A Study of Daclatasvir and Sofosbuvir With Ribavirin in Subjects With Cirrhosis and Genotype 3 Hepatitis C Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Daclatasvir and Sofosbuvir With Ribavirin in Subjects With Cirrhosis and Genotype 3 Hepatitis C Infection (NCT02673489), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR12).

2. Clinical Question

3. Trial Design

This was a Phase 3, single-group study of daclatasvir, sofosbuvir, and ribavirin in people with cirrhosis and genotype 3 hepatitis C infection. The registry record lists enrollment of 106 and a completed status. It records a start date of 2016-03-15 and a primary completion date of 2017-03-02. These details describe the registry record; they do not establish how many participants contributed to each outcome analysis.

The treatment regimen was oral daclatasvir 60 mg once daily, sofosbuvir 400 mg once daily, and ribavirin 1000-1200 mg per day based on weight, given for 24 weeks. The record specifies no masking and no randomized allocation. With one treatment group and no reported concurrent control, the design can describe responses and safety observations among treated participants, but it cannot estimate a randomized between-group treatment contrast.

The primary outcome was the percentage of participants with SVR12, assessed at follow-up Week 12. The outcome description says that measurements after the start of non-study anti-HCV medication during treatment or follow-up were excluded. It also specifies a modified intention-to-treat approach based on treated subjects and a Next Value Carried Backwards approach for the numerator. The record does not explain these procedures in further detail.

Enrollment is listed as 106, while the overall safety group lists 78 participants at risk. The registry record does not explain the difference or give a participant flow accounting for enrollment, treatment, and outcome availability. It also does not report a protocol-based sample-size justification or a statistical analysis plan.

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: Of the 106 subjects enrolled, 78 participants entered the treatment period and received study treatment; 28 participants were enrolled but did not enter the treatment period. 26 were due to no longer meeting study criteria; 1 was due to poor/non-compliance (missed Day 1 visit); and 1 was other (missed screening window).

Treatment Period

Reasons for not completing this period:

Follow Up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated participants

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 Percentage of Participants With Sustained Virologic Response (SVR12), measured over Week 12.

The primary endpoint is the percentage of participants who achieved sustained virologic response at follow-up Week 12, called SVR12. The registry definition requires HCV RNA below the lower limit of quantitation, with target detected or target not detected. In general, a virologic response endpoint records whether the target virus is measurable at a specified follow-up point; it is not, by itself, a measure of every aspect of health or a comparison against another treatment.

The registry record defines the analysis population as all treated participants and describes a modified intention-to-treat approach based on treated subjects. It says measurements are excluded after non-study anti-HCV medication is started during treatment or follow-up. The response numerator uses a Next Value Carried Backwards approach. The record does not provide enough detail to explain all implementation decisions behind that approach.

The endpoint metadata specify a 95% confidence interval, which would convey uncertainty around the estimated percentage. However, the primary endpoint result and its confidence interval are not reported in the registry record. Therefore, the endpoint definition is available, but the magnitude and precision of the observed SVR12 percentage cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, while either interval can still be compatible with a range of underlying values. The registry record specifies a 95% confidence interval for the primary percentage, but the interval itself and the corresponding endpoint estimate are not reported. Precision for SVR12 therefore cannot be judged from the posted results.

What is the endpoint counting?

The primary outcome is a percentage of participants meeting the SVR12 response definition. The record defines response by HCV RNA below the lower limit of quantitation at follow-up Week 12, with target detected or target not detected. It describes the primary population as all treated participants and says the modified intention-to-treat approach is based on treated subjects. It also says the numerator uses a Next Value Carried Backwards approach. These are important features of the reported method, but the registry record does not provide a full algorithm for assigning outcomes when measurements are missing or when participants have multiple relevant measurements.

Why does the single-group design affect interpretation?

In general, a randomized comparison can estimate a difference between assigned groups while reducing certain sources of confounding. A single-group study does not have that concurrent randomized contrast. The results can describe outcomes in participants who received the regimen, but cannot directly establish how those outcomes compare with another regimen or with an untreated group. The registry lists allocation as not applicable, masking as none, and the model as single group. The record does not report a comparator arm.

How should the posted safety counts be read?

The registry reports numbers of participants at risk and affected for serious and other adverse events. These counts are descriptive summaries. They do not, on their own, identify whether an event was caused by treatment, nor do they provide a randomized comparison of event frequencies. The serious-event terms are accompanied by percentages, but the registry record does not report event-level narratives or attribution information in the details.

What does the planning illustration represent?

In general, sample-size planning asks how many participants a future comparison might require under stated assumptions. The record’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These assumptions describe a planning illustration, not the original single-group trial design. They do not establish the trial’s own sample-size justification, and the record does not report that justification. A planning calculation is not observed power and does not change the interpretation of the missing SVR12 result.

What statistical details remain unavailable?

The registry record does not report the primary endpoint estimate, its confidence interval, or an analysis result. It does not report the statistical analysis plan, any interim analyses, a protocol-based sample-size calculation, or the methods used to choose among multiple outcomes for formal testing. It also does not provide enough detail to reconstruct the handling of every missing or post-treatment measurement. These gaps prevent a complete audit of the analysis from the registry entry 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("HCV Treatment Naive", "HCV Treatment Experienced")
n      <- c(54, 24)
events <- c(50, 18)
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 Treatment Naive  54  50  92.6  82.1  97.9  82.4  97.1  82.4  97.0
ARM  HCV Treatment Experienced  24  18  75.0  53.3  90.2  55.1  88.0  54.9  87.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary SVR12 outcome and secondary outcomes concerning SVR12 by baseline NS5A resistance-associated polymorphism status and HCV RNA findings through follow-up Week 24. Listing several outcomes raises a general statistical issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the testing strategy accounts for multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or which outcomes were subject to formal hypothesis testing. It is therefore not possible to determine how multiplicity was handled.

Missing-data handling is only partly described for the primary endpoint. The record says that HCV RNA measurements after the start of non-study anti-HCV medication during treatment or follow-up are excluded. It also identifies a modified intention-to-treat approach based on treated subjects and a Next Value Carried Backwards approach for the numerator. The record does not explain the full procedure, how participants without an eligible measurement were classified, or how many such participants there were. Those details are not reported in the registry record.

The population is described as all treated participants, but the number contributing to the primary outcome is not reported. Enrollment is 106, whereas the safety group lists 78 at risk; the registry record does not explain this difference. Those figures refer to distinct record elements and should not be assumed to describe the same analysis population. No complete participant flow or outcome-specific denominator is reported. Without those details and the primary result, readers cannot evaluate the impact of missing outcomes on the estimated SVR12 percentage.

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: cholecystitis (4.2%), streptococcal bacteraemia (4.2%), accidental overdose (4.2%), depression (4.2%), ascites (1.9%).

The overall safety group lists 78 participants at risk. Within that group, 8 participants are reported as affected by serious adverse events, 63 as affected by other adverse events, and deaths are reported as 0. These are descriptive counts in the registry record. They should not be interpreted as proof that the regimen caused each event, and the single-group design provides no concurrent randomized safety comparison.

The registry separately lists HCV treatment-naive and treatment-experienced groups. The naive group has 54 participants at risk, with 4 affected by serious adverse events and 44 affected by other adverse events; deaths are 0. The experienced group has 24 participants at risk, with 4 affected by serious adverse events and 19 affected by other adverse events; deaths are 0. These groupings do not constitute randomized comparisons, and the counts should not be interpreted as showing a causal difference between treatment-history groups.

Serious adverse event terms listed include cholecystitis, streptococcal bacteraemia, accidental overdose, and depression, each reported as 4.2%, and ascites and chest discomfort, each reported as 1.9%. The registry record does not provide further event-level context in these summaries. Enrollment is 106, but the overall safety group lists 78 at risk; the record does not explain that denominator difference.

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

The registry record identifies a clinically specific study population: people with cirrhosis and genotype 3 hepatitis C infection. It describes a 24-week regimen of daclatasvir, sofosbuvir, and weight-based ribavirin, and defines SVR12 as the primary outcome. Those details make the research question and intended endpoint clear.

However, the primary endpoint estimate and its 95% confidence interval are not reported in the registry record. The posted results therefore cannot show what percentage achieved SVR12 or how precise that estimate was. An endpoint definition should not be mistaken for a finding, and the treatment regimen’s intended purpose should not be treated as evidence of the observed outcome.

The design is single group, with no reported randomized comparator. Accordingly, even a reported response percentage would describe the treated participants rather than quantify a randomized difference between treatments. The same caution applies to the safety counts: they summarize reported events in the group and do not, by themselves, establish causation.

The safety record includes counts for serious and other adverse events and reports zero deaths in the listed groups. It does not resolve why the overall safety population at risk is 78 when enrollment is 106, or whether the primary endpoint population has the same denominator. The record also does not supply a complete participant flow or enough detail to independently reconstruct the primary analysis.

In general, clinical decisions require consideration of evidence beyond a registry entry, including the full study context and other relevant evidence. The registry information supports a statistical reading of the design, endpoint definition, and available safety summaries, but not a conclusion about comparative benefit or the treatment’s overall effect.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its clear endpoint definition sits alongside a missing primary outcome result. The registry specifies SVR12, its follow-up timing, the response criterion, an analysis population, and a 95% confidence interval. Yet the result and interval are not reported in the registry record. This distinction matters: a detailed outcome definition helps readers understand what was intended to be measured, but it cannot substitute for the estimate needed to assess the observed response and its precision.

The single-group design is another important feature. Without a randomized control, the study record describes participants treated with the regimen but does not provide a concurrent treatment contrast. This limits what can be inferred from outcome percentages and makes comparisons with other groups especially vulnerable to differences in population, follow-up, and measurement.

The record also illustrates why denominators and analysis populations need to be explicit. Enrollment is listed as 106, while the overall safety group lists 78 at risk. The record does not explain the difference, and it does not report the primary endpoint denominator. Readers cannot assume that enrollment, safety, and efficacy populations are interchangeable.

Finally, safety counts and event terms are useful descriptive information, but they do not establish causation or comparative risk. The registry provides some counts and percentages while leaving key analysis and participant-flow details unreported. Together, these features show why statistical interpretation depends not only on the endpoint and observed counts, but also on transparent results, denominators, comparator structure, and analysis methods.

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 interpreting efficacy is that the registry record does not report the SVR12 estimate or its specified 95% confidence interval. The outcome definition is available, but there is no reported result from which to assess response magnitude or precision. The record also does not give the number of participants contributing to that endpoint.

The study is single group, with no reported randomized comparator. Its findings therefore cannot supply a randomized comparison against another treatment or no treatment. Masking is listed as none. The record does not report enough information to assess how the absence of masking may have affected measurement or reporting.

Enrollment is 106, while the overall safety group lists 78 participants at risk. The registry record does not explain this discrepancy or provide a full participant flow. The relationship between the enrolled, treated, safety, and primary-outcome populations is therefore unclear from the record.

The primary outcome description names a modified intention-to-treat approach, excludes measurements after non-study anti-HCV medication begins, and uses Next Value Carried Backwards for the numerator. The record does not fully describe implementation, missing-outcome classifications, or the number of participants affected by these rules. A statistical analysis plan, multiplicity strategy, interim analysis details, and sample-size justification are not reported in the registry record.

Safety summaries provide counts and selected event terms, but the record does not establish event causality. The safety groups are descriptive and do not support randomized comparisons between treatment-history subgroups.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Daclatasvir and Sofosbuvir With Ribavirin in Subjects With Cirrhosis and Genotype 3 Hepatitis C Infection — NCT02673489.
• Registry record last updated 2018-05-08; status last verified 2018-04.
• Results first posted 2018-03-29.
• 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 a completed Phase 3, single-group study of daclatasvir, sofosbuvir, and ribavirin in people with cirrhosis and genotype 3 hepatitis C infection. Enrollment is listed as 106. Treatment was oral daclatasvir 60 mg once daily, sofosbuvir 400 mg once daily, and ribavirin 1000-1200 mg per day based on weight, for 24 weeks.

The primary outcome was SVR12, defined by HCV RNA below the lower limit of quantitation at follow-up Week 12. The outcome estimate and its 95% confidence interval are not reported in the registry record. The overall safety group lists 78 participants at risk, 8 affected by serious adverse events, 63 affected by other adverse events, and 0 deaths. The record does not explain the difference between enrollment and the safety denominator.