DAA Based Therapy for Recently Acquired Hepatitis C (DARE-C): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for DAA Based Therapy for Recently Acquired Hepatitis C (DARE-C) (NCT01743521), a non-randomized phase 4 study. The primary outcome is SVR12 (Sustain Virological Response, HCV RNA Undetectable 12 Weeks Post-treatment).

2. Clinical Question

3. Trial Design

This was a Phase 4, parallel-group study with non-randomized allocation and no masking. The registry records an enrollment of 14 and identifies the sponsor as the Kirby Institute. The recorded start was 2013-01, primary completion was 2015-11, and the study status is completed. These design details describe how the study was registered; they do not supply an outcome analysis.

The three groups were defined by an HCV RNA response-guided treatment schedule. Group A was assigned 8 weeks total therapy if HCV RNA was undetectable after 2 weeks of therapy. Group B was assigned 12 weeks total therapy if HCV RNA was undetectable after 4 weeks. Group C was assigned 24 weeks total therapy if HCV RNA was undetectable after 8 weeks; this schedule comprised 12 weeks of TPV/PEG-IFN/RBV followed by 12 weeks of PEG-IFN/RBV. The registry does not describe how participants were allocated among these strategies or provide further rules for treatment assignment.

Because allocation was not randomized, the groups should not be treated as exchangeable treatment arms. A comparison of their outcomes would not, by itself, isolate the effect of treatment duration. The record does not report a control group, a randomization procedure, masking procedures beyond none, or a statistical analysis plan. It also does not report a sample-size justification. The planning assumptions listed for a sample-size illustration are not a description of the trial’s own design or justification.

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 SVR12 (Sustain Virological Response, HCV RNA Undetectable 12 Weeks Post-treatment), measured over 12 weeks post-treatment.

The primary endpoint is SVR12, defined in the registry as a negative qualitative HCV RNA result 12 weeks after therapy completion. It is recorded as a percentage of participants. In statistical terms, this is a binary outcome at the participant level: each participant either meets the stated endpoint definition or does not, and the percentage describes the proportion meeting it in the endpoint population.

SVR12 is used as a post-treatment measure of virological response. Measuring HCV RNA after therapy has ended distinguishes this endpoint from an undetectable result during treatment or at the end of treatment. The registry also lists SVR24 and several measures of undetectable HCV RNA at earlier time points among secondary outcomes, but those measure different points in the treatment course or follow-up.

The primary endpoint’s measurement definition and timeframe are recorded, but the registry record does not report the number or percentage of participants who achieved SVR12, an uncertainty interval, or a statistical comparison. It also does not report the endpoint analysis population or how missing endpoint measurements were handled. Consequently, the endpoint can be described from its definition, but its observed value and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint such as SVR12, the basic descriptive statistic is the proportion of participants who meet the endpoint definition. The numerator is the number meeting the definition, and the denominator is the number included in the relevant analysis. A confidence interval describes the uncertainty around an estimated proportion under the assumptions of the method used. It is not a guarantee that the true value lies within a particular interval. The registry record does not report an SVR12 numerator, denominator, estimate, confidence interval or method for calculating one, so none can be interpreted for this study.

What does non-randomized allocation mean?

In a randomized comparison, chance assignment is used to make groups comparable on average, subject to random variation. In a non-randomized study, group membership is not established by that mechanism. Here, the registry identifies three response-guided durations and labels allocation non-randomized. The point at which HCV RNA becomes undetectable is part of the group definitions, so the groups are distinguished by response timing as well as by the subsequent treatment schedule. A direct difference in their outcomes would therefore mix any duration association with differences in group membership and response history. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured confounding; whether adjustment was undertaken is not reported in the registry record.

Why does the denominator matter?

A percentage is meaningful only in relation to the participants counted in its denominator. The study enrollment is 14, while the adverse-event section gives separate at-risk counts for its group categories. Those entries describe the recorded adverse-event data and should not be substituted for primary endpoint denominators. The registry record does not explain the relationship between enrollment, group membership, and the populations used for each outcome. It also does not report whether endpoint data were available for all enrolled participants.

What would an uncertainty interval add?

A point estimate alone gives a central summary, while an interval communicates how much uncertainty is compatible with the data under a specified statistical model. With limited data, an interval may be broad; its width depends on the observed information and the method. The record contains no endpoint interval, so the precision of any SVR12 estimate cannot be assessed. No result should be inferred from the enrollment count alone.

How should the planning illustration be read?

The registry describes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. It says the illustration is based on the observed effect, not the trial’s own design, and that non-time-to-event planning values are participants per arm. However, no resulting sample-size values or effect values appear in the record. These assumptions should not be mistaken for a documented design calculation, a retrospective assessment of power, or evidence about the observed treatment outcomes. Sample-size calculations are planning tools; they do not determine whether a result is clinically important or precisely estimated.

What can a p-value establish?

A p-value, when calculated under a specified statistical model, describes how compatible the observed data are with a particular null hypothesis. It does not give the probability that the null hypothesis is true, measure the size or importance of an effect, or resolve bias in a non-randomized comparison. No p-value or hypothesis test is reported for this study. As a result, there is no reported test to interpret, and a missing test result is not equivalent to a non-significant result.

Why do multiple outcomes matter?

When several outcomes or time points are examined, repeated statistical testing can increase the chance of seeing at least one apparently unusual result under a collection of null hypotheses. Methods for controlling or describing that issue depend on the analysis plan and the role assigned to each outcome. The registry identifies a primary endpoint and multiple secondary outcomes, but does not report a multiplicity strategy or outcome analyses. The number of listed outcome measures alone does not show how many tests were conducted.

In short, the study’s binary endpoint, group structure and planning assumptions can be described, but the analysis methods actually used and the resulting estimates are not reported in the registry record. The record does not provide enough information to reconstruct an endpoint analysis or assess the statistical precision of treatment-group comparisons.

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("Group A - 8 Weeks Total Therapy", "Group B - 12 Weeks Total Therapy", "Group C - 24 Weeks Total Therapy")
n      <- c(7, 3, 2)
events <- c(5, 3, 2)
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  Group A - 8 Weeks Total Therapy  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5
ARM  Group B - 12 Weeks Total Therapy  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Group C - 24 Weeks Total Therapy  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry names SVR12 as the primary endpoint and lists secondary outcomes that include SVR24, end-of-treatment undetectable HCV RNA, undetectable HCV RNA at Weeks 1 through 4, and selected decreases in absolute neutrophil count and platelets. It records 15 outcome measures overall. A list of outcomes does not establish how many were analyzed, which comparisons were prespecified, or whether any statistical adjustment was planned for multiple testing. A multiplicity strategy is not reported in the registry record.

The record reports zero analyses. It does not provide endpoint results, confidence intervals, p-values, or a statistical analysis plan. Therefore, there is no basis for evaluating whether the primary endpoint was analyzed as planned or how secondary findings should be interpreted alongside it. The additional outcome measures beyond those specifically listed are not described in detail in the registry record.

Missing-data methods are not reported. The record does not state how participants with an unavailable HCV RNA measurement were handled, whether outcomes were analyzed in an intention-to-treat or other analysis population, or whether any sensitivity analysis was conducted. The primary endpoint population field is blank. Without these details, the endpoint denominator and the consequences of missing observations cannot be assessed.

The registry’s sample-size assumptions describe a planning illustration, not the trial’s own design justification. The actual sample-size justification is not reported in the registry record. These omissions limit assessment of the planned inferential strategy, but they do not establish that any particular analysis or method was used.

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: appendicitis (33.3%), skin cancer (14.3%), axillary abscess (14.3%).

The serious adverse-event entries are presented by the three therapy groups, with separate counts for participants at risk and participants affected. Group A records 7 at risk and 2 affected; Group B records 3 at risk and 1 affected; Group C records 2 at risk and 0 affected. Death counts are not reported in the registry record. These are counts, not comparative estimates, and the record does not provide an inferential analysis or additional context for judging differences between groups.

The other adverse-event category records 7 at risk and 7 affected in Group A, 3 at risk and 3 affected in Group B, and 2 at risk and 2 affected in Group C. The registry’s category labels distinguish these entries from serious adverse events; they should not be combined or treated as equivalent severity measures. The record does not report event-level details for these category totals.

The listed top serious terms are Appendicitis at 33.3%, Skin cancer at 14.3%, and Axillary Abscess at 14.3%. These percentages are registry entries; the record does not explain their denominator or provide a complete event listing alongside them. The small group counts, non-randomized allocation and lack of reported analysis constrain comparisons. These figures describe what the registry records and do not by themselves establish causation or comparative safety.

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

The record documents a completed Phase 4 study intended to examine safety and efficacy of response-guided triple therapy for early chronic HCV infection. It specifies an SVR12 primary endpoint and three treatment-duration strategies tied to the timing of undetectable HCV RNA. Those details clarify the question the study set out to address.

The record does not report the primary endpoint result or any analysis. It therefore does not establish how many participants achieved SVR12, how precisely that outcome was estimated, or whether the three groups differed in their outcomes. It also does not establish that the treatment strategies were equivalent or that one duration was better than another. Absence of a result in the record is not evidence that the endpoint was not achieved; it means the registry record does not report the result.

The non-randomized allocation is central to what a group comparison could mean. The groups are defined by different HCV RNA response times and corresponding treatment schedules, and they are explicitly not a like-for-like control comparison. Any raw contrast would not by itself identify the effect of duration. The registry does not report an adjusted comparative analysis that might account for measured group differences.

Safety entries give counts by group and a short list of serious-event terms, but do not provide a full account of events, a causal assessment or comparative statistical analysis. The deaths field is not reported in the registry record. These entries should be read as registry descriptions rather than as proof that treatment caused or did not cause particular events.

In general, a study can inform a question only to the extent that its population, allocation, outcome measurement and analysis support the intended inference. Here, the population and treatment rules are described at a high level, while important details about analysis populations, missing outcomes and statistical methods are absent. The record supports a careful account of the study design and reported safety counts, but not a conclusion about efficacy or comparative treatment effects.

14. Why This Trial Matters Statistically

This study is statistically notable because it links treatment duration to an observed response: the timing of undetectable HCV RNA defines the groups and guides the intended total therapy duration. That structure raises a specific interpretive issue. A comparison of outcomes across groups would not simply compare durations among otherwise comparable participants, because response timing is also part of how the strategies are defined.

The registry explicitly marks the allocation as non-randomized and warns that the arms are not a like-for-like control comparison. This matters when interpreting any apparent difference: group contrasts can reflect who entered each group and when they responded, as well as the duration strategy. The causal question about treatment duration is therefore distinct from the descriptive question of what outcomes were recorded within each group.

The primary endpoint is clearly defined as a post-treatment HCV RNA outcome at 12 weeks. That clarity is useful for understanding what the study intended to measure. At the same time, the registry’s absence of outcome analyses means the definition cannot be paired with an estimate or uncertainty interval. A well-defined endpoint does not substitute for reporting its observed value, denominator and analysis method.

The record also illustrates why planning calculations and observed trial results must remain distinct. It describes assumptions for a sample-size planning illustration based on an observed effect, but does not report the resulting values or a trial-specific design justification. Such assumptions cannot be treated as evidence that the study had a particular power or that any treatment effect was detected. The registry’s completed status and enrollment count likewise do not reveal the precision of an unreported endpoint.

For biostatistical interpretation, the main contribution of the record is therefore methodological context: a response-guided, non-randomized design; a specified binary primary outcome; and safety counts reported for small group categories. It also demonstrates how missing analyses, unspecified denominators and absent missing-data methods constrain what can be concluded from a registry entry.

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 registry gives limited detail about participant eligibility and baseline characteristics. It identifies chronic hepatitis C and describes the infection as recently acquired or early chronic, but does not report a fuller population profile. Without such information, it is not possible to assess how similar participants were across the three groups or how broadly any unreported results might apply.

The treatment strategies are response-guided, and allocation is non-randomized. The timing of undetectable HCV RNA is part of each group definition, which makes the groups structurally different. The registry does not describe the allocation process in detail or report an adjusted analysis. Any comparative interpretation would therefore face potential selection and confounding concerns.

Important outcome-analysis information is absent. The record does not report SVR12 results, outcome denominators, confidence intervals, p-values, analysis populations, missing-data handling or sensitivity analyses. It records 15 outcome measures but does not report a multiplicity approach. The sample-size justification for the study itself is not reported in the registry record.

Safety reporting is also limited in this record. It gives group-level at-risk and affected counts, a few top serious-event terms and no reported death counts. The record does not give a complete event listing or explain the denominator used for the listed serious-event percentages. The relationship between the enrollment count and the adverse-event denominators is not explained in the registry record.

These limitations restrict interpretation of the registry entry; they do not show that analyses or additional information do not exist elsewhere. Based on this record, however, the observed primary outcome, its precision and comparative treatment effects cannot be assessed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: DAA Based Therapy for Recently Acquired Hepatitis C (DARE-C) — NCT01743521.
• Registry record last updated 2017-03-29; status last verified 2017-02.
• Results first posted 2016-10-20.
• 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

The registry record describes NCT01743521, DAA Based Therapy for Recently Acquired Hepatitis C (DARE-C), a Phase 4, parallel, non-randomized study sponsored by the Kirby Institute. It records enrollment of 14, a start date of 2013-01, primary completion in 2015-11 and completed status. The study’s stated purpose was to examine safety and efficacy of response-guided triple therapy with TPV/PEG-IFN/RBV.

Three response-guided schedules are described: 8 weeks of total therapy after undetectable HCV RNA at 2 weeks, 12 weeks after undetectable HCV RNA at 4 weeks, and 24 weeks after undetectable HCV RNA at 8 weeks, with the final schedule including 12 weeks of TPV/PEG-IFN/RBV and 12 weeks of PEG-IFN/RBV. The primary endpoint is SVR12, defined as negative qualitative HCV RNA 12 weeks after therapy completion.

The registry lists 15 outcome measures and records zero analyses. Primary and secondary outcome results, analysis methods, missing-data handling and the trial’s sample-size justification are not reported in the registry record. The adverse-event entries provide group counts and selected serious-event terms, but do not establish comparative safety.