Viral Kinetics, Interferon Stimulated Genes (ISGs) and mirRNA Among Subjects Infected With Different Hepatitis C Virus Genotypes During Therapy With Sofosbuvir and GS-5816: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Viral Kinetics, Interferon Stimulated Genes (ISGs) and mirRNA Among Subjects Infected With Different Hepatitis C Virus Genotypes During Therapy With Sofosbuvir and GS-5816 (NCT02468648), a na phase 2 study. The primary outcome is Number of Participants With Sustained Virologic Response.

2. Clinical Question

3. Trial Design

This completed phase 2 study enrolled 72 participants with chronic hepatitis C. It used a single-group design: participants received the combination of sofosbuvir and GS-5816, and the registry lists no concurrent comparator. Allocation is recorded as not applicable and masking as none. The record identifies the National Institute of Diabetes and Digestive and Kidney Diseases as sponsor.

Eligibility covered adults with hepatitis C virus genotypes 1–4 who had either never been treated or had previously received an interferon regimen, with or without ribavirin, that did not clear the virus. The treatment description specifies a single pill containing sofosbuvir and GS-5816, taken once daily for 12 weeks. The study was intended to examine viral kinetics, interferon-stimulated genes and microRNA across genotypes during therapy, alongside safety and virologic outcomes.

The registry describes screening that included medical history, physical examination, laboratory tests, questionnaires, liver imaging and an electrocardiogram. Eligible participants were to have a liver biopsy. The design description also mentions six study visits, including a further liver biopsy at week 4, followed by five visits after the last dose. It does not provide a complete account of all procedures at every visit in the available record.

The absence of a control arm matters for interpretation. Changes observed during the study cannot be contrasted with a concurrent group to distinguish the treatment course from other explanations for change. The registry record does not report the rationale for the sample size, the intended genotype-specific enrollment, or a detailed statistical analysis plan. The study dates are recorded as starting on 2015-06-09, with primary completion on 2018-09-14, and its status is completed.

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 Number of Participants With Sustained Virologic Response, measured over 12 weeks.

The primary endpoint is the number of participants with sustained virologic response. The registry defines this as absence of detectable virus 12 weeks after completion of antiviral therapy. It is a count endpoint: it records how many participants met the response definition, rather than measuring the amount of virus as a continuous value. The registry labels its timeframe as 12 weeks.

A sustained response measured after treatment is used to assess whether virus remains detectable beyond the period of drug administration. It is distinct from a measurement of viral levels during treatment, which can describe early viral kinetics but does not by itself establish the endpoint definition. The registry also lists secondary outcomes concerning the number of participants who sustained virologic response and the number who maintained hepatitis C virus RNA below the lower limit of quantification in liver and serum.

The primary endpoint’s result is not reported in the registry record. Consequently, the endpoint definition can be described, but the number meeting it, the number assessed, and any estimate of response precision cannot be stated from this record. Details such as how missing endpoint measurements were handled are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with a binary primary outcome summarized as a participant count. The primary outcome asks whether each participant met a specified condition: absence of detectable virus 12 weeks after completion of therapy. A count can be informative as a direct description of observed participants, but its interpretation depends on knowing who was evaluated and how incomplete assessments were treated. Those details are not reported in the registry record for this endpoint.

What does a count endpoint convey?

General: For a binary outcome, each person is classified into one of two states under the study definition, such as meeting or not meeting the response criterion. The count of people meeting the criterion is a straightforward summary of observed events. A count alone does not describe uncertainty, and it does not reveal the result among people whose outcome was missing or not assessed. A proportion or interval may also be useful, but no primary endpoint proportion or confidence interval is reported in the registry record.

The endpoint is time-specific: it concerns virus detectability 12 weeks after therapy completion. That timing is part of the definition, rather than a claim that all participants were measured at precisely the same calendar date. The record does not describe visit windows, laboratory assay details, or the rules used to classify results near a detection threshold. Such operational details are not reported in the registry record.

Why does the design affect the analysis?

General: In a randomized comparison, treatment groups can be compared under an analysis plan that accounts for the design. In a single-group study, the observed outcome is a description of the enrolled group. Without a concurrent control group, an analysis cannot estimate a randomized between-group treatment contrast. This is why the study’s enrollment and outcome counts should not be treated as though they came from two comparable arms.

The registry records no allocation and no masking. It identifies the model as single group, and explicitly notes that this is not a randomized comparison. The record does not explain whether any analyses were planned to adjust for baseline characteristics, genotype, or treatment history. It does not report whether exploratory subgroup analyses were performed. These features should not be inferred from the study’s scientific aim to examine differences across genotypes.

How should uncertainty be understood?

General: A confidence interval expresses statistical uncertainty around an estimate under stated assumptions and an analysis method. Its width is influenced by the amount of information and the variability of the data. It does not account automatically for selection bias, measurement problems, missing outcomes, or the lack of a control group. Since no primary endpoint estimate or interval is reported in the registry record, its precision cannot be assessed from the posted result information.

General: A p-value, when used, quantifies how incompatible the observed data are with a specified statistical model or null hypothesis. It does not measure the probability that a treatment works, and it does not communicate the size or practical importance of an effect. No p-value or hypothesis test for the primary endpoint is reported in the registry record. There are also no listed analysis entries.

What do the planning assumptions mean?

The registry describes sample-size calculations as planning illustrations based on an observed effect, not as the trial’s own design. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are not the described design of this study, which used a single group. Any planning figures associated with those assumptions should therefore be read as hypothetical planning scenarios, not as evidence that the study had a particular probability of detecting an effect.

General: “Observed power” is not a substitute for an uncertainty interval around an observed result. A sample-size illustration describes what might be planned under specified assumptions; it does not change the precision of results already observed. The assumptions cannot be treated as the study’s prespecified design choices. The registry does not report the study’s own sample-size justification, and no sample-size calculation should be interpreted as a post hoc measure of whether the results are reliable.

Why do distributions matter?

General: Some statistical methods rely on assumptions about the distribution of outcomes. For count outcomes, especially when counts vary more than a simple model expects, over-dispersion can make standard errors too small if it is ignored. This study’s primary endpoint, however, is a count of participants meeting a binary response definition, not a reported recurrent-event count. No over-dispersion assessment or model for the primary outcome is reported in the registry record, so a specific modeling approach cannot be attributed to the investigators.

The registry lists four outcome measures, including the primary sustained-response count and secondary outcomes concerning sustained response and HCV RNA below the lower limit of quantification in liver and serum. It does not specify the statistical methods used for those outcomes, the estimates produced, or how measures from different sources were combined. Those analytic details are not reported in 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("Combination of Sofosbuvir and GS-5816")
n      <- c(71)
events <- c(70)
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  Combination of Sofosbuvir and GS-5816  71  70  98.6  92.4  100.0  92.4  99.8  92.5  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary count of participants with sustained virologic response and secondary measures concerning sustained response and HCV RNA below the lower limit of quantification in liver and serum. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if many tests are conducted. General: Multiplicity procedures are methods for managing the interpretation of a family of tests, for example by adjusting thresholds or by designating a primary outcome in advance. The registry record does not report whether a multiplicity adjustment was planned or used.

The record does not give a statistical analysis plan or list analysis entries. It therefore does not specify which outcome analyses were confirmatory or exploratory, what test methods were used, or how any repeated measurements over time were analyzed. The timing of the primary endpoint is stated as 12 weeks after therapy, but visit windows and rules for handling measurements outside that timing are not reported in the registry record.

Missing-data handling is also not reported in the registry record. There is no description of whether missing endpoint measurements were excluded, counted as nonresponse, imputed, or addressed through sensitivity analyses. The record does not specify analysis populations, such as whether the primary analysis included all enrolled participants or only those who completed treatment and follow-up. Although enrollment is listed as 72, that number alone does not establish the number with an observed primary endpoint.

General: Missing outcomes can affect both the count and its interpretation, especially when the likelihood of missingness is related to participants’ condition or experience. Different assumptions about unobserved outcomes can produce different conclusions. Without the analysis population and missing-data rules, readers cannot determine how the registry would classify participants without an endpoint measurement. These are limitations of the reported information, not grounds for assuming that data were missing or that a particular method was used.

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: pain after a radiological biopsy and direct cannulation of the portal vein (1.4%), small bowel obstruction (1.4%).

The registry lists one treatment group, with 72 participants at risk for serious adverse events and 2 participants affected by such events. It separately lists 72 at risk for other adverse events and 67 affected. One death is recorded. These are counts in the registry record, not estimates from a comparison between randomized groups.

The two top serious-event terms are “Pain after a radiological biopsy and direct cannulation of the portal vein” and “Small bowel obstruction,” each reported as 1.4%. These terms and percentages should be read as the registry’s event listings. The record does not describe whether the events were judged related to study treatment, how severity or seriousness was adjudicated, or whether any participant experienced more than one event. The one death should not be assumed to be treatment-related; causality is not reported in the registry record.

General: Serious adverse events and other adverse events are separate categories in safety reporting. A participant count is not necessarily the same as an event count, because a participant may have more than one event. The record’s category labels do not by themselves establish the timing, duration, severity or cause of each event. The available figures support a descriptive account of events recorded in this group, but not a conclusion about comparative safety or causation.

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

The posted record identifies a completed phase 2 investigation of sofosbuvir and GS-5816 in a single group of adults with chronic hepatitis C. It gives a definition for the primary sustained virologic response endpoint and records adverse-event counts. It does not report the primary endpoint count or a statistical estimate of the response. Accordingly, the registry information does not allow readers to quantify how many participants met the primary response definition or how precise such an estimate would be.

The record also cannot establish a treatment effect relative to another option. There was no concurrent comparator, and the study was not a randomized comparison. An observed outcome in the treated group, even if reported, would describe that group under the study conditions; it would not on its own separate treatment effects from other possible explanations. The registry’s objective of examining variation across virus genotypes should not be mistaken for reported evidence of genotype-specific differences. Such results are not reported in the registry record.

The adverse-event counts describe what was recorded for the combination group. They do not establish the cause of an event or death. The registry does not report a comparative safety estimate, nor does it provide information sufficient to assess differences in event risk against an untreated or alternative-treatment group.

General: Statistical evidence should be interpreted in light of the endpoint definition, design, completeness of follow-up and uncertainty in the estimate. A well-defined outcome is helpful, but it cannot compensate for an absent result or create a control comparison where none exists. Confidence intervals and analysis details would help readers assess precision, while a concurrent comparison would be needed to estimate a comparative effect under a randomized design. These results and design limitations do not support medical recommendations or a conclusion that treatment does or does not work.

The most defensible conclusion from the registry record is therefore narrow: it documents the study design, the intended primary endpoint and descriptive safety counts, but does not report the primary efficacy result or an inferential analysis. Questions about response magnitude, subgroup patterns, missing outcomes and treatment attribution remain unanswered in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how the design determines which questions can be answered. Its scientific aim concerned viral kinetics, interferon-stimulated genes and microRNA among people with different hepatitis C virus genotypes during therapy. Its primary clinical endpoint was a count of participants with sustained virologic response. Those biological questions and the clinical endpoint are related areas of inquiry, but the registry does not provide analysis results that connect them.

The single-group structure is central. Descriptive counts can characterize outcomes among enrolled participants, but without a concurrent comparator they do not estimate a randomized difference between treatment strategies. This distinction is important even when a study has a clearly defined endpoint and a specified follow-up timeframe. Design determines the scope of an estimate; statistical methods cannot manufacture a control group after the fact.

The record also illustrates why reporting the endpoint result, analysis population, missing-data approach and uncertainty matters. A response count without the number evaluated or an interval can be difficult to interpret. The registry lists 72 enrolled participants, but does not report the primary endpoint result or how incomplete follow-up was handled. The count of enrolled participants should not automatically be treated as the count with an observed endpoint.

Finally, the planning assumptions are not the design itself. The registry describes a hypothetical two-arm, equal-allocation planning illustration, while the actual trial is recorded as single group. Distinguishing planning scenarios from observed design and results prevents sample-size calculations from being mistaken for evidence about trial power or treatment effect. Taken together, these distinctions help readers separate the study’s purpose, the evidence actually reported and the inferences the design permits.

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 main trial-specific limitation is the absence of a concurrent comparison group. The record identifies a single-group study with no allocation and no masking. This design allows description of participants receiving the combination but does not provide a randomized estimate of the difference from another treatment or from no treatment.

The primary endpoint result is not reported in the registry record. As a result, the number meeting the sustained virologic response definition, the number with an assessed endpoint and any measure of statistical uncertainty cannot be described. The record also does not report genotype-specific outcome results, even though the study’s stated focus includes different virus genotypes.

The description identifies 72 enrolled participants and outlines treatment and follow-up procedures, but the analysis population and completion counts are not reported in the registry record. Missing-data rules, sensitivity analyses, endpoint assessment details and assay procedures are also not reported. This limits assessment of how reliably the endpoint was measured and how incomplete observations may have been handled.

Safety information is descriptive. The record gives counts for serious and other adverse events and records one death, but does not report treatment attribution or a comparison group. The listed serious-event terms do not resolve the cause or clinical course of events. Finally, the statistical analysis plan, sample-size justification and multiplicity approach are not reported in the registry record. These gaps constrain interpretation; they should not be filled by assuming methods or results that are not documented.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Viral Kinetics, Interferon Stimulated Genes (ISGs) and mirRNA Among Subjects Infected With Different Hepatitis C Virus Genotypes During Therapy With Sofosbuvir and GS-5816 — NCT02468648.
• Registry record last updated 2020-03-19; status last verified 2018-09-14.
• Results first posted 2020-03-19.
• 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 is a completed phase 2, single-group study of sofosbuvir and GS-5816 in adults with chronic hepatitis C. The registry records 72 enrolled participants and describes daily combination treatment for 12 weeks. Eligible participants had hepatitis C virus genotypes 1–4 and were either previously untreated or had not cleared the virus after an interferon regimen, with or without ribavirin.

The primary endpoint is the number of participants with absence of detectable virus 12 weeks after completion of antiviral therapy. Its result is not reported in the registry record. The safety record lists 2 participants affected by serious adverse events, 67 by other adverse events, and 1 death; the event listings do not establish treatment causality. No randomized comparison, analysis entries, detailed analysis plan, or primary endpoint uncertainty estimate is reported. The study is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.