A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada (NCT02985450), a registered phase not stated study. The primary outcome is Anti-HBs Titres (IU/L).

2. Clinical Question

The study addresses hepatitis B immunity and vaccine response among adults with non-alcoholic fatty liver disease (NAFLD) in Canada. Its registry summary gives two aims: to assess the prevalence of hepatitis B immunity in a prospectively evaluated cohort, and to examine antibody responses after hepatitis B vaccination. The primary comparison described in the record concerns anti-HBs titres in low- and high-risk obesity groups among patients with NAFLD.

The primary endpoint is a continuous antibody-titre measure, recorded in IU/L, at the specified time after vaccination. The registry record does not report the observed group titres or an estimate of the comparison, so the magnitude and precision of any difference cannot be assessed.

3. Trial Design

This was a prospective study sponsored by the University of Calgary. The registry record lists an enrollment of 82 and a completed status. The recorded study start is 2016-08, and primary completion is recorded as 2021-01. The study concerned hepatitis B immunity and vaccination in patients with NAFLD in Canada.

The intervention listed is Engerix-B. The primary endpoint description specifies measurement 1 month after completion of the vaccine series. The comparison is between patients classified as having low- or high-risk obesity. The record does not give the criteria for these categories, the number of participants in either category, or details of the vaccination schedule beyond the reference to completing the series.

The study is not described as a randomized comparison, and allocation is not stated. The two obesity-risk groups should therefore not be read as randomized treatment arms or as a controlled comparison of vaccine against no vaccine. Differences between the groups could reflect characteristics other than the risk grouping, but the registry record does not provide enough detail to assess those characteristics or any adjustment for them.

The registry summary also describes an aim to assess hepatitis B immunity in the cohort, alongside the aim of evaluating vaccine response. These aims address related but distinct questions: the prevalence of existing immunity is not the same outcome as antibody titres after vaccination. The primary endpoint named in the record is the post-series anti-HBs titre comparison. Other design details, including recruitment procedures, eligibility criteria, follow-up beyond the stated endpoint timing, and the analysis plan, 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: No significant events were noted. 7 patients were lost to follow-up.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Anti-HBs levels were compared between two groups: low and high-risk obesity patients with NAFLD.

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: 7 patients lost to follow-up.

6. Primary Endpoint

The registry lists the primary outcome as Anti-HBs Titres (IU/L), measured over 1 month after completion of the vaccine series.

The primary endpoint is anti-HBs titre, measured in IU/L, at 1 month after completion of the vaccine series. The registry describes the measure as a mean with standard deviation and states that the comparison is between low- and high-risk obesity groups among patients with NAFLD. The stated purpose is to examine how NAFLD-associated metabolic risk factors and liver inflammation or fibrosis affect vaccine response.

In general, a continuous antibody titre retains information about the level of the measured response rather than reducing it immediately to a category. A group mean describes the average titre, while the standard deviation describes how much individual measurements vary around that average. These summaries are useful for comparing distributions at group level, but they do not show the full distribution or identify how many individuals reached a particular threshold. The registry summary mentions protective anti-HBs titres, but does not specify a threshold for the primary comparison.

The timing makes the endpoint a measure of response after the vaccine series, rather than a measure of immunity before vaccination or long-term persistence. The registry record does not report the observed means, standard deviations, group sizes, or a between-group estimate. Thus, the endpoint is defined, but its results and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, anti-HBs titre in IU/L. The registry specifies that the result is summarized by a mean and standard deviation and measured 1 month after completion of the vaccine series. It describes a comparison between low- and high-risk obesity groups in patients with NAFLD. The registry record does not report the statistical procedure used to make that comparison.

What does a mean describe?

In general, the mean is the arithmetic average of the observed values in a group. It gives a concise description of the group's central level, but can be influenced by unusually high or low measurements. For a titre measure, the mean alone does not show whether values cluster closely together or vary widely. That is why the standard deviation is also relevant: it describes the spread of individual observations around the mean. It is not the uncertainty around the estimated mean; a confidence interval or standard error is used for that inferential purpose.

The choice of summary and comparison method matters when data are strongly skewed or include extreme observations. In general, analysts may inspect distributions and consider whether a mean-based analysis is a suitable summary, or whether a transformation or another method is needed. The registry record does not state that such checks, transformations, or alternative analyses were used. No distributional information is reported, so the shape of the titre data cannot be evaluated.

What would a group comparison estimate?

In general, a comparison of group means estimates how far apart the average measured titres are in the groups being compared. A confidence interval would show the statistical uncertainty around that estimated contrast under the chosen model and assumptions. A p-value, if reported, would summarize how compatible the observed data are with a specified null model; it would not measure the size or clinical importance of a difference. The registry record does not report a mean contrast, confidence interval, or p-value for the primary endpoint.

Precision depends on the amount and variability of observed data, among other factors. The enrollment of 82 is a study-level figure and cannot be substituted for endpoint-specific group sizes. The record does not report how many participants were measured at the endpoint, how many were included in each risk group, or whether all enrolled participants were analyzed. As a result, endpoint precision cannot be inferred from enrollment alone.

Why does the comparison structure matter?

In general, randomization can help balance measured and unmeasured characteristics between treatment groups, whereas a comparison of naturally occurring or otherwise non-randomized groups may remain affected by differences between those groups. This study is not described as a randomized comparison, and allocation is not stated. The low- and high-risk obesity groups are the stated comparison for the primary endpoint; they are not identified as randomized arms. An observed group contrast, if available, would therefore require cautious interpretation, particularly if other factors related to titre also differ between groups.

Adjustment for relevant covariates can address some measured differences when suitable data and a prespecified or otherwise justified model are available. It cannot automatically remove bias from unmeasured factors, and the choice of adjustment variables affects interpretation. The registry record does not report a model, covariates, stratification, or adjusted estimates. It is therefore not possible to tell whether the primary comparison was unadjusted or adjusted.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; it says the target effect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the planned analysis achieved a particular precision. The registry record does not report numerical planning estimates in the details available for this interpretation. These assumptions also do not establish that the study itself used equal allocation or a normal approximation for its analysis.

The record does not report the analysis plan, handling of missing observations, model diagnostics, sensitivity analyses, or the method used to calculate uncertainty. Those omissions limit assessment of whether the analysis matched the endpoint distribution and comparison structure. General statistical principles explain what the summaries and estimates would mean; they do not substitute for the missing endpoint results or analysis details.

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("BMI < 35", "BMI > 35")
n   <- c(40, 28)
m   <- c(642, 385)
sp  <- c(68.2, 79)
sd  <- sp      # posted standard deviations
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  BMI < 35  40  642.000  68.200  620.189  663.811
CARM  BMI > 35  28  385.000  79.000  354.367  415.633

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, while the primary endpoint described in the record is anti-HBs titre at 1 month after completion of the vaccine series. Details of the other outcome measure are not reported in the registry record. The record does not state how outcomes were designated beyond identifying the primary endpoint, nor does it describe a multiplicity strategy or adjustment for multiple comparisons.

In general, evaluating multiple outcomes or multiple subgroup comparisons can increase the chance of finding an apparently notable result by chance. A prespecified analysis plan and an explicit approach to multiplicity help readers understand how confirmatory claims were controlled. Since no outcome-level results or multiplicity methods are reported, it is not possible to assess that issue for this study.

Missing-data methods and analysis populations are also not reported in the registry record. The enrollment figure does not establish the number with a post-series titre, the number included in the primary comparison, or whether any observations were excluded. The record does not describe imputation, complete-case analysis, reasons for missing measurements, or sensitivity analyses. These details matter because missing endpoint measurements can affect both the representativeness of the analyzed participants and the estimated group contrast.

The record therefore does not support a judgment about whether missingness or multiple testing influenced the reported findings. The endpoint results and relevant analysis details are not reported in the registry record.

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.

The registry safety figures list the HBV Vaccine Cohort with 82 participants at risk for serious adverse events and zero affected. For other adverse events, the record lists 82 at risk and zero affected. Deaths are recorded as zero, and no serious adverse-event terms are listed.

These figures are registry counts, not a complete description of the nature, timing, duration, or severity of all possible reactions. The record does not provide event-specific details, follow-up duration for safety surveillance, or an explanation of how adverse events were collected. A zero recorded count means that no affected participants are reported in these registry fields; it does not establish that no events occurred outside the recorded definitions or observation process.

The listed safety counts do not address the primary antibody-titre comparison, and they do not establish comparative safety against an untreated or randomized control group. The study is not described as a randomized comparison. Safety figures should therefore be read as registry-reported counts for the stated cohort, rather than as evidence of a causal safety difference or a general conclusion about risk.

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

The record establishes that a prospective study was conducted on hepatitis B immunity and vaccination in adults with NAFLD in Canada, and that anti-HBs titre after the vaccine series was the named primary endpoint. It identifies a comparison between low- and high-risk obesity groups and marks the study as completed. The endpoint timing, unit, and summary measure are also specified.

What the record does not establish is the observed vaccine response in either group. The primary endpoint values, group sizes, between-group estimate, and uncertainty are not reported in the registry record. Without those results, it is not possible to say whether the groups differed, how large a difference may have been, or whether the data were precise enough to distinguish a meaningful contrast from uncertainty.

The registry summary's statements about existing immunity and reduced responses in obesity describe the study rationale. They are not a substitute for outcome results. Similarly, completion status and the enrollment figure do not indicate whether the primary question was answered conclusively. They do not reveal endpoint completeness, the balance of group sizes, or the statistical uncertainty of an estimate.

In general, an antibody titre is a measured biological response, while a clinical outcome concerns a person's health status or experience. The registry identifies anti-HBs titres as the response measure but does not report a clinical outcome comparison. The record therefore cannot establish from the described endpoint alone how any titre difference relates to clinical outcomes.

The study's non-randomized comparison also constrains causal interpretation. Even if a group difference were reported, differences in participant characteristics could contribute to it. The record does not provide an adjusted analysis or enough information to determine the extent to which such differences were considered. The appropriate reading is that the registry defines a research question, but the available result details do not answer it quantitatively.

14. Why This Trial Matters Statistically

This study raises a statistical question about how a continuous antibody response varies across obesity-risk groups among adults with NAFLD. That framing matters because the outcome is not simply whether a participant is classified as immune or not immune: the named primary measure is an anti-HBs titre in IU/L, summarized as a mean and standard deviation. A continuous endpoint can retain differences in measured response, although the distribution and the relevance of particular titre levels also matter.

The registry also distinguishes two related objectives: assessing hepatitis B immunity in the cohort and examining response after vaccination. Those questions require different outcome definitions and interpretation. Existing immunity is not interchangeable with a post-vaccination titre, and a post-series measurement does not by itself describe longer-term persistence. The record specifies a post-series measurement time, but does not report the numerical endpoint findings.

The comparison structure is important as well. Low- and high-risk obesity groups are described, but randomization is not reported and the study is not a randomized comparison. This means that an association between group classification and titres, if estimated, would need to be interpreted in light of possible differences between groups. The registry record does not provide enough analysis detail to assess adjustment for those differences.

Finally, the record illustrates why endpoint definitions and completed status are not sufficient for statistical interpretation. Readers need group summaries, an effect estimate, uncertainty, and information about the analysis population to judge the strength and precision of evidence. Those primary results are not reported in the registry record. The study question is identifiable, but its quantitative answer cannot be assessed from the available record details.

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 the study is that the registry record does not report the primary endpoint results. Group means, standard deviations, group sizes, the estimated contrast, and its uncertainty are not available. This prevents assessment of the direction, magnitude, and precision of the primary comparison.

The obesity-risk categories are not defined in the record. Without their criteria, readers cannot determine how participants were classified or how comparable the groups may have been. The record also does not report participant characteristics by group, the measurement or categorization of metabolic risk factors, or methods for assessing liver inflammation and fibrosis.

The comparison is not described as randomized, and allocation is not stated. The registry does not report whether the primary analysis adjusted for potential confounders. Any group contrast would therefore need cautious interpretation, and the available information cannot establish a causal effect of obesity-risk status on vaccine response.

Additional limitations arise from missing methodological details. Eligibility criteria, recruitment procedures, endpoint-specific analysis counts, missing-data handling, analysis populations, model assumptions, and sensitivity analyses are not reported in the registry record. The record identifies the endpoint timing and summary form, but does not describe how titres were measured or how the statistical comparison was conducted.

The safety fields report zero affected participants for the listed adverse-event categories, but event definitions and surveillance details are not reported. These registry counts cannot replace a fuller account of event ascertainment. Together, the absent outcome results and limited methods detail restrict conclusions to describing the study question and the registry information, rather than evaluating the evidence for a group difference.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada — NCT02985450.
• Registry record last updated 2021-11-03; status last verified 2018-06.
• Results first posted 2021-11-03.
• 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

The registry record describes a completed prospective study sponsored by the University of Calgary, with enrollment of 82. The recorded study start is 2016-08 and primary completion is 2021-01. The study concerns hepatitis B immunity and vaccination in adults with NAFLD in Canada, with Engerix-B listed as the biological intervention.

The primary endpoint is anti-HBs titre in IU/L, summarized as a mean and standard deviation at 1 month after completion of the vaccine series. The stated comparison is between low- and high-risk obesity groups. The record does not describe a randomized comparison, and allocation is not stated.

Primary endpoint results, group sizes, and the analysis details needed to assess the comparison are not reported in the registry record. The safety fields list zero affected participants for serious and other adverse events, and zero deaths. The record identifies the study question, but does not provide a numerical answer to its primary comparison.