Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin for Treatment-Naïve Hemodialysis Patients With Chronic Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin for Treatment-Naïve Hemodialysis Patients With Chronic Hepatitis C (NCT00491244), a randomized phase 4 study. The primary outcome is Sustained Virologic Response (SVR)Rate.

2. Clinical Question

The clinical question concerns whether the recorded response counts differed between the two randomized groups. The registry identifies the primary outcome as the Sustained Virologic Response (SVR)Rate and reports participant counts. The posted arm results are 130 of 189 participants in the peginterferon-and-ribavirin group and 72 of 188 in the peginterferon group. The comparison therefore focuses on the proportion of participants with the recorded response, not on a time-to-event outcome or a change in a continuous measurement.

The comparison is relevant to this patient population because the registry background describes treatment questions particular to people receiving dialysis, including concerns about ribavirin and anemia. Those background statements establish the context of the study question; they do not establish the comparative safety or effectiveness of the assigned treatments. The interpretation below is limited to the posted outcomes and the design information in the registry record.

3. Trial Design

This was a randomized, parallel-group Phase 4 trial with no masking. The registry lists 377 enrolled participants and identifies National Taiwan University Hospital as the sponsor. The recorded study start is 2007-06, primary completion is 2013-09, and status is completed. The condition listed is chronic hepatitis C.

Participants were assigned to peginterferon alfa-2a plus ribavirin or peginterferon alfa-2a alone. The combination regimen is described as pegylated interferon alfa-2a 135 ug/week plus ribavirin 200 mg/day. The monotherapy regimen is described as pegylated interferon alfa-2a 135 ug/week. Both regimens had durations of 24 to 48 weeks according to genotype: 48 weeks for genotype 1 and 24 weeks for genotype 2. The registry record does not report how randomization was generated, whether allocation was concealed, or how adherence and treatment changes were handled.

The primary outcome population is described as all participants who received at least one dose of study medication. The posted primary results include 189 participants in the combination group and 188 in the monotherapy group, with response counts of 130 and 72, respectively. The registry also identifies adverse event-related withdrawal rate as a secondary outcome, but the posted outcome information summarized in the record does not give a numerical result for that measure.

Randomization supports a comparative design, while the absence of masking means participants and study personnel were not masked according to the registry. The record does not explain the practical implications of that design feature for outcome assessment or care. Details such as baseline characteristics, the original sample-size justification, interim analyses, and the trial’s complete statistical plan are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: All participants were analyzed if they received at least one dose of the study medication

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 Sustained Virologic Response (SVR)Rate, measured over 1.5 year.

Sustained virologic response is the primary endpoint. The registry records it as the number of participants with the response, with a timeframe of 1.5 year. The endpoint is therefore presented as a binary outcome at the participant level: each participant is counted as having or not having the recorded response. The registry’s primary outcome population includes participants who received at least one dose of study medication.

In general, a sustained virologic response endpoint is used in hepatitis C research to assess whether the virus remains suppressed after treatment, rather than simply whether a short-term change occurred during treatment. That general rationale explains why a durable response is clinically and scientifically informative. The registry record does not provide a more detailed operational definition of SVR, such as the exact virologic threshold or assessment schedule, so those particulars are not reported in the registry record.

The posted counts are 130 of 189 participants for peginterferon and ribavirin and 72 of 188 for peginterferon alone. Counts and denominators make the outcome interpretable as a comparison of response frequency across the randomized groups. They do not by themselves describe the timing of response, missing outcome handling, or the extent to which participants completed the assigned regimen. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Peginterferon: 38.3% (72/188) versus 68.8% (130/189) on control; risk difference -30.5 percentage points (95% CI -40.1 to -20.9), risk ratio 0.56 (0.45–0.68); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

For the primary outcome, the registry reports a participant count with the event in each arm. This is a binary outcome: participants contribute either a response event or no response event. The two groups can be compared using measures that describe relative frequency, such as a risk ratio, or absolute difference, such as a risk difference. The sponsor reports a risk ratio; the simple recalculation uses a risk difference. These measures answer related but distinct questions and have different null values.

What does the risk ratio express?

In general, a risk ratio compares the event frequency in one group with the event frequency in another. A value of 1 represents equal event frequencies under the ratio’s specified ordering; a value above 1 means the numerator group has the higher frequency, and a value below 1 means it has the lower frequency. The sponsor reports a risk ratio of 1.80 for the combination group, with a 95% confidence interval from 1.46 to 2.21. The confidence interval excludes 1, and the reported p-value is < 0.001. Interpretation depends on keeping the group ordering in view.

What does a risk difference express?

In general, a risk difference subtracts one group’s event frequency from the other’s. A value of zero represents equal event frequencies, while the sign indicates which group has the higher frequency given the subtraction order. The recalculation compares peginterferon alone against the combination group, so its negative direction corresponds to fewer recorded responses in the monotherapy group. This absolute-scale measure is not numerically interchangeable with the sponsor’s relative-scale risk ratio.

The recalculation is unadjusted and uses the posted arm-level counts. It does not account for covariates, stratification, or other possible features of the original analysis. The record does not report enough detail to determine whether the sponsor’s analysis used any such adjustment. No discrepancy is flagged between the posted results and the recalculation; the two presentations nevertheless use different effect measures and comparison order.

How should the p-value be read?

In general, a p-value describes how incompatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. It does not give the probability that the null is true, and it does not measure clinical importance. The sponsor reports p < 0.001, and the unadjusted recalculation also reports p < 0.001. These values indicate strong statistical evidence against equal response frequencies under their respective analyses, while the effect estimates and intervals convey magnitude and precision.

The sponsor identifies a Chi-squared method for the reported analysis. In general, a chi-squared test assesses whether observed categorical counts differ from what would be expected under a null hypothesis of no association or no group difference. Its use is consistent with a comparison of event and non-event counts across groups. The registry record does not describe the exact test implementation, any continuity correction, or any covariate adjustment, so those details are not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion arises when observed variation is greater than a statistical model expects. It can make model-based standard errors too small if the model does not account for the extra variability, leading to confidence intervals that are too narrow and p-values that are too small. This issue is particularly relevant for some count or clustered-data models. The posted primary endpoint is binary participant counts, and the sponsor reports a chi-squared analysis; the registry does not report an over-dispersion assessment or a model requiring such an adjustment. This general consideration should not be taken as evidence that over-dispersion occurred in this trial.

For precision, the sponsor reports a 95% confidence interval for the risk ratio. In general, a confidence interval is a range of effect values compatible with the data and analysis at the stated confidence level. It is not a guarantee that the true effect lies in that particular interval, nor does it capture all sources of uncertainty, such as bias from trial conduct or incomplete outcome reporting. Its width reflects statistical precision under the analysis assumptions.

The registry describes the primary analysis population as participants who received at least one dose. In general, an analysis restricted by treatment exposure can differ from an analysis of all randomized participants, particularly if participants who never receive treatment are excluded. The record does not report how many randomized participants, if any, were excluded under this rule, nor how missing outcome data were treated. It also does not report whether an intention-to-treat analysis was conducted. Those aspects of the analysis population and missing data handling cannot be inferred from the posted counts.

10. Confidence Intervals and Precision

The sponsor’s reported risk ratio is 1.80, with a 95% confidence interval from 1.46 to 2.21. In general, a confidence interval describes a range of effect sizes compatible with the data under the statistical model and its assumptions. Here, the interval lies above the risk-ratio null value of 1, matching the reported p-value of < 0.001. It indicates that the sponsor’s analysis estimates a higher response frequency in the combination group, while also showing uncertainty about the exact size of that relative difference.

A confidence interval communicates sampling uncertainty, not every form of uncertainty. It does not account for possible selection effects, outcome misclassification, incomplete follow-up, or limitations in generalizing beyond the enrolled population unless those issues are explicitly incorporated into the analysis. The registry record does not provide enough information to assess those sources of uncertainty fully.

The recalculated risk-difference estimate and its interval are based on the posted counts and are unadjusted. They use the reverse comparison order from the sponsor’s risk ratio: peginterferon alone relative to the combination group. The negative direction is consistent with the lower response count in the monotherapy group. The sponsor’s relative measure and the recalculated absolute measure answer different questions, so their numeric values cannot be directly compared as though they were on the same scale.

The posted counts, 130 of 189 and 72 of 188, also show that both groups contribute substantial outcome information. However, sample size alone does not establish that an estimate is precise enough for every decision. Precision should be judged from the effect estimate and its interval, together with concerns about the analysis population and outcome completeness. The registry record does not report the original design assumptions or detailed missing-data methods, which limits assessment of those issues.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on fractions of the observed effect, not the trial’s original design justification. These are participants per arm, not total events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each scenario uses the stated fraction of the observed effect as the effect to detect. The original trial’s own planning assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design that would have an 80% probability of detecting the specified effect under the planning assumptions, if that effect were the true one. The 90% power column gives the corresponding per-arm planning number for a 90% probability. These are prospective design quantities, not evidence about the probability that the completed trial detected an effect or the probability that its finding is true.

The planning scenarios include detecting 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The listed per-arm numbers increase as the effect to detect becomes smaller: for the 100% scenario, 41 participants per arm for 80% power and 55 for 90%; for the 75% scenario, 73 and 97; and for the 50% scenario, 160 and 213. In general, smaller effects are harder to distinguish from random variation, so more participants are needed to achieve the same planned power, assuming the other design conditions remain fixed.

These figures are planning illustrations, not observed power. They rely on the observed effect as their starting point, which can itself be uncertain, and they do not replace the trial’s unreported original sample-size rationale.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.688; treatment proportion p₁ = 0.383; average p̄ = 0.535.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7053 = 1.3824.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6716 = 0.5652.
4. n = (1.3824 + 0.5652)² / (-0.3049)² = 40.8, rounded up to 41 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.687830687830688                          # control proportion
p1 <- 0.382978723404255                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(491244)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 41 (80% power), 55 (90% power)
 75% of observed effect: n per arm = 73 (80% power), 97 (90% power)
 50% of observed effect: n per arm = 160 (80% power), 213 (90% power)
power.prop.test: 40.8 
Simulated power at n = 41 per arm: 0.821 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The sponsor’s own analysis reports a Chi-squared method and a risk ratio of 1.80, with a 95% confidence interval from 1.46 to 2.21 and p < 0.001. Its listed analysis group is the peginterferon-and-ribavirin arm. The risk ratio is a relative measure, and the reported value indicates a higher recorded response frequency in the combination group under the sponsor’s comparison.

The simple recalculation uses the posted counts and expresses the comparison as a risk difference, with peginterferon alone minus the combination group. That estimate has a negative direction, consistent with the lower response count in the monotherapy group. The recalculation is unadjusted and uses a different effect measure and comparison order; it should not be read as reproducing the sponsor’s risk ratio. Both analyses report p < 0.001, but the sponsor’s analysis is the trial’s own reported inferential result.

No discrepancy is flagged between the posted summary and the recalculation. The registry record does not report additional details about the sponsor’s test implementation, adjustment strategy, or analysis code, so those features should not be assumed.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary outcome as sustained virologic response and identifies adverse event-related withdrawal rate as a secondary outcome. It reports two outcome measures and two analyses. The record does not describe a multiplicity adjustment, a hierarchy among outcomes, or a prespecified strategy for controlling the chance of false-positive findings across multiple tests. These details are not reported in the registry record. The primary result should therefore be distinguished from additional outcomes rather than treated as though every analysis had a stated multiplicity plan.

The primary outcome population is described as participants who received at least one dose of study medication. This is an exposure-based analysis description; the registry does not state whether the analysis included every randomized participant. It does not report the number randomized who may not have received a dose or explain how such participants were handled. An intention-to-treat analysis is not reported in the registry record.

The arm-level denominators and response counts are posted, but the record does not describe how missing SVR assessments were treated, whether any outcomes were imputed, or how participants lost to follow-up were classified. It also does not report whether sensitivity analyses tested alternative assumptions about missing outcomes. These omissions matter because the interpretation of a binary endpoint can depend on how participants without an observed result are handled.

The registry does not report a detailed statistical analysis plan, protocol deviations, interim analyses, stopping rules, or a sample-size justification for the original trial. It also does not provide enough information to determine whether the posted analysis was prespecified or whether the analysis population changed over time. None of these features should be inferred from the numerical results alone. The posted analysis remains interpretable as reported, but its statistical context is incomplete.

Overall, the central limitation for assessing multiplicity and analysis populations is not evidence of a particular problem; it is that the registry record does not provide the necessary details. The absence of reporting should not be interpreted as proof that a method was or was not used.

15. 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: pneumonia (1.6%), postural dizziness (1.1%), cholangitis (0.5%), major depression (0.5%), peptic ulcer bleeding (0.5%).

The registry reports serious adverse events in 8 of 189 participants in the peginterferon-and-ribavirin group and 7 of 188 participants in the peginterferon group. Other adverse events are reported in 170 of 189 and 154 of 188 participants, respectively. These are descriptive counts with group denominators. They do not, by themselves, establish a difference in risk or a causal relation between a treatment and an event.

The serious adverse event terms listed include pneumonia (1.6%), postural dizziness (1.1%), cholangitis (0.5%), major depression (0.5%), peptic ulcer bleeding (0.5%), and Salmonella gastroenteritis (0.5%). The registry does not provide a statistical comparison for these terms in the posted information. It also does not report event-level exposure time or details needed to assess recurrent events, severity grading, or attribution to study treatment.

Deaths are not reported in the adverse-event summary. The listed serious-event counts should therefore be read as the reported participant counts, not as a complete account of all possible safety outcomes or as evidence that the groups had equivalent safety profiles.

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

The posted results show more recorded sustained virologic responses in the peginterferon-and-ribavirin group than in the peginterferon group: 130 of 189 compared with 72 of 188. The sponsor’s risk ratio is 1.80, with a 95% confidence interval from 1.46 to 2.21 and p < 0.001. The unadjusted recalculation, using the opposite group order for a risk difference, likewise has a direction corresponding to fewer recorded responses in the monotherapy group.

These findings describe the analyzed participants and the outcome as recorded in the registry. They do not prove that the same result would occur in every population or setting. The trial enrolled treatment-naïve hemodialysis patients with chronic hepatitis C, and the record does not provide enough information to judge how well the participants represent other patients or care contexts.

The results also do not settle the balance of response and adverse events. Serious adverse events are reported for 8 of 189 participants in the combination group and 7 of 188 in the monotherapy group, while other adverse events are listed for 170 of 189 and 154 of 188 participants. These are descriptive summaries without a posted comparative safety analysis. The registry record does not report detailed event timing, treatment attribution, or a complete analysis of withdrawals.

Statistical evidence against equal response frequencies is not the same as proof of a particular mechanism or a judgment about clinical importance. The risk ratio and confidence interval describe the comparative outcome under the sponsor’s analysis, while the design and analysis limitations affect how broadly the estimate can be interpreted. In particular, missing-data methods, analysis of all randomized participants, baseline characteristics, allocation procedures, and the original statistical plan are not reported in the registry record.

The appropriate conclusion is therefore bounded: the posted analysis records a higher SVR frequency in the combination group, and the sponsor reports a statistically clear relative difference. The registry information alone does not answer all questions about safety, durability beyond the stated timeframe, or applicability outside the studied population.

17. Why This Trial Matters Statistically

This trial addresses a statistical comparison in a population for whom the registry background describes uncertainty about interferon-based treatment and concerns about combining ribavirin with treatment in dialysis. From a methods perspective, the contrast is useful because the two randomized groups share peginterferon alfa-2a, while one group also receives ribavirin. The posted outcome therefore gives a direct comparison of the assigned regimens in the enrolled study population, subject to the limitations of the registry information.

The result also illustrates why effect measures should be read in context. The sponsor reports a relative measure, the risk ratio, whereas the simple recalculation expresses an absolute difference. Relative measures describe proportional contrast; absolute measures describe the difference in event frequency. The sign and direction of a risk difference depend on which group is subtracted from which, so group order must be stated explicitly.

The posted counts and confidence interval help distinguish evidence for a group difference from precision about its size. The sponsor’s interval excludes the risk-ratio null value, while the planning illustration shows that required sample sizes depend strongly on the effect assumed to be detectable. Those planning numbers are not evidence of achieved power, and the original design assumptions are not reported.

Finally, the record demonstrates the limits of registry-level interpretation. A clear primary result does not replace reporting on missing data, analysis populations, trial procedures, multiplicity, or safety comparisons. Statistical conclusions become more transparent when those elements accompany the effect estimate and outcome counts.

18. 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 provides the primary outcome counts and the sponsor’s risk-ratio analysis, but important design and analysis details are not reported. Randomization is stated, yet the method used to generate the sequence and whether allocation was concealed are not reported in the registry record. Masking is listed as none. Baseline characteristics and balance between groups are not included in the information, limiting assessment of the enrolled groups.

The outcome population is described as participants who received at least one dose. The record does not report how this relates to all randomized participants, whether any randomized participants were excluded, or how missing SVR assessments were handled. It also does not state whether an intention-to-treat analysis or sensitivity analyses were conducted. The operational definition and assessment schedule for SVR are not described beyond the 1.5 year timeframe.

The original sample-size justification, complete statistical analysis plan, interim analyses, stopping rules, and multiplicity approach are not reported in the registry record. The posted planning illustration is based on the observed effect and cannot establish what assumptions guided trial enrollment.

Safety information is limited to reported counts of serious and other adverse events and a list of serious event terms with percentages. The record does not provide a comparative statistical analysis, event timing, exposure-adjusted rates, or detailed treatment attribution. The secondary outcome of adverse event-related withdrawal rate is identified, but a numerical result is not reported in the posted information.

These limitations constrain assessment of precision, bias, generalizability, and the balance of outcomes. They do not establish that any particular bias or unreported analysis occurred; they indicate which questions cannot be resolved from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin for Treatment-Naïve Hemodialysis Patients With Chronic Hepatitis C — NCT00491244.
• Registry record last updated 2014-02-10; status last verified 2014-01.
• Results first posted 2013-12-13.
• 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.

22. Record Summary

NCT00491244 is a completed, randomized, parallel-group Phase 4 trial sponsored by National Taiwan University Hospital. It enrolled 377 treatment-naïve hemodialysis patients with chronic hepatitis C and compared peginterferon alfa-2a plus low-dose ribavirin with peginterferon alfa-2a alone. The trial had no masking.

The primary outcome was sustained virologic response at 1.5 year. The posted counts were 130 of 189 in the combination group and 72 of 188 in the monotherapy group. The sponsor reported a risk ratio of 1.80, with a 95% confidence interval from 1.46 to 2.21 and p < 0.001. Serious adverse events were reported for 8 of 189 and 7 of 188 participants, respectively.

The record does not report the original sample-size justification, detailed missing-data handling, or a complete statistical plan. The result is best understood as the posted comparative analysis for this trial population, with those reporting limitations in mind.