Evaluation of Rapid Virologic Response Among HCV Patients Treated With PegIntron and Rebetol in Brazil (Study P05427): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Rapid Virologic Response Among HCV Patients Treated With PegIntron and Rebetol in Brazil (Study P05427) (NCT00724854), a registered phase not stated study. The primary outcome is Number of Participants With Rapid Virologic Response After 4 Weeks of Treatment.

2. Clinical Question

The central statistical question is descriptive: what number of participants in each recorded group met the early response definition? The record also identifies a prognostic question, asking whether participants with rapid virologic response subsequently achieved sustained virologic response. Those questions should be distinguished. The first concerns an early measurement after treatment begins; the second concerns how that measurement relates to a later outcome.

The record reports enrollment of 1146 and lists chronic hepatitis C and hepatitis C as conditions. It describes groups based on HCV infection status, including co-infection with HIV. Because allocation is not stated and the groups differ in infection status, a contrast between their outcomes would not by itself estimate the effect of one treatment versus another. The record does not describe an untreated or alternative-treatment comparison group.

The primary outcome is named and defined, but its results are not reported in the registry record. Accordingly, the number of participants meeting the RVR definition in each group, and any statistical comparison of those numbers, cannot be described from the registry information. The prediction question is also not answered by the stated record results: the presence of secondary outcome titles does not provide the underlying results or an estimate of the relationship between RVR and SVR.

3. Trial Design

The registry identifies this as the APEGIN trial, a study of PegIntron and Rebetol in participants with hepatitis C. Its objective was to assess rapid virologic response after 4 weeks of treatment in each group and to assess whether RVR was a reliable predictor of sustained virologic response. The treatment components are listed as PegIntron (peginterferon alfa-2b; SCH 54031) and Rebetol (ribavirin; SCH 18908).

The registry record gives enrollment as 1146, a start date of 2006-08, primary completion as 2009-09, and status as completed. The named groups are mono-infected with HCV and co-infected with HCV and HIV. A group labelled not evaluated also appears in the adverse-event information. These are infection-status and evaluation categories; the record does not describe them as randomized treatment arms.

Allocation is not stated. The registry information therefore does not establish random assignment, concealment, or a treatment-control structure. It would be inappropriate to interpret differences between the HCV-only and HCV/HIV groups as causal treatment effects. These groups may differ in characteristics other than infection status, and the available record does not provide details needed to account for such differences.

The primary endpoint is the number of participants with RVR at treatment week 4, defined as HCV RNA negative after 4 weeks of treatment. Secondary outcome titles include SVR, SVR among participants with RVR, response at treatment week 48 for genotypes 2 and 3 and treatment week 72 for genotypes 1, 4, and 5 among participants with RVR, and baseline characteristics among participants with SVR. The registry lists 5 outcome measures, but the results and analytical details for those outcomes are not reported in the registry record.

The record lists no analyses. It does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. Those elements cannot be reconstructed from the study objective or outcome descriptions.

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:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Rapid Virologic Response After 4 Weeks of Treatment, measured over Assessed at Treatment Week 4.

The primary endpoint is the number of participants with rapid virologic response at treatment week 4. RVR is defined in the registry as a negative HCV RNA result after 4 weeks of treatment. This is a binary outcome for each participant: the definition is either met or not met. The endpoint is expressed as a count of participants, rather than as a continuous measurement such as the amount of change in viral load.

An early virologic measure can be useful in a study because it describes response at a specified time during treatment. The registry's objective goes beyond counting early responses: it also asks whether RVR is a reliable predictor of SVR. In the record, SVR is defined as undetectable viral load at 24 weeks post-treatment. Prediction requires examining how early response status relates to the later outcome; simply reporting the number with RVR does not establish predictive accuracy.

The primary endpoint title and definition do not include a reported result. The registry record therefore does not give the number meeting the RVR definition in either infection-status group, the proportion meeting it, or an uncertainty estimate. No conclusion about the frequency of early response can be drawn from the endpoint description alone.

For a binary endpoint, counts are most informative when interpreted with their relevant denominators and with a clear definition of which participants were assessed. Those outcome-specific details are not reported in the registry record. The adverse-event denominators are not a substitute for endpoint denominators, because they pertain to safety information rather than the primary efficacy outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: each participant either met the RVR definition or did not. For binary outcomes, a basic summary can include the number meeting the definition and the number assessed. A proportion can also be useful because it relates the event count to its denominator. The registry gives the endpoint definition but does not report its result or outcome-specific denominator, so neither a count nor a proportion can be interpreted from the record.

What does a confidence interval describe?

General explanation: a confidence interval expresses the uncertainty around an estimate under a statistical model and its assumptions. For a proportion, an interval helps show how precisely the underlying proportion is estimated from the observed participants. A narrow interval indicates greater precision than a wide interval, but an interval does not remove possible bias from participant selection, measurement, missing data, or study design. No confidence interval for RVR or SVR is reported in the registry record.

What would be needed to assess prediction?

General explanation: assessing an early measure as a predictor of a later outcome requires paired information: each participant's RVR status and later SVR status. Such data can describe how often participants with early response later had SVR, and how often those without early response later had SVR. Measures of predictive performance can summarize different aspects of this relationship. They answer a different question from the overall frequency of RVR. The registry identifies the prediction objective but does not report the paired results or analyses needed to assess it.

The secondary outcome titles refer to SVR, SVR among participants with RVR, and responses at specified treatment weeks for genotype groups. Those titles indicate planned or registered outcome concepts, not statistical results. The record does not report estimates, uncertainty intervals, test results, or analysis populations for them. Without these details, neither the direction nor the precision of any outcome relationship can be described.

Why does allocation matter?

General explanation: random allocation can support a causal comparison by balancing, on average, characteristics other than the assigned intervention. Observational or nonrandomized group comparisons may instead reflect both the group definition and other differences among participants. Here, the recorded categories distinguish mono-infection from HCV/HIV co-infection, and allocation is not stated. These categories are not a like-for-like control comparison. The record does not establish that a comparison between them isolates the effect of treatment or any treatment component.

The record lists equal-allocation and normal-approximation assumptions for planning illustrations, along with a two-sided significance level of 0.05 and an effect defined as a stated fraction of the observed effect. Such assumptions describe a planning exercise, not the trial's observed treatment effect and not observed power. The record does not report the trial's own sample-size justification. The illustration cannot be used to infer how the study was designed or whether it was adequately powered for its registered outcomes.

How should a p-value be read?

General explanation: a p-value is a measure of how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that a hypothesis is true, nor a measure of clinical importance. A p-value alone does not describe effect size or precision. The registry record lists no analyses and reports no p-values, so there is no test result to interpret for the primary endpoint.

Over-dispersion is a general concern when counts vary more than a statistical model expects. A model that assumes less variability than the data contain can produce uncertainty estimates that are too small. This issue is most relevant to count outcomes modeled with a distributional assumption; it is not possible to assess over-dispersion for the RVR endpoint from the registry description alone. The endpoint is a count of participants meeting a binary definition, and the record does not provide model details or outcome data.

Multiplicity concerns arise when many outcomes, groups, or statistical tests are considered. In general, testing several hypotheses can increase the chance that at least one result appears noteworthy by chance. The presence of several registered secondary outcomes makes the analysis plan and any approach to multiplicity relevant, but neither the plan nor any multiplicity adjustment is reported in the registry record. No confirmatory interpretation of secondary findings can be made without those details and the actual results.

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("Mono-infected With HCV", "Co-infected With HCV and HIV")
n      <- c(1010, 72)
events <- c(551, 32)
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  Mono-infected With HCV  1010  551  54.6  51.4  57.7  51.5  57.6  51.5  57.6
ARM  Co-infected With HCV and HIV  72  32  44.4  32.7  56.6  33.5  55.9  33.5  55.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including the primary RVR endpoint and secondary outcomes addressing SVR, SVR among participants with RVR, responses at treatment week 48 or 72 for specified genotype groups, and baseline characteristics among participants with SVR. Considering multiple outcomes can raise multiplicity concerns. General explanation: when many hypotheses are tested, the chance of at least one apparently unusual result can increase, so a prespecified analysis plan may identify which outcomes are confirmatory and whether adjustments are intended. The statistical plan and any multiplicity approach are not reported in the registry record.

The record reports no analyses. It does not state whether any interim analyses were conducted, and does not give rules for stopping or adjusting analyses. These details are not reported in the registry record; their absence should not be filled in by assumption.

The registry does not describe missing-data handling, outcome-specific analysis populations, or the number of participants assessed for RVR and SVR. It does not state whether the analyses used all enrolled participants, a subset with available measurements, or another defined population. The group denominators listed for adverse events do not establish the denominators used for efficacy outcomes. Missingness can affect both the estimated event frequency and the interpretation of participant-level prediction, especially if availability of later outcome measurements differs according to earlier response or participant characteristics.

Because outcome results and analysis populations are unavailable, it is not possible to judge whether missing data altered the reported estimates, whether sensitivity analyses were conducted, or how secondary outcomes were handled. These reporting gaps limit assessment of both statistical robustness and the reach of any intended conclusions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (3.1%), depression (3.1%), pancytopenia (1.6%), abdominal pain (1.6%), ascites (1.6%).

The safety record lists serious adverse events by participant group. In the mono-infected HCV group, 52 of 1010 participants were recorded as having a serious adverse event. In the co-infected HCV and HIV group, the figure is 0 of 72. In the not-evaluated group, it is 8 of 64. These counts should be read with their stated denominators, not as standalone measures of risk.

The record also lists other adverse events affecting 762 of 1010 participants in the mono-infected group, 61 of 72 in the co-infected group, and 42 of 64 in the not-evaluated group. Serious and other adverse-event counts describe separate reporting categories in the registry information; the counts should not be added together because the record does not establish that the categories are mutually exclusive.

Listed serious-event terms include DIARRHOEA and DEPRESSION at 3.1% each, and PANCYTOPENIA, ABDOMINAL PAIN, ASCITES, and VOMITING at 1.6% each. The record does not provide further denominators or participant-level detail for these term percentages. A reported percentage for an event term should not be assumed to represent a risk comparison between groups.

These are descriptive safety figures, not evidence of a comparative treatment effect. Group composition, follow-up, and the relation of the event figures to treatment exposure are not fully described in the registry record. Death counts are not reported in the registry record.

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

The registry record establishes that the trial aimed to count RVR after 4 weeks of treatment with PegIntron and Rebetol, using a negative HCV RNA result as the definition. It also states an objective of assessing whether RVR predicts SVR, defined as undetectable viral load at 24 weeks post-treatment. Those definitions clarify the intended questions, but they do not answer them.

The record does not report how many participants achieved RVR, how many achieved SVR, or how early and later outcomes were associated. It also does not report estimates of uncertainty or statistical test results. Therefore, no conclusion about the observed frequency of RVR, the precision of that frequency, or the predictive value of RVR can be drawn from the available registry results.

The record's groups are defined by infection status, and allocation is not stated. A difference between mono-infected and co-infected participants would not constitute a randomized treatment comparison. Any apparent difference could reflect the population categories or other participant differences, and the registry does not provide analyses that would resolve that issue. The available information does not support a causal claim about the medicines relative to an alternative treatment or no treatment.

The safety counts describe reported adverse events in the listed groups. They do not by themselves establish comparative safety, and the event-term percentages cannot be interpreted as comparative risks without additional denominator and analysis details. The completed study status indicates completion as recorded, but does not supply missing primary or secondary outcome results.

In general, statistical interpretation depends on the outcome estimate, its uncertainty, the analysis population, and the design used to obtain the comparison. For this trial, the registry provides endpoint definitions, study-group descriptions, selected safety counts, and planning assumptions, but not the efficacy estimates or analytical information needed for a fuller assessment. The meaning of the record is therefore limited to the study's stated aims and reported descriptive information.

14. Why This Trial Matters Statistically

This trial is statistically notable because it links an early binary response measure to a later outcome. These are related but distinct questions: how many participants meet the early definition, and how informative that early status is about a later response. The distinction matters whenever an early marker is presented as a potential predictor. Counts at the early time point alone cannot establish the marker's predictive performance.

The design information also illustrates why group labels must be interpreted carefully. The registry describes mono-infection and HCV/HIV co-infection groups, not randomized treatment assignments. Since allocation is not stated, the groups cannot be treated as interchangeable arms in a controlled treatment comparison. Clear description of the population and comparison structure is essential before drawing causal conclusions from observed differences.

The record's safety information reinforces the importance of denominators and subgroup context. Serious adverse-event counts are reported alongside group-specific numbers at risk, but the registry does not provide a randomized comparator or enough detail to establish how comparable the groups are. Descriptive counts can document what was recorded without establishing why events occurred or whether rates differ because of treatment.

Finally, the record shows the gap between registered questions and assessable statistical results. Outcome definitions and secondary outcome titles do not substitute for estimates, uncertainty intervals, analysis populations, and analysis methods. Without these, readers cannot judge precision, assess the RVR-to-SVR relationship, or evaluate multiplicity and missing-data handling. The trial is therefore a useful example of why statistical interpretation depends not only on naming outcomes, but also on complete reporting of results and design.

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 main limitation of the registry information is that it does not report the primary RVR result or analyses. Although the endpoint is defined as a count at treatment week 4, the number meeting the definition, its denominator, and any uncertainty estimate are not reported in the registry record. The same limitation applies to the secondary outcomes: their titles are listed, but outcome estimates and analyses are not.

Allocation is not stated. The named groups differ by HCV infection status, and the registry does not present them as randomized intervention groups. They therefore cannot be interpreted as a like-for-like control comparison. The record does not provide enough detail to assess possible group differences or how such differences were handled analytically.

The record does not report analysis populations, missing-data methods, a statistical analysis plan, multiplicity handling, or interim analyses. It also does not report the trial's own sample-size justification. The planning assumptions listed in the record are illustrations and do not fill these gaps or establish observed power.

The safety information includes group-specific serious and other adverse-event counts, but it does not provide enough detail to assess comparability of follow-up or event ascertainment between groups. The listed serious-event term percentages lack further denominator and participant-level context in the record. Death counts are not reported in the registry record.

These limitations concern what can be learned from the registry record; they do not establish that particular analyses or study procedures were absent. Where details are unavailable, they are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Rapid Virologic Response Among HCV Patients Treated With PegIntron and Rebetol in Brazil (Study P05427) — NCT00724854.
• Registry record last updated 2015-02-25; status last verified 2015-02.
• Results first posted 2011-01-10.
• 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

The registry record describes the completed APEGIN trial of PegIntron and Rebetol in participants with hepatitis C, with enrollment of 1146. The primary objective was to count rapid virologic responses after 4 weeks of treatment, with RVR defined as negative HCV RNA. A further objective was to assess whether RVR predicted sustained virologic response, defined as undetectable viral load at 24 weeks post-treatment.

The recorded groups distinguish participants mono-infected with HCV from those co-infected with HCV and HIV. Allocation is not stated, and the groups are not a like-for-like control comparison. The registry record lists secondary outcomes and descriptive safety counts, but reports no analyses and does not report the primary or secondary efficacy results. Statistical conclusions about RVR frequency, the RVR-SVR relationship, or comparative treatment effects are therefore not available from this record.