Adherence in Patients Receiving PegIntron/Rebetol for Hepatitis C in Conjunction With a Psychotherapy Support Program (Study P04252): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adherence in Patients Receiving PegIntron/Rebetol for Hepatitis C in Conjunction With a Psychotherapy Support Program (Study P04252) (NCT00723892), a registered phase not stated study. The primary outcome is Number of Participants Who Complete Treatment With PegIntron/Rebetol Therapy for Hepatitis C When Administered With a Patient Psychotherapy Support Program as Compared to a Group Without a Psychotherapy Support Program..

2. Clinical Question

3. Trial Design

This completed study is registered as NCT00723892 and is titled “Adherence in Patients Receiving PegIntron/Rebetol for Hepatitis C in Conjunction With a Psychotherapy Support Program (Study P04252).” Its official title describes an observatory on treatment adhesion among people with chronic hepatitis C receiving ViraferonPeg and Rebetol alongside a psychotherapeutic assistance program. Merck Sharp & Dohme LLC is named as sponsor. The recorded start is 2005-07, and primary completion is 2009-05.

The registry describes two treatment groups: participants receiving PegIntron/Rebetol with a psychotherapy support program, and participants receiving PegIntron/Rebetol alone. The listed interventions are peginterferon alfa-2b (PegIntron), Rebetol (ribavirin), and the psychotherapy support program. The allocation method is not stated. The registry explicitly identifies the comparison as nonrandomized, so differences between the groups may reflect factors other than the support program. The record does not give details on how participants entered either group or how treatment decisions were made.

The primary outcome is the number of participants who complete PegIntron/Rebetol therapy, assessed 12 months after treatment onset. The registry also lists the average length of treatment among participants on therapy. It reports 2 outcome measures and 0 analyses. In particular, the record does not report group-specific completion results or an analysis comparing the groups. It also does not describe a statistical analysis plan, interim analyses, or a sample-size justification for the study’s own design. The planning assumptions described in the record are illustrations based on an observed effect, not evidence of the trial’s original design rationale.

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: Only 568 participants were assigned to treatment as they were foreseen to complete treatment, were consulted, and met inclusion criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants foreseen to complete treatment, consulted and assigned to treatment 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 Number of Participants Who Complete Treatment With PegIntron/Rebetol Therapy for Hepatitis C When Administered With a Patient Psychotherapy Support Program as Compared to a Group Without a Psychotherapy Support Program., measured over 12 months after onset of treatment.

The primary endpoint counts participants who complete treatment with PegIntron/Rebetol therapy for hepatitis C. The comparison asks whether completion differs between participants receiving the psychotherapy support program and participants receiving no psychotherapy support program. The assessment time is 12 months after onset of treatment. The registry describes the analyzed population as participants foreseen to complete treatment, consulted and assigned to treatment, but does not give the number analyzed or further define that population.

Completion is relevant to the study’s stated adherence question: the registry summary explains that psychiatric adverse events during treatment may prompt early discontinuation. A count of completers can describe whether treatment was completed in each group, but interpreting the count requires the group denominators and a clear account of who was included in the analysis. For a comparison, an effect estimate and its uncertainty are also important. These results are not reported in the registry record. The endpoint description alone therefore states what the study intended to assess, not what it found.

The record lists average length of treatment as a secondary outcome. This could describe treatment duration among participants on treatment, but its results and analysis are not reported in the registry record. Neither outcome, without reported group results and suitable analysis, establishes that the support program caused a change in adherence.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level outcome: a participant either completes treatment or does not, according to the study’s endpoint definition. The registry describes the measure as a number of participants. For a binary outcome, a useful report ordinarily gives the number with the event and the number assessed in each group, followed by a comparison expressed as an effect estimate with uncertainty. The registry record does not report those primary-outcome results. The outcome type and assessment time are stated, but the resulting data and comparison are not.

What does a confidence interval tell the reader?

General statistical explanation: a confidence interval conveys uncertainty around an estimated effect under the assumptions of the method used. A relatively narrow interval indicates greater precision than a wide interval, while the interval’s location helps show which effect values are compatible with the data. It does not guarantee that the study design is unbiased, and it cannot address systematic differences created by nonrandom allocation. No primary-outcome confidence interval is reported in the registry record, so the precision of the comparison is unknown.

Why does allocation matter?

General statistical explanation: random allocation is intended to balance, on average, factors that could influence both group membership and the outcome. In a nonrandomized comparison, the groups can differ for reasons other than the intervention. Statistical adjustment can sometimes address measured differences, but it cannot automatically resolve unmeasured confounding or errors in how variables are recorded. Here, allocation is not stated and the registry identifies the comparison as nonrandomized. The record does not describe baseline characteristics, covariate adjustment, or a method for controlling confounding. The statistical interpretation must therefore remain descriptive rather than causal.

What is over-dispersion, and is it relevant?

General statistical explanation: over-dispersion is a mismatch in which observed variability is greater than a model assumes. It can affect standard errors and confidence intervals in some count-data models. The primary outcome in this study is described as a count of participants completing treatment, which is also a binary event measured across participants. The registry does not report a model or analysis for this outcome, so it is not possible to determine whether over-dispersion was considered or whether it applies to any reported analysis. No specific model should be inferred from the endpoint description alone.

How should the planning assumptions be read?

The record describes a planning illustration computed from the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says that the effect to detect is the stated fraction of the observed effect. It also distinguishes planning outputs for time-to-event outcomes from those for other outcomes: the former refer to a total number of events, while the latter refer to participants per arm. These are planning conventions, not outcome findings. Sample-size calculations are planning illustrations, never observed power. The observed effect and numerical planning outputs are not reported in the registry record, so their implications cannot be assessed.

General statistical explanation: sample-size planning estimates the amount of information a future study might need under assumptions about the outcome, effect, allocation and analysis. If those assumptions do not match the actual design or the true effect, the planning result may not describe the study’s achieved precision. Planning based on an observed effect also depends on how that effect was estimated. The registry does not report the study’s own sample-size justification or statistical analysis plan, and the planning description should not be taken as evidence that the design was prospectively sized for the primary endpoint.

The registry reports 0 analyses. It does not report a statistical test, model, adjusted or unadjusted estimate, or sensitivity analysis for the primary outcome. A statistical method cannot be reconstructed from a stated endpoint alone. The same applies to the listed secondary outcome, average length of treatment: its analysis method and results are not reported in the registry record. Any recalculation from summary statistics would require posted summary values, which are not reported in the registry record.

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("PegIntron/Rebetol and Psychotherapy Support Progra", "PegIntron/Rebetol Alone (no Psychotherapy)")
n      <- c(313, 255)
events <- c(206, 168)
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  PegIntron/Rebetol and Psychotherapy Support Progra  313  206  65.8  60.3  71.1  60.4  70.8  60.4  70.8
ARM  PegIntron/Rebetol Alone (no Psychotherapy)  255  168  65.9  59.7  71.7  59.9  71.4  59.9  71.4

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists average length of treatment as a secondary outcome. It reports 2 outcome measures and 0 analyses. The record does not report a multiplicity strategy, such as whether or how interpretation would account for testing more than one outcome. Without reported analyses, there is no basis to determine how multiple outcomes were handled or whether any adjustment was applied.

Missing-data handling is not reported in the registry record. In general, missing outcome status can affect a completion comparison if the likelihood of missingness differs between groups or relates to treatment completion. A reader would need to know how unknown status was classified, whether participants were excluded, and how the analysis population was defined in practice. The record describes the primary population as participants foreseen to complete treatment, consulted and assigned to treatment, but does not give further operational details or the number analyzed.

The registry does not report an intention-to-treat analysis, a per-protocol analysis, or another named analysis population. It does not state how deviations from treatment, early discontinuation, or incomplete follow-up were handled in the endpoint analysis. It also does not report imputation or sensitivity analyses. These omissions limit assessment of the primary comparison, particularly because completion and discontinuation are central to the study question. A statistical analysis plan and the handling of missing data are not 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

Serious events with the highest arm-level rate: anaemia (0.2%), myocardial infarction (0.2%), basedow's disease (0.2%), drug intolerance (0.2%), bronchopulmonary aspergillosis (0.2%).

The registry’s serious adverse event summary lists 11 serious adverse events among 614 participants at risk. For other adverse events, it lists 0 among 614 participants at risk. These figures are reported for all enrolled participants, not separately by psychotherapy-support group. The registry does not provide a group-specific safety comparison or an analysis relating adverse events to the intervention.

The listed serious-event terms include Anaemia, Myocardial Infarction, Basedow's Disease, Drug Intolerance, Bronchopulmonary Aspergillosis, and Pulmonary Tuberculosis. Each term is reported as 0.2%. The record does not give the event counts for each term in the summary, and the listed terms should not be added together to infer a total: the record does not state whether participants could appear under more than one term or whether the list is exhaustive. Deaths are not reported in the registry record.

These figures describe events recorded in the registry; they do not establish that an event was caused by a particular treatment or support program. Interpretation is limited by the absence of group-specific data and details on collection, follow-up, and attribution.

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

The study was designed to examine treatment completion during PegIntron/Rebetol therapy with or without a psychotherapy support program. The registry’s rationale is that psychiatric adverse events may prompt early discontinuation. The primary endpoint and assessment time are specified, so the intended adherence question is clear: whether the groups differed in the number completing therapy at 12 months after onset.

However, the registry record does not report the group-specific completion counts or a statistical comparison. It therefore does not establish whether completion was higher or lower in either group, how large any difference was, or how precisely it was estimated. The listed secondary outcome also has no reported result. Study completion status and enrollment do not substitute for reporting endpoint findings.

Even with outcome results, the comparison would require cautious interpretation because allocation was not stated and the record identifies the study as nonrandomized. Differences in completion could reflect characteristics or circumstances that differ between groups, as well as any contribution of the support program. The record does not provide the information needed to assess those potential explanations or to determine whether an adjusted analysis was performed.

The findings that can be described are therefore limited to the registered study question, design context, endpoint definition, and safety summary. The record does not support a claim that psychotherapy support changed adherence, nor does it show that the program had no effect. Absence of a reported comparison is not evidence that the groups had equal outcomes. The appropriate interpretation is that the registry record does not contain the results needed to answer the primary question.

14. Why This Trial Matters Statistically

This trial raises a practical statistical question about adherence: whether a psychotherapy support program, offered alongside PegIntron/Rebetol therapy, is associated with treatment completion. The registry links this question to concern about psychiatric adverse events and early discontinuation. Defining completion as the primary endpoint and stating its assessment time makes the intended outcome recognizable, but a clearly specified question is only the starting point for inference.

The design information matters because the arms were not randomized and allocation is not stated. In such a comparison, measured and unmeasured differences between groups can complicate attribution. This is why group descriptions, baseline information, the analysis population, adjustment methods, and uncertainty around the result are important parts of a statistical report. Those details are not reported in the registry record.

The record also illustrates the distinction between outcome reporting and planning. The described sample-size assumptions concern an illustration based on an observed effect; they do not supply the missing treatment-completion results and are not observed power. Statistical planning cannot replace reporting what happened in each group. Without endpoint counts and a comparison, neither effect size nor precision can be evaluated.

For clinical researchers, the key statistical lesson is that a registry question, an endpoint definition, and enrollment information do not by themselves answer a comparative-effectiveness question. Results must be presented with denominators, clear population definitions, and an analysis that reflects the design. The registry’s safety figures provide additional descriptive information, but they are not a group-specific assessment of the psychotherapy program.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation in the registry record is the absence of primary-outcome results. Completion counts by group, group denominators for the endpoint, a comparative estimate, and its uncertainty are not reported. The record reports 0 analyses, so no statistical analysis of the primary question is available for interpretation.

The comparison is nonrandomized, and allocation is not stated. The record does not provide baseline group characteristics, details of assignment, or an adjustment strategy. It is therefore not possible to assess whether the groups were similar or how potential confounding was addressed. The description of the primary population is limited to participants foreseen to complete treatment, consulted and assigned to treatment; further eligibility and analysis-population details are not reported.

Missing-data methods, outcome ascertainment details, and handling of deviations from treatment are not reported in the registry record. The record also does not describe a multiplicity strategy, statistical analysis plan, or the study’s own sample-size justification. Although planning assumptions are described, the observed effect and numerical planning outputs are not reported in the registry record. The safety summary is not separated by arm, and deaths are not reported in the registry record. These gaps limit both the efficacy interpretation and the safety comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Adherence in Patients Receiving PegIntron/Rebetol for Hepatitis C in Conjunction With a Psychotherapy Support Program (Study P04252) — NCT00723892.
• Registry record last updated 2015-10-30; status last verified 2015-10.
• Results first posted 2010-09-20.
• 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

NCT00723892 is a completed study sponsored by Merck Sharp & Dohme LLC, with recorded start 2005-07 and primary completion 2009-05. It enrolled 614 participants and concerned chronic hepatitis C treatment with PegIntron/Rebetol, comparing therapy with and without a psychotherapy support program. The primary endpoint was the number completing treatment at 12 months after onset. Average length of treatment was listed as a secondary outcome.

The registry identifies the comparison as nonrandomized and does not state allocation. It reports 2 outcome measures and 0 analyses. Primary completion results and comparative estimates are not reported in the registry record. The safety summary lists 11 serious adverse events among 614 at risk and 0 other adverse events among 614 at risk; deaths are not reported in the registry record.