POTENTE Study: A Study of Early Virological Response in Naive Patients With Chronic Hepatitis C, Genotype 2 or 3, Treated With PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Copegus (Ribavirin).: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for POTENTE Study: A Study of Early Virological Response in Naive Patients With Chronic Hepatitis C, Genotype 2 or 3, Treated With PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Copegus (Ribavirin). (NCT00700401), a registered phase not stated study. The primary outcome is Percentage of Participants With Sustained Virological Response at Week 48.

2. Clinical Question

The study’s stated focus was the predictive value of a virological response at Week 4 for sustained virological response. Participants with a Week 4 response were to continue treatment for 24 weeks and then have a 24 week treatment-free follow-up. The description says that Week 4 non-responders would enter a separate protocol for further treatment. This was an observational study, not a randomized comparison: the registry record does not describe allocation to alternative treatment arms.

The primary endpoint is a proportion within the treated study population. It describes how many participants met the specified virological criterion, rather than the difference in response between treatments. The registry record identifies 262 enrolled participants, while the study description gives a target sample size of 100 individuals. These figures describe enrollment and the stated target; they do not establish how many participants had an evaluable Week 48 result. The numerical primary result is not reported in the registry record, so the endpoint cannot be quantified from the posted information.

3. Trial Design

POTENTE is described as a prospective, observational study of treatment-naïve participants with chronic hepatitis C, genotype 2 or 3. Its status is COMPLETED, and the registry record gives a start of 2008-11 and primary completion of 2010-11. Enrollment was 262. The study description states that the target sample size was 100 individuals; the reason enrollment differed from that target is not reported in the registry record.

The intervention was a combination of peginterferon alfa-2a and ribavirin. The described regimen was PEGASYS 180 micrograms/week sc plus Copegus 800mg/day po. Participants with a virological response at Week 4 were described as continuing treatment for 24 weeks, followed by a 24 week treatment-free follow-up. Week 4 non-responders were described as entering a separate protocol, MV21371, for further treatment. This account describes the planned study pathway; participant-level completion of each stage is not reported in the registry record.

The design is single arm. There is no concurrent control group against which to compare the regimen, and the registry record does not state an allocation method. The study can therefore describe outcomes among participants in the observed treatment group, but it cannot isolate a treatment effect by comparing that group with a randomized alternative. Differences between participants with and without an early response may also reflect differences in participant characteristics or other factors; the registry record does not report an adjusted analysis to address such differences.

The primary outcome is the percentage of participants with sustained virological response at Week 48. The stated intention-to-treat population includes all participants who received at least one dose of study drug. The registry record lists secondary outcomes covering early and later virological response, relapse, positive predictive value, adverse events, and changes in laboratory parameters. Specific statistical procedures, outcome analysis details, and a sample-size justification 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population included all participants who received at least one dose of study drug.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intention-to-treat (ITT) population included all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virological Response at Week 48, measured over At Week 48.

The primary endpoint is the percentage of participants with sustained virological response at Week 48. The registry definition requires undetectable hepatitis C virus RNA at 24 weeks after the last dose of study drug. The stated detection limit was 15 international units (IU) per milliliter (mL) by qualitative polymerase chain reaction (PCR). The endpoint is therefore a binary participant-level outcome: each participant either meets the stated response definition or does not.

A sustained response measured after treatment ends is used to describe whether virological suppression persists through the specified follow-up period. In this study, the Week 48 timeframe and the definition based on time after the final dose are both part of how the outcome is characterized. The registry record does not report the numerical percentage or its 95% confidence interval, so the size and precision of the observed response cannot be assessed from the posted result information.

General: A percentage communicates the frequency of an outcome in a defined population. A confidence interval conveys uncertainty around an estimate; a narrower interval generally indicates greater precision, while a wider interval indicates less precision. It does not show the range of individual participant outcomes. Interpretation also depends on the population included and on how missing outcome measurements are handled. The registry record defines the intention-to-treat population as participants who received at least one dose, but does not report the method used for missing Week 48 measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record names a percentage as the primary outcome and specifies a 95% confidence interval as its dispersion measure. It does not report the numerical percentage, confidence limits, or a statistical method used to calculate them. The method used for the primary analysis is therefore not reported in the registry record.

What does a percentage measure?

General: For a binary outcome, a percentage describes the proportion of participants meeting a defined criterion in a stated analysis population. The endpoint is whether a participant had undetectable HCV RNA according to the registry’s definition. To interpret a percentage, readers need both the number meeting the criterion and the number included in the analysis. The record identifies an intention-to-treat population of participants who received at least one dose, but does not report the number with an evaluable Week 48 outcome or the numerator and denominator used for the primary result.

The 262 enrolled participants should not automatically be treated as the denominator for the primary endpoint. Enrollment is a study-level count, while outcome analysis may depend on whether endpoint data were collected and on the prespecified handling of missing measurements. The registry record does not report the Week 48 analysis denominator or a missing-data rule.

What does the confidence interval add?

General: A confidence interval expresses uncertainty about an estimated quantity under the assumptions of the method used to calculate it. It is not a range intended to contain most individual participant outcomes. Its width is influenced by factors such as the amount of outcome information and the variability of the data. For a percentage, a confidence interval helps readers distinguish a comparatively precise estimate from one with substantial uncertainty. The registry record specifies a 95% confidence interval but does not post its limits, so its precision cannot be evaluated.

Does the study estimate a treatment effect?

The design is single arm, with no concurrent control comparison described. The primary percentage is consequently an outcome description for the treated group, not a between-group treatment contrast. General: A randomized comparison can help separate differences associated with assigned treatment from differences that arise because groups have different characteristics. In a single-arm study, that direct comparison is absent. The registry record does not report an adjusted comparison with an external group or another method for estimating a comparative treatment effect.

The stated scientific interest in Week 4 response concerns prediction of a later response. General: A predictive analysis would need to describe how early response relates to the later endpoint, including the relevant classification or model and its uncertainty. A positive predictive value, which is listed as a secondary outcome, describes the proportion of those classified as early responders who later meet the outcome definition, when defined for that analysis. The numerical value and analysis method are not reported in the registry record. The study’s stated aim alone does not supply those results.

What can be said about sample-size planning?

The study description gives a target sample size of 100 individuals, and the registry record lists enrollment of 262. The justification for the target, including any assumptions about the anticipated response rate or desired precision, is not reported in the registry record. The record also does not describe a protocol-based power calculation.

General: A sample-size calculation is a planning exercise based on assumptions about the effect or outcome of interest, variability, significance level, allocation, and desired power or precision. It is not evidence that a study observed an effect of the assumed size. Planning illustrations based on an observed effect are hypothetical calculations and must not be interpreted as observed power. A larger enrolled count does not establish that a study was adequately powered for every listed outcome; that depends on the planned question, assumptions, analysis population, and available endpoint data.

The stated illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. Those are assumptions for a planning illustration, not a description of the POTENTE design: the study itself is single arm. The registry record does not give a numerical illustration result or establish that these assumptions were used to plan the study.

What statistical details remain unclear?

The registry record does not report the primary analysis method, a model for the association between Week 4 and Week 48 response, adjustment variables, handling of missing outcomes, or whether any sensitivity analyses were conducted. Interim analyses and a formal statistical analysis plan are not reported in the registry record. The number of analyses recorded is zero, which does not supply the missing analysis details or numerical outcome estimates.

General: Over-dispersion matters when a statistical model assumes less variability than is present in the data. If that assumption is violated, standard errors and confidence intervals may be too small, and hypothesis tests may be poorly calibrated. This is a general consideration for some outcome models; the registry record does not identify an over-dispersion issue or report a model for which it could be assessed. Likewise, no modeling assumption should be attributed to this study without a reported analysis method.

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-2a + Ribavirin")
n      <- c(262)
events <- c(138)
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-2a + Ribavirin  262  138  52.7  46.4  58.8  46.6  58.6  46.6  58.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and secondary outcomes concerning rapid response at Week 4, response at Week 24, relapse, positive predictive value, adverse events, and changes in hematology and biochemistry parameters. It does not report a multiplicity strategy, such as a procedure to control the chance of false-positive findings across multiple statistical tests. The specific testing plan and any hierarchy among secondary outcomes are not reported in the registry record.

General: When several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. Multiplicity procedures can address that issue, but the appropriate approach depends on the objectives and analysis plan. Without a reported plan and numerical analyses, the listed outcomes should not be treated as a set of confirmatory findings.

The primary population is described as intention-to-treat and includes all participants who received at least one dose of study drug. The registry record does not state how participants with missing Week 48 measurements were handled, whether a specific imputation method was used, or how withdrawal or entry into the separate protocol affected endpoint analysis. The number who completed follow-up and the number with evaluable primary endpoint data are not reported in the registry record.

General: Missing outcome data can affect both the estimated percentage and its uncertainty, especially when the likelihood of missingness is related to response or participant characteristics. Different assumptions about missing outcomes can produce different interpretations. Sensitivity analyses can assess how conclusions change under alternative assumptions, but such analyses are not reported in the registry record.

The study description’s treatment pathway distinguishes Week 4 responders from non-responders and describes separate follow-up for the latter. The exact analysis population for the predictive question, and whether participants entering the separate protocol contributed Week 48 outcomes to the primary analysis, are not reported in the registry record. No interim analysis information is reported in the registry record.

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: upper gastrointestinal haemorrhage (1.1%), abdominal pain (0.4%), anorectal operation (0.4%), appendicitis (0.4%), arthralgia (0.4%).

The registry record lists 262 participants at risk for adverse events in the peginterferon alfa-2a plus ribavirin group. It reports 13 participants with serious adverse events and 179 with any adverse events. These are participant counts in the recorded treatment group. The registry also lists serious event terms, including Upper gastrointestinal haemorrhage at 1.1%, and Abdominal pain, Anorectal operation, Appendicitis, Arthralgia, and Cellulitis, each at 0.4%.

The event-term percentages describe the listed terms; they should not be read as a treatment-versus-control difference. The study is single arm, so the registry record gives no concurrent comparator for evaluating whether event frequency differed from another treatment or from no treatment. The record does not provide a death count; it is not reported in the registry record.

General: Serious adverse events and any adverse events are distinct categories. A participant may have more than one event, so event-term counts or percentages need not represent mutually exclusive groups of people. A count of participants with an event also does not establish that the event was caused by study treatment. Interpretation depends on definitions, duration of observation, completeness of reporting, and the method used to collect events. Those details are not all reported in the registry record.

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

The study addresses a clinically relevant statistical question: whether an early virological response could help predict a later sustained response among treatment-naïve participants with chronic hepatitis C, genotype 2 or 3, receiving peginterferon alfa-2a plus ribavirin. The registry record defines the primary endpoint and describes a pathway in which Week 4 responders continued treatment and then entered treatment-free follow-up. These details clarify the intended question and measurement schedule.

What the posted information does not establish is the numerical rate of sustained virological response. Although the primary outcome is specified as a percentage with a 95% confidence interval, neither the estimate nor the interval is reported in the registry record. The numerical results for Week 4 response, predictive value, relapse, and the other listed outcomes are likewise not reported in the registry record. Thus, the stated purpose cannot be evaluated using a reported primary estimate or a reported analysis of prediction.

The single-arm design also means that the outcome cannot be interpreted as a comparative treatment effect. Even if a response percentage were available, it would describe the observed participants and would not alone show what would have occurred under a different treatment or control condition. The registry record does not describe random allocation or a concurrent comparison arm.

General: Statistical evidence is most informative when the outcome definition, estimate, uncertainty, analysis population, missing-data approach, and design can be considered together. A clear endpoint definition helps specify what was counted, but it cannot substitute for a numerical result. Likewise, enrollment gives context about the study size, but does not establish how many participants contributed data to the primary analysis.

The adverse-event counts describe reported events in the treatment group. Without a comparator and fuller details on ascertainment and analysis, they should not be used to infer comparative safety or causation. The registry record supports a description of what was planned and which counts were recorded, while leaving the primary outcome magnitude and several important analysis details unresolved.

14. Why This Trial Matters Statistically

This study is statistically notable for linking an early measurement to a later outcome. Its stated aim was to investigate the predictive value of Week 4 virological response for sustained response. Such a question differs from asking whether a treatment outperforms another treatment: it asks whether information available early in a treatment course is associated with a later endpoint among participants on the study pathway.

The registry record also illustrates why endpoint definitions and timing matter. Sustained virological response is defined through undetectable HCV RNA at 24 weeks after the last dose, with a stated detection limit and assay. The treatment description includes different pathways for Week 4 responders and non-responders. For interpretation, readers need to know how those pathways relate to the primary analysis population and whether follow-up was complete. Those analysis details are not reported in the registry record.

At the same time, the single-arm design sets a clear boundary on inference. It can describe outcomes in the enrolled treatment group, but it does not provide a randomized comparison for estimating a treatment contrast. This distinction is important when reading an outcome percentage: a response proportion is not, on its own, evidence of benefit relative to another option.

The contrast between the stated target sample size of 100 individuals and enrollment of 262 is also a reminder that enrollment alone does not explain statistical planning. The justification for the target and the primary analysis method are not reported in the registry record. Nor is the numerical primary result available in the posted record. These gaps make it impossible to assess the estimate’s precision or to judge the reported predictive question from the registry information alone.

General: A transparent report of estimates, uncertainty, analysis populations, missing-data handling, and multiplicity decisions allows readers to assess how robustly a study addresses its question. The registry record provides some design and endpoint definitions, but does not report many of those statistical details. Distinguishing what the design can answer from what remains unreported is essential to reading this study accurately.

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 primary limitation for interpreting the posted findings is that a numerical estimate for sustained virological response and its 95% confidence interval are not reported in the registry record. The record therefore does not permit assessment of the primary endpoint’s magnitude or precision. Numerical results for the stated early-response predictive question are also not reported.

The single-arm, observational design has no concurrent comparator described. It can characterize outcomes in the treatment group, but cannot establish a comparative treatment effect through a like-for-like control comparison. The registry record does not state an allocation method, and does not report adjusted analyses that might address differences among participants with different Week 4 response status.

The registry record gives an intention-to-treat definition requiring at least one dose, but does not report the primary analysis denominator, completion of follow-up, or handling of missing Week 48 measurements. It also does not explain how participants entering the separate protocol were handled in the primary or predictive analyses. These omissions matter because they affect which participants contribute to the reported outcome and how uncertainty should be interpreted.

The target sample size is stated as 100 individuals, while enrollment is 262. The reason for the difference and the statistical justification for the target are not reported in the registry record. The primary analysis method, any prespecified adjustment, sensitivity analyses, interim analyses, and multiplicity approach are also not reported. Consequently, the statistical plan cannot be reconstructed from the registry record.

Safety interpretation is limited by the lack of a concurrent comparator and by absent details on event collection, follow-up time by participant, and attribution. The listed participant counts and serious event terms describe the recorded group, but do not determine whether events were caused by treatment or how rates compare with another group.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: POTENTE Study: A Study of Early Virological Response in Naive Patients With Chronic Hepatitis C, Genotype 2 or 3, Treated With PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Copegus (Ribavirin). — NCT00700401.
• Registry record last updated 2016-06-21; status last verified 2016-05.
• Results first posted 2016-06-21.
• 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

POTENTE was a prospective, observational, single-arm study of treatment-naïve participants with chronic hepatitis C, genotype 2 or 3. The registry record lists Hoffmann-La Roche as sponsor, a start of 2008-11, primary completion of 2010-11, COMPLETED status, and enrollment of 262. The study description gives a target sample size of 100 individuals.

The intervention was peginterferon alfa-2a plus ribavirin. The primary outcome was the percentage with sustained virological response at Week 48, defined as undetectable HCV RNA 24 weeks after the last dose. The primary outcome value and its 95% confidence interval are not reported in the registry record.

The registry record describes the study’s interest in Week 4 response as a predictor of sustained response and lists secondary virological, safety, hematology, and biochemistry outcomes. It reports 13 participants with serious adverse events and 179 with any adverse events among 262 at risk in the treatment group. A comparator arm, detailed statistical analysis plan, missing-data methods, and numerical primary result are not reported in the registry record.