Relapse Rate in Hepatitis C Patients Treated With Peginterferon Alfa-2b Plus Ribavirin in Common Clinical Practice in France (P05484)(Completed): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Relapse Rate in Hepatitis C Patients Treated With Peginterferon Alfa-2b Plus Ribavirin in Common Clinical Practice in France (P05484)(Completed) (NCT00725842), a registered phase not stated study. The primary outcome is Number of Participants With Positive Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) at 24 Weeks Off-treatment.

2. Clinical Question

The study also aimed to identify factors predictive of relapse. Listed secondary outcomes include relapse among participants with rapid, early, or slow virologic response; assessment of pretreatment risk factors among participants with sustained virologic response; and positive HCV RNA at 72 weeks off treatment. The registry record does not report results for these questions.

3. Trial Design

This was a post-treatment follow-up study of participants previously treated with peginterferon alfa-2b plus ribavirin according to common clinical practice in France. The treatment had been completed before participants enrolled. The described treatment was first-line therapy, and the end-of-treatment duration was 24 or 48 weeks according to product labeling.

The registry describes a single treated group, not a randomized comparison. An allocation method is not stated, and the record does not describe a concurrent control group. The study can therefore describe outcomes in the selected treated population, but the design as recorded does not support a direct comparison of treatment strategies.

The registry lists an enrollment of 97. Its primary-outcome population description states that 7 participants were excluded from analysis because of protocol violations and that 90 underwent HCV-RNA testing at Week 24 after the end of treatment. The record does not explain the specific violations or provide additional participant-flow details.

The registry start is 2009-01 and primary completion is 2011-06. The title includes “Completed,” while the recorded study status is TERMINATED. The record does not explain this difference or give further information about the termination.

The study objective included identifying predictive factors, but the registry record does not report which factors were assessed, how they were modeled, or what analysis plan was used. It also does not report a sample-size justification for the original study. Consequently, the design description supports interpretation of the follow-up question and population, but not reconstruction of unreported design or analysis decisions.

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: Of the 97 participants who started the study, 7 were excluded from analysis because of protocol violations. 90 participants underwent HCV-RNA testing at Week 24 post EOT.

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 Positive Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) at 24 Weeks Off-treatment, measured over 24 weeks post end of treatment (EOT).

The primary endpoint is the number of participants with positive hepatitis C virus RNA at 24 weeks after the end of treatment with peginterferon alfa-2b plus ribavirin. RNA was measured by polymerase chain reaction. Under the registry definition, participants with positive HCV RNA at that follow-up were considered to have relapsed. The endpoint is therefore a binary status for each participant at a specified post-treatment assessment, reported as a participant count.

This endpoint is used to operationalize relapse after an end-of-treatment negative result. It asks whether detectable viral RNA is present at the defined follow-up, rather than measuring change in symptoms or comparing assigned treatments. The endpoint’s interpretation depends on the population being assessed: it concerns participants described as having negative HCV RNA at the end of treatment, not every person who might receive the treatment.

The registry record states that 90 participants underwent the Week 24 test after 7 exclusions from the 97 who started the study. However, it does not report how many of those tested had positive HCV RNA. The primary outcome count and the corresponding relapse rate are therefore not reported in the registry record, and no rate can be inferred from the testing denominator alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the endpoint counts. The registry describes the primary outcome as a number of participants, with each tested participant classified according to HCV RNA status at 24 weeks after the end of treatment. This is a binary outcome at a defined follow-up: positive or not positive. In general, a count can be paired with a denominator to describe the proportion experiencing an event. Here, the testing population is described as 90 participants, but the positive count is not reported in the registry record. A proportion or relapse rate therefore cannot be reconstructed from the record.

Why the follow-up definition matters. The endpoint is conditional on the participant having negative HCV RNA at the end of treatment, as described in the study population. It measures a later positive result, not persistent positivity during treatment. The timing and status definition are part of the outcome itself. In general, changing the assessment time or the population considered at risk can change the interpretation of a relapse measure. The registry specifies the primary assessment at 24 weeks after treatment, while a listed secondary outcome concerns positive HCV RNA at 72 weeks off treatment.

Descriptive estimates and uncertainty. In general, a confidence interval expresses the uncertainty around an estimated quantity, such as an event proportion. A narrow interval indicates greater precision under the method used; a wide interval indicates less precision. A point estimate alone does not show that uncertainty. The registry record does not report a primary relapse estimate or confidence interval, so neither the event frequency nor its precision can be evaluated from the posted primary outcome information. No p-value for the primary outcome is reported either.

Predictive-factor analyses. The study objective includes identifying factors predictive of relapse, and the secondary outcomes refer to response categories and pretreatment risk factors. In general, such analyses may estimate how outcomes vary across participant characteristics or assess several characteristics together. Their interpretation depends on the variables selected, their definitions, the model form, the amount of outcome information, and how missing observations are handled. The registry record does not report the specific factors, statistical model, estimates, or model diagnostics. It is therefore not possible to assess the strength, precision, or reliability of any predictive findings from this record.

Prediction and causation are different statistical questions. A factor may help distinguish participants with different observed outcomes without being a cause of those outcomes. A predictive association in this treated cohort would also not establish that an intervention on the factor would change relapse risk. Those broader conclusions require a design and analysis suited to causal inference; no such comparative analysis is described in the registry record.

Comparison and allocation. No randomized treatment comparison is described, and allocation is not stated. The record identifies a treated group rather than like-for-like treatment arms. Consequently, comparisons between treatment strategies are not supported by the design information recorded. General methods for comparing groups require an appropriate comparator and attention to differences in participant characteristics, treatment selection, and follow-up. The registry does not report such a comparison for the primary question.

Planning calculations. General sample-size illustrations are planning exercises, not findings about participants and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; the effect to detect is defined as a fraction of the observed effect. These assumptions do not describe a randomized design in this registry record, which has no like-for-like control comparison. The record does not report the study’s own sample-size justification. No planning illustration can substitute for the unreported primary outcome or establish how precise the observed result was.

What is and is not documented. The registry specifies the PCR-based outcome definition and the follow-up time, as well as the number of participants tested for the primary assessment. It does not report the primary event count, inferential estimates, analysis model, or analysis plan. General statistical explanations can clarify what such methods would mean, but they cannot recover unreported methods or results. Interpretation should therefore remain descriptive and limited to the study population and endpoint details that the registry record actually states.

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("Peg-IFN Alfa-2b + Ribavirin")
n      <- c(90)
events <- c(13)
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  Peg-IFN Alfa-2b + Ribavirin  90  13  14.4  7.9  23.4  8.6  23.2  8.7  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary questions concerning relapse among participants with rapid, early, or slow virologic response; pretreatment risk factors among participants with sustained virologic response; and positive HCV RNA at 72 weeks off treatment. Considering several outcomes or predictors can create multiplicity: the more questions examined, the greater the chance that some apparent findings arise by chance. In general, prespecified hypotheses and methods to address multiplicity can help readers interpret multiple tests. The registry record does not report whether hypotheses were prespecified beyond the listed outcomes, whether multiplicity was addressed, or which analyses were conducted.

The primary-outcome population description states that 7 of the 97 participants who started the study were excluded because of protocol violations and that 90 underwent HCV-RNA testing at Week 24 after the end of treatment. The specific protocol violations and any further reasons for unavailable outcomes are not reported in the registry record. It is not possible to determine whether exclusions were related to prognosis or outcome, or how sensitive findings might be to alternative handling of excluded participants.

The record does not describe the analysis populations used for secondary outcomes, the amount of missing data at later follow-up, or the methods used to handle missing observations. In general, complete-case analyses can be affected if participants with observed outcomes differ from those without them. The direction and size of any such effect cannot be inferred without information about missingness and the analysis approach.

The registry record also does not report an interim-analysis plan or a statistical analysis plan. Absence of those details in the record should not be treated as evidence that a particular method was or was not used; the methods 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyperthyroidism (1.0%), death (1.0%), malaise (1.0%), staphylococcal sepsis (1.0%), femoral neck fracture (1.0%).

The safety summary lists 96 participants at risk for serious adverse events and 5 participants affected. It separately lists 96 at risk for other adverse events and 21 affected. These figures describe the safety summary, not the primary efficacy population, which is described as 90 participants who underwent HCV-RNA testing after exclusions. The registry record does not explain why the safety denominator differs from the study enrollment or primary testing population.

The listed serious-event terms each have a reported frequency of 1.0%: hyperthyroidism, death, malaise, staphylococcal sepsis, femoral neck fracture, and road traffic accident. A separate death count is not reported in the registry record. The record does not give event timing, severity details beyond the serious-event classification, relationship to treatment, or the method used to select the listed terms.

These safety figures should be read as reported event summaries, not as evidence that an event was caused by treatment. The registry record does not provide a control group for estimating comparative safety, and the listed figures alone do not establish comparative risk. The safety data also do not supply the missing primary relapse result.

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

The registry record establishes the study’s intended clinical question and the operational definition of relapse. It describes follow-up of participants who had completed peginterferon alfa-2b plus ribavirin and had negative HCV RNA at the end of treatment. Positive HCV RNA at 24 weeks after treatment was defined as relapse, and 90 participants underwent testing at that time after 7 protocol-violation exclusions from the 97 who started.

The record does not report how many tested participants had positive HCV RNA. It therefore does not establish the observed relapse frequency or the precision of that frequency. It also does not report results for the proposed predictive-factor analyses or the listed secondary outcomes. Conclusions about whether relapse was common or uncommon, which characteristics predicted relapse, or how outcomes changed at later follow-up cannot be drawn from the registry record.

The study’s treated cohort is not a comparison of treatment options. Treatment was completed before enrollment, and no randomized or like-for-like control group is described. Accordingly, the record cannot show a comparative treatment effect. It also cannot establish that the treatment caused or prevented the outcome.

Any findings from this study would apply most directly to the described population: participants in common clinical practice in France who received the combination as first treatment and met the end-of-treatment virologic criteria. They should not automatically be generalized to other populations, treatment settings, regimens, or follow-up definitions.

The title’s “Completed” wording and the recorded status of TERMINATED are inconsistent labels within the registry entry; the record does not explain the discrepancy. This status issue does not supply missing outcome data. The defensible interpretation is limited to what the registry states about the population, endpoint, and testing, while treating unreported results and methods as unknown.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between treatment response at the end of therapy and relapse after therapy has ended. The endpoint is defined through a follow-up HCV-RNA measurement, so the question is not simply whether participants had a negative result during treatment. It asks whether the specified virologic status persisted to the registry’s post-treatment assessment.

The participant flow also matters to interpretation. The record reports 97 study starters, exclusions of 7 participants because of protocol violations, and HCV-RNA testing in 90 at Week 24 after the end of treatment. Keeping the enrollment, excluded group, and tested population distinct prevents a reader from treating them as interchangeable denominators. Because the primary event count is not reported, the tested denominator alone cannot supply a relapse estimate.

The study’s common-practice setting and post-treatment enrollment give the question a descriptive focus. At the same time, the absence of a stated allocation method and a like-for-like control comparison limits causal and comparative conclusions. This is an important design lesson: a cohort can address the frequency of an outcome in a defined group, but it does not answer the same question as a randomized comparison.

The record also illustrates why a stated aim is not equivalent to a reported finding. The objective includes identifying predictive factors, but no factors, model results, or uncertainty estimates are reported. Statistical interpretation depends on the analyses and outcomes actually documented, not only on the questions investigators intended to study.

Finally, the registry entry makes the boundary between a defined endpoint and an available result clear. The measurement method, timing, and classification are described, while the primary count and analytical detail are absent. A precise endpoint definition is valuable, but it cannot replace reporting the event data and methods needed to evaluate frequency, precision, and predictive claims.

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 registry record does not report the number of participants with positive HCV RNA at the primary assessment. Without that result, the central relapse question cannot be quantified, and no estimate or precision assessment can be checked.

The analyzed population is smaller than the number who started the study: 7 participants were excluded because of protocol violations, and 90 underwent the Week 24 test. The registry does not identify the specific violations or describe additional missing outcome information. It is therefore not possible to assess whether exclusions or unavailable assessments could have influenced the observed outcome.

The study follows participants after treatment completed before enrollment. This selects a population based on treatment history and end-of-treatment virologic status. The resulting question is narrower than an assessment of outcomes among all participants who begin treatment. The record does not provide information to determine how the included group compares with people who did not meet those criteria.

No randomized comparison or like-for-like control group is described, and allocation is not stated. The study’s results, if available, would not by themselves establish comparative treatment effects. The registry also does not report the predictive-factor model, analysis plan, multiplicity approach, confidence intervals, or p-values. Consequently, the robustness and precision of any such findings cannot be assessed from the record.

Safety summaries use 96 participants at risk, whereas the primary-outcome description concerns 90 tested participants; the registry does not explain the difference. The title labels the study “Completed,” while the recorded status is TERMINATED, without an explanation. Reasons for termination and the study’s own sample-size justification are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Relapse Rate in Hepatitis C Patients Treated With Peginterferon Alfa-2b Plus Ribavirin in Common Clinical Practice in France (P05484)(Completed) — NCT00725842.
• Registry record last updated 2015-09-21; status last verified 2015-09.
• Results first posted 2012-08-07.
• 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

NCT00725842 concerns relapse and predictive factors after peginterferon alfa-2b plus ribavirin treatment for chronic hepatitis C in common clinical practice in France. Treatment was completed before enrollment. The primary endpoint was positive HCV RNA by PCR at 24 weeks after the end of treatment, defined as relapse.

The record reports 97 participants starting the study, 7 excluded from analysis because of protocol violations, and 90 undergoing Week 24 HCV-RNA testing. The primary positive-result count, relapse rate, and analysis results are not reported in the registry record. Secondary questions concern response categories, pretreatment risk factors, and positive HCV RNA at 72 weeks off treatment.

The registry dates are 2009-01 for study start and 2011-06 for primary completion. The title includes “Completed,” while the recorded status is TERMINATED. No randomized comparison is described, and the record does not explain the status discrepancy.