Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085) (NCT00759109), a randomized phase 3 study. The primary outcome is Number of Participants With the Development of Hepatocellular Carcinoma (HCC).

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 3 randomized trial with a parallel-group model and no masking. The recorded enrollment is 150. The primary outcome is reported for an intention-to-treat population, with 74 participants in the PegIntron arm and 72 in the observation control arm. These outcome denominators should not be treated as a reconciliation of the enrollment figure; the registry record does not explain the difference.

Participants assigned to Arm A received peginterferon alfa-2b, 50 μg weekly by subcutaneous injection, for 3 years. Participants assigned to Arm B were observed and received no treatment. The stated study period for the primary outcome covered 3 years of treatment and 2 years of follow-up. The brief summary describes the target population as adults with cirrhosis and initial signs of portal hypertension, a high proliferation rate, and no response to previous interferon-based treatment. Details of allocation concealment, recruitment procedures, and the implementation of randomization are not reported in the registry record.

The trial is listed as completed. Its recorded start is 2002-03 and its primary completion is 2009-11. These registry dates do not, by themselves, describe the timing or completeness of participant follow-up. The record lists six outcome measures, including the primary HCC outcome and secondary outcomes involving hepatic decompensation, survival, virological response, and PCNA-LI. Results are posted for some secondary measures, but the registry record does not report analyses for all listed outcomes.

Because masking is listed as none, participants and study personnel were not masked according to the registry description. That is relevant when interpreting outcomes and study conduct, although the primary endpoint used specified clinical and imaging criteria. The record does not report whether outcome assessors were masked or provide further detail about endpoint adjudication.

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: The Intent-to-Treat (ITT) population included all randomized participants who took at least one dose of medication, and presented at least one further efficacy evaluation. No efficacy assessment post-baseline was obtained for 4 participants in the control group, therefore the ITT population included 146 (74 PegIntron + 72 Control) participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population

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 Number of Participants With the Development of Hepatocellular Carcinoma (HCC), measured over During 3 years of treatment and 2 years of follow-up.

The primary endpoint was the number of participants who developed hepatocellular carcinoma during 3 years of treatment and 2 years of follow-up. The registry states that liver ultrasound examinations for focal lesions and blood AFP testing were performed every 6 months during the study. HCC was determined by either a focal lesion on ultrasound with metastases confirmed by fine needle biopsy, or a focal lesion on ultrasound together with AFP above 400 ng/mL.

This endpoint addresses the trial's stated prevention question by recording whether participants met the specified criteria for HCC. It is a binary outcome at the participant level: each participant either met the endpoint definition during the stated period or did not. Counting participants with the event allows a direct comparison of event risks between randomized groups. It does not, on its own, describe the timing of each diagnosis or the severity and course of disease after diagnosis.

The posted outcome counts were 15 among 74 participants in the PegIntron arm and 11 among 72 in the control arm. The estimated risk difference, defined in the comparison as intervention minus control, was 0.050. Its confidence interval extends from -0.074 to 0.174. The interval therefore includes values consistent with either direction of difference. The registry record does not provide participant-level data, a detailed account of adjudication, or additional information about endpoint completeness.

7. Results Posted in the Registry

• Arm A - PegIntron: 20.3% (15/74) versus 15.3% (11/72) on control; risk difference 5.0 percentage points (95% CI -7.4 to 17.4), risk ratio 1.33 (0.65–2.69); unadjusted two-proportion z-test p = 0.431.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Development of Hepatic Decompensation

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Arm A - PegIntron: 5.4% (4/74) versus 12.5% (9/72) on control; risk difference -7.1 percentage points (95% CI -16.3 to 2.1), risk ratio 0.43 (0.14–1.34); unadjusted two-proportion z-test p = 0.132.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm A - PegIntron and the control. The interval gives the range of effects that remain compatible with the data.

Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm A - PegIntron: mean -2.00 versus -0.90 on control; difference -1.10 (95% CI -2.48 to 0.28), standardized effect d = -0.38; z-test p = 0.119.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm A - PegIntron and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add context but do not resolve the uncertainty in the primary HCC comparison. The posted measures cover hepatic decompensation and change in PCNA-LI, alongside listed outcomes for survival and virological response. The directions of the available secondary estimates are not uniform in their implications, and their confidence intervals include the respective null values. They therefore do not form a consistent, precise body of evidence that materially settles the primary question.

Secondary outcomes can help describe whether a treatment strategy may be associated with other clinical or biological changes, but they answer different questions from the primary endpoint. A change in a proliferation index is not the same outcome as developing HCC, and hepatic decompensation is not a substitute for the HCC endpoint. Similarity or difference in direction across outcomes cannot establish the causal pathway or explain the primary result.

The registry lists survival time and virological response among the secondary outcomes, but results for those measures are not reported in the registry record. The record identifies four secondary outcomes as posted, while the outcome list includes additional measures. The absence of posted results is not evidence of no effect or no events; it means those results cannot be evaluated from the registry record.

Unadjusted secondary comparisons carry less weight because multiple outcomes create more opportunities for chance findings, particularly when no multiplicity strategy is reported. The registry record does not report an adjustment for multiple testing or a hierarchy for interpreting secondary endpoints. Secondary findings should therefore be treated as supportive or exploratory, with attention to their uncertainty, rather than as independent confirmation of the primary result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Development of Hepatic Decompensation
• Survival Time of Participants
• Number of Patients With a Virological Response Rate
• Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: the registry counts participants who developed HCC during the stated period. A binary outcome can be described as an event count and a risk, where risk is the proportion of a group experiencing the event. The comparison reports a risk difference, a risk ratio, and an odds ratio. Each expresses the contrast between groups on a different scale. A risk difference is an absolute contrast; a risk ratio compares risks multiplicatively; an odds ratio compares odds. They are related but not interchangeable, and each is most informative when read with its uncertainty interval.

What does the risk difference represent?

The estimated risk difference is 0.050, with the PegIntron arm compared against control. The point estimate is the observed contrast on the risk-difference scale. A value of zero represents no difference on this scale. The confidence interval, from -0.074 to 0.174, crosses that null value, so the posted estimate does not rule out a difference in either direction. The estimate is not a statement that every participant's outcome changed by that amount; it is a group-level contrast.

How should the p-value be read?

The unadjusted p-value is 0.431. In general, a p-value assesses how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A large p-value does not demonstrate equivalence. Equivalence or non-inferiority requires a prespecified margin and an analysis designed for that question; such a margin is not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimate. Its endpoints reflect the data and the assumptions of the calculation, and a wider interval signals less precision. A confidence interval is not a guarantee that the true effect lies within its endpoints. For this primary outcome, the interval includes the null value and allows estimates on either side, so it does not establish a precise direction of difference. The interval should be considered alongside the event counts and the point estimate rather than in isolation.

Why are several effect measures reported?

Risk differences are often useful for understanding absolute contrasts, while risk ratios and odds ratios describe relative contrasts. The posted risk ratio is 1.327, with a confidence interval from 0.654 to 2.691. The posted odds ratio is 1.41, with a confidence interval from 0.599 to 3.32. The intervals for both relative measures include their null value of one. These estimates are alternative summaries of the same primary comparison, not separate independent findings. When the event is not rare, odds ratios and risk ratios can differ in interpretation, so the measure and its scale should be named explicitly.

What does intention-to-treat mean in this record?

In general, intention-to-treat analysis compares participants according to their randomized assignment, regardless of treatment received after assignment. It preserves the randomized comparison and estimates the effect of assignment to the trial strategies. The primary outcome is identified as using the ITT population. The registry record does not describe in detail how deviations, incomplete observations, or missing outcomes were handled, so the exact implementation cannot be assessed from the posted information.

What is not reported about the statistical plan?

The registry record does not report a primary analysis method beyond the posted comparison statistics, a multiplicity adjustment, an interim-analysis plan, or the original sample-size justification. It lists no reported analyses for the secondary outcomes. Randomization and a parallel-group design are recorded, but details such as allocation concealment and endpoint-assessor masking are not reported. Those omissions limit the ability to evaluate whether the posted estimates follow a prespecified analysis plan or how sensitive they may be to analytic choices.

The planning illustrations use the observed effect as a starting point and list assumed fractions of that effect. They are not reconstructions of the original trial design. Their assumptions are stated separately with the planning estimates: two-sided significance level 0.05, equal allocation between arms, and a normal approximation. General statistical concepts such as confidence intervals and p-values describe how results are interpreted; they do not fill gaps in the registry's account of its own protocol or analysis.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.050, and its 95% confidence interval is -0.074 to 0.174. The interval includes zero, so the data are compatible with no difference as well as with estimates in either direction. It is not narrow enough to identify a precise effect. The positive point estimate alone should not be used to claim that HCC risk was higher in the PegIntron group, because the uncertainty interval also allows a negative difference.

The relative estimates are likewise uncertain. The risk ratio is 1.327, with a confidence interval from 0.654 to 2.691. The odds ratio is 1.41, with a confidence interval from 0.599 to 3.32. Both intervals include one, the null value for those measures. The interval widths indicate that the data permit a range of materially different relative effects; the posted estimates do not sharply distinguish among them.

A confidence interval is a measure of statistical uncertainty under the analysis assumptions, not a guarantee about the true effect and not a range containing a stated percentage of individual outcomes. Precision is affected by the amount of information available, including the number of observed events and the variability inherent in the outcome. The posted group sizes and event counts provide the basis for the primary comparison, but the registry record does not give a fuller account of missing outcome data or the interval calculation method.

For the other posted outcomes, confidence intervals also cross their respective null values: the hepatic decompensation risk-difference interval is -0.163 to 0.021, and the PCNA-LI mean-difference interval is -2.484 to 0.283. These secondary estimates also remain uncertain. They should be interpreted as exploratory descriptions rather than as precise confirmation of a treatment effect.

12. 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 planning estimates are participants per arm, not total event counts. They are illustrations based on the observed effect, not the trial's original enrollment target or a reconstruction of its design. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The registry record does not report the trial's own original sample-size assumptions or justification.

For the primary HCC risk difference, planning for 100% of the observed effect gives 920 participants per arm for 80% power and 1,231 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,590 participants per arm for 80% power and 2,128 participants per arm for 90% power. Planning for 50% of the observed effect gives 3,475 participants per arm for 80% power and 4,651 participants per arm for 90% power.

In plain terms, power is the chance that a study would meet its chosen statistical criterion if the assumed effect were the true effect and the planning assumptions held. The 80% and 90% columns describe different target probabilities of detecting the assumed effect under those conditions. The smaller the effect targeted, the more participants the illustration requires. This is not observed power: it is a prospective planning calculation, not a measure of what the completed trial achieved.

These estimates use the observed effect as their reference and should not be mistaken for evidence that the observed effect is the true or clinically important effect. Because the primary estimate is imprecise, different choices about the effect worth detecting could lead to different planning needs. The illustrations are statistical planning aids, not recommendations about a future study design.

13. 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 = 0.153; treatment proportion p₁ = 0.203; average p̄ = 0.178.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5406 = 1.0596.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5395 = 0.4540.
4. n = (1.0596 + 0.4540)² / (0.0499)² = 919.3, rounded up to 920 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 <- 0.152777777777778                          # control proportion
p1 <- 0.202702702702703                          # 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(759109)
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 = 920 (80% power), 1,231 (90% power)
 75% of observed effect: n per arm = 1,590 (80% power), 2,128 (90% power)
 50% of observed effect: n per arm = 3,475 (80% power), 4,651 (90% power)
power.prop.test: 919.3 
Simulated power at n = 920 per arm: 0.801 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record specifies the primary HCC outcome and identifies the analysis population as ITT. It does not report a complete statistical analysis plan, an adjustment for testing multiple outcomes, an order of priority among secondary outcomes, or an interim-analysis plan. The number of listed outcomes makes the absence of a reported multiplicity strategy relevant: when many hypotheses are examined, chance findings become more likely unless the analysis accounts for that process.

The record lists secondary outcomes for hepatic decompensation, survival time, virological response, and PCNA-LI. It does not report analyses for the secondary outcomes in its analysis listing. Some secondary endpoint results are posted, but results for survival time and virological response are not reported in the registry record. No further explanation for unreported results is available, and no conclusion about why they are absent is warranted.

The primary endpoint is identified as assessed in the ITT population, but the registry record does not describe missing-data methods, handling of participants without complete follow-up, or the number of missing endpoint assessments. It also does not provide a detailed flow of participants through follow-up. Consequently, the effect of incomplete outcome ascertainment cannot be evaluated from the posted information.

The study is recorded as randomized and unmasked, but details of allocation concealment and any masking of outcome assessors are not reported in the registry record. The primary endpoint uses defined ultrasound, biopsy, and AFP criteria, yet the record does not describe independent adjudication or procedures for resolving uncertain cases. These reporting gaps do not show that the trial methods were inadequate; they limit what can be verified from the registry.

The original sample-size justification, stopping rules, and handling of protocol deviations are also not reported in the registry record. The planning illustrations available with the posted results are based on the observed effect and specified planning assumptions, not evidence of the original design. Keeping these distinctions clear prevents retrospective planning calculations from being mistaken for prespecified analysis decisions.

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: hepatic neoplasm malignant (20.3%), cerebral haemorrhage (5.4%), ascites (2.7%), hepatic failure (2.7%), epilepsy (2.7%).

The registry reports serious adverse events for an at-risk group of 74 in the PegIntron arm and 76 in the control arm. Serious events affected 36 participants in the PegIntron arm and 30 in the control arm. Other adverse events affected 55 and 36 participants, respectively. These are reported counts and at-risk denominators; they should not be confused with the primary endpoint denominators or treated as a matched efficacy comparison.

The listed serious-event terms include HEPATIC NEOPLASM MALIGNANT at 20.3%, CEREBRAL HAEMORRHAGE at 5.4%, ASCITES at 2.7%, HEPATIC FAILURE at 2.7%, EPILEPSY at 2.7%, and THORACIC VERTEBRAL FRACTURE at 2.6%. The registry record does not give enough detail in these summaries to determine event timing, recurrence, severity beyond the serious-event classification, or whether each event was judged related to treatment. Death totals are not reported in the registry record.

These figures describe events recorded in the trial; they do not establish that treatment caused an event or that the groups had different underlying safety risks. A fuller safety comparison would require consistent definitions, follow-up information, and the relevant analysis details.

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

The posted primary result is an uncertain comparison of HCC event counts between assignment to peginterferon alfa-2b and assignment to observation. The estimated risk difference is 0.050, with a 95% confidence interval from -0.074 to 0.174 and an unadjusted p-value of 0.431. The point estimate is positive, but the interval includes zero and estimates on either side. The result does not establish a clear difference between the groups.

That conclusion is not the same as proving that the strategies are equivalent, or proving that there is no effect. The confidence interval remains compatible with a range of possible effects, and the registry record does not report an equivalence margin or a non-inferiority analysis. The result also does not establish that peginterferon alfa-2b increases HCC risk merely because the point estimate is positive. Uncertainty in the estimate matters as much as its direction.

The finding applies to the randomized comparison described in the registry: adults with hepatitis C-related cirrhosis, initial signs of portal hypertension, a high proliferation rate, and previous non-response to interferon-based therapy. The regimen was 50 μg weekly for 3 years, with 2 years of follow-up, and the comparator was observation without treatment. It should not be extended automatically to other populations, treatment regimens, or follow-up periods.

The endpoint records whether participants met the registry's HCC definition over the stated period. It does not explain the biological process leading to HCC, establish how quickly events occurred, or describe outcomes after diagnosis. Nor do the secondary outcomes, with their own uncertainties and incomplete reporting, turn the primary result into a definitive conclusion.

The record's omissions also matter. Details about missing assessments, endpoint adjudication, multiplicity, and the original sample-size rationale are not reported in the registry record. These limitations affect how completely the trial can be evaluated from the posted information. The appropriate reading is therefore descriptive and cautious: the reported data yield an imprecise estimate, not a definitive claim that the treatment works or does not work.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison and a clear endpoint definition are not enough by themselves to produce a decisive answer. The design compares assignment to a specified treatment strategy with observation, and the primary outcome has operational criteria involving ultrasound, biopsy, and AFP. Yet the primary estimate remains imprecise, with a confidence interval spanning zero and both directions of effect. Interpreting the point estimate without its interval would overstate what the data establish.

It also demonstrates the value of distinguishing event counts from comparative evidence. Counts describe what was observed in each group; a treatment-effect estimate and its uncertainty address how those observations compare. The reported risk difference, risk ratio, odds ratio, and p-value are different summaries of the same primary outcome, not independent confirmations. Their intervals show why a single apparent direction should not be treated as conclusive.

The record is also a useful example of how registry reporting shapes statistical interpretation. It names the ITT population and provides posted primary results, but does not report the original sample-size justification, missing-data procedures, multiplicity strategy, or a complete analysis plan. Those details influence the strength and reproducibility of an interpretation. Their absence is a limitation of the record, not proof of a flaw in trial conduct.

Finally, planning illustrations based on an observed effect are not substitutes for the assumptions that would have informed the original design. Reading those illustrations separately from the completed-trial results helps avoid confusing prospective planning with retrospective evidence. Together, these points make the trial useful for understanding how randomized design, endpoint definition, effect measures, uncertainty, and registry completeness each contribute to a statistical assessment.

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 primary estimate is imprecise: its confidence interval includes zero and extends to both negative and positive values. The trial result therefore does not identify a clear direction of difference. The posted event counts and outcome denominators are limited, and the registry does not explain why the recorded enrollment differs from the primary endpoint denominators.

The registry record does not report details of missing endpoint assessments, participant flow through follow-up, or how incomplete observations were handled. Although the primary endpoint is identified as ITT, the analysis implementation cannot be fully assessed without those details. The record also does not describe endpoint adjudication, assessor masking, or how uncertain ultrasound, biopsy, or AFP findings were resolved.

Masking is listed as none. This may be relevant to study conduct and outcome ascertainment, though the record does not state whether outcome assessors were masked. Allocation concealment and other randomization procedures are not reported in the registry record. These are reporting limitations, not evidence that the procedures were absent.

Secondary findings do not provide a clear, complete corroboration of the primary outcome. The registry does not report multiplicity handling, a hierarchy among secondary endpoints, or analyses for all listed outcomes. Survival and virological response results are not reported in the registry record. The serious adverse-event summary also lacks detail about event timing and treatment attribution, and death totals are not reported in the registry record.

The original sample-size rationale, interim-analysis plans, and full statistical plan are not reported in the registry record. The planning illustrations based on observed effects cannot fill those gaps. Finally, the results concern the specified population, regimen, comparator, and follow-up period; the record does not establish how well they generalize beyond those circumstances.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085) — NCT00759109.
• Registry record last updated 2017-04-07; status last verified 2017-03.
• Results first posted 2011-04-18.
• 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

NCT00759109 is recorded as a completed, randomized phase 3 parallel-group trial with no masking. It compared weekly peginterferon alfa-2b, 50 μg subcutaneously for 3 years, with observation and no treatment in adults with hepatitis C-related cirrhosis and the stated prior treatment non-response and high proliferation characteristics. The planned outcome period covered 3 years of treatment and 2 years of follow-up.

The primary endpoint was participants developing HCC, assessed in the ITT population using ultrasound and AFP criteria, with biopsy confirmation for one specified route to endpoint classification. The posted comparison gives a risk difference of 0.050, a 95% confidence interval from -0.074 to 0.174, and an unadjusted p-value of 0.431. The interval is compatible with effects in either direction, so the result is not precise enough to establish a clear group difference.

The record lists secondary clinical and biological outcomes, but not all have posted results. Important details concerning missing data, multiplicity, the original sample-size rationale, and the full statistical plan are not reported in the registry record.