This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Vitamin D Absorption in HIV Infected Young Adults Being Treated With Tenofovir Containing cART (NCT01751646), a randomized na study. The primary outcome is Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01751646 |
| Phase | NA |
| Condition | HIV Infection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 214 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of North Carolina, Chapel Hill |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents and young adults with HIV infection who were receiving combination antiretroviral therapy that included tenofovir disoproxil fumarate. The registry describes the background regimen as including at least three FDA-approved antiretroviral drugs for at least 180 days. The study enrolled 214 participants.
Intervention
Vitamin D3 50,000 IU given orally every four weeks by directly observed therapy. The intervention description also mentions a daily multivitamin containing no more than 600 IU of vitamin D3 and 200 mg of calcium.
Comparator
An oral vitamin D3 placebo every four weeks by directly observed therapy. The placebo-group description also mentions a daily multivitamin containing no more than 600 IU of vitamin D3 and 200 mg of calcium.
Primary question
Did the randomized groups differ in percent change from baseline to week 48 in spine bone mineral density measured by dual-energy X-ray absorptiometry? The registry reports the group medians and a Wilcoxon (Mann-Whitney) comparison.
The clinical question is about a measured bone-density outcome in a defined treatment context, not about vitamin D use in all people with HIV or all people receiving antiretroviral therapy. The trial record identifies the condition as HIV infection and the primary outcome as lumbar spine bone mineral density from L1 to L4. It does not establish that the result applies to populations outside the described age and treatment context.
3. Trial Design
The registry describes a randomized, parallel-group study comparing vitamin D3 with vitamin D3 placebo. Its masking field is recorded as triple, while the official title describes the trial as double-blind and placebo-controlled. The record does not explain the difference in masking terminology. The study is listed as phase NA and completed. Enrollment was 214. The study began in 2012-10, and primary completion was recorded in 2016-06.
The intervention was vitamin D3 50,000 IU orally every four weeks by directly observed therapy. Participants assigned to placebo received placebo orally on the same schedule, also by directly observed therapy. The arm descriptions mention a multivitamin for both groups, with no more than 600 IU of vitamin D3 and 200 mg of calcium, and describe daily self-administration. Other details of the arm descriptions are not reported in the registry record.
The study is described as a 48 week prospective study among adolescents and young adults with HIV who were receiving a tenofovir-containing combination antiretroviral regimen. The primary endpoint uses baseline and week 48 measurements. The registry's primary-outcome population is described as participants with both baseline and week 48 data. It includes some participants who completed week 48 evaluations but were discontinued before later visits, so the analyzed population is not described simply as those who completed the full study.
The registry record does not report the randomization procedure, allocation concealment method, detailed protocol for masking, site count, or a sample-size justification. These omissions prevent a fuller assessment of how allocation was implemented and how the planned enrollment related to the intended statistical precision.
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
| Stage | Group A: Vitamin D3 50,000 IU | Group B: Vitamin D3 Placebo |
|---|---|---|
| STARTED | 109 | 105 |
| COMPLETED | 98 | 87 |
| NOT COMPLETED | 11 | 18 |
Reasons for not completing this period:
| Reason | Group A: Vitamin D3 50,000 IU | Group B: Vitamin D3 Placebo |
|---|---|---|
| Lost to Follow-up | 5 | 1 |
| Withdrawal by Subject | 0 | 4 |
| Starting hormone therapy | 1 | 0 |
| Missed 4 or more consecutive DOT visits | 2 | 3 |
| Inadvertent enrollment | 1 | 1 |
| Moved out of the area | 1 | 5 |
| Inability to attend required visits | 0 | 1 |
| Off study due to multiple obligations | 0 | 1 |
| Fails to comply with study requirements | 0 | 1 |
| Childcare issues | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Subjects who had baseline and wk 48 data. This includes subjects enrolled in v1.0, who completed wk 48 evaluations, but were prematurely discontinued before the wk 96 or Post-wk 48 visits and therefore not counted as having completed the study. Thus, the number analyzed may be greater than the number completed in the Participant Flow section.
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.
Population: The baseline analysis population includes all participants randomized to Group A or Group B who received the intervention, with the exception of two participants (one in each group) who were later determined to have been inadvertent enrollments who did not meet eligibility criteria.
| Characteristic | Unit | Group A: Vitamin D3 50,000 IU | Group B: Vitamin D3 Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 108 | 104 | 212 | |
| Age, Continuous | years | 21.84 (SD 1.95) | 21.85 (SD 1.55) | 21.84 (SD 1.76) |
| Sex: Female, Male: Female | Participants | 18 | 15 | 33 |
| Sex: Female, Male: Male | Participants | 90 | 89 | 179 |
| Race/Ethnicity, Customized: Race – Black | Participants | 78 | 79 | 157 |
| Race/Ethnicity, Customized: Race – Non-black | Participants | 30 | 25 | 55 |
| Race/Ethnicity, Customized: Ethnicity – Hispanic or Latino | Participants | 21 | 24 | 45 |
| Race/Ethnicity, Customized: Ethnicity – Non-Hispanic or Non-Latino | Participants | 87 | 79 | 166 |
| Race/Ethnicity, Customized: Ethnicity – Unknown/Not reported | Participants | 0 | 1 | 1 |
| Season Enrolled: Winter | Participants | 44 | 39 | 83 |
| Season Enrolled: Spring | Participants | 43 | 42 | 85 |
| Season Enrolled: Summer | Participants | 15 | 18 | 33 |
| Season Enrolled: Fall | Participants | 6 | 5 | 11 |
| Lumbar spine bone mineral density (BMD) | g/cm^2 | 1.06 (0.99 to 1.19) | 1.08 (0.98 to 1.20) | 1.07 (0.99 to 1.19) |
| Lumbar spine BMD (L1-L4) (Z-score) | z-score | -0.65 (-1.40 to 0.00) | -0.70 (-1.60 to 0.20) | -0.70 (-1.50 to 0.10) |
| Total Hip BMD | g/cm^2 | 1.06 (0.95 to 1.16) | 1.05 (0.95 to 1.17) | 1.06 (0.95 to 1.17) |
| Total hip BMD (Z-score) | Z-score | -0.40 (-1.10 to 0.10) | -0.65 (-1.35 to 0.00) | -0.50 (-1.20 to 0.00) |
| Femoral neck BMD | g/cm^2 | 0.98 (0.88 to 1.12) | 1.00 (0.88 to 1.12) | 0.99 (0.88 to 1.12) |
| Femoral neck BMD (Z-score) | Z-score | -0.50 (-1.20 to 0.30) | -0.60 (-1.30 to 0.25) | -0.60 (-1.20 to 0.30) |
| Whole Body BMD | g/cm^2 | 1.18 (1.10 to 1.25) | 1.17 (1.07 to 1.26) | 1.17 (1.09 to 1.25) |
| Whole body BMD (Z-score) | Z-score | -0.60 (-1.35 to 0.10) | -0.80 (-1.65 to 0.10) | -0.70 (-1.60 to 0.10) |
| Whole Body Bone Mineral Content (BMC) | g | 2636.03 (2368.41 to 2938.59) | 2596.06 (2316.00 to 2936.00) | 2627.16 (2338.39 to 2938.59) |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups, measured over Baseline and wk 48.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | percent change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is percent change from baseline to week 48 in dual-energy X-ray absorptiometry-measured bone mineral density at the spine. The description specifies lumbar spine measurements from L1 to L4. Bone mineral density is a quantitative measure of mineral content relative to scanned bone area, and change over time allows the study to compare trajectories from a common baseline rather than only comparing week 48 values.
The endpoint is relevant to the stated study question because the trial concerns bone mineral density among young people receiving tenofovir-containing therapy. The registry also lists secondary outcomes involving bone mineral content and bone mineral density at other sites or time points, but the primary comparison is specifically the percent change in spine bone mineral density at week 48.
The registry reports the primary outcome as a median with inter-quartile range. The reported median percent change was 0.19 in the vitamin D3 group and 0.09 in the placebo group. Numerical inter-quartile ranges are not reported in the registry record. The primary analysis is identified as a Wilcoxon (Mann-Whitney) test, with p = 0.117. A between-group effect estimate with a confidence interval is not reported in the registry record. Therefore, the reported medians describe the groups, while the test result supplies a rank-based comparison without a directly reported estimate of the size and precision of the between-group contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary endpoint, the registry reports a median percent change in spine bone mineral density of 0.19 for the vitamin D3 group and 0.09 for the placebo group among participants with baseline and week 48 data. The registry's reported Wilcoxon (Mann-Whitney) comparison has p = 0.117. This is the posted primary analysis and should be read as a comparison of the distributions of the observed outcome ranks, not as a direct estimate of the difference between the two medians.
The p-value does not measure the size of the difference or the probability that the study hypothesis is true. In general, a p-value describes how compatible the observed data are with a specified null model under the assumptions of the test. It is not a measure of clinical importance. The registry does not report a confidence interval for the between-group primary contrast, so the precision of that contrast cannot be read directly from an estimate-and-interval pair. The group medians alone do not convey the full distribution or its uncertainty.
The primary analysis population is described as participants with baseline and week 48 data. The arm counts used for the primary results are 99 in the vitamin D3 group and 89 in the placebo group. These are analysis counts, not a statement that every enrolled participant contributed to this endpoint. The registry's population description notes participants who completed week 48 evaluations but were discontinued before later visits. The record does not report a complete accounting of missing primary outcome values or the method used to address missingness.
Other posted results concern 25-OHD serum concentrations by efavirenz use and a range of bone outcomes. They address additional questions and should not be treated as replacements for the randomized primary comparison. For the efavirenz subgroup comparisons, recalculated mean contrasts and intervals are unadjusted. Their interpretation is limited by uncertainty and by the absence of a reported multiplicity strategy. The registry also reports within-group tests for changes in 25-OHD, which do not by themselves test whether the changes differed between efavirenz-use groups.
Overall, the posted primary result is a modestly separated pair of medians accompanied by a rank-based p-value, without a reported between-group effect estimate and confidence interval. That combination permits description of the observed data and the test result, but not a precise statement about the range of plausible between-group effects. It also does not justify a causal conclusion beyond the scope of the randomized comparison and the analysis population described in the registry.
9. Statistical Methods Explained
The primary outcome is summarized by a median and an inter-quartile range. The median is the middle of an ordered set of observations. The inter-quartile range describes the span from the lower quarter to the upper quarter of the observed distribution and is a measure of spread. In general, these summaries are useful when the distribution may not be well represented by a mean and standard deviation. The registry identifies the dispersion as an inter-quartile range, but numerical inter-quartile ranges are not reported in the registry record.
What does the Wilcoxon (Mann-Whitney) test compare?
The registry identifies the primary comparison as a Wilcoxon (Mann-Whitney) test. In general, this is a rank-based method: observations from the two groups are ordered together, and the test evaluates whether the ranks tend to differ between groups. It does not automatically test a difference between medians in every setting. Interpreting it specifically as a median comparison requires additional assumptions about the shapes of the group distributions. The registry reports p = 0.117 for the primary comparison but does not report a rank-based effect estimate or confidence interval.
A p-value is evaluated relative to a statistical model and a null hypothesis. In general, a small p-value indicates that the observed data would be relatively unusual under that null model, while a larger value indicates less evidence against it. Neither kind of result gives the probability that the null hypothesis is true. A p-value also does not describe the magnitude of an effect or whether it matters clinically. Those questions require estimates and an assessment of their precision and relevance.
How should a confidence interval be understood?
In general, a confidence interval is a range of values generated by a method that, over repeated applications under its assumptions, has a stated coverage property. It communicates uncertainty around an estimated effect more directly than a p-value alone. The primary registry result does not include a between-group confidence interval, so no such interval can be interpreted for the primary contrast. In the secondary efavirenz analyses, recalculated intervals accompany unadjusted mean contrasts. They should be interpreted as uncertainty around those recalculated contrasts, not as registry-reported adjusted treatment effects.
For the efavirenz analyses, recalculated mean differences are based on posted group means and standard deviations. These are simple, unadjusted comparisons. For example, baseline 25-OHD concentration was reported as a mean of 17.02 ng/mL among participants using efavirenz and 19.61 ng/mL among those not using efavirenz. The recalculated mean difference for no efavirenz use relative to efavirenz use is 2.59, with an interval from 0.028 to 5.152 and an unadjusted p-value of 0.048. These results concern an observational subgroup distinction within the trial record; they are not a randomized comparison of efavirenz assignment.
At week 48, the reported mean 25-OHD concentrations were 28.24 ng/mL with efavirenz use and 29.68 ng/mL without efavirenz use. The recalculated mean difference is 1.44, with an interval from -1.877 to 4.757 and an unadjusted p-value of 0.395. For change from baseline to week 48, the reported means were 10.97 ng/mL and 9.79 ng/mL, respectively. The recalculated mean difference for no efavirenz use relative to efavirenz use is -1.18, with an interval from -4.657 to 2.297 and an unadjusted p-value of 0.506. These calculations do not replace the registry's own analyses.
The registry separately reports Wilcoxon signed-rank tests within each efavirenz-use group for changes in 25-OHD, both with p < 0.001. A within-group test asks whether observed values changed within that group under the test's assumptions. It does not test whether the amount of change differs between groups. A direct between-group comparison of change addresses a different question. General statistical practice distinguishes these questions because significance in one group, or in both groups, is not itself evidence of a difference between groups.
What do the planning illustrations mean?
The planning illustrations are based on observed secondary mean differences, not on the trial's reported design calculations. Their assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects set to stated fractions of the observed effects. In general, a sample-size calculation estimates the number of participants needed under its assumptions to attain a chosen probability of detecting a specified effect. It is a planning aid, not evidence that the completed trial had a particular probability of finding a result, and it is not observed power. The registry record does not report the trial's own sample-size justification.
In general, over-dispersion means that data vary more than a model assumes. When present, standard errors and inferential results from a model that fails to account for that extra variation may be unreliable. The primary analysis is identified as rank-based, and the registry does not report an over-dispersion model or a model-based estimate for the primary endpoint. The relevant method-specific issue is therefore to understand what the rank test compares and to avoid interpreting its p-value as an effect size.
All recalculated secondary contrasts are unadjusted. In general, examining many outcomes and subgroup comparisons increases the chance that at least one result will appear notable by chance. Adjustment methods, prespecified hierarchy, or other multiplicity procedures can address aspects of that problem, but a strategy for the posted secondary results is not reported in the registry record. This is why isolated secondary p-values should be treated as exploratory unless a prespecified analysis plan establishes otherwise.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wilcoxon (Mann-Whitney) | not reported | 0.117 |
The registry reports a Wilcoxon (Mann-Whitney) analysis for the primary comparison, with p = 0.117. It does not provide a sponsor-reported between-group effect estimate or confidence interval for that endpoint. The arm results are reported as medians, but the registry does not provide the numerical inter-quartile ranges. A separate recalculated primary contrast is therefore not presented alongside the registry analysis.
The secondary efavirenz mean contrasts are simple, unadjusted recalculations from posted group summaries. The registry does not report corresponding between-group analyses for those subgroup comparisons. It does report within-group Wilcoxon signed-rank tests for 25-OHD change, with p < 0.001 in each group. Those tests address within-group change, whereas the recalculated contrasts address differences between efavirenz-use groups. The analyses are not interchangeable and may differ in both question and method.
For the primary endpoint, the registry analysis remains the relevant reported analysis; no discrepancy between a recalculation and the registry analysis is identified. The secondary recalculations should be understood as descriptive, unadjusted checks based on the posted summaries, not as sponsor analyses or as replacements for a full analysis using participant-level data.
11. Multiplicity, Missing Data and Analysis Populations
The registry record contains many outcome measures and analyses, including bone outcomes at different anatomical sites and time points and 25-OHD outcomes by efavirenz use. It does not report a multiplicity adjustment, a testing hierarchy, or another strategy for controlling the interpretation of multiple comparisons. Without such information, the secondary p-values should not be treated as if they were each the sole planned test. The primary outcome has a registry-reported comparison, but the record does not describe how the primary and secondary testing families were defined.
The primary analysis population is described as participants with baseline and week 48 data. The registry notes that this includes participants enrolled in version 1.0 who completed week 48 evaluations but were discontinued before later visits. The primary endpoint counts are 99 for vitamin D3 and 89 for placebo. Enrollment was 214, but the record does not provide a full participant-flow account linking enrollment, randomization, follow-up, and analysis for this endpoint. It does not state that the primary analysis was intention-to-treat.
Details of missing outcome data are not reported in the registry record. The record does not specify the amount or reasons for missing baseline or week 48 measurements, whether imputation was used, or how sensitivity to missing-data assumptions was assessed. Since the primary endpoint population requires both measurements, the observed result is based on participants meeting that data requirement; the possible effect of missing outcomes cannot be assessed from the posted description.
The registry also does not report the trial's sample-size justification, interim analyses, or a detailed statistical analysis plan. The planning illustrations associated with recalculated secondary comparisons are not the trial's own design calculations. These omissions limit assessment of prespecification, statistical power as planned, and whether the final analyses followed an intended hierarchy. They do not invalidate the posted results, but they constrain how confidently the results can be interpreted as confirmatory.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group A: Vitamin D3 50,000 IU | 5 | 109 | 4.6% |
| Group B: Vitamin D3 Placebo | 6 | 105 | 5.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group A: Vitamin D3 50,000 IU | 0 of 109 |
| Group B: Vitamin D3 Placebo | 0 of 105 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group A: Vitamin D3 50,000 IU | 6 of 109 |
| Group B: Vitamin D3 Placebo | 8 of 105 |
Most frequent serious adverse event terms
| Event term | Organ system | Group A: Vitamin D3 50,000 IU | Group B: Vitamin D3 Placebo |
|---|---|---|---|
| Suicidal ideation | Psychiatric disorders | 0 of 109 | 2 of 105 |
| Cellulitis | Infections and infestations | 0 of 109 | 2 of 105 |
| Suicide attempt | Psychiatric disorders | 1 of 109 | 0 of 105 |
| Mental Status Changes | Psychiatric disorders | 1 of 109 | 0 of 105 |
| Acute psychosis | Psychiatric disorders | 0 of 109 | 1 of 105 |
| Cellulitis Streptococcal | Infections and infestations | 0 of 109 | 1 of 105 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 1 of 109 | 0 of 105 |
| Tooth abscess | Infections and infestations | 1 of 109 | 0 of 105 |
| Gastroenteritis | Infections and infestations | 1 of 109 | 0 of 105 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group A: Vitamin D3 50,000 IU | Group B: Vitamin D3 Placebo |
|---|---|---|---|
| Colitis | Gastrointestinal disorders | 2 of 109 | 0 of 105 |
| Blood Creatinine Increased | Investigations | 1 of 109 | 1 of 105 |
| Proctitis | Gastrointestinal disorders | 1 of 109 | 0 of 105 |
| Gastroenteritis | Infections and infestations | 1 of 109 | 0 of 105 |
| Head injury | Injury, poisoning and procedural complications | 0 of 109 | 1 of 105 |
| Laceration | Injury, poisoning and procedural complications | 0 of 109 | 1 of 105 |
| Soft tissue injury | Injury, poisoning and procedural complications | 0 of 109 | 1 of 105 |
| Tendon Rupture | Injury, poisoning and procedural complications | 0 of 109 | 1 of 105 |
| Alanine Aminotransferase Increased | Investigations | 0 of 109 | 1 of 105 |
| Aspartate Aminotransferase Increased | Investigations | 0 of 109 | 1 of 105 |
Serious events with the highest arm-level rate: suicidal ideation (1.9%), cellulitis (1.9%), acute psychosis (1.0%), cellulitis streptococcal (1.0%), suicide attempt (0.9%).
The registry reports serious adverse events among 109 participants at risk in the vitamin D3 group and 105 at risk in the placebo group. It records 5 participants with serious adverse events in the vitamin D3 group and 6 in the placebo group. The registry also reports other adverse events among the same at-risk group sizes: 6 affected participants in the vitamin D3 group and 8 in the placebo group. Deaths are recorded as 0 in each group.
These figures are counts of affected participants relative to the registry's stated at-risk groups. They do not by themselves establish whether an event was caused by the intervention, and they do not describe severity beyond the registry's serious-event classification. The record lists serious-event terms including Suicidal ideation (1.9%), Cellulitis (1.9%), Acute psychosis (1.0%), Cellulitis Streptococcal (1.0%), Suicide attempt (0.9%), and Mental Status Changes (0.9%). The listed terms should not be interpreted as intervention-related events, or assigned to a particular arm, without further information not reported in the registry record.
The registry record does not provide event-level timing, duration, relatedness assessment, or a detailed account of recurrent events. These aggregate figures describe the posted safety counts but do not support a broader safety conclusion on their own.
13. What the Result Does, and Does Not, Mean
The primary result describes observed percent change in spine bone mineral density at week 48 among participants with baseline and week 48 data. The registry reports medians of 0.19 for vitamin D3 and 0.09 for placebo, along with a Wilcoxon (Mann-Whitney) p-value of 0.117. This is a summary of the observed groups and the reported rank-based test. It is not a direct estimate of the magnitude or precision of a between-group difference.
The result does not establish that the groups were identical. A non-small p-value is not proof of no effect, just as a smaller p-value would not by itself establish a meaningful effect. The registry does not report a confidence interval for the primary between-group contrast, leaving the range of effects compatible with the data unclear from the posted summary. The median values alone cannot show how much individual observations varied or whether the full distributions had similar shapes.
The result also does not establish an effect in all people with HIV, in all age groups, or among people receiving other antiretroviral regimens. The population described was adolescents and young adults with HIV receiving tenofovir-containing combination therapy. The primary outcome analysis required baseline and week 48 data, and the registry does not fully characterize missing data or the analysis population beyond its description.
Secondary results address other outcomes and subgroup distinctions, but the registry does not report a multiplicity strategy. Recalculated efavirenz comparisons are unadjusted and are not randomized comparisons of efavirenz use. They should not be used to make a broad causal claim. The within-group 25-OHD tests likewise do not answer whether changes differed between groups.
In short, the registry documents a randomized comparison and its observed primary summaries, but the posted primary analysis does not include a between-group estimate with a confidence interval. The record therefore supports a careful description of what was observed and how it was tested, not a definitive claim about the size, precision, or clinical importance of a treatment effect.
14. Why This Trial Matters Statistically
This trial is statistically informative because it places a randomized comparison around a clearly specified longitudinal outcome: percent change in lumbar spine bone mineral density from baseline to week 48. The median summary and rank-based test show how the registry analyzed that endpoint, while also highlighting the distinction between a test result and an effect estimate. Readers need both magnitude and uncertainty to assess what a comparison can say; the primary registry results do not report a between-group estimate and confidence interval.
The record also illustrates why analysis populations matter. Enrollment was 214, while the primary outcome counts were 99 and 89. The registry defines the primary population by availability of baseline and week 48 data and notes that some participants did not continue to later visits. Those details matter when judging to whom the observed endpoint summaries apply and what conclusions missing measurements might affect.
Finally, the study has many secondary measures and analyses. Distinguishing randomized treatment comparisons from subgroup descriptions, and within-group change tests from between-group comparisons, is essential to avoid overstating isolated results. The registry does not report a multiplicity plan or sample-size justification, so secondary findings and planning illustrations require particular caution. These are general lessons in interpreting clinical-trial records: match each statistic to its question, population, and uncertainty, and do not treat a collection of unadjusted results as a single confirmatory answer.
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.
Several features of the registry record limit statistical interpretation. The primary outcome reports group medians, but numerical inter-quartile ranges are not reported in the registry record. The reported primary p-value is not accompanied by a between-group effect estimate and confidence interval. This leaves the size and precision of the primary contrast difficult to assess from the registry summary alone.
The primary analysis population consists of participants with baseline and week 48 data. Although the record notes participants who completed week 48 but not later visits, it does not provide a complete participant flow, reasons for missing endpoint data, or a missing-data method. It also does not state that the primary analysis was intention-to-treat. Consequently, the potential influence of missing outcome data and the exact relationship between randomized and analyzed populations cannot be fully evaluated.
The record lists many secondary endpoints and analyses but does not report a multiplicity strategy, a hierarchy of outcomes, or which secondary analyses were prespecified as confirmatory. Some secondary calculations are unadjusted and based on group summaries; they cannot account for participant-level covariates or substitute for the trial's full analysis. The efavirenz-use comparisons are subgroup associations, not randomized comparisons of efavirenz use.
The registry does not report the sample-size justification, interim analyses, detailed statistical analysis plan, allocation concealment, or full masking procedures. Its masking field is recorded as triple, while the official title says double-blind; the record does not explain the terminology. The primary outcome population description refers to later visits beyond week 48, but details of follow-up and discontinuation are limited. These omissions do not erase the reported results, but they restrict evaluation of design decisions, analysis choices, and the robustness of the findings.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Vitamin D Absorption in HIV Infected Young Adults Being Treated With Tenofovir Containing cART — NCT01751646.
- Registry record last updated 2019-03-27; status last verified 2018-11.
- Results first posted 2019-03-11.
- 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.
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19. Record Summary
NCT01751646 is a completed randomized, parallel-group, placebo-controlled study of vitamin D3 in adolescents and young adults with HIV receiving tenofovir-containing combination antiretroviral therapy. Enrollment was 214. The primary outcome was percent change from baseline to week 48 in DXA-measured lumbar spine bone mineral density. The registry reports medians of 0.19 for vitamin D3 and 0.09 for placebo, with a Wilcoxon (Mann-Whitney) p-value of 0.117.
The primary outcome counts were 99 and 89, and the analyzed population was described as participants with baseline and week 48 data. The registry also posts secondary bone and 25-OHD outcomes, safety counts, and within-group analyses. A primary between-group effect estimate with a confidence interval, detailed missing-data methods, multiplicity procedures, and the trial's sample-size justification are not reported in the registry record. Secondary recalculations are unadjusted and should be distinguished from registry-reported analyses.