Effect of Insulin Resistance on the Safety and Efficacy of Pegylated Interferon and Ribavirin Treatment in HCV (Study P05562): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Insulin Resistance on the Safety and Efficacy of Pegylated Interferon and Ribavirin Treatment in HCV (Study P05562) (NCT00705224), a registered phase not stated study. The primary outcome is Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study.

2. Clinical Question

The study asked whether insulin resistance was associated with the safety and efficacy of pegylated interferon and ribavirin treatment among treatment-naïve people with chronic hepatitis C. It also aimed to determine how common insulin resistance was in different populations of people with chronic hepatitis C. The record describes treatment according to routine clinical practice in Russia, rather than a randomized comparison of treatment strategies.

3. Trial Design

The registry record identifies this as an observational, multicenter study in Russia. Its official title describes evaluation of the influence of insulin resistance on safety and efficacy among different populations of patients with hepatitis C. Enrollment was 250. The study status is completed, with a start date of 2008-05 and primary completion in 2010-08.

Participants were treatment-naïve people with chronic hepatitis C of any genotype. Pegylated interferon and ribavirin were given as standard treatment according to routine clinical practice. The record does not specify that participants were randomly allocated, and allocation is not stated. It therefore does not establish a like-for-like control comparison between separate treatment arms. The registry record also does not report the number of participants who received each treatment duration or the number who completed follow-up.

The primary outcome was the percentage achieving sustained virological response at the end of the study. Secondary outcomes concerned response at the end of treatment, virological relapse, and early virological response, with outcome descriptions organized by genotype and baseline insulin resistance. These additional outcomes address different stages or patterns of virological response; they are not substitutes for the primary outcome.

The record describes the study question and outcome framework, but does not report primary or secondary outcome estimates. It also does not report a sample-size justification, detailed statistical analysis plan, or planned handling of potential confounding. Those omissions limit how much can be concluded about the study's comparative analyses from the registry record alone.

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: Completer set for the primary analysis included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study.

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 Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study, measured over 24 weeks following completion of 24 or 48 weeks of therapy.

The primary endpoint was the percentage of participants with sustained virological response assessed at the end of the study. The record defines sustained virological response as undetectable plasma hepatitis C virus RNA 24 weeks after treatment ended. The assessment was made at Visit 4, which was Week 48 or Week 72 depending on whether treatment lasted 24 or 48 weeks.

This endpoint distinguishes a response that remains detectable after treatment has ended from a measurement taken during treatment or at its completion. As a general statistical point, an outcome defined at a specified follow-up time gives a consistent target for describing response, provided the assessment and analysis population are clearly defined. Here, the registry's primary analysis population was the completer set: participants who received at least one dose and had sustained virological response data at the end of the study.

The registry record does not report the number or percentage achieving this endpoint, nor its stated 95% confidence interval. Thus, the endpoint is defined, but its observed result and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For the primary outcome, the registry describes a binary event: a participant either met the definition of sustained virological response at the specified follow-up or did not. The outcome is summarized as a percentage of participants. As a general statistical explanation, a percentage is meaningful only alongside its denominator and a clear rule for deciding which participants contribute. The registry specifies the primary analysis population, but does not give its size or the outcome count.

What a confidence interval contributes

The outcome description names a 95% confidence interval. In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a particular analysis method. It is not a guarantee that an individual participant's outcome will fall within an interval, and it does not by itself address bias, confounding, or missing data. Since the interval and the estimate are not reported in the registry record, their precision cannot be evaluated.

Why the study design affects interpretation

The registry identifies the study as observational and does not state an allocation method. In general, observational comparisons do not have the protection against measured and unmeasured differences that random allocation is intended to provide. For example, participants in different insulin-resistance groups may also differ in other characteristics associated with response. Statistical adjustment can sometimes address measured differences, but the registry record does not report whether adjustment was planned or performed. No specific adjusted or unadjusted estimate is reported.

Outcome comparisons by genotype and baseline insulin resistance may be informative as descriptions of patterns. In general, however, dividing participants into subgroups reduces the information available within each comparison. The resulting estimates can be less precise, and differences between subgroups should not be treated as established merely because their point estimates differ. Interpretation requires the subgroup counts, estimates, uncertainty intervals, and analysis plan, none of which are reported for these outcomes in the registry record.

Planning calculations are not observed power

The planning assumptions describe illustrations based on the observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Such assumptions can be used for planning illustrations, but they do not establish that the study was designed with those assumptions. They also do not show the probability that the completed study detected an effect. The registry record does not report its sample-size justification, and planning illustrations are not a substitute for outcome estimates with uncertainty intervals.

As a general matter, calculations based on an observed effect can be sensitive to that estimate, particularly when it is uncertain. A calculation under equal allocation also relies on that allocation assumption; the record does not describe a randomized two-arm allocation. The illustration assumptions should therefore be read as planning scenarios, not as a description of how participants were assigned or as evidence about the study's realized statistical power.

What cannot be reconstructed

The registry record does not report the statistical tests or models used, whether analyses were adjusted, how repeated or incomplete observations were handled, or whether any interim analyses took place. It also does not report subgroup denominators or outcome estimates. These details are needed to assess the statistical analysis beyond the definitions and population description that are recorded. General explanations of percentages, confidence intervals, observational comparisons, and subgroup precision do not fill those evidence gaps.

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("Pegylated Interferon and Ribavirin")
n      <- c(223)
events <- c(181)
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  Pegylated Interferon and Ribavirin  223  181  81.2  75.4  86.1  75.5  85.8  75.5  85.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes. The secondary outcomes cover sustained response by genotype and baseline insulin resistance, response at the end of treatment, virological relapse, and early virological response. Considering several outcomes and subgroups creates a multiplicity issue: as a general statistical matter, the more comparisons examined, the greater the chance that some results may appear notable by chance alone. The registry record does not report whether a multiplicity adjustment or a hierarchy for interpreting these outcomes was planned.

The primary analysis population included participants who received at least one dose and had end-of-study sustained virological response data. This definition makes clear that participants without those data were not included in that stated population. It does not explain how many participants lacked data, why data were missing, or whether missingness differed across participant groups. A method for imputing or otherwise handling missing outcomes is not reported in the registry record.

Enrollment of 250 should not be confused with the primary analysis denominator. The denominator may be smaller under the stated completer-set definition, but its size is not reported. No secondary-outcome analysis population or missing-data method is described. Consequently, the extent to which incomplete follow-up could affect the outcome percentages cannot be assessed from this record.

The statistical analysis plan, including any interim analyses, is not reported in the registry record. The presence or absence of adjustments, prespecified subgroup tests, or other analysis decisions should not be assumed.

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: drug exposure during pregnancy (0.4%), acoustic neuritis (0.4%).

For the pegylated interferon and ribavirin group, the registry lists 250 participants at risk for serious adverse events and 2 participants affected. It separately lists 250 at risk for other adverse events and 177 affected. These are posted counts; they should not be interpreted as a comparison with an untreated group or with another regimen.

The listed serious adverse event terms are Drug Exposure During Pregnancy and Acoustic Neuritis, each reported as 0.4%. The record does not provide further detail about timing, severity beyond the serious-event classification, relationship to treatment, or the number of events for each term. Deaths are not reported in the registry record.

As a general statistical point, adverse-event counts depend on the definitions used, the participants monitored, and the observation period. A count of participants affected is not necessarily a count of all event episodes. The registry's reported figures should therefore be read within the stated group and outcome categories; they do not establish comparative risk or causation.

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

The registry record establishes that the study examined pegylated interferon and ribavirin treatment in treatment-naïve patients with chronic hepatitis C, and that it focused on insulin resistance, safety, and sustained virological response. It defines the primary response outcome and identifies secondary outcomes involving genotype, insulin resistance, end-of-treatment response, relapse, and early response.

It does not report the primary outcome percentage, the confidence interval, or results for the secondary outcomes. As a result, the posted record cannot show what proportion achieved sustained virological response or whether response differed across insulin-resistance or genotype groups. It also cannot show the size or precision of any such difference.

The study is observational, and allocation is not stated. Therefore, the record does not establish a randomized causal comparison. Even if subgroup outcome estimates were available, differences could reflect participant characteristics other than insulin resistance; the adjustment strategy is not reported. The record also does not provide the primary analysis denominator or information about missing outcome data beyond defining the completer set.

The safety counts describe participants affected in the recorded treatment group. They do not establish that treatment caused an event, and they do not quantify a comparison with another treatment strategy. The listed serious-event terms and percentages are descriptive registry entries, not a complete account of clinical context.

In short, the record supports understanding what investigators intended to measure and how the primary endpoint was defined. It does not support a conclusion about the efficacy of treatment, the effect of insulin resistance, or comparative safety. Such conclusions require outcome results and sufficient detail about the analyses and populations.

14. Why This Trial Matters Statistically

This study is statistically interesting because it frames treatment response around a participant characteristic, insulin resistance, rather than only reporting an overall response outcome. Its registry description also identifies genotype as a factor for examining sustained response, end-of-treatment response, relapse, and early response. That structure raises familiar questions about subgroup estimates, precision, and how multiple comparisons should be interpreted.

The endpoint definition is also important: sustained virological response was assessed 24 weeks after treatment ended, with the scheduled study visit depending on whether the treatment duration was 24 or 48 weeks. A clearly timed endpoint helps define the target quantity, while the completer-set rule shows that the primary analysis depended on both treatment exposure and end-of-study response data.

At the same time, this record illustrates why study design and outcome reporting matter. Observational comparisons can be affected by differences among participant groups, and the record does not state an adjustment strategy. Enrollment is reported, but the primary analysis denominator and outcome estimates are not. Without those results, statistical precision and subgroup patterns cannot be evaluated.

The study therefore provides a useful example of the distinction between a registered question and an answer supported by reported results. Definitions, planned outcomes, and safety counts help characterize the research, but they do not replace efficacy estimates, uncertainty intervals, and transparent analysis details.

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 consequential limitation for interpreting this registry record is that it does not report the primary sustained virological response percentage or its 95% confidence interval. Secondary outcome results are also not reported. The record therefore permits no assessment of the magnitude, direction, or precision of the efficacy findings.

The planned enrollment was 250, but the number in the primary analysis is not reported. The primary population required at least one treatment dose and end-of-study response data. The record does not state how many participants failed to meet that definition or describe the reasons for missing outcome data. This prevents assessment of how the completer-set restriction may affect interpretation.

The study is observational, and allocation is not stated. The registry record does not report whether analyses adjusted for participant differences, how insulin resistance was defined or measured, or how subgroup analyses were conducted. It also does not provide treatment-duration counts or detailed treatment schedules beyond routine clinical practice and the 24- or 48-week durations referenced in the endpoint description.

Finally, the statistical plan is not reported in the registry record. Methods for addressing multiplicity, missing data, potential confounding, or interim analyses are not specified. These are limitations of the available record; they do not establish what analyses were or were not conducted outside the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Insulin Resistance on the Safety and Efficacy of Pegylated Interferon and Ribavirin Treatment in HCV (Study P05562) — NCT00705224.
• Registry record last updated 2015-07-01; status last verified 2015-06.
• Results first posted 2011-09-16.
• 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

NCT00705224 is a completed observational multicenter study of pegylated interferon and ribavirin treatment among treatment-naïve patients with chronic hepatitis C in Russia. Enrollment was 250. The study examined insulin resistance in relation to treatment safety and efficacy and aimed to assess its prevalence in different patient populations.

The primary endpoint was the percentage achieving sustained virological response 24 weeks after treatment ended. The registry defines the primary analysis population as participants who received at least one dose and had end-of-study response data. It also lists secondary outcomes involving genotype, baseline insulin resistance, end-of-treatment response, relapse, and early response.

The primary and secondary outcome results, primary analysis denominator, statistical analysis plan, and sample-size justification are not reported in the registry record. Safety entries include 2 participants affected by serious adverse events and 177 affected by other adverse events in the listed treatment group.