A Study of Peginterferon Alfa-2a (40KD) (PEGASYS®) in Participants With Hepatitis B Envelope Antigen (HBeAg) - Positive Chronic Hepatitis B: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Peginterferon Alfa-2a (40KD) (PEGASYS®) in Participants With Hepatitis B Envelope Antigen (HBeAg) - Positive Chronic Hepatitis B (NCT00436163), a na phase 4 study. The primary outcome is Number of Hepatitis B Envelope Antigen (HBeAg) Positive Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) Less Than (<) 1,00,000 Copies Per Milliliter (Copies/mL).

2. Clinical Question

3. Trial Design

This is a completed phase 4 study registered as NCT00436163. Its title concerns peginterferon alfa-2a in participants with HBeAg-positive chronic hepatitis B; the official title refers to a Baltic post-marketing program in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B. The brief summary describes an evaluation in treatment-naive Baltic participants with HBeAg-positive chronic hepatitis B. The registry lists 39 participants as enrolled.

The design is single-group, with allocation listed as NA and masking listed as none. Participants received peginterferon alfa-2a 180 mcg subcutaneously once per week for 48 weeks. The study summary describes a 24 week period without treatment after the treatment period. The primary outcome is measured at Week 72. The brief summary also states that anticipated time on study treatment was 3-12 months; the regimen description separately specifies 48 weeks of treatment.

The record gives a study start of 2007-03 and primary completion of 2010-05, and lists the overall status as completed. Hoffmann-La Roche is listed as sponsor. A single-group design can describe outcomes among participants who received the intervention, but it does not supply a concurrent control outcome. Differences between participants who do and do not meet an outcome cannot, by themselves, establish what would have happened under another treatment or without treatment.

The registry lists 8 outcome measures and 0 analyses. It does not report a randomized allocation, a comparator arm, or masking. Details of a protocol-defined statistical analysis plan, including any prespecified adjustments or interim analyses, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least 1 dose of peginterferon alfa-2a. Here, Number of participants analyzed = participants who were HBeAg positive at baseline.

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: All enrolled participants who received at least 1 dose of peginterferon alfa-2a.

6. Primary Endpoint

The registry lists the primary outcome as Number of Hepatitis B Envelope Antigen (HBeAg) Positive Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) Less Than (<) 1,00,000 Copies Per Milliliter (Copies/mL), measured over Week 72.

The primary endpoint is the number of baseline HBeAg-positive participants whose HBV-DNA was below 1,00,000 copies/mL at Week 72. The record defines baseline HBeAg-positive participants as those with HBV-DNA greater than 1,00,000 copies/mL at baseline. The endpoint therefore describes how many participants in that baseline subgroup met the stated HBV-DNA threshold at the specified follow-up time.

A count is useful for conveying how many people in the analyzed group met a defined outcome. It is not, on its own, a rate or proportion: interpretation as a proportion would require the corresponding analysis denominator. The registry says that the primary outcome population includes enrolled participants who received at least 1 dose, with the number analyzed restricted to participants who were HBeAg-positive at baseline. That subgroup's size is not reported in the registry record.

As a general statistical point, a biologically or clinically defined threshold turns a continuous measurement into a binary classification: each participant is counted as meeting or not meeting the threshold. This can make a result straightforward to interpret against the specified cutoff, but it discards information about how far individual measurements lie from that cutoff. The registry record does not report the primary endpoint count, so it is not possible to describe the observed outcome or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and lists the primary outcome as a number of participants. It does not report a statistical analysis method, an estimate of uncertainty, or an inferential test for that outcome. The explanations below distinguish the design information in the registry from general statistical principles.

What does a count measure?

The primary endpoint counts participants who satisfy a binary condition: HBV-DNA below 1,00,000 copies/mL at Week 72 among participants who were HBeAg-positive at baseline. A count is the number of people meeting the condition. To understand how common the outcome was within the analyzed group, readers also need the number of people evaluated. A count without that denominator cannot be interpreted as a proportion. The record specifies that the primary population was limited to baseline HBeAg-positive participants who received at least 1 dose, but does not report the size of that subgroup or the endpoint count.

In general, binary outcomes simplify a measurement into two categories, such as meeting or not meeting a threshold. This can be helpful when the cutoff is meaningful to the study question. It also loses detail: participants just above or below the threshold are categorized differently, even if their measurements are close, while participants with very different values on the same side of the cutoff are grouped together.

Why does the study design matter?

In a single-group study, outcome summaries describe the observed participants. A treatment-versus-control effect ordinarily requires a contrast between outcomes in groups that represent the alternative conditions being compared. This record lists no comparator arm and no random allocation. Therefore, even if the outcome count were available, it would not by itself estimate how outcomes would differ under another treatment or no treatment.

General statistical methods can quantify uncertainty around an outcome estimate, but they cannot correct the absence of a comparison group. A confidence interval around a single-group proportion, for example, would reflect sampling uncertainty under its assumptions; it would not account for all possible differences between this group and an unobserved alternative group. No such interval is reported for the primary outcome in the registry record.

What do the sample-size assumptions describe?

The planning illustration assumptions are described as a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They refer to an effect expressed as a stated fraction of the observed effect. The record specifies that these are planning illustrations computed from the observed effect, not the trial's own design. In general, such illustrations ask how many participants might be needed under selected assumptions for a hypothetical comparison. They are not evidence that the original study was designed that way and are not observed power.

The illustrations are described as reporting participants per arm for non-time-to-event outcomes, while time-to-event calculations use a total number of events under a Schoenfeld approach. These are general planning conventions, not descriptions of the single-group trial design. The registry record does not report the trial's sample-size justification or a two-arm allocation plan. The observed effect used for any illustration, and the resulting planning values, are not reported in the record.

What can be inferred from the reported analysis information?

The registry lists 0 analyses. That does not establish that no analyses were conducted; it means the record does not list analysis entries. The statistical plan, treatment of missing measurements, and any method for handling multiple outcomes are not reported in the registry record. Without those details, it is not possible to determine whether analyses followed a prespecified plan or how any particular estimate was obtained.

General statistical practice distinguishes prespecified primary analyses from additional analyses, because choices made after results are known can affect interpretation. Likewise, an analysis population should be defined in advance and described clearly. Here, the primary endpoint population is partly specified by receipt of at least 1 dose and baseline HBeAg-positive status, but the analyzed number and missing-data handling are not reported. These omissions limit reproducibility and make it harder to assess how representative the endpoint result would be of all enrolled participants.

Multiplicity refers generally to the interpretive challenge created when several outcomes or statistical tests are examined. This record lists 8 outcome measures, including the primary endpoint and secondary outcome topics, but does not report a multiplicity strategy. The presence of multiple outcomes does not establish that a particular adjustment was required or performed; the analysis plan is not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Peginterferon Alfa-2a")
n      <- c(22)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Peginterferon Alfa-2a  22  6  27.3  10.7  50.2  13.2  48.2  13.2  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and identifies a primary endpoint alongside secondary outcomes. The secondary topics include HBV-DNA below 400 copies/mL, HBsAg-negative status, anti-HBs-positive status, mean ALT concentrations, HBeAg-negative status, and anti-HBe-positive status. The registry lists 0 analyses. It does not report whether the outcomes were tested as a family, whether any adjustment for multiple comparisons was planned, or how multiple analyses were prioritized. Those details are not reported in the registry record.

As a general statistical concept, when many outcomes or hypotheses are assessed, the chance of finding at least one apparently notable result can increase. Strategies for addressing multiplicity depend on the study objectives and analysis plan. The list of outcomes alone does not show which methods, if any, were used, and the absence of a reported analysis entry should not be taken as proof that no analysis occurred.

The primary population is described as all enrolled participants who received at least 1 dose, with the number analyzed defined as participants who were HBeAg-positive at baseline. The registry does not give that number, the number with a Week 72 measurement, or the number excluded from the endpoint analysis. It also does not report whether missing measurements were imputed, treated as failures, or handled by another method. No particular missing-data method should be inferred.

These gaps make it difficult to assess the endpoint denominator, the possible impact of missing follow-up, or consistency between the stated analysis population and the participants contributing data. Clear reporting of analysis populations, missing-data procedures, and multiplicity plans would support interpretation; those 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.

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 lists 39 participants at risk for serious adverse events in the peginterferon alfa-2a group and 0 participants affected by serious adverse events. It lists 39 participants at risk for other adverse events and 15 affected. These are counts as recorded; no percentages are calculated. The record does not list any top serious adverse event terms.

As a general reading principle, the number at risk gives the group size used for the safety summary, while the number affected counts participants with the event category. The serious and other adverse event figures are separate summaries and should not be added together. The record does not provide event-level detail for the 15 participants affected by other adverse events, so their types, severity, timing, and overlap cannot be described from this information.

The registry's serious adverse event count is a reported summary for this group. It does not establish that no serious events occurred outside the reporting definitions or observation window, and the record does not provide further detail about ascertainment or follow-up for safety. As this is a single-group study, these counts do not provide a comparison of safety outcomes against another treatment group.

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

The record establishes that this completed phase 4 study enrolled 39 participants and used a single-group design in which participants received peginterferon alfa-2a. It defines a primary outcome based on the number of baseline HBeAg-positive participants with HBV-DNA below 1,00,000 copies/mL at Week 72. It also gives counts for participants affected by serious and other adverse events.

The primary outcome result is not reported in the registry record. Neither the endpoint count nor the size of the baseline HBeAg-positive analysis subgroup is available. The record therefore does not support a statement about how many participants met the endpoint, what proportion met it, or how precisely that outcome was estimated. Secondary outcome results are also not reported in the record.

Even if a primary outcome count were available, the single-group design would describe outcomes in the treated participants rather than provide a direct treatment comparison. There is no concurrent control group listed, and the record lists allocation as NA and masking as none. A difference from baseline, or an outcome observed at follow-up, would not alone establish what would have occurred under another treatment or without treatment.

General statistical interpretation distinguishes an observed outcome from a causal treatment effect. Causal comparisons depend on design and assumptions about how groups represent the alternative conditions. A single-group outcome can be useful as a description of participants and as part of a broader evidence base, but it cannot alone isolate the effect of treatment from other explanations.

The safety counts should likewise be read descriptively. The record reports 0 participants affected by serious adverse events and 15 affected by other adverse events among the listed groups of 39 at risk. Without a comparator, event-level details, and fuller reporting of the safety observation process, those counts do not quantify comparative safety. No medical recommendation follows from these registry summaries.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a registry can specify an outcome and population while leaving the result and analysis details unavailable. The primary outcome has a defined measurement threshold and time point, and the record identifies a baseline subgroup. Those details establish what the endpoint was intended to count. Yet without the numerator and denominator, readers cannot estimate the frequency of the outcome or assess its precision.

The single-group design also illustrates the difference between describing an observed outcome and estimating a comparative effect. A group outcome can answer what was observed among those participants, if results are reported. It cannot, by itself, show how that outcome differs from what would have occurred in a comparison condition. Recognizing this distinction prevents an outcome description from being interpreted as a treatment contrast.

The record also shows why analysis-population reporting matters. The enrolled group contains 39 participants, while the primary endpoint is restricted to those who received at least 1 dose and were HBeAg-positive at baseline. Reporting the number meeting those criteria and the number with endpoint data would make the denominator transparent. The registry does not report these counts.

Finally, the outcome list raises general questions about multiplicity, and the limited analysis entries leave the statistical plan unclear. Reporting how multiple outcomes, missing data, and analysis populations were handled would make results easier to evaluate and reproduce. The available record supports careful interpretation of the design and endpoint definition, while the missing outcome and methods information limits further statistical conclusions.

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 primary limitation for interpretation is that the primary endpoint result is not reported in the registry record. The endpoint denominator is also unavailable: the record does not state how many participants were HBeAg-positive at baseline, how many received at least 1 dose, or how many had data at Week 72. Although 39 participants were enrolled, that figure should not be assumed to be the analysis population.

The single-group design has no concurrent control, and the registry lists allocation as NA and masking as none. It therefore cannot provide a direct comparison of outcomes between treatment and a control condition. The record does not report how baseline measurements, follow-up measurements, or other factors were handled in any analysis.

Further details of statistical methods are limited. The registry lists 0 analyses, and does not report a statistical analysis plan, confidence intervals, hypothesis tests, interim analyses, or a sample-size justification. It also does not report how missing endpoint data were handled or whether any multiplicity strategy was used for the 8 outcome measures. These elements should not be inferred from the stated outcome definitions.

The official title refers to a program involving both HBeAg-positive and HBeAg-negative chronic hepatitis B, while the brief summary describes treatment-naive Baltic participants with HBeAg-positive disease and the primary endpoint focuses on baseline HBeAg-positive participants. The record does not provide additional participant characteristics or results that would clarify the analyzed population beyond those descriptions. The safety summaries give counts but no serious event terms and no details about the other adverse events. These reporting limits constrain what can be concluded from the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Peginterferon Alfa-2a (40KD) (PEGASYS®) in Participants With Hepatitis B Envelope Antigen (HBeAg) - Positive Chronic Hepatitis B — NCT00436163.
• Registry record last updated 2016-10-24; status last verified 2016-08.
• Results first posted 2016-10-24.
• 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

NCT00436163 is a completed phase 4, single-group study sponsored by Hoffmann-La Roche. The registry lists 39 participants enrolled, a study start of 2007-03, and primary completion of 2010-05. The brief summary describes treatment-naive Baltic participants with HBeAg-positive chronic hepatitis B receiving peginterferon alfa-2a 180 mcg subcutaneously once per week for 48 weeks, followed by a 24 week treatment-free follow-up.

The primary outcome is the number of baseline HBeAg-positive participants with HBV-DNA below 1,00,000 copies/mL at Week 72. The result and analysis denominator are not reported in the registry record. The registry lists 8 outcome measures and 0 analyses. In the safety summary, 0 of 39 participants were affected by serious adverse events, and 15 of 39 were affected by other adverse events. No control group is listed, so outcomes are descriptive rather than comparative.