Efficacy and Safety of Sofosbuvir Plus Ribavirin in Japanese Adults With Chronic Genotype 2 HCV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Sofosbuvir Plus Ribavirin in Japanese Adults With Chronic Genotype 2 HCV Infection (NCT01910636), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

These details frame the scope of the evidence. The study can describe outcomes among participants treated with SOF+RBV, but its single-group design does not provide a concurrent control outcome for estimating a treatment contrast. The registry lists sustained virologic response at 4 and 24 weeks after treatment, viral breakthrough, and viral relapse as secondary outcomes. The record identifies 153 participants as enrolled; the analyzed denominator for SVR12 is not reported in the registry record.

3. Trial Design

This was a Phase 3b, multicenter, open-label study sponsored by Gilead Sciences. The registry identifies the design as single-group, with allocation recorded as NA and masking as none. The listed regimen was sofosbuvir plus ribavirin for 12 weeks. The study was completed; its recorded start was 2013-02 and primary completion was 2014-03.

The target population was Japanese adults with chronic genotype 2 HCV infection. The official title specifies treatment-naïve and treatment-experienced participants. The registry reports 153 enrolled participants. Enrollment is not necessarily the same as the denominator used for a particular endpoint: the primary endpoint population is defined as the Full Analysis Set, but the number in that set is not reported in the registry record.

In a single-group study, outcomes are observed under the listed regimen without a contemporaneous control arm in the record. This supports a descriptive account of outcomes in the enrolled study population. It does not, on its own, separate the regimen’s effect from other influences on outcomes or establish how outcomes would have differed under another treatment.

The primary outcome was the percentage of participants with SVR12, measured at Posttreatment Week 12. The record also names SVR4 and SVR24, viral breakthrough, and viral relapse among secondary outcomes. Although the registry states that there were 5 outcome measures, the names and definitions of all measures are not reported in the registry record. The analysis methods, including any adjustment procedures or interim analyses, are not reported in the registry record.

The record gives no detailed account of treatment adherence, participant flow, or the handling of withdrawals and missing endpoint measurements. Those details matter when interpreting a percentage endpoint because the result depends on which participants are included and how unavailable measurements are treated. They cannot be inferred from the enrollment count or from the endpoint definition alone.

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.

Before assignment: 188 participants were screened.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: participants who were enrolled, received at least 1 dose of study drug, and had chronic genotype 2 HCV infection.

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: Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), measured over Posttreatment Week 12.

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after stopping study treatment (SVR12). The record defines a response as HCV RNA < the lower limit of quantitation, specified as 25 IU/mL, at 12 weeks after treatment discontinuation. The endpoint population is the Full Analysis Set: participants who were enrolled, received at least 1 dose of study drug, and had chronic genotype 2 HCV infection.

SVR12 is a binary outcome: each participant either meets the stated virologic criterion at the specified assessment or does not. Reporting the percentage offers a direct description of how often the endpoint was observed in the defined analysis population. The timing and assay threshold are part of the endpoint definition; measurements at a different time or using a different threshold would not have the same definition.

As a general statistical point, a binary endpoint is often summarized by a proportion and may be accompanied by a confidence interval. A confidence interval communicates the uncertainty around an estimated proportion; it does not resolve limitations in the study design or make the result causal. The registry record does not report the SVR12 estimate, its denominator, or its confidence interval. The endpoint’s definition is reported, but its observed result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group trial with no masking. Those design features determine what statistical comparisons are available. A single-group study can estimate outcomes observed among participants receiving the listed regimen, but it does not contain a concurrent control group for a between-group estimate. The registry specifically flags that this is not a randomized comparison and that arms are not a like-for-like control comparison. There is no recorded allocation process for assigning participants among treatment groups.

What does a binary endpoint represent?

SVR12 is defined as a binary outcome: HCV RNA is either below the stated LLOQ at the specified posttreatment assessment or it is not. The registry defines the threshold as < 25 IU/mL at 12 weeks after stopping treatment. A percentage for this endpoint would be calculated from the participants classified as meeting the criterion in the relevant analysis population. The registry record does not report that percentage or the endpoint denominator, so neither can be reconstructed from the information recorded.

As a general statistical explanation, a proportion summarizes the frequency of an outcome in a defined group. Its interpretation depends on a clear numerator, denominator, outcome definition, and approach to missing measurements. The Full Analysis Set definition is reported, but the count in that population and the treatment of missing SVR12 assessments are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the method used to calculate it. A wider interval indicates less precision than a narrower one. It does not mean that all values inside it are equally likely, and it does not address bias from study design or measurement. No primary endpoint estimate or confidence interval is reported in the registry record, so the precision of the SVR12 result cannot be evaluated.

For a single-group proportion, statistical uncertainty concerns the estimate in the observed study population and the assumptions of the interval method. It is distinct from uncertainty about what would have happened under a different regimen. A control group and suitable design are needed to estimate that contrast; a confidence interval around a single-group percentage cannot supply it.

What do the planning assumptions describe?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the planning quantities are described as participants per arm; time-to-event quantities are described as total events. These are general planning assumptions, not a description of this trial’s single-group design. The sample-size justification for the trial is not reported in the registry record.

As a general explanation, a planning calculation asks how much information a future study might need under chosen assumptions. It is not an observed result and does not establish that a completed study had a particular probability of detecting an effect. The record does not report a trial-specific planning rationale or a statistical analysis plan. No sample-size illustration should be read as observed power or as evidence that the planned assumptions were met in this study.

What can the safety counts establish?

The record reports counts of serious and other adverse events for the SOF+RBV group. These are descriptive safety summaries. A count can indicate that events were recorded, but by itself it does not describe their timing, duration, severity beyond the serious classification, relationship to study treatment, or clinical course. The registry lists two serious event terms with percentages, but does not report detailed case narratives or a fuller breakdown in the registry record.

As a general statistical point, adverse event counts and percentages should be interpreted using their stated population at risk and the study’s event-collection rules. They should not be treated as proof that an event was caused by treatment. The record does not describe the event definitions, collection window, or attribution procedures. The safety figures therefore offer limited descriptive information rather than a complete comparative safety assessment.

In general, over-dispersion matters when observed variability is greater than a model assumes; ignoring it can make uncertainty estimates too small. That concept does not supply a missing analysis for this trial. The registry does not report a model for the primary binary endpoint, an over-dispersion assessment, or any adjusted estimate. It is not appropriate to infer a statistical method from the endpoint type alone.

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("SOF+RBV Treatment Naive", "SOF+RBV Treatment Experienced")
n      <- c(90, 63)
events <- c(88, 60)
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  SOF+RBV Treatment Naive  90  88  97.8  92.2  99.7  92.3  99.4  92.3  99.3
ARM  SOF+RBV Treatment Experienced  63  60  95.2  86.7  99.0  86.9  98.4  86.9  98.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of SVR12 and secondary outcomes of SVR4, SVR24, viral breakthrough, and viral relapse. It also reports 5 outcome measures in total. The names and definitions of all measures are not reported in the registry record. The record reports 0 analyses, and it does not provide outcome estimates or hypothesis tests for the listed measures.

Multiplicity arises when several outcomes or statistical tests are considered: the chance of at least one apparently notable result can increase if many tests are performed without an appropriate plan. As a general statistical point, a prespecified hierarchy or adjustment method can help address that issue. The registry record does not report whether such a strategy was planned or used, nor does it report a statistical analysis plan. No multiplicity adjustment should be assumed.

The primary analysis population is defined as the Full Analysis Set, comprising participants who were enrolled, received at least 1 dose of study drug, and had chronic genotype 2 HCV infection. The number in that population is not reported in the registry record. The record does not say how withdrawals, missing HCV RNA measurements, or other unavailable outcome data were handled. It also does not report sensitivity analyses for missing data.

As a general point, missing-data handling can affect a percentage endpoint because the denominator and the classification of participants without an assessment influence the estimate. The registry’s enrollment count of 153 does not resolve those questions and should not be treated as the SVR12 denominator. Without a reported endpoint result, analysis denominator, and missing-data approach, the primary outcome cannot be independently interpreted for either magnitude or robustness.

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 (0.7%), allergy to arthropod sting (0.7%).

The registry lists 2 serious adverse events among 153 participants at risk in the SOF+RBV group. It also records 69 other adverse events among 153 at risk. The serious event terms listed are anaemia at 0.7% and allergy to arthropod sting at 0.7%. These entries are descriptive safety figures; they are not a comparison with a control group.

The term percentages do not, by themselves, explain whether events were considered related to treatment, when they occurred, whether they resolved, or whether a participant had more than one event. The registry record does not report those details. It also does not provide a complete account of event definitions, collection procedures, or follow-up for safety outcomes.

The deaths field is not reported in the registry record. That should not be interpreted as confirmation that no deaths occurred. In general, an adverse event recorded during a study does not establish that treatment caused it; causal attribution requires information beyond a count. Because the study has no recorded comparator group, these safety figures cannot establish a relative safety difference.

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

The record describes a completed Phase 3b study of sofosbuvir plus ribavirin for 12 weeks in Japanese adults with chronic genotype 2 HCV infection. It identifies SVR12 as the primary endpoint and defines the virologic threshold and assessment time. These details clarify what the study was designed to evaluate.

The primary endpoint result is not reported in the registry record. As a result, the record does not establish the observed SVR12 percentage, the number analyzed for that endpoint, or the precision of an estimate. It also does not report results for the listed secondary outcomes. The absence of these results from the registry record is not evidence that the outcomes were favorable or unfavorable.

The single-group design is another important boundary. A descriptive outcome in participants receiving SOF+RBV would not, by itself, show what would have happened under a different treatment. No randomized comparator is recorded, and the registry notes that the study is not a like-for-like control comparison. Therefore, the design does not support a direct comparative treatment effect.

The safety entries show recorded serious and other adverse event counts, and two serious event terms with their percentages. They do not provide the context needed to assess timing, attribution, event course, or relative risk. The record does not report deaths, rather than reporting that there were none.

In general, statistical interpretation requires both the numerical estimate and its uncertainty, as well as a clear understanding of who was analyzed and how missing data were handled. Those elements are not reported for the primary endpoint. The registry record therefore supports an account of the design, endpoint definition, and selected safety entries, but not a conclusion about the size or precision of the primary outcome or a comparative treatment effect.

14. Why This Trial Matters Statistically

This trial raises core statistical questions about the difference between describing outcomes and estimating comparative effects. A single-group study can characterize outcomes among participants who received the listed regimen. Without a recorded control group, however, it cannot provide a direct randomized contrast against another treatment. Recognizing that distinction prevents a descriptive percentage from being read as a comparative effect.

The endpoint definition is also statistically important. SVR12 specifies both the timing of assessment and the HCV RNA threshold, < 25 IU/mL. A clear definition makes the target outcome interpretable, but a definition alone is not a result. The registry does not report the endpoint estimate, analysis denominator, or confidence interval, so the magnitude and precision of the outcome cannot be assessed from the record.

The Full Analysis Set definition illustrates why analysis populations matter. Participants must meet the stated enrollment, treatment-exposure, and disease criteria. The enrolled count does not tell readers how many met the analysis definition or contributed an endpoint assessment. Missing-data procedures and participant flow are not reported in the registry record, limiting the ability to assess how well the estimate would represent the intended population.

The record also names multiple outcome measures without reporting their results or a plan for handling multiplicity. As a general statistical issue, interpreting several outcomes requires attention to which were primary, which were secondary, and whether testing was adjusted or hierarchically organized. The registry identifies a primary outcome but does not report the analysis plan.

Finally, the safety entries demonstrate the limits of raw counts. They describe events recorded in the treated group, but without comparative data and contextual details they do not quantify relative risk or establish causation. These distinctions are useful in evaluating what a registry record can support and what remains uncertain.

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.

Several trial-specific limitations affect interpretation. The study is recorded as single-group and open-label, with no comparator group and no masking. The registry explicitly notes that it is not a randomized comparison and that arms are not a like-for-like control comparison. Any outcome described for participants receiving SOF+RBV therefore lacks a concurrent control contrast in this record.

The primary endpoint result is not reported in the registry record. Neither its analyzed denominator nor a confidence interval is available. The enrollment figure of 153 cannot be substituted for the endpoint denominator because the Full Analysis Set has additional eligibility criteria and its size is not reported.

The registry does not report how missing SVR12 measurements or withdrawals were handled. It also does not report participant flow, adherence information, analysis methods, interim analyses, or a statistical analysis plan. These omissions limit assessment of possible selection effects, robustness to missing data, and the methods used to estimate outcomes.

Although the record states that there were 5 outcome measures, it names the primary endpoint and several secondary outcomes but does not report all outcome definitions or results. It does not describe any approach to multiplicity. The sample-size assumptions recorded for a planning illustration describe a two-arm framework, whereas this trial is identified as single-group; the trial’s own sample-size justification is not reported in the registry record.

Safety information is also limited to selected counts and serious-event terms. The record does not report event timing, attribution, duration, follow-up, or a comparative safety group. Deaths are not reported in the registry record. These gaps mean the listed safety counts should be treated as partial descriptive information rather than a complete account.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Sofosbuvir Plus Ribavirin in Japanese Adults With Chronic Genotype 2 HCV Infection — NCT01910636.
• Registry record last updated 2015-03-24; status last verified 2015-03.
• Results first posted 2015-03-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes NCT01910636, a completed Phase 3b, multicenter, open-label, single-group study sponsored by Gilead Sciences. It enrolled 153 participants and evaluated sofosbuvir plus ribavirin for 12 weeks in Japanese adults with chronic genotype 2 HCV infection, including treatment-naïve and treatment-experienced participants.

The primary outcome was SVR12, defined as HCV RNA < 25 IU/mL at 12 weeks after treatment discontinuation. Its result and analysis denominator are not reported in the registry record. Secondary outcomes include SVR4, SVR24, viral breakthrough, and viral relapse; their results are not reported.

The safety record lists 2 serious adverse events and 69 other adverse events among 153 at risk. Anaemia and allergy to arthropod sting are each listed at 0.7% as serious event terms. Deaths are not reported in the registry record. The design does not include a recorded randomized comparator, so the record supports descriptive interpretation rather than a direct treatment comparison.