Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus (NCT01471574), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12).

2. Clinical Question

This is a question about the observed response in the study group, not a randomized estimate of the difference between treatment and control. The endpoint is a virologic measure at a specified follow-up time. Although the registry identifies it as the primary endpoint, it does not report the percentage, the participant count used to calculate it, or its 95% confidence interval. Thus, the clinical question is defined, but the posted primary endpoint result cannot be assessed for magnitude or precision from the registry record.

3. Trial Design

The registry describes a phase 3, open-label, single-group study sponsored by Bristol-Myers Squibb. It lists 549 enrolled participants and a completed status. The recorded study start is 2011-12, and primary completion is recorded as 2014-06. The condition is hepatitis C, genotype 1, in people coinfected with HIV; the study purpose concerns participants with untreated hepatitis C.

The listed treatment combines daclatasvir, pegylated interferon-alfa 2a, and ribavirin. The record identifies no masking and gives allocation as NA. It does not identify a separate control group, so the design does not support a randomized, between-group treatment contrast. The group descriptions in the safety information distinguish HAART status and daclatasvir dose categories, but the registry does not describe these as randomized comparison arms. The arm description field contains no further description.

The primary endpoint is sustained virologic response at follow-up week 12 (SVR12). The analysis population is defined as all participants who received at least 1 dose of study therapy. The size of that analysis population is not reported in the registry record. The registry lists six outcome measures, including additional virologic, HIV RNA, genetic-subgroup, and safety outcomes, but does not provide numerical results for the primary endpoint in the information available for this analysis.

Enrollment is not interchangeable with the number analyzed for a particular endpoint. Participants may enter an analysis population under endpoint-specific rules, and those rules can differ across outcomes. The registry's stated primary analysis population gives a minimum exposure criterion, but additional handling of missing measurements or other eligibility conditions is 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: Of 549 participants enrolled, 301 were randomized to receive treatment. Of the 248 participants who were not randomized, 204 no longer met study criteria, and 44 discontinued due to other reasons.

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: The analysis was performed in all 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 study therapy.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12), measured over Follow-up Week 12.

SVR12 is the registry's primary endpoint. It is defined as HCV values below the lower limit of quantitation, with target detected or target not detected, at follow-up week 12. The record says HCV RNA was measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. The endpoint is expressed as a percentage of participants, and the stated dispersion measure is a 95% confidence interval.

As a general statistical explanation, a binary endpoint classifies each participant according to whether the specified condition is met. A percentage describes the proportion meeting that condition in the analysis population. The confidence interval communicates uncertainty around an estimated percentage: it gives a range of values compatible with the data under the method used, rather than guaranteeing that the true value lies within that range.

A follow-up endpoint makes the assessment time explicit. For this outcome, the relevant measurement is at follow-up week 12, not an unspecified time during treatment. The registry definition includes both target-detected and target-not-detected results when HCV RNA is below the lower limit of quantitation. That detail matters because a below-quantitation result is not defined as requiring target not detected.

The registry does not report the observed percentage, the number meeting the definition, the analysis denominator, or the 95% confidence interval. Consequently, the endpoint definition can be explained, but its observed magnitude and precision cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available for this study is limited. The registry identifies a percentage endpoint and a 95% confidence interval, but does not report the numerical endpoint estimate, its denominator, or the method used to construct the interval. It also records zero analyses in the analysis listing. Therefore, the statistical concepts below explain how such results are generally interpreted; they do not describe an unreported analysis method used by the study.

What does a percentage endpoint represent?

As a general explanation, a binary outcome assigns each participant to one of two categories for the endpoint: meeting the stated definition or not meeting it. The percentage is the count meeting the definition relative to the analysis denominator. For this study, the definition is HCV RNA below the lower limit of quantitation at follow-up week 12, with target detected or target not detected. The registry specifies an analysis population of participants who received at least 1 dose of study therapy, but does not provide its size or the number with an endpoint measurement.

A percentage should always be read with its denominator and outcome definition. If some participants lack a measurement, the way those participants are classified or excluded can change the estimate. General approaches include analyzing only participants with observed measurements or assigning a defined outcome to missing measurements. The registry record does not report which approach was used, so no missing-data assumption should be attributed to this study.

What does a confidence interval add?

As a general explanation, a confidence interval expresses the uncertainty associated with an estimate. For a percentage, its width is influenced by the amount of information available and by the observed event frequency, as well as by the interval method. A narrower interval generally indicates greater precision than a wider interval. The stated 95% confidence level describes the interval procedure's long-run coverage property under its assumptions; it is not a 95% probability statement about this particular interval after it has been calculated.

No interval bounds are reported for SVR12. The reader therefore cannot judge whether the estimate, if available, would be precise or highly uncertain. The interval method is also not reported in the registry record, so it is not possible to assess whether it used a particular approximation or small-sample adjustment.

Why does the design affect interpretation?

As a general explanation, a single-group study estimates outcomes within the group observed. A randomized controlled design can estimate a between-group contrast by comparing outcomes under assigned treatment strategies, subject to its assumptions and conduct. This study is recorded as single-group, without masking, and with allocation listed as NA. A within-group response percentage therefore cannot be interpreted as a randomized treatment effect or as evidence of the size of a causal effect relative to an untreated or alternative-treatment group.

Open-label describes the absence of masking in the record. The registry does not explain how this feature affected outcome measurement or reporting. SVR12 is based on a laboratory measurement, and the record identifies a central laboratory assay, but that fact does not establish that all other sources of bias were absent.

What do the planning assumptions mean?

The registry's planning-illustration assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. These assumptions describe a planning framework, not the original trial design. The study itself is recorded as single-group, so an equal-allocation, two-arm illustration should not be mistaken for a description of randomized groups in this trial. No numerical planning estimates are reported in the registry record.

As a general explanation, a sample-size illustration asks how many participants might be needed under stated assumptions to detect a specified effect with a selected design and error rate. Its result depends on the assumed effect and method. It is not an observed outcome and is not observed power. The sample-size justification for the original study, including the assumptions used by its investigators, is not reported in the registry record.

Why can over-dispersion matter?

As a general explanation, over-dispersion occurs when outcome variability is greater than a statistical model assumes. If a model underestimates variability, standard errors and confidence intervals may be too small, and tests may appear more conclusive than warranted. This is a general consideration for statistical modeling, not a reported feature or analysis of this study. The registry record does not identify a model for the primary binary endpoint, so no claim about over-dispersion in the trial analysis is justified.

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("Highly Active Anti-Retroviral Therapy (HAART):Dacl", "HAART Therapy: Daclatasvir, 60 mg", "HAART: Daclatasvir, 30 mg + 60 mg", "HAART Therapy: Daclatasvir 30 or 60 or 90 mg", "Non-HAART Therapy: Daclatasvir, 60 mg")
n      <- c(132, 39, 106, 277, 24)
events <- c(99, 28, 76, 203, 21)
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  Highly Active Anti-Retroviral Therapy (HAART):Dacl  132  99  75.0  66.7  82.1  67.0  81.6  67.0  81.6
ARM  HAART Therapy: Daclatasvir, 60 mg  39  28  71.8  55.1  85.0  56.2  83.5  56.1  83.4
ARM  HAART: Daclatasvir, 30 mg + 60 mg  106  76  71.7  62.1  80.0  62.5  79.4  62.5  79.4
ARM  HAART Therapy: Daclatasvir 30 or 60 or 90 mg  277  203  73.3  67.7  78.4  67.8  78.2  67.8  78.1
ARM  Non-HAART Therapy: Daclatasvir, 60 mg  24  21  87.5  67.6  97.3  69.0  95.7  68.8  95.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures: the primary SVR12 percentage and secondary outcomes concerning HCV RNA thresholds, HIV RNA among participants receiving HAART, SVR12 by IL28B genotype, and safety. Listing several outcomes creates a general multiplicity consideration if multiple hypotheses are tested or multiple results are interpreted as confirmatory. As a general explanation, evaluating many outcomes can increase the chance of at least one apparently unusual finding when each is assessed separately. Statistical plans may address this by defining a hierarchy, adjusting significance thresholds, or treating some analyses as exploratory.

The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or a statistical analysis plan. It also reports zero analyses in the analysis listing. The numerical results and inferential tests for the listed outcomes are not reported in the registry record, so there is no basis for describing an adjustment or deciding which results were treated as confirmatory.

The primary analysis population is defined as participants who received at least 1 dose of study therapy. The number in that population, endpoint-specific denominators, and the extent of missing outcome data are not reported in the registry record. The handling of missing primary endpoint measurements is also not reported. As a general explanation, different missing-data rules can yield different denominators and estimates; conclusions about bias or sensitivity analyses require knowing the rule and the missingness pattern.

Interim analyses, stopping rules, and details of the statistical plan are not reported in the registry record. These omissions should not be filled by assumption. They limit the ability to assess how outcomes were selected, how missing measurements were handled, and whether reported analyses followed a prespecified plan.

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: diarrhoea (2.6%), nausea (2.6%), appendicitis (2.6%), pancytopenia (2.6%), renal failure acute (2.6%).

The safety record lists four categories distinguished by HAART status and daclatasvir dose. In the HAART, daclatasvir 30 mg category, 12 serious-event-affected participants are listed among 132 at risk. In the HAART, daclatasvir 60 mg category, the corresponding figures are 6 among 39. In the HAART, daclatasvir 30 mg + 60 mg category, they are 6 among 106. In the non-HAART, daclatasvir 60 mg category, they are 0 among 24. These are category-specific figures and should not be combined into a pooled estimate.

The registry lists Diarrhoea, Nausea, Appendicitis, Pancytopenia, Renal failure acute, and Sepsis at 2.6% each among the top serious-event terms. The number of deaths is not reported in the registry record. The record also lists other adverse-event-affected counts for each category, but does not provide definitions or further detail for those figures in the information available.

As a general statistical caution, descriptive counts do not by themselves establish that risks differ between categories. The categories are not identified as randomized comparison groups, and their sizes vary. The serious-event figures therefore describe what is recorded within each category; they do not establish a comparative treatment effect or explain why an event occurred.

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

The registry record defines a primary question about SVR12 after a regimen of daclatasvir, pegylated interferon-alfa 2a, and ribavirin in people with untreated hepatitis C and HIV coinfection. It specifies that SVR12 means HCV values below the lower limit of quantitation, with target detected or target not detected, at follow-up week 12. It also identifies the primary analysis population as those who received at least 1 dose of study therapy.

However, the primary endpoint percentage, numerator, denominator, and 95% confidence interval are not reported in the registry record. The central efficacy result therefore cannot be described as high, low, precise, or uncertain. The lack of a posted estimate should not be interpreted as a positive or negative outcome; it is an absence of the numerical result needed to make that assessment.

Even if a within-group percentage were available, the single-group design would describe the observed outcome in the study population rather than provide a randomized comparison with another treatment or no treatment. As a general explanation, causal comparisons require a suitable comparison strategy and careful attention to design and analysis. The registry record does not identify a separate control group for this study.

The reported safety counts and serious-event terms offer descriptive information, but they do not establish comparative safety. The registry does not report the number of deaths. The additional outcome titles indicate other measures of interest, but their numerical findings are not reported in the registry record. Thus, the record supports interpretation of the study's structure, definitions, and selected safety counts, but does not support conclusions about the size of the primary virologic response or comparative treatment effects.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly specified primary outcome and the absence of its numerical result in the registry record. The endpoint definition identifies the laboratory threshold, the follow-up time, and the analysis population criterion. Those details are essential for understanding what an eventual percentage would mean. Without the estimate, denominator, and confidence interval, however, neither the outcome magnitude nor its precision can be evaluated.

The single-group design also sets an important interpretive boundary. A percentage within one group can describe the recorded response among analyzed participants, but it does not itself estimate a randomized difference. The open-label designation and absence of a listed comparator are part of the context for interpreting any observed outcome. These are design characteristics, not evidence of a particular direction or size of bias.

The record further illustrates why outcome titles and outcome results are distinct. It lists multiple virologic and safety measures, but the titles do not communicate their numerical findings. Multiplicity and missing-data methods matter when several outcomes are assessed, yet the registry does not report those methods. Clear endpoint definitions are useful, but they cannot substitute for reporting analysis populations, missingness, estimates, and uncertainty.

Finally, the safety record presents counts within categories distinguished by HAART status and dose. Such descriptive data can be read as category-specific observations, while avoiding an unsupported like-for-like comparison. This distinction between description and causal comparison is central to sound statistical interpretation of non-randomized, single-group evidence.

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 SVR12 estimate and its 95% confidence interval are not reported in the registry record. The number of participants meeting the endpoint and the endpoint denominator are also absent. Although enrollment is listed as 549, the primary analysis population is defined by treatment exposure, and its size is not reported.

The record does not describe handling of missing week-12 measurements, the statistical method for the confidence interval, or any sensitivity analyses. It does not report a statistical analysis plan, multiplicity procedures, interim analyses, stopping rules, or the sample-size justification for the original design. As a result, these aspects cannot be evaluated without guessing.

The study is listed as single-group, open-label, with allocation recorded as NA and no separate comparator identified. This limits interpretation to within-group description rather than randomized comparative effect estimation. The registry does not provide further details about the dose-category structure or establish that those categories are comparable.

For safety, serious-event counts are available for four categories, but the number of deaths is not reported. The serious-event terms are listed with percentages, without further detail in the registry record about their analysis or context. The registry lists additional outcomes but does not report their numerical results. These limitations concern what can be established from the registry record; they do not establish that unreported analyses or information do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus — NCT01471574.
• Registry record last updated 2016-01-29; status last verified 2015-12.
• Results first posted 2015-12-17.
• 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

NCT01471574 is a completed phase 3, open-label, single-group study sponsored by Bristol-Myers Squibb. The registry lists 549 enrolled participants, a start of 2011-12, and primary completion in 2014-06. The study concerns untreated hepatitis C and HIV coinfection, with hepatitis C genotype 1 listed as the condition. The regimen is daclatasvir with pegylated interferon-alfa 2a and ribavirin.

The primary outcome is the percentage with SVR12, defined using HCV values below the lower limit of quantitation at follow-up week 12. The analysis population includes participants who received at least 1 dose. The primary percentage, denominator, and 95% confidence interval are not reported in the registry record. Safety information lists serious-event counts across four HAART and dose categories and six serious-event terms at 2.6% each; deaths are not reported. The registry does not report a separate comparator, missing-data approach, multiplicity strategy, or original sample-size justification.