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 Randomized Trial of Vitamin B12 in Pregnant Indian Women (NCT00641862), a randomized na study. The primary outcome is Changes in Maternal Serum B12 Concentration From 1st to 3rd Trimester.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00641862 |
| Phase | NA |
| Condition | Pregnancy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 366 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Harvard School of Public Health (HSPH) |
| Results posted | Yes |
2. Clinical Question
Population
Pregnant Indian women enrolled in a randomized trial. The registry lists enrollment of 366, while its brief summary describes a trial among 300 pregnant Indian women; the registry record does not explain this difference. For the primary outcome, serum samples were available for analysis among 102 of the original 183 participants in each arm.
Intervention
Vitamin B12 supplementation. The registry identifies the intervention as a dietary supplement, but the dose, formulation, and schedule are not reported in the registry record.
Comparator
Placebo. The registry also states that all women received standard prenatal obstetric care, including routine iron and folate supplementation.
Primary question
How did maternal serum B12 concentration change from the first to the third trimester in the vitamin B12 and placebo arms? The posted results report arm-specific median changes and interval bounds. They do not report a direct estimate of the difference between arms or a statistical test for that comparison.
3. Trial Design
The registry describes a randomized, parallel-group trial comparing vitamin B12 with placebo in pregnant Indian women. The masking field says quadruple masking. The brief summary separately calls the trial double-blind. The registry record does not explain how those descriptions relate, identify which groups of people were masked, or describe how masking was maintained. Allocation concealment procedures are not reported in the registry record.
The brief summary says participants received standard prenatal obstetric care, including routine supplementation with iron and folate. This background care is relevant to interpreting the comparison: the intervention was added to the stated routine care, rather than compared with no prenatal care. The vitamin B12 dose and schedule, and the placebo's composition, are not reported in the registry record.
The listed enrollment is 366. The brief summary describes a trial among 300 women, and the registry record does not reconcile those figures. For the primary serum outcome, the record says samples were available for 102 of the original 183 participants in each arm. These are the participants with samples available for that analysis; the registry record does not state whether they represent every randomized participant who had reached the relevant follow-up.
The registry lists the trial as completed and gives its start as 2008-12 and primary completion as 2011-01. Harvard School of Public Health is listed as sponsor. The phase is listed as NA. Details of eligibility criteria, recruitment procedures, the randomization sequence, and trial conduct beyond the listed design features 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.
Overall Study
| Stage | Vitamin B12 | Placebo |
|---|---|---|
| STARTED | 183 | 183 |
| COMPLETED | 139 | 145 |
| NOT COMPLETED | 44 | 38 |
Analysis population for the primary outcome, as defined in the registry: Serum samples were available for analysis among 102 of the original 183 participants in each arm.
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 | Vitamin B12 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 183 | 183 | 366 | |
| Age, Continuous | years | 22 (20 to 24) | 22 (20 to 24) | 22 (20 to 24) |
| Sex: Female, Male: Female | Participants | 183 | 183 | 366 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in Maternal Serum B12 Concentration From 1st to 3rd Trimester, measured over from 1st to 3rd trimester.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | pmol/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the change in maternal serum vitamin B12 concentration from the first to the third trimester, measured in pmol/L. It describes change over the stated pregnancy interval rather than a single measurement at one time point. A change outcome can help distinguish the direction and extent of movement in a biomarker during follow-up, while the randomized comparison is intended to assess whether patterns differ between the intervention and comparator groups.
The registry identifies the summary parameter as the median and the intended measure of dispersion as the inter-quartile range. The median is the middle value when observations are ordered, and the inter-quartile range describes the spread across the central half of observations. These summaries can be useful when data are skewed or contain values that make the mean less representative of a typical observation. That is a general statistical rationale, not a reported explanation for the choices in this trial.
The registry's posted arm results give a median change and lower and upper bounds for each group. The inter-quartile range itself is not populated in the posted results. The registry record does not specify the laboratory assay, the precise calculation of individual change, or how measurements below assay limits were handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the vitamin B12 arm, the posted median change in maternal serum B12 concentration was 3.0 pmol/L, with lower and upper bounds of -54.8 and 83.5. For the placebo arm, the posted median change was -37.6 pmol/L, with bounds of -66.5 and -10.9. These are arm-specific summaries among participants with serum samples available for analysis. They describe the reported distributions of change within each arm, not a direct estimate of the randomized contrast.
The posted values do not establish the size or precision of the difference between arms. A comparison of the arm medians is not the same as an estimated treatment effect, and no between-arm estimate, standard error, p-value, or adjusted analysis is reported. The record also does not label the lower and upper bounds as confidence intervals or specify their construction. They should therefore be read as the bounds displayed with the arm results, not assigned a particular inferential interpretation on the basis of this record alone.
The median change in the vitamin B12 arm is positive, while the median change in the placebo arm is negative. That descriptive contrast is not, by itself, a test of whether the groups differ. The posted bounds also describe considerable uncertainty or spread around the arm-level results, but their statistical meaning cannot be determined from the registry record without a definition of the interval. The inter-quartile range is named as the dispersion measure in the endpoint description, yet no inter-quartile range is posted for either arm.
The record says serum samples were available for 102 of the original 183 participants in each arm. The results therefore concern the participants with available samples, and the record does not explain why samples were unavailable for others or how availability was handled in the analysis. If the likelihood of having a sample is related to participant characteristics or outcome values, the analyzed groups may not fully represent the randomized groups. Whether that occurred cannot be determined from the posted information.
Overall, the registry reports arm-specific median changes but does not report the statistical analysis needed to quantify or test the randomized comparison. No conclusion about the magnitude, precision, or statistical significance of a difference between groups can be drawn from these arm summaries alone. The sponsor's own analysis does not appear in the record, so there is no sponsor-reported comparative result to use in interpreting this outcome.
9. Statistical Methods Explained
What does a median change describe?
A median is a rank-based summary: it identifies the central observation after values are ordered. For a change endpoint, each participant's change is ordinarily derived from measurements at the stated time points, and the median then summarizes those changes within a group. The registry reports the endpoint as a median, but does not describe the participant-level calculation or the handling of missing measurements. The reported medians are thus best understood as summaries of the available outcome data, with the exact analysis details not reported in the registry record.
The median is not interchangeable with the mean. It is less influenced by unusually large or small observations, which can make it informative when a distribution is asymmetric. It also does not show the full distribution: very different patterns of individual values can share the same median. The record names the inter-quartile range as the dispersion measure, but the posted result has no inter-quartile range values. Readers therefore cannot use the record to assess that specified measure of within-arm spread.
What do the posted bounds mean?
Each arm result includes a lower and upper bound alongside its median. An interval can serve different purposes: it might describe uncertainty about an estimated quantity, or it might summarize the range of observed data under a stated convention. Its meaning depends on how it was calculated. The registry record does not identify the bounds as confidence intervals, give a confidence level, or state the calculation method. They should not be treated as a confidence interval or as a range containing a specified proportion of participants without that information.
In general, a confidence interval expresses uncertainty around an estimate under a statistical model and analysis procedure. A narrower interval usually indicates greater precision under that procedure, while a wider one indicates less precision. This general interpretation cannot be applied fully to these particular bounds because their construction is not reported. The record also does not provide the interval for a between-arm contrast, which would address the randomized comparison more directly than two separate arm summaries.
Why is a direct randomized contrast important?
Randomization makes the comparison between assigned groups the central basis for estimating an intervention effect. Arm-specific outcomes show what was observed within each group, but the effect of assignment is a contrast between groups, with an estimate and uncertainty calculated according to a defined method. Comparing the direction of two medians informally does not account for sampling variability and does not supply a formal test. The record contains no direct contrast estimate, its uncertainty, or a p-value for the primary outcome.
Different methods can be appropriate for comparing change distributions, depending on the outcome distribution, trial design, and analysis plan. Those choices can include methods based on ranks or models for the outcome, but the appropriate method cannot be identified from the posted summaries alone. No specific comparative method, covariate adjustment, or model is reported in the registry record. It would not be appropriate to reconstruct a trial analysis from the two arm summaries.
What does the analysis population represent?
The primary outcome description states that serum samples were available for analysis among 102 of the original 183 participants in each arm. This identifies sample availability for the outcome but does not establish whether the analysis followed an intention-to-treat principle, included all randomized participants with available measurements, or used another analysis population. The record does not describe whether samples were collected at both time points for every analyzed participant, how missing samples were handled, or whether any imputation was used.
Missing outcome data can affect both precision and representativeness. If missingness is unrelated to outcomes and relevant participant characteristics, the main consequence may be reduced information. If availability is related to the outcome or to factors associated with it, estimates based only on observed samples can be biased. These are general possibilities, not claims about what happened in this trial. The registry record does not provide reasons for missing samples or analyses that would assess their impact.
What is not stated about the statistical plan?
The record does not report the planned primary analysis, the method used to calculate the displayed bounds, assumptions about the outcome distribution, or a statistical analysis plan. It also does not report a sample-size justification, interim analyses, or any rule for stopping the trial early. The endpoint is described using a median and inter-quartile range, but that description alone does not identify the test or model used for a group comparison.
The registry lists secondary outcomes covering infant development and other assessments, and reports that 11 secondary outcomes were posted. It records 12 outcome measures and zero analyses. These entries indicate that outcome measures were registered, but they do not supply results or specify how outcomes were prioritized in statistical testing. The record does not report adjustment for testing multiple outcomes. Without the analysis plan and outcome-level results, readers cannot determine how the primary and secondary analyses were conducted or how multiplicity was handled.
These limitations concern what can be learned from the registry record, not proof that particular analyses were or were not performed outside it. A registry entry may contain less methodological detail than a full report, but no unposted methods or findings can be assumed when interpreting this result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 12 outcome measures, including the primary maternal serum B12 outcome and secondary measures covering infant cognitive, language, and motor development, as well as other assessments. It reports 11 secondary outcomes posted and zero analyses. The registered outcomes indicate a broad set of measurements, but the record does not provide the analysis results for those secondary measures. Nor does it report a prespecified hierarchy, a plan for controlling the chance of false-positive findings across outcomes, or any adjustment for multiple testing.
Multiplicity matters because testing several outcomes can increase the chance that at least one appears unusual through random variation. This is a general statistical concern; it does not establish that any reported result in this trial is false. Since the record does not contain the secondary analyses or a multiplicity strategy, their results and the approach to interpreting them are not reported in the registry record.
For the primary outcome, the record states that samples were available for 102 of the original 183 participants in each arm. It does not report why samples were unavailable, whether missingness differed in any relevant way, or how missing data were handled. It also does not identify the analysis population as intention-to-treat, per-protocol, or another defined population. Consequently, the outcome analysis cannot be assumed to include all randomized participants, and the effect of missing data cannot be assessed from the posted information.
The registry enrollment is 366, while the brief summary describes 300 women. The registry record does not explain the discrepancy. It also does not connect either figure to the population used in the primary outcome analysis beyond stating the original 183 participants in each arm and the sample availability. These entries should be kept distinct rather than treated as interchangeable descriptions of the analysis population.
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 |
|---|---|---|---|
| Vitamin B12 | 0 | 183 | 0.0% |
| Placebo | 0 | 183 | 0.0% |
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 |
|---|---|
| Vitamin B12 | 0 of 183 |
| Placebo | 0 of 183 |
The registry's adverse-event entries list 183 participants at risk in each arm for serious adverse events and 0 serious events in each arm. The entries for other adverse events also list 183 at risk in each arm and 0 events in each arm. No serious adverse-event terms are listed. These are the adverse-event figures recorded in the registry; they do not establish that no events occurred outside the recorded reporting window or under definitions not described in the entry.
Death counts are not reported in the registry record. The record does not describe the adverse-event collection period, event definitions, severity grading, relatedness assessment, or completeness of reporting. Without those details, the counts cannot characterize the full safety profile or support comparisons beyond the figures entered in the registry. A zero count is a statement about the posted event data, not proof that an intervention has no risks.
Safety interpretation also depends on exposure duration and follow-up, which are not specified for these adverse-event entries. The outcome results should therefore be read narrowly: the registry lists zero serious and zero other adverse events for the stated at-risk groups, does not list serious-event terms, and does not report death counts.
12. What the Result Does, and Does Not, Mean
The posted primary outcome describes maternal serum B12 concentration change from the first to the third trimester among participants with available samples. It reports a median change of 3.0 pmol/L for vitamin B12 and -37.6 pmol/L for placebo, accompanied by lower and upper bounds. The descriptive pattern differs between the arm medians, but the registry does not provide a direct estimate or test of the randomized comparison. These results therefore do not quantify the intervention effect or establish whether the observed arm summaries differ beyond sampling variation.
The endpoint is a biomarker outcome. The record's stated primary question concerns maternal serum B12 concentration, while its brief summary also names maternal hemoglobin, maternal weight gain, and infant birthweight as secondary aims. Other registered secondary outcomes assess infant development. The presence of these aims does not mean their results are available: the registry lists 11 secondary outcomes posted but zero analyses. No findings for those outcomes should be inferred from the primary biomarker result.
The record describes routine iron and folate supplementation as part of standard prenatal care for all women. Thus, the described comparison is vitamin B12 supplementation against placebo in the context of that care. The vitamin B12 dose, adherence, and intervention schedule are not reported in the registry record, limiting interpretation of the intervention's implementation.
The primary result is based on available serum samples, and the record does not explain missing samples or identify the analysis population. The arm-specific bounds are not defined as confidence intervals in the record, and the intended inter-quartile ranges are not populated. Accordingly, the precision and distributional detail of the posted estimates cannot be fully evaluated.
These data support a narrow description of the recorded arm summaries and adverse-event counts. They do not, on their own, establish a causal effect estimate, the clinical meaning of any biomarker change, or results for the unreported secondary analyses. Such conclusions would require fuller analysis and methodological information than the registry record contains.
13. Why This Trial Matters Statistically
This trial illustrates why a registry result needs to be read at the level of the estimand and analysis population. The registered primary outcome is a change in a maternal biomarker over pregnancy, and the posted values are arm-specific medians among participants with serum samples available. Those summaries are informative descriptions, but they do not substitute for a direct randomized contrast. A reader needs the between-arm estimate and its uncertainty to assess the comparative result; neither is reported in the registry record.
It also demonstrates the distinction between an endpoint's stated summary measure and the information actually posted. The record names the median and inter-quartile range, yet only the median and lower and upper bounds appear in the arm results. The bounds are not defined, and no inter-quartile range is reported. That difference affects how precisely the data can be interpreted: an endpoint description is not enough to establish what a displayed interval represents.
Missing outcome data are another central statistical consideration. The record identifies the number of original participants in each arm and the smaller set with available serum samples, but does not explain sample availability or describe its consequences. It therefore offers a useful reminder that a randomized design does not automatically resolve bias from missing outcome measurements. The reasons for missingness and the analysis population matter when interpreting results.
Finally, the registry contains several discrepancies or omissions relevant to appraisal: enrollment and the brief summary describe different participant counts; masking is described with different terms in separate fields; secondary outcomes are listed without posted analyses; and statistical methods for the primary comparison are absent. These points do not prove that the trial was conducted improperly. They delimit what can be concluded from the registry record and why transparent reporting of analysis methods and comparative estimates is important.
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 primary outcome is reported only as arm-specific medians with lower and upper bounds. The record does not provide a direct between-arm estimate, its uncertainty, or a p-value. It also does not explain how the bounds were calculated, and it does not populate the stated inter-quartile range. These omissions prevent a complete assessment of comparative effect and precision.
Only participants with available serum samples contribute to the stated primary analysis description: 102 of the original 183 participants in each arm. The record does not state why samples were unavailable, whether both time-point samples were required, or how missing outcome data were handled. It does not identify the analysis population or report sensitivity analyses. The potential impact of missing samples therefore cannot be evaluated.
The registry lists enrollment of 366, whereas the brief summary describes 300 women. The record does not explain the difference. It also uses quadruple masking in the design field and double-blind in the brief summary without clarifying the terminology or which parties were masked. Details of randomization procedures, intervention dose and schedule, adherence, and laboratory measurement are not reported in the registry record.
The statistical plan is not described in enough detail to identify the comparative method, adjustment strategy, or approach to multiple outcomes. Although secondary outcomes are listed, their analyses and results are not posted. The record does not report a sample-size justification, interim analyses, or how adverse events were collected and defined. These limitations restrict interpretation to the information entered in the registry and should not be resolved by assuming unreported methods or findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized Trial of Vitamin B12 in Pregnant Indian Women — NCT00641862.
- Registry record last updated 2020-07-28; status last verified 2020-07.
- Results first posted 2016-10-17.
- 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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18. Record Summary
The registry describes a completed, randomized, parallel-group trial of vitamin B12 versus placebo among pregnant Indian women. The design field reports quadruple masking, while the brief summary describes the trial as double-blind. All women were to receive standard prenatal obstetric care, including routine iron and folate supplementation. Harvard School of Public Health is listed as sponsor.
The primary outcome is change in maternal serum B12 concentration from the first to the third trimester, summarized by arm using medians. The posted results are based on serum samples available for 102 of the original 183 participants in each arm. The record does not report a direct between-arm analysis, define the displayed bounds, or explain missing samples. It lists secondary outcomes but does not post their analyses. Serious and other adverse-event counts are recorded as 0 in each arm; death counts are not reported in the registry record.