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 B12, Neurodevelopment and Growth in Nepal (NCT02272842), a randomized phase 2, phase 3 study. The primary outcome is The Bayley Scales of Infant Development Version 3.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02272842 |
| Phase | Phase 2, Phase 3 |
| Condition | Development, Vitamin Deficiency, Malnutrition |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 600 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Centre For International Health |
| Results posted | Yes |
2. Clinical Question
The trial asks whether daily vitamin B12 supplementation for one year changes growth, neurodevelopment, and hemoglobin concentration in malnourished infants in Bhaktapur municipality in Nepal. The registry record describes the study population as 600 malnourished infants and identifies neurodevelopment as the primary outcome. Growth and hemoglobin are also stated aims, while several secondary outcomes address development, vitamin status, adverse effects, and other measures.
The intervention is a daily paste containing vitamin B12. The comparison is a daily paste without vitamin B12; both pastes also contain other vitamins. The study is described as randomized and placebo-controlled, with half of the children assigned to each paste. The primary neurodevelopmental assessment is scheduled at 12 months.
The central statistical question is whether the distribution of the measured developmental scores differs between the intervention groups at the stated assessment time, and how precisely any difference is estimated. The registry record does not report group-specific primary scores, an estimated between-group effect, or its uncertainty. It therefore does not establish the direction or size of a primary-outcome difference. The record describes intended questions and outcomes, but those aims should not be mistaken for evidence that an outcome changed.
The study rationale identifies vitamin B12 deficiency, poor growth, and developmental concerns as relevant to the target population. It also refers to an earlier study in Indian children. That background explains the question being tested, but it is not a result of this Nepal trial and cannot substitute for its comparison of randomized groups.
3. Trial Design
The registry record describes a randomized, placebo-controlled, parallel-group trial, listed as phase 2 and phase 3. Masking is recorded as quadruple. These design features indicate an intended comparison between two groups assigned to different pastes, with masking intended to reduce the influence of treatment knowledge on trial conduct or assessment. The record does not specify which roles were masked or how masking was implemented.
The listed enrollment is 600, and the study description says half of the children would receive each paste. The intended population is malnourished infants in Bhaktapur municipality in Nepal. The intervention paste contains vitamin B12 at 2µg per 10 mL and is administered every day; it also contains 1 RDA of several other vitamins. The placebo paste is described as containing no vitamin B12, while also containing 1 RDA of several vitamins. Thus, the planned contrast focuses on adding vitamin B12 to a paste that includes other vitamins.
The registry lists a start date of 2015-04-20 and a primary completion date of 2018-02-28. The study status is recorded as unknown. These registry entries do not establish whether recruitment, follow-up, or analyses were completed as planned.
The primary endpoint is the Bayley Scales of Infant Development version 3 at 12 months. The record names cognitive, fine motor, gross motor, receptive language, and expressive language scaled scores. It also lists growth velocity, predictors and subgroups related to development or supplementation, vitamin status markers, other developmental tools, immediate adverse effects, leucocyte telomere length, and sleep duration among secondary outcomes. The registry record does not describe the detailed statistical analysis plan, allocation procedure, or follow-up schedule for each secondary outcome.
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 | 300 | 300 |
| COMPLETED | 284 | 290 |
| NOT COMPLETED | 16 | 10 |
Reasons for not completing this period:
| Reason | Vitamin B12 | Placebo |
|---|---|---|
| Lost to Follow-up | 8 | 8 |
| Withdrawal by Subject | 8 | 2 |
Analysis population for the primary outcome, as defined in the registry: Cognitive, Fine Motor, Gross Motor, Receptive language, and Expressive language scaled scores of the Bayley Scales of Infant Development version 3. This scale measures different aspects of neurodevelopment. The mean (SD) scores are usually 100 (15), and 95% of the population has scores between 70 and 130 (theoretical max/means 0/200). The higher scores, the better neurodevelopment; the scale is normalized on age.
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 | 300 | 300 | 600 | |
| Age, Continuous | Months | 8.0 (SD 1.8) | 8.1 (SD 1.8) | 8.0 (SD 1.8) |
| Sex: Female, Male: Female | Participants | 149 | 142 | 291 |
| Sex: Female, Male: Male | Participants | 151 | 158 | 309 |
| Race/Ethnicity, Customized: Nepalese | Participants | 300 | 300 | 600 |
| Length (cm) | cm | 65.837 (SD 3.0) | 65.94 (SD 2.9) | 65.9 (SD 3.0) |
| Weight (kg) | kg | 7.3 (SD 0.92) | 7.3 (SD 0.92) | 7.3 (SD .92) |
6. Primary Endpoint
The registry lists the primary outcome as The Bayley Scales of Infant Development Version 3, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Scaled Scores |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is neurodevelopment assessed at 12 months with the Bayley Scales of Infant Development version 3. The record names five domains: cognitive, fine motor, gross motor, receptive language, and expressive language. Scores are described as scaled scores, summarized using means and standard deviations. The instrument is intended to assess different aspects of development and is normalized on age, so interpretation accounts for the child’s age at assessment.
The registry description states that scores are higher with better measured neurodevelopment. It gives usual scale mean and standard deviation values of 100 (15), and says 95% of the population has scores between 70 and 130; the theoretical maximum and means are listed as 0/200. These are scale characteristics in the record, not results from children in this trial.
Using a standardized developmental assessment allows the study to compare measured domains between randomized groups at a specified time. Reporting each domain matters because a single overall score could conceal differing patterns across cognitive, motor, or language measures. The registry record does not explain whether the five domain scores were intended to be analyzed as separate primary outcomes, combined, or handled using another prespecified approach.
No group-specific Bayley scores, between-group estimates, confidence intervals, or tests of statistical significance are reported in the registry record. The stated endpoint therefore identifies what was to be measured, but the posted information does not show the trial’s primary outcome findings or their precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record states a clear randomized comparison and identifies a primary developmental assessment at 12 months. It does not report the arm-specific Bayley results or an estimate comparing the groups. Consequently, the direction, magnitude, and precision of any difference in the primary outcome cannot be described from the registry record. The record’s stated hypotheses are not outcome findings.
The primary outcome includes cognitive, fine motor, gross motor, receptive language, and expressive language scaled scores. Without separate results for these domains, it is not possible to determine whether the posted data show a consistent pattern or whether findings differ across domains. Nor is it possible to assess whether any observed difference would be large or small relative to the scale’s usual values. Those scale characteristics provide context, not a substitute for trial-specific estimates.
Statistical interpretation ordinarily considers an effect estimate together with its uncertainty. A confidence interval communicates a range of values compatible with the data under the analysis used; a narrow interval indicates greater precision than a wide one. No primary-outcome estimate or confidence interval is reported in the registry record, so neither the size of an effect nor the range of plausible values can be assessed.
The record lists 12 outcome measures and 2 analyses, but does not describe how the primary domains or secondary outcomes were handled in the analysis. This matters because interpreting several outcomes or domains requires clarity about which comparisons were planned and how multiplicity was addressed. The registry record also does not report the analysis populations, missing outcome counts, or methods for incomplete data. These omissions limit assessment of how the reported results, if available elsewhere, relate to the randomized groups.
The listed enrollment and the adverse-event counts do not establish the primary developmental result. Safety summaries describe different outcomes from developmental scores, and group counts alone cannot answer the primary question. In particular, the registry record reports adverse event counts but gives no basis for inferring a developmental effect from them.
Overall, the registry record is informative about the intended design, population, intervention, and endpoint, but does not provide the primary outcome comparison. Any interpretation of developmental benefit, harm, or no difference would require outcome estimates and their uncertainty, which are not reported in the registry record.
9. Statistical Methods Explained
The design is a randomized parallel-group comparison. In general, randomization aims to make assigned groups comparable at the start of a trial with respect to both measured and unmeasured characteristics. If follow-up and analysis preserve the randomized comparison, differences in outcomes can be interpreted as comparisons between assigned groups, subject to issues such as missing data, adherence, and measurement. The registry record identifies randomization but does not report the allocation sequence, concealment procedures, or the analysis population.
The trial is described as placebo-controlled and quadruple-masked. In general, masking can reduce the influence of expectations on participant experience, clinical care, outcome assessment, or analysis. The registry record does not identify the four roles covered by the masking label, nor does it describe procedures for maintaining or assessing masking. Therefore, the label alone does not establish how masking operated in practice.
The primary outcome is continuous: Bayley scaled scores are summarized as means and standard deviations. In general, a mean describes the group’s average score, while a standard deviation describes the spread of scores around that average. A comparison of group means estimates an average difference, but the estimate needs an uncertainty measure, such as a confidence interval, to show its precision. No trial-specific primary means, standard deviations, mean differences, or confidence intervals are reported in the registry record.
What does a confidence interval add?
As a general statistical explanation, a confidence interval expresses uncertainty around an estimated effect. It helps distinguish a precisely estimated small difference from an estimate whose uncertainty includes a broad range of possible effects. A confidence interval does not by itself establish clinical importance, and its interpretation depends on the analysis and assumptions used. The registry record does not report a confidence interval for the primary endpoint.
Why does multiplicity matter?
As a general statistical explanation, when researchers examine multiple outcomes, domains, time points, or subgroups, the chance of finding an apparently unusual result can increase if all comparisons are treated as independent confirmatory tests. Prespecified outcome hierarchies or adjustment methods can help clarify which results are confirmatory and how to interpret the others. This trial lists several Bayley domains and multiple secondary outcomes, but the registry record does not describe a multiplicity strategy or indicate how the domains were classified for testing.
What is over-dispersion?
As a general explanation, over-dispersion arises when count data vary more than a chosen statistical model expects. It can make standard errors too small if the extra variation is ignored. This concept is more relevant to event counts or other count outcomes than to a comparison of continuous Bayley scores. The registry record does not report an over-dispersion model or describe such an analysis, so no conclusion about its use is warranted.
How should planning calculations be read?
The registry record describes planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that non-time-to-event illustrations are expressed as participants per arm for 80% or 90% power, while time-to-event illustrations use total events. These are planning conventions, not observed trial results and not observed power. The record does not report the effect estimates or calculated participant requirements needed to assess a specific illustration. The described planning approach should not be treated as evidence that the trial had adequate power for its primary endpoint.
What can be said about the analysis?
The registry record lists 12 outcome measures and 2 analyses, but does not describe the statistical models, covariate adjustments, handling of repeated observations, or procedures for missing data. These details affect how estimates are constructed and how uncertainty is quantified. Without them, a reader cannot assess whether the analysis followed a prespecified plan or how robust results would be to alternative reasonable choices. No adjusted or recalculated primary comparison is reported in the registry record, so there is no basis to compare a sponsor analysis with a recalculation.
10. Multiplicity, Missing Data and Analysis Populations
The registry record names multiple outcomes and developmental domains, but does not describe a strategy for controlling or interpreting multiplicity. The primary Bayley endpoint includes cognitive, fine motor, gross motor, receptive language, and expressive language scores. The record also lists secondary outcomes involving growth, vitamin status, development measured by other tools, adverse effects, telomere length, and sleep duration. It does not state whether the five Bayley domains were each treated as primary, whether one was designated as the principal comparison, or whether any adjustment was planned for multiple testing.
The registry lists 12 outcome measures and 2 analyses. Those counts do not reveal which outcomes were analyzed together, whether analyses were prespecified, or whether any outcomes were omitted from reported results. The registry record does not report test statistics, p-values, effect estimates, or a statistical analysis plan that would clarify these issues.
Missing-data reporting is also limited. The registry record does not report how many children had primary outcome measurements, the reasons for missing assessments, or the methods used to handle incomplete observations. It does not describe whether all randomized children were included in the primary analysis or whether an alternative analysis population was used. These details matter because missing outcome data can affect precision and, depending on why data are missing, can affect the interpretation of group comparisons.
As a general statistical point, a complete account of multiplicity and missing data helps readers judge the strength and reliability of findings. In this record, the relevant procedures are not reported in the registry record, so no conclusion about their adequacy can be drawn.
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 | 2 | 300 | 0.7% |
| Placebo | 0 | 300 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Vitamin B12 | 0 of 300 |
| Placebo | 0 of 300 |
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 | 70 of 300 |
| Placebo | 63 of 300 |
Most frequent serious adverse event terms
| Event term | Organ system | Vitamin B12 | Placebo |
|---|---|---|---|
| Abscess | Infections and infestations | 1 of 300 | 0 of 300 |
| Burn | Skin and subcutaneous tissue disorders | 1 of 300 | 0 of 300 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vitamin B12 | Placebo |
|---|---|---|---|
| Regurgitation following paste administration. | Gastrointestinal disorders | 70 of 300 | 63 of 300 |
| Lower respiratory infection | Respiratory, thoracic and mediastinal disorders | 6 of 300 | 8 of 300 |
| Febrile seizures | Nervous system disorders | 6 of 300 | 2 of 300 |
| Urinary tract infection | Renal and urinary disorders | 3 of 300 | 0 of 300 |
| Constipation | Gastrointestinal disorders | 1 of 300 | 1 of 300 |
Serious events with the highest arm-level rate: abscess (0.3%), burn (0.3%).
The registry lists serious adverse event counts of 2 in the Vitamin B12 group and 0 in the placebo group. It lists 300 at risk in each group. It also lists other adverse event counts of 70 in the Vitamin B12 group and 63 in the placebo group, with 300 at risk in each group, and reports 0 deaths in both groups. These are counts as recorded; they do not by themselves explain the nature, timing, duration, or cause of each event.
The serious-event terms listed are Abscess and Burn, each recorded as 0.3%. The registry entry does not link those terms to a specific treatment group in the information available, so they should not be assigned to one group based on these figures alone. The record does not provide event-level descriptions, definitions of severity, or information on whether events were judged related to the intervention.
In general, adverse-event counts describe observed events within the recorded follow-up and should be interpreted alongside how events were defined, collected, and attributed. The registry record does not report those details or provide a statistical comparison of the groups for safety outcomes. These figures therefore describe the posted safety counts without establishing that the intervention caused or prevented an event.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, placebo-controlled study of vitamin B12 supplementation in malnourished infants in Nepal, with neurodevelopment assessed using the Bayley Scales of Infant Development version 3 at 12 months. It establishes the research question, planned comparison, and primary measure. It does not report the group-specific primary scores or a between-group estimate. Therefore, the posted record does not establish whether the groups differed in measured neurodevelopment, nor how precisely any difference was estimated.
The trial’s stated hypotheses also concern growth and hemoglobin concentration, and the record lists multiple secondary outcomes. The presence of an outcome in the protocol description means that it was a question of interest; it does not establish a result. Without the corresponding group summaries and effect estimates, no direction or size of effect can be stated for those outcomes.
The Bayley scale description gives general context for interpreting scores, including usual scale values and the fact that higher scores indicate better measured neurodevelopment. Those characteristics do not show where children in this trial scored or whether a group difference was present. Similarly, the adverse-event counts describe recorded events but do not resolve the developmental question or establish causation.
In general, statistical evidence is best interpreted using the estimated effect, its uncertainty, the analysis population, and the completeness of follow-up. The registry record does not report these details for the primary outcome. It is therefore not possible to judge the size, precision, or robustness of a primary comparison from this record alone. This is a limit of what is reported, not evidence for either a positive or a null finding.
The record also lists the study status as unknown. The listed primary completion date is 2018-02-28, but that entry does not establish the status of the analysis or whether results were fully reported. The appropriate conclusion is narrow: the record describes a trial designed to test these questions, while its primary developmental results are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of a randomized comparison that targets a defined population and a development-focused outcome. The intervention and placebo both include other vitamins, while the intervention paste additionally contains vitamin B12. That design makes the intended contrast more specific than a comparison of a multivitamin paste with no paste, although the registry record does not provide adherence or exposure results.
The primary outcome is not a single undifferentiated measure: it includes cognitive, fine motor, gross motor, receptive language, and expressive language scores. This creates an important interpretive issue. A clear analysis needs to identify how each domain contributes to the primary question and how conclusions are drawn when domains do not show the same pattern. The registry record does not report that analysis strategy.
The study also illustrates why effect estimates and uncertainty matter more than a statement of aims or a count of participants. The registry lists enrollment of 600, but without primary outcome results, group summaries, and uncertainty estimates, that figure alone cannot tell readers what the data show or how precisely the question was answered. Nor can planning assumptions establish observed power or prove that a particular comparison was adequately powered.
Finally, the record links developmental outcomes with growth, hemoglobin, vitamin status, and safety outcomes. These related questions can provide a broader view of the study, but they also require transparent reporting of outcome selection, missing data, and multiplicity. Because those statistical details and the primary comparison are not reported in the registry record, the design is clearer than the evidential result. That distinction is essential when interpreting a trial record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most important limitation for interpretation is that the registry record does not report the primary outcome results. It names the Bayley Scales of Infant Development version 3 at 12 months but provides no group means, standard deviations, between-group estimates, confidence intervals, or significance tests. The direction and magnitude of the primary comparison therefore cannot be assessed.
The endpoint description includes five developmental domains, but the record does not clarify how those domains were combined or prioritized analytically. It also does not state how the listed secondary outcomes were incorporated into the analysis or how multiplicity was handled. The registry record lists 12 outcome measures and 2 analyses without describing the models or the specific comparisons.
The record does not report the analysis population, numbers with available outcome data, reasons for missing assessments, or methods for addressing missing data. It also does not describe adherence to daily supplementation, intervention exposure, or any procedures for checking the success of masking. These omissions limit assessment of trial conduct and of how closely outcome comparisons represent the intended randomized contrast.
The listed enrollment is 600, but the record does not establish from this entry whether that enrollment was achieved or how many children contributed to the primary analysis. The status is recorded as unknown. Although a primary completion date is listed, it does not resolve these reporting uncertainties.
Finally, the safety summary gives counts but little event-level context, and does not report attribution or timing. These limitations do not establish that the trial was conducted inadequately; they describe what cannot be evaluated from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Vitamin B12, Neurodevelopment and Growth in Nepal — NCT02272842.
- Registry record last updated 2023-09-18; status last verified 2022-07.
- Results first posted 2021-05-25.
- 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
NCT02272842 is listed as a randomized, quadruple-masked, parallel, placebo-controlled study in malnourished infants in Bhaktapur municipality in Nepal. The registry lists phase 2 and phase 3, enrollment of 600, a start date of 2015-04-20, a primary completion date of 2018-02-28, and status unknown.
The intervention is a daily paste containing vitamin B12 at 2µg per 10 mL and other vitamins; the placebo paste contains other vitamins but no vitamin B12. The primary endpoint is the Bayley Scales of Infant Development version 3 at 12 months, with cognitive, fine motor, gross motor, receptive language, and expressive language scores. Growth, hemoglobin, and several other outcomes are also listed.
Arm-specific primary outcome results and the statistical details needed to interpret them are not reported in the registry record. The registry lists serious adverse event counts of 2 and 0, other adverse event counts of 70 and 63, and 0 deaths in both groups.