Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia (NCT01741545), a non-randomized phase 3 study. The primary outcome is Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12.

2. Clinical Question

Statistically, this is a question about the proportion meeting a defined response criterion after treatment, rather than a direct comparison of randomized treatment groups. The endpoint is intended to describe response at a specified follow-up time. Without a posted endpoint estimate, the registry record does not establish the response proportion or its precision for either cohort or for the study population overall.

3. Trial Design

The registry describes a completed Phase 3 study with non-randomized allocation, no masking and a parallel model. Enrollment is listed as 71. Participants had chronic hepatitis C and underlying hemophilia. The official title specifies treatment-naïve participants and those who were prior relapsers to peginterferon alfa-2a and ribavirin.

The treatment groups were organized by genotype. Cohort A covered genotypes 2 and 3 and received lambda 180 μg by subcutaneous injection once weekly, ribavirin 200 mg orally twice daily, and daclatasvir 60 mg orally once daily for 12 weeks. Cohort B covered genotypes 1b and 4. It received lambda 180 μg once weekly and ribavirin 200 mg twice daily for 24 weeks, while daclatasvir 60 mg once daily was given for 12 weeks.

Because allocation was non-randomized and the cohorts differed by genotype and treatment duration, their outcomes should not be treated as if they came from equivalent randomized arms. The registry does not report the allocation procedure, whether treatment assignment depended on participant characteristics, or a planned between-cohort comparison. Those details are not reported in the registry record.

The registry lists nine outcome measures: the primary SVR12 endpoint and secondary measures covering virologic response at other time points, treatment-emergent symptoms and laboratory abnormalities, adverse events, serious adverse events, discontinuations, dose reductions and deaths. The registry does not report statistical analyses for these outcomes. Although the study status is completed, completion alone does not supply the missing endpoint estimates or analysis details.

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 71 participants were enrolled, of which 51 subjects were randomized and treated.

Treatment Period

Reasons for not completing this period:

Follow-up Period (24 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed in modified intent to treat (mITT) population defined as participants meeting the response criteria over 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.

Population: All treated participants.

6. Primary Endpoint

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

The primary endpoint is the percentage of participants achieving sustained virologic response at follow-up Week 12. The registry defines response as HCV RNA below the lower limit of quantitation, with the target either detected or not detected. This is a binary outcome for each participant: the participant either meets the stated response criterion or does not.

In general, a proportion communicates how common a defined outcome was in the analyzed group. It is useful for a response endpoint because it directly describes the share of participants who met the criterion at a specified assessment time. A confidence interval, when reported, conveys uncertainty around that estimated proportion; it does not guarantee that the true value lies within a particular interval.

The registry states that the analysis used a modified intent-to-treat population, defined as participants meeting the response criteria over all treated participants. It does not give the number analyzed, the observed number meeting the endpoint, the percentage, or a confidence interval. Those results are not reported in the registry record. The absence of an estimate means the primary endpoint cannot be quantitatively interpreted from the registry information.

The brief study summary describes the target as not detected, while the primary outcome description permits the target to be detected or not detected, provided HCV RNA is below the lower limit of quantitation. The primary outcome definition is the more detailed registry definition; the record does not explain this difference in wording.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a proportion estimate?

The primary outcome is a percentage, a form of binary endpoint. Each participant is classified according to whether the prespecified response criterion was met at follow-up Week 12. In general, the estimated proportion is the number of participants meeting the criterion divided by the number included in the analysis. The registry defines the analysis population but does not report the numerator, denominator or resulting percentage. These values are not reported in the registry record.

A percentage is descriptive of the analyzed participants. It should not automatically be read as a causal effect of treatment, particularly in a non-randomized study without a control group. The proportion may depend on which participants were treated, assessed and included in the analysis, as well as on the outcome definition.

What does a confidence interval add?

The primary outcome lists a 95% confidence interval as its measure of dispersion. In general, a confidence interval expresses statistical uncertainty around an estimate. It gives a range of values compatible with the data and the method used, under the method’s assumptions. It is not a guarantee that the underlying value lies in that range, and it does not account for every source of uncertainty, such as systematic differences between non-randomized groups.

The registry record does not report the SVR12 estimate or its interval. Without both, readers cannot assess how precise the primary estimate was. Confidence intervals for the safety percentages are also not described in the available record.

Why does the analysis population matter?

The registry says that the primary analysis used a modified intent-to-treat population and defines it as participants meeting the response criteria over all treated participants. This wording identifies an analysis population, but it does not explain how participants without an evaluable follow-up result were handled. It also does not give the number included in the analysis. The precise operational rules for the modified intent-to-treat population are not reported in the registry record.

In general, an analysis population affects the interpretation of a proportion because excluding participants or treating missing outcomes in a particular way can alter its numerator, denominator or both. Clear reporting therefore includes the number assessed, the number meeting the endpoint and how missing assessments were handled. Those details are not reported.

How should cohort comparisons be understood?

The record describes a non-randomized parallel study with cohorts separated by genotype and different treatment durations. In general, random allocation helps balance measured and unmeasured participant characteristics between groups. Without randomization, group differences may be related to characteristics that also influence the outcome. Therefore, a contrast between these cohorts would be descriptive unless a suitable design and analysis supported a causal interpretation. The registry does not report a planned inferential comparison or an adjusted model.

The record lists zero analyses. It does not state which statistical tests or models were used for the primary endpoint or secondary outcomes. Any particular test, adjustment method or model specification is therefore not reported in the registry record.

How do planning calculations differ from observed evidence?

In general, a sample-size calculation estimates how many participants would be needed under stated assumptions to detect a specified effect with a chosen significance level and power. The planning assumptions described for this trial use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and effects defined as fractions of the observed effect. These assumptions describe a planning illustration, not the trial’s own design or a reported sample-size justification. The registry does not report the protocol’s sample-size justification.

Such planning illustrations are not observed power. They do not show how likely the completed study was to detect an effect after the data were collected, and they do not replace the observed estimate and its confidence interval. For non-time-to-event outcomes, the stated illustration convention is participants per arm. The trial itself is non-randomized, so equal allocation between two arms is an assumption of the planning illustration, not a description of the reported cohort allocation. Numerical planning outputs are not reported in the registry record.

Over-dispersion is a general concern when outcomes vary more than a simple statistical model expects. In a binary endpoint, unmodeled differences among participants or sites can make uncertainty larger than a basic model suggests. This is a general statistical consideration; the registry does not report an over-dispersion assessment or a model addressing it.

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("Cohort A", "Cohort B")
n      <- c(12, 39)
events <- c(11, 35)
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  Cohort A  12  11  91.7  61.5  99.8  64.6  98.5  64.0  98.1
ARM  Cohort B  39  35  89.7  75.8  97.1  76.4  95.9  76.3  95.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures: SVR12 as the primary measure, plus secondary measures of rapid virologic response, complete early virologic response, end-of-treatment response, SVR24, treatment-emergent cytopenic abnormalities, flu-like and musculoskeletal symptoms, adverse events and serious adverse events, and Grade 3 to 4 laboratory abnormalities.

When several outcomes or multiple comparisons are tested, the chance of at least one apparently unusual result can increase. In general, multiplicity methods can control or describe that issue, depending on the analysis plan. The registry record does not report whether any multiplicity adjustment was planned or used, how secondary outcomes were prioritized, or whether any interim analyses were conducted. Those details are not reported in the registry record. The record lists no statistical analyses.

The primary analysis population is described as modified intent-to-treat, but the number included and the handling of missing Week 12 measurements are not stated. The record does not describe imputation, censoring, exclusion rules, or sensitivity analyses for missing outcome data. These details are not reported in the registry record.

In general, missing outcome data can affect a proportion if the participants with missing assessments differ from those with observed assessments. The direction and extent of any effect depend on the missingness pattern and the analysis assumptions. Without the number of missing assessments and the analysis rules, the robustness of the primary estimate cannot be evaluated. The registry also does not report whether the primary endpoint was analyzed separately by cohort or across cohorts.

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: hepatitis acute (2.6%), jaundice (2.6%), haemorrhoids (2.6%), arthritis bacterial (2.6%).

The registry lists 12 participants at risk in Cohort A and 39 in Cohort B for the serious adverse event information. It records 0 participants with a serious adverse event in Cohort A and 4 in Cohort B. The counts for other adverse events are 10 in Cohort A and 36 in Cohort B. Deaths are listed as 0 in both cohorts.

These figures are counts within the recorded safety groups, not estimates of a comparative treatment effect. Because allocation was non-randomized and the cohorts differ by genotype and treatment duration, the counts should not be read as a controlled comparison. The registry does not report statistical tests or confidence intervals for these safety counts.

The serious adverse event terms listed are Hepatitis acute, Jaundice, Haemorrhoids and Arthritis bacterial, each reported as 2.6%. The record does not explain whether these terms represent distinct participants or whether a participant could contribute more than one term. It also does not provide details establishing whether an event was considered related to study treatment. These limitations matter when interpreting the listed percentages: they describe recorded events, but do not alone establish cause or comparative risk.

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

The registry record establishes that the study evaluated a three-drug regimen in participants with chronic hepatitis C and underlying hemophilia, with cohorts organized by genotype. It also defines the primary outcome as SVR12 and describes the treatment schedules. These details clarify what was studied and what response was intended to be measured.

The record does not report the primary SVR12 percentage, the number of participants achieving it, or a confidence interval. Therefore, it does not provide a quantitative estimate of the primary outcome’s frequency or precision. The completed status does not fill this gap: a study can be completed while results remain absent from the registry record.

The design also limits what could be inferred from a cohort contrast. Non-randomized allocation and the genotype-based cohort definitions do not provide a like-for-like control comparison. Even if separate outcomes were available, differences between cohorts could not automatically be attributed to treatment schedule or another single factor. The record does not report a control group or an adjusted comparison.

The safety counts provide a descriptive account of recorded serious and other adverse events in the listed safety groups, along with no recorded deaths in either cohort. They do not establish that treatment caused an event, and they do not determine how the safety profile compares with another treatment or with no treatment.

In general, an endpoint estimate and its uncertainty answer a different question from whether a treatment effect is causal. The estimate describes outcomes in an analyzed population; the design and analysis determine how far a causal interpretation is justified. Here, the primary estimate and its uncertainty are not reported, and the non-randomized design has no stated control arm. The available record therefore supports description of the study and selected safety counts, but not a numerical conclusion about SVR12 or a controlled treatment effect.

14. Why This Trial Matters Statistically

This trial raises several statistical issues that are important in clinical research. First, a clearly defined endpoint is not the same as a reported result. The record defines SVR12 and specifies the follow-up time, but does not report the estimate, analysis denominator or confidence interval. Without those quantities, readers cannot judge either the observed response frequency or its precision.

Second, the study design shapes the interpretation. The registry describes non-randomized allocation and genotype-defined cohorts with different treatment schedules. This makes it important to distinguish descriptive cohort outcomes from treatment comparisons. In general, randomization supports comparability between treatment groups; a non-randomized design requires particular caution about differences that may influence outcomes.

Third, analysis populations and missing data are central to proportion endpoints. The registry names a modified intent-to-treat population but does not provide its size or explain how missing follow-up results were handled. Those details determine how the reported endpoint would represent participants enrolled or treated.

Finally, a list of multiple outcomes raises questions about prespecification and multiplicity. The registry does not report whether secondary outcome analyses were adjusted or whether interim analyses occurred. These omissions do not prove that such procedures were absent; they mean the procedures are not reported in the registry record. Clear statistical reporting would allow readers to distinguish planned analyses from exploratory ones and to understand how uncertainty was handled across outcomes.

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.

A major limitation of the available registry record is that it does not report the primary SVR12 result, its denominator or its confidence interval. The endpoint’s clinical definition is stated, but its observed frequency and statistical precision cannot be evaluated.

The record lists enrollment as 71, while the safety groups list 12 at risk in Cohort A and 39 in Cohort B. It does not reconcile these quantities or state how many participants entered the primary analysis. They should be understood as separately reported figures, not assumed to describe the same analysis population.

The study was non-randomized, and the cohorts differed by genotype and treatment duration. The registry does not describe a control group or a planned adjusted comparison. This limits causal interpretation and makes direct cohort comparisons potentially confounded. The allocation procedure and reasons for assignment are not reported in the registry record.

The registry does not explain the handling of missing Week 12 endpoint data, provide details of the modified intent-to-treat analysis, or describe statistical tests and models. It also does not report multiplicity procedures, interim analyses or a protocol sample-size justification. These are reporting gaps; the record does not establish whether any such procedures were performed.

For safety, the listed counts and percentages do not include event narratives, treatment attribution, or confidence intervals. The record also does not clarify whether serious adverse event terms refer to separate participants. These limits constrain interpretation of the safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia — NCT01741545.
• Registry record last updated 2020-08-11; status last verified 2020-08.
• Results first posted 2019-06-24.
• 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

NCT01741545 is a completed Phase 3, non-randomized, parallel study sponsored by Bristol-Myers Squibb. It enrolled 71 participants with chronic hepatitis C and underlying hemophilia. The two cohorts were defined by genotype and received lambda, ribavirin and daclatasvir on different schedules.

The primary endpoint was the percentage achieving SVR12 at follow-up Week 12, defined by HCV RNA below the lower limit of quantitation. The record describes a modified intent-to-treat analysis population but does not report the primary estimate, analysis denominator or confidence interval. It lists safety counts for Cohort A and Cohort B, including 0 and 4 participants with serious adverse events, respectively, and 0 deaths in both cohorts.

Statistical analyses, missing-data methods, multiplicity procedures and the primary endpoint result are not reported in the registry record.