Bacille Calmette-Guerin (BCG) Vaccine for Immune Protection Against Infections: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bacille Calmette-Guerin (BCG) Vaccine for Immune Protection Against Infections (NCT04884308), a non-randomized phase 2 study. The primary outcome is BCG Uptake.

2. Clinical Question

3. Trial Design

This completed phase 2 pilot study evaluated the immunologic effects of intradermal BCG vaccination in adults with cystic fibrosis, adults with non-cystic fibrosis bronchiectasis, and healthy volunteers. Johns Hopkins University is listed as the sponsor. The registry lists enrollment of 30, a parallel model, non-randomized allocation, and no masking. The study start date is 2021-04-28 and the primary completion date is 2023-12-30.

The three groups reflect different participant health categories rather than arms assigned by randomization. The registry cautions that they are not a like-for-like control comparison. This distinction matters when interpreting any differences between groups: disease status, rather than random allocation, defines group membership, and the record does not establish that other group characteristics were balanced. A formal randomized comparison is not described.

The listed intervention is BCG TICE Vaccine, a biological intervention. The brief description characterizes the work as a pilot study of intradermal BCG vaccination. The registry lists one outcome measure and no statistical analyses. It identifies the primary outcome as a continuous measure summarized by a mean and standard error, with a 3-month timeframe. Numerical outcome estimates and details of the statistical test used are not reported in the registry record.

The registry record therefore supports a description of the study structure and its intended immune-response measurement, but not an estimate of the magnitude or precision of the primary finding. The groups can be described as enrolled cohorts, but the available record does not support treating them as randomized treatment and control arms.

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

Analysis population for the primary outcome, as defined in the registry: Analyzed all participants enrolled

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.

Population: Data is presented for all patients enrolled that received BCG vaccination (N=30)

6. Primary Endpoint

The registry lists the primary outcome as BCG Uptake, measured over 3 months.

The primary outcome is titled “BCG Uptake.” Its description defines the measure as change in concentration of interferon (IFN) gamma levels in blood after BCG incubation relative to baseline. The measure is expressed in spot forming units (SFUs), described as a measure of immune response by mononuclear cells in response to M. avium lysate. Higher values are identified in the record as indicating a stronger immune response. The specified timeframe is 3 months, and the outcome population is all participants enrolled.

This type of measure is used to characterize an immune response in laboratory terms. It is not, by its description, a clinical outcome such as infection occurrence or symptom change. The endpoint title should therefore be read alongside its measurement description: the record specifies an assay-based change in IFN gamma response, rather than a direct count of vaccine organisms or a measure of protection against infection.

The registry lists the outcome as continuous, summarized using a mean and standard error. However, the numerical mean, standard error, group-specific estimates, and any interval around the estimate are not reported in the registry record. The precise calculation of change from baseline and any handling of values outside the assay range are also not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting this trial requires separating three things: the design, the endpoint, and the statistical evidence actually reported. The design describes a non-randomized, parallel pilot study. The endpoint describes an assay-based measure of immune response. The registry record does not give the numerical endpoint results or list statistical analyses. Each part answers a different question, and none should be used as a substitute for the others.

What does a non-randomized parallel design imply?

A parallel design means participant groups are considered over the same general study period rather than participants crossing from one assigned intervention to another. Here, the groups are defined as cystic fibrosis, non-cystic fibrosis bronchiectasis, and healthy volunteers. Allocation is listed as non-randomized, and masking as none. The record cautions that the groups are not like-for-like controls. Because group membership is not established by random assignment, measured differences can reflect participant characteristics as well as any immune response associated with vaccination. Whether and how analyses addressed such differences is not reported in the registry record.

Non-randomization does not make the observations unusable. It does change the strength and scope of comparisons that can be made. A descriptive account of responses in each group is distinct from a causal estimate of what vaccination changes relative to an appropriate control. The registry record does not report a randomized contrast, a separate control arm, or a formal primary comparison between the cohorts.

What does a mean and standard error describe?

The outcome is continuous and the registry identifies the summary as a mean with standard error. A mean describes the central value of a set of measurements. The standard error describes the precision of the estimated mean, given the observed data and the method used to estimate it. It is not the same as the spread of individual measurements: a measure of individual variability and a measure of uncertainty in the mean answer different questions.

For a complete statistical interpretation, the estimate and its uncertainty need to be available together. An estimate without a measure of precision does not show how reliably it represents the underlying group. Conversely, a standard error cannot be interpreted without knowing the corresponding estimate and the analysis population. Neither the mean nor the standard error for the primary outcome is reported in the registry record.

Why does an interval matter?

In general, a confidence interval presents a range of values compatible with the data and the assumptions of a statistical procedure. It communicates uncertainty about an estimate, rather than a guarantee that the true value lies within a particular realized interval. A narrow interval indicates greater precision under the model; a wide interval indicates less precision. No confidence interval for the primary outcome is reported in the registry record, so the endpoint’s precision cannot be judged this way.

A p-value, when reported, addresses how compatible the data are with a specified statistical null model under its assumptions. It does not quantify the size or clinical importance of an effect, and it cannot replace the estimate and its uncertainty. No p-value or test statistic is reported for the primary outcome. The record therefore does not support a significance-based conclusion.

How should planning illustrations be read?

The planning description states that illustrations use the observed effect as a reference, with the effect to detect expressed as a fraction of that observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, the descriptions concern participants per arm for 80% power; these are planning assumptions, not observed trial results. Sample-size illustrations are not observed power and do not show that a study had a particular probability of detecting an effect after the data were collected.

Such planning calculations depend on their assumed effect and analysis structure. Here, the underlying numerical outcome estimates and the numerical planning results are not reported in the registry record. Further, an equal-allocation two-arm planning model differs from the actual non-randomized groups described in the study record. The illustrations should therefore be treated as hypothetical planning information, not as evidence that the participant groups were balanced or that a particular comparison was performed.

Why can over-dispersion matter?

In general, over-dispersion occurs when the variability in data is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too small, potentially making evidence appear more precise than it is. Appropriate methods may account for extra variability, but they require information about the data and analysis. The registry record does not describe a model for the primary outcome, assess over-dispersion, or report enough detail to determine whether this issue applied.

The endpoint is reported in SFUs, but the record does not give the distribution of those measurements, the number of observations contributing to each group estimate, or the exact calculation used to derive change from baseline. Consequently, it is not possible to assess whether a normal approximation was appropriate for the endpoint analysis. The normal approximation in the planning description should not be interpreted as a stated analysis method for the observed outcome.

Overall, the registry gives the endpoint definition and a limited description of the study structure. The numerical estimate, uncertainty, inferential test, and detailed model choices needed for a full statistical reading are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Cystic Fibrosis", "Non Cystic Fibrosis Bronchiectasis", "Healthy Volunteer")
n   <- c(14, 2, 14)
m   <- c(48.06, 0.84, 35.97)
sp  <- c(23.52, 16.92, 23.64)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Cystic Fibrosis  14  48.060  88.004  -2.752  98.872
CARM  Non Cystic Fibrosis Bronchiectasis  2  0.840  23.928  -214.149  215.829
CARM  Healthy Volunteer  14  35.970  88.453  -15.101  87.041

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, titled “BCG Uptake,” but it does not report a statistical analysis for that measure. No multiplicity adjustment or hierarchy among primary and secondary outcomes is described in the registry record. With one listed outcome, the record does not indicate how multiple comparisons or multiple time points were handled, if any were considered outside the listed measure. Those analysis details are not reported in the registry record.

Missing-data handling is also not described. The record says that the primary outcome population was all participants enrolled, but it does not state how many contributed a measurement, whether any values were missing, or how missing measurements were treated. It does not report imputation, exclusion rules, sensitivity analyses, or reasons for missingness. These details matter because an analysis population described as all enrolled participants does not, on its own, show that every enrolled participant had an evaluable endpoint.

The registry lists no statistical analyses. Therefore, no analysis population beyond the stated outcome population, covariate adjustment, or method for handling repeated or incomplete measurements can be verified from the record. This is a reporting limitation, not proof that these methods were absent from any separate analysis.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts are zero in each listed group. The safety denominators are 14 for cystic fibrosis, 2 for non-cystic fibrosis bronchiectasis, and 14 for healthy volunteers; the number affected by serious adverse events is 0 in each group. No deaths are recorded in any of the groups. The record lists no top serious adverse event terms.

For other adverse events, 12 of 14 participants are listed as affected in the cystic fibrosis group, 1 of 2 in the non-cystic fibrosis bronchiectasis group, and 12 of 14 among healthy volunteers. These are registry counts, not comparative estimates. The group denominators differ, and the non-cystic fibrosis bronchiectasis safety group is especially small. The counts do not establish that an event was caused by vaccination, nor do they support a reliable ranking of risk across the groups.

The record does not provide event descriptions for the other adverse events in this summary, their severity, timing, or participant-level details. Zero recorded serious events should be read as the observed registry count, not as proof that serious events cannot occur. Safety interpretation is limited by the small pilot enrollment and the available reporting.

13. What the Result Does, and Does Not, Mean

The study record establishes that a completed phase 2 pilot evaluated immune responses after intradermal BCG vaccination in people with cystic fibrosis, people with non-cystic fibrosis bronchiectasis, and healthy volunteers. It defines the primary measure as change in IFN gamma response in blood after BCG incubation relative to baseline, expressed in SFUs, with measurement at 3 months. It also gives adverse-event counts by group.

Those descriptions do not establish the size or direction of the primary endpoint result. The numerical mean and standard error are not reported in the registry record, and the record lists no statistical analyses. It is therefore not possible to assess the outcome’s precision, determine whether group responses differed, or evaluate a statistical test from the registry information. The outcome definition says higher values indicate a stronger immune response, but the record does not connect any numerical change to clinical outcomes.

The endpoint is an assay-based immune measure. It is not a reported measure of infection occurrence, disease progression, or another clinical outcome. The record does not establish that the measured response corresponds to protection against infection. That distinction is important: a laboratory response can characterize immune activity without, by itself, demonstrating a clinical effect.

The non-randomized design also limits causal interpretation. Participant cohorts defined by health status cannot automatically be treated as interchangeable controls. The registry explicitly cautions that the groups are not a like-for-like control comparison. No randomized comparison is described.

The appropriate reading is therefore narrow: this record describes the study’s population, intervention, immune assay, and safety counts, but does not report the numerical primary result needed to judge its magnitude or precision. It supports no treatment recommendation and does not establish whether BCG vaccination changes clinically meaningful outcomes.

14. Why This Trial Matters Statistically

This study is statistically notable because it puts an immune-response measure into a pilot study spanning two respiratory disease cohorts and healthy volunteers. That design raises a useful interpretive question: how can assay responses be described across populations that differ in health status without treating those groups as randomized controls? The registry record itself flags this issue by identifying non-randomized allocation and warning that the arms are not a like-for-like control comparison.

The endpoint also illustrates why measurement definitions matter. “BCG Uptake” is the registry title, while the accompanying description specifies a change in IFN gamma levels after incubation, measured in SFUs. Reading the measurement description alongside the title helps clarify that the recorded outcome is an immune-response assay, rather than a direct measure of a clinical event. This distinction affects which conclusions the endpoint can support.

The record is also a reminder that an endpoint definition alone is not enough for statistical interpretation. To assess magnitude and precision, readers need estimates and uncertainty; to assess inferential claims, they need the analysis and its assumptions. Those numerical results and analyses are not reported in the registry record. The record’s planning description cannot fill that gap, because sample-size illustrations are hypothetical planning tools rather than observed evidence.

Finally, the safety counts show why denominators and study scale matter. Counts from small groups can describe what was recorded, but they provide limited information for comparing event frequencies. Taken together, the design, endpoint, missing analysis details, and safety denominators make this trial a useful example of how registry descriptions define the scope of interpretation as much as they describe the study itself.

15. 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 principal limitation for interpreting efficacy or immune-response findings is that the numerical primary outcome results are not reported in the registry record. The mean, standard error, group-specific estimates, and any confidence interval or test statistic are unavailable. Although the registry identifies all enrolled participants as the outcome population, it does not report the number with evaluable measurements or the handling of missing data.

The design is non-randomized, and the participant groups are defined by health status. The registry cautions that they are not a like-for-like control comparison. Differences in response between these groups would not, on their own, establish a causal effect. The record does not report adjustment methods or enough participant-level characteristics to evaluate comparability.

The endpoint is an assay-based measure, not a clinical infection outcome. The record says that higher SFU values indicate a stronger immune response, but it does not report a clinical threshold or link the assay change to patient-centered outcomes. The calculation details for the change from baseline are not reported in the registry record.

The total enrollment was 30. Safety denominators were 14 for cystic fibrosis, 2 for non-cystic fibrosis bronchiectasis, and 14 for healthy volunteers. These group sizes limit the amount of information available for interpreting uncommon events or comparing safety patterns. The registry does not describe event-level detail for the other adverse events in this summary.

Finally, the record does not report the statistical test, model, multiplicity approach, missing-data method, or analysis-specific population. These reporting gaps prevent a full assessment of assumptions and robustness. They do not show that no additional analysis exists outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bacille Calmette-Guerin (BCG) Vaccine for Immune Protection Against Infections — NCT04884308.
• Registry record last updated 2025-02-10; status last verified 2025-01.
• Results first posted 2025-02-10.
• 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.

19. Record Summary

NCT04884308 is a completed phase 2 pilot study sponsored by Johns Hopkins University. It evaluated intradermal BCG TICE Vaccine in adults with cystic fibrosis, adults with non-cystic fibrosis bronchiectasis, and healthy volunteers. Enrollment was 30. The study had a parallel model, non-randomized allocation, and no masking. Its start date was 2021-04-28, and its primary completion date was 2023-12-30.

The primary outcome, titled “BCG Uptake,” is described as change in blood IFN gamma response after BCG incubation relative to baseline, measured in SFUs at 3 months. The record lists one outcome measure and no statistical analyses. Numerical primary outcome results are not reported in the registry record.

No serious adverse events or deaths are listed for the groups. Other adverse events were recorded in each group, with the counts and denominators. The non-randomized cohort design and absent numerical outcome analyses limit conclusions about comparative immune response and clinical meaning.