Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients (NCT00018031), a na phase 2 study. The primary outcome is Participants With Viral Decline at Day 3 & 28 With Predictors of Post Treatment Response.

2. Clinical Question

In practical terms, the study's statistical question was predictive rather than a randomized comparison of treatments. It examined viral kinetics during treatment in people coinfected with HIV and HCV and related those measurements to a later treatment-response outcome. The registry describes the primary measure as participants with post-treatment SVR, while the outcome description says that early viral decline and viral load were used to predict SVR. These are related but not identical pieces of information: the early measurements define the proposed predictor, and SVR is the later response of interest. The record does not provide enough outcome detail to assess how accurately the predictor classified response.

3. Trial Design

The registry identifies this as a phase 2, non-randomized, open-label, single-group study. Its stated aim was to assess HCV viral kinetics as predictors of clinical response among people with hepatitis C infection coinfected with HIV-1 and treated with peginterferon alfa-2b and ribavirin. The study is marked completed, with enrollment of 36. The record lists no randomized allocation and no masking.

The regimen described for the study was weekly injection of peginterferon alfa-2b with weight-based ribavirin (1-1.2g/day) for 48 weeks. The record's brief description says that potential participants were adults aged 21 years and older with chronic HCV infection and an HCV viral load greater than 2000 copies/mL. That description concerns eligibility; it does not establish the characteristics of every enrolled participant. The record does not report the number who started treatment, completed treatment, or were included in each analysis.

Because the design has a single group, it can describe outcomes among treated participants and explore whether viral measurements are associated with later response. It cannot provide a randomized estimate comparing this regimen with another treatment or with no treatment. Open-label conduct also means that masking was not part of the design, although the registry does not say how this affected particular outcome assessments.

The registry gives a start date of 2001-06 and a primary completion date of 2009-04. It does not report a detailed statistical analysis plan, a sample-size justification, planned interim analyses, or procedures for allocation. These details should not be inferred from the phase designation or the fact that the study has a reported enrollment. The registry record also does not identify any analysis results; its analysis count is listed as 0.

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: Open label study. The participants were only excluded if they did not meet eligibility criteria, such as pregnancy, availability to make frequent clinic visits and able to meet laboratory safety criteria as described in the clinical protocol.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants with Virologic decline at both Day 3 and absolute HCV VL at Week 28 were analyzed

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 Participants With Viral Decline at Day 3 & 28 With Predictors of Post Treatment Response, measured over Day 3 and Day 28.

The primary outcome is titled “Participants With Viral Decline at Day 3 & 28 With Predictors of Post Treatment Response.” The unit is participants with post-treatment SVR, and the measure is a count. The description says that HCV viral kinetics were used to predict sustained virologic response in people coinfected with HIV and HCV. It defines the predictor using a viral decline greater than 1.0 log at day 3 together with an HCV viral load less than 5.0 log IU/ml at day 28.

SVR is a later response outcome, while the day 3 and day 28 viral measurements are early or on-treatment markers intended to predict it. In general, a predictor is useful only to the extent that it distinguishes people who later do and do not experience the outcome. Reporting the number meeting a predictor definition alone would not establish its predictive accuracy; that assessment also needs outcome information and an analysis linking the marker to the later response.

The record does not report the primary endpoint count, an estimate of SVR, or a measure of predictive performance. It also uses both “Day 28” and “Week 28” in describing the viral-load timing: the outcome title and description refer to Day 28, while the population description refers to Week 28. The registry record does not resolve that wording difference. No additional endpoint calculation or interpretation of predictive accuracy is possible from the posted result information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation starts with the distinction between the study design, the outcome definition, and the results actually reported. The registry identifies a single-group study and gives a primary outcome definition, but lists no analyses and reports no numerical primary outcome result. The outcome definition can be explained, but it cannot be treated as an observed finding. No inferential test, effect estimate, or uncertainty interval for the primary outcome is reported in the registry record.

What does a single-group design estimate?

In general, a single-group study can describe outcomes observed in the enrolled and analyzed participants. It can also examine associations between measurements, such as early viral changes and a later response. Without a concurrent comparator, it does not provide a randomized contrast between treatment strategies. A change observed during treatment may be clinically or scientifically relevant, but a before-and-after or within-group description does not isolate the effect of treatment from other explanations.

Here, the registry records a single group receiving peginterferon alfa-2b and ribavirin. It does not identify a randomized control arm. Accordingly, a comparative effect against another treatment cannot be estimated from the design description. This limitation remains even if a numerical outcome were available: an outcome count in the treated group would describe that group, not establish what a control group would have experienced.

How should a binary outcome be read?

The primary outcome is classified as binary and its unit is participants with post-treatment SVR. In general, a binary outcome records whether each participant meets a defined condition or does not. A count is a tally, whereas a proportion or risk relates that count to an eligible denominator. Interpreting a count requires knowing which participants were assessed and what rule determined inclusion in the analysis. The registry does not report the primary count or its analysis denominator, so a response proportion cannot be read from the record.

The stated viral criteria are a decline greater than 1.0 log at day 3 and a viral load less than 5.0 log IU/ml at day 28. The record describes those criteria as being used to predict SVR. In general, predictive performance requires relating the predictor classification to the later outcome. A complete assessment might report how often the predictor and outcome agreed, along with measures of uncertainty, but no such performance results are reported. The record's wording also varies between Day 28 and Week 28 for the viral-load timing, and does not clarify the discrepancy.

What do estimates and confidence intervals convey?

In general, an estimate summarizes the observed data for a target quantity, such as a response proportion or a difference between groups. A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies in the interval, and its interpretation depends on the method and study design. For this trial, the primary estimate and any confidence interval are not reported in the registry record. Statistical precision therefore cannot be evaluated for the main endpoint.

A p-value, when reported, addresses how compatible the data are with a specified null model under stated assumptions. It does not measure the size or clinical importance of an effect, and it does not replace an estimate with an interval. The registry record lists no analyses, so it does not report a primary p-value or an inferential model to interpret. No statistical test or adjustment should be inferred from the outcome title alone.

Why can over-dispersion matter?

In general, over-dispersion occurs when count or binary data vary more than an assumed statistical model expects. If a model ignores that extra variability, its standard errors may be too small and its uncertainty intervals or tests may be misleading. Methods that account for over-dispersion can be appropriate in some settings, but selecting one requires details about the data structure and analysis objective. The registry does not report a model, dispersion estimate, or analysis method for this outcome, so there is no basis to say whether over-dispersion was assessed or relevant to the sponsor's analysis.

How should planning illustrations be interpreted?

In general, sample-size calculations are planning tools: they describe the amount of information a proposed design might need under specified assumptions. They are not observed results and are not a measure of the study's observed power. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of an observed effect. The notes distinguish illustrations for time-to-event outcomes from those for other outcomes.

Those assumptions do not match the registry's description of a single-group study as a randomized two-arm comparison. Moreover, no numerical observed primary effect is reported, so a planning illustration based on a fraction of that effect cannot be checked against the primary endpoint in the registry record. The illustrations should be understood as conditional planning scenarios, not as a reconstruction of the trial's original design or evidence of achieved power. The record does not report the study's own sample-size justification or its statistical plan.

These general concepts clarify what information would be needed to assess the analysis, but they do not fill gaps in the record. The participant-level analysis population, missing outcome handling, model specification, covariate adjustment, multiplicity procedure, and sensitivity analyses are not reported in the registry record. Without those details and the outcome results, the primary analysis cannot be independently evaluated from this registry entry.

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("Peginterferon Alfa-2b, Ribavirin")
n      <- c(23)
events <- c(8)
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  Peginterferon Alfa-2b, Ribavirin  23  8  34.8  16.4  57.3  18.8  55.1  18.8  55.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and zero analyses. It does not report a statistical analysis plan, a testing hierarchy, or an adjustment for multiple comparisons. Therefore, it is not possible to determine whether the study assessed additional outcomes or predictors outside the registry entry, how any tests were prioritized, or whether multiplicity was addressed. In general, testing multiple hypotheses can increase the chance of finding an apparently notable result by chance; prespecified hypotheses and transparent reporting help readers understand that risk. No specific multiplicity procedure should be attributed to this trial.

Missing-data handling is also not reported in the registry record. The outcome depends on viral measurements at day 3 and day 28 and a post-treatment response, but the record does not say how many participants had each measurement, how missing measurements were handled, or whether all enrolled participants were included in the endpoint analysis. Enrollment of 36 is not necessarily the analysis denominator. The record does not report treatment completion, withdrawals, exclusions, or reasons for missing data.

The analysis population is not defined beyond the outcome description's reference to participants with virologic decline and absolute HCV viral load. The record does not clarify whether that phrase describes eligibility for the analysis, a subset defined by observed measurements, or another population. It also does not report an intention-to-treat population, a per-protocol population, or sensitivity analyses. The wording refers to viral load at both Day 28 and Week 28 in different places, with no clarification of the intended timing.

These omissions limit assessment of selection and attrition. In general, an analysis restricted to participants with complete measurements can differ from one that includes all participants, particularly if missingness is related to response or tolerability. The record does not provide enough information to judge whether that concern arose or how it was addressed.

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: carcinoma (2.8%), vision changes (2.8%), unusual affect or behavior (2.8%).

The registry lists serious adverse events for a group titled “Peg-interefron Alfa 2b, Ribavirin.” It records 36 at risk and 3 affected for serious adverse events. For other adverse events, it records 36 at risk and 20 affected. These are counts in the registry record, not comparative estimates against an untreated or randomized control group. The record does not explain the event-collection period or provide a causal assessment for each event.

The listed serious-event terms are Carcinoma, Vision Changes, and Unusual affect or behavior, each reported as 2.8%. These percentages should be read as registry-listed term frequencies, not as measures of treatment effect or as proof that treatment caused the events. The record does not provide event-level timing, severity details beyond the serious-event classification, or the number of events within each term beyond the listed percentages.

The deaths field is null. Deaths are therefore not reported in the registry record; null should not be interpreted as a reported zero. More generally, safety counts describe what the registry captured and do not establish comparative risk in a single-group study. The record does not report a control group for safety comparisons.

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

The record describes a completed phase 2 study intended to examine whether HCV viral kinetics predict post-treatment SVR among people coinfected with HIV and HCV who received peginterferon alfa-2b and ribavirin. It defines a proposed predictor using a viral decline greater than 1.0 log at day 3 together with a viral load less than 5.0 log IU/ml at day 28. This information explains the research question and outcome definition, but it is not itself a result.

The registry record does not report the number of participants who met the primary outcome, the SVR result, or an estimate of how well the viral criteria predicted response. It therefore does not support a conclusion about the frequency of response or the accuracy of the proposed predictor. Nor does it report a confidence interval or other measure of uncertainty for the primary outcome. The available record cannot show whether the observed data were consistent with a strong, weak, or absent predictive relationship.

The single-group, non-randomized design means that the study is not a controlled comparison of treatment strategies. Even if outcomes had been reported, the treatment group's experience alone would not establish a causal difference relative to another regimen or no treatment. The posted safety counts likewise are not comparative safety estimates. They describe events in the recorded group and do not establish that treatment caused them.

The registry entry also leaves important interpretive details unreported, including the analyzed population, missing-data handling, analysis model, multiplicity procedures, and sample-size justification. Its outcome wording differs on whether the viral-load measurement is at Day 28 or Week 28. These issues make it difficult to reconstruct the intended analysis or assess its robustness. A reader should distinguish what is registered—the study aim, design, regimen, and endpoint definition—from what is absent: numerical primary results and their statistical uncertainty.

In short, the record documents a study designed to investigate a predictive question, but does not supply results that answer it. This is a limitation of the information reported in the registry record, not evidence for or against the proposed relationship.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated scientific question and a reported statistical result are different things. The registry identifies viral kinetics as potential predictors of post-treatment SVR and gives a threshold-based description of the proposed marker. That helps define what investigators intended to study. Without the observed endpoint result and an analysis linking the marker to later response, however, the predictive question remains unanswered in the registry record.

It also highlights the distinction between prediction and treatment comparison. A single-group study can investigate whether measurements within a treated group are associated with later outcomes. It does not provide a randomized contrast that estimates how outcomes would differ under another treatment strategy. Those are separate statistical aims and require different design and interpretation.

The record's outcome wording emphasizes a combined early-viral criterion, while the primary measure is described in terms of participants with post-treatment SVR. This makes transparent reporting of the predictor definition, endpoint, analysis population, and result especially important. The Day 28 versus Week 28 wording difference further shows why precise timepoint descriptions matter when interpreting a proposed predictor.

Finally, enrollment and safety counts cannot stand in for efficacy estimates, predictive accuracy, or precision. With no primary numerical result, no reported interval, and no analysis listed, readers cannot assess the magnitude or uncertainty of the main finding. The entry is statistically informative about the intended design and question, but incomplete as a report of the answer.

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 principal limitation for interpreting this particular registry entry is that no numerical primary outcome result or analysis is reported. The endpoint definition identifies early HCV viral criteria and post-treatment SVR, but the record does not state how many participants met the endpoint, how many experienced SVR, or how predictive performance was assessed. Statistical uncertainty for the primary result is also not reported.

The study is non-randomized and single-group, with no like-for-like comparator. This limits any causal or comparative interpretation of outcomes. The record does not report how many enrolled participants started or completed the regimen or contributed data at each outcome timepoint. It also does not specify missing-data procedures, analysis populations, model choice, adjustment variables, or sensitivity analyses.

The primary outcome description contains a timing inconsistency: the title and description refer to Day 28, while the population description refers to Week 28. The record does not clarify which timepoint is intended. The endpoint title refers to viral decline at Day 3 and 28, whereas the description specifies a Day 3 decline combined with a Day 28 viral-load threshold; the relationship between those phrasings is not further explained.

The statistical analysis plan, sample-size justification, interim-analysis plans, and multiplicity handling are not reported in the registry record. The stated planning illustrations rely on a two-arm allocation assumption, whereas the registered study is single-group; they are not a substitute for the study's own design rationale or for its missing results. Finally, the safety record does not report deaths as a numerical value and does not provide event-level timing or causal attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients — NCT00018031.
• Registry record last updated 2014-10-01; status last verified 2014-09.
• Results first posted 2014-10-01.
• 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

The registry describes NCT00018031, “Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients,” as a completed phase 2, open-label, non-randomized, single-group study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). Enrollment is recorded as 36. The study examined viral kinetics as predictors of clinical response in people with HCV and HIV-1 coinfection.

The regimen was weekly peginterferon alfa-2b injection with weight-based ribavirin (1-1.2g/day) for 48 weeks. The primary outcome concerns participants with post-treatment SVR and describes a predictor using a viral decline greater than 1.0 log at day 3 and HCV viral load less than 5.0 log IU/ml at day 28. The registry record does not report a numerical primary outcome result or analysis.

Safety listings record 3 affected among 36 at risk for serious adverse events and 20 affected among 36 at risk for other adverse events. Deaths are not reported in the registry record. The record also does not report the statistical plan, analyzed population, or missing-data procedures.