This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation (NCT01938625), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01938625 |
| Phase | Phase 2 |
| Condition | Hepatitis C, Chronic |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 35 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Janssen R&D Ireland |
| Results posted | Yes |
2. Clinical Question
Population
Participants had recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. The primary analysis population was defined as enrolled participants who took at least 1 dose of investigational medication. Eligibility differed between the study parts: Part 1 included participants with Metavir fibrosis scores F1-F2, while Part 2 allowed scores F1-F4.
Intervention
The treatment regimen combined simeprevir, daclatasvir, and ribavirin. Participants also continued stable immunosuppressant therapy. The study description identifies cyclosporine or tacrolimus for Part 1 and tacrolimus for Part 2.
Comparator
The registry record does not describe a randomized control group or a like-for-like treatment comparator. Allocation was non-randomized, and the study was open-label. Comparisons between the immunosuppressant groups would therefore not be randomized comparisons.
Primary question
The primary endpoint was the percentage of participants achieving sustained virologic response 12 weeks after the end of treatment, assessed at Week 36. The registry describes SVR12 as HCV RNA less than 25 IU/mL, detectable or undetectable, at that follow-up point. The observed percentage and its 95% confidence interval are not reported in the registry record.
The study also aimed to evaluate pharmacokinetics of immunosuppressant therapy when given with simeprevir and daclatasvir. The brief summary specifies cyclosporine for Part 1 and tacrolimus, while the title and study description emphasize the antiviral regimen and post-transplant setting. Pharmacokinetic results are not reported in the registry record.
3. Trial Design
This was a Phase 2, open-label, non-randomized, parallel study. The registry lists enrollment of 35 participants and a completed status. It identifies Janssen R&D Ireland as the sponsor. The study began on 2013-12-12, and primary completion was recorded as 2015-04-27.
Participants received a combination regimen of simeprevir, daclatasvir, and ribavirin. The study was organized into two parts with different eligibility and immunosuppressant descriptions. Part 1 included participants with Metavir fibrosis scores F1-F2 who received stable cyclosporine or tacrolimus therapy alongside the antiviral combination. Part 2 included participants with scores F1-F4 and stable tacrolimus therapy. The registry record does not report how participants were assigned to the two parts.
Because allocation was non-randomized and masking was absent, the study does not provide a blinded randomized comparison of the listed groups. The two parts also differ in their fibrosis eligibility and immunosuppressant descriptions. Any contrast between those groups could reflect differences in who entered each part, rather than an isolated effect of the immunosuppressant or antiviral regimen.
The primary analysis set included enrolled participants who took at least 1 dose of investigational medication. The primary endpoint was the percentage achieving SVR12 at Week 36, with a 95% confidence interval specified as the measure of precision. The registry record does not report the primary estimate, the interval, or results for the pharmacokinetic objectives. It also does not report a sample-size justification or details of the procedures used to assign participants to study parts.
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: The study was conducted in 2 parts (part 1 and part 2) to sequentially enroll the participants. All analyses were conducted on the overall study population (part 1 and part 2 combined).
Overall Study
| Stage | Cyclosporine | Tacrolimus |
|---|---|---|
| STARTED | 10 | 25 |
| COMPLETED | 10 | 23 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Cyclosporine | Tacrolimus |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| Adverse Event | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) analysis set included all enrolled participants who took at least 1 dose of investigational medication.
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.
| Characteristic | Unit | Cyclosporine | Tacrolimus | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 25 | 35 | |
| Age, Continuous | years | 64.5 (52 to 69) | 61 (27 to 69) | 62 (27 to 69) |
| Sex: Female, Male: Female | Participants | 4 | 9 | 13 |
| Sex: Female, Male: Male | Participants | 6 | 16 | 22 |
| Region of Enrollment: Germany | Participants | 1 | 6 | 7 |
| Region of Enrollment: Spain | Participants | 3 | 9 | 12 |
| Region of Enrollment: Poland | Participants | 0 | 7 | 7 |
| Region of Enrollment: Italy | Participants | 6 | 3 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12), measured over Week 36.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with sustained virologic response 12 weeks after the end of treatment, assessed at Week 36. The registry defines achievement as HCV RNA less than 25 IU/mL, whether detectable or undetectable, at 12 weeks after treatment ended. The analysis population included enrolled participants who took at least 1 dose of investigational medication.
SVR12 is a virologic follow-up measure: it records whether the specified viral RNA threshold is met at a defined time after the treatment period. Reporting the endpoint as a percentage expresses the proportion of the analysis population meeting that definition. A 95% confidence interval is intended to convey uncertainty around that estimated proportion. It does not show the range of outcomes for individual participants.
The registry record does not report the observed percentage, the number of participants meeting the endpoint, or the 95% confidence interval. As a result, the posted record does not establish the precision of the primary estimate or allow its magnitude to be assessed. The endpoint definition and timeframe are reported, but the primary outcome result is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the question and endpoint but does not post the primary SVR12 result. It gives no observed percentage, event count, or 95% confidence interval for the primary endpoint. Consequently, the direction, magnitude, and precision of the primary outcome cannot be assessed from the registry record. The absence of a posted estimate is not evidence that the outcome was zero or that participants failed to meet the endpoint.
The study enrolled 35 participants, and the analysis population was defined as enrolled participants who took at least 1 dose of investigational medication. Enrollment alone does not reveal how many participants were included in the endpoint analysis, how many had outcome data, or how missing outcome measurements were handled. Those details are not reported in the registry record.
The design also limits comparisons. Allocation was non-randomized and the study was open-label, with no described randomized control group. The study parts had different fibrosis eligibility and different immunosuppressant descriptions. Therefore, the registry record does not support interpreting any contrast between the cyclosporine and tacrolimus groups as a randomized treatment effect. Group membership may be associated with other differences, and the record does not report an adjustment strategy that could address them.
Serious adverse event figures are reported separately for the cyclosporine and tacrolimus groups. The record lists 4 affected participants among 10 at risk in the cyclosporine group and 4 among 25 at risk in the tacrolimus group. These are descriptive counts in groups that were not randomized to a like-for-like comparison. They do not, on their own, establish that one immunosuppressant group had a higher or lower risk attributable to treatment. The deaths field has no reported count.
The registry lists secondary outcomes covering SVR at other follow-up times, HCV RNA measures, on-treatment failure, viral breakthrough, and viral relapse. Their numerical results are not reported in the registry record. Thus, the record supports a description of planned outcome domains, but not an evaluation of their observed frequencies or their relationship to the primary endpoint.
Overall, the posted information is most useful for understanding the study population, treatment context, endpoint definition, and reported adverse-event counts. It does not provide the outcome estimates needed to judge the observed virologic response or its statistical precision. A conclusion about efficacy, comparative effects, or the statistical strength of the primary result would go beyond what is reported.
9. Statistical Methods Explained
What does a percentage endpoint represent?
For a binary outcome such as achieving SVR12, each participant is classified according to whether the endpoint definition was met. The percentage expresses the share of the analysis population classified as having the outcome. This is a general explanation of binary endpoints; it does not supply an unreported result for this study. The registry record specifies the population definition and endpoint criteria but does not report the number meeting the endpoint or the resulting percentage.
What does a confidence interval add?
A confidence interval describes statistical uncertainty around an estimated quantity. For a percentage endpoint, it helps readers understand how precisely the observed proportion is estimated, given the data and the method used to construct the interval. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. A confidence interval is not a range containing a specified share of individual participant outcomes, and it does not by itself establish that an effect is clinically important. The primary endpoint lists a 95% confidence interval, but the interval itself is not reported in the registry record.
Why does the allocation method matter?
Random allocation is a method for creating comparison groups in a way that reduces systematic differences at the start of a study. In this trial, allocation is listed as non-randomized, and masking is listed as absent. The registry also describes two parts with different fibrosis eligibility and immunosuppressant regimens. Consequently, a comparison between the groups could reflect differences in participant characteristics, study-part eligibility, or other factors, as well as any treatment-related difference. The record does not describe a randomized comparison or an adjustment method for such differences.
Open-label means the study is not masked. As a general matter, knowledge of treatment can affect some study processes, such as participant reporting or investigator assessments, depending on the outcome and how it is measured. SVR12 is defined by an HCV RNA measurement, but the registry does not report laboratory procedures, assessment safeguards, or other details that would permit further evaluation of measurement processes.
How should the analysis population be understood?
The primary analysis set included all enrolled participants who took at least 1 dose of investigational medication. This definition is reported in the registry. It does not establish how participants without an endpoint measurement were treated in the analysis. The handling of missing outcome data, withdrawals, and other departures from the planned follow-up is not reported in the registry record. As a general statistical principle, the analysis population and missing-data rules affect which participants contribute to an estimate and how that estimate should be interpreted.
What can be inferred from the adverse-event counts?
The serious adverse-event information is presented as counts of affected participants and participants at risk for each immunosuppressant group. These counts describe what the registry reports for those groups. They are not a randomized comparison, and the record does not provide a comparative statistical analysis. General statistical interpretation also depends on the event definitions, observation period, and completeness of reporting; these details are not reported in the registry record.
What is known about the statistical plan?
The registry identifies a percentage endpoint and a 95% confidence interval, but the statistical methods used to calculate the interval are not reported in the registry record. Details such as the exact estimator, handling of missing outcomes, covariate adjustment, and any planned sensitivity analyses are not reported. The registry lists no analyses in the record. Interim analyses and a broader statistical analysis plan are not reported in the registry record.
General statistical practice distinguishes an estimate from the planning assumptions used to design a study. A sample-size justification explains how enrollment targets may have been selected; it is not an outcome result. The sample-size justification is not reported in the registry record. Any planning illustration is not observed power and cannot replace the actual endpoint estimate and its uncertainty. Since the primary result is absent, the observed effect needed to interpret an illustration based on that effect is also not reported in the registry record.
Multiplicity refers to the statistical issue that arises when several hypotheses or outcomes are assessed. Without an analysis plan, it is not possible to determine whether any formal adjustment was planned or how the primary and secondary outcomes were prioritized analytically. The registry names the primary endpoint and lists secondary outcome domains, but a multiplicity strategy is not reported in the registry record. This limits what can be said about confirmatory interpretation across outcomes.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Cyclosporine | 10 | 10 | 100.0% | 69.2% to 100.0% | 72.2% to 100.0% | 71.5% to 99.8% |
| Tacrolimus | 25 | 22 | 88.0% | 68.8% to 97.5% | 70.0% to 95.8% | 69.8% to 95.6% |
R code and output
arm <- c("Cyclosporine", "Tacrolimus")
n <- c(10, 25)
events <- c(10, 22)
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 Cyclosporine 10 10 100.0 69.2 100.0 72.2 100.0 71.5 99.8
ARM Tacrolimus 25 22 88.0 68.8 97.5 70.0 95.8 69.8 95.611. Multiplicity, Missing Data and Analysis Populations
The registry identifies SVR12 as the primary outcome and lists secondary outcomes covering SVR at other follow-up times, HCV RNA thresholds, on-treatment failure, viral breakthrough, and viral relapse. It does not report a multiplicity procedure. In general, multiplicity matters when several outcomes or hypotheses are evaluated because repeated testing can affect the interpretation of nominal statistical evidence. Whether any such adjustment was planned or used is not reported in the registry record.
The primary analysis population included enrolled participants who took at least 1 dose of investigational medication. The record does not explain how missing Week 36 measurements, withdrawal, or other incomplete follow-up were handled. It also does not report the number analyzed for the primary endpoint or the number with missing outcome data. These omissions make it difficult to assess how the endpoint estimate might depend on participant follow-up and analysis choices.
The registry lists no analyses in the record. A complete statistical analysis plan, interim analyses, sensitivity analyses, and a sample-size justification are not reported in the registry record. The primary estimate and confidence interval are also absent. Therefore, it is not possible to assess the planned inferential approach, the implementation of the analysis population, or the robustness of the result to alternative assumptions about missing data.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Cyclosporine | 4 | 10 | 40.0% |
| Tacrolimus | 4 | 25 | 16.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cyclosporine | 10 of 10 |
| Tacrolimus | 23 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Cyclosporine | Tacrolimus |
|---|---|---|---|
| Pyrexia | General disorders | 3 of 10 | 0 of 25 |
| Anaemia | Blood and lymphatic system disorders | 0 of 10 | 1 of 25 |
| Abdominal Pain Upper | Gastrointestinal disorders | 0 of 10 | 1 of 25 |
| Diarrhoea | Gastrointestinal disorders | 1 of 10 | 0 of 25 |
| Vomiting | Gastrointestinal disorders | 0 of 10 | 1 of 25 |
| Hyperbilirubinaemia | Hepatobiliary disorders | 0 of 10 | 1 of 25 |
| Escherichia Urinary Tract Infection | Infections and infestations | 1 of 10 | 0 of 25 |
| Genital Herpes | Infections and infestations | 1 of 10 | 0 of 25 |
| Pneumonia | Infections and infestations | 0 of 10 | 1 of 25 |
| Urinary Tract Infection | Infections and infestations | 0 of 10 | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cyclosporine | Tacrolimus |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 7 of 10 | 11 of 25 |
| Asthenia | General disorders | 5 of 10 | 7 of 25 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 10 | 5 of 25 |
| Headache | Nervous system disorders | 1 of 10 | 4 of 25 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 10 | 3 of 25 |
| Diarrhoea | Gastrointestinal disorders | 1 of 10 | 3 of 25 |
| Nausea | Gastrointestinal disorders | 1 of 10 | 3 of 25 |
| Hyperbilirubinaemia | Hepatobiliary disorders | 2 of 10 | 2 of 25 |
| Photosensitivity Reaction | Skin and subcutaneous tissue disorders | 1 of 10 | 3 of 25 |
| Vertigo | Ear and labyrinth disorders | 0 of 10 | 3 of 25 |
Serious events with the highest arm-level rate: pyrexia (30.0%), diarrhoea (10.0%), escherichia urinary tract infection (10.0%), genital herpes (10.0%), facial bones fracture (10.0%).
The registry reports serious adverse-event counts by immunosuppressant group. In the cyclosporine group, 4 participants were affected among 10 at risk. In the tacrolimus group, 4 participants were affected among 25 at risk. These figures describe the counts recorded for each group; they do not establish a causal difference between the groups.
The study was non-randomized, open-label, and divided into parts with different eligibility and immunosuppressant descriptions. The groups should therefore not be read as equivalent comparison arms. The registry also lists serious adverse-event terms with percentages: Pyrexia, 30.0%; Diarrhoea, 10.0%; Escherichia Urinary Tract Infection, 10.0%; Genital Herpes, 10.0%; Facial Bones Fracture, 10.0%; and Syncope, 10.0%. The record does not provide further context for interpreting these term-level percentages, including their group-specific distribution.
Death counts are not reported in the registry record. The serious adverse-event figures should be read as descriptive safety reporting, not as proof that an event was caused by a particular drug or that the groups differ in risk.
13. What the Result Does, and Does Not, Mean
The record establishes that a Phase 2 study was conducted in participants with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. It describes a regimen containing simeprevir, daclatasvir, and ribavirin, and defines SVR12 as the primary endpoint at Week 36. It also describes the planned pharmacokinetic question involving immunosuppressant therapy and lists secondary virologic and failure outcomes.
However, the registry record does not report the primary SVR12 estimate, its confidence interval, or the numerical results for the listed secondary outcomes. It therefore cannot show how many participants achieved the primary endpoint, how precise an estimated response was, or how outcomes varied across the study parts. The absence of posted results does not establish that the regimen succeeded or failed.
The safety record provides serious adverse-event counts by group and a list of serious event terms with percentages. Those entries are descriptive. Because the study was not randomized and the groups had different study-part characteristics, they do not establish comparative safety effects or causation. The record does not report deaths.
More broadly, a trial design and an endpoint definition answer different questions from an outcome estimate. The design describes who was studied and how treatment was organized; the endpoint specifies what was measured. An estimate and its uncertainty are needed to assess the observed outcome. For this trial, those primary statistical results are not reported in the registry record, so conclusions about the magnitude or precision of the response cannot be drawn from the posted information.
14. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between a clearly specified endpoint and an absent endpoint result. The record defines SVR12, identifies the analysis population, and specifies a 95% confidence interval, but does not report the observed percentage or interval. This illustrates why endpoint definitions alone do not permit evaluation of an outcome: the estimate and its uncertainty are also needed.
The non-randomized design is important when reading the two immunosuppressant groups. Their descriptions are embedded in study parts with different fibrosis eligibility, and the record does not describe random assignment. As a general principle, group contrasts in such a design may reflect differences in participant selection or other characteristics, rather than an isolated treatment effect. The posted serious adverse-event counts should be interpreted in that descriptive context.
The study also raises familiar reporting questions about analysis populations, missing outcome data, and multiplicity. The registry defines who was eligible for the primary analysis but does not report how missing endpoint measurements were handled. It lists several secondary outcome domains but does not report a multiplicity strategy. These omissions constrain assessment of how results would be analyzed and how strongly they could support inferential claims.
For clinical research readers, the record therefore offers useful design and measurement details while leaving key statistical results unavailable. Keeping those categories separate—design, endpoint definition, and observed evidence—helps avoid treating a study objective as though it were a finding.
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 for interpreting this trial from the registry record is that numerical results for the primary endpoint are not reported. The observed SVR12 percentage, the number achieving SVR12, and the 95% confidence interval are not reported in the registry record. Numerical findings for the listed secondary outcomes are also not reported.
The study was non-randomized and open-label, and the registry does not describe a like-for-like control comparison. The two study parts differ in fibrosis eligibility and immunosuppressant descriptions. The method used to assign participants to parts and any strategy for addressing differences between groups are not reported in the registry record.
The primary analysis set is defined as enrolled participants who took at least 1 dose of investigational medication, but the record does not report the number contributing endpoint data, the extent of missing follow-up, or how missing values were handled. The statistical method for calculating the confidence interval, any covariate adjustment, and sensitivity analyses are not reported. A statistical analysis plan, interim analyses, multiplicity handling, and sample-size justification are also not reported in the registry record.
For safety, the record gives serious adverse-event counts by group and lists event terms with percentages, but it does not provide a randomized comparison or report deaths. These entries cannot establish causation or comparative effects. The absence of further detail limits interpretation of the safety summaries.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation — NCT01938625.
- Registry record last updated 2018-11-21; status last verified 2018-11.
- Results first posted 2018-11-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry record describes a completed Phase 2, open-label, non-randomized, parallel study with enrollment of 35 participants. The study involved simeprevir, daclatasvir, and ribavirin in participants with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. Stable immunosuppressant therapy differed by study part.
The primary endpoint was the percentage achieving SVR12 at Week 36, defined by HCV RNA less than 25 IU/mL, detectable or undetectable. A 95% confidence interval was specified. The primary result and numerical findings for the secondary outcomes are not reported in the registry record. The record also does not report a sample-size justification or detailed statistical analysis plan.
Serious adverse-event counts are reported for the cyclosporine and tacrolimus groups, along with a list of serious event terms and percentages. Death counts are not reported in the registry record. Given the non-randomized design and differences between study parts, the group figures are descriptive rather than a like-for-like comparison.