Efficacy and Safety of Danoprevir/r + PR 12week Triple Therapy in Treatment Naive Non-Cirrhotic G1 CHC China III: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Danoprevir/r + PR 12week Triple Therapy in Treatment Naive Non-Cirrhotic G1 CHC China III (NCT03020082), a na phase 3 study. The primary outcome is Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

The clinical question concerns whether a 12-week regimen of ritonavir-boosted danoprevir, peginterferon alfa-2a and ribavirin was evaluated for sustained virologic response after treatment in treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 1. The registry identifies sustained virologic response 12 weeks after discontinuation of therapy (SVR12) as the primary outcome.

This was a single-group study, not a randomized comparison. The central statistical question is therefore descriptive: what proportion of the study group met the SVR12 endpoint? The registry record does not report the number or proportion meeting the endpoint, so it does not permit an estimate of the observed response rate or its precision. It also does not provide a concurrent control group for estimating a between-group treatment effect.

Because there is no concurrent comparator, any reported response proportion would describe outcomes in this treated group; on its own, it would not estimate how outcomes differ from another treatment or from no treatment. The registry record also does not report the virologic assay, response threshold, or detailed analysis population used to define and calculate SVR12.

3. Trial Design

This is a completed phase III, multicenter, open-label, single-group study. The registry lists enrollment of 141 and chronic hepatitis C as the condition. Its title and official title describe treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 1. The record gives a study start of 2016-06 and primary completion of 2017-05.

The study regimen combined ritonavir-boosted danoprevir with peginterferon alfa-2a and ribavirin. The regimen description specifies danoprevir/ritonavir 100mg/100mg BID, subcutaneous peginterferon alfa-2a at 180 mcg weekly, and oral ribavirin for 12 weeks. The described ribavirin dose is 500mg BID for body weight <75Kg and 600mg BID for body weight ≥75Kg. These are regimen details in the registry; the record does not report adherence, dose modifications, or treatment discontinuations.

Open-label means masking is listed as none. A single-group design does not include a like-for-like control group, and allocation is listed as NA. Consequently, the registry does not provide a randomized estimate comparing this regimen with another regimen. The primary outcome is the proportion of participants with SVR12, with the timeframe stated as 12 weeks. The primary outcome result itself is not reported in the registry record.

The registry identifies Ascletis Pharmaceuticals Co., Ltd. as sponsor and reports the study status as completed. A planned sample size rationale, detailed eligibility criteria, site-level information, the statistical analysis plan, and protocol deviations are not reported in the registry record. The completion status does not by itself establish how many participants completed treatment or had outcome data available; those details are not reported.

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

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 Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12), measured over 12 weeks.

The primary endpoint is the proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12). It is recorded as a participant count, with the outcome timeframe stated as 12 weeks. A proportion summarizes how frequently the defined outcome occurred within the study group; its interpretation depends on both the outcome definition and the population included in the calculation.

As a general statistical and clinical concept, assessing response after treatment has ended is intended to distinguish a sustained post-treatment response from a response measured only during therapy. The endpoint name places the assessment 12 weeks after discontinuation, but the registry record does not report the assay, the viral-load threshold, the visit window, or the operational criteria used to classify a participant as having SVR12. Those details should not be inferred from the endpoint title alone.

The registry record does not report the number of participants who achieved SVR12, the denominator used for the primary analysis, a confidence interval, or a hypothesis test. Therefore, no observed response proportion or measure of its precision can be described from this record. The endpoint is suitable for describing response in a single group, but without a concurrent comparator it cannot, by itself, quantify a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the registry can and cannot establish. The study design and the reported endpoint determine the appropriate interpretation; a named outcome does not itself provide an estimate, and an enrollment count does not substitute for a result.

What does a single-group design estimate?

A single-group study can describe the frequency of an outcome among participants observed under the study regimen. For a binary endpoint such as whether a participant meets a response definition, the basic descriptive quantity is the number meeting the definition relative to the number evaluated. The registry identifies SVR12 as a participant-count outcome, but reports neither the numerator nor the primary analysis denominator. Thus, the response frequency cannot be recovered from the record.

A comparative effect answers a different question: how outcomes differ between groups. Estimating that difference requires a suitable comparator and an analysis that accounts for the design. This study is recorded as single-group, with allocation listed as NA, so there is no like-for-like control comparison in the registry. A response proportion from one group, even if reported, would not by itself show what would have happened under another regimen.

What does a confidence interval contribute?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity. For a response proportion, it would help distinguish a relatively precise estimate from one that remains compatible with a broader range of possible underlying response frequencies. Its width depends on factors such as the amount of outcome information and the method used. The registry does not report a confidence interval for SVR12, and the missing endpoint count means that one cannot be reconstructed from the registry record.

A confidence interval would not repair the absence of a comparator. It could describe uncertainty in a single-group response estimate, but it would not remove confounding or establish a comparative causal effect. Nor does an interval alone determine clinical importance; that interpretation depends on the question and context, which cannot be posted by statistical precision alone.

Why do analysis populations and missing outcomes matter?

The denominator is part of the endpoint definition in practice. An analysis might include participants according to their enrollment, treatment exposure, or availability of endpoint measurements, but the registry record does not identify which approach was used for SVR12. It also does not report whether missing endpoint values were excluded, counted as nonresponse, or handled by another method. These choices can change a proportion and its uncertainty. The enrollment figure therefore should not be treated as the primary endpoint denominator without documentation.

Missingness can also affect interpretation. If outcome availability is related to response or tolerability, an analysis restricted to observed outcomes may not describe all enrolled participants in the same way as an analysis that includes everyone. This is a general concern, not a claim about what occurred in this study: the registry does not report the extent or pattern of missing SVR12 data.

How should the planning assumptions be read?

The registry describes sample-size calculations as planning illustrations based on the observed effect, rather than the trial’s own design. It states a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Those assumptions define a hypothetical planning exercise. They do not describe the single-group study structure, and they are not evidence that the study had a particular probability of detecting an effect.

Sample-size planning asks how much information may be needed to detect a prespecified effect under stated assumptions. It is not the same as observed power, which is not a useful substitute for reporting the estimate and its uncertainty after results are available. The observed effect, the stated fractions, and the numerical planning illustrations are not reported in the registry record. No sample-size justification for the actual study is reported either. The planning description also distinguishes participant-per-arm illustrations from total-event planning for time-to-event outcomes; this primary endpoint is a participant-count outcome, not a time-to-event endpoint.

Why is over-dispersion relevant in general?

For count or binary data, statistical models often rely on assumptions about how much variability is expected. Over-dispersion means that observed variation is greater than a model assumes, which can make standard errors too small and confidence intervals too narrow if it is ignored. Whether a particular model requires an over-dispersion adjustment depends on the data structure and chosen analysis. The registry does not report a model, an over-dispersion assessment, or a variance adjustment for the primary endpoint, so none should be attributed to this study.

Multiplicity is another general issue when many outcomes or statistical tests are interpreted together: repeated testing can increase the chance of at least one apparently notable result by chance. The registry lists one outcome measure, but does not report the full analysis plan, secondary testing strategy, or any multiplicity procedure. The number of listed outcome measures alone is not enough to establish what analyses were planned or how results were interpreted.

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("Danoprevir, Ritonavir, Peg-IFN,RBV")
n      <- c(141)
events <- c(136)
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  Danoprevir, Ritonavir, Peg-IFN,RBV  141  136  96.5  91.9  98.8  92.0  98.5  92.0  98.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, SVR12, as the primary endpoint. It does not report a detailed statistical analysis plan, a hierarchy of endpoints, a family of planned hypothesis tests, or a multiplicity adjustment. In general, multiplicity matters when investigators interpret several statistical tests together, because repeated testing can increase the chance of a chance finding. The available record does not establish whether additional analyses were planned outside the listed outcome measure or how they were to be handled.

The registry record does not report the SVR12 result, its analysis denominator, or an inferential analysis. It also does not report an analysis population such as all enrolled participants or participants with an observed endpoint. Enrollment of 141 should not be assumed to equal the number included in the primary analysis.

Missing endpoint data and their handling are not reported in the registry record. There is no information on the amount or reasons for missing SVR12 assessments, loss to follow-up, exclusions, or imputation. As a general point, a response proportion may depend on whether missing outcomes are omitted or treated according to a specified rule. Without those details, readers cannot assess how missingness might affect the reported endpoint estimate; in this record, no estimate is reported at all.

The sample-size description refers to planning illustrations based on an observed effect and hypothetical equal allocation between two arms. It does not provide the study’s own sample-size justification or establish what analyses were prespecified. The actual analysis plan, any interim analyses, and the rationale for sample size are not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (0.7%), ventricular tachyarrhythmia (0.7%), tuberculosis (0.7%), transient ischemic attack (0.7%), acquired digital fibrokeratoma (0.7%).

The registry records one treatment group, with 141 at risk for serious adverse events and 141 at risk for other adverse events. It lists 5 participants with serious adverse events, 76 with other adverse events, and 0 deaths. These are descriptive counts in the registry record, not comparative estimates against a control group.

The serious-event terms listed are neutropenia, Ventricular tachyarrhythmia, Tuberculosis, Transient ischemic attack, and Acquired digital fibrokeratoma; each is reported as 0.7%. The registry does not explain whether these terms are mutually exclusive, whether participants could contribute to more than one term, or how the percentages were calculated. They should not be combined into a total or interpreted as a complete account of all serious events.

Counts and percentages describe events recorded during the study; by themselves they do not establish whether the regimen caused an event. Without a comparator, they also cannot quantify whether event risk differed from another treatment. The registry record does not report detailed event definitions, timing, severity grading, relatedness assessments, or exposure-adjusted analyses. No further causal or comparative safety conclusion can be drawn from these figures alone.

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

The record establishes that a completed, open-label, single-group phase III study evaluated a regimen of ritonavir-boosted danoprevir, peginterferon alfa-2a and ribavirin in treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 1. It identifies SVR12 as the primary outcome and gives the regimen and study dates. It also reports descriptive adverse-event counts for the treatment group.

The record does not report the primary endpoint result. Consequently, it cannot show the observed SVR12 proportion, how precise that estimate was, or how many participants contributed to its calculation. A study’s purpose and endpoint do not establish its outcome. The reported enrollment also cannot be used as a substitute for the missing endpoint result or denominator.

The single-group design means there is no concurrent control comparison in the registry. Even if a response proportion were available, it would describe the study group and would not alone establish the difference attributable to the regimen compared with another treatment. The registry also does not report the detailed analysis plan, missing-data handling, or analysis populations needed to evaluate how an endpoint estimate was constructed.

The safety figures similarly describe recorded events in the group and do not establish causation or comparative risk. They should be interpreted alongside the limitations in event definitions and analysis details, which are not reported in the registry record.

In general, statistical evidence is most informative when an estimate is presented with its uncertainty, a clear denominator and a design suited to the question. Those elements are not available for the primary efficacy endpoint in this record. The absence of a reported result does not mean that the outcome was absent or that the study failed to measure it; it means that the registry record does not provide enough information to characterize that result.

14. Why This Trial Matters Statistically

This study illustrates why the design and the completeness of results matter as much as an endpoint name. SVR12 is identified as the primary outcome, but the registry record does not report the endpoint count or proportion. Without that estimate, readers cannot assess the observed response frequency or its precision. A stated study objective is not a substitute for numerical results.

The single-group design also defines the scope of any conclusion. It can support a description of outcomes in the study group when results are reported, but it does not create a direct comparison with another regimen. That distinction is central to biostatistical interpretation: descriptive outcome frequency and comparative treatment effect are different estimands and require different evidence.

The record provides useful context about the intended population, the regimen, study status, and adverse-event counts. It also highlights the need for transparent reporting of endpoint definitions, analysis populations, missing data, and uncertainty. Without those elements, even a result expressed as a simple proportion may be difficult to evaluate or compare with other evidence.

The planning description offers another important statistical lesson. Planning illustrations based on hypothetical two-arm assumptions are not the same as the design actually recorded, and they are not evidence of observed power. A sample-size rationale should be interpreted in light of the question and design it was built to address. The actual study’s sample-size justification and detailed analysis plan are not reported in the registry record.

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 for interpreting efficacy is that the registry record identifies SVR12 as the primary endpoint but does not report its result. No response count, proportion, confidence interval, or hypothesis-test result is available. The endpoint denominator and analysis population are also not reported, so enrollment cannot be assumed to represent the number evaluated.

The single-group design has no like-for-like control comparison. As a result, the record cannot estimate a comparative treatment effect or distinguish an outcome associated with the regimen from other influences. The study is open-label, with masking listed as none; the registry does not describe procedures that might reduce bias in outcome assessment.

Operational details for SVR12 are not reported, including the assay, response threshold, assessment window, and criteria for handling unavailable assessments. The registry also does not report the statistical analysis plan, missing-data methods, multiplicity procedures, or the study’s sample-size justification. These omissions limit assessment of how a primary result would have been defined and analyzed.

Safety information is limited to group-level counts and listed serious-event terms. Detailed event definitions, timing, severity, relatedness, and comparative rates are not reported. The record therefore supports only a descriptive reading of those counts and does not support causal attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Danoprevir/r + PR 12week Triple Therapy in Treatment Naive Non-Cirrhotic G1 CHC China III — NCT03020082.
• Registry record last updated 2021-03-23; status last verified 2017-01.
• Results first posted 2021-03-23.
• 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

NCT03020082 is a completed, open-label, phase III, single-group study sponsored by Ascletis Pharmaceuticals Co., Ltd. The registry reports enrollment of 141, a start date of 2016-06, and primary completion in 2017-05. The population is described as treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 1.

The regimen combined ritonavir-boosted danoprevir with weekly peginterferon alfa-2a and ribavirin for 12 weeks. The primary outcome was the proportion of participants with SVR12. The registry record does not report the primary outcome result, its analysis denominator, or an inferential analysis. It records 5 participants with serious adverse events, 76 with other adverse events, and 0 deaths in the treatment group.

No comparator group, detailed analysis plan, missing-data handling, or sample-size justification is reported in the registry record.