Safety and Efficacy Study of Sofosbuvir Plus Ribavirin in Treatment-Naive Adults With Genotype 1 and 3 Chronic HCV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Sofosbuvir Plus Ribavirin in Treatment-Naive Adults With Genotype 1 and 3 Chronic HCV Infection (NCT01896193), a randomized phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

The clinical question combines treatment duration and viral genotype. Those dimensions matter when interpreting the comparisons: a contrast between groups that differ in both genotype and duration cannot attribute an observed difference to duration alone. The registry record describes the study as evaluating antiviral efficacy, safety, and tolerability, but the primary result reported is the percentage meeting the SVR12 definition.

3. Trial Design

The registry record describes a phase 3b, multicenter, randomized, open-label, parallel-group study. It enrolled 127 participants and is marked completed. The study evaluated sofosbuvir plus ribavirin for 16 weeks or 24 weeks in treatment-naive adults with chronic genotype 1 or genotype 3 HCV infection. Masking was not used.

The four reported groups combine treatment duration and genotype: 16 weeks and 24 weeks for genotype 1, and 16 weeks and 24 weeks for genotype 3. The posted primary outcome values are 50.0% for the 16-week genotype 1 group, 76.5% for the 24-week genotype 1 group, 86.7% for the 16-week genotype 3 group, and 90.3% for the 24-week genotype 3 group. The arm sizes listed for these outcomes are 32, 34, 30, and 31, respectively. These are the outcome-specific group sizes reported in the registry record.

The primary endpoint population is described as randomized participants who received at least one dose of study drug and had genotype 1 or genotype 3 infection. This is the stated Full Analysis Set definition; the registry record does not provide further detail about handling participants without an evaluable posttreatment result.

The primary outcome timeframe is Posttreatment Week 12. Secondary outcomes named in the record include SVR at 4 and 24 weeks after discontinuation, on-treatment virologic failure, and virologic relapse. The record includes posted relapse percentages, but values for the other named secondary outcomes are not reported in the registry record. Original sample-size assumptions and the trial's statistical analysis plan are not reported in the registry record.

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: 139 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: participants with genotype 1 or 3 HCV infection who were randomized and received at least one 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: Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug

6. Primary Endpoint

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

The primary endpoint is the percentage of participants with sustained virologic response at 12 weeks after discontinuing study treatment. The registry definition requires HCV RNA < 25 IU/mL at that follow-up point. It therefore represents a prespecified virologic status at a particular time after treatment, rather than a direct measure of symptoms or a broader measure of health.

A percentage is useful because it expresses how often the endpoint occurred in each group relative to the participants assessed in that group. It allows readers to compare observed outcome frequencies across the four genotype-and-duration groups. The registry reports percentages but does not provide confidence intervals for the individual arm percentages.

In general, a posttreatment virologic endpoint can describe whether suppression is sustained after study treatment has ended. That is distinct from an on-treatment measurement, which would describe viral status while treatment is ongoing. The registry record also lists SVR at other follow-up times and virologic failure and relapse as secondary outcomes, but it does not report values for every named secondary measure.

The primary endpoint is reported for the Full Analysis Set, defined in the record as randomized participants with genotype 1 or genotype 3 infection who received at least one dose of study drug. The record does not describe additional rules for missing endpoint measurements or imputation.

7. Results Posted in the Registry

• SOF+RBV 24 Weeks, GT1: 76.5% (26/34) versus 50.0% (16/32) on control; risk difference 26.5 percentage points (95% CI 4.0 to 48.9), risk ratio 1.53 (1.03–2.27); unadjusted two-proportion z-test p = 0.025.
• SOF+RBV 16 Weeks, GT3: 86.7% (26/30) versus 50.0% (16/32) on control; risk difference 36.7 percentage points (95% CI 15.5 to 57.8), risk ratio 1.73 (1.19–2.52); unadjusted two-proportion z-test p = 0.002.
• SOF+RBV 24 Weeks, GT3: 90.3% (28/31) versus 50.0% (16/32) on control; risk difference 40.3 percentage points (95% CI 20.1 to 60.5), risk ratio 1.81 (1.25–2.60); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants Experiencing Virologic Relapse

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • SOF+RBV 24 Weeks, GT1: 23.5% (8/34) versus 50.0% (16/32) on control; risk difference -26.5 percentage points (95% CI -48.9 to -4.0), risk ratio 0.47 (0.23–0.95); unadjusted two-proportion z-test p = 0.025.
  • SOF+RBV 16 Weeks, GT3: 13.3% (4/30) versus 50.0% (16/32) on control; risk difference -36.7 percentage points (95% CI -57.8 to -15.5), risk ratio 0.27 (0.10–0.71); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for SOF+RBV 24 Weeks, GT1 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for SOF+RBV 16 Weeks, GT3 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes named in the registry cover virologic response at other follow-up times, on-treatment virologic failure, and virologic relapse. The posted relapse percentages follow a pattern broadly consistent with the primary outcome pattern: the groups with higher SVR12 percentages generally have lower reported relapse percentages. This is a descriptive relationship across the reported groups, not an independent confirmation of the primary endpoint.

The registry record does not report results for every named secondary outcome. Values for SVR4, SVR24, and on-treatment virologic failure are not reported in the registry record. The record lists no reported analyses for secondary outcomes. Consequently, the secondary evidence available for interpretation is incomplete, and no conclusion about the unreported measures can be drawn from their names alone.

In general, secondary endpoints can provide context about different stages or aspects of treatment response. However, each additional endpoint and comparison creates another opportunity for a chance finding. If multiple tests are performed without adjustment, their p-values do not retain the same overall error control as a single prespecified test. The registry record does not report a multiplicity plan, and the posted secondary comparisons are unadjusted.

These secondary results therefore carry less weight than a prespecified primary analysis would, particularly when the analysis plan and multiplicity handling are unavailable. Their pattern can be considered alongside SVR12, but it should not be treated as independent proof or as a substitute for the missing secondary outcome results.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
• Percentage of Participants Experiencing On-treatment Virologic Failure
• Percentage of Participants Experiencing Virologic Relapse

9. Statistical Interpretation

10. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the event occurred. Here the event is achieving SVR12, and the posted arm results are percentages of participants meeting that definition. General statistical interpretation of a percentage depends on knowing both the number with the event and the denominator assessed. The registry supplies arm sizes and percentages, while the comparison summaries also give event counts.

What does a risk difference describe?

A risk difference is the event proportion in one group minus the event proportion in the reference group. It is an absolute contrast on the probability scale. A positive value in these SVR12 comparisons means that the event proportion was higher in the named comparison group than in the 16-week genotype 1 reference group. For genotype 1, the posted risk difference is 0.265; for 16-week genotype 3 it is 0.367; and for 24-week genotype 3 it is 0.403. These are unadjusted recalculations from posted summary statistics, rather than an adjusted model estimate reported by the sponsor.

In general, absolute contrasts are often easier to interpret clinically than relative measures because they directly describe the difference in event probability. But the meaning of a contrast depends on the comparison being made. When the groups differ in genotype as well as treatment duration, the contrast cannot isolate a duration effect. The registry's reference group is the 16-week genotype 1 group, so comparisons to genotype 3 groups combine differences in population characteristics with any treatment-duration difference.

How should the confidence interval be read?

A confidence interval expresses statistical uncertainty around an estimate. In general, it gives a range of values that are reasonably compatible with the observed data and the method's assumptions. It is not a guarantee that the true value lies inside that particular interval, and it does not describe variation between individual participants. The risk-difference intervals are 0.040 to 0.489 for 24-week genotype 1, 0.155 to 0.578 for 16-week genotype 3, and 0.201 to 0.605 for 24-week genotype 3. Each interval is above zero, but the width of the intervals shows that the magnitude remains uncertain.

What does an unadjusted p-value indicate?

A p-value summarizes how unusual data at least as incompatible with a null hypothesis would be if that null hypothesis and the test assumptions were true. It is not the probability that the null hypothesis is true, and it does not indicate the size or importance of an effect. The posted unadjusted values are p = 0.025, p = 0.002, and p < 0.001 for the three primary contrasts. Because they are unadjusted, they do not account for the set of comparisons or other outcomes considered.

In general, a small p-value can coexist with considerable uncertainty about the precise effect size, particularly when groups are small. A p-value also does not correct for design limitations, such as a contrast that changes more than one factor. Interpretation should therefore consider the effect estimate, interval, population, comparison structure, and analysis plan together.

Why do the analysis population and endpoint definition matter?

The registry defines the primary Full Analysis Set as randomized participants with genotype 1 or genotype 3 infection who received at least one dose of study drug. That definition clarifies who is intended to contribute to the primary outcome, but the registry record does not describe how missing posttreatment measurements were handled. In general, excluding participants without an observed endpoint can affect a percentage if the probability of missingness differs across outcome groups. Without the missing-data rules and counts, the direction or size of any such effect cannot be assessed.

Finally, the trial is described as randomized, but the posted comparisons are simple unadjusted calculations from summary counts. The registry record reports no analysis entries. It does not report a statistical analysis plan, adjustment variables, or multiplicity procedure. These omissions prevent confirmation that the displayed contrasts correspond to the trial's prespecified primary analysis.

11. Confidence Intervals and Precision

The confidence intervals for the primary risk differences are broad relative to the point estimates. For 24 weeks versus 16 weeks in genotype 1, the risk difference was 0.265, with a confidence interval from 0.040 to 0.489. For 16-week genotype 3 versus the reference, it was 0.367, with an interval from 0.155 to 0.578. For 24-week genotype 3 versus the reference, it was 0.403, with an interval from 0.201 to 0.605.

In general, confidence intervals communicate the range of effect sizes that remain compatible with the observed data under a particular method. An interval is not a measure of the chance that the true effect is at any one point in the range. The intervals are all above zero, but they still span a range of possible risk differences, so the exact magnitude is not precisely determined.

The group sizes for the primary outcome range from 30 to 34. With group sizes of this scale, estimates can be sensitive to a small number of outcomes. The reported arm percentages are presented without arm-level confidence intervals, so the comparison intervals are the available precision summaries for the primary contrasts.

These intervals apply to the specific contrasts against the 16-week genotype 1 reference. They do not provide an interval for a direct comparison of the two genotype 3 durations. Nor do they adjust for multiple comparisons or account for any covariates. Their interpretation is therefore limited to the unadjusted comparisons and the data used to calculate them.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures express the number of participants per arm for 80% power and the number of participants per arm for 90% power. They are not total sample sizes. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It uses a selected fraction of the observed effect as the effect to detect. The trial's own original design assumptions are not reported in the registry record.

The 80% power column describes the planned chance of detecting the assumed effect at the stated significance level if that effect and the calculation assumptions were true. The 90% column uses a higher target chance of detection under the same type of assumptions. These are planning targets, not guarantees about the result of a future study. The figures depend on the effect size chosen: planning for 75% or 50% of the observed effect requires more participants per arm than planning for the full observed effect.

For example, the planning rows are labeled by the fraction of the observed effect being targeted, with participant counts given separately for the 80% and 90% targets. Smaller effects are harder to distinguish from random variation, so more participants are generally needed to detect them with the same power and significance level. The table and curve should be read as illustrations of this relationship, not as evidence about the design or conduct of the completed trial.

This is not observed power. It is a planning calculation based on the observed effect and the stated assumptions, and it does not tell how likely the reported result was to occur or whether the original study was adequately planned.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.500; treatment proportion p₁ = 0.765; average p̄ = 0.632.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6819 = 1.3365.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6557 = 0.5518.
4. n = (1.3365 + 0.5518)² / (0.2647)² = 50.9, rounded up to 51 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.5                          # control proportion
p1 <- 0.764705882352941                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1896193)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 51 (80% power), 68 (90% power)
 75% of observed effect: n per arm = 95 (80% power), 126 (90% power)
 50% of observed effect: n per arm = 219 (80% power), 293 (90% power)
power.prop.test: 50.9 
Simulated power at n = 51 per arm: 0.804 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record names one primary outcome and several secondary outcomes, including SVR4, SVR24, on-treatment virologic failure, and relapse. It does not report how many primary or secondary comparisons were prespecified for formal testing, whether any outcomes were hierarchical, or whether p-values were adjusted for multiplicity. The record also reports no analysis entries. As a result, the posted unadjusted p-values cannot be interpreted as controlling the overall chance of a false positive across all outcomes and comparisons considered.

In general, multiplicity arises when researchers test several hypotheses. Even if each individual test uses a conventional significance threshold, the chance of at least one false positive across a set of tests may be higher than for a single test. Adjustment methods or a prespecified testing sequence can address this issue, but the registry record does not report whether such methods were used. The posted p-values should therefore be treated as unadjusted evidence for their individual contrasts, not as multiplicity-controlled trial-wide findings.

The record defines the primary Full Analysis Set as randomized participants with genotype 1 or genotype 3 infection who received at least one dose of study drug. It does not report endpoint-specific missingness, the number with unavailable SVR12 measurements, or methods for imputation or other missing-data handling. In general, missing outcome data can influence a percentage if missingness is related to the likelihood of the outcome. Without details, the direction and extent of any influence cannot be evaluated.

Further analysis-population details are not reported in the registry record. The record does not describe a per-protocol population, an intention-to-treat analysis rule beyond the stated Full Analysis Set definition, or sensitivity analyses for missing data. Nor does it report covariate adjustment, a model for separating genotype from duration, or a protocol-level statistical analysis plan. These gaps limit assessment of whether the posted comparisons match the intended confirmatory analysis.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: pneumonia (1.6%), foot fracture (1.5%).

The registry reports serious adverse events affecting 1 participant in the 16-week group and 1 participant in the 24-week group. The corresponding numbers at risk are 62 and 65. The record also reports other adverse events affecting 16 participants in the 16-week group and 21 participants in the 24-week group, with the same group-specific numbers at risk listed.

The serious-event terms listed include pneumonia at 1.6% and foot fracture at 1.5%. The registry record does not specify which treatment-duration group each term belongs to in the information, so those percentages should not be assigned to a particular group. Death counts are not reported in the registry record.

These figures describe reported event counts and should be read separately from the efficacy endpoint. The registry record does not provide further detail about event severity beyond the serious-event classification, event timing, relatedness to study treatment, or the types of the other adverse events. Without that context, the counts alone do not establish comparative safety or explain the clinical significance of individual events.

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

The posted results show SVR12 percentages of 50.0% and 76.5% in the genotype 1 groups, and 86.7% and 90.3% in the genotype 3 groups, for 16 weeks and 24 weeks respectively. The unadjusted risk-difference comparisons against the 16-week genotype 1 reference are positive, with confidence intervals above zero. The reported data therefore describe higher observed SVR12 percentages in the other groups relative to that reference.

They do not establish that longer treatment alone caused the differences. The contrasts involving genotype 3 change genotype as well as treatment duration relative to the reference, and the registry does not report a direct genotype 3 duration comparison. Even the genotype 1 duration contrast is presented as an unadjusted calculation from summary statistics rather than a reported sponsor analysis. The registry record does not provide adjustment or a formal model separating these factors.

Statistical significance does not by itself show that an effect is clinically important, nor does it establish certainty about its size. The confidence intervals leave a range of plausible magnitudes, and the group sizes are limited. The reported p-values are unadjusted, while the registry record does not describe a multiplicity plan. Missing outcome handling and the trial's original statistical plan are also not reported.

The findings apply to the population and endpoint as defined in the record: treatment-naive adults with genotype 1 or genotype 3 chronic HCV infection, with SVR12 based on HCV RNA < 25 IU/mL at posttreatment Week 12. They do not establish outcomes in populations not described by the registry record, nor do the posted numbers alone provide a complete account of safety, other secondary outcomes, or longer-term outcomes.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical comparison must be interpreted in light of its group structure. The four reported arms vary by genotype and treatment duration. A contrast against one reference group can therefore answer only the question represented by that particular pairing; it cannot automatically be generalized to a duration effect across genotypes. The genotype 3 contrasts are especially important to read as comparisons with the genotype 1 reference, not as direct tests of 16 versus 24 weeks within genotype 3.

It also demonstrates the distinction between an observed percentage and an inferential estimate. The arm percentages describe what was recorded, while risk differences and confidence intervals summarize contrasts and their uncertainty. The intervals are informative about precision, but they cannot correct for an unsuitable comparison or for missing analytic details.

Finally, registry reporting affects what can be concluded. The record identifies a primary endpoint and population and lists secondary outcomes, but it does not provide the full statistical analysis plan, multiplicity handling, or missing-data methods. It reports no analysis entries. A transparent distinction between posted group summaries, unadjusted recalculations, and a sponsor's prespecified analysis is essential when interpreting trial evidence.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations are specific to the results reported for this trial. The primary comparisons use the 16-week genotype 1 group as a common reference, while the other groups differ by genotype, duration, or both. Consequently, the comparisons do not provide a clean estimate of the effect of duration within genotype 3, and the comparisons involving genotype 3 cannot separate genotype from treatment duration.

The primary arm percentages are based on group sizes of 32, 34, 30, and 31. The registry record does not provide confidence intervals for the individual arm percentages, although it provides intervals for the risk-difference comparisons. The record does not report the sponsor's primary analysis, covariate adjustment, or the original statistical analysis plan. No discrepancy is flagged for the recalculations, but these remain unadjusted comparisons from posted summary data.

Reporting of secondary outcomes is incomplete: the record names several secondary measures but provides results for relapse only. It does not report a multiplicity plan, missing-data handling, endpoint-specific missingness, or sensitivity analyses. Safety reporting also lacks detail on the nature and treatment relatedness of events, and deaths are not reported in the registry record. These limitations restrict the interpretation of efficacy comparisons and prevent a complete assessment of the broader outcome profile.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Sofosbuvir Plus Ribavirin in Treatment-Naive Adults With Genotype 1 and 3 Chronic HCV Infection — NCT01896193.
• Registry record last updated 2015-05-29; status last verified 2015-05.
• Results first posted 2015-04-17.
• 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.

22. Record Summary

The registry record describes a completed, randomized, open-label, parallel phase 3b study of sofosbuvir plus ribavirin for 16 or 24 weeks in treatment-naive adults with genotype 1 or genotype 3 chronic HCV infection. Enrollment was 127. The primary outcome was SVR12, defined as HCV RNA < 25 IU/mL at posttreatment Week 12, in the stated Full Analysis Set.

Reported SVR12 percentages were 50.0% and 76.5% for genotype 1, and 86.7% and 90.3% for genotype 3, for the 16-week and 24-week groups respectively. Unadjusted risk-difference comparisons use the 16-week genotype 1 group as the reference. The registry record does not report a sponsor analysis, a multiplicity plan, missing-data methods, or the original sample-size assumptions.