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 Using BCG to Protect Senior Citizens During the COVID-19 Pandemic (NCT04542330), a randomized phase 3 study. The primary outcome is Acute Infection.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04542330 |
| Phase | Phase 3 |
| Condition | Covid19, Non-specific Effects of Vaccines, Heterologous Immunity |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 1700 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bandim Health Project |
| Results posted | Yes |
2. Clinical Question
Population
Senior citizens aged 65 years or above during the COVID-19 pandemic. The brief summary describes this age group as the intended population. The registry lists enrollment as 1700, while the brief summary describes a study population of 1900; the reason for this difference is not reported in the registry record.
Intervention
BCG-Denmark, an intradermal BCG vaccine. The brief summary describes administration of a standard dose. The registry record identifies the vaccine as the active intervention.
Comparator
Placebo, described as saline. The control-arm description specifies sterile 0.9 % NaCl administered by intradermal injection.
Primary question
Whether assignment to BCG-Denmark, compared with saline, changes the number of acute-infection events during 12 months after inclusion. Acute infection was defined using a composite of infection attended by a physician, antibiotic use, hospitalization due to infection, or death due to infection.
3. Trial Design
The registry describes a phase 3, randomized, double-masked, parallel-group, placebo-controlled trial. Participants were assigned to BCG-Denmark or saline, with the brief summary specifying a 1:1 allocation. The registry lists enrollment as 1700. The brief summary, however, says the study population was 1900 seniors; the reason for the discrepancy is not reported in the registry record.
The intended population was seniors aged 65 years or above. The trial began on 2020-09-15, had a primary completion date of 2023-01-11, and is listed as completed. The registry does not report the number screened, reasons for exclusion, or the number included in each analysis population.
The intervention was BCG-Denmark, given by intradermal injection. The comparator was saline, described as sterile 0.9 % NaCl administered intradermally. Further details of the vaccine description are incomplete in the registry record. The record does not explain which people involved in the trial were masked or how masking was maintained.
The primary outcome was acute infection, counted as recurrent events over 12 months after inclusion. Secondary outcomes listed include verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalization. The primary endpoint combines several clinical events, and the registry says its subcomponents were also analyzed separately. Comparative outcome estimates and details of the analysis populations 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.
Before assignment: Screening details: We screened 1,816 persons for inclusion; 140 fulfilled an exclusion criterion or declined to participate, and 1,676 were included and randomised to BCG (N=838) or placebo (N=838).
Overall Study
| Stage | BCG-Denmark | Control |
|---|---|---|
| STARTED | 838 | 838 |
| COMPLETED | 838 | 838 |
| NOT COMPLETED | 0 | 0 |
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 | BCG-Denmark | Control | Total |
|---|---|---|---|---|
| Participants analysed | 838 | 838 | 1676 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 838 | 838 | 1676 |
| Age, Continuous | years | 70.5 (67.6 to 74.1) | 70.7 (67.9 to 74.1) | 70.6 (67.7 to 74.1) |
| Sex: Female, Male: Female | Participants | 461 | 461 | 922 |
| Sex: Female, Male: Male | Participants | 377 | 377 | 754 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Denmark | participants | 838 | 838 | 1676 |
| History of previous BCG vaccination | Participants | 817 | 818 | 1635 |
| Scar from previous BCG vaccination | Participants | 717 | 725 | 1442 |
| COVID-19 vaccinated before inclusion | Participants | 180 | 174 | 354 |
6. Primary Endpoint
The registry lists the primary outcome as Acute Infection, measured over 12 months after inclusion.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint counts acute-infection events during 12 months after inclusion. It is a composite: an event could be an infection attended by a physician, use of antibiotics, hospitalization due to infection, or death due to infection. The registry describes these as recurrent events, meaning the endpoint can count more than one event for a participant rather than recording only whether that participant ever had an event.
A composite endpoint can capture several clinically relevant manifestations within one outcome definition. In general, it may also increase the number of events available for analysis, but its interpretation depends on which components occur and how often. Components may differ in severity and in how they are identified. The registry states that each component was analyzed separately, but does not report component-specific results, event-adjudication procedures, or whether events could meet more than one component definition.
The endpoint is relevant to the trial’s stated aim of assessing acute infection during the pandemic, but it is broader than confirmed SARS-CoV-2 infection. Antibiotic use or a physician-attended infection, for example, does not by itself identify a particular pathogen. The registry separately lists verified SARS-CoV-2 infection and self-reported respiratory symptoms as secondary outcomes.
No comparative result for the primary endpoint is reported in the registry record. Therefore, the record does not establish the observed difference in event counts, the precision of an estimate, or the contribution of the separate components.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the trial design and endpoint but does not report a comparative efficacy estimate for acute infection. There is no reported group-level primary-outcome event count, effect estimate, confidence interval, or p-value in the record. The direction and precision of any treatment-group contrast therefore cannot be assessed from the registry information available.
The endpoint is an event count rather than a simple count of participants who experienced at least one event. This distinction matters: a comparison of recurrent event counts can reflect both how many participants experience events and how often events recur. Without group-specific counts and a defined analysis, the record does not show which of these patterns may have contributed to a result.
The composite combines physician-attended infection, antibiotic use, infection-related hospitalization, and death due to infection. In general, a composite result should be interpreted alongside its components, because the overall contrast can be influenced by components that differ in frequency or clinical importance. Although separate analyses are mentioned, their estimates are not reported in the registry record. Nor are the rules for handling events that might satisfy more than one component definition reported.
The stated study objective includes reducing acute infection, while secondary objectives address SARS-CoV-2 infection and self-reported respiratory illness. These outcomes answer related but distinct questions. A result for the composite would not, by itself, identify an effect on verified SARS-CoV-2 infection or on any one component. The registry record does not report comparative results for the listed secondary outcomes either.
The record lists 1700 as enrollment, while the brief summary describes a study population of 1900. This discrepancy complicates interpretation of the planned and analyzed populations; its explanation is not reported in the registry record. The numbers assigned to each arm for analysis, exclusions, and missing outcome data are also not reported.
Safety entries describe serious adverse events and other events by group, but they do not substitute for comparative efficacy results. The record does not report enough detail to determine causal attribution, the statistical approach to safety comparisons, or the completeness of event ascertainment. Overall, the registry record documents a randomized comparison and a defined primary endpoint, but does not provide the results needed to estimate the treatment contrast or its uncertainty.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups by chance. In general, this helps make the groups comparable at the start with respect to both measured and unmeasured characteristics, although chance imbalances can still occur. It supports a comparison based on assigned group, provided the analysis population and handling of follow-up are clearly described. The registry identifies the study as randomized and describes a 1:1 allocation in its brief summary. The sequence-generation and allocation-concealment procedures are not reported in the registry record.
What does double masking mean?
The trial is listed as double-masked. In general, masking can limit the influence of treatment knowledge on participant reports, clinical decisions, and outcome assessment. The label alone does not identify which people were masked, what procedures preserved masking, or whether masking was assessed. Those details are not reported in the registry record.
How should a recurrent-event endpoint be understood?
The primary outcome counts recurrent acute-infection events during 12 months after inclusion. A recurrent-event analysis is intended to account for more than the first event per participant. General methods for event counts may require attention to the distribution of counts and to over-dispersion. Over-dispersion means that event counts vary more than a simple model assumes; ignoring it can lead to uncertainty estimates that are too small. This is a general statistical consideration, not a statement about the method used in this trial. The registry does not report the model, the treatment-effect measure, or whether over-dispersion was assessed.
Other general considerations include differences in time under observation and the possibility that a first event affects the chance of later events. The registry describes a 12-month timeframe but does not report how incomplete follow-up, death from causes other than infection, or event timing was handled in the primary analysis. It also does not state whether events were independently adjudicated.
Why does the composite definition matter?
A composite combines multiple event types into one endpoint. In general, this can produce a broader measure and may yield more events than a narrow endpoint, but the meaning of the combined estimate depends on its components. Components may differ in severity, frequency, and ascertainment. The registry definition includes physician-attended infection, antibiotic use, infection-related hospitalization, and death due to infection. It says the components were also analyzed separately, but their results and analysis methods are not reported in the registry record.
For a count composite, an overall event-count contrast does not necessarily represent a contrast in the number of participants affected. It may reflect differences in first events, recurrences, or both. To distinguish these interpretations, readers need group-specific event counts, participant counts, and the statistical model or estimand. Those details are not reported in the registry record.
What do the planning illustrations represent?
The registry describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The assumed effect to detect is a stated fraction of the observed effect. Such illustrations are hypothetical planning calculations, not observed power and not evidence that the study had a particular chance of detecting an effect. The registry does not report the trial’s own sample-size justification or explain whether these assumptions were used in the original design.
In general, planning calculations depend on the assumed effect, variability, significance level, allocation, and analysis method. For event-count outcomes, assumptions about event rates and dispersion can be important. The brief summary mentions an expected incidence of acute infection of 20% and a 25% risk reduction in the intervention group, but the summary text is truncated. It does not provide a complete account of the planned outcome model or its assumptions. The enrollment discrepancy—1700 in the registry and 1900 in the brief summary—also leaves the intended target unclear.
No recalculated treatment comparison is available from the reported information. Recalculation from summary statistics would not replace the sponsor’s analysis where that analysis is reported; in this case, comparative primary-outcome results are not reported in the registry record. A confidence interval, when reported, generally describes the range of effect estimates compatible with the data and model at the stated confidence level. Without an estimate and interval, statistical precision cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary composite outcome and secondary outcomes that include verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalization. It also says the primary endpoint’s subcomponents were analyzed separately. Multiple outcomes and component analyses raise a general multiplicity issue: the more comparisons made, the greater the chance of at least one apparently notable result by chance if no adjustment or prespecification is applied. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or which comparisons were designated confirmatory.
The registry record does not report the statistical analysis plan, so it is not possible to determine how outcome definitions, model choices, or analysis populations were specified before results were known. It also does not report how missing outcome data, loss to follow-up, withdrawals, or incomplete observation were handled. These details matter for an outcome observed over 12 months, particularly when recurrence and time under observation may affect event counts.
Analysis populations, such as whether participants were analyzed according to randomized assignment, are not reported in the registry record. The group-specific number included in each analysis and the extent of missingness are also not reported. No imputation method, sensitivity analysis, interim analysis, or stopping rule is described. These statements concern what is documented in the registry record; they do not establish that such procedures were absent from trial conduct.
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 |
|---|---|---|---|
| BCG-Denmark | 78 | 838 | 9.3% |
| Control | 63 | 838 | 7.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BCG-Denmark | 1 of 838 |
| Control | 3 of 838 |
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 |
|---|---|
| BCG-Denmark | 52 of 838 |
| Control | 8 of 838 |
Most frequent serious adverse event terms
| Event term | Organ system | BCG-Denmark | Control |
|---|---|---|---|
| Cardiac disorders | Cardiac disorders | 19 of 838 | 18 of 838 |
| Infections | Infections and infestations | 18 of 838 | 11 of 838 |
| General disorders | General disorders | 8 of 838 | 8 of 838 |
| Gastrointestinal disorders | Gastrointestinal disorders | 8 of 838 | 7 of 838 |
| Vascular | Vascular disorders | 7 of 838 | 7 of 838 |
| Neoplasms | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 5 of 838 | 8 of 838 |
| Injuries | Injury, poisoning and procedural complications | 10 of 838 | 3 of 838 |
| Renal disorders | Renal and urinary disorders | 2 of 838 | 1 of 838 |
| Respiratory | Respiratory, thoracic and mediastinal disorders | 2 of 838 | 0 of 838 |
| Eye disorders | Eye disorders | 0 of 838 | 2 of 838 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BCG-Denmark | Control |
|---|---|---|---|
| Vaccination site reactions | General disorders | 52 of 838 | 8 of 838 |
Serious events with the highest arm-level rate: cardiac disorders (2.3%), infections (2.1%), injuries (1.2%), neoplasms (1.0%), general disorders (1.0%).
The safety entries list serious adverse events for BCG-Denmark and control, with 838 at risk in each group. The record lists 78 serious adverse events for BCG-Denmark and 63 for control. It also lists 52 other adverse events for BCG-Denmark and 8 for control, and deaths of 1 and 3, respectively. These are the recorded counts; they should not be treated as comparative risk estimates without knowing the event definitions, analysis method, and follow-up completeness.
The registry also lists serious-event terms with percentages: cardiac disorders, 2.3%; infections, 2.1%; injuries, 1.2%; neoplasms, 1.0%; general disorders, 1.0%; and gastrointestinal disorders, 1.0%. The record does not specify the denominator or whether these percentages refer to both groups combined, so they should not be interpreted as group-specific rates. It also does not report whether the listed terms are mutually exclusive or how events were coded.
Counts of adverse events and deaths alone do not establish that an event was caused by a study intervention. Attribution procedures, definitions, and comparative uncertainty are not reported in the registry record. The figures describe safety reporting, not a causal conclusion.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, double-masked, parallel-group trial compared intradermal BCG-Denmark with saline in senior citizens during the COVID-19 pandemic. It defines a primary composite outcome of recurrent acute-infection events over 12 months after inclusion. It also lists secondary outcomes and safety entries.
The record does not report comparative primary-outcome results. It therefore does not show whether event counts differed between groups, how large any difference was, or how precisely it was estimated. It also does not report comparative results for the secondary outcomes. No conclusion about the direction or size of an effect on acute infection, SARS-CoV-2 infection, or respiratory symptoms can be drawn from the registry record alone.
Even if a composite result were available, it would not automatically answer whether each component changed in the same way. The composite includes multiple types of events, and the registry does not report the component-specific estimates. Likewise, an event-count outcome is not identical to the proportion of participants who experienced at least one event. Those are different summaries and can yield different interpretations.
The safety entries report recorded event counts but do not provide enough information to infer causation or to compare safety precisely. The record does not describe the methods for assessing attribution, the denominator for the listed serious-event percentages, or the completeness of event reporting.
The trial’s existence and design may be relevant to researchers studying non-specific vaccine effects, but a design description is not evidence of an outcome. The enrollment discrepancy and missing analysis details further limit interpretation. The registry record supports a description of what was planned and recorded; it does not, as presented, establish whether BCG-Denmark changed the measured outcomes.
13. Why This Trial Matters Statistically
This trial addresses a statistical question that extends beyond a single pathogen-specific endpoint. Its primary outcome combines several kinds of acute infection-related events, while secondary outcomes include verified SARS-CoV-2 infection and self-reported respiratory symptoms. The distinction between these endpoints matters: a broad event count, a pathogen-specific outcome, and a self-reported symptom measure capture different aspects of health and rely on different forms of ascertainment.
The primary outcome is recurrent, so analysis concerns event counts rather than only first events or the number of participants ever affected. In general, recurrent-event endpoints require methods and assumptions that reflect repeated observations within a participant. The registry record does not report the model or its assumptions, making it impossible to assess how this feature was handled statistically.
The trial also illustrates why outcome definitions and component results matter for a composite. A single summary can combine events with different clinical meanings and frequencies. Reporting component-specific findings alongside an overall composite can clarify what drives an estimate; the registry says components were analyzed separately, but does not report those results.
Finally, the enrollment discrepancy and absence of comparative outcome estimates show the limits of interpreting a registry entry as a results report. Design features and safety counts provide useful context, but they do not replace effect estimates, uncertainty intervals, analysis-population details, and transparent reporting of missing data. The registry record captures the research question and some trial conduct details, while leaving the central efficacy comparison unresolved.
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 registry record does not report comparative efficacy estimates, confidence intervals, p-values, or group-specific primary-outcome event counts. As a result, the size, direction, and precision of the primary comparison cannot be evaluated. Secondary-outcome results and the separate analyses of primary-endpoint components are also not reported.
Enrollment is described inconsistently: the registry lists 1700, while the brief summary describes a study population of 1900. The reason is not reported in the registry record. Numbers randomized, analyzed, withdrawn, or lost to follow-up are not reported, nor are the analysis populations or the handling of missing data.
The record does not report the statistical analysis plan, event-adjudication procedures, model for recurrent counts, assumptions about dispersion, multiplicity approach, or sensitivity analyses. The composite endpoint joins events with different definitions and potential levels of severity; component-specific outcome results are unavailable. Details on masking roles and maintenance are also not reported.
Safety entries lack reported definitions, attribution methods, and an identified denominator for the listed serious-event percentages. The registry record also does not establish whether the listed safety counts represent unique participants or events. These limits constrain interpretation of both comparative efficacy and safety from the registry information alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Using BCG to Protect Senior Citizens During the COVID-19 Pandemic — NCT04542330.
- Registry record last updated 2024-08-22; status last verified 2024-03.
- Results first posted 2024-08-22.
- 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 phase 3 randomized, double-masked, parallel-group trial of BCG-Denmark versus saline among senior citizens aged 65 years or above. Enrollment is listed as 1700, although the brief summary describes a study population of 1900. The trial began on 2020-09-15 and had a primary completion date of 2023-01-11.
The primary outcome was recurrent acute-infection events over 12 months after inclusion, defined by physician-attended infection, antibiotic use, infection-related hospitalization, or death due to infection. Secondary outcomes included verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalization. Comparative outcome estimates and key analysis details are not reported in the registry record. Safety entries list serious and other adverse events and deaths, but do not establish causation.