Real World Study: Genotype 1 Chronic Hepatitis C Virus Treatment and Evaluation of Real World SVR and PRO: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Real World Study: Genotype 1 Chronic Hepatitis C Virus Treatment and Evaluation of Real World SVR and PRO (NCT02461745), a non-randomized phase 4 study. The primary outcome is Sustained Virological Response (SVR) at Week 12.

2. Clinical Question

3. Trial Design

This was a Phase IV, open-label, multisite study sponsored by Kaiser Permanente. Its stated focus was the real-world sustained virological response rate, adherence, and patient-reported outcomes during and after treatment for non-cirrhotic adults with genotype 1 chronic hepatitis C. The registry records 200 participants enrolled. The study status is completed; the recorded start was 2015-06 and primary completion was 2017-05.

The design is listed as parallel and non-randomized, with no masking. The two treatment groups corresponded to genotype 1a and genotype 1b. The genotype 1a group received ombitasvir, paritaprevir/ritonavir, and dasabuvir with ribavirin for 12 weeks. The genotype 1b group received the same named antiviral combination without ribavirin for 12 weeks. Thus, both genotype and regimen distinguish the groups. Their outcomes cannot be interpreted as if participants had been randomly assigned to otherwise comparable treatments.

The primary outcome was sustained virological response at Week 12, defined in the record as a percentage among participants who completed the 12-week treatment course. The listed secondary outcome was sustained virological response at Week 4. The registry also describes adherence and patient-reported outcomes as study aims, but does not provide further outcome definitions or numerical results for those aims in the record summarized.

The registry record does not report the method used to select participants for each genotype group, a protocol-level sample-size justification, or details of treatment assignment beyond the non-randomized parallel design. It also does not report additional information about study sites or the timing of assessments beyond the stated outcome timeframes.

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: 228 study participants screened for the study had 28 days from signing the study consent form to their first dose of study drug to confirm their eligibility to continue with the study. The screening period was also used as a wash-out period for concomitant medications that may interact with the study drug.

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 Sustained Virological Response (SVR) at Week 12, measured over 12 weeks.

The primary endpoint is sustained virological response at Week 12. The registry defines it as the percentage of study participants achieving that response per protocol among those who completed the 12-week treatment course. The endpoint is recorded as a count of participants, making it a binary outcome at the participant level: each participant either meets the stated response definition or does not.

SVR is used as an outcome because it captures whether the specified virological response is present at the stated follow-up time. Reporting both the number meeting the definition and the number in the analysis population is important for interpreting a percentage. In this record, the denominator is restricted to treatment completers rather than being explicitly defined as all enrolled participants. That distinction matters because a completer-based percentage describes the analyzed group, not automatically everyone who entered the study.

The registry record gives the endpoint definition and timeframe but does not report the numerical Week 12 result, the number of completers, or the number achieving SVR. The actual response percentage and its precision therefore cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation starts with the outcome definition and the population to which it applies. In this study, the primary outcome is a participant count for a binary event: achieving sustained virological response at Week 12. The registry describes the result as a percentage among participants who completed the treatment course. A percentage summarizes the proportion meeting the definition within a specified group; interpreting it requires knowing both the number with the event and the denominator used.

What does a binary endpoint tell us?

A binary endpoint records whether each participant meets a defined condition. For an outcome such as SVR, the event count and analysis-population size together describe the observed proportion. That proportion is a descriptive estimate, not a guarantee that the same proportion would be observed in another group of participants. Sampling variability means estimates can differ even when the underlying response probability is unchanged.

A confidence interval is a general statistical way to express the uncertainty around an estimated effect or proportion. It gives a range of values compatible with the data under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval alone resolves bias in the study design. The registry record does not report a Week 12 estimate or confidence interval, so the precision of the primary outcome cannot be assessed.

Why does the analysis population matter?

The primary outcome is defined per protocol among participants who completed 12 weeks of treatment. Restricting an analysis to completers answers a question about that selected group. If completion is related to prognosis, treatment experience, or the chance of observing the outcome, the completer group may differ from all enrolled participants. This is a general concern with completer-based analyses, not evidence that such selection occurred in this study. The registry record does not report the number of completers, reasons for non-completion, missing outcome counts, or methods used to address missing data.

An intention-to-treat analysis, as a general concept, evaluates participants according to their original assignment regardless of treatment completion. That approach is often important in randomized trials, but this study is listed as non-randomized and does not report such an analysis. The registry record does not state whether any other analysis population was used.

What does non-randomized grouping mean?

Random allocation can help balance measured and unmeasured characteristics between treatment groups. In a non-randomized study, group membership may be associated with participant characteristics that also relate to outcomes. Here, the groups are defined by genotype, and their regimens differ in ribavirin use. A direct difference between the groups would therefore not isolate the effect of ribavirin. General statistical adjustment can account for measured covariates when suitable data and a prespecified method are available, but adjustment cannot automatically remove unmeasured confounding. The registry record does not report an adjusted comparative analysis or the covariates used for one.

The parallel design means the record describes distinct groups rather than a crossover in which participants receive treatments in different periods. The lack of masking means participants and study personnel were not blinded according to the registry’s masking field. For an objective laboratory-based outcome, masking may be less directly relevant than for subjective patient-reported outcomes, but procedures for outcome assessment are not reported in the registry record. Patient-reported outcomes can be influenced by expectations or awareness of treatment, so their interpretation depends on the measurement instrument and collection procedures, which are not detailed.

How should planning assumptions be read?

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, not the study’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are assumptions for a planning calculation, not evidence that the trial used that design or achieved a particular probability of detecting an effect. Sample-size illustrations are planning quantities, not observed power. The registry record does not report a protocol sample-size justification or numerical sample-size illustration results in the information summarized.

In general, a normal approximation uses a mathematical distribution to estimate uncertainty or required sample size. Its suitability depends on the data and assumptions, including the size of the groups and the event frequency. Equal allocation is an assumption about the relative size of groups in a calculation; it does not describe the actual genotype groups in this study. Since the study’s grouping was non-randomized, the planning assumptions should not be mistaken for an analysis of the two observed groups.

What can the posted analyses establish?

The registry records no analyses. It therefore does not provide a reported treatment contrast, hypothesis test, confidence interval, or adjusted estimate for the primary endpoint. The absence of those analyses in the registry record does not establish what analyses may have been conducted elsewhere; those details are not reported in the registry record. Likewise, an outcome definition alone is not a result. Statistical interpretation must distinguish the plan or definition from observed counts and from an inferential comparison.

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("Genotype 1a", "Genotype 1b")
n      <- c(123, 67)
events <- c(116, 66)
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  Genotype 1a  123  116  94.3  88.6  97.7  88.7  97.2  88.7  97.2
ARM  Genotype 1b  67  66  98.5  92.0  100.0  92.0  99.7  92.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as SVR at Week 12 and a secondary outcome as SVR at Week 4. Although two outcome measures are recorded, the registry record does not report numerical results for either one. It also records no analyses. There is therefore no posted set of outcome tests or estimates from which to assess how multiple statistical comparisons were handled.

Multiplicity is a general concern when several outcomes, time points, or comparisons are tested. Repeated testing can increase the chance of finding an apparently notable result by chance if the analyses are interpreted without accounting for the number of tests. A prespecified testing hierarchy or other adjustment can address this concern, but the registry record does not report a multiplicity procedure or statistical analysis plan. It would be inappropriate to assume that an adjustment was or was not used outside the record.

The primary endpoint is defined among participants who completed the 12-week treatment course. The number of participants in that analysis population, missing Week 12 measurements, and reasons for missingness are not reported in the registry record. The record also does not describe imputation, sensitivity analyses, or how participants who discontinued treatment were treated in the endpoint analysis. These omissions limit assessment of how representative the completer-based result would be, even if the numerical result were available.

The record does not report a separate intention-to-treat result or other analysis populations. The distinction matters because analysis populations can yield different estimates when participants do not complete treatment or lack outcome measurements. Without population counts and missing-data methods, neither the extent nor the consequences of missing information can be determined from 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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute pancreatitis (1.4%), small cell carcinoma (1.4%), urothelial carcinoma (1.4%), acute congestive heart failure (0.8%), acute psychosis (0.8%).

The registry reports serious adverse-event counts by genotype group. In the genotype 1a group, 4 participants were affected among 130 at risk; in the genotype 1b group, 3 were affected among 70 at risk. For other adverse events, the reported counts are 102 among 130 at risk in genotype 1a and 30 among 70 at risk in genotype 1b. The record lists 0 deaths in each group.

The serious-event terms listed include Acute Pancreatitis, Small Cell Carcinoma, and Urothelial Carcinoma, each shown as 1.4%; Acute Congestive Heart Failure, Acute Psychosis, and Cellulitis/ Sepsis, each shown as 0.8%. These entries are registry listings, not a basis for attributing a particular event to treatment. The record does not describe the denominator or calculation underlying each listed percentage.

These counts are descriptive. Because treatment groups were not randomized and differed in genotype and regimen, a comparison of counts does not isolate a treatment effect. The registry record does not report an adjusted safety comparison, exposure-adjusted rates, or further detail needed to assess timing and attribution. Zero recorded deaths means no deaths are listed for these groups in the record; it does not establish the absence of other safety concerns.

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

The registry record establishes that a completed, open-label Phase IV study evaluated treatment in adults with non-cirrhotic genotype 1 chronic hepatitis C and specified SVR at Week 12 as its primary outcome. It also documents the two genotype-based regimens, a secondary SVR outcome at Week 4, and adverse-event counts by group. These details describe the study’s focus and the information entered in the registry.

The record does not report the numerical Week 12 SVR result, the number of treatment completers, or a confidence interval. It therefore cannot show the size or precision of the observed response proportion. The same limitation applies to the listed Week 4 outcome, whose numerical result is not reported. Adverse-event counts do not fill this gap: they describe safety entries, not the primary efficacy endpoint.

The study does not provide a randomized comparison between the regimens. Genotype groups also differ in ribavirin use, so a difference between them would not by itself establish that a particular treatment component caused an outcome difference. No comparative statistical analysis is reported in the registry record.

These limitations do not mean that the study produced no results or that no other analysis exists. They mean that those results and analyses are not reported in the registry record. The statistical conclusions supported by this record are therefore limited to the design, outcome definitions, group descriptions, and posted adverse-event counts. The record alone does not establish treatment efficacy, comparative effectiveness, or a causal interpretation of safety differences.

14. Why This Trial Matters Statistically

This study illustrates why a real-world treatment question and a comparative treatment question are not the same. The registry focuses on SVR, adherence, and patient-reported outcomes in a clinical setting, but the described groups are organized by genotype and receive regimens that differ in ribavirin use. That design can describe experience within each group, while a direct comparison between groups would be vulnerable to confounding.

It also highlights the importance of linking an endpoint definition to its analysis population. The primary outcome is a Week 12 response percentage among treatment completers. Without the number who completed treatment, the response numerator, and the handling of missing outcomes, the reader cannot judge the denominator or precision. A clearly named endpoint is valuable, but it is not a substitute for the observed result and its uncertainty.

The registry further distinguishes a study’s stated aims from results actually reported. SVR at Week 4 is listed as a secondary outcome, and adherence and patient-reported outcomes are described as study aims, but numerical findings for these outcomes are not reported in the record. The absence of analyses also means that no inferential comparison is available there.

Finally, safety counts require the same attention to group structure and denominator as efficacy results. The posted counts can be described, but they should not be read as evidence of a causal difference between regimens. Together, these features make the record a useful example of how design, analysis population, reporting completeness, and causal interpretation shape what can be learned from clinical registry results.

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 consequential limitation for interpreting efficacy is that the registry record does not report the numerical primary outcome. It gives the SVR definition and timeframe but not the number achieving SVR, the number completing treatment, or the resulting percentage. No confidence interval or inferential estimate is reported, so the magnitude and precision of the endpoint cannot be assessed.

The primary endpoint is restricted to participants who completed the 12-week course. The registry record does not report how many participants did not complete treatment, why they did not complete it, whether outcome data were missing, or how missingness was handled. These details are necessary to understand how the completer population relates to the recorded enrollment of 200.

The non-randomized design limits causal interpretation. The genotype groups were assigned different regimens, with ribavirin included for genotype 1a and not for genotype 1b. The record does not report an adjusted comparative analysis or enough information to assess potential confounding. The groups should not be treated as interchangeable control arms.

Further limitations of the registry record are that it does not report the protocol’s sample-size justification, a statistical analysis plan, multiplicity procedures, or numerical results for the secondary SVR outcome. Although patient-reported outcomes and adherence are among the stated aims, their measurement details and numerical findings are not reported in the registry record. The serious adverse-event entries also lack the additional detail needed to assess attribution or compare safety across groups. These limitations concern what is recorded and should not be taken as proof that information was not collected elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Real World Study: Genotype 1 Chronic Hepatitis C Virus Treatment and Evaluation of Real World SVR and PRO — NCT02461745.
• Registry record last updated 2021-01-22; status last verified 2021-01.
• Results first posted 2021-01-22.
• 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 describes a completed, Phase IV, open-label, multisite, non-randomized parallel study sponsored by Kaiser Permanente. Recorded enrollment was 200. The study concerned non-cirrhotic adults aged 18 years and older with genotype 1 chronic hepatitis C. The genotype 1a group received ombitasvir, paritaprevir/ritonavir, and dasabuvir with ribavirin for 12 weeks; the genotype 1b group received the named antiviral combination without ribavirin for 12 weeks.

The primary outcome was SVR at Week 12 among participants completing treatment, and SVR at Week 4 was listed as a secondary outcome. The numerical results for these outcomes and any statistical analyses are not reported in the registry record. Serious adverse events affected 4 of 130 participants at risk in genotype 1a and 3 of 70 in genotype 1b; no deaths are listed. Because the groups were non-randomized and differed by genotype and regimen, the record does not support a like-for-like treatment comparison.