The Relationship Between Vitamin D and Hepatitis B Virus Replication: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Relationship Between Vitamin D and Hepatitis B Virus Replication (NCT03068767), a randomized na study. The primary outcome is The Dynamic Change of HBV DNA.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. The brief summary says 149 HBV carriers with inadequate serum vitamin D levels were randomized to receive vitamin D or to a control group without vitamin D supplementation. The posted outcome groups contain 75 participants in the vitamin D group and 74 in the control group. The trial status is completed.

The intervention is identified as vitamin D, and the arm description specifies 2000 IU/day for 2 months. The control arm is described as receiving no vitamin D supplement. The registry does not report whether the control group received a placebo, whether other care was standardized, or whether participants or outcome assessors were aware of group assignment beyond the general masking entry of none.

The registry lists the study model as parallel and allocation as randomized. Details of sequence generation, allocation concealment, stratification, or the process used to assign participants are not reported in the registry record. The listed phase is NA. The registry gives a start date of 2016-09 and a primary completion date of 2019-01-01.

The primary outcome concerns serum HBV DNA, reported in IU/mL, with a stated timeframe of baseline and after 2-month vitamin D supplement. The record lists two outcome measures but posts no secondary results. It also posts no analysis records. The randomized design is relevant to interpreting a group comparison, but the registry does not provide enough detail to establish precisely how the primary outcome was summarized or which participants contributed to the reported comparison.

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: All had positive hepatitis B surface antigen (HBsAg) for more than 6 months. Those with positive anti-hepatitis C virus (HCV) antibody, other known causes of chronic hepatitis or receiving antiviral treatment currently were excluded. Those who had HBsAg loss, undetectable HBV DNA and adequate vitamin D level (≥30 ng/mL) were excluded.

Overall Study

Reasons for not completing this period:

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: Those who had HBsAg loss, undetectable HBV DNA and adequate vitamin D level (≥30 ng/mL) were excluded. The eligible subjects were randomized into two groups by using the computer random distribution.

6. Primary Endpoint

The registry lists the primary outcome as The Dynamic Change of HBV DNA, measured over baseline, after 2-month vitamin D supplement.

The primary endpoint is titled “The Dynamic Change of HBV DNA.” The record says serum HBV DNA levels were measured in CH-B patients before and after 2-month vitamin D supplement, and identifies IU/mL as the unit. HBV DNA is the laboratory measure selected to characterize viral replication in this trial. Comparing its values across the randomized groups addresses whether the posted outcome summaries differ between participants assigned to supplementation and those assigned to control.

The outcome is continuous, and the registry identifies the summary measure as a mean with standard deviation. A mean gives a measure of the group’s central value, while the standard deviation describes variation among the observations. These summaries can help describe the observed values, but they do not by themselves show how each participant changed from baseline.

Although the title emphasizes dynamic change and the timeframe names baseline and the period after supplementation, the posted arm summaries do not separately identify baseline values and follow-up values or explicitly label a change score. The record therefore does not make clear whether the reported mean difference compares follow-up values, changes from baseline, or another endpoint summary. That distinction matters because a comparison of follow-up values is not necessarily the same analysis as a comparison of within-person changes. The exact operational definition of the endpoint is not reported in the registry record.

7. Results Posted in the Registry

• Vitamin D Group: mean 3.15 versus 3.14 on control; difference 0.01 (95% CI -0.39 to 0.41), standardized effect d = 0.01; z-test p = 0.961.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous, and the registry reports group means and standard deviations. A mean summarizes the central location of a set of measurements. A standard deviation describes how dispersed measurements are around that mean. These summaries are useful for a simple group comparison, but they do not show the distribution’s full shape, whether there are outliers, or how values changed within individual participants.

The reported contrast is a mean difference: the vitamin D group mean minus the control group mean. The estimate is 0.01 IU/mL. The sign indicates the direction of the arithmetic contrast as reported, but its small magnitude relative to the uncertainty means the estimate should not be treated as a precise characterization of the true group difference. The record does not state whether this contrast is based on follow-up levels, individual changes, or a different definition of the primary endpoint.

A confidence interval gives a range of values that are reasonably compatible with the observed data under the statistical model and its assumptions. In repeated use of the same method, intervals constructed this way have a specified long-run coverage property. For an individual trial, the interval is best read as a measure of uncertainty around the estimate, rather than as a guarantee that the true effect lies inside it. The reported interval is -0.393 to 0.413 IU/mL. Because it crosses zero, it is consistent with a negative difference, no difference, or a positive difference within its limits.

The unadjusted p-value is 0.961. A p-value quantifies how unusual data at least as incompatible with the null hypothesis would be if that hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of the effect. “Unadjusted” indicates that the posted value is not described as adjusted for other variables or for multiple comparisons. The registry does not provide a fuller analysis specification, so details of the test and its assumptions are not reported in the registry record.

For a continuous outcome, a two-group mean comparison commonly relies on assumptions about the observations and the sampling distribution of the estimate. General statistical considerations include whether observations are independent, whether the outcome distribution or sample size supports the approximation used, and whether the groups have substantially different variability. The posted standard deviations are 1.14 and 1.36. The registry does not report diagnostic checks, a robust analysis, or a method for handling departures from assumptions. If measurements are highly skewed or contain influential extreme values, a mean and standard deviation may not fully characterize the data; that is a general consideration, not a finding about this trial.

Repeated measurements require an additional distinction. If the scientific target is change from baseline, an analysis might compare participant-level change scores or model measurements across time while accounting for their within-person relationship. These approaches answer related but not identical questions. The registry identifies a baseline and after-2-month timeframe, but it does not describe the analysis used to account for the repeated measurements. No separate baseline or follow-up means are posted in the primary outcome summary. Consequently, the displayed contrast should not automatically be interpreted as a direct estimate of within-person change.

Randomization can support a fair comparison by balancing prognostic factors on average across assigned groups, but it does not remove uncertainty or guarantee that every characteristic is balanced in a particular trial. The record identifies randomized allocation, but details of sequence generation and concealment are not reported in the registry record. The registry also lists no masking. Knowledge of assignment can affect behavior, follow-up, or assessment in some settings; whether it influenced this outcome is not established by the record.

The posted group sizes are 75 and 74. The registry does not explain whether all randomized participants were included in the primary analysis, whether the analysis followed assigned groups, or how missing measurements were treated. Those details matter because excluding participants or analyzing only complete measurements can alter the target comparison and introduce bias under some conditions. No participant flow or missing-data analysis is posted in the material summarized by the registry outcome record.

The record lists two outcome measures, but no secondary results, and it lists no analysis records. The analysis plan, covariate adjustments, treatment of multiple outcomes, and prespecified handling of interim analyses are not reported in the registry record. It is therefore not possible to determine from the registry whether the posted comparison represents the sole prespecified primary analysis or whether other analyses were conducted. General principles such as prespecifying the outcome definition and analysis help reduce selective interpretation, but the record does not document those details for this trial.

10. Confidence Intervals and Precision

The confidence interval for the mean difference is -0.393 to 0.413 IU/mL, around a point estimate of 0.01 IU/mL. This interval communicates uncertainty more fully than the point estimate alone: it shows a span of values compatible with the posted data and analysis under the method’s assumptions. Since zero is within the interval, the result does not distinguish clearly between a difference in one direction, no difference, and a difference in the other direction.

The interval is not a statement that every value inside it is equally likely, and it does not assign a probability to the true effect. It is also not a range for individual participants’ HBV DNA values. It concerns uncertainty in the estimated difference between group means. The group standard deviations, 1.14 and 1.36, describe variation among observations, which is a different kind of uncertainty from the confidence interval for the contrast.

Precision depends on the amount and variability of the data and on the analysis. Although the posted group sizes are 75 and 74, the registry does not report details such as missing outcome measurements, the exact endpoint calculation, or the statistical model. Those omissions make it harder to assess all sources of uncertainty. In particular, the title and timeframe refer to change from baseline, while the posted result does not clearly identify whether it is a change comparison or a comparison of values at a particular time.

The interval should be interpreted alongside the outcome’s clinical meaning. The registry does not report a threshold for a meaningful difference in HBV DNA, so the interval alone cannot determine whether its values would be clinically important. It quantifies statistical uncertainty for the posted mean difference; it does not settle the practical significance of that difference.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. They are participants per arm for 80% power and participants per arm for 90% power; they are not total event counts. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect.

At 100% of the observed effect, the illustration gives 246,884 participants per arm for 80% power and 330,507 participants per arm for 90% power. At 75% of the observed effect, it gives 438,904 participants per arm for 80% power and 587,568 participants per arm for 90% power. At 50% of the observed effect, it gives 987,534 participants per arm for 80% power and 1,322,027 participants per arm for 90% power. These figures are calculations under the stated planning assumptions, not observed trial enrollment targets.

In plain terms, the 80% power column describes the planned number per arm for a design with an 80% chance of detecting the specified effect under the assumptions if that effect is the true one. The 90% column describes the analogous planning target for a 90% chance. Higher target power generally requires more participants for a given effect and assumptions. Smaller effects also require more participants to distinguish them from random variation, as reflected by the increasing figures for the smaller fractions.

The observed trial enrolled 149 participants in total, with 75 in the vitamin D group and 74 in control. The planning figures should not be read as evidence about the trial’s observed power or as a retrospective verdict on its design. This is not observed power. The trial’s original sample-size assumptions and justification are not reported in the registry record. The curve is a planning display of the relationship between assumed effect size and sample-size requirements, not a plot of additional trial observations.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.010; pooled standard deviation σ = 1.254.
2. n = 2 × (1.96 + 0.842)² × 1.254² / 0.010² = 246,883.3, rounded up to 246,884 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.00999999999999979                      # observed difference in means
sigma <- 1.25408502570626                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3068767)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 246,884 (80% power), 330,507 (90% power)
 75% of observed effect: n per arm = 438,904 (80% power), 587,568 (90% power)
 50% of observed effect: n per arm = 987,534 (80% power), 1,322,027 (90% power)
power.t.test: 246884.2 
Simulated power at n = 246,884 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures but posts no secondary outcome results. It lists no analysis records. The primary comparison is reported with an unadjusted p-value of 0.961. The record does not state whether any adjustment for multiple outcomes or multiple analyses was planned or performed. Since the number and nature of analyses actually conducted are not detailed, the potential effect of multiplicity on interpretation cannot be assessed from the registry record.

Multiplicity is a general statistical concern when several outcomes, time points, subgroups, or analytic choices are examined. Each additional test can increase the chance of seeing an apparently notable result by chance if the testing strategy is not accounted for. That does not establish that such a problem occurred in this trial. It means that a clear prespecified analysis plan and complete outcome reporting are useful for judging how a result fits into the broader set of analyses. Those details are not reported in the registry record.

The record does not report the analysis population, such as whether the primary comparison included all randomized participants or only participants with available outcome measurements. It also does not describe how missing measurements were handled, whether any participants withdrew, or whether analyses followed assigned groups. These omissions matter because analysis choices can affect comparability and precision, particularly when outcome availability differs between groups or relates to participants’ outcomes.

The primary outcome timeframe names baseline and after 2-month vitamin D supplement, but the posted summary does not clearly identify the analysis as a change score or a follow-up comparison. The specific endpoint calculation and any adjustment for baseline values are not reported in the registry record. Without those details, the result cannot be fully connected to a defined repeated-measures analysis.

No interim analyses or stopping rules are described in the registry record. No subgroup analyses or sensitivity analyses are posted. These absences should be understood as limits of the registry information, not proof that such analyses were or were not undertaken. The available result supports interpretation of the posted comparison only, while broader conclusions about the analysis strategy remain uncertain.

14. 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 registry reports serious adverse events for 75 participants at risk in the vitamin D group and 74 in the control group. It lists 0 serious adverse events in each group and 0 deaths in each group. The top serious-event terms list is empty. These are the posted counts; the registry does not provide additional detail about definitions, event review, or the period over which safety was assessed.

For other adverse events, the registry lists 3 in the vitamin D group and 6 in the control group, with 75 and 74 participants at risk, respectively. These counts are not serious adverse events and should not be combined with the serious-event figures. The record does not provide event types or severity details for these other events, nor does it specify whether the counts refer to participants with an event or total event occurrences.

Zero reported serious adverse events does not establish that no harm is possible or that all potential harms were captured. It describes the registry entries for this study. The record’s safety figures should be read alongside their limited detail and the trial’s specific population, treatment period, and reporting scope.

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

The primary posted comparison describes a mean HBV DNA difference of 0.01 IU/mL between the vitamin D and control groups. The confidence interval ranges from -0.393 to 0.413, and the unadjusted p-value is 0.961. These statistics show that the recorded comparison does not provide clear evidence of a difference under its analysis, while the interval retains uncertainty about the size and direction of possible differences.

This result does not prove that the groups are identical. A failure to find statistical evidence of a difference is not equivalent to demonstrating that any difference is absent or too small to matter. The registry does not report a threshold for clinical importance, and the confidence interval includes a range of values on both sides of zero. The available statistics therefore do not establish the practical importance of the possible differences.

The record also does not clearly identify whether the reported contrast is based on HBV DNA at follow-up, change from baseline, or another summary. Although the registered outcome title refers to dynamic change and the timeframe includes baseline and the period after supplementation, separate measurements and a specific change analysis are not posted. The result should not be described as a definitive estimate of within-person change without that clarification.

The randomized design is relevant to the intended comparison, but the registry does not report allocation procedures, missing-data handling, or the analysis population. The lack of masking is recorded, while the consequences of that feature for outcome measurement are not established. No secondary results or analysis records are posted. Thus, the result is limited to the primary comparison as registered, rather than offering a full evaluation of all measured outcomes or possible analyses.

Nothing in these statistics alone answers broader questions about the biological relationship between vitamin D and HBV replication or establishes what an individual should do. The data describe a specific randomized comparison in HBV carriers with inadequate serum vitamin D levels, with a stated supplementation period of 2 months. Interpretations beyond that comparison would require evidence and details not reported in this registry record.

16. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can produce a point estimate close to zero while still leaving uncertainty about the plausible range of differences. The reported mean difference is 0.01 IU/mL, but its confidence interval extends from -0.393 to 0.413. Looking at the estimate and interval together is more informative than treating the p-value alone as a conclusion.

The p-value of 0.961 does not quantify the probability that there is no effect, and it does not measure the importance of an effect. The interval shows why a non-significant result should not automatically be interpreted as proof of equivalence: the record does not define an equivalence margin, and the interval includes values on either side of zero. A formal claim of equivalence would require a clearly specified margin and an analysis designed for that question, neither of which is reported in the registry record.

The trial also highlights the importance of aligning an outcome title, its timeframe, and its analysis. The registry names “The Dynamic Change of HBV DNA” and gives baseline and after-2-month timing, but the posted summary does not clearly specify whether the comparison is of follow-up values or changes. This distinction affects the scientific meaning of the estimate and the assumptions needed to interpret it.

Finally, sample-size planning depends strongly on the effect assumed to be worth detecting. The planning illustrations show substantially larger participant requirements when the target effect is a smaller fraction of the observed effect. Those calculations are separate from the trial’s original design, which is not reported in the registry record. Together, these features make the record useful for understanding uncertainty, endpoint definition, and planning assumptions without turning one comparison into a broader claim.

17. 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 main limitation of the posted result is uncertainty about the exact endpoint calculation. The outcome title refers to dynamic change, and the timeframe mentions baseline and after 2-month supplementation, but the arm summaries do not separately present baseline and follow-up values or identify a participant-level change measure. It is therefore unclear exactly what the mean difference represents.

The registry does not report detailed eligibility criteria, participant characteristics, allocation concealment, or the method used to generate the random sequence. It records no masking. The record does not establish whether these features affected the comparison, but their absence limits assessment of the trial’s conduct and the groups’ comparability.

The analysis population and missing-data procedures are not reported in the registry record. The posted group sizes do not by themselves establish how many participants had usable measurements at each time point or how incomplete outcome data were addressed. No analysis records, secondary results, or detailed statistical plan are posted, so covariate adjustment, model choice, and sensitivity analyses cannot be assessed.

The registry reports a mean and standard deviation for a continuous outcome, but does not describe the outcome distribution, diagnostic checks, or alternative methods. It also does not report a threshold for a clinically meaningful HBV DNA difference. The confidence interval can describe statistical uncertainty, but without a stated importance threshold it cannot resolve practical significance.

Safety reporting is limited to counts of serious and other adverse events and deaths. Event descriptions and further assessment details are not reported. These limits apply to what can be concluded from the registry record; they do not establish that additional data or analyses were not collected elsewhere.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: The Relationship Between Vitamin D and Hepatitis B Virus Replication — NCT03068767.
• Registry record last updated 2020-02-12; status last verified 2020-02.
• Results first posted 2020-02-12.
• 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.

21. Record Summary

The completed trial randomized 149 HBV carriers with inadequate serum vitamin D levels to a vitamin D group or a control group. The vitamin D group received 2000 IU/day for 2 months, while the control group received no vitamin D supplement. The registry describes a randomized, parallel-group design with no masking.

The primary outcome concerns serum HBV DNA in IU/mL, with a stated baseline and after-2-month timeframe. The posted group means are 3.15 for 75 participants in the vitamin D group and 3.14 for 74 participants in control. The mean difference is 0.01 IU/mL, with a confidence interval from -0.393 to 0.413 and an unadjusted p-value of 0.961.

The registry posts no secondary results or analysis records. The exact meaning of the reported comparison, missing-data handling, and analysis population are not reported in the registry record. Serious adverse events and deaths are recorded as 0 in both groups; other adverse events are listed as 3 and 6, respectively.