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 and OmegA-3 TriaL: Effects on Bone Structure and Architecture (VITAL) (NCT01747447), a randomized na study. The primary outcome is Change in Bone Density.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01747447 |
| Phase | NA |
| Condition | Bone Density, Body Composition, Bone Health |
| Allocation | Randomized |
| Design model | Factorial |
| Masking | Triple |
| Enrollment | 771 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Brigham and Women's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study included a sub-cohort of 771 participants in VITAL. The registry describes the parent trial as involving U.S. men and women without a prior history of cancer, heart disease, or stroke. The ancillary study focused on skeletal health and body composition. Some bone-density measurements were excluded because of metal artifacts, severe osteoarthritis, severe scoliosis, degenerative disc disease, or bilateral breast implants; the number of measurements affected is not reported in the registry record.
Intervention
The interventions were daily vitamin D3 at 2,000 IU/d and daily fish oil at 1 g/d, with EPA and DHA in a 1.2:1 ratio. The factorial arrangement included participants assigned to active supplement combinations as well as combinations involving placebo.
Comparator
Vitamin D was compared with its placebo, and omega-3 fatty acids were compared with their placebo. The four combinations were daily vitamin D and fish oil, vitamin D with fish oil placebo, vitamin D placebo with fish oil, and placebo for both supplements.
Primary question
The primary endpoint was change in bone density over 2 years, assessed by DXA. The study aimed to determine whether vitamin D and/or omega-3 supplementation produced small increases or reduced bone loss in spine, hip, and total body areal bone density. The registry record does not report the endpoint results or a statistical test answering that question.
3. Trial Design
This was a randomized, triple-masked, factorial ancillary study, sponsored by Brigham and Women's Hospital. The registry lists enrollment as 771 and status as completed. The study start is recorded as 2012-08, and primary completion as 2017-12. The phase is listed as NA.
The four assigned regimens combined active or placebo vitamin D3 with active or placebo fish oil. The active vitamin D regimen was 2,000 IU/d. The active fish oil regimen was 1 g/d, with EPA and DHA in a 1.2:1 ratio. The registry descriptions identify the daily preparations, but do not report adherence or treatment exposure over time.
In a factorial design, treatment assignments are arranged so that effects of each intervention can be considered across the levels of the other intervention. This can support evaluation of vitamin D, omega-3 fatty acids, and whether their effects differ when used together. The registry record does not report the planned statistical model, whether interaction was tested, or how the treatment comparisons were specified.
The ancillary study took place within VITAL, whose stated purpose was to investigate whether daily vitamin D3 or fish oil reduced the risk of cancer, heart disease, and stroke in people without a prior history of those illnesses. The ancillary question concerned skeletal health and body composition rather than those parent-trial conditions. The registry lists change in bone structure as a secondary outcome and five outcome measures, but does not provide an analysis count beyond 0 in the analysis field.
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 | ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids | ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids | PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids | PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids |
|---|---|---|---|---|
| STARTED | 193 | 195 | 195 | 188 |
| COMPLETED | 170 | 177 | 176 | 164 |
| NOT COMPLETED | 23 | 18 | 19 | 24 |
Analysis population for the primary outcome, as defined in the registry: Some measurements were excluded due to metal artifacts, severe osteoarthritis, severe scoliosis, degenerative disc disease, and bilateral breast implants.
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.
| Characteristic | Unit | ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids | ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids | PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids | PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 193 | 195 | 195 | 188 | 771 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 119 | 117 | 118 | 112 | 466 |
| Age, Categorical: >=65 years | Participants | 74 | 78 | 77 | 76 | 305 |
| Age, Continuous | Years | 63.5 (SD 6.5) | 63.7 (SD 5.5) | 64 (SD 6.3) | 63.9 (SD 6.3) | 63.8 (SD 6.1) |
| Sex: Female, Male: Female | Participants | 88 | 91 | 97 | 84 | 360 |
| Sex: Female, Male: Male | Participants | 105 | 104 | 98 | 104 | 411 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 10 | 3 | 6 | 10 | 29 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 172 | 183 | 179 | 169 | 703 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 11 | 9 | 10 | 9 | 39 |
| Race/Ethnicity, Customized: Non-Hispanic White | Participants | 155 | 162 | 157 | 156 | 630 |
| Race/Ethnicity, Customized: African American | Participants | 18 | 17 | 17 | 15 | 67 |
| Race/Ethnicity, Customized: Hispanic (non-African American) | Participants | 8 | 3 | 6 | 9 | 26 |
| Race/Ethnicity, Customized: Asian/Pacific Islander | Participants | 5 | 4 | 4 | 2 | 15 |
| Race/Ethnicity, Customized: American Indian/Alaskan Native | Participants | 1 | 1 | 3 | 0 | 5 |
| Race/Ethnicity, Customized: Other | Participants | 3 | 6 | 2 | 1 | 12 |
| Region of Enrollment: United States | Participants | 193 | 195 | 195 | 188 | 771 |
| Body Mass Index | kg/m^2 | 27.5 (SD 4.7) | 26.9 (SD 4.7) | 27.7 (SD 5.0) | 26.8 (SD 4.6) | 27.2 (SD 4.8) |
| Fat Mass Index | kg/m^2 | 10.3 (SD 4.1) | 10.2 (SD 3.9) | 10.7 (SD 3.8) | 9.9 (SD 3.6) | 10.3 (SD 3.9) |
| Leisure Time Physical Activity | hr/wk | 22.7 (9.7 to 43.7) | 21.5 (7.7 to 35.6) | 21.6 (8.4 to 36.0) | 20.4 (6.9 to 36.9) | 21.5 (6.9 to 43.7) |
| Diabetes History | Participants | 20 | 24 | 18 | 21 | 83 |
| Current Smoking | Participants | 14 | 12 | 9 | 13 | 48 |
| Any Fracture History | Participants | 13 | 19 | 15 | 14 | 61 |
| Parental History of Hip Fracture | Participants | 23 | 31 | 24 | 24 | 102 |
| Baseline Calcium Supplement Use | Participants | 29 | 40 | 36 | 27 | 132 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Bone Density, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | g/cm^2 |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in bone density over 2 years, measured in g/cm^2 and summarized as a mean with standard deviation. The registry description identifies DXA assessment at the spine, hip, and total body. Bone density is a continuous measurement, so the endpoint can describe average change across participants rather than simply classifying each person as having or not having an event.
As a general statistical rationale, repeated measurement of a continuous bone-density outcome can capture shifts in the distribution of measured skeletal density. The mean describes the average level or change, while the standard deviation describes the spread of participant measurements around that average. Neither summary alone shows how individual participants changed, and the mean can conceal variation in responses.
The registry states that the endpoint was intended to determine whether vitamin D and/or omega-3 supplementation produced small increases or reduced bone loss. This is the stated research aim, not a reported finding. The posted record does not include primary endpoint means, standard deviations, between-group estimates, confidence intervals, or p-values. It also notes that some measurements were excluded for metal artifacts, severe osteoarthritis, severe scoliosis, degenerative disc disease, and bilateral breast implants. The number excluded and the implications for the endpoint analysis are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically interpretable primary measure: change in areal bone density, expressed in g/cm^2, over 2 years. It also defines the target anatomical assessments as spine, hip, and total body DXA. However, it does not post the outcome values needed to judge the direction, size, or precision of any treatment contrast. No conclusion about the observed bone-density changes can be drawn from the registry information presented.
The record's description of the study says it would test vitamin D supplementation versus placebo on skeletal health and body composition, while the listed arms and interventions also incorporate fish oil and fish oil placebo. That factorial structure allows the study to address the supplements within a shared trial framework. The record does not state which marginal comparisons or combination contrasts were the primary statistical comparisons, nor whether a possible interaction between supplements was part of the analysis.
The primary endpoint is specified as a mean, with standard deviation as the dispersion measure. Those summaries would describe the average observed change and the variability among measurements, but treatment interpretation would also require a contrast between randomized groups and its uncertainty. Such results, including confidence intervals and p-values, are not reported in the registry record. The phrase “Reported values are rounded up” appears in the endpoint description; the record does not explain the rounding procedure or provide values to which it applies.
Some measurements were excluded for named imaging or anatomical reasons. This information matters because the measured sample contributing to an endpoint could differ from the enrolled sample. The registry does not report how many measurements were excluded, whether exclusions were applied before or after treatment assignment was considered, or how missing endpoint data were handled. Consequently, the size and direction of any potential selection effect cannot be assessed from the record.
The serious adverse-event fields describe counts in treatment groups, and the record lists several serious-event terms with percentages. Those figures are descriptive registry entries; without a defined analysis, follow-up details, or comparative uncertainty, they do not establish whether rates differed between assigned regimens. Likewise, completion status does not substitute for reporting endpoint findings. The statistical evidence for the primary question remains unreported in the registry record.
9. Statistical Methods Explained
What does a mean and standard deviation describe?
The registry identifies the primary endpoint as a mean of a continuous measure and names standard deviation as its dispersion measure. In general, a mean summarizes the central level of the observed measurements. A standard deviation describes how dispersed those measurements are around the mean. These are descriptive summaries: they do not, by themselves, estimate the difference between randomized groups or quantify the uncertainty in that difference.
For a treatment comparison, an estimate of the between-group difference would indicate the direction and magnitude of the observed contrast. A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. Its width conveys precision: a narrower interval indicates greater precision than a wider one. No treatment estimates or confidence intervals for the primary endpoint are reported in the registry record, so the precision of an effect cannot be assessed.
How does the factorial arrangement matter?
The four arms combine active or placebo vitamin D with active or placebo fish oil. In general, factorial designs can estimate the effect of each intervention by comparing participants assigned to its active and placebo levels, while accounting for assignment to the other intervention. They can also be used to ask whether the effect of one intervention changes depending on whether the other is active. That latter question concerns interaction.
Interaction is not simply whether one combination has a different mean from another. It asks whether the contrast associated with one treatment varies across the levels of the other treatment. The registry does not report the statistical model, the planned contrasts, or whether interaction was prespecified or assessed. Therefore, the factorial layout can be described, but the intended inferential approach cannot be reconstructed from the registry record.
What can be learned from a p-value?
As a general statistical explanation, a p-value measures how incompatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not quantify clinical importance. Interpretation depends on the exact contrast, model, outcome definition, and analysis population. No primary endpoint p-value is reported in the registry record, and the analysis field lists 0 analyses.
A p-value also does not replace an effect estimate and its confidence interval. A small p-value may accompany an imprecisely estimated or modest effect, while a larger p-value may reflect limited information rather than evidence that groups are equivalent. Because the primary outcome results are absent, these distinctions cannot be applied to the trial's findings.
Why does measurement variability matter?
DXA values are continuous measurements, and their spread affects the precision of a group mean and a treatment contrast. In general, greater variability makes it harder to distinguish a treatment contrast from random variation unless the study contains enough informative measurements. Exclusions can also affect the observed spread and the population represented by the analysis. The registry names reasons for excluding some measurements but does not report the number excluded or the resulting analysis sample.
The endpoint description indicates that values are rounded up. Rounding can affect how precisely a posted mean or contrast can be interpreted, particularly when differences are small. No endpoint values are posted in the registry record, so the effect of rounding cannot be evaluated.
How should planning calculations be understood?
Sample-size calculations are planning illustrations, not evidence about the results. The stated illustration uses the observed effect as its reference and considers an effect equal to a stated fraction of that observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The instructions distinguish event totals for time-to-event calculations from participants per arm for other outcomes.
These assumptions describe an illustrative calculation rather than the trial's own design justification. The registry record does not report the protocol's sample-size justification. It also does not provide the observed primary endpoint effect or numerical sample-size illustration results, so no planning count or effect magnitude can be interpreted from this record. Such calculations should not be described as observed power: they do not establish the probability that the completed study detected an effect.
Overall, the registry supports a description of the endpoint type, measurement scale, study structure, and some design assumptions used for planning illustrations. It does not support an independent reconstruction of the primary analysis or a quantitative interpretation of the primary result. The sponsor's analysis cannot be compared with a recalculation because primary outcome summaries and sponsor analysis results are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The factorial layout creates several plausible treatment questions: the effect of vitamin D, the effect of omega-3 fatty acids, the combined regimen, and whether the effects depend on each other. The record does not identify a hierarchy among these questions or describe any adjustment for multiple comparisons. It also lists change in bone structure as a secondary outcome and five outcome measures. The registry record does not report how multiplicity across outcomes, anatomical sites, treatment contrasts, or time points was addressed.
The primary outcome description covers spine, hip, and total body areal bone density. The record does not state whether these were separate endpoints, components of a composite, or repeated locations within a single outcome definition. It says the primary outcome has several categories or time points and is not reduced to one comparison. The posted information therefore does not support treating the outcome as a single simple contrast.
Some measurements were excluded for metal artifacts, severe osteoarthritis, severe scoliosis, degenerative disc disease, and bilateral breast implants. The count excluded, the extent of missing measurements, and the methods used to handle missing data are not reported in the registry record. The analysis populations, including whether all randomized participants were included in the primary analysis, are also not reported in the registry record.
As a general statistical point, missing-data assumptions matter because an analysis of observed measurements may represent a selected subset if the chance of a measurement being unavailable is related to participant characteristics or outcomes. Without counts and methods, the impact cannot be assessed. No interim analyses or multiplicity strategy are reported in the registry record.
11. 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 |
|---|---|---|---|
| Active Vitamin D | 39 | 388 | 10.1% |
| Vitamin D Placebo | 37 | 383 | 9.7% |
| Active Omega-3 Fatty Acids | 35 | 388 | 9.0% |
| Omega-3 Fatty Acids Placebo | 41 | 383 | 10.7% |
| Active Vitamin D/Active Omega-3 Fatty Acids | 20 | 193 | 10.4% |
| Active Vitamin D/Placebo Omega-3 Fatty Acids | 19 | 195 | 9.7% |
| Placebo Vitamin D/Active Omega-3 Fatty Acids | 15 | 195 | 7.7% |
| Placebo Vitamin D/Placebo Omega-3 Fatty Acids | 22 | 188 | 11.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Active Vitamin D | 8 of 388 |
| Vitamin D Placebo | 3 of 383 |
| Active Omega-3 Fatty Acids | 3 of 388 |
| Omega-3 Fatty Acids Placebo | 8 of 383 |
| Active Vitamin D/Active Omega-3 Fatty Acids | 2 of 193 |
| Active Vitamin D/Placebo Omega-3 Fatty Acids | 6 of 195 |
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 |
|---|---|
| Active Vitamin D | 301 of 388 |
| Vitamin D Placebo | 280 of 383 |
| Active Omega-3 Fatty Acids | 286 of 388 |
| Omega-3 Fatty Acids Placebo | 295 of 383 |
| Active Vitamin D/Active Omega-3 Fatty Acids | 152 of 193 |
| Active Vitamin D/Placebo Omega-3 Fatty Acids | 149 of 195 |
Most frequent serious adverse event terms
| Event term | Organ system | Active Vitamin D | Vitamin D Placebo | Active Omega-3 Fatty Acids | Omega-3 Fatty Acids Placebo | Active Vitamin D/Active Omega-3 Fatty Acids | Active Vitamin D/Placebo Omega-3 Fatty Acids |
|---|---|---|---|---|---|---|---|
| Malignant Cancer | General disorders | 22 of 388 | 19 of 383 | 15 of 388 | 26 of 383 | 9 of 193 | 13 of 195 |
| Gastrointestinal Bleeding | Gastrointestinal disorders | 10 of 388 | 10 of 383 | 9 of 388 | 11 of 383 | 6 of 193 | 4 of 195 |
| Major Cardiovascular Events | Cardiac disorders | 7 of 388 | 4 of 383 | 7 of 388 | 4 of 383 | 5 of 193 | 2 of 195 |
| Hypercalcemia | Endocrine disorders | 3 of 388 | 5 of 383 | 7 of 388 | 1 of 383 | 3 of 193 | 0 of 195 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Active Vitamin D | Vitamin D Placebo | Active Omega-3 Fatty Acids | Omega-3 Fatty Acids Placebo | Active Vitamin D/Active Omega-3 Fatty Acids | Active Vitamin D/Placebo Omega-3 Fatty Acids |
|---|---|---|---|---|---|---|---|
| Stomach Pain | Gastrointestinal disorders | 145 of 388 | 128 of 383 | 139 of 388 | 134 of 383 | 77 of 193 | 68 of 195 |
| Constipation | Gastrointestinal disorders | 121 of 388 | 133 of 383 | 118 of 388 | 136 of 383 | 53 of 193 | 68 of 195 |
| Nausea | Gastrointestinal disorders | 88 of 388 | 77 of 383 | 80 of 388 | 85 of 383 | 43 of 193 | 45 of 195 |
| Easy Bruising | Skin and subcutaneous tissue disorders | 62 of 388 | 61 of 383 | 59 of 388 | 64 of 383 | 29 of 193 | 33 of 195 |
| Blood in Urine | Renal and urinary disorders | 18 of 388 | 27 of 383 | 22 of 388 | 23 of 383 | 8 of 193 | 10 of 195 |
| Kidney Stones | Renal and urinary disorders | 17 of 388 | 11 of 383 | 16 of 388 | 12 of 383 | 10 of 193 | 7 of 195 |
| Frequent Nosebleeds | General disorders | 10 of 388 | 20 of 383 | 17 of 388 | 13 of 383 | 7 of 193 | 3 of 195 |
| Parathyroid Condition | Endocrine disorders | 1 of 388 | 4 of 383 | 3 of 388 | 2 of 383 | 0 of 193 | 1 of 195 |
| Kidney Failure or Dialysis | Renal and urinary disorders | 1 of 388 | 0 of 383 | 1 of 388 | 0 of 383 | 1 of 193 | 0 of 195 |
Serious events with the highest arm-level rate: malignant cancer (6.9%), gastrointestinal bleeding (3.7%), major cardiovascular events (2.6%), hypercalcemia (2.1%).
The registry lists serious-event fields by treatment group, including the number at risk and the number affected, and separately lists deaths. For example, the active vitamin D group lists 388 at risk for serious events and 39 affected, while the vitamin D placebo group lists 383 at risk and 37 affected. These are descriptive counts in the registry; they are not adjusted comparisons and do not include a reported uncertainty estimate.
The record also lists serious-event terms and percentages: Malignant Cancer at 6.9%, Gastrointestinal Bleeding at 3.7%, Major Cardiovascular Events at 2.6%, and Hypercalcemia at 2.1%. The registry does not explain the denominator or specify whether these terms overlap, so the percentages should be read as posted rather than combined or compared through calculations.
Deaths are recorded in the group fields, but the registry does not provide a statistical comparison or explanatory context for those counts. The follow-up period for these safety fields, event ascertainment details, and definitions of the “other” adverse-event fields are not reported in the registry record. These entries alone do not establish a causal relationship or a difference in safety between regimens.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, triple-masked factorial ancillary study enrolled 771 participants and assessed a two-year change in bone density using DXA. It identifies the supplement regimens and describes the intended focus on skeletal health and body composition. It also records reasons why some measurements were excluded and provides group-level serious-event entries.
Those design details do not reveal the primary outcome result. The registry does not report mean changes, treatment contrasts, confidence intervals, or p-values for bone density. It is therefore not possible to determine from this record whether the observed values favored one assigned regimen, how large any contrast was, or how precisely it was estimated. The stated research aim should not be mistaken for an outcome finding.
As a general principle, an estimated difference and its uncertainty address distinct questions. The estimate describes the observed contrast; the uncertainty indicates how much precision the data and analysis support. Neither alone establishes the importance of a result, and neither can be evaluated without the endpoint analysis.
The record also does not describe the primary analysis population, missing-data handling, multiplicity adjustment, or planned model. These omissions limit assessment of whether the reported analysis, if available elsewhere, would match the randomized design and stated endpoint. Completion status indicates that the study is recorded as completed; it does not supply the missing results.
The safety fields can be read as registry counts and listed event percentages, but not as a definitive comparative safety analysis. Without event definitions, follow-up information, and statistical contrasts, they do not establish that one regimen caused more or fewer events. The responsible interpretation is limited to the study's stated design and posted descriptive entries, with efficacy and comparative safety findings not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable for combining two supplement assignments in a factorial design while examining a continuous imaging endpoint. Such a design can make it possible to evaluate treatment effects within a shared study, and potentially to examine whether the effect of one supplement varies with the other. The registry's four regimen descriptions make that structure clear, even though the planned comparisons and model are not reported.
The outcome also illustrates the distinction between a stated research question and a reported result. The registry defines change in bone density over 2 years, names the measurement method and units, and identifies the anatomical sites. Yet it does not post the outcome summaries or inferential statistics. A well-described endpoint is not enough to determine an effect or its precision.
Measurement exclusions are another important feature. Reasons include imaging artifacts and specified anatomical conditions. Such exclusions can affect which observations contribute to an analysis, making reporting of counts and handling methods important for judging representativeness and potential bias. Those details are not reported in the registry record.
Finally, the registry includes serious-event counts and listed event percentages, but not a comparative safety analysis. The distinction between descriptive safety reporting and statistical comparison is essential: counts can describe what was recorded without resolving whether observed group differences are meaningful or attributable to assignment. The record therefore offers useful design and outcome-definition information, while leaving key inferential questions unanswered.
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 main limitation for interpreting the trial statistically is the absence of primary endpoint results in the registry record. No means, standard deviations, treatment contrasts, confidence intervals, or p-values are reported for change in bone density. The record also lists 0 analyses. Consequently, the magnitude and precision of any treatment effect cannot be assessed.
The endpoint spans spine, hip, and total body, but the record does not explain how those measurements were organized into the primary analysis or how multiple locations were handled. It also does not state the planned statistical model, treatment contrasts, interaction assessment, or multiplicity approach. These omissions are especially relevant to interpreting a factorial design.
The record notes exclusions of some measurements because of metal artifacts, severe osteoarthritis, severe scoliosis, degenerative disc disease, and bilateral breast implants. It does not give the number of excluded measurements, the number contributing to each analysis, or the method used to address missing data. It is not possible to assess how those exclusions affected the analyzed population.
Adherence, duration of actual exposure, and detailed outcome-assessment procedures are not reported in the registry record. The safety entries lack reported comparative estimates and uncertainty, and the registry does not explain the denominators for the listed serious-event percentages. The protocol's sample-size justification and interim analyses are also not reported in the registry record. These limitations constrain interpretation of both the primary question and the safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture (VITAL) — NCT01747447.
- Registry record last updated 2026-04-28; status last verified 2026-04.
- Results first posted 2021-03-29.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
The record describes a completed, randomized, triple-masked factorial ancillary study sponsored by Brigham and Women's Hospital, with enrollment of 771. The study started in 2012-08 and reached primary completion in 2017-12. Its primary endpoint was change in spine, hip, and total body areal bone density, measured by DXA over 2 years and summarized as a mean with standard deviation.
The four regimens combined vitamin D3 at 2,000 IU/d or placebo with fish oil at 1 g/d or placebo. The active fish oil description specifies EPA and DHA in a 1.2:1 ratio. The record lists change in bone structure as a secondary outcome and five outcome measures.
Primary endpoint results and analysis details are not reported in the registry record. The record includes serious-event counts, deaths, and listed serious-event terms, but does not provide comparative safety estimates. Some measurement exclusions are noted, while their number and handling are not reported.