Efficacy and Safety of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis (NCT02128542), a na phase 4 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy.

2. Clinical Question

This question concerns a virologic outcome after treatment has ended, rather than a comparison of treatment strategies. The outcome is a proportion: it represents participants meeting the stated RNA threshold within the defined analysis population. Interpreting that proportion would require the observed result and its uncertainty, neither of which is reported in the registry record. The study also lists secondary outcomes concerning SVR4, viral breakthrough, viral relapse, and resistance-associated variants. Those outcomes address other aspects of response and safety, but the record does not provide their numerical results in the registry record described for this analysis.

3. Trial Design

This was a Phase 4, multicenter, open-label study of sofosbuvir plus ribavirin in genotype 2 HCV-infected U.S. veterans with cirrhosis. The registry describes the study as a single-group design, with one treatment group receiving sofosbuvir plus ribavirin for 12 weeks. Allocation is listed as not applicable, and masking is listed as none. There is no concurrent control group for estimating a between-group treatment contrast.

The registry lists enrollment as 66. Enrollment is not necessarily the denominator for every outcome: the primary outcome specifies a Full Analysis Set consisting of participants enrolled and given at least 1 dose of study drug. The record does not state how many participants met that outcome-population definition or how many contributed data to each secondary outcome.

The study start is recorded as 2014-06, and primary completion as 2015-06. Its status is completed. The stated primary endpoint is the percentage of participants with SVR 12 weeks after discontinuation of therapy, with the timeframe identified as posttreatment Week 12. The treatment period and the endpoint follow-up are distinct: the endpoint is assessed after treatment has stopped.

Because the design has a single group, the study can describe outcomes among participants receiving the regimen but does not directly estimate how those outcomes compare with an alternative. Open-label status means masking is not part of the design as recorded; further details about outcome assessment procedures are not reported in the registry record. The protocol, sample-size justification, and statistical analysis plan are not reported in the registry record.

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: 113 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug

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 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) 12 Weeks After Discontinuation of Therapy, measured over Posttreatment Week 12.

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after discontinuing therapy, or SVR12. The registry defines SVR12 as HCV RNA < the lower limit of quantitation, specified as 25 IU/mL, at 12 weeks after treatment stops. The outcome is therefore a binary classification for each participant: the stated RNA criterion is either met or not met at the specified follow-up. The reported group-level measure would be the percentage meeting the definition.

SVR12 is used as a posttreatment virologic endpoint because it assesses whether the specified RNA threshold is met after the treatment period has ended. That makes it distinct from a measurement taken while participants are receiving therapy. The definition also makes the timing and threshold part of the endpoint; a result at another time or under another threshold would not be the same endpoint as defined in this record.

The primary outcome’s population is the Full Analysis Set: participants enrolled in the study who received at least 1 dose of study drug. The registry record does not report the observed SVR12 percentage, its 95% confidence interval, or the number of participants contributing to that result. Without those results, the magnitude and precision of the endpoint cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage, which is a summary of a binary endpoint across the defined analysis population. Each participant is classified according to whether the SVR12 criterion is met. A group percentage describes the proportion meeting that criterion; it does not show the distribution of individual RNA measurements or explain why a participant did or did not meet the definition.

What does a confidence interval add?

A confidence interval describes uncertainty around an estimated quantity under the statistical method used. For a percentage, the interval indicates a range of values compatible with the observed data and the method’s assumptions. A narrower interval generally indicates greater statistical precision, while a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its endpoints, and it cannot resolve limitations such as the absence of a comparator or questions about how participants were selected.

The primary endpoint lists a 95% confidence interval as its dispersion measure, but the interval endpoints and the observed percentage are not reported in the registry record. Consequently, neither the point estimate nor its precision can be evaluated. The confidence interval’s stated level identifies the kind of uncertainty summary intended; it does not substitute for the missing numerical result.

Why does the analysis population matter?

The primary outcome specifies a Full Analysis Set consisting of participants who enrolled and received at least 1 dose of study drug. That definition determines which participants are intended to contribute to the endpoint. It is not necessarily identical to enrollment, and the registry record does not report the number meeting the definition or the number included in the primary calculation. The record also does not describe how participants without an observed posttreatment result were handled.

Missing outcome data can affect a percentage because the analysis must determine how participants without an observed endpoint are represented. Different approaches can produce different estimates, particularly if missingness is related to participants’ health or outcomes. The registry record does not report the amount or pattern of missing primary outcome data or the method used to address it. These omissions prevent assessment of how sensitive an estimate might be to missingness.

What can a single-group design estimate?

A single-group study can describe the outcome frequency among participants who received the study regimen. It does not provide a randomized comparison against another regimen, because there is no concurrent comparator group. A percentage observed in such a group is not itself a treatment-versus-control effect. Differences from another study or population would be subject to differences in eligibility, follow-up, measurement, and analysis, among other factors; such comparisons are not reported in the registry record.

Open-label status means participants and study personnel were not masked as described in the record. The consequences of this feature depend on the outcome and assessment process. The primary endpoint is based on an RNA threshold, but further information on laboratory procedures, endpoint adjudication, or quality controls is not reported in the registry record. It would be inappropriate to infer details beyond the stated endpoint definition.

How should planning calculations be understood?

Sample-size calculations are planning illustrations, not observed outcomes and not evidence that a study had a particular probability of detecting an effect. The stated planning assumptions describe a hypothetical two-arm calculation with equal allocation, a two-sided significance level of 0.05, and a normal approximation. The calculation is described as using a fraction of the observed effect. These are planning assumptions, not the design of this single-group trial, and they should not be read as a randomized comparison conducted in the study.

In general, a planning calculation asks how many participants per arm would be needed under specified assumptions to target a particular power and effect. Its output depends on the assumed effect and method. It does not establish the effect that would occur in a future study, nor does it describe the precision achieved in the present study. The protocol’s own sample-size justification is not reported in the registry record. The observed primary effect needed to interpret the planning illustration is also not reported in the registry record.

The record lists 6 outcome measures and 0 analysis entries. A listed outcome indicates that it was part of the registered outcome information; it does not, on its own, disclose the statistical model or establish that a numerical result was reported. Details of the analysis method for the primary percentage, including any adjustment, 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("SOF+RBV 12 Weeks (TN)", "SOF+RBV 12 Weeks (TE)")
n      <- c(47, 19)
events <- c(36, 16)
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 12 Weeks (TN)  47  36  76.6  62.0  87.7  62.8  86.4  62.7  86.4
ARM  SOF+RBV 12 Weeks (TE)  19  16  84.2  60.4  96.6  62.4  94.5  62.1  94.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, including SVR4, viral breakthrough, viral relapse, and resistance-associated variants. Considering multiple outcomes can raise multiplicity concerns: when many statistical tests are performed, the chance of at least one apparently notable result can increase. Whether and how that issue was addressed depends on the prespecified analysis strategy. A multiplicity procedure or hierarchy is not reported in the registry record, so it is not possible to determine whether adjustments were planned or used.

The primary outcome population is defined as participants enrolled and given at least 1 dose of study drug. The registry does not report the number who met that definition, the number with an observed SVR12 result, or the handling of participants with missing outcome data. Missing-data methods can affect the interpretation of an outcome percentage, particularly when the reasons for missingness may relate to participants’ outcomes. The amount, pattern, and treatment of missing data are not reported in the registry record.

The record lists 0 analysis entries. It does not provide the statistical analysis plan, the method used to calculate the primary percentage or confidence interval, or details of any interim analyses. Those features are not reported in the registry record and should not be inferred from the endpoint definition. The listed analysis population supplies a basic inclusion rule, but not enough information to reconstruct the analysis or assess the effect of alternative missing-data and multiplicity choices.

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 (1.5%), cardiac failure congestive (1.5%), nausea (1.5%), oesophageal varices haemorrhage (1.5%), chest pain (1.5%).

The registry reports 8 participants affected by serious adverse events, with 66 at risk, and 45 participants affected by other adverse events, also with 66 at risk. These counts describe participants recorded in each category. They are not counts of all event episodes, and the categories should not be added together: the record does not state whether a participant could appear in both. The figures do not establish that an event was caused by study treatment.

Several serious adverse event terms are listed with a reported percentage of 1.5% each: anaemia, cardiac failure congestive, nausea, oesophageal varices haemorrhage, chest pain, and bacteraemia. The record does not provide further detail in the stated details about timing, severity beyond the serious-event classification, outcomes, or treatment attribution for these terms. The death count is not reported in the registry record; a missing count should not be interpreted as zero.

Because this was a single-group study, these safety counts are descriptive. They do not estimate how event frequency would differ under another treatment or without treatment. The registry record also does not report comparative safety analyses or additional detail on how adverse events were assessed.

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

The record establishes that this completed Phase 4 study assessed a 12-week course of sofosbuvir plus ribavirin in U.S. veterans with genotype 2 HCV infection and compensated cirrhosis. It defines SVR12 using a specified HCV RNA threshold and a posttreatment follow-up time. It also identifies a Full Analysis Set for the primary outcome and reports selected adverse-event counts. These details describe the study’s question and framework.

The registry record does not report the primary SVR12 percentage or its 95% confidence interval. Thus, the magnitude of the primary outcome and its statistical precision cannot be stated. The secondary outcomes are listed, but their numerical results are not reported in the registry record. A statistical interpretation of efficacy cannot be made from the endpoint definition alone.

The design also does not support a direct randomized comparison: it is a single-group, open-label study with no concurrent comparator. Even if an outcome percentage were available, it would describe the study group rather than establish a difference attributable to treatment relative to another strategy. The results would also pertain to the enrolled study population and should not be assumed to apply identically to people outside it.

The adverse-event counts provide descriptive safety information, not proof of causation or comparative risk. Further safety details, including the death count, are not reported in the registry record. Taken together, the posted information supports a description of the trial design and selected safety reporting, but does not provide the primary efficacy result needed to characterize the observed virologic outcome.

14. Why This Trial Matters Statistically

This study raises several statistical issues that matter when reading a clinical-trial result. Its primary endpoint is a percentage defined by a clear virologic threshold and posttreatment time, but the registry record does not report the estimate or confidence interval. That absence illustrates why an endpoint definition and a numerical result are different kinds of information: the definition tells readers what was to be measured, while the result and its uncertainty are needed to assess what was observed.

The single-group design is another important feature. An outcome percentage in a treated group can describe that group, but it does not provide the same evidence as a randomized contrast. Without a concurrent comparator, the study does not directly estimate how outcomes would differ under an alternative regimen. This distinction remains important even when the clinical endpoint is objectively defined.

The stated analysis population also matters. A Full Analysis Set based on enrollment and receipt of at least 1 dose identifies who is eligible for the primary outcome analysis, but the registry does not report the number analyzed or how missing results were handled. Those details are necessary for evaluating the denominator and possible sensitivity of the estimate.

Finally, the sample-size assumptions describe a planning illustration using a two-arm framework, whereas the study itself is single-group. Keeping planning assumptions separate from the actual trial design prevents a hypothetical calculation from being mistaken for observed comparative evidence. These design and reporting distinctions are central to interpreting the record without overstating what it establishes.

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 registry record’s main limitation for interpreting efficacy is that it does not report the primary SVR12 percentage or its confidence interval. The recorded endpoint definition alone cannot establish the observed response or its precision. Numerical results for the named secondary outcomes are also not reported in the registry record.

The single-group design has no concurrent comparator, so the study does not provide a randomized estimate of a treatment contrast. Open-label status is recorded, but additional information about endpoint assessment procedures is not reported in the registry record. The study population is specific to U.S. veterans with genotype 2 HCV infection and compensated cirrhosis; the record does not establish how results would generalize beyond that population.

The enrollment figure does not give the number included in the primary outcome analysis. The registry defines the Full Analysis Set but does not report its size, the number with observed SVR12, or how missing outcomes were handled. The statistical analysis plan, protocol-based sample-size justification, multiplicity approach, and interim analyses are not reported in the registry record.

Safety reporting is also limited in the registry entries. The record includes counts for participants with serious and other adverse events and lists selected serious-event terms, but does not give additional context on timing, event outcomes, or attribution. The death count is not reported in the registry record. These limits mean the available safety information is descriptive rather than comparative.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis — NCT02128542.
• Registry record last updated 2016-08-03; status last verified 2016-06.
• Results first posted 2016-08-03.
• 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

This is a completed Phase 4, multicenter, open-label, single-group study of sofosbuvir plus ribavirin for 12 weeks in U.S. veterans with genotype 2 HCV infection and compensated cirrhosis. Enrollment is listed as 66. The primary endpoint is SVR12, defined as HCV RNA < 25 IU/mL at 12 weeks after treatment discontinuation, in participants enrolled and given at least 1 dose of study drug.

The registry record does not report the primary SVR12 percentage or its 95% confidence interval. It lists secondary virologic and resistance outcomes and reports 8 participants affected by serious adverse events and 45 affected by other adverse events. The study has no concurrent comparator, and further details about the statistical analysis plan, missing-data handling, and multiplicity are not reported in the registry record.