Multidisciplinary Support Program in Chronic Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multidisciplinary Support Program in Chronic Hepatitis C (NCT01850745), a registered phase not stated study. The primary outcome is Adherence to Treatment.

2. Clinical Question

The study also lists sustained virological response (SVR) as a secondary treatment-efficacy outcome. However, the registry record does not report SVR results. The stated aim was to evaluate the MSP in relation to both adherence and treatment efficacy. These are distinct questions: adherence concerns how much of the prescribed treatment was received over the treatment period, while SVR concerns a virological outcome. The record describes the intended comparison, but the absence of outcome results means that the posted information cannot show whether adherence or SVR differed between the cohorts.

3. Trial Design

The study enrolled 447 patients with chronic hepatitis C receiving antiviral treatment. It compared three cohorts assembled at different times: a control group recruited during 2002-2004, an MSP-pilot group recruited during 2005-2006, and an MSP-validation group recruited during 2007-2009. The group sizes were 147, 131, and 169 participants, respectively.

The control group was retrospective and received usual treatment with peginterferon-2a and ribavirin without multidisciplinary support. The pilot and validation cohorts were prospective and received usual pharmacological treatment alongside the MSP. Thus, the intervention of interest was the additional support program, not a different antiviral regimen.

This is not a randomized comparison: allocation is not stated in the registry record. The control and MSP cohorts were recruited in different calendar periods, and the control was retrospective whereas the intervention cohorts were prospective. Those design features mean the cohorts are not a like-for-like randomized contrast. Differences in outcomes, if reported, could reflect the program, differences between participants, changes over time, or other factors; the record does not provide information that would separate these explanations.

The study status is completed. The record lists a start of 2003-01 and primary completion of 2009-01. It identifies adherence to treatment as the primary outcome, measured as the number of participants, and SVR as a secondary outcome. Although the registry lists two outcome measures, it reports zero analyses. The statistical analysis plan, allocation procedure, sample-size justification for the trial, and any interim analyses 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

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 Adherence to Treatment, measured over 48 months.

The primary endpoint is adherence to treatment, recorded as a number of participants. The registry defines adherent patients as those who received equal to or more than 80% of the total dose of pegylated interferon and ribavirin during equal to or more than 80% of the treatment duration. The stated weekly dose for pegylated interferon is 180 microg/week, and the stated daily dose for ribavirin is 1200 mg/d. The treatment duration in this definition is 48 weeks.

The registry defines non-adherent patients using a lower-than-80% threshold for total dose received during less than 80% of treatment duration. The record's wording does not describe every possible combination of dose received and duration, so it is not possible to infer how any other pattern was classified.

Adherence is relevant to this study's question because the stated aim was to evaluate whether multidisciplinary support was associated with patients receiving the intended antiviral treatment. It is not itself a virological outcome. SVR is listed separately as a secondary outcome measuring treatment efficacy, but no SVR results are reported.

The primary outcome timeframe is stated as 48 months, while the adherence definition refers to a treatment duration of 48 weeks. The registry record does not explain this difference. It also does not report the number or proportion of participants meeting the adherence definition in any cohort, nor a comparative estimate or uncertainty interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes an observational, non-randomized cohort comparison rather than a randomized allocation. The control group was retrospective, while the pilot and validation cohorts were prospective. The groups were recruited in different calendar periods. These design details matter because the comparison does not isolate the support program from all other differences that may occur between cohorts.

What does randomization contribute?

General statistical explanation: randomization assigns participants to groups by chance. When conducted appropriately, it can balance measured and unmeasured participant characteristics on average, making a treatment comparison less vulnerable to confounding. This study is not described as randomized, and its allocation procedure is not stated. Therefore, the registry record does not support treating the cohort contrast as though treatment assignment were randomized.

In a non-randomized comparison, confounding is a concern when a characteristic is associated both with group membership and with the outcome. Recruitment period and retrospective versus prospective data collection are relevant features of this study design. Other possible sources of differences between cohorts cannot be identified from the record. Whether any adjustment was attempted, which variables might have been included, and how adjusted estimates would compare with unadjusted estimates are not reported in the registry record.

What does the primary endpoint measure?

The primary endpoint is a participant count based on the registry's adherence definition. It classifies adherence by the amount of pegylated interferon and ribavirin received and the duration of treatment. A binary endpoint of this kind distinguishes participants who meet a defined criterion from those who do not, but its interpretation depends on the exact classification rule and the availability of the underlying dose and duration information. The record gives thresholds for adherent and non-adherent patients but does not describe how other possible combinations were handled.

The primary outcome timeframe is listed as 48 months, while the definition refers to a 48-week treatment duration. The record does not reconcile these descriptions. It also does not report outcome counts, the statistical model, or the measure used to compare groups. No specific method for estimating an adherence difference can therefore be attributed to the registry's analysis.

How should uncertainty be understood?

General statistical explanation: an effect estimate summarizes the observed contrast between groups. A confidence interval expresses uncertainty around that estimate, with its width influenced by the amount of information and variability in the data. A narrow interval indicates greater precision than a wide interval, but neither the interval nor the estimate alone resolves bias from non-random group assignment. Here, no adherence or SVR estimate and no confidence interval are reported in the registry record, so neither the magnitude nor the precision of a cohort contrast can be assessed.

General statistical explanation: a p-value describes how incompatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, and it does not quantify the size or importance of an effect. The registry record reports zero analyses and does not give p-values for the listed outcomes. There is no reported inferential result to interpret.

What do the planning assumptions mean?

The registry record describes sample-size illustrations based on a fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning illustrations, not the trial's own design justification. The record does not report a trial sample-size justification. The illustrations are not observed power and do not establish that this cohort study was adequately powered. No numerical planning results are reported in the registry record, so specific participant requirements cannot be discussed.

General statistical explanation: planning calculations estimate the amount of information that may be needed to detect a specified effect under stated assumptions. Such calculations depend on assumptions about the effect and analysis and should not be interpreted as evidence that an effect was present. In this study, the stated illustrations are distinct from results observed among participants.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when count data vary more than a chosen statistical model expects. If a model assumes less variability than the data contain, standard errors may be too small and confidence intervals or tests may be misleading. Appropriate modeling depends on the outcome structure and analysis plan. The registry record does not report a count model, a dispersion assessment, or an analysis of the primary endpoint, so over-dispersion cannot be assessed as a feature of the reported analysis.

In short, the registry record gives enough information to describe the cohorts and the endpoint definition, but not enough to reconstruct the statistical analysis. The analysis population, handling of missing observations, covariate adjustment, effect measure, uncertainty intervals, hypothesis tests, and any interim analyses 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("Control", "Validation Cohort", "Pilot Cohort")
n      <- c(147, 169, 131)
events <- c(116, 155, 124)
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  Control  147  116  78.9  71.4  85.2  71.6  84.7  71.6  84.7
ARM  Validation Cohort  169  155  91.7  86.5  95.4  86.6  95.0  86.6  95.0
ARM  Pilot Cohort  131  124  94.7  89.3  97.8  89.4  97.4  89.4  97.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists adherence to treatment as the primary outcome and SVR as a secondary outcome. It does not report analyses for either outcome, and it does not describe a statistical plan for handling multiple outcomes or comparisons. Whether a multiplicity adjustment was planned or performed is not reported in the registry record.

General statistical explanation: when several outcomes, time points, subgroups, or comparisons are tested, the chance of obtaining at least one apparently notable result can increase. A prespecified analysis plan can identify which outcomes are primary and how multiple testing will be handled. The registry identifies a primary and a secondary outcome, but it does not state how the study would control or interpret multiplicity across them. With no outcome analyses reported, there is no multiplicity-adjusted or unadjusted result to interpret.

Missing-data methods are also not reported in the registry record. The record does not describe how incomplete dose histories, missing treatment-duration information, loss to follow-up, or unavailable virological assessments were handled. It does not state whether participants with missing outcome information were excluded, classified in a particular way, or included through an imputation method.

The analysis populations are not reported in the registry record. It is therefore unknown whether analyses included all enrolled participants, only those with evaluable outcome data, or another defined subset. The cohort enrollment totals should not be assumed to be the denominators for every outcome.

These omissions limit assessment of bias and reproducibility. In general, missingness can affect estimates when the likelihood of having an observed outcome is related to participant characteristics or outcomes. The record does not provide enough information to determine whether missing data occurred or how any such data might have influenced the findings.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: depression major (1.5%).

The registry lists serious adverse-event participant counts for the control, validation, and pilot cohorts. Each cohort has 2 participants recorded as affected by a serious event. The corresponding numbers at risk are 147 in control, 169 in validation, and 131 in pilot. The record also lists zero deaths for each cohort.

For other adverse events, the participant counts recorded as affected are 52 in control, 14 in validation, and 4 in pilot; the respective numbers at risk are 147, 169, and 131. These are participant counts, not a comparative statistical analysis. The registry does not report confidence intervals, hypothesis tests, or an adjusted comparison of event occurrence between cohorts.

The serious-event listing includes the term “Depression major” with 1.5%. The record does not identify the cohort or denominator associated with that term in the available listing, so it should not be assigned to a particular group. The event counts do not establish whether differences between cohorts reflect the MSP, the treatment, participant characteristics, or differences in observation and reporting. The registry record also does not provide further detail about event timing, severity criteria, or attribution.

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

The record documents a study designed to examine adherence to antiviral treatment and treatment efficacy in chronic hepatitis C, comparing a conventional approach with a multidisciplinary support program. It describes a retrospective control cohort and prospective intervention cohorts, their enrollment sizes, and the adherence definition. It also lists participant counts for serious and other adverse events.

It does not report the primary endpoint results. No group-level adherence counts, comparative effect estimate, confidence interval, or p-value are reported in the registry record. SVR is identified as a secondary outcome, but its results are also not reported. The available information therefore cannot establish whether adherence or SVR differed between the cohorts, or how precise any difference might have been.

The design also constrains what a group difference could mean. The comparison is not randomized, allocation is not stated, and the cohorts were recruited during different periods using different prospective or retrospective approaches. Even if outcome estimates were available, these features would make causal interpretation dependent on information about participant characteristics, outcome collection, and statistical adjustment that the registry does not report.

The record describes sample-size illustrations based on a fraction of an observed effect and specified planning assumptions. Such illustrations are planning tools, not evidence of an observed result or the probability that the study detected an effect. The registry record does not report the trial's own sample-size justification or numerical results from the illustrations.

Accordingly, the posted information supports a description of the intended clinical question, cohort structure, endpoint definition, and recorded event counts. It does not support a conclusion about the program's effect on adherence or SVR. Nor do the event counts alone establish a treatment-related safety difference. Those questions require outcome analyses and detail not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a useful statistical question about how a support program might be evaluated alongside a standard pharmacological regimen. The intervention is an additional multidisciplinary program, while the antiviral treatment is described as usual treatment across the cohorts. Separating the program's association from the effects of treatment and from differences among patient groups is central to interpreting this kind of comparison.

The cohort structure illustrates why study design and statistical analysis must be read together. A retrospective control group and prospective intervention groups recruited in different periods can differ in ways that are not captured by enrollment totals. Statistical adjustment may address measured differences under appropriate assumptions, but the registry record does not report whether adjustment was used or which information was available.

The endpoint definition also matters. Adherence is operationalized using thresholds for both dose received and treatment duration, while the registry lists a 48-month timeframe and refers to a 48-week duration in the definition. That distinction affects how the outcome should be understood, yet the record does not explain it. Clear endpoint definitions and consistent reporting are necessary for readers to judge what an adherence count represents.

Finally, the record demonstrates the difference between describing a trial and reporting its results. It identifies the question, groups, and outcome measures but reports no analyses for the listed outcomes. Without effect estimates and measures of uncertainty, readers cannot assess the direction, magnitude, or precision of a comparative result. The study remains statistically interesting as an example of how non-randomized cohort comparisons require careful attention to comparability, outcome definitions, missing information, and transparent analysis reporting.

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 of the available record is the absence of primary and secondary outcome results. It reports no adherence counts, SVR findings, comparative estimates, confidence intervals, or p-values. The record therefore does not permit evaluation of the primary research question or the precision of any outcome difference.

The comparison is non-randomized, and allocation is not stated. The control cohort is retrospective, while the MSP cohorts are prospective and come from later recruitment periods. These features create potential for differences in participant mix, clinical practice, and outcome ascertainment. The registry does not report baseline characteristics or methods that could help assess or adjust for such differences.

The endpoint description has an unresolved timing discrepancy: the primary outcome timeframe is 48 months, while the adherence definition refers to a 48-week treatment duration. The registry does not clarify how these relate. The definition also specifies criteria for adherent and non-adherent patients but does not explain classification of all other possible dose-duration combinations.

Important analytic details are not reported in the registry record, including the analysis population, missing-data handling, statistical models, covariate adjustment, multiplicity approach, and interim analyses. A trial-specific sample-size justification is also not reported. These omissions prevent assessment of the analysis assumptions and reproducibility.

Finally, adverse-event counts are descriptive and lack a reported comparative analysis. Details on event timing, attribution, and the cohort associated with the listed serious-event term are not available in the record. These limitations concern what can be learned from the registry information and do not establish that the study itself did not collect additional data.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multidisciplinary Support Program in Chronic Hepatitis C — NCT01850745.
• Registry record last updated 2021-09-20; status last verified 2013-05.
• Results first posted 2018-07-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed study of a multidisciplinary support program for patients with chronic hepatitis C receiving peginterferon-2a and ribavirin. Enrollment was 447 across a retrospective control group and prospective pilot and validation cohorts. The primary outcome was adherence to treatment; SVR was listed as a secondary outcome.

The study was not randomized, and allocation is not stated. The cohorts were recruited during different periods. The registry reports no analyses and does not report results for adherence or SVR. It also does not report the trial's statistical analysis plan, missing-data approach, or analysis populations.

Participant counts for serious and other adverse events and deaths are listed by cohort. These are descriptive counts, not comparative estimates. The posted record supports a description of the design and outcome definitions, but does not establish an effect of the support program on adherence, SVR, or safety.