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 Causes of Rotavirus Vaccine Failure in Zambian Children (NCT01886833), a registered phase not stated study. The primary outcome is Proportion of Immunized Infants Exposed to High Breast Milk Anti-rotavirus Immunoglobulin-A Who Fail to Seroconvert.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01886833 |
| Phase | Phase not stated |
| Condition | Diarrhoea |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 420 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Centre for Infectious Disease Research in Zambia |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled 420 mother-infant pairs through Kamwala health facility in Lusaka, Zambia. The registry reports paired rotavirus-specific IgA measurements at baseline and after vaccination for 216 infants. The cohort was recruited in the context of routine immunization services.
Intervention
Infants received routine rotavirus vaccination with Rotarix, described as a two-dose vaccine. This is an observational study, not a randomized comparison of assigned treatments. Maternal serum and breast-milk IgA were collected at the time of vaccination, with infant serum IgA measured after vaccination.
Comparator
The central comparison is between infants exposed to different levels of maternal breast-milk anti-rotavirus IgA, with high exposure of interest and undetectable or low exposure described in the registry. The registry does not report a randomized control group or a like-for-like treatment comparison.
Primary question
The primary question is whether infants exposed to high breast-milk anti-rotavirus IgA fail to seroconvert after vaccination. The registry frames maternal immunity as a possible contributor to failed seroconversion. Because exposure is observed rather than assigned, the question concerns an association in the cohort; it cannot by itself establish that maternal IgA caused an outcome. The primary assessment is specified for 1 month following full immunization.
3. Trial Design
NCT01886833, titled “Causes of Rotavirus Vaccine Failure in Zambian Children,” is recorded as a completed observational study. Its official title describes an observational study in the context of routine immunization services. The registry lists enrollment of 420 and identifies a prospective cohort of mother-infant pairs. Recruitment was associated with Kamwala health facility in Lusaka. The recorded study start is 2012-04-01, and the primary completion date is 2015-04-30.
Rather than assigning participants to different vaccine regimens, the study was designed to examine possible reasons for variation in response to routine rotavirus vaccination. The registry describes collecting maternal serum and breast-milk IgA at vaccination and measuring infant anti-rotavirus-specific serum IgA 1 month following the second dose of Rotarix. Follow-up was described as extending for up to four years. These features make the study an observational cohort: exposure and outcomes are measured among participants in routine care, without a stated randomized treatment allocation.
The stated hypotheses concern high maternal rotavirus-specific immunity and infant seroconversion, malnutrition and post-vaccination rotavirus gastroenteritis, and possible changes in circulating rotavirus strains detected in vaccinated children with severe diarrhoea. A listed secondary outcome concerns failure to seroconvert among immunized infants with low micronutrient levels, indicated by serum zinc and vitamin A. The registry lists five outcome measures, but does not report the results for them in the record.
The registry identifies a single “Mother-Infant Pair” group. Allocation to comparison arms is not stated, and the study should not be read as a like-for-like control comparison. Details of the statistical analysis plan, sample-size justification, adjustment strategy, and handling of potential confounding 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 | Mother-infant Pair IgA |
|---|---|
| STARTED | 420 |
| COMPLETED | 216 |
| NOT COMPLETED | 204 |
Reasons for not completing this period:
| Reason | Mother-infant Pair IgA |
|---|---|
| IgA not available from both periods | 204 |
Analysis population for the primary outcome, as defined in the registry: Of the 420 participants that were enrolled in the study, we had rotavirus specific paired IgA at baseline and post vaccination for 216 infants.
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 | Mother-Infant Pair |
|---|---|---|
| Participants analysed | 420 | |
| Age, Continuous | months | 27 (18 to 46) |
| Sex: Female, Male: Female | Participants | 232 |
| Sex: Female, Male: Male | Participants | 188 |
| Region of Enrollment: Zambia | participants | 420 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Immunized Infants Exposed to High Breast Milk Anti-rotavirus Immunoglobulin-A Who Fail to Seroconvert, measured over 1 month following full immunization.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Proportion of exposed infants |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the proportion of infants exposed to high breast-milk anti-rotavirus immunoglobulin-A who fail to seroconvert. The time frame is 1 month following full immunization. The registry describes maternal serum and breast-milk IgA collection at vaccination, followed by measurement of infant anti-rotavirus-specific serum IgA 1 month after the second dose of Rotarix. It also describes maternal IgA status as the primary exposure, with high-level exposure and undetectable or low-level exposure as the categories of interest.
Seroconversion is used as an immunological response measure: in general, it indicates a change in an antibody measure after vaccination according to a specified definition. The exact threshold or operational definition used for seroconversion is not reported in the registry record. Nor does the record give the number or proportion of infants in the high-exposure group who failed to seroconvert. It reports that 216 infants had paired rotavirus-specific IgA measurements at baseline and after vaccination, out of 420 enrolled participants. That count describes the available paired measurements; it does not establish the primary endpoint result.
In general, an endpoint that relates an observed maternal exposure to an infant response can help describe whether the two vary together in a cohort. Because maternal IgA was not assigned, the endpoint does not on its own separate its association from other factors that may accompany maternal immunity. The intended endpoint is relevant to the stated hypothesis, but its interpretation depends on the missing outcome definition, estimate, and analysis details.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and cohort size, but it does not report the primary endpoint estimate. In particular, it gives no result for the proportion of infants exposed to high breast-milk anti-rotavirus IgA who failed to seroconvert, and no estimate comparing high exposure with low or undetectable exposure. There is consequently no reported effect estimate, confidence interval, or p-value from which to judge the size or precision of an association.
The 216 infants with paired baseline and post-vaccination IgA measurements are an important part of the record. This number is not the same as a reported endpoint result: the registry does not state how these infants were distributed across maternal IgA exposure categories or how many did or did not seroconvert. It also does not explain why paired measurements are not reported for all 420 enrolled participants. Without those details, the recorded enrollment cannot be treated as the denominator for the primary endpoint.
The study's observational cohort design affects what an eventual association could mean. In general, an observed relationship between maternal antibody levels and infant antibody response could reflect the exposure of interest, other participant characteristics, or a combination of factors. The registry lists malnutrition as another hypothesis, but does not report an adjusted model or describe how other potential influences were handled. An association would therefore not establish that breast-milk IgA caused a failure to seroconvert.
The record also describes hypotheses about micronutrients, post-vaccination gastroenteritis, and circulating strains. The stated hypotheses provide context, but results for these questions are not reported in the registry record. The entry lists five outcome measures and zero analyses. That does not establish what analyses may have been conducted outside the record; it means the registry entry does not provide analysis results to evaluate.
The adverse-event information is separate from the primary immunological endpoint. The record reports 51 participants affected in the serious adverse-event group, with 420 at risk, and lists serious-event terms with percentages. It does not provide enough detail to connect those figures to the primary exposure comparison or to infer causation. Taken together, the posted information supports a description of the research question, enrollment, available paired measurements, and reported safety entries. It does not support a quantitative conclusion about the primary association.
9. Statistical Methods Explained
The available record identifies an observational cohort and a proportion-based primary outcome, but does not report the statistical methods used to analyze that outcome. The concepts below explain how such data are commonly interpreted in general; they are not a claim that the study used a particular method.
What does the primary proportion represent?
In general, a proportion is the number of participants meeting a defined outcome divided by the number of participants in the relevant group. For this study, that would require a clear definition of high maternal breast-milk IgA exposure, a clear definition of failure to seroconvert, and the number of infants with both exposure and outcome information. The registry describes the exposure and endpoint but does not report those group counts or the operational definition of seroconversion. The proportion itself is therefore not available to interpret.
A proportion is a summary of the observed participants, not a complete description of uncertainty. A confidence interval is a range of values compatible with the observed data under a statistical model. In general, it conveys how precisely an estimate is measured; a wider interval indicates less precision than a narrower one. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the association cannot be assessed from this entry.
Why does the cohort design matter?
In general, an observational cohort follows participants and records exposures and outcomes without randomly assigning the exposure. This design can describe patterns and associations in the enrolled population. However, participants with different exposure levels may also differ in other ways. If those characteristics relate to the outcome, an unadjusted association may not represent the independent relationship between exposure and response. Statistical adjustment can sometimes address measured differences, but cannot automatically remove bias from unmeasured factors. The registry does not report whether adjusted analyses were performed or which variables might have been included.
Randomization is a method for creating comparable groups, on average, by assigning an intervention through chance. No randomized allocation is stated for this study, and its listed group is “Mother-Infant Pair.” It is therefore inappropriate to interpret the record as a randomized comparison. The registry also does not describe a control arm or a protocol-defined comparison group beyond the maternal IgA exposure categories in the primary question.
How should the paired measurements be read?
The registry reports paired rotavirus-specific IgA measurements at baseline and after vaccination for 216 infants among the 420 enrolled. Paired measurements mean that both time points are available for an infant. In general, such paired data can support assessment of change within participants, but the analysis still depends on the definition of change and the handling of missing measurements. The entry does not report why paired results are available for only part of the enrolled cohort, whether those with paired data differ from other participants, or what missing-data methods were used. The paired count alone does not show the direction or magnitude of antibody change.
In general, missing data can affect an estimate when the likelihood of having a measurement is related to exposure or outcome. If participants without a post-vaccination result differ systematically from those with one, an analysis limited to complete pairs may not represent the whole enrolled cohort. This is a methodological concern to consider, not evidence that such a bias occurred in this study. The registry does not report enough information to assess it.
What can the planning illustrations establish?
The registry describes sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not evidence that the study used those assumptions to set enrollment. They do not represent observed power, and they do not establish the power of the cohort analyses. The record does not report the study's own sample-size justification or whether the planning comparison corresponds to the actual observational design.
In general, sample-size planning asks how much information may be needed to detect a specified difference under chosen assumptions. It depends on the outcome, target effect, variability, design, and analysis. If the assumed effect is based on an observed estimate, the illustration is conditional on that estimate and on the selected fraction; it does not validate the effect or guarantee a result. Since no primary estimate is reported in this registry entry, the planning assumptions cannot be used to infer the study's observed result.
What does over-dispersion mean in general?
For count outcomes, some statistical models assume that variability follows a particular relationship to the average count. Over-dispersion occurs when the observed variation is greater than that assumption allows. If present, it can make standard errors too small under a model that ignores it, which can make confidence intervals look more precise than warranted. This general concept is not a reported finding about this study. The primary endpoint is described as a proportion, and the registry record does not report a count model, an over-dispersion assessment, or an analysis method.
Finally, the record lists five outcome measures and zero analyses. In general, multiple outcomes or multiple statistical tests raise questions about how results are selected and how false-positive findings are controlled. The entry does not report a multiplicity plan, a hierarchy of secondary outcomes, or analysis results. No inferential conclusion can be reconstructed from the outcome count alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and zero analyses. This means the record does not present analysis results for the primary or secondary outcomes. It does not establish whether analyses were conducted elsewhere. The registry does not report a multiplicity strategy, such as a prespecified hierarchy of outcomes or a method for accounting for multiple statistical tests. In general, when several outcomes are examined, readers need to know whether and how the interpretation accounts for that multiplicity; without a reported plan or results, that assessment cannot be made.
For missing data, the central recorded count is 216 infants with paired rotavirus-specific IgA measurements at baseline and after vaccination, among 420 enrolled participants. The registry does not report why paired measurements are unavailable for other enrolled participants, whether they completed vaccination, or whether missingness was related to maternal IgA exposure or infant response. It also does not describe imputation, sensitivity analyses, or other missing-data procedures. The difference between enrollment and paired measurement availability should not be interpreted as a specific reason for missingness.
The record does not define the analysis population for the primary endpoint, state whether all enrolled participants were eligible for each outcome, or report how exclusions were handled. It does not provide the primary endpoint denominator by exposure category. It also does not report an intention-to-treat or per-protocol analysis population. Such labels should not be inferred for this observational cohort in the absence of a stated analysis definition.
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 |
|---|---|---|---|
| Mother-Infant Pair | 51 | 420 | 12.1% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Mother-Infant Pair | 0 of 420 |
Most frequent serious adverse event terms
| Event term | Organ system | Mother-Infant Pair |
|---|---|---|
| Hospitalization | General disorders | 39 of 420 |
| death from unknown causes | General disorders | 4 of 420 |
| fever and convulsions | General disorders | 2 of 420 |
| Diarrhoea | Gastrointestinal disorders | 1 of 420 |
| Diarrhoea plus vomiting | Gastrointestinal disorders | 1 of 420 |
| acute pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 420 |
| severe burns | Social circumstances | 1 of 420 |
| Fever and malaria | Infections and infestations | 1 of 420 |
| injuries | Injury, poisoning and procedural complications | 1 of 420 |
Serious events with the highest arm-level rate: hospitalization (9.3%), death from unknown causes (1.0%), fever and convulsions (0.5%), diarrhoea (0.2%), diarrhoea plus vomiting (0.2%).
The registry lists 420 participants at risk in the mother-infant pair group and reports 51 affected in the serious adverse-event group. For other adverse events, the corresponding affected count is recorded as 0 among 420 at risk. The serious-event terms listed include hospitalization at 9.3%, death from unknown causes at 1.0%, fever and convulsions at 0.5%, diarrhoea at 0.2%, diarrhoea plus vomiting at 0.2%, and acute pneumonia at 0.2%.
These are registry safety entries, not results of a randomized safety comparison. The record does not give event dates, follow-up duration for each event, participant-level overlap between terms, or a causal assessment attributing events to vaccination. The percentages are listed as serious-event terms; the record does not explain their calculation or specify whether participants could appear under more than one term. The group-level deaths field is not reported, even though a death-related term appears in the listed serious-event terms. These entries should therefore be read as reported safety information, not as proof that vaccination caused an event or as a complete accounting of event timing and relationships.
12. What the Result Does, and Does Not, Mean
The registry record identifies a completed observational study asking whether high maternal breast-milk anti-rotavirus IgA is associated with infant failure to seroconvert following routine rotavirus vaccination. It documents enrollment of 420 mother-infant pairs and paired baseline and post-vaccination rotavirus-specific IgA measurements for 216 infants. It also states a primary assessment time of 1 month following full immunization and describes several related hypotheses.
Those details do not reveal whether the primary hypothesis was supported. No primary endpoint proportion, exposure-group comparison, confidence interval, or p-value is reported in the registry record. The number of paired measurements cannot substitute for an outcome estimate, because it does not indicate how many infants seroconverted or how results differed by maternal IgA exposure. Results for the other listed hypotheses are also not reported in the entry.
Even if an association were reported, the observational design would matter. In general, an association does not by itself show that maternal IgA caused a response or failure to respond. Other characteristics may be related to both exposure and outcome, and the registry does not describe an adjustment strategy. A causal interpretation would require assumptions and evidence beyond the enrollment and measurement counts.
The safety entries likewise require careful scope. They report serious adverse-event counts and terms, but do not establish that an event was caused by vaccination or describe event timing and overlap in enough detail to resolve those questions. No medical conclusion should be drawn from these figures alone.
The main statistical conclusion is therefore about what the record can support: it documents the study's question, design, enrollment, available paired measurements, and safety listings, while leaving the outcome estimates and analytical details unavailable. The absence of reported results is not evidence for either the presence or absence of an association.
13. Why This Trial Matters Statistically
This study matters statistically because it asks a mechanistic question in the setting of routine immunization while measuring maternal exposure and infant antibody response over time. The cohort design can describe how those measures vary together among participating mother-infant pairs. That is distinct from estimating the effect of an assigned intervention, and it makes careful attention to selection, missing measurements, and potential confounding especially important.
The registry's enrollment of 420 and report of paired IgA measurements for 216 infants illustrate why the analysis denominator matters. A reader needs to know which participants contributed to each outcome, how exposure groups were formed, and whether missing measurements could be related to response. The record does not provide these details or the primary endpoint counts, so the central association cannot be evaluated quantitatively.
The study also frames more than one biological hypothesis, including maternal immunity, micronutrient levels, and circulating strains. In general, multiple questions can help explore a complex research problem, but they also make prespecification and transparent reporting important. The record lists five outcome measures and zero analyses, and does not report a multiplicity plan or analysis results. This limits what can be learned from the registry entry about which hypothesis was tested most directly or how uncertainty was handled.
Finally, the study underscores the difference between a research question and a reported result. A plausible hypothesis, a completed study status, and a substantial enrollment do not show whether an association was observed or how precise it was. Clear endpoint definitions, denominators, estimates, uncertainty intervals, and analysis methods are necessary for readers to judge the evidence.
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.
Several limitations are specific to the information recorded for this cohort. First, the registry describes paired baseline and post-vaccination IgA data for 216 infants, while enrollment was 420. The reason for this difference and the characteristics of participants without paired measurements are not reported. This prevents assessment of whether the measured subset represents the enrolled cohort for the primary endpoint.
Second, the registry does not provide the primary outcome counts or estimate, the maternal IgA exposure-group denominators, or a confidence interval. It also does not report the operational definition of seroconversion. Without those items, readers cannot assess the observed association, its precision, or the endpoint's exact classification rule.
Third, the study is observational and takes place within routine immunization services. The registry does not report a randomized allocation, a control group, or an adjustment strategy for potential confounding. The record therefore does not support treating exposure categories as equivalent to randomized groups or interpreting an association as a causal effect.
Fourth, details of missing-data handling, analysis populations, multiplicity, interim analyses, and the statistical analysis plan are not reported in the registry record. The registry also does not report results for the five listed outcome measures. These omissions restrict assessment of analytic choices and the completeness of outcome reporting. The reported safety terms lack details on timing, overlap, and causal assessment, which also limits their interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Causes of Rotavirus Vaccine Failure in Zambian Children — NCT01886833.
- Registry record last updated 2018-08-23; status last verified 2018-07.
- Results first posted 2018-08-23.
- 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
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01886833, “Causes of Rotavirus Vaccine Failure in Zambian Children,” is recorded as completed. The registry identifies an observational prospective cohort with enrollment of 420 mother-infant pairs in the context of routine immunization services in Lusaka, Zambia. The recorded study start is 2012-04-01, and the primary completion date is 2015-04-30.
The primary question concerns failure to seroconvert among infants exposed to high breast-milk anti-rotavirus IgA, with assessment 1 month following full immunization. Paired rotavirus-specific IgA measurements at baseline and after vaccination are reported for 216 infants. The registry lists five outcome measures and zero analyses, and does not report a primary endpoint estimate or statistical analysis results.
Safety entries include 51 affected in the serious adverse-event group among 420 at risk, alongside listed serious-event terms and percentages. The record does not establish causation or provide detailed event timing. Overall, it documents the study design and measurements but does not provide the results needed to evaluate the primary association.