Determine the Efficacy and Safety of Harvoni in Genotype 1 Chronic Hepatitis c Infected People Who Are Alcoholics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Determine the Efficacy and Safety of Harvoni in Genotype 1 Chronic Hepatitis c Infected People Who Are Alcoholics (NCT02759861), a na phase 4 study. The primary outcome is The Number of Subjects Who Achieve Negative RNA in Alcoholics.

2. Clinical Question

The study asked whether treatment-naive people described as alcoholic subjects, with chronic genotype 1 hepatitis C infection, achieved a negative RNA result after receiving Harvoni. Its primary outcome was the number of participants with negative RNA 12 weeks after the end of therapy, described in the registry record as sustained viral response. The study also listed an outcome concerning sustained viral response among subjects with an advanced fibrosis score of F3/F4.

Because the study had no comparison group, its primary question is descriptive rather than a randomized comparison of treatments. The record does not give an efficacy estimate, an uncertainty interval, or a statistical test for the primary outcome. It also does not report the result for the advanced-fibrosis outcome. The clinical question and the available registry results therefore need to be distinguished: the record describes what the investigators set out to measure, but does not provide the outcome data needed to quantify the observed response.

3. Trial Design

This was a phase IV, open-label, single-group study sponsored by the University of Nebraska. The registry record lists an enrollment of 16 and a completed status. The recorded start date is 2016-08-01, and the primary completion date is 2020-08-01. Allocation is listed as not applicable, and masking as none.

Participants received Harvoni, with treatment lasting 8 or 12 weeks depending on clinical data. The registry record does not explain the criteria for choosing between those durations, nor does it provide a more detailed treatment protocol. Since there was one group and no comparator, the design does not support a direct between-group estimate of treatment effect. Outcomes can be described within the enrolled group, but changes cannot be separated from other influences using a concurrent control group.

The primary outcome was a participant count: the number who achieved negative RNA 12 weeks after the end of Harvoni therapy. The record also lists a secondary outcome concerning participants with an advanced fibrosis score of F3/F4 who achieved sustained viral response. Two outcome measures are recorded, while the registry record lists zero analyses. It does not provide a statistical analysis plan, a sample-size justification, details of interim analyses, or the number of participants included in each outcome analysis.

Enrollment and the safety denominators are not identical: the record lists 16 enrolled, while the adverse-event group lists 15 participants at risk. The reason for this difference is not reported in the registry record. No inference about withdrawal, eligibility, or outcome availability can be made from those counts alone.

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.

Overall Study

Reasons for not completing this period:

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 The Number of Subjects Who Achieve Negative RNA in Alcoholics, measured over 12 weeks after the end of Harvoni therapy.

The primary endpoint is the number of participants who achieved negative RNA 12 weeks after the end of Harvoni therapy. The registry describes this as sustained viral response in treatment-naive heavy alcohol drinking patients. It is recorded as a count of participants, rather than as a continuous measurement or a time-to-event outcome.

This kind of endpoint is used to describe whether the prespecified response was observed at a defined follow-up point. A count can communicate how many participants met the outcome, while the denominator is needed to interpret that count as a proportion of the assessed group. The registry record does not report the primary outcome count, its analysis denominator, or an uncertainty interval, so the response frequency cannot be characterized from the record.

In general, a follow-up measurement after treatment distinguishes a response that is assessed after therapy ends from a measurement made during treatment. The record sets the timing at 12 weeks after the end of therapy, but does not detail how RNA was measured, how missing measurements were handled, or whether any additional confirmation was required. Those procedures are not reported in the registry record.

The secondary outcome concerns sustained viral response among subjects with an advanced fibrosis score of F3/F4. That subgroup outcome may address a clinically relevant characteristic of participants, but the registry record does not report its count or define the assessment population for that analysis. Neither outcome should be interpreted as a comparative treatment effect in this single-group study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count tell us?

A binary outcome classifies each participant into one of two categories, such as meeting or not meeting an outcome definition. The primary endpoint is recorded as a count of participants who had negative RNA at the specified follow-up. In general, the count is most interpretable alongside the denominator of participants assessed. If the denominator is unclear or some participants lack outcome measurements, the meaning of the count can change depending on how those cases are treated. The registry record does not report the primary count, its denominator, or the handling of missing outcome data.

How would uncertainty be described?

In general, a confidence interval accompanies an estimate to express statistical uncertainty under a specified model. For a binary outcome, the interval for a response proportion depends on both the number meeting the outcome and the denominator. Different interval methods can behave differently when counts are small or outcomes are uncommon, so the analysis method matters. No primary estimate, confidence interval, or interval method is reported in the registry record. Statistical precision therefore cannot be evaluated from the listed endpoint definition alone.

What does a single-group design allow?

A single-group study can describe outcomes in the participants who received the intervention. It does not create a randomized control group against which to compare those outcomes. General causal interpretation is consequently limited: an outcome observed after treatment cannot, from this design alone, be attributed solely to the intervention. The record lists one group receiving Harvoni and no comparator. It does not identify a reference value or benchmark for a one-group hypothesis test.

How should the planning assumptions be read?

The registry record describes planning illustrations based on a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect equal to a stated fraction of the observed effect. For time-to-event outcomes, the description says the illustration concerns total events; for other outcomes, it concerns participants per arm. These are planning assumptions, not a report of the trial's observed power. Equal allocation between two arms is not the design recorded for this study, which is single-group. The registry record does not report the trial's own sample-size justification, and the planning assumptions should not be treated as evidence that the protocol used them.

In general, a sample-size calculation estimates how much information a planned study may need under chosen assumptions about the outcome, target effect, significance level, and statistical method. Changing those assumptions changes the planning result. Planning values based on a fraction of an observed effect are illustrative: they describe hypothetical targets, not effects actually observed in a separate trial group. They do not establish that a study was adequately powered after the fact. The actual outcome data and analysis are needed to assess what the study found and how precisely it was estimated.

Why does dispersion matter?

General statistical explanation: dispersion describes variation beyond what a basic probability model would expect. For count outcomes, over-dispersion means observed counts vary more than the selected model allows. If ignored, standard errors and intervals can be too optimistic, because the model understates variability. The primary endpoint in this record is a participant count, but the registry does not report a dispersion estimate or a model-based analysis. This concept should not be taken to mean that over-dispersion was present in this study.

What can be inferred from the analysis listing?

The registry record lists two outcome measures and zero analyses. That listing does not supply an analysis method, an effect estimate, a test statistic, or a p-value. It also does not establish whether analyses occurred outside what is recorded in the registry. Any such detail is not reported in the registry record. The primary outcome's timing is specified as 12 weeks after the end of therapy, but the record does not report how participants treated for 8 or 12 weeks were handled in the analysis, beyond describing the duration as dependent on clinical data.

General explanation: hypothesis tests and confidence intervals answer different but related questions. A test evaluates compatibility with a stated null hypothesis under assumptions; an interval conveys uncertainty around an estimate. Neither can be reconstructed from an outcome title alone. In a single-group study, the null hypothesis would also require a defined comparator or reference value, which is not reported. No specific test or interval can therefore be attributed to this study based on 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("Harvoni x 8 or 12 Weeks")
n      <- c(15)
events <- c(14)
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  Harvoni x 8 or 12 Weeks  15  14  93.3  68.1  99.8  70.2  98.8  69.8  98.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: the primary count of participants achieving negative RNA and a secondary outcome for participants with an F3/F4 advanced fibrosis score who achieve sustained viral response. It lists zero analyses. The record does not report whether statistical testing was planned, which outcomes were tested, or how multiple outcomes or subgroup analyses were handled. A multiplicity adjustment or hierarchy among outcomes is not reported in the registry record.

When several outcomes are tested, general statistical practice considers whether repeated testing changes the chance of at least one apparently notable result. Possible approaches include prespecifying a primary outcome, controlling an error rate, or treating secondary findings as exploratory. The registry record identifies a primary outcome and a secondary outcome, but does not describe any such procedure. No conclusion about multiplicity control can be drawn from the outcome labels alone.

Missing-data procedures are also not reported. The record does not state how participants without a measurement at the 12-week follow-up were handled, whether the analysis used all enrolled participants or an outcome-specific population, or how missing assessments affected the denominator. The population field for the primary endpoint is blank. The enrollment of 16 and the safety denominator of 15 do not resolve the efficacy analysis population.

In general, missing outcome data can affect both the estimated response and its precision, depending on why data are missing and how the analysis handles them. Without the number assessed and the prespecified handling method, the impact cannot be evaluated. Analysis populations, including any intention-to-treat or per-protocol group, are not reported in the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists one group, “Harvoni x 8 or 12 Weeks.” It reports 15 participants at risk for serious adverse events and 0 affected, and 15 at risk for other adverse events and 13 affected. It also lists 1 death. These are counts as recorded; the registry record does not provide event descriptions, timing, severity breakdowns beyond the serious-versus-other categories, or the death's relationship to any adverse event.

The safety denominator of 15 differs from the overall enrollment of 16. The reason is not reported in the registry record, so the counts should not be silently recast using the enrollment total. A zero count in this group means no serious adverse events were recorded for the listed participants at risk; it does not establish that the underlying risk is zero. With no event count beyond the registry entry and no comparative group, the record does not support a comparative safety estimate.

The record lists no top serious-event terms. It does not state whether the death was considered treatment-related, nor does it report causality assessments. The count should not be interpreted as establishing cause. Safety figures describe what was entered in the registry and are not a substitute for detailed event-level reporting.

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

The record identifies a completed phase IV study of Harvoni in treatment-naive alcoholic subjects with chronic genotype 1 hepatitis C. It specifies a primary outcome: the number of participants with negative RNA 12 weeks after the end of therapy. It also identifies a secondary outcome concerning sustained viral response in participants with an advanced fibrosis score of F3/F4. These details define the questions of interest, but they do not establish the outcomes.

The primary efficacy result is not reported in the registry record. No count, denominator, estimate, or confidence interval is given. Therefore, the degree of response and its statistical precision cannot be described from this record. The secondary outcome is also listed without a result. The absence of reported results should not be interpreted as evidence that no participants achieved the outcomes, or that all participants did.

The single-group, open-label design has no randomized comparator. Even if a response count were available, it would describe participants in this group rather than quantify a causal difference between treatments. The record does not report a reference response rate or a statistical test against one. It also does not report the sample-size justification, analysis populations, or missing-data procedures needed to understand the analysis in further detail.

The safety entry records 0 serious adverse events among 15 participants at risk, 13 with other adverse events among 15 at risk, and 1 death. These figures should be understood as descriptive registry counts. The record does not explain the difference between 16 enrolled and 15 at risk, or report the nature or attribution of the events. It does not support a conclusion about comparative safety or the cause of the death.

In general, the distinction between a study question and a study result is essential: a registered endpoint is a planned measurement, not a finding. The registry record makes the endpoint and study structure clear enough to identify the intended question, but the posted information does not provide the efficacy result needed to answer it.

14. Why This Trial Matters Statistically

This trial is statistically notable because it asks an outcome question in a population described as treatment-naive alcoholic subjects with chronic genotype 1 hepatitis C, while using a single-group design. The primary endpoint is clearly timed relative to therapy completion, at 12 weeks after the end of Harvoni therapy. That timing defines when the response count was intended to be assessed, but the result itself is not reported in the registry record.

The case also illustrates why outcome definitions, analysis populations, and results all matter. A count without its denominator cannot show the response frequency, and an estimate without an interval cannot convey its precision. The registry record lists an enrollment of 16 but does not report how many participants contributed to the primary outcome analysis. It also lists 15 participants at risk in the safety group, with no explanation for the difference from enrollment.

Design and planning assumptions should be interpreted together. The study is single-group, whereas the described planning illustration assumes equal allocation between two arms. Such an illustration is not a description of the trial's actual allocation or observed power. The registry record does not report the trial's own sample-size justification or statistical analysis plan.

Finally, a registered question is not the same as a reported answer. The primary and secondary outcomes are named, but their efficacy results are absent. Keeping that distinction explicit prevents the study's purpose, design assumptions, and safety counts from being mistaken for an efficacy finding.

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 most direct limitation of the registry record is that it does not report the primary efficacy result. Without the number achieving negative RNA, the analysis denominator, or an uncertainty interval, the endpoint cannot be quantitatively interpreted. The secondary outcome for participants with an F3/F4 advanced fibrosis score is also listed without a result.

The single-group, open-label design has no concurrent comparator and does not support a randomized treatment contrast. Allocation is recorded as not applicable, and masking as none. The record does not report a reference rate or other benchmark that would allow the primary count to be assessed against a defined comparison value.

The registry record gives an enrollment of 16, while the safety group lists 15 participants at risk. It does not explain this difference, identify the primary analysis population, or describe how missing outcome assessments were handled. It also does not report detailed eligibility criteria, measurement procedures, or the basis for selecting 8 or 12 weeks of therapy beyond saying that duration depended on clinical data.

The statistical analysis plan, sample-size justification, interim analyses, and multiplicity procedures are not reported in the registry record. The described planning assumptions use equal allocation between two arms, which does not match the recorded single-group design. Safety reporting is limited to summary counts; event details and attribution are not provided. These limitations concern what can be determined from the registry record and do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Determine the Efficacy and Safety of Harvoni in Genotype 1 Chronic Hepatitis c Infected People Who Are Alcoholics — NCT02759861.
• Registry record last updated 2023-12-29; status last verified 2023-12.
• Results first posted 2023-02-23.
• 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 NCT02759861, a completed phase IV, open-label, single-group study sponsored by the University of Nebraska. It lists 16 enrolled participants with chronic genotype 1 hepatitis C. The intervention was Harvoni, identified in the official title as ledipasvir/sofosbuvir, for 8 or 12 weeks depending on clinical data.

The primary outcome was the number of participants with negative RNA 12 weeks after the end of therapy. A secondary outcome concerned sustained viral response among participants with an advanced fibrosis score of F3/F4. The primary and secondary efficacy results are not reported in the registry record, which lists zero analyses.

The safety group lists 15 participants at risk, 0 with serious adverse events, 13 with other adverse events, and 1 death. The reason the safety denominator differs from enrollment, and details about event attribution, are not reported.