An Observational Study on Predictive Factors of Response in Patients With Chronic Hepatitis C Treated With Pegasys (Peginterferon Alfa-2a) and Ribavirin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study on Predictive Factors of Response in Patients With Chronic Hepatitis C Treated With Pegasys (Peginterferon Alfa-2a) and Ribavirin (NCT01392742), a registered phase not stated study. The primary outcome is Percentage of Participants With Sustained Virological Response (SVR).

2. Clinical Question

The broader research question concerns which host-, virus- and treatment-related factors, as well as early virological responses, predict later sustained response among patients receiving this regimen. Listed secondary outcomes include predictive values at Week 4 and Week 12 and correlations with rapid and early virological response. The listed outcomes describe questions the study set out to examine; their presence does not establish that a particular predictor was associated with the outcome.

Because this is observational, findings about predictors would describe patterns among the participants studied. They would not, on their own, establish that a factor caused a response or that the treatment caused an outcome. The registry record does not provide the detailed predictor estimates needed to assess those relationships.

3. Trial Design

The record identifies NCT01392742 as a prospective observational study of patients with chronic hepatitis C receiving Pegasys (peginterferon alfa-2a) and ribavirin. Its stated focus is predictors of early on-treatment response and sustained virological response. The record lists Hoffmann-La Roche as sponsor, a start date of 2011-05-31, primary completion on 2014-07-31, and status as completed.

The study description says data would be collected while participants were on treatment for 24 or 48 weeks and again 24 weeks after the end of treatment. The primary outcome timeframe is 24 weeks after the end of treatment, up to Week 96. The actual treatment period is used in the outcome definition, so the endpoint is tied to each participant's treatment end rather than a single stated follow-up time for everyone.

The record lists one cohort description, but the arm description itself is blank. It does not state an allocation method. It is not a randomized comparison, and the available record does not establish a like-for-like control group. Treatment duration and cumulative doses by genotype appear among the secondary outcomes, but the outcome titles alone do not report those data or explain treatment decisions.

The record lists 12 outcome measures and 11 analyses. It does not report a sample-size justification, a detailed statistical analysis plan, an interim-analysis plan, or how the 11 analyses map to the outcome measures. These omissions limit what can be inferred about the study's prespecified analysis strategy. The sample-size illustrations associated with the results are planning exercises, not evidence of the study's design or its achieved power.

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: Per Protocol (PP) population included all participants without any protocol violation.

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: Intent-to-treat (ITT) population included all screened participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virological Response (SVR), measured over 24 weeks after End of treatment (EOT) (up to Week 96).

The primary endpoint is the percentage of participants with sustained virological response (SVR). The registry defines SVR as HCV RNA being undetectable 24 weeks after completion of the actual treatment period, based on a single last undetectable HCV RNA PCR measured at least 140 days after treatment. The timeframe is 24 weeks after end of treatment, up to Week 96.

This is a binary outcome at the participant level: each participant either meets the registry definition or does not. The percentage expresses how common the defined response was in the analysis population. As a general statistical point, a binary endpoint can summarize the proportion meeting a clinical or laboratory criterion, while its precision depends on the number of participants with an evaluable outcome and the amount of uncertainty around the estimate.

The outcome is used to assess whether an undetectable viral RNA result persists after treatment has ended, rather than measuring only an on-treatment response. The registry specifies the Per Protocol population: participants without any protocol violation. The record does not report the observed percentage, the number meeting the definition, a confidence interval, or the number included in the endpoint analysis. Therefore, the endpoint definition is available, but the result and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a percentage, so it can be understood as a binary outcome summarized across participants. In general, a participant either meets the operational definition of SVR or does not. The registry definition requires undetectable HCV RNA 24 weeks after the actual treatment period, with the specified PCR timing. The analysis population is the Per Protocol population, described as participants without any protocol violation. The registry record does not report the resulting numerator or denominator.

What does a percentage estimate?

In general, a percentage for a binary outcome estimates the proportion of the target analysis population meeting the stated criterion. Its interpretation depends on the population used, whether outcomes were observed for all eligible participants, and whether the endpoint was defined consistently. Here, the record supplies the endpoint definition and population description, but not the observed percentage or the number with an evaluable outcome. The proportion and its precision therefore cannot be reconstructed from the registry record.

A confidence interval is a general way to express uncertainty around an estimate. It does not guarantee that the true value lies within the interval, nor does it resolve bias from selection, measurement, or analysis choices. The registry record does not report a confidence interval for the primary endpoint. It also does not identify the method used to estimate uncertainty, so no particular interval procedure should be assumed.

How should predictor analyses be understood?

The study's stated aim is to evaluate predictors of early response and SVR. Its secondary outcome titles include positive predictive value at Week 4 and Week 12, correlations with rapid virological response and early virological response, and predictive power values for host-, virus- and treatment-related factors and virological response. In general, positive predictive value describes the proportion of people with a positive test or predictor who also have the outcome, within the population and definitions used. It depends on the context in which the predictor is assessed and does not, by itself, show that the predictor causes the outcome.

Correlation describes how two measured quantities vary together; it does not establish that one produces the other. Predictor analyses can also be affected by confounding, where another factor relates to both the predictor and outcome. In general, adjustment methods can address measured covariates under their assumptions, but the registry record does not report which methods were used, what covariates were considered, or the estimates obtained. The listed outcome names should therefore not be read as evidence of a particular association.

What do the sample-size illustrations represent?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are computed from the observed effect, with the effect to detect expressed as a stated fraction of that observed effect. For time-to-event tables, the stated quantity is the total number of events; for other tables, it is participants per arm. These are planning illustrations, not the study's own sample-size justification and not observed power. The registry record does not report the protocol's sample-size rationale.

In general, a planning calculation estimates the sample size associated with a chosen statistical target and a set of assumptions. It does not describe the precision actually achieved in a completed study. In this case, the registry record does not report the primary endpoint result needed to assess the observed effect in context, and no illustration should be interpreted as an observed treatment effect or as proof that the study had adequate power.

What analysis details remain unknown?

The registry record lists 12 outcome measures and 11 analyses, but does not report the detailed statistical methods, model specifications, or mapping between those entries. It does not state whether estimates were adjusted, how continuous predictors were handled, or how the precision of predictor estimates was calculated. These details are necessary for a full appraisal of the statistical analysis. General statistical principles can explain what such methods would do, but they cannot fill in methods that are 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("HCV Infected Participants")
n      <- c(331)
events <- c(128)
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  HCV Infected Participants  331  128  38.7  33.4  44.2  33.6  44.0  33.6  44.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and 11 analyses. When multiple outcomes or predictor relationships are examined, there can be more opportunities for apparently notable findings to arise by chance. As a general statistical explanation, multiplicity methods can control or describe this issue, but the choice depends on which hypotheses were planned and how they relate to one another. The record does not report a multiplicity adjustment, a hierarchy among outcomes, or which analyses were considered confirmatory. It is therefore not possible to determine how the number of analyses affected interpretation.

The Per Protocol population is defined as all participants without any protocol violation. This clarifies the stated primary analysis population, but the record does not say how many participants met that definition or were included in the endpoint analysis. It also does not report how participants with missing HCV RNA measurements, incomplete follow-up, or other unavailable outcome data were handled. Missing-data rules, imputation methods, and sensitivity analyses are not reported in the registry record.

As a general point, excluding participants with protocol violations can make the analysis population differ from the enrolled population. The meaning of an estimate may then depend on which participants remain and why others are excluded. Without a participant flow, exclusions, and missing-outcome information, the potential effect of those decisions cannot be assessed. The registry record also does not report whether an intention-to-treat analysis or another analysis population was used alongside the Per Protocol population.

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: anaemia (0.9%), pyrexia (0.5%), anaemia haemolytic (0.2%), astenia (0.2%), leucopenia (0.2%).

The registry lists safety figures for HCV-infected participants. It reports 17 participants with serious adverse events among 440 at risk, and 273 with other adverse events among 440 at risk. These are the recorded counts and denominators; no percentage has been calculated from them. The death count is not reported in the registry record.

The listed serious adverse event terms and percentages are Anaemia, 0.9%; Pyrexia, 0.5%; Anaemia haemolytic, 0.2%; Astenia, 0.2%; Leucopenia, 0.2%; and Neutropenia, 0.2%. These term-level percentages should be read as reported, not as estimates of treatment causation. The registry information does not establish that the events were caused by the treatment.

In general, adverse-event counts describe events recorded under a study's safety reporting rules; they do not alone establish comparative risk. This is an observational study without a like-for-like control comparison established in the record. The safety figures therefore do not support a treatment-versus-control comparison. The registry record does not report further detail about event severity beyond the serious-event classification, timing, duration, or the method used to attribute events.

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

The record establishes that a prospective observational study was conducted to examine early response and sustained virological response among patients with chronic hepatitis C receiving Pegasys plus ribavirin. It gives a definition of SVR and names a Per Protocol population. It also lists outcomes about early virological response, predictive values, correlations, and treatment characteristics by genotype. These registry entries describe the study's purpose and planned outcome framework.

They do not establish the observed frequency of SVR. The registry record does not report the primary endpoint percentage, the number meeting its definition, or an interval expressing uncertainty. Thus, the record cannot show how precisely the endpoint was estimated. The absence of a reported result should not be interpreted as a result of zero response, nor as evidence of a high response.

The design also limits what can be concluded about cause and effect. Since the record describes an observational study and does not establish a randomized or like-for-like control comparison, the findings cannot be interpreted as a causal comparison of treatment against an alternative. Associations between predictors and response, if reported elsewhere, would need to be interpreted in light of possible confounding and the methods used to analyze them. Those estimates and methods are not reported in the registry record.

The safety counts describe reported events in the listed group, but do not establish that treatment caused those events or quantify comparative safety. More broadly, the outcome titles do not substitute for their numerical results. The most defensible reading is that the registry documents the study's scope, timing, endpoint definition, and selected safety counts, while leaving the main efficacy result and key analysis details unreported.

14. Why This Trial Matters Statistically

This study raises a statistically useful question: whether early on-treatment measurements and other patient, virus, or treatment characteristics can help predict a later virological outcome. Prediction is distinct from causal explanation. A factor can be useful for distinguishing participants with different outcomes without being the cause of those outcomes. Keeping those questions separate is particularly important in an observational study.

The endpoint definition also illustrates why timing and measurement rules matter. SVR is anchored to the end of the actual treatment period and requires an undetectable HCV RNA result after treatment. The stated follow-up is 24 weeks after end of treatment, up to Week 96, and the definition specifies a single last undetectable PCR measured at least 140 days post-treatment. Those operational details determine which participants meet the endpoint; they are not interchangeable with an on-treatment response.

Statistically, a complete interpretation requires more than an outcome label. The observed proportion, analysis denominator, and uncertainty are necessary to assess the endpoint result. Predictor findings also require estimates, uncertainty, and details about adjustment and multiplicity. The registry record defines several relevant questions but does not report those results or methods, making it a useful example of the difference between a study's stated aims and the evidence available for quantitative interpretation.

The listed planning illustrations also underline a separate distinction: calculations based on an observed effect can support hypothetical future planning, but they are not observed power and do not replace the study's original design rationale. The registry record does not report that rationale. Careful separation of observed outcomes, planning assumptions, and unreported methods helps prevent overstatement.

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 central limitation for interpretation is that the registry record does not report the primary endpoint result. Without the SVR percentage, event count, analysis denominator, or confidence interval, neither the observed response frequency nor its precision can be assessed. The record also does not report the numerical results for the secondary outcomes named in the study description.

The record describes an observational cohort and does not establish a randomized or like-for-like control comparison; allocation is not stated. This prevents a direct causal interpretation of any treatment-related association based on the record alone. The blank cohort arm description and lack of detail about how treatment was selected also leave the structure of the analyzed cohort unclear.

Several further analysis details are not reported: the sample-size justification, statistical analysis plan, interim analyses, multiplicity approach, and methods for missing data. The record does not state how many participants were in the Per Protocol analysis or how protocol violations and incomplete follow-up affected inclusion. It also does not provide predictor estimates, adjustment methods, or their uncertainty. These omissions limit assessment of selection, confounding, and the robustness of any association.

The safety information is also limited to reported counts and selected serious adverse event terms. The death count is not reported, and the registry entries do not establish causality or provide a comparison group. These limitations concern what can be concluded from the registry record; they do not establish that unreported results were absent from other study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Observational Study on Predictive Factors of Response in Patients With Chronic Hepatitis C Treated With Pegasys (Peginterferon Alfa-2a) and Ribavirin — NCT01392742.
• Registry record last updated 2017-04-10; status last verified 2017-03.
• Results first posted 2015-12-14.
• 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

NCT01392742 is a completed prospective observational study sponsored by Hoffmann-La Roche. It concerns chronic hepatitis C and patients receiving Pegasys (peginterferon alfa-2a) plus ribavirin. The registry lists enrollment of 443, a start date of 2011-05-31, and primary completion on 2014-07-31.

The primary outcome is the percentage of participants with SVR, defined by undetectable HCV RNA 24 weeks after the actual treatment period, with the specified PCR timing. The primary analysis population is Per Protocol, defined as participants without any protocol violation. The primary endpoint result and its uncertainty are not reported in the registry record.

The record lists 12 outcome measures and 11 analyses, including early-response and predictor questions. It reports safety counts of 17 serious adverse events and 273 other adverse events among 440 at risk; the death count is not reported. Allocation is not stated, and the study is not a randomized comparison.