Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C in Canada: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C in Canada (NCT02581189), a registered phase not stated study. The primary outcome is Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12).

2. Clinical Question

3. Trial Design

This was a completed observational study in Canada, titled AMBER. The registry describes its purpose as examining real-world effectiveness of the ombitasvir/paritaprevir/ritonavir regimen, with or without dasabuvir and ribavirin, in clinical practice. The registry gives enrollment as 565. The study start date is 2015-10-13, and the primary completion date is 2017-12-20. The listed condition is chronic hepatitis C, and the status is completed.

The treatment combinations were ombitasvir/paritaprevir/ritonavir alone, with ribavirin, with dasabuvir, or with both dasabuvir and ribavirin. The described population for these regimens had HCV genotype 1 or 4. The record gives dose and schedule details and indicates treatment up to 24 weeks. It says treatment was used according to local label recommendations. These details characterize the regimens, but do not establish that every participant received the same combination or duration.

The record does not state how treatment allocation occurred. It identifies the study as observational and expressly warns that the regimen arms are not a like-for-like control comparison. No randomized assignment should therefore be inferred. Nor does the registry record describe a separate untreated or active-control group. The enrollment figure is not a substitute for the analysis-population sizes: the primary outcome refers specifically to a core population and a core population with sufficient follow-up, whose sizes are not reported in the registry record.

As an observational study, the record describes effectiveness in clinical practice rather than a controlled efficacy comparison. That distinction affects interpretation. Treatment selection and participant characteristics may differ across regimen groups, and the record does not report an analysis that accounts for such differences. The registry also does not report a detailed statistical analysis plan, the rationale for enrollment, or whether interim analyses were planned.

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: Safety population: all enrolled participants receiving at least 1 dose of the ABBVIE REGIMEN.The prescribed ABBVIE REGIMEN needed to be known. 565 participants enrolled; treatment not started in 28 participants; 3 withdrew consent and no start of treatment was recorded; Two of the 3 deaths noted below occurred during the SAE collection period.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Core population (CP) and core population with sufficient follow-up data 12 weeks after the last actual dose of study drug (CPSFU12) are defined in the outcome measure description

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 population: all enrolled participants who received at least one dose of the ABBVIE REGIMEN. The prescribed ABBVIE REGIMEN needed to be known.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12), measured over 12 weeks after the last actual dose of study drug.

The primary endpoint is the percentage of participants achieving sustained virologic response 12 weeks after the last actual dose of study drug, abbreviated SVR12. The record defines response as HCV RNA less than 50 IU/mL at that follow-up point. It is therefore a binary outcome for an individual participant: the endpoint classification depends on whether the stated RNA criterion is met at the specified time.

In general, a follow-up virologic endpoint can describe whether viral RNA remains below a prespecified threshold after treatment has ended. Reporting a percentage makes the outcome interpretable as the share of a defined population meeting the response criterion. A confidence interval, when reported, conveys uncertainty around that estimated percentage; it does not by itself establish that the treatment caused the outcome.

The registry defines two relevant populations. The core population includes participants who met all inclusion criteria and were adequately treated according to standard of care and local label recommendations for their disease characteristics. The core population with sufficient follow-up includes core-population participants meeting specified follow-up or failure-related criteria. The registry record does not report the SVR12 percentage, the 95% confidence interval, or the number analyzed in either population. Thus, the endpoint is clearly defined, but its observed result cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure: a participant either meets the registry’s SVR12 definition or does not. The reported summary would ordinarily express the share meeting the definition as a percentage. In general, a percentage is an estimate based on the participants included in its denominator; it does not describe people outside that analysis population. Here, the registry defines the relevant populations but does not report their sizes or the observed percentage.

The endpoint’s stated dispersion measure is a 95% confidence interval. In general, a confidence interval represents uncertainty in an estimate under the statistical procedure used to construct it. A narrower interval indicates greater precision than a wider interval, while neither interval width nor interval inclusion alone answers whether a treatment caused an outcome. The registry record does not give the interval limits or describe the calculation used for this endpoint, so its precision cannot be assessed and the exact method cannot be identified.

The registry’s core population definition is important to the estimand—the quantity the analysis is intended to describe. It consists of participants who met all inclusion criteria and were adequately treated according to standard of care and local label recommendations for characteristics including cirrhotic status and genotype. The core population with sufficient follow-up, abbreviated CPSFU12, is drawn from that core population and is defined using follow-up HCV RNA information and specified exceptions. These restrictions shape who contributes to the primary outcome estimate; they are not interchangeable with the overall enrollment figure.

The CPSFU12 criteria include evaluable HCV RNA data at least 70 days after the last actual dose; an HCV RNA value at least 50 IU/mL at the last post-baseline measurement; or a last post-baseline HCV RNA value less than 50 IU/mL but no measurement at least 70 days after the last dose for reasons related to safety or virologic failure. The registry gives dropping out due to an adverse event as an example of a safety-related reason. These criteria specify which participants can be included in the defined population, but do not report how many met each criterion or how many did not have adequate follow-up.

In general, missing outcome information can affect both the denominator and the interpretation of a percentage. If follow-up is incomplete, excluding participants, classifying them as nonresponders, or applying another rule can produce different estimates. A prespecified population definition can make the target clear, but a transparent report also needs the number of participants evaluated and a description of missingness. The registry record gives population criteria and lists a secondary outcome concerning missing SVR12 data and/or nonresponders who did not meet specific criteria. It does not report the numerical missing-data results or a broader missing-data analysis.

For an observational study, the treatment groups are not automatically exchangeable. In general, participants receiving different regimen combinations may differ in ways related to treatment selection and outcome. Random assignment is one way to balance such factors on average, but the registry describes this study as observational and says allocation is not stated. It also cautions that the arms are not a like-for-like control comparison. The record does not report an adjusted model, covariate set, or method for handling confounding. Thus, no adjusted treatment effect or causal contrast can be inferred.

The posted planning illustrations are described as based on the observed effect, using two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. In general, such calculations explore planning implications under assumptions. They are not evidence that the study had a particular probability of finding a result, and they are not observed power. The registry record does not state that these assumptions were the study’s original design assumptions or sample-size justification. No numerical planning outputs are reported in the record summarized by the registry entries.

For binary outcomes, general statistical methods may compare proportions, but the registry reports 0 analyses. It does not identify a test, model, adjustment strategy, hypothesis hierarchy, or inferential result. No method should be attributed to the study beyond the endpoint’s stated 95% confidence interval. The absence of a reported analysis does not mean that no analysis was performed outside the registry; it means the statistical procedure is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures. The primary outcome is SVR12, and the secondary outcomes include virologic response at end of treatment, relapse, viral breakthrough, on-treatment virologic failure, meeting relapse criteria, premature study drug discontinuation, and missing SVR12 data and/or nonresponders who did not meet specified criteria. Listing multiple outcomes raises the general issue of multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase. Whether and how to address this depends on the analysis plan and inferential goals.

The registry record does not report a multiplicity adjustment, outcome hierarchy beyond identifying the primary endpoint, or a statistical analysis plan. It also lists 0 analyses. No claim can therefore be made about adjusted significance levels, prespecified testing order, or which secondary results were intended to be confirmatory. The listed outcomes should be treated as outcome definitions, not as evidence that a particular analysis was carried out or yielded a finding.

Missing follow-up is explicitly relevant to the primary endpoint. The core population with sufficient follow-up is defined using HCV RNA measurements, including specified circumstances involving no measurement at least 70 days after the last dose. A secondary outcome also concerns missing SVR12 data and certain nonresponders. In general, missingness can change the population represented by an estimate and can bias an estimate when the reasons for missingness are related to outcome. The registry record does not report the number missing, their reasons, the handling used in any analysis, or sensitivity analyses.

The separate core and sufficient-follow-up populations clarify intended eligibility for the endpoint, but their observed sizes and outcome results are not reported in the registry record. The overall enrollment figure should not be substituted for those denominators.

11. 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: acute kidney injury (3.8%), nausea (3.8%), pyrexia (3.8%), vomiting (3.8%), abdominal pain (3.8%).

The registry lists serious adverse event counts by regimen group, together with the number at risk for the serious-event listing. For ombitasvir/paritaprevir/ritonavir alone, the record gives 0 serious events among 1 participant at risk. For the combination with ribavirin, it gives 1 among 26. For the combination with dasabuvir, it gives 9 among 210, and for the combination with dasabuvir and ribavirin, it gives 15 among 297. The record also lists deaths as 0, 0, 2, and 1, respectively, across those groups.

These are descriptive counts in an observational study, not randomized safety comparisons. Group sizes and participant characteristics differ, and the registry cautions that the arms are not like-for-like control groups. The counts alone cannot establish that a regimen caused an event or that one regimen is safer than another. The record lists acute kidney injury, nausea, pyrexia, vomiting, and abdominal pain at 3.8% each among its top serious terms, and hepatic encephalopathy at 0.5%. The term-specific denominators and event counts are not reported in the registry record. These percentages should therefore be read as registry-listed summaries, not as directly comparable rates across arms.

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

The registry record documents a Canadian observational study of ombitasvir/paritaprevir/ritonavir, with or without dasabuvir and ribavirin, and specifies SVR12 as the primary outcome. It defines SVR12 using HCV RNA less than 50 IU/mL 12 weeks after the last actual dose. It also defines a core population and a population with sufficient follow-up. Those details establish what the primary endpoint was intended to measure and which eligibility rules were attached to its analysis.

However, the registry record does not report the observed SVR12 percentage, its 95% confidence interval, or the analysis-population sizes. It therefore does not allow readers to quantify the observed response frequency or its precision. The fact that enrollment was 565 does not supply the endpoint denominator, because the endpoint population is defined by additional inclusion, treatment, and follow-up criteria.

The study’s observational design also limits interpretation of differences among regimen groups. Allocation is not stated, and the registry explicitly says the arms are not a like-for-like control comparison. In general, group differences can reflect differences in who received each regimen, as well as differences in treatment. Without a reported adjusted analysis and adequate information about potential confounding, group contrasts cannot be interpreted as causal treatment effects.

The listed secondary outcomes and safety counts provide additional descriptions of what was considered or recorded, but they do not replace the missing primary endpoint result. The registry record does not report numerical secondary outcome findings or a statistical analysis plan. Accordingly, the documented information supports statements about design, definitions, treatment combinations, and selected safety counts; it does not establish the magnitude, precision, or causal interpretation of the primary outcome.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a clearly defined endpoint and a reported endpoint result. The registry gives a detailed SVR12 definition, including the measurement threshold, follow-up timing, and populations to which the endpoint applies. Yet the observed percentage and confidence interval are not reported in the registry record. Without those values and denominators, the central outcome cannot be quantitatively interpreted.

The record also makes the observational nature of the evidence explicit. The study was intended to examine treatment in Canadian clinical practice, and its regimen combinations reflect use according to local label recommendations. Such evidence can describe experience outside tightly controlled trial conditions. At the same time, nonrandom allocation and non-comparable treatment arms make causal comparison difficult. The record’s warning against treating the arms as like-for-like is essential to appropriate interpretation.

Another statistical point is the role of analysis populations. The stated enrollment is not necessarily the denominator for a follow-up endpoint. Here, eligibility for the core population depends on inclusion criteria and adequate treatment, while the sufficient-follow-up population also depends on specified RNA data and follow-up circumstances. Reporting those population sizes and the missing-data pattern would be necessary to understand how the observed endpoint estimate was formed.

Finally, the record lists multiple outcomes but no analyses. This distinction matters: outcome definitions indicate what was of interest, whereas statistical results require reported estimates and methods. The available record is therefore useful for understanding the study question and its measurement framework, but not for judging the size or precision of the primary result.

14. 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 central limitation for interpreting this record is that it does not report the primary SVR12 percentage or its 95% confidence interval. It also does not report the numbers in the core population or the core population with sufficient follow-up. The overall enrollment of 565 cannot resolve these omissions because the primary endpoint applies to defined subsets.

The study is observational, allocation is not stated, and the registry explicitly cautions that the regimen groups are not like-for-like controls. The record does not report adjustment for differences between treatment groups, a covariate strategy, or an analysis to address confounding. As a result, regimen-group contrasts cannot be treated as causal estimates from the information recorded.

The registry provides detailed criteria for sufficient follow-up but does not report how many participants had missing SVR12 information, the reasons for missingness, or how missing outcomes were handled in any analysis. It lists a secondary outcome related to missing data and nonresponders meeting specified criteria, but numerical results are not reported in the registry record.

The record also does not report a detailed statistical analysis plan, multiplicity procedures, interim analyses, or a sample-size justification. Although planning illustrations are described using assumptions, those are not identified as the study’s original design rationale and are not observed power. The registry lists 0 analyses, so inferential methods and numerical secondary outcome findings cannot be evaluated from this record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C in Canada — NCT02581189.
• Registry record last updated 2019-03-27; status last verified 2019-03.
• Results first posted 2019-03-27.
• 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.

18. Record Summary

NCT02581189 is a completed observational study in Canada of ombitasvir/paritaprevir/ritonavir, with or without dasabuvir and ribavirin, for chronic hepatitis C. The registry gives enrollment as 565 and identifies SVR12 as the primary outcome, defined as HCV RNA less than 50 IU/mL 12 weeks after the last actual dose of study drug. Treatment groups are not randomized like-for-like comparisons, and allocation is not stated.

The registry defines the primary analysis populations and lists secondary virologic and treatment-discontinuation outcomes. It does not report the observed primary outcome percentage, its 95% confidence interval, or the sizes of the primary analysis populations. It lists descriptive serious adverse event counts by regimen group, but those counts do not support causal or direct comparative safety conclusions.