Sofosbuvir/Velpatasvir in Adults With Chronic Hepatitis C Virus Infection Who Are on Dialysis for End Stage Renal Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sofosbuvir/Velpatasvir in Adults With Chronic Hepatitis C Virus Infection Who Are on Dialysis for End Stage Renal Disease (NCT03036852), a na phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

3. Trial Design

This was a phase 2, multicenter, open-label, single-group study of SOF/VEL in adults with chronic HCV infection who were on dialysis for end stage renal disease. The study title and summary specify treatment for 12 weeks and include participants with HCV infection of any genotype. The registry record lists 59 enrolled participants, identifies the study as completed, and gives the start date as 2017-03-22 and primary completion date as 2018-08-13.

The design has one treatment group, with no randomized allocation or masking. Allocation is listed as not applicable and masking as none. These details matter for interpretation: the study can describe outcomes among the participants who received the treatment, but it does not create a randomized between-group comparison. Differences from an external population or from another study would not be equivalent to a comparison made within a randomized trial.

The primary outcome was SVR12, defined using HCV RNA below the lower limit of quantitation at posttreatment week 12. The primary endpoint population is described as the Full Analysis Set: enrolled participants who received at least 1 dose of study drug. The record also lists secondary outcomes covering other sustained-response time points, HCV RNA during and after treatment, virologic failure, viral resistance, and pharmacokinetic measures.

The registry record lists 15 outcome measures, but does not report the primary endpoint result, its confidence interval, or analysis details such as the method used to calculate that interval. The study's protocol details, sample-size justification, interim analyses, and full statistical analysis plan are not reported in the registry record. Those omissions limit conclusions about how planned analyses compare with the results posted for the study.

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: 78 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set included participants who are enrolled into the study and received at least 1 dose of study drug.

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: The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12), measured over Posttreatment Week 12.

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after stopping study treatment. SVR12 is defined in the registry record as HCV RNA below the lower limit of quantitation, specified as 15 IU/mL, at posttreatment week 12. The endpoint therefore describes whether participants met a prespecified virologic threshold at a particular time after treatment ended.

A percentage is useful for a binary outcome because it expresses the share of the defined analysis population meeting the endpoint. It is a cohort-level summary; it does not describe every participant's individual course. The registry record identifies the Full Analysis Set as enrolled participants who received at least 1 dose of study drug. It does not report how many participants had an evaluable HCV RNA result at the endpoint time or how missing endpoint measurements were handled.

The record specifies a 95% confidence interval as the endpoint's dispersion measure. In general, a confidence interval communicates uncertainty around an estimated percentage, with narrower intervals indicating greater precision under the method used. The actual percentage and interval are not reported in the registry record. Without them, neither the observed response proportion nor its precision can be evaluated from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a confidence interval convey?

In general, a confidence interval presents a range of values compatible with an estimated outcome under a specified statistical method. For a percentage, it helps show how precisely the observed proportion is estimated. A confidence interval is not a guarantee that the true value lies in the particular reported interval, and it is not a measure of the probability that a treatment works. Its interpretation depends on the data, the analysis population, and the calculation method.

The registry record names a 95% confidence interval for SVR12 but does not report the interval or the method used to calculate it. Different methods can behave differently, particularly when counts are small or proportions are near the ends of their possible range. The analysis method is not reported in the registry record, so it is not possible to determine which approach was used or assess its assumptions.

How should a binary endpoint be understood?

SVR12 is a binary outcome at the participant level: each participant either meets the stated HCV RNA threshold at the specified follow-up time or does not. The overall endpoint is expressed as a percentage of the analysis population. In general, binary endpoints allow a straightforward description of how many participants meet a definition, while the estimate's uncertainty depends on the observed count and denominator. Neither the SVR12 count nor its denominator is reported in the registry record.

The primary analysis population is described as participants enrolled and given at least 1 dose. This definition identifies who may contribute to the primary endpoint analysis, but does not tell how absent measurements, withdrawals, or other post-enrollment circumstances were handled. Such handling can change the denominator or the classification of outcomes. The missing-data approach is not reported in the registry record.

Why does the single-group design matter?

In general, random allocation helps make treatment groups comparable at baseline by distributing measured and unmeasured characteristics across groups. A single-group study has no such internal contrast. Its observed outcome can describe what occurred among participants receiving the study treatment, but it cannot separate treatment effects from other explanations using a randomized comparator. This is a design limitation, not a defect in the calculation of a response percentage.

This study is listed as single group, with allocation not applicable and masking none. Accordingly, interpretation should focus on the cohort's descriptive outcomes, not a treatment-versus-control effect. The registry record does not report a comparator or a between-group treatment estimate.

What can be said about sample-size planning?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated target effect is expressed as a stated fraction of the observed effect. These are planning assumptions for an illustration, not the design features of this single-group trial. No resulting planning sample sizes are reported in the registry record, and the study's own sample-size justification is not reported in the registry record.

In general, a sample-size calculation asks how many participants would be needed under particular assumptions to reach a specified precision or probability of detecting a specified effect. Such a calculation depends on the endpoint, analysis, assumed effect, variability, and design. A planning illustration is not an observed result, and it is not observed power. The record's illustration should not be read as proof that the trial had adequate or inadequate power for its actual endpoint.

Why are multiplicity and over-dispersion relevant in general?

When a study assesses multiple outcomes or comparisons, the chance of at least one apparently notable result can increase if each is examined separately. Statistical methods may account for this multiplicity, but the appropriate approach depends on the analysis plan and the role of each endpoint. The record lists 15 outcome measures, including the primary endpoint and several secondary outcomes. It does not report a multiplicity adjustment or a strategy for interpreting multiple tests; these details are not reported in the registry record.

Over-dispersion is a general concern when observed variation exceeds what a chosen statistical model assumes. It can make model-based uncertainty estimates too narrow if ignored. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report the models or detailed analyses needed to assess it, so no claim can be made that over-dispersion was present or that a particular adjustment was used.

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("SOF/VEL (Total)", "SOF/VEL (GT-1)", "SOF/VEL (GT-2)", "SOF/VEL (GT-3)", "SOF/VEL (GT-4)", "SOF/VEL (GT-6)")
n      <- c(59, 25, 7, 16, 4, 2)
events <- c(56, 23, 7, 15, 4, 2)
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  SOF/VEL (Total)  59  56  94.9  85.9  98.9  86.1  98.3  86.1  98.2
ARM  SOF/VEL (GT-1)  25  23  92.0  74.0  99.0  75.0  97.8  74.9  97.6
ARM  SOF/VEL (GT-2)  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  SOF/VEL (GT-3)  16  15  93.8  69.8  99.8  71.7  98.9  71.3  98.5
ARM  SOF/VEL (GT-4)  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  SOF/VEL (GT-6)  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 15 outcome measures, including SVR12 and secondary virologic, resistance, and pharmacokinetic outcomes. Assessing several outcomes raises a general multiplicity issue: the more separate hypotheses or comparisons examined, the greater the chance that at least one result appears notable by chance. Studies may address this through a prespecified hierarchy, adjustment, or a clearly descriptive interpretation. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how the analyses accounted for the number of outcomes.

The Full Analysis Set for the primary outcome is described as participants enrolled who received at least 1 dose of study drug. That definition does not specify how missing HCV RNA measurements at posttreatment week 12 were treated, whether any participants were excluded from the endpoint calculation, or how the analysis handled discontinuation. Those details are not reported in the registry record. The endpoint result itself and its denominator are also not reported, preventing assessment of the effect of missing data on the estimate.

In general, missing outcomes can affect both the estimated percentage and its precision. A complete-case approach, an imputation approach, or another rule can yield different interpretations; none should be assumed without a stated method. The registry record does not report sensitivity analyses for missing data. It also does not report interim analyses or the full statistical analysis plan. These absences leave uncertainty about the planned handling of multiplicity and incomplete outcomes.

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: atrial fibrillation (1.7%), cardiac failure congestive (1.7%), cellulitis (1.7%), device related infection (1.7%), lower respiratory tract infection viral (1.7%).

The registry record lists 59 participants at risk in the SOF/VEL group. It reports 11 participants with serious adverse events, 33 with other adverse events, and 2 deaths. These are descriptive counts from the treatment group; no comparator group is reported. They should not be interpreted as estimates of excess risk relative to another treatment or to no treatment.

The record lists six serious adverse-event terms, each with a percentage of 1.7%: atrial fibrillation, cardiac failure congestive, cellulitis, device related infection, lower respiratory tract infection viral, and pneumonia. The listed terms describe events recorded as serious; the record does not report whether they were considered related to study treatment. The percentages should be read as posted, without inferring a causal relationship or a comparison that is absent from the study design.

In general, adverse-event counts are not by themselves proof that treatment caused an event. Interpretation also depends on how events were defined, collected, timed, and assessed, as well as on participants' underlying health and the availability of a comparison group. Those details are not reported in the registry record. The listed counts also do not, by themselves, summarize severity for events outside the serious-event listing or establish the completeness of event follow-up.

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

The study record establishes that a phase 2, open-label, single-group study enrolled adults with chronic HCV infection who were receiving dialysis for end stage renal disease. Participants received SOF/VEL for 12 weeks, and the primary endpoint was SVR12. The endpoint definition specifies HCV RNA below 15 IU/mL at posttreatment week 12. These details describe the study question and the intended measure.

The record does not report the primary endpoint percentage or 95% confidence interval. Therefore, it does not permit a quantitative statement about the observed SVR12 result or how precisely it was estimated. Specifying an outcome is not the same as reporting its result. The secondary outcomes are listed, but their findings are not reported in the registry record either.

Even if a single-group response percentage were available, it would describe the observed participants rather than establish a causal contrast with another treatment. Without a randomized comparator, other factors cannot be separated from treatment using a within-trial between-group comparison. The design can provide descriptive information, but its structure does not support the same comparative inference as a randomized trial.

The adverse-event counts are also descriptive. The record reports serious and other adverse events and deaths, but does not report treatment attribution or a comparator safety estimate. The listed serious-event terms should not be treated as proof that the study drug caused them.

In general, results from a study apply most directly to the participants and conditions represented in that study. The registry record does not report detailed eligibility criteria or participant characteristics beyond the stated population, so the boundaries of generalizability cannot be fully assessed. No medical conclusion about an individual's care follows from the registry description. The main statistical reading is limited: the population, treatment duration, and primary outcome are described, while the outcome estimate and important analytic details are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of a clearly defined binary endpoint in a specific clinical population. The registry record states the response threshold, the time at which response was assessed, and the analysis population. Clear definitions are important because a percentage is interpretable only when the endpoint and denominator are understood. Here, the SVR12 definition uses HCV RNA below the lower limit of quantitation at posttreatment week 12, while the primary analysis population includes enrolled participants who received at least 1 dose.

The study also illustrates why design and outcome reporting must be considered together. A single-group, open-label study can describe outcomes among treated participants, but it does not create a randomized treatment contrast. A response estimate and its confidence interval, if reported, would describe the cohort and its precision; they would not alone identify what would have happened under a different treatment condition.

The listed secondary outcomes span several kinds of measures: binary response outcomes, changes in HCV RNA, resistance, and pharmacokinetic parameters. In general, multiple outcome families require careful planning and interpretation, especially when several analyses are considered. The registry record lists these outcomes but does not report the results or multiplicity approach.

Finally, the absence of the primary result in the registry record is itself important for statistical interpretation. A registered definition cannot substitute for an estimated outcome, and safety counts without attribution or a comparator do not establish causality. Distinguishing design, endpoint definitions, estimates, uncertainty, and causal claims helps keep conclusions aligned with what the record actually reports.

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 interpretation is that the registry record does not report the primary SVR12 percentage or its 95% confidence interval. Without an estimate, numerator, denominator, or interval, the endpoint's observed magnitude and precision cannot be assessed. Results for the listed secondary outcomes are also not reported in the registry record.

The study had a single group, with no comparator and no random allocation. This limits causal interpretation because outcomes cannot be contrasted with a concurrent control group assigned under the same study conditions. Masking is listed as none, and the record does not report further procedures that might affect outcome assessment.

The Full Analysis Set definition is stated, but the registry record does not report how missing endpoint measurements, treatment discontinuation, or participants without an assessment at posttreatment week 12 were handled. It also does not report the statistical method for the confidence interval, a multiplicity strategy, interim analyses, or the full statistical analysis plan. The study's sample-size justification is not reported in the registry record; a planning illustration is not a substitute for that justification.

The safety record includes adverse-event counts and serious-event terms, but does not report treatment attribution or a comparator safety analysis. Further details on event definitions and assessment are not reported in the registry record. These limitations are specific to the information available and do not establish that an analysis or procedure was absent from the full study documentation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sofosbuvir/Velpatasvir in Adults With Chronic Hepatitis C Virus Infection Who Are on Dialysis for End Stage Renal Disease — NCT03036852.
• Registry record last updated 2020-03-06; status last verified 2019-11.
• Results first posted 2019-11-12.
• 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 NCT03036852, a completed phase 2, multicenter, open-label, single-group study sponsored by Gilead Sciences. It enrolled 59 adults with chronic HCV infection who were on dialysis for end stage renal disease. Participants received SOF/VEL for 12 weeks. The record gives a start date of 2017-03-22 and a primary completion date of 2018-08-13.

The primary endpoint was the percentage with SVR12, defined as HCV RNA below 15 IU/mL at posttreatment week 12. The Full Analysis Set included enrolled participants who received at least 1 dose. The registry record does not report the primary endpoint result or its 95% confidence interval. Safety listings report 11 participants with serious adverse events, 33 with other adverse events, and 2 deaths; treatment attribution is not reported in the registry record.