A Study to Evaluate Paritaprevir With Ritonavir (ABT-450/r) When Given Together With Ombitasvir and With and Without Ribavirin (RBV) in Treatment-Naïve Participants With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Paritaprevir With Ritonavir (ABT-450/r) When Given Together With Ombitasvir and With and Without Ribavirin (RBV) in Treatment-Naïve Participants With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV) (NCT01458535), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 [(Extended Rapid Virologic Response (eRVR)].

2. Clinical Question

The study concerned antiviral activity, safety and pharmacokinetics in treatment-naïve participants. Its stated primary endpoint focuses on a laboratory measure of viral RNA during treatment rather than a comparison of randomized treatment strategies. The endpoint description defines suppression as HCV RNA below 25 IU/mL; participants with missing data were counted as failures for this analysis.

Other registered outcomes include sustained virologic response at 12 and 24 weeks after treatment, early RNA response, virologic failure during treatment and virologic relapse through the post-treatment period. The record names these outcomes but does not report their results. It also does not provide the length of treatment for the cohorts. The available information therefore identifies the clinical question and the outcomes of interest, but not the observed antiviral response on the primary endpoint.

3. Trial Design

This was a Phase 2, open-label, multicenter study with sequential arms. The registry reports nonrandomized allocation, no masking and a single-group model. It records an enrollment of 61 and a completed study, with a start date of 2011-09 and primary completion in 2013-05. The sponsor is listed as AbbVie (prior sponsor, Abbott).

The arm descriptions distinguish six cohorts by genotype and whether ribavirin was included. In each cohort, participants received ABT-450/r (200/100 mg) once daily and ABT-267 (25 mg) once daily. The ribavirin cohorts also received weight-based ribavirin divided twice daily. The cohort descriptions cover participants with genotype 1, genotype 2 or genotype 3 infection, both with and without ribavirin.

Because assignment was not randomized and no masking was used, the cohorts do not constitute a randomized comparison. Differences between the cohorts could reflect differences in participant characteristics, genotype, regimen or other factors; the registry record does not describe an analysis that separates these influences. In particular, the with-ribavirin and without-ribavirin cohorts should not be interpreted as though participants had been randomly allocated to those options.

The registry record does not report the sequence or timing of cohort enrollment, treatment duration, eligibility criteria beyond treatment-naïve status and genotype, or a sample-size justification. It also does not report a detailed protocol for allocation to the different cohorts. The design information supports a descriptive reading of the separate groups and their outcomes, rather than a causal comparison between regimens.

Although the registry identifies a single-group model, it also lists the six genotype-and-regimen arm descriptions. These fields characterize the study as a nonrandomized investigation with distinct cohorts, not a trial in which a concurrent randomized control group provides a direct estimate of treatment contrast. The reported total enrollment cannot by itself show how many participants contributed to each efficacy endpoint; endpoint-specific denominators 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).

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: 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 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 [(Extended Rapid Virologic Response (eRVR)], measured over Week 4 through Week 12.

The primary endpoint is the percentage of participants whose HCV RNA was below the lower limit of quantitation from Week 4 through Week 12. The registry calls this extended rapid virologic response. Its endpoint description specifies an RNA threshold below 25 IU/mL and says that participants with missing data were imputed as failures. The efficacy analysis population included all participants who received at least 1 dose of study drug, described as the ITT population.

As a general statistical concept, a virologic endpoint uses a laboratory measurement to classify whether viral RNA is detectable or quantifiable under a prespecified threshold. Such a measure can describe response during the treatment period. A percentage expresses how many participants in the analysis population met the endpoint, but the percentage is informative only alongside its denominator and, ideally, an estimate of uncertainty.

The registry record does not report the number or percentage meeting this primary endpoint, its denominator, a confidence interval or a hypothesis-test result. Thus, the endpoint definition is available, but the observed response cannot be characterized from the registry record. Nor can the primary endpoint alone answer questions about sustained response after treatment, which is why the registry also lists post-treatment virologic outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a percentage, with participants classified according to whether HCV RNA was below the lower limit of quantitation during the stated Week 4 through Week 12 interval. The outcome description says the threshold was below 25 IU/mL and that missing data were imputed as failures. The analysis population included participants who received at least 1 dose of study drug. The record does not report the observed numerator, denominator, percentage, confidence interval or test result for this endpoint.

What does a percentage endpoint represent?

As a general statistical explanation, a percentage for a binary endpoint summarizes the proportion of an analysis population meeting a defined condition. Each participant is classified into one of two categories for that endpoint: meeting the condition or not meeting it. A percentage can be easy to communicate, but it does not convey how uncertain the estimate is. The denominator matters because estimates based on fewer observations tend to be less precise than estimates based on more observations. No endpoint-specific denominator is reported for the primary result in the registry record.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data under a stated statistical procedure. It communicates precision as well as the point estimate. A narrow interval indicates greater precision than a wide interval, while neither interval by itself establishes that a treatment caused an outcome. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed. A statistical test result is also not reported.

Why does the study structure matter?

General statistical interpretation depends on how treatment groups were formed. Random allocation can help balance measured and unmeasured participant characteristics between groups, on average, and supports a more direct comparison of assigned strategies. Here, the registry describes nonrandomized allocation and no masking, with cohorts organized by genotype and ribavirin use. The groups therefore do not supply a randomized comparison. Differences in outcomes across cohorts could be associated with factors other than the regimen, and the record does not describe an adjustment strategy that would address that issue.

The registry also describes the arms as sequential. Sequential enrollment can mean that groups were not recruited concurrently, but the record does not provide timing details sufficient to characterize how the sequence affected enrollment or comparison. No assumptions about the sequence, its rationale or its effects should be made. In general, changes over calendar time, enrollment practices or other circumstances can complicate comparisons across sequential groups; whether any such factors applied is not reported in the registry record.

How should missing outcome data be understood?

The primary endpoint description specifies that missing values were imputed as failures. This is a rule for assigning an endpoint classification when the relevant data are missing. As a general matter, counting missing results as failures can avoid treating an unobserved outcome as a successful response, but it also means that the estimate depends on the missing-data rule. The record does not report the number of participants with missing primary endpoint data or the reasons data were missing. It does not report whether alternative missing-data analyses were conducted.

The record describes the primary efficacy population as all participants who received at least 1 dose, identified as ITT. This is the population definition stated for the efficacy analysis; it should not be assumed to match the denominator for every registered outcome. Endpoint-specific analysis populations and denominators are not reported in the registry record. Nor does the record explain whether participants who discontinued or lacked follow-up contributed to each secondary outcome.

What can be inferred from the adverse-event summaries?

The adverse-event information presents the number of participants at risk and the number affected, separately for serious events and other events, by cohort. These are descriptive summaries. As a general statistical concept, counts and proportions can convey how many participants experienced an event, but they do not by themselves estimate a causal treatment effect. The cohorts are small and nonrandomized, and the record does not provide comparative uncertainty intervals or a controlled statistical analysis of adverse-event risk.

The serious-event terms are listed with percentages, but the registry does not provide enough context to establish whether these terms were related to study treatment or how they were selected for the displayed list. The listed event terms should therefore be read as reported categories, not as a ranking of causality or severity. The number of deaths is not reported in the registry record.

What is known about multiplicity and planning?

Several outcomes are registered, but the statistical plan for managing multiple outcome tests is not reported in the registry record. As a general concept, evaluating many endpoints can increase the chance of finding an apparently notable result by chance if each is tested independently without an appropriate strategy. The record does not say whether any adjustment, hierarchy or prespecified testing sequence was used. It also does not provide the rationale for the planned enrollment or a trial-specific sample-size calculation.

A planning illustration may use assumptions such as a significance level, allocation pattern and target power to describe how a future study might be sized. Such an illustration is not an observed trial result, and it does not establish that this study was designed with those assumptions. The registry does not report a sample-size justification for this trial. In general, power refers to the probability of detecting a specified effect under stated assumptions; it is not a measure of the probability that a finding is true. No observed-power conclusion can be drawn from the record.

In summary, the available methods information defines the primary binary endpoint, the efficacy population and the handling of missing primary data. It does not provide the result estimates or the full statistical analysis plan needed to assess the estimate, multiplicity, subgroup comparisons or comparative treatment effects. Interpretations should remain descriptive and limited to the design and counts actually recorded.

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("ABT-450/r and ABT-267 Plus RBV in Genotype 1 Parti", "ABT-450/r and ABT-267 Plus RBV in Genotype 2 Parti", "ABT-450/r and ABT-267 Plus RBV in Genotype 3 Parti", "ABT-450/r and ABT-267 in Genotype 1 Participants", "ABT-450/r and ABT-267 in Genotype 2 Participants", "ABT-450/r and ABT-267 in Genotype 3 Participants")
n      <- c(10, 10, 10, 10, 10, 11)
events <- c(10, 9, 7, 9, 8, 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  ABT-450/r and ABT-267 Plus RBV in Genotype 1 Parti  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8
ARM  ABT-450/r and ABT-267 Plus RBV in Genotype 2 Parti  10  9  90.0  55.5  99.7  59.6  98.2  58.7  97.7
ARM  ABT-450/r and ABT-267 Plus RBV in Genotype 3 Parti  10  7  70.0  34.8  93.3  39.7  89.2  39.0  89.1
ARM  ABT-450/r and ABT-267 in Genotype 1 Participants  10  9  90.0  55.5  99.7  59.6  98.2  58.7  97.7
ARM  ABT-450/r and ABT-267 in Genotype 2 Participants  10  8  80.0  44.4  97.5  49.0  94.3  48.2  94.0
ARM  ABT-450/r and ABT-267 in Genotype 3 Participants  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary virologic outcomes, including sustained response after treatment, early RNA response, virologic failure and relapse. It reports three analyses, but the analysis details and any hierarchy among outcomes are not reported in the registry record. No multiplicity adjustment or other strategy for controlling the chance of false-positive findings across multiple tests is described. As a general statistical principle, when multiple outcomes are tested, interpretation depends in part on whether and how that multiplicity was addressed. The registry record does not permit that assessment.

For the primary endpoint, participants with missing data were imputed as failures. This rule is explicitly stated for the Week 4 through Week 12 endpoint. The record does not report how many primary endpoint values were missing, why they were missing or whether a sensitivity analysis using another assumption was conducted. Handling of missing data for the secondary outcomes is not reported in the registry record; the primary-endpoint rule should not automatically be assumed to apply to them.

The efficacy population included all participants who received at least 1 dose of study drug, identified as ITT. The registry does not report outcome-specific denominators or clarify the populations used for each secondary analysis. It also does not provide a sample-size justification, planned power, or details of interim analyses. Those design and analysis details cannot be reconstructed from the endpoint list or enrollment alone.

Because the study was nonrandomized, missing-data handling and multiplicity are not the only interpretive concerns. Cohort differences by genotype and ribavirin use also limit direct comparisons. The record does not report adjusted comparative estimates that might account for these differences.

12. 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: haematemesis (10.0%), clostridial infection (10.0%), facial bones fracture (10.0%), lumbar vertebral fracture (10.0%), rib fracture (10.0%).

The registry reports adverse-event counts separately for the six genotype-and-regimen cohorts. For serious adverse events, the affected counts are 1 of 10, 0 of 10 and 0 of 10 in the genotype 1, 2 and 3 cohorts with ribavirin, respectively; without ribavirin, the corresponding counts are 1 of 10, 1 of 10 and 1 of 11. The registry also lists other adverse-event counts of 9 of 10, 9 of 10 and 8 of 10 with ribavirin, and 9 of 10, 9 of 10 and 10 of 11 without ribavirin.

These are descriptive counts in small, nonrandomized cohorts. They do not establish whether an event was caused by a study drug, and they should not be used as a direct comparison between regimens. The serious-event terms listed in the record are haematemesis, clostridial infection, facial bones fracture, lumbar vertebral fracture, rib fracture and road traffic accident, each reported at 10.0%. The registry does not establish a causal link between these terms and treatment. The number of deaths is not reported in the registry record, which is different from a reported count of zero.

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

The registry record supports a description of a Phase 2 investigation in treatment-naïve participants with genotype 1, 2 or 3 chronic hepatitis C. It specifies the treatment combinations, the primary endpoint definition, the efficacy analysis population and some adverse-event counts. These details explain what the study set out to evaluate and how the primary endpoint was defined.

However, the record does not report the observed primary endpoint percentage. It also does not report results for the listed secondary outcomes, confidence intervals for efficacy estimates, or statistical tests. Consequently, the record alone does not quantify the proportion meeting the primary virologic endpoint, how precise such an estimate was, or whether sustained responses occurred at the registered follow-up times. An outcome definition is not a result.

The nonrandomized structure also limits what can be inferred about differences between the cohorts. Participants were in genotype-specific groups, and groups either received ribavirin or did not. Since assignment was not randomized, contrasts across these groups cannot be interpreted as unbiased causal estimates of the effect of adding ribavirin or changing another aspect of treatment. No adjusted comparative analysis is reported in the registry record.

Similarly, adverse-event counts describe what was recorded in these cohorts but do not show that the study drugs caused the events. The event terms and percentages should be interpreted as registry summaries, not as proof of attribution. The record does not report the number of deaths.

These limitations do not make the registered information meaningless. The design and endpoint descriptions are useful for understanding the scope of the investigation, and the adverse-event data provide a descriptive account of reported counts. But those details should not be extended into claims about comparative efficacy, treatment effects, or the clinical meaning of a response. Such conclusions require outcome results and an analysis suited to the study design. The registry record does not report those efficacy results or the full analysis plan.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why endpoint definitions and study design need to be read together. The primary outcome is defined precisely as a percentage meeting a laboratory threshold over a specified treatment interval, and missing values are explicitly counted as failures. Those details determine what the intended endpoint represents. Yet without the observed percentage and its denominator, the endpoint cannot be quantitatively interpreted.

The record also illustrates the limits of cross-cohort comparisons in a nonrandomized study. Its groups differ by genotype and ribavirin use, and they were not formed by random allocation. Even if outcomes were reported for each group, differences would not necessarily isolate the effect of a regimen. Statistical adjustment can sometimes address measured differences, but no such comparative estimates or adjustment methods are reported in the registry record, and adjustment cannot automatically resolve unmeasured confounding.

Safety summaries likewise require context. Counts of participants affected are useful descriptions, but small cohort sizes and the absence of randomized assignment limit direct comparisons. The seriousness of an event and whether it was caused by treatment are distinct questions; the event list alone does not answer the causal question.

Finally, this record shows the difference between a registered outcome and a posted result. It lists a primary endpoint, multiple secondary outcomes and an efficacy population, but does not report the primary or secondary efficacy estimates. Without those results, statistical precision, evidence against a null hypothesis and between-group effects cannot be evaluated. Careful interpretation means separating what the design intended to measure from what the available record actually quantifies.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation is that the registry record does not report the primary endpoint result. It defines the Week 4 through Week 12 RNA threshold and the missing-data rule, but provides no observed percentage, endpoint denominator, confidence interval or test result. Results for the registered secondary outcomes are also not reported in the registry record. Efficacy and precision therefore cannot be assessed from the available record.

The study was open-label and nonrandomized. Its genotype-specific cohorts with and without ribavirin are not randomized comparison groups, so any difference across them could be confounded by participant or cohort characteristics. The record does not report adjusted comparisons or enough design detail to assess whether potential differences were addressed. It also describes sequential arms but does not report the timing or operational details needed to evaluate possible effects of sequence.

The registry does not report treatment duration, endpoint-specific denominators, the number or reasons for missing primary data, or missing-data sensitivity analyses. The primary endpoint counts missing observations as failures, but the handling of missing observations for other outcomes is not reported. A sample-size justification, detailed statistical analysis plan, multiplicity strategy and interim-analysis information are also not reported in the registry record.

Safety data are presented as cohort-level counts. The small cohort sizes and nonrandomized design limit comparative interpretation, and the listed serious-event terms do not establish treatment causation. The number of deaths is not reported in the registry record. These limits mean that the available safety summaries should be treated as descriptive, not as evidence of comparative risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate Paritaprevir With Ritonavir (ABT-450/r) When Given Together With Ombitasvir and With and Without Ribavirin (RBV) in Treatment-Naïve Participants With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV) — NCT01458535.
• Registry record last updated 2016-07-11; status last verified 2016-05.
• Results first posted 2016-07-11.
• 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

NCT01458535 is a completed Phase 2, open-label, multicenter, nonrandomized study of ABT-450/r and ABT-267, with or without ribavirin, in treatment-naïve participants with genotype 1, 2 or 3 chronic hepatitis C. Enrollment was 61. The primary endpoint was the percentage with HCV RNA below the lower limit of quantitation from Week 4 through Week 12; missing data were counted as failures in the primary analysis.

The registry lists six genotype-and-regimen cohorts and several post-treatment and on-treatment virologic outcomes. It reports cohort-level serious and other adverse-event counts, but the primary and secondary efficacy results are not reported in the registry record. Because allocation was nonrandomized, the cohorts do not provide a like-for-like randomized comparison. The available information supports a descriptive account of design and safety counts, but not a quantified efficacy or comparative treatment conclusion.