Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C (NCT01821625), a na phase 2, phase 3 study. The primary outcome is Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines..

2. Clinical Question

In statistical terms, the registered question is whether the planned combination could be administered through the prescribed course in this patient group. The record does not establish a comparative question about what would have happened without eltrombopag, because it has no control arm. Nor does completion alone establish antiviral benefit: treatment completion and viral response are different outcomes. The registry record does not report a formal analysis testing a hypothesis about either outcome.

3. Trial Design

This is a single-group study listed as phase 2 and phase 3. Allocation is recorded as not applicable, and masking is recorded as none. The registry record reports enrollment of 7 participants and describes all study patients as undergoing the intervention. There is no randomized or concurrently controlled comparison in the design information.

The intervention description combines eltrombopag with antiviral triple therapy using interferon, ribavirin and boceprevir. Eltrombopag is described as a lead-in treatment alongside the antiviral regimen. The study’s stated rationale is that supporting platelet counts might permit the initiation and completion of antiviral therapy in chronic hepatitis C patients with low platelets. This is the investigators’ hypothesis, not a result established by the posted data.

The registry record gives a start date of 2013-04 and a primary completion date of 2015-04, and lists the study status as terminated. It does not report why the study was terminated, so no conclusion about the reason or its effect on the results can be drawn from the record. The length of therapy could depend on liver disease status, antiviral response and treatment tolerance. The described minimum full course is 30 weeks, with a maximum of 56 weeks; the primary endpoint timeframe is up to 56 weeks.

With no control group, observed outcomes can describe what happened among the enrolled participants, but they cannot by themselves distinguish the effects of eltrombopag from those of the antivirals, participant characteristics, or other influences. The record does not report a protocol, detailed eligibility criteria, or a statistical analysis plan. Those omissions limit assessment of how the study was intended to handle treatment decisions, follow-up and analysis.

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:

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 Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines., measured over Up to 56 weeks.

The primary endpoint is the count of study participants who completed antiviral therapy according to boceprevir prescribing guidelines. It is a binary participant-level outcome in the sense that each participant either met the completion criterion or did not. The registry record sets the assessment timeframe as up to 56 weeks and explains that treatment length could depend on liver disease status, antiviral response and tolerance.

Completion is a practical endpoint for a regimen whose duration can vary. It captures whether a patient reached the end of the prescribed course, rather than simply whether treatment was started. That makes it relevant to the study’s stated aim of enabling antiviral treatment in people with low platelet counts. However, completion is not the same as viral clearance or sustained response. The registry record notes that one patient completed therapy and experienced a sustained viral response, but this does not turn the primary endpoint into a virologic endpoint.

The posted description does not provide a completion count for all participants or an endpoint analysis. It therefore does not support a calculated completion rate or a precise estimate of the probability of completion. It also does not report a formal definition of how the prescribing guidelines were operationalized for analysis beyond the endpoint wording.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a single-group design and reports a binary primary outcome: whether a participant completed therapy according to the stated guidelines. The outcome is expressed as a count of participants. The record does not report an analysis method, an estimate of the completion probability, a confidence interval or a hypothesis test. The explanation below describes general statistical principles relevant to reading this kind of outcome; it does not imply that these methods were used in the study.

What does a binary endpoint represent?

In general, a binary endpoint classifies each participant into one of two outcome states, such as completion or non-completion. A count records how many participants fall into a state, while a rate or proportion places that count in relation to the number whose endpoint status is known. Counts alone do not fully describe a rate unless the relevant denominator and handling of participants without known status are clear. The registry record does not provide a complete endpoint-status breakdown for all enrolled participants, so a completion rate should not be inferred from the reported statement about one patient.

Why does a single-group design matter?

In general, an outcome observed in one group describes that group under its study conditions. A control group helps estimate how outcomes differ under an alternative strategy, subject to the design and analysis assumptions. Without such a group, the observed outcome cannot isolate the contribution of one treatment component from the other components or from changes that might have occurred for other reasons. Here, eltrombopag was combined with antiviral therapy, and the record describes no separate comparison arm. This means the posted outcome is descriptive rather than a treatment-effect estimate.

How should uncertainty be considered?

In general, a confidence interval expresses the range of effect or outcome values compatible with the observed data under a specified statistical model. Wider intervals indicate less precision. For a small study, an observed count may be compatible with a broad range of underlying event probabilities, so a count should not be treated as a precise estimate. The registry record does not report a confidence interval for completion or for the safety outcomes. No interval should be presumed from the counts alone.

A p-value, when used, summarizes how unusual data would be under a specified null hypothesis and model; it is not the probability that a treatment works, nor does it measure the size or practical importance of an effect. The record lists no analyses and no p-values. There is no reported inferential comparison to interpret, and the single-group design would not supply a randomized between-group contrast in any case.

What do the planning assumptions mean?

General planning calculations translate a chosen effect size and statistical assumptions into an illustrative sample size. Such calculations depend on the endpoint, allocation, significance level, power target, and the effect assumed for planning. The planning assumptions described for the calculation use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. Those assumptions do not match the registry’s single-group design. Any resulting two-arm planning illustration should therefore be read as a hypothetical planning exercise, not as a description of this study’s design or evidence.

Sample-size illustrations based on an observed effect are especially sensitive when the observed experience is sparse. They are not observed power, do not show that the study had a particular probability of detecting an effect, and do not repair the absence of a control group. The registry record does not report that these assumptions were used to plan the trial, nor does it report the trial’s own sample-size justification.

What information would support an analysis?

For a complete binary endpoint analysis, readers would need a clearly defined analysis population, endpoint status for each participant or adequate aggregate counts, and a stated approach to participants whose status is unknown. The registry record does not report the analysis population or missing-data handling. It also does not give the number of analyses, beyond listing no analyses in the record. These omissions prevent assessment of the endpoint calculation, uncertainty, or any adjustment for multiple testing. The available counts can be reported as posted, but they do not support reconstructing an unreported analysis.

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("Thrombocytopenic (Low Platelet) Patients")
n      <- c(7)
events <- c(1)
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  Thrombocytopenic (Low Platelet) Patients  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no analyses. It does not report a statistical analysis plan, a multiplicity procedure, or whether additional outcomes were assessed but not registered in this record. With no reported inferential analyses, there is no described family of tests or adjustment strategy to evaluate. The presence of a single listed primary endpoint does not establish that only one outcome was considered during the study.

Missing-data handling is not reported in the registry record. The primary outcome is described as a count of participants completing therapy, but the record does not give endpoint status for all enrolled participants or explain how incomplete follow-up, treatment discontinuation, or unknown status would be handled. The analysis population is also not reported. Consequently, the denominator and the treatment of participants without a known endpoint cannot be assessed from the posted information.

These gaps matter because a completion count can be interpreted only in relation to who was assessed and how unknown outcomes were classified. If participants with incomplete follow-up differ from those with observed outcomes, an analysis that excludes them could describe a selected subset. That is a general concern, not a claim about what happened in this study. The registry record does not provide enough information to determine whether missingness occurred or whether it affected the reported outcome.

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 3% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports serious adverse events for the thrombocytopenic patient group as 0 affected among 7 at risk. It reports other adverse events as 3 affected among 7 at risk, and deaths as 0. These are counts, not percentages or comparative risks. The record lists no top serious adverse-event terms.

Serious adverse events and other adverse events are separate categories in the posted safety information; the counts should not be combined. The registry record does not report detailed event definitions, event-level descriptions, attribution to study drugs, or the safety observation period. Therefore, the counts do not show whether an event was judged related to eltrombopag or to the antiviral regimen.

Zero recorded serious adverse events does not prove that serious events are impossible or that risk is absent. Likewise, the count of other adverse events does not by itself establish cause. Because the group is small and there is no control arm, these figures are descriptive of what the record reports, rather than a comparative safety estimate.

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

The posted record describes a study of eltrombopag added to antiviral therapy in chronic hepatitis C patients with low platelet counts. It reports a primary endpoint focused on completion of therapy and states that one patient completed treatment and experienced a sustained viral response. The safety record reports no serious adverse events among those listed at risk, three participants with other adverse events, and no deaths. These statements describe the posted information; they are not estimates of comparative treatment effects.

The information does not establish that eltrombopag enabled treatment completion, because there is no control group and the record does not report a complete endpoint breakdown. It also does not establish that the regimen caused or prevented adverse events. Completion is not equivalent to sustained viral response, and the one reported case should not be generalized to all participants or other patients.

The record does not report a statistical analysis, uncertainty interval, missing-data method, analysis population, or reason for termination. It therefore cannot show how precise the endpoint findings are or whether the outcome information is complete. The planning assumptions described for hypothetical sample-size illustrations do not supply evidence about treatment effects and should not be mistaken for an analysis of the study’s results.

The defensible reading is narrow: this was a terminated single-group study with enrollment of 7 participants, limited posted outcome information, and descriptive safety counts. A causal comparison, a precise completion probability, and a broader conclusion about antiviral response or safety are not supported by the registry record.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between a clinically motivated hypothesis and evidence capable of testing that hypothesis. The investigators proposed that eltrombopag might permit antiviral therapy in patients with low platelets. The registered design has one group and no control arm, so the outcomes can describe the enrolled participants but cannot estimate what would have happened under an alternative treatment strategy.

The endpoint also highlights the difference between treatment process and treatment response. Completing antiviral therapy is a meaningful measure of whether a course was carried through, while sustained viral response is a separate virologic outcome. The record mentions one patient with both completion and sustained response, but it does not report a full outcome analysis. Keeping these endpoints distinct avoids treating completion as proof of antiviral response.

The small enrollment and limited reporting make precision central to interpretation. Counts are important, but without complete outcome status and an uncertainty estimate they do not show how narrowly the results characterize the population. Likewise, zero recorded serious adverse events is a description of the observed record, not evidence that such events cannot occur.

Finally, hypothetical sample-size planning assumptions should be matched to the design they describe. Assumptions about equal allocation between two arms do not reflect the registry’s single-group structure. This example underscores why readers should distinguish planning calculations from observed results, and why design, endpoint definition, follow-up and analysis reporting all shape what conclusions are justified.

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 record reports a single-group design, enrollment of 7 participants and study termination, but does not give a reason for termination. The absence of a comparator limits interpretation to descriptive experience and prevents a direct estimate of the effect of adding eltrombopag to antiviral therapy. The registry record also does not report the detailed eligibility criteria, participant characteristics, or the distribution of platelet counts, so the enrolled group cannot be characterized further from the posted information.

Outcome reporting is limited. The record identifies a completion endpoint and states that one patient completed therapy and experienced a sustained viral response, but it does not provide a complete endpoint count, the status of every participant, or an uncertainty interval. The record lists no analyses and does not describe the analysis population, missing-data methods, or a statistical plan. The reason for termination and its implications for follow-up are also not reported.

Safety information is similarly brief: the record gives aggregate counts but no event descriptions, attribution, detailed definitions or observation period. These limitations mean the safety counts cannot establish whether events were related to treatment or permit a comparative risk assessment. Together, the single-group design, small enrollment and limited outcome and safety details constrain both precision and causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C — NCT01821625.
• Registry record last updated 2019-11-13; status last verified 2019-10.
• Results first posted 2019-10-22.
• 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 NCT01821625, a phase 2 and phase 3 single-group study of eltrombopag with antiviral triple therapy for chronic hepatitis C patients with low platelet counts. It reports enrollment of 7 participants, no masking, and a terminated status. The primary endpoint is the count of participants completing antiviral therapy according to boceprevir prescribing guidelines, with a timeframe of up to 56 weeks.

The outcome description states that one patient completed therapy and experienced a sustained viral response. Safety counts report 0 serious adverse events among 7 at risk, 3 participants with other adverse events among 7 at risk, and 0 deaths. The registry record lists no analyses and does not report a control group, missing-data approach, statistical analysis plan, or reason for termination. The findings are therefore limited to descriptive information, without a comparative treatment-effect estimate.