 3 study. The primary outcome is Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD).

2. Clinical Question

The question concerns a selected group of survivors with a BMD Z-score below the reference mean, not all childhood leukemia survivors. The trial description also says researchers sought to examine the frequency and severity of diminished bone mineral density and factors that might be associated with it. The registered primary outcome, however, is the effect of taking calcium and vitamin D supplements on BMD, measured with QCT Z-scores. The listed secondary outcomes include QCT and DXA scan scores and mean QCT Z-scores by vitamin D receptor genotype. The record does not give numerical results for those outcomes.

3. Trial Design

This was a completed Phase 3, randomized, double-blind, parallel trial sponsored by St. Jude Children's Research Hospital. The registry lists enrollment as 429 and gives a start date of 2000-07 and a primary completion date of 2009-06. The intervention comparison was between nutritional counseling plus placebo and nutritional counseling plus calcium and vitamin D. The supplement regimen is described as calcium, 1000mg/day, and vitamin D, 800 units/day, for a 2 year period.

The randomized outcome population was a subset of the enrolled participants: the record says 275 participants with BMD z-scores < 0 were randomized, with 134 assigned to placebo and 141 assigned to supplements. It separately lists 149 patients as ineligible for randomization. The reasons for ineligibility and the criteria used to identify participants for randomization are not reported in the registry record. These figures describe different parts of the study population and should not be treated as interchangeable denominators.

Randomization is intended to make the assigned groups comparable on average, while a parallel design means each participant is assigned to one group rather than switching between the interventions. Double masking is recorded, but the record does not specify which people were masked or how masking was maintained. Details about the randomization procedure, allocation concealment, recruitment locations, and planned follow-up for each participant are not reported in the registry record.

The primary outcome was assessed at baseline, 12 months, 24 months, and at 36 months or study end. This schedule identifies planned assessment times, but does not establish that every randomized participant had a measurement at every time. The numbers assessed at each time and the reasons for any missing measurements are not reported in the registry record.

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: 424 total patients were enrolled on the study. 149 patients were ineligible for randomization. 275 patients were identified with Bone Mineral Density (BMD) Z-scores \> 0 and thus were eligible for intervention and were randomized to receive either Calcium and Vitamin D supplementation or placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the 275 pts identified with BMD z-scores \< 0, 134 were randomized to the placebo group and 141 to the supplement group. Bone Mineral Density QCT Z-scores were calculated at baseline, 12 months, 24 months, and at 36 months or study end.

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 Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD), measured over Baseline, 12 months, 24 months, and at 36 months or study end.

The primary endpoint is BMD measured using a QCT-derived Z-score. A Z-score expresses how far a participant's BMD is from the mean for age- and gender-appropriate controls, in standardized units. The registry describes BMD as a measure of bone strength. Using a standardized score makes the outcome interpretable relative to the age- and gender-appropriate reference group specified in the record.

The registry lists the endpoint at baseline, 12 months, 24 months, and at 36 months or study end. It specifies the median and full range as the summary measures. In general, a median describes the central value after ordering observations, while the full range describes the lowest and highest observed values. Those summaries can convey the distribution differently from a mean and standard deviation, particularly when measurements are not symmetrically distributed. This is a general statistical explanation; the registry does not state why these summaries were selected.

The record gives interpretive bands for the Z-score: 0 to +2 is considered normal, above +2 elevated, from 0 to -1 a mild BMD deficit, between -1 and -2 moderate deficits, and below -2 severe deficits. These are the registry's stated categories, not observed trial findings. The record does not provide the median or full-range values for either randomized group, or numerical comparisons between groups. It therefore does not establish from the information reported which group had higher or lower scores at any assessment time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry records a randomized, double-blind, parallel design. Random assignment is a method for allocating participants to intervention groups by chance. In general, this can reduce systematic differences between groups at assignment, although it does not guarantee that every characteristic is balanced in a particular trial. A parallel design assigns each participant to one intervention group for the comparison. The record does not describe the randomization sequence or allocation concealment, so those implementation details cannot be assessed.

What does the Z-score represent?

The primary endpoint uses a standardized QCT score. In general, standardization expresses an observation in relation to a reference distribution, allowing the observation to be described in units of the reference distribution's spread. Here, the registry specifically defines the score in relation to the mean BMD for age- and gender-appropriate controls. A score below 0 indicates a value below that stated reference mean. The trial identified participants with BMD z-scores < 0 for randomization. The registry does not report the reference data or further details of the score calculation.

The registry lists descriptive categories for interpreting scores: 0 to +2 as normal, above +2 as elevated, from 0 to -1 as a mild BMD deficit, between -1 and -2 as moderate deficits, and below -2 as severe deficits. These categories translate a continuous score into ranges. In general, categorization can make results easier to describe in terms of severity bands, but it discards some detail about differences between scores within a band. The endpoint summary is listed as a median and full range; the record does not say that the primary analysis tested these categories.

Why report a median and full range?

In general, a median identifies the middle observation after the values are ordered. It is less influenced by unusually high or low values than a mean. The full range gives the observed minimum and maximum, and therefore describes the outer spread, but it does not show how observations are distributed between those endpoints. These explanations are general. The registry names the median and full range but does not report the values or explain the choice of summaries.

For this trial, a useful treatment comparison would need to relate the randomized groups' outcomes, rather than interpret one group's score in isolation. Baseline and follow-up measurements could be used to describe the score pattern over time, but the record does not specify whether the analysis compared follow-up values, changes from baseline, or another summary. It also does not report the model or test used for the primary outcome. No specific analysis method should be inferred from the endpoint description alone.

How should multiple assessment times be understood?

The registry lists baseline, 12 months, 24 months, and at 36 months or study end. Repeated measurements from the same participant are generally related rather than independent. In general, an analysis of repeated measurements can account for that within-participant relationship, whereas treating each measurement as independent may not. The statistical model, handling of measurements taken at different times, and definition of the final assessment are not reported in the registry record. It is also not stated how many randomized participants contributed data at each time.

The primary outcome is not reduced to a single comparison in the record: it spans multiple assessment times. Without a specified contrast or numerical results, a reader cannot identify whether the intended inference focused on one time point, a trajectory over time, or another summary. This matters because different choices answer different statistical questions. This is a general point about repeated-measure outcomes, not a description of an analysis method documented for this trial.

What does the planning illustration mean?

The registry's planning assumptions describe a calculation based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such a calculation is a planning illustration, not an observed trial outcome and not the trial's original sample-size justification. In general, sample-size planning asks how many participants per arm would be needed to target a specified probability of detecting an effect under stated assumptions. It is not observed power, and it does not show that the trial actually achieved that probability.

The record does not report the trial's original sample-size justification, and it does not provide a numerical observed effect or numerical planning outputs in the information described. The original statistical plan, including its primary analysis method, is not reported in the registry record. A planning calculation based on an observed effect would also depend on the uncertainty and definition of that effect; the record does not provide those details.

What can be said about uncertainty?

In general, a confidence interval pairs an estimate with an uncertainty range under a chosen statistical model. Its width is influenced by the amount and variability of data and by the analysis. A p-value addresses compatibility with a specified null hypothesis under model assumptions, not the practical importance of an effect. Neither can be reconstructed from the group counts alone. Numerical estimates, confidence intervals, and p-values for the primary outcome are not reported in the registry record, so no precision or significance assessment can be made from the available outcome information.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is assessed at baseline, 12 months, 24 months, and at 36 months or study end. The registry also lists secondary outcomes involving QCT and DXA scan scores and mean QCT Z-scores by Apa1 and Bsm 1 vitamin D receptor genotype. It reports 10 outcome measures and 13 analyses. The registry does not explain how these outcomes and analyses were defined, or which were considered confirmatory.

When several outcomes, time points, or analyses are examined, the chance of at least one apparently unusual result can increase. In general, multiplicity methods specify how to interpret multiple statistical tests, such as by adjusting testing thresholds or identifying a limited set of primary comparisons. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or a prespecified primary time point. No specific adjustment should be assumed.

Missing-data handling is not reported in the registry record. The outcome schedule identifies planned assessments, but does not state how many participants contributed at each time, whether any data were missing, why measurements might be missing, or how missing values were handled in analysis. The analysis population is also not reported: the record does not say whether analyses followed randomized assignment, included only participants with available measurements, or used another population definition.

The registry reports 429 enrolled, 275 participants with BMD z-scores < 0 randomized, and 149 patients ineligible for randomization. These counts do not describe follow-up completeness or the number analyzed for each endpoint. The reasons for ineligibility and any exclusions after randomization are not reported in the registry record. Without analysis denominators and missing-data methods, the extent to which outcome estimates represent all randomized participants cannot be assessed.

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.

The registry lists 134 participants at risk in the placebo group and reports 0 affected by serious adverse events and 0 affected by other adverse events. For the supplement group, it lists 141 at risk, with 0 affected by serious adverse events and 0 affected by other adverse events. For patients ineligible for randomization, it lists 149 at risk, with 0 affected in each of those categories. These are the registry's group-level counts.

The figures indicate that the record lists no affected participants in either adverse-event category for these groups. They should be read as registry-reported counts, not as proof that no adverse event of any kind occurred during the study. The time period covered by these figures and the procedures used to collect or classify events are not reported in the registry record. The list of top serious adverse event terms is empty, and deaths are not reported in the registry record.

The ineligible group is separate from the randomized placebo and supplement groups. Its safety figures should not be interpreted as another randomized treatment arm. The record does not provide event-level descriptions, severity breakdowns beyond the serious and other categories, or explanations for the zero affected counts. These safety entries alone do not establish comparative safety or explain why no events are listed.

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

The registry record describes a randomized comparison of calcium and vitamin D supplementation against placebo among childhood acute lymphoblastic leukemia survivors with BMD Z-scores < 0. It identifies the planned QCT Z-score endpoint and assessment times and reports the numbers assigned to each group. This establishes what question the trial was designed to address, but the record information described does not include numerical primary-outcome results.

Without group medians, ranges, a between-group estimate, or an uncertainty interval, the direction, size, and precision of any difference cannot be determined. The planned follow-up times do not reveal what happened to BMD Z-scores. Likewise, the score categories describe how values may be classified relative to the reference distribution; they do not show how many participants fell into any category. A lack of numerical results in the record should not be read as evidence of no difference.

The registry's completed status and enrollment count do not show that every enrolled or randomized participant completed every assessment. The number of participants included in analyses, missing measurements, and reasons for missingness are not reported in the registry record. Those details would be important for understanding how closely outcome summaries reflect the randomized population.

The record also does not report the original sample-size justification, primary statistical model, multiplicity approach, or numerical primary-outcome analyses. Consequently, the statistical strength and clinical importance of any treatment contrast cannot be evaluated from these details. The listed secondary outcomes and number of analyses indicate that the study included additional measurements, but their numerical results and analysis methods are not described in the registry information.

In general, randomized assignment supports interpretation of a between-group comparison when the analysis preserves assignment and relevant follow-up is appropriately handled. That principle does not supply the missing result or guarantee that every aspect of trial conduct was free of bias. The registry record supports describing the design and outcome question, but not a conclusion about whether supplementation changed BMD or how large any change might have been.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a clearly stated outcome framework and a reportable treatment estimate. The registry identifies a randomized, double-blind, parallel comparison, defines a QCT-based BMD Z-score, and gives planned measurement times. Those details clarify the intended comparison. However, without the numerical group results and uncertainty measures, the central statistical question cannot be answered from the registry record.

The choice of a standardized score is relevant because the registry defines it against age- and gender-appropriate controls. The randomized population was selected using a BMD Z-score below 0, so the results, if reported, would pertain to that selected group rather than automatically representing all childhood acute lymphoblastic leukemia survivors. The separate count for participants ineligible for randomization also emphasizes that enrollment and the randomized outcome population are not the same description of the study.

The repeated assessment schedule and multiple listed outcomes raise questions that matter when interpreting clinical-trial statistics: which time point or summary carries the primary inference, how repeated measurements are modeled, how multiple analyses are handled, and how missing observations affect the analysis. The registry record does not report those statistical details. Their absence limits interpretation even though the design and endpoint are described.

More broadly, the record demonstrates why group counts and trial completion status cannot stand in for outcome estimates. Statistical interpretation requires the observed outcome summaries and a clear account of how comparisons were made. Here, the design and measurement plan are identifiable, while the numerical primary result and its precision are not reported in the registry record.

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 principal limitation for interpreting this trial from the registry record is that numerical results for the primary endpoint are not reported. The record specifies median and full-range summaries and the assessment schedule, but does not give the values for either randomized group or a between-group contrast. Confidence intervals and p-values are also not reported in the registry record.

The randomized population is described as participants with BMD z-scores < 0, but further eligibility criteria and participant characteristics are not reported in the registry record. The reasons that 149 patients were ineligible for randomization are also not reported. This limits assessment of how the randomized participants compare with the broader enrolled group and which survivors the results might represent.

Although the record lists baseline, 12-month, 24-month, and 36-month or study-end assessments, it does not report the number measured at each time. Follow-up completion, reasons for missing measurements, and missing-data methods are not reported in the registry record. The analysis population and any exclusions after randomization are likewise not described.

The registry reports 10 outcome measures and 13 analyses, and lists several scan-based secondary outcomes and genotype-related summaries. It does not report which comparisons were prespecified as confirmatory, how multiple analyses were addressed, or the statistical model used for the primary endpoint. The original sample-size justification and operational details of masking and randomization are not reported in the registry record.

Finally, the safety entries provide group counts with 0 affected participants in the serious and other adverse-event categories, but do not describe the event-collection period or methods. Deaths are not reported in the registry record. These limitations constrain interpretation of both efficacy outcomes and safety reporting; they do not establish that an unreported result was null.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors — NCT00186901.
• Registry record last updated 2017-05-10; status last verified 2011-12.
• Results first posted 2012-03-27.
• 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

NCT00186901 is a completed Phase 3 randomized, double-blind, parallel trial sponsored by St. Jude Children's Research Hospital. The registry lists enrollment of 429, a start date of 2000-07, and a primary completion date of 2009-06.

The trial compared nutritional counseling plus placebo with nutritional counseling plus calcium, 1000mg/day, and vitamin D, 800 units/day, for a 2 year period. The primary outcome was QCT-derived BMD Z-score at baseline, 12 months, 24 months, and at 36 months or study end. The registry reports 275 participants with BMD z-scores < 0 randomized: 134 to placebo and 141 to supplements; 149 patients were ineligible for randomization.

Numerical primary-outcome results, analysis methods, missing-data handling, and multiplicity procedures are not reported in the registry record. The safety entries list 0 affected by serious adverse events and 0 affected by other adverse events in each of the placebo, supplement, and ineligible groups.