Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Hungary: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Hungary (NCT02636608), a registered phase not stated study. The primary outcome is Percentage of Participants Achieving Sustained Virological Response 12 Weeks Post-treatment (SVR12).

2. Clinical Question

3. Trial Design

This was an observational study of treatment for chronic hepatitis C, conducted in Hungary. The study title identifies real-world evidence as its focus. The brief description says it sought evidence about effectiveness as well as patient-reported outcomes, work productivity and safety for an interferon-free regimen containing paritaprevir/ritonavir and ombitasvir, with or without dasabuvir and ribavirin. The registry lists enrollment of 244 participants and a completed status.

Participants received paritaprevir/ritonavir with ombitasvir, with or without dasabuvir and with or without ribavirin, for 12 or 24 weeks. The regimen and duration were according to HCV genotype or subtype and stage of liver disease. The registry record does not state how treatment choices were allocated. It does not describe randomization, and it explicitly does not support treating the listed treatment groups as a like-for-like control comparison. As a result, these data describe outcomes among people receiving the recorded regimens, rather than a randomized estimate of the effect of one regimen compared with another.

The primary endpoint was the percentage achieving sustained virological response 12 weeks after the last dose of study drug. The endpoint timeframe could therefore fall at week 24 or week 36, depending on treatment regimen. The endpoint population was the Core population, defined by adequate treatment according to the standard of care and local label recommendations for each participant’s disease characteristics, including cirrhotic status and genotype.

The record lists 21 outcome measures, including the primary endpoint and secondary virological, adherence and other measures. It records 0 analyses. The primary endpoint’s result, confidence interval and analysis details are not reported in the registry record. The record also does not report a statistical analysis plan, a sample-size justification, or how participants were distributed across treatment groups beyond the adverse-event counts.

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: The Core population, defined as enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

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: Treated participants

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Sustained Virological Response 12 Weeks Post-treatment (SVR12), measured over 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen).

The primary endpoint is the percentage of participants achieving sustained virological response 12 weeks after the last dose of study drug. The registry defines response as HCV RNA below 50 IU/mL at that follow-up point. It states that a participant with missing HCV RNA was counted as a virological failure. The endpoint was assessed in the Core population, which includes enrolled participants adequately treated according to standard of care and local label recommendations for their disease characteristics.

Sustained virological response is a virological endpoint: it uses a laboratory measure of HCV RNA at a specified time after treatment ends. Measuring response after the last dose, rather than only during treatment, makes the endpoint a measure of whether the defined response is sustained to the scheduled follow-up. That is the general rationale for using a post-treatment response endpoint; it does not establish the result in this study.

The follow-up time was 12 weeks after the last dose, corresponding to week 24 or week 36 depending on the treatment regimen. The registry record does not report the number or percentage meeting the endpoint, nor the 95% confidence interval listed as the measure of dispersion. Without those results, the magnitude and precision of the primary endpoint cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record’s primary endpoint is a percentage: the proportion of the defined Core population who achieved sustained virological response 12 weeks after the last dose of study drug. The posted endpoint definition specifies a laboratory threshold, HCV RNA below 50 IU/mL, and treats missing HCV RNA as virological failure. This gives a rule for classifying participants, but the registry record does not report the resulting count, percentage or confidence interval.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimate under the statistical method used to calculate it. For a percentage, it gives a range of values compatible with the data and method, rather than making the estimate exact. The registry identifies a 95% confidence interval as the endpoint’s dispersion measure, but it does not report the interval or the percentage it would accompany. The width of an interval cannot be assessed without the result and its underlying information.

Why does the observational design matter?

In a randomized comparison, random assignment is intended to make treatment groups comparable on average, supporting a causal interpretation of a between-group contrast under appropriate assumptions. This study is observational, and the registry does not state how treatment was allocated. Its treatment descriptions say that regimen and duration followed HCV genotype or subtype and liver-disease stage. Those features are therefore part of the treatment context, and the record does not establish that the regimen groups were comparable. The group labels should be read as descriptions of treatment received, not as evidence of randomized assignment.

Confounding is a general concern in observational comparisons: characteristics related both to treatment selection and to outcome can make a crude difference difficult to interpret as a treatment effect. The registry record does not provide an adjustment strategy, adjusted estimates or a statistical analysis plan. It is therefore not possible to determine from the record whether or how such factors were considered. The counts should not be converted into a causal comparison.

How should the endpoint population be read?

The Core population was defined as enrolled participants who were adequately treated according to standard of care and local label recommendations for their specific disease characteristics, including cirrhotic status and genotype. That definition sets the population for the primary endpoint; it does not necessarily mean all enrolled participants contributed to it. The record does not report the Core-population size, endpoint denominator or number of missing measurements. The missing-data rule says missing HCV RNA counted as failure, but does not supply the number of participants to whom that rule applied.

Classifying missing measurements as failures is one possible endpoint rule. In general, such a rule can affect an estimated percentage, particularly when missingness is common or differs across groups. The record does not report the missing-data frequency or any sensitivity analysis using alternative assumptions. It is therefore not possible to assess how much missing measurements influenced the endpoint estimate.

What can planning calculations say?

General sample-size calculations estimate how many participants might be needed under specified assumptions about the effect to detect, significance level, allocation and statistical method. They are planning illustrations, not evidence about what happened in a completed study and not observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the target effect is described as a stated fraction of the observed effect. The registry record does not report a sample-size justification from the study protocol or provide the observed primary endpoint effect needed to interpret such planning scenarios. Any planning illustration should therefore be kept separate from observed outcomes.

For proportions, a comparison can be affected by the underlying event proportions, group sizes and the way participants enter each analysis. General methods may use different approaches to estimate uncertainty or adjust for covariates. The registry record does not identify the test or model used for the primary endpoint, any covariate adjustment, or assumptions about the outcome distribution. Those methods are not reported in the registry record and should not be inferred from the endpoint type alone.

What does the number of listed outcomes imply?

The record lists 21 outcome measures and 0 analyses. A list of planned or defined outcomes does not reveal which analyses were conducted, which results were available, or how statistical testing was handled. Multiplicity means the challenge of interpreting results when many outcomes or comparisons are tested: as the number of tests increases, the chance of at least one nominally unusual result can increase under general statistical principles. The registry does not report a multiplicity strategy. No claim about correction, prespecified testing order or interim analyses can be made from this record.

In sum, the definitions make clear what the primary endpoint was intended to measure and how missing HCV RNA was classified. They do not disclose the estimate, its uncertainty, or enough analysis detail to reconstruct or evaluate the statistical result.

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("Paritaprevir/Ritonavir + Ombitasvir ± Dasabuvir ± ")
n      <- c(238)
events <- c(225)
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  Paritaprevir/Ritonavir + Ombitasvir ± Dasabuvir ±   238  225  94.5  90.8  97.1  90.9  96.8  90.9  96.8

11. Multiplicity, Missing Data and Analysis Populations

The record lists 21 outcome measures, including sustained virological response at 12 weeks after treatment, other virological outcomes and adherence measures. It records 0 analyses. The number of outcomes alone does not show how many statistical tests were conducted or whether a formal testing hierarchy was used. A multiplicity procedure, adjustment or prespecified order of testing is not reported in the registry record. Interim analyses are also not reported in the registry record.

For the primary endpoint, participants with missing HCV RNA were counted as virological failures. That rule is explicit, but the record does not report how many measurements were missing, how many participants were included in the Core population, or the endpoint denominator. It does not report sensitivity analyses or other missing-data handling for secondary outcomes. General statistical interpretation depends on both the missing-data rule and the amount and pattern of missingness; the record does not give enough information to assess their impact.

The Core population is defined by adequate treatment according to standard of care and local label recommendations for disease characteristics. The record does not state how many enrolled participants met this definition or provide results for alternative analysis populations. It also does not report a detailed statistical analysis plan or an explanation of how the endpoint estimate and confidence interval were calculated. These omissions limit assessment of outcome selection, completeness and robustness, without implying that any particular analysis was or was not performed.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (1.0%), cardiac failure (1.0%), general physical health deterioration (1.0%), sepsis (1.0%), oedema peripheral (0.7%).

The registry record lists adverse-event counts for two groups: paritaprevir/ritonavir, ombitasvir and dasabuvir without RBV, and the same regimen with RBV. The serious-event fields list 3 events among 138 participants at risk in the group without RBV and 4 among 105 at risk in the group with RBV. The death counts are 0 and 3, respectively. The record also lists other-event counts of 0 among 138 and 16 among 105. These are the recorded counts; they do not, by themselves, show that treatment caused an event.

The record lists serious-event terms and their stated percentages: ANAEMIA, CARDIAC FAILURE, GENERAL PHYSICAL HEALTH DETERIORATION and SEPSIS are each 1.0%; OEDEMA PERIPHERAL and INTERVERTEBRAL DISC DISORDER are each 0.7%. These terms should be read as reported safety descriptions, not as a complete account of all possible events or proof of causation.

The groups are not a randomized, like-for-like comparison, and allocation is not stated. Their counts should not be treated as a comparative treatment effect. The record does not provide additional detail about event definitions, follow-up completeness or causal assessment. The percentages and counts describe what was recorded, while their interpretation is limited by the observational design and the information available in the registry record.

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

The record establishes the study’s stated purpose and the endpoint definition, not the primary endpoint result. It says the study sought real-world evidence about effectiveness, patient-reported outcomes, work productivity and safety for an interferon-free regimen. It defines sustained virological response using HCV RNA below 50 IU/mL at 12 weeks after the last dose, with missing HCV RNA classified as failure. But the percentage achieving that endpoint and its 95% confidence interval are not reported in the registry record. There is therefore no posted primary estimate to interpret for magnitude or precision.

The observational design also sets a limit on what treatment-group differences could mean. Participants received regimen and duration according to HCV genotype or subtype and liver-disease stage; allocation is not stated. The registry explicitly cautions that the arms are not a like-for-like control comparison. Descriptive differences between groups would not, by themselves, establish that a regimen component caused an outcome difference.

The safety fields provide counts, deaths and selected serious-event terms, but they do not establish causation or comparative safety. The listed groups differ in the number at risk and are not randomized comparison groups. No treatment benefit or harm conclusion follows from these data alone.

More broadly, an endpoint definition is not an endpoint result, and a completed study status does not supply missing statistical estimates. The registry record lists 21 outcome measures and 0 analyses; outcomes beyond the stated safety information are not reported in the registry record. It does not report a statistical analysis plan, a sample-size justification, adjustment methods or a multiplicity strategy. Those omissions mean that the intended effectiveness question cannot be answered from the registry record alone. The appropriate reading is descriptive: the record identifies who was studied, what treatment was received, what response was meant to count, and some safety counts, while leaving the primary efficacy estimate and its statistical context unreported.

14. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates how a real-world treatment question differs from a randomized comparison. The treatment descriptions are tied to genotype or subtype and stage of liver disease, while the record does not state how treatment was allocated. Such clinical context can shape which regimen a participant receives. It therefore matters that the registry warns the treatment groups are not like-for-like controls: the group labels alone do not support a causal comparison.

The primary endpoint is clearly operationalized. It specifies a post-treatment timing, a laboratory threshold and a rule for missing HCV RNA, and it identifies the Core population. These details are important because the definition determines which observations count as response and which participants are intended to contribute. At the same time, a precise definition cannot substitute for the estimate. The registry record does not report the response percentage or its 95% confidence interval, so statistical precision cannot be assessed.

The record also shows why outcome lists and posted analyses should be distinguished. It lists 21 outcome measures but 0 analyses. The number of measures signals a broad study scope, but it does not disclose which analyses were performed or how multiplicity was handled. The analysis plan, sample-size justification and interim analyses are not reported in the registry record.

Finally, the safety information is descriptive and must be read in the context of an observational design. Counts and reported terms can identify what the registry records, but they cannot alone settle whether an event was caused by treatment or whether one regimen is safer than another. The study’s statistical importance lies in the combination of a real-world question, a defined endpoint and important gaps in posted analysis results—not in a treatment conclusion that the record does not provide.

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 principal limitation for interpreting effectiveness is that the registry record does not report the primary endpoint result. Although it defines sustained virological response and identifies a 95% confidence interval as the dispersion measure, neither the percentage nor the interval is reported. The endpoint numerator and denominator are also not reported, so the estimate and its precision cannot be checked.

The study is observational, and allocation is not stated. The record describes treatment and duration as dependent on HCV genotype or subtype and stage of liver disease, and it cautions that the arms are not a like-for-like control comparison. Without reported adjustment methods or an analysis plan, the registry information does not allow an assessment of whether potential differences between participants were addressed.

The Core population is defined, but its size and relationship to the 244 enrolled participants are not reported. The endpoint rule counts missing HCV RNA as failure, yet the number with missing measurements and any sensitivity analyses are not reported. These details are necessary to understand how complete the endpoint data were and how sensitive the result might be to missingness.

The record lists 21 outcome measures and 0 analyses, but does not report a multiplicity strategy, interim analyses, or a detailed statistical plan. It also does not report a study-specific sample-size justification. The adverse-event counts and selected serious-event terms are descriptive; additional information about event definitions, completeness and causal assessment is not reported in the registry record. These limitations restrict interpretation of both effectiveness and safety and do not justify filling in unreported results or methods.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Hungary — NCT02636608.
• Registry record last updated 2019-07-26; status last verified 2019-01.
• Results first posted 2019-07-26.
• 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

NCT02636608 is a completed observational study in Hungary of paritaprevir/ritonavir and ombitasvir, with or without dasabuvir and ribavirin, for chronic hepatitis C. The registry lists enrollment of 244 participants. Treatment lasted 12 or 24 weeks according to HCV genotype or subtype and stage of liver disease.

The primary endpoint was the percentage achieving sustained virological response 12 weeks after the last dose, defined as HCV RNA below 50 IU/mL; missing HCV RNA counted as failure. The endpoint population was the Core population. The primary result and its 95% confidence interval are not reported in the registry record.

The record lists 21 outcome measures and 0 analyses. It includes adverse-event counts and selected serious-event terms for groups with and without RBV, but these are not randomized comparison groups. Statistical plan details, including multiplicity handling and a study-specific sample-size justification, are not reported in the registry record.