Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin (NCT00491179), a non-randomized phase 4 study. The primary outcome is 1.Number of Participants With Sustained Virologic Response (SVR) 2.Number of Participants Who Droppoed Out of the Study Prematurely Due to Adverse Events (AEs).

2. Clinical Question

The study asks whether retreatment with pegylated interferon alfa-2a plus low-dose ribavirin can be followed by sustained virologic response in dialysis patients with chronic hepatitis C who had failed interferon alfa or pegylated interferon alfa monotherapy. It also records premature withdrawal due to adverse events. The record defines sustained virologic response as undetectable HCV RNA six months off therapy using a real-time PCR test.

The study is identified as a pilot study. Its clinical question is therefore best read as a description of outcomes in a selected retreatment setting, rather than as a randomized test of treatment against an untreated or alternative-treatment control. The registry record does not report an outcome estimate that would establish the size or precision of any observed response.

3. Trial Design

This is a completed, phase 4, non-randomized, open-label, parallel-group pilot study registered as NCT00491179. The registry lists enrollment of 35 and identifies National Taiwan University Hospital as the sponsor. The record gives a start date of 2006-06 and a primary completion date of 2008-06. It describes chronic hepatitis C and hemodialysis as the conditions under study.

The parallel groups correspond to HCV genotype and treatment duration. Participants in the genotype 1 group were assigned the recorded pegylated interferon alfa-2a and ribavirin regimen for 48 weeks; the genotype 2 group was assigned the same recorded doses for 24 weeks. Because allocation was non-randomized and the groups represent different genotypes and treatment durations, their outcomes should not be treated as if they arose from randomized assignment to competing treatments. Differences between the groups could reflect group composition or other factors, and the registry record does not report an adjustment strategy that would address this.

Masking is listed as none. This indicates that the registry does not describe masking of the study; the record does not specify a separate blinded outcome-assessment process. The study is marked completed, but completion status alone does not provide the outcome results.

The registry lists an enrollment figure but does not give the number analyzed in each group for the primary outcomes. Arm-level counts for sustained virologic response and adverse-event withdrawal are not reported in the registry record. The detailed protocol, eligibility criteria beyond the description of prior treatment failure and dialysis, sample-size justification, and statistical analysis plan are also not reported in the registry record. These absences limit what can be inferred about the intended comparisons and the handling of the enrolled participants.

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: Wash out period: 6 months after last interferon intervention

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Outcome measures:intention-to-treat (ITT) analysis Imputation technique: last observation carried forward

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as 1.Number of Participants With Sustained Virologic Response (SVR) 2.Number of Participants Who Droppoed Out of the Study Prematurely Due to Adverse Events (AEs), measured over 1.5 year.

The primary outcomes are the number of participants with sustained virologic response and the number who withdrew prematurely because of adverse events. The registry defines sustained virologic response as undetectable HCV RNA six months off therapy, measured by real-time PCR with the Cobas TaqMan HCV Test v2.0. The stated limit of detection is < 25 IU/mL. This endpoint uses a laboratory measure of viral RNA after treatment has ended, rather than relying only on symptoms or a measurement taken during therapy.

In general, a sustained virologic response endpoint is used to describe whether a treatment-period change remains detectable at a specified follow-up point. Its interpretation depends on the timing of the measurement, the assay definition, and how participants without an observed measurement are handled. The registry states a timeframe of 1.5 year for the primary outcome measure and separately defines the response in relation to six months off therapy. It does not report the actual response counts or the timing of individual assessments.

The other primary outcome captures premature withdrawal attributed to adverse events. It addresses treatment discontinuation due to tolerability, but it does not by itself describe the full range, severity, or duration of adverse events. The registry record does not report arm-level results for either primary outcome, so neither response frequency nor adverse-event withdrawal frequency can be estimated from the posted primary endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help define what a study estimates, how uncertainty is represented, and how incomplete observations are handled. The registry record gives some outcome-analysis details but does not report a full statistical plan or endpoint results. The concepts below explain how to read the methods that are stated without implying analyses or findings that are not recorded.

What does non-randomized allocation imply?

Random allocation is used to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. In a non-randomized study, group membership may be related to clinical features, treatment decisions, or other factors. That creates a risk of confounding: an outcome difference may reflect group composition as well as treatment. Here the registry describes groups by genotype and treatment duration, making a direct treatment contrast especially difficult to interpret. General statistical principle: adjustment can sometimes address measured differences, but it cannot guarantee removal of bias from unmeasured factors. The record does not report an adjustment method.

What would a confidence interval convey?

In general, a confidence interval describes the uncertainty around an estimated effect under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values corresponding to no difference may leave the direction or size of an effect uncertain. No confidence intervals or primary effect estimates are reported in the registry record. This means there is no posted interval from which to judge the precision of a treatment contrast.

How should significance tests be read?

A p-value assesses how compatible observed data are with a specified null model, given the assumptions of the test. It does not measure the probability that a treatment works, and it does not describe the magnitude or clinical importance of an effect. The registry record does not report primary outcome p-values. The sample-size assumptions mention a two-sided significance level of 0.05 for planning illustrations, but that planning assumption is not a reported test result for this study.

What do the planning assumptions mean?

The sample-size description characterizes its calculations as planning illustrations based on the observed effect, with equal allocation between arms and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, it describes the total number of events; for other illustrations, it describes participants per arm for 80% power or other specified planning power. These are design calculations, not observed outcomes and not observed power. The record does not report the observed effect or the planning-illustration values, so those quantities cannot be interpreted numerically from the registry record.

Why does over-dispersion matter in general?

For count outcomes, a simple model may assume that variability follows a specified distribution. Over-dispersion means that observed variability is greater than that model allows. If ignored, standard errors can be too small and uncertainty can appear less than it is. The registry describes the primary outcomes as participant counts with events, but it does not report a count-model specification, an over-dispersion assessment, or a model-based analysis. This general issue should not be mistaken for a finding about this study.

What does last observation carried forward assume?

Last observation carried forward fills a missing later measurement using a participant’s most recent observed value. In general, this creates an assumption that the carried value is an acceptable stand-in for the unobserved outcome. That assumption may be implausible when a clinical measure can change after the last observation, and the method can affect both estimated event frequencies and uncertainty. The registry states that this technique was used for the intention-to-treat outcome analysis, but it does not report the amount or pattern of missing data or sensitivity analyses using other assumptions.

Can the group outcomes be interpreted causally?

A causal interpretation requires more than observing different outcomes. The groups need to be sufficiently comparable, the outcome definitions and follow-up must be appropriate, and the analysis must address relevant sources of bias. Non-randomized allocation and genotype-specific group assignment weaken the basis for attributing any group contrast to treatment. Since the registry record does not report primary outcome counts or an analysis estimate, even a descriptive contrast cannot be reconstructed. Statistical methods can clarify the limits of inference, but they cannot recover results that are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The record lists two primary outcome components: sustained virologic response and premature withdrawal due to adverse events. It also lists histologic response as a secondary outcome. Testing or interpreting several outcomes raises a general multiplicity issue: as the number of statistical comparisons increases, the chance of at least one apparently notable result can also increase. A prespecified hierarchy or adjustment can help define how multiple outcomes should be interpreted. The multiplicity strategy is not reported in the registry record.

The record identifies an intention-to-treat analysis population and last observation carried forward as the imputation technique. In general, intention-to-treat analysis aims to retain participants in their assigned or defined study groups, while an imputation rule specifies how missing outcome information is treated. The entry does not report how many participants had missing outcome data, how many were included in each endpoint analysis, whether all enrolled participants contributed to each analysis, or whether sensitivity analyses were conducted. The detailed statistical analysis plan is not reported in the registry record.

These omissions matter because endpoint definitions alone do not reveal how incomplete follow-up affects an estimate. Last observation carried forward may yield a different result from approaches that model missingness or use alternative assumptions. Without missing-data counts and sensitivity results, the robustness of any endpoint estimate cannot be assessed. Moreover, the registry record does not report the primary outcome counts or inferential results needed to evaluate multiplicity in practice. The stated analysis population and imputation method should therefore be read as limited descriptions of the planned or reported approach, not as evidence that missingness or multiple outcomes had no effect on interpretation.

11. 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: optic neuritis (10.0%), interstitial pneumonia (4.0%).

The adverse-event record lists the genotype 1 group, treated for 48 weeks, with 25 at risk in the serious-event field and 2 affected; its other-event field lists 25 at risk and 22 affected. For the genotype 2 group, treated for 24 weeks, the corresponding serious-event figures are 10 at risk and 1 affected, while the other-event field lists 10 at risk and 8 affected. These are descriptive entries, not randomized comparisons.

The record also lists optic neuritis at 10.0% and interstitial pneumonia at 4.0% among the top serious terms. It does not specify the denominator or clarify in the adverse-event entry how those percentages were calculated. They should not be read as group-specific risks or compared with the affected counts without that information. The record does not provide event timing, recurrence, severity grading beyond the serious-event classification, or a causal attribution assessment.

These figures describe the entries in the registry record; they do not establish whether an event was caused by treatment or how safety compares with another regimen. The primary outcome of withdrawal due to adverse events is also not reported by group, so the adverse-event fields cannot be used to reconstruct that endpoint.

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

This trial record describes retreatment of dialysis patients with chronic hepatitis C using pegylated interferon alfa-2a plus low-dose ribavirin. It specifies different treatment durations by genotype and identifies sustained virologic response and premature withdrawal due to adverse events as primary outcomes. It also records a secondary histologic response outcome and limited adverse-event information. These details establish the study question and some outcome definitions, but they do not provide the primary results.

The registry record does not report the number of participants with sustained virologic response or the number who withdrew because of adverse events in either group. It also does not report comparative estimates, confidence intervals, or p-values. Therefore, the posted record cannot establish the observed response frequency, the uncertainty around a response estimate, or a difference between groups. It cannot be used to conclude that the treatment is effective or ineffective.

The non-randomized, open-label design further limits comparisons. The groups correspond to different genotypes and durations, rather than randomized alternatives. Any contrast between them would be vulnerable to differences in group composition and could not be attributed to treatment duration or another treatment feature without suitable methods and assumptions. No such adjusted comparative analysis is reported.

The listed serious-event figures are descriptive and have unclear denominators for the serious terms. They do not replace a complete safety analysis or provide a controlled estimate of risk. The registry record also does not report missing-data quantities, the details of sensitivity analyses, or the multiplicity strategy.

In general, a completed study registration is not equivalent to a complete report of its outcomes. The record is useful for identifying the intended clinical question, treatment schedules, and stated outcome methods, while its omissions prevent a reliable assessment of effect size, statistical precision, and comparative safety.

13. Why This Trial Matters Statistically

This study is statistically important as an example of how design and reporting determine what can be learned from clinical research. The registry identifies a specific population—dialysis patients with chronic hepatitis C who had failed prior interferon monotherapy—and a retreatment regimen that combines pegylated interferon alfa-2a with low-dose ribavirin. It distinguishes treatment duration according to genotype and defines outcomes that include both virologic response and withdrawal due to adverse events.

Those features make careful interpretation necessary. The non-randomized allocation means that the groups do not provide a randomized comparison, and the genotype-specific schedules make group contrasts difficult to attribute to treatment duration. These design limits are not resolved by the study being marked completed or by a sample-size planning illustration. Planning calculations describe hypothetical detection targets under stated assumptions; they are not evidence that a result was observed or that an estimate is precise.

Outcome reporting is equally central. Without primary outcome counts and estimates, readers cannot evaluate the observed response, the frequency of adverse-event withdrawal, or statistical uncertainty. The stated intention-to-treat population and last observation carried forward method provide some information about analysis, but missing-data counts and sensitivity analyses are not reported. The record also does not describe how multiple outcomes were handled statistically.

The statistical lesson is that a clear endpoint definition is valuable but insufficient on its own. Interpretation requires the observed data, an appropriate analysis, a transparent account of missingness, and a design that supports the intended comparison. This record documents the clinical question and some methods, while leaving the main outcome evidence unavailable in the registry entry.

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.

Several limitations specific to this record constrain interpretation. The study is non-randomized and open-label, and the treatment groups are defined by genotype as well as treatment duration. They therefore do not constitute a randomized comparison of alternative regimens or durations. The registry does not report adjustment methods that might address measured differences between groups, and no method can fully remove uncertainty from unmeasured confounding.

Most importantly, arm-level primary outcome results are not reported in the registry record. There are no stated counts for sustained virologic response or premature withdrawal due to adverse events, and no effect estimates or uncertainty intervals. Although the study is marked completed, completion status does not fill this reporting gap. The number analyzed in each group for each outcome is also not reported.

The registry states an intention-to-treat population and last observation carried forward but does not give missing-data counts, reasons for missingness, or sensitivity analyses. The analysis plan, multiplicity approach, and sample-size justification are not reported. Planning illustrations are described in general terms, but their numerical results and the observed effect used as a basis are not reported in the registry record.

The safety entry provides limited counts and serious-event terms, but the denominator and calculation basis for the listed term percentages are not clear. It also does not provide event timing, recurrence, or a full account of severity and attribution. Together, these limitations mean the record supports description of the study design and recorded safety fields, but not a precise assessment of efficacy, comparative effects, or overall safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin — NCT00491179.
• Registry record last updated 2009-11-13; status last verified 2009-10.
• Results first posted 2009-11-13.
• 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

NCT00491179 is a completed phase 4, non-randomized, open-label, parallel-group pilot study sponsored by National Taiwan University Hospital. It enrolled 35 and studied pegylated interferon alfa-2a plus ribavirin in dialysis patients with chronic hepatitis C who had failed interferon alfa or pegylated interferon alfa monotherapy. The genotype 1 regimen was listed for 48 weeks and the genotype 2 regimen for 24 weeks.

The primary outcomes were sustained virologic response and premature withdrawal due to adverse events. The record defines the response using undetectable HCV RNA six months off therapy and states an intention-to-treat analysis with last observation carried forward. It also lists histologic response as a secondary outcome.

Arm-level primary outcome counts and comparative estimates are not reported in the registry record. Non-randomized, genotype-specific groups do not provide a like-for-like control comparison. The entry contains limited adverse-event figures, but the serious-term percentage denominators are not stated.