Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant (NCT02032875), a non-randomized phase 3 study. The primary outcome is Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12).

2. Clinical Question

3. Trial Design

This was a completed Phase 3 study with non-randomized allocation, no masking, and a parallel model. Enrollment was 116. The registry lists the condition as hepatitis C and names Bristol-Myers Squibb as sponsor. The study started in 2014-03, and primary completion was in 2014-11. These dates describe the recorded trial timeline; they do not establish when each participant entered or completed treatment.

The design separated participants into a post-liver transplant cohort and a cirrhotic cohort. Both received daclatasvir, sofosbuvir, and ribavirin. The post-transplant regimen is described as daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin dosed according to baseline hemoglobin, creatinine clearance, and tolerated dose, taken daily for 12 weeks. The cirrhotic cohort description likewise lists oral treatment for 12 weeks. The brief summary says treatment duration could be extended for cirrhotic participants under certain conditions, but the conditions and the number who may have received an extension are not reported in the registry record.

Participants were followed for 24 weeks after treatment. The primary endpoint focuses specifically on genotype 1 infection in the post-transplant cohort, while listed secondary outcomes include SVR12 for other genotype groupings, HCV RNA measurements at several treatment and follow-up times, and adverse events. The trial's broad enrollment description and its narrower primary population should not be conflated: the primary estimate, if available, would answer a question about the specified post-transplant genotype 1 population, not automatically every cohort or genotype.

Because treatment was not randomized and every cohort received the combination, the design does not provide a randomized treatment-versus-control estimate. The registry record does not report a comparator arm, masking, or an allocation process beyond non-randomization. It also does not report a statistical analysis plan or a rationale for the enrollment target. The design can describe outcomes among treated participants, but by itself it cannot isolate a causal treatment effect from the course of disease, participant characteristics, or other influences.

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: A total of 116 participants were enrolled, of which 113 received study treatment (60 cirrhotic cohort, 53: post-liver transplant cohort). Remaining 3 participants no longer met study criteria. Of the 60 participants in the cirrhotic cohort, 57 did not receive a treatment extension and 3 received a treatment extension after liver transplant.

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 HCV genotype 1 infected post-transplant participants who received at least 1 dose of study therapy.

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: All participants who received at least 1 dose of active study therapy.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12), measured over Post-treatment follow-up Week 12.

The primary endpoint is the percentage of HCV genotype 1-infected post-liver transplant participants who achieved SVR12. SVR12 was defined as HCV RNA below the lower limit of quantitation, stated as <25 IU/mL, at post-treatment follow-up Week 12. The record says the measurement used the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. The endpoint population consisted of post-transplant participants with genotype 1 infection who received at least 1 dose of study therapy.

SVR12 is a binary outcome at a specified follow-up point: each person either meets the RNA threshold or does not, based on the endpoint definition and the available measurement. Reporting the percentage gives the proportion of the defined analysis population meeting that criterion. A confidence interval can express uncertainty around that proportion; the registry identifies a 95% confidence interval as the dispersion measure, but does not report the numerical estimate or interval.

The endpoint uses a laboratory threshold rather than symptoms or a clinician-rated outcome. It is therefore important to interpret it as a virologic measure at the stated time, not as a complete account of health status or long-term outcomes. For participants who missed the Week 12 follow-up visit, the record says SVR12 was imputed using the next and closest available HCV RNA measurement after the Week 12 window. The number of participants affected by this procedure and the resulting endpoint estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a percentage endpoint and a 95% confidence interval as its dispersion measure. It does not report the primary numerical result, the confidence interval limits, the statistical test, or a detailed analysis plan. The methods discussion below explains general concepts relevant to interpreting this type of outcome; it does not establish which unreported procedures the trial used.

What does a percentage endpoint represent?

For a binary outcome, a percentage describes the share of the analysis population classified as meeting the outcome definition. In this trial, the classification is based on whether HCV RNA was below the stated laboratory threshold at post-treatment Week 12. The denominator is determined by the analysis population, which the registry describes as genotype 1-infected post-transplant participants who received at least 1 dose. Without the numerator, denominator used in the reported analysis, and resulting estimate, the endpoint definition alone does not reveal the observed percentage.

A binary percentage compresses individual outcomes into a group summary. It does not show how outcomes varied among people, the timing of changes between measurements, or other clinical outcomes. The registry's secondary outcomes include HCV RNA status at specified treatment and follow-up weeks, which are distinct summaries at different time points. Those measurements should not be treated as interchangeable with the primary SVR12 endpoint.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimate, including uncertainty that can arise because the observed participants are only a sample from a broader population of interest. Its width depends on factors such as the estimate, the amount of information, and the method used. A confidence interval is not a guarantee that a particular range contains the true value, nor does it resolve design limitations such as non-random allocation.

The registry calls for a 95% confidence interval, but the interval itself is not reported in the registry record. Without its limits, readers cannot judge how precise the reported primary proportion would be. Nor can the width be reconstructed from the enrollment figure: the primary analysis population is narrower than enrollment, and the actual analysis denominator and observed outcome count are not reported. No calculation should substitute for the absent analysis result.

Why does the design affect interpretation?

Randomization, in general, helps balance measured and unmeasured characteristics across groups on average, supporting a fair treatment comparison. This trial is recorded as non-randomized, and both cohorts received the combination. Its parallel structure means cohorts were followed as separate groups, but parallel groups are not automatically valid comparators. The cohorts are distinguished by transplant status and cirrhosis, so a difference in their outcomes could reflect their clinical circumstances rather than a treatment contrast.

Masking can, in general, reduce the influence of knowledge of treatment assignment on some assessments or decisions. The record lists no masking. The primary endpoint is laboratory-based, but the registry does not report whether any other protections or review procedures were used. Such procedures should not be assumed. More broadly, the record does not report adjusted analyses that might address differences in participant characteristics.

How should planning illustrations be understood?

General sample-size planning asks how many participants may be needed under specified assumptions to detect an effect with a chosen statistical criterion. The planning illustration described for this analysis uses an observed effect as its basis, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is set as a stated fraction of the observed effect. These are illustration assumptions, not the trial's own design justification. The record does not report a sample-size rationale, and the trial itself was non-randomized rather than an equal-allocation randomized comparison.

Such illustrations are not observed power. They do not show the probability that the completed trial detected an effect, and they do not establish that the trial was adequately powered for its actual design. A planning value depends on its assumptions, including the effect chosen, allocation, and statistical model. If an observed effect is uncertain, planning around it can also produce an unstable target. No numerical planning results are reported in the registry record, so no number of participants per arm for 80% power or other target can be stated.

More generally, over-dispersion matters when variation in observed outcomes exceeds what a chosen model assumes. If it is ignored, uncertainty estimates can be too small and intervals too narrow. That issue is a general statistical consideration; the record does not report an over-dispersion analysis, a model for the primary endpoint, or whether such a concern arose in this trial.

What cannot be inferred from missing statistical detail?

The absence of a reported test or analysis model is not evidence that no analysis was performed. It means the registry record does not permit readers to identify the method, assess its assumptions, or reproduce the result. The record reports zero analyses in its analysis listing, but does not explain whether that means no analysis entries were registered or whether results were analyzed elsewhere. It also does not report p-values, adjusted estimates, subgroup analysis methods, or a prespecified statistical hierarchy.

General interpretation should therefore remain descriptive. The endpoint has a clear threshold and time point, and the registry names the intended confidence level. But there is no numerical estimate to interpret, no interval to assess, and no documented randomized comparison from which to estimate a treatment contrast. Statistical methods cannot recover missing outcome data or remove the confounding risks inherent in the non-randomized design.

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("Post-liver Transplant Cohort: Daclatasvir+Sofosbuv")
n      <- c(41)
events <- c(39)
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  Post-liver Transplant Cohort: Daclatasvir+Sofosbuv  41  39  95.1  83.5  99.4  83.9  98.7  83.8  98.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes covering SVR12 for all genotypes and specified genotype groups, serial HCV RNA status during treatment and follow-up, SVR12 by CC or non-CC genotype, serious adverse events and other adverse-event categories, and treatment-emergent Grade 3-4 laboratory abnormalities. It records 8 outcome measures and 0 analyses. The listed outcomes represent multiple questions, but the record does not report a testing hierarchy, multiplicity adjustment, or rules for interpreting a family of statistical tests. It is therefore not possible to determine whether any reported secondary findings would have been adjusted for multiple comparisons.

The primary endpoint definition includes a specific approach for missed Week 12 visits: SVR12 was imputed from the next and closest available HCV RNA measurement after the Week 12 window. The number of missed visits, the number of endpoint values imputed, and sensitivity analyses under alternative assumptions are not reported in the registry record. The record also does not state how other missing measurements or withdrawals were handled.

Analysis populations can affect a percentage because they determine which participants contribute to the numerator and denominator. The primary population is defined as genotype 1-infected post-transplant participants who received at least 1 dose. The record does not provide the analyzed denominator, a participant disposition account, or definitions for additional analysis populations. It would therefore be inappropriate to assume an intention-to-treat, per-protocol, or safety population beyond the explicit primary population description.

These gaps limit assessment of the robustness of the results. A reader cannot tell whether the imputation approach materially changed the endpoint estimate, whether results differed across analysis populations, or how multiplicity was addressed. The numerical endpoint results and supporting analysis details are not reported in the registry record.

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: hepatocellular carcinoma (5.0%), polyarthritis (1.9%), hepatic encephalopathy (1.9%), acute kidney injury (1.9%), localised intraabdominal fluid collection (1.9%).

The registry lists serious adverse events separately for the two treated cohorts. In the post-liver transplant cohort, 5 serious adverse events are listed among 53 at risk. In the cirrhotic cohort, 10 are listed among 60 at risk. These are event-summary counts as recorded; they should not be read as a randomized comparison because cohort assignment was non-randomized and the clinical populations differ. The record does not provide an adjusted comparison or a treatment-free control group.

Separate other-event fields list 38 among 53 at risk in the post-transplant cohort and 42 among 60 at risk in the cirrhotic cohort. These figures are distinct from the serious-event counts. The registry record does not further define the other-event field in the information, so it should not be relabeled as a specific severity category. Death counts are not reported in the registry record.

The listed serious-event terms include hepatocellular carcinoma at 5.0%, and polyarthritis, hepatic encephalopathy, acute kidney injury, localised intraabdominal fluid collection, and upper respiratory tract infection at 1.9% each. The record does not supply the event-term denominators or explain whether terms could overlap within participants. These term percentages should therefore be read as registry-reported descriptors, not added together or interpreted as independent risks. The count and percentage summaries alone do not establish whether an event was caused by treatment.

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

The posted record defines a clinical question: whether HCV genotype 1-infected post-transplant participants who received at least 1 dose achieved SVR12, based on HCV RNA below the stated threshold at post-treatment Week 12. It also describes treatment in a cirrhotic cohort and lists secondary virologic and safety outcomes. However, the numerical primary result is not reported in the registry record. Without that estimate and its confidence interval, the observed frequency and precision of SVR12 cannot be evaluated.

Even if a primary percentage were available, its interpretation would be limited to the defined population and endpoint. It would not automatically apply to all enrolled participants, the cirrhotic cohort, other genotypes, or outcomes beyond the specified follow-up. SVR12 is a laboratory outcome at a defined time, not a complete measure of every aspect of health or a direct account of long-term outcomes. The registry reports 24 weeks of post-treatment follow-up, but does not provide the numerical results for that period.

The design also limits what can be concluded. Both cohorts received the combination, allocation was non-randomized, and no control group is described. A treated-cohort outcome is descriptive; it does not by itself identify what would have happened to comparable participants under another treatment or without treatment. The two cohorts are not a substitute for a control group because they represent different clinical settings.

The safety counts are useful as descriptions of events recorded in the cohorts, but they do not establish causation or comparative safety. The serious-event totals, other-event counts, and selected event-term percentages must be read within their reported definitions and denominators. Death counts and fuller analysis details are not reported in the registry record.

Accordingly, the record supports statements about the study design, endpoint definition, follow-up schedule, and selected adverse-event summaries. It does not support a numerical conclusion about the primary endpoint, a precise estimate of its uncertainty, or a causal claim about treatment benefit or harm. Missing results are not evidence that an outcome did or did not occur; they leave that question unresolved in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated endpoint is not the same as a fully interpretable result. The primary question is defined with a specific population, laboratory threshold, and follow-up time. The record also specifies a 95% confidence interval as the dispersion measure. Yet the percentage and interval are absent. Without both the estimate and a measure of its precision, readers cannot assess how frequent the endpoint was in the analysis population or how uncertain that estimate may be.

It also demonstrates why study structure must be considered before interpreting cohort outcomes. The trial was non-randomized, and both groups received the combination. Although the cohorts are presented in parallel, their different clinical contexts do not create an unbiased treatment comparison. Separating post-transplant and cirrhotic participants is useful for describing distinct populations, but it does not make one group an appropriate control for the other.

The distinction between the broad trial population and the primary analysis population is another important statistical issue. The study included cirrhotic and post-transplant participants, while the primary endpoint applies only to genotype 1-infected post-transplant participants who received at least 1 dose. Generalizing beyond that group would require additional results and justification. The record lists secondary questions addressing genotypes, time points, and safety, but does not provide their analyses.

Finally, the record highlights the value of transparent reporting of missing-data handling, analysis populations, and multiplicity. It gives a method for imputing a missed Week 12 endpoint measurement, but not how many values were imputed or whether sensitivity analyses were conducted. Those details help readers understand the dependence of a result on analytic choices. In their absence, careful interpretation means distinguishing what the registry defines and counts from what it does not report.

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 principal limitation for statistical interpretation is that the primary SVR12 estimate and its 95% confidence interval are not reported in the registry record. The endpoint definition is detailed, but the numerical outcome, analysis denominator, and number of participants meeting the threshold are unavailable. The listed enrollment of 116 does not supply the primary analysis denominator, because the endpoint population is restricted to genotype 1-infected post-transplant participants who received at least 1 dose.

The non-randomized design has no described control group, so the trial cannot provide a randomized comparison with another treatment or no treatment. Its two cohorts differ in clinical setting, and direct comparisons could be confounded by those differences. The record does not report adjusted comparisons or enough participant characteristics to assess how groups might differ.

The record describes imputation for missed Week 12 visits, using the next and closest available HCV RNA measurement after the visit window. It does not report how often this occurred, the missing-data pattern, or sensitivity analyses. It also does not define all analysis populations, report participant flow, or explain the analysis listing that contains 0 analyses.

Other limitations include the absence of a reported statistical analysis plan, sample-size justification, multiplicity approach, primary endpoint test, or numerical secondary outcome results. The registry describes that cirrhotic treatment could be extended under certain conditions but does not specify the conditions or the number affected. Safety data include selected counts and term percentages, but the record does not provide a detailed account of event-term denominators or death counts. These omissions restrict assessment of precision, robustness, and comparability; they do not establish that the underlying outcomes were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant — NCT02032875.
• Registry record last updated 2017-02-09; status last verified 2016-12.
• Results first posted 2015-10-20.
• 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 completed Phase 3 trial enrolled 116 participants and used a non-randomized, unmasked, parallel design. It studied daclatasvir, sofosbuvir, and ribavirin in cirrhotic and post-liver transplant cohorts, with 24 weeks of post-treatment follow-up. The primary endpoint was SVR12 among HCV genotype 1-infected post-transplant participants who received at least 1 dose, defined by HCV RNA below the lower limit of quantitation at post-treatment Week 12.

The registry record does not report the numerical primary endpoint result or its confidence interval. It lists serious-event counts of 5 among 53 at risk in the post-transplant cohort and 10 among 60 at risk in the cirrhotic cohort, with additional other-event counts and selected serious-event terms. The non-randomized design and missing numerical efficacy results limit comparative and causal interpretation.