An Observational Study on Dual And Triple Therapies Based on Peginterferon Alfa (e.g. Pegasys) in Patients With Chronic Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study on Dual And Triple Therapies Based on Peginterferon Alfa (e.g. Pegasys) in Patients With Chronic Hepatitis C (NCT01447446), a registered phase not stated study. The primary outcome is Percentage of Participants With Sustained Virological Response at 24 Weeks Post Completion of the Treatment Period (SVR24).

2. Clinical Question

3. Trial Design

This was a prospective, multicenter, observational cohort study of peginterferon-based treatment for chronic hepatitis C. The registry lists the study as completed, with a recorded enrollment of 4442. The study start is recorded as 2011-09 and primary completion as 2015-07. Participants received treatment according to current product information and local labeling, rather than being assigned by randomization in the study description.

The treatment groups comprised dual therapy with peginterferon alfa-2a or alfa-2b plus ribavirin, and triple therapy combining either peginterferon formulation and ribavirin with boceprevir or telaprevir. Follow-up was intended to continue through treatment and for up to 24 weeks after treatment. The primary endpoint is specified at 24 weeks after treatment, with a timeframe stated as up to 118 weeks.

This design describes treatment as used in clinical practice, but it does not by itself make the regimen groups exchangeable. The registry states that allocation was not stated and that the arms are not a like-for-like control comparison. Differences in patient characteristics, treatment selection, and clinical circumstances could therefore accompany differences between the observed groups. Details of adjustment methods, eligibility implementation, recruitment procedures, and the statistical analysis plan are not reported in the registry record.

The record lists 14 outcome measures and 0 analyses. Listed secondary outcomes include virological response at treatment time points and end of treatment, relapse, breakthrough, sustained response among participants with dose reductions or interruptions, early response categories, extended rapid response, treatment duration, and treatment according to product labeling. The endpoint definitions and the registry's outcome list describe intended measurements; they do not supply numerical outcome findings.

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: Core population: treatment-naive/experienced participants who were without contraindication to Peg-IFN and RBV, end stage renal disease, major organ transplantation, co-infection with hepatitis B or HIV, acute hepatitis and with positive HCV RNA at baseline, known genotype, 1 of 6 treatment (excluding non-G1 participants receiving triple therapy).

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: Core population: treatment-naive/experienced participants who were without contraindication to Peg-IFN and RBV, end stage renal disease, major organ transplantation, co-infection with hepatitis B or HIV, acute hepatitis and with positive HCV RNA at baseline, known genotype, 1 of 6 treatment (excluding non-G1 participants receiving triple therapy).

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virological Response at 24 Weeks Post Completion of the Treatment Period (SVR24), measured over 24 weeks after end of treatment (up to 118 weeks).

The primary endpoint is the percentage of participants with sustained virological response 24 weeks after completing treatment, called SVR24 in the registry. It is a binary outcome at the participant level: a participant either meets the specified virological response definition or does not. The reported group percentage would describe the fraction meeting that definition, while its confidence interval would express uncertainty around the estimated percentage.

The assay criteria differ in wording by regimen type. For dual therapy, the definition uses HCV RNA below 50 IU/mL at the specified follow-up, measured with an assay whose detection limit is no greater than 50 IU/mL; if a quantitative test was used, its quantification limit also had to be no greater than 50 IU/mL. For triple therapy, the definition is undetectable HCV RNA at follow-up using a test with a detection limit no greater than 50 IU/mL.

As a general statistical concept, a sustained response endpoint captures a measurement after treatment has ended, rather than only an on-treatment measurement. The common follow-up point makes the endpoint interpretable across regimens when the definitions and measurement procedures are applied consistently. It does not remove the limitations of observational comparisons or establish that any group difference was caused by treatment. The registry record does not report the primary endpoint percentage, its 95% confidence interval, or the number of participants contributing to that endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does an observational cohort estimate?

In general, an observational cohort records outcomes among people receiving care without random assignment by the study. A percentage in a treatment group describes the observed frequency of an outcome among the participants included in that analysis. It does not automatically estimate what would have happened to those same participants under a different regimen. That causal question requires assumptions and methods that address differences between groups.

For this study, the registry describes multiple dual and triple regimens, says allocation was not stated, and cautions that the groups are not a like-for-like control comparison. Thus, an unadjusted difference in response or adverse events could reflect differences in who received each regimen as well as any treatment-related difference. The analysis approach used to address such factors is not reported in the registry record.

What does the confidence interval communicate?

In general, a confidence interval gives a range of values compatible with the observed data under the specified statistical method. A narrower interval indicates greater statistical precision for that estimate, while a wider interval indicates less precision. A 95% confidence interval is specified for the primary outcome, but the estimate and interval themselves are not reported in the registry record. An interval cannot be reconstructed from the endpoint definition alone.

Precision is distinct from validity. A confidence interval can quantify sampling uncertainty under a model, but it does not correct confounding, systematic selection, measurement error, or incomplete follow-up. Nor does an interval establish that an observed difference is clinically important. Interpretation requires the estimate, its interval, the analysis population, and an understanding of the design limitations.

How should binary outcomes be read?

The primary endpoint is a percentage of participants meeting a defined response criterion. In general, such an outcome reduces each participant's result to whether the criterion was met at the specified assessment. The denominator matters: a percentage based on everyone enrolled may differ from one based only on participants with an observed follow-up test. The registry record does not report the endpoint-specific denominator or missing-data handling.

The definition also depends on HCV RNA measurement and assay thresholds. Consistent application of the stated criteria is important when comparing groups. The registry specifies somewhat different wording for dual and triple therapy, including the requirement for undetectable RNA in the triple therapy definition. Whether measurement procedures were otherwise harmonized is not reported in the registry record.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, standard errors may be too small and confidence intervals too narrow. This consideration can matter in clustered or heterogeneous data, but the registry record does not report a model for the primary endpoint or whether over-dispersion was assessed. It would therefore be inappropriate to claim that a particular correction was or was not used.

What do the planning calculations represent?

The registry's accompanying planning approach is described as an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed around those assumptions or that the corresponding power was observed. The registry explicitly distinguishes planning illustrations from the trial's own design. A sample-size illustration is not a substitute for reporting the observed endpoint estimate and its uncertainty.

In general, planning calculations describe how much information a future comparison might require under specified assumptions. Their relevance depends on the chosen effect, outcome variability, allocation, analysis, and missingness. The study's own sample-size justification and analysis plan are not reported in the registry record. No planning value should be interpreted as an observed 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("Dual Therapy: Peg-IFN Alfa-2a + Ribavirin", "Dual Therapy: Peg-IFN Alfa-2b + Ribavirin", "Triple Therapy: Boceprevir + Peg-IFN Alfa-2a + Rib", "Triple Therapy: Boceprevir + Peg-IFN Alfa-2b + Rib", "Triple Therapy: Telaprevir + Peg-IFN Alfa-2a + Rib", "Triple Therapy: Telaprevir + Peg-IFN Alfa-2b + Rib")
n      <- c(2312, 496, 292, 93, 821, 86)
events <- c(1205, 245, 136, 47, 474, 41)
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  Dual Therapy: Peg-IFN Alfa-2a + Ribavirin  2312  1205  52.1  50.1  54.2  50.1  54.2  50.1  54.2
ARM  Dual Therapy: Peg-IFN Alfa-2b + Ribavirin  496  245  49.4  44.9  53.9  45.0  53.8  45.0  53.8
ARM  Triple Therapy: Boceprevir + Peg-IFN Alfa-2a + Rib  292  136  46.6  40.7  52.5  40.9  52.3  40.9  52.3
ARM  Triple Therapy: Boceprevir + Peg-IFN Alfa-2b + Rib  93  47  50.5  40.0  61.1  40.6  60.5  40.5  60.5
ARM  Triple Therapy: Telaprevir + Peg-IFN Alfa-2a + Rib  821  474  57.7  54.3  61.1  54.3  61.1  54.3  61.1
ARM  Triple Therapy: Telaprevir + Peg-IFN Alfa-2b + Rib  86  41  47.7  36.8  58.7  37.4  58.1  37.4  58.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, spanning several virological response time points, relapse, breakthrough, response after dose reductions or treatment interruptions, response categories during the first 12 weeks, treatment duration, and treatment according to product labeling. When many outcomes or time points are examined, there are more opportunities for apparently notable findings to arise by chance. As a general statistical principle, multiplicity procedures can address that issue, but the registry record does not report whether any were planned or applied.

The record lists 0 analyses and does not report outcome estimates or tests for the primary or secondary outcomes. It therefore does not establish which outcomes were analyzed, how they were prioritized, or whether there were prespecified subgroup analyses. A complete statistical analysis plan is not reported in the registry record.

Missing-data handling is also not reported. For a follow-up endpoint, missing measurements can affect the analysis denominator and the estimated response percentage. In general, complete-case analysis, imputation, and other approaches rely on different assumptions; no particular approach can be attributed to this study from the registry information. The number of participants with an observed SVR24 measurement, reasons for missingness, and any sensitivity analyses are not reported in the registry record.

The primary endpoint description refers to a core population with specified clinical and virological characteristics, but that description ends mid-phrase in the registry record. The full analysis-population definition, how eligibility was determined, and whether other analysis populations were used are not reported. These gaps limit assessment of selection into the endpoint analysis and the impact of missing outcomes.

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: anaemia (6.9%), neutropenia (1.4%), diarrhoea (1.2%), vomiting (1.2%), asthenia (1.2%).

The safety record gives serious adverse event counts and other adverse event counts separately for each regimen group. For example, the serious-event counts are 148 among 2312 at risk for dual therapy with peginterferon alfa-2a and ribavirin, and 33 among 496 at risk for dual therapy with peginterferon alfa-2b and ribavirin. For triple therapy, the serious-event counts are 43 among 292 at risk with boceprevir and peginterferon alfa-2a, 9 among 93 at risk with boceprevir and peginterferon alfa-2b, 163 among 821 at risk with telaprevir and peginterferon alfa-2a, and 4 among 86 at risk with telaprevir and peginterferon alfa-2b.

These are descriptive registry counts, not adjusted comparisons. The other adverse event counts are also listed by group, but should not be combined with serious-event counts or treated as a comparative rate without the relevant analysis. The registry names Anaemia at 6.9%, Neutropenia at 1.4%, Diarrhoea at 1.2%, Vomiting at 1.2%, Asthenia at 1.2%, and Optic neuritis at 1.2% among the top serious adverse event terms. The denominator and any event-specific observation time for those percentages are not reported in the registry record. Death counts are not reported in the registry record.

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

The registry record identifies the clinical question and the response definition: sustained virological response at 24 weeks after treatment. It also describes the regimens observed and gives serious and other adverse event counts by group. These details can clarify what the study set out to assess and what kinds of outcomes it recorded.

The primary numerical result is not reported in the registry record. Consequently, the record does not establish the observed SVR24 percentage, its precision, or whether response differed across the listed regimens. It would be incorrect to infer a result from the study title, enrollment, endpoint definition, or treatment descriptions. The absence of a reported estimate in this record is not evidence that an outcome did or did not occur.

Even if group outcome estimates were available, the observational design would remain important. The registry says allocation was not stated and that the arms are not a like-for-like control comparison. In general, observed differences may reflect patient selection, clinical circumstances, or other group differences, in addition to any effect of treatment. An estimate from an observational comparison is not automatically a causal effect.

The safety counts describe events recorded in the groups; they do not establish that one regimen caused more or fewer events than another. Such a comparison would need clearly defined populations and time at risk, appropriate analyses, and consideration of differences between groups. The record does not report those comparative analyses. Thus, the supported interpretation is descriptive: the registry lists specific regimen groups, outcome definitions, and event counts, while leaving the main efficacy estimate and important analysis details unreported.

14. Why This Trial Matters Statistically

This study is statistically relevant because it describes treatment use across dual and triple peginterferon-based regimens in a prospective, multicenter observational setting. Clinical practice cohorts can document outcomes among people receiving different regimens outside a randomized allocation scheme. Such information can be useful for understanding what was observed in the recorded cohort, provided that descriptive findings are kept distinct from causal conclusions.

The record also illustrates why endpoint definitions and analysis populations matter. SVR24 is tied to a follow-up time after treatment and to assay-specific criteria. Interpretation depends on who was included in the analysis, how missing follow-up was handled, and whether measurement was sufficiently consistent across groups. Those details are not fully reported in the registry record.

Statistically, the central limitation is that the record defines a primary outcome but does not provide its estimate or confidence interval. It lists 14 outcome measures and 0 analyses, and it does not report an analysis plan or adjustment methods. The stated warning that the treatment arms are not like-for-like reinforces the need to avoid reading any descriptive group contrast as a randomized comparison.

The study therefore matters as a case in separating a registry's design and outcome specifications from the results needed to assess magnitude and precision. Enrollment and treatment-group descriptions establish context; they do not substitute for outcome estimates, denominators, uncertainty intervals, or transparent methods. The safety counts similarly show how raw event summaries can inform description without establishing comparative safety effects.

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 registry record does not report the primary SVR24 estimate or its 95% confidence interval. It also does not report the endpoint analysis denominator, the number of missing follow-up measurements, or the methods used to handle missing data. These omissions prevent assessment of the precision and completeness of the primary result from this record.

The study is observational, allocation is not stated, and the registry explicitly cautions that the treatment groups are not like-for-like controls. Baseline characteristics by group, adjustment methods, and the statistical analysis plan are not reported. Consequently, the record does not establish whether or how measured or unmeasured differences between participants were addressed.

The primary population description is incomplete, ending before its full exclusion criteria are given. The registry also does not report how the analysis population was constructed or whether separate populations were used for efficacy and safety. Although the study lists several secondary outcome categories, their estimates and analysis details are not reported.

The safety record provides event counts and selected serious-event percentages, but does not report a comparative safety analysis, the denominator for the listed term percentages, or event-specific time at risk. Death counts are not reported in the registry record. These limitations make the safety information descriptive and restrict comparisons between regimens.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Observational Study on Dual And Triple Therapies Based on Peginterferon Alfa (e.g. Pegasys) in Patients With Chronic Hepatitis C — NCT01447446.
• Registry record last updated 2017-03-30; status last verified 2016-12.
• Results first posted 2017-03-30.
• 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

NCT01447446 is a completed prospective, multicenter observational cohort study of dual and triple peginterferon-based therapies for chronic hepatitis C, with enrollment recorded as 4442. Its primary outcome is the percentage of participants with SVR24, defined using HCV RNA assay criteria. The registry describes treatment groups receiving peginterferon alfa-2a or alfa-2b with ribavirin, with boceprevir or telaprevir added in triple therapy.

The registry lists 14 outcome measures and 0 analyses. It does not report the primary endpoint estimate or confidence interval, and it cautions that the groups are not like-for-like controls. Serious and other adverse event counts are recorded by regimen, but the available safety information is descriptive. Important analysis details, including missing-data handling and adjustment methods, are not reported in the registry record.