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 Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin in Participants With Chronic Hepatitis C Who Failed Prior Direct-Acting Antiviral Therapy (MK-5172-048) (NCT02105454), a na phase 2 study. The primary outcome is Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02105454 |
| Phase | Phase 2 |
| Condition | Hepatitis C Virus |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 79 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants had chronic hepatitis C virus infection, genotype 1, and had failed prior direct-acting antiviral therapy. The primary endpoint was defined for a per-protocol population, which excludes participants with important protocol deviations that may substantially affect the efficacy endpoints. The registry record does not report the number included in that population or further details about the participants who contributed to the primary endpoint.
Intervention
Participants received grazoprevir 100 mg once per day, elbasvir 50 mg once per day, and ribavirin 800 - 1400 mg total daily dose divided twice per day based on body weight, for 12 weeks. The study evaluated this combination regimen; the registry record does not describe a comparison of different doses or treatment durations.
Comparator
This was a single-group study. The registry record does not report a concurrent placebo group, usual-care group, or active-comparator group. Consequently, the posted results cannot make a randomized, like-for-like comparison between the combination regimen and another treatment.
Primary question
The primary question was what percentage of participants achieved sustained virologic response 12 weeks after the end of all study therapy. SVR12 required HCV RNA below the limit of quantification, <15 IU/mL in plasma, whether target was detected but unquantifiable or undetectable. The primary endpoint timeframe was up to 24 weeks.
The trial is registered as NCT02105454 and is listed as completed. It enrolled 79 participants. The primary endpoint concerns a virologic measurement after treatment, rather than a comparison of outcomes between assigned groups. The registry record does not report the SVR12 percentage or its confidence interval, so the primary question cannot be answered from the outcome information recorded there.
3. Trial Design
NCT02105454 is a Phase II trial of grazoprevir, elbasvir and ribavirin in participants with chronic hepatitis C who failed prior direct-acting antiviral therapy. The registry record describes the study as single-group, with allocation listed as NA and masking listed as none. It is not a randomized comparison and does not include a like-for-like control group in the posted design.
The listed regimen was grazoprevir 100 mg once per day, elbasvir 50 mg once per day, and ribavirin 800 - 1400 mg total daily dose divided twice per day based on body weight, for 12 weeks. The listed population was participants with HCV genotype 1 who had failed prior direct-acting antiviral therapy. Enrollment was 79. The registry record does not state how many enrolled participants were included in the per-protocol analysis.
The study start date is 2014-05-23, and the primary completion date is 2015-05-04. Its status is completed. The primary endpoint was the percentage achieving SVR12, defined using HCV RNA measurement 12 weeks after the end of all study therapy. The stated endpoint timeframe was up to 24 weeks. A secondary outcome concerned SVR12 by prior direct-acting antiviral therapy.
The registry record lists four outcome measures and no posted analyses. It does not report a statistical analysis plan, a sample-size justification for the trial design, or whether interim analyses were conducted. The sample-size planning assumptions described for the planning illustration should not be read as evidence of the trial's original design or analysis plan.
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: Following 12 weeks of treatment with grazoprevir (GZR), elbasvir (EBR) and ribavirin (RBV), participants were followed-up for an additional 24 weeks.
Overall Study
| Stage | GZR 100 mg + EBR 50 mg + RBV for 12 Weeks |
|---|---|
| STARTED | 79 |
| COMPLETED | 78 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | GZR 100 mg + EBR 50 mg + RBV for 12 Weeks |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
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 | GZR 100 mg + EBR 50 mg + RBV for 12 Weeks |
|---|---|---|
| Participants analysed | 79 | |
| Age, Continuous | Years | 54.4 (SD 9.6) |
| Sex: Female, Male: Female | Participants | 33 |
| Sex: Female, Male: Male | Participants | 46 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12), measured over Up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants achieving sustained virologic response 12 weeks after the end of all study therapy, abbreviated SVR12. The registry definition requires HCV RNA below the limit of quantification, <15 IU/mL in plasma. It includes either a detected but unquantifiable target or an undetectable result. The primary endpoint is defined for the per-protocol population and has a stated timeframe of up to 24 weeks.
As a general statistical concept, an endpoint needs a prespecified definition so that observations can be classified consistently. SVR12 uses a laboratory threshold and a specified time after therapy; it is therefore distinct from measuring HCV RNA while participants are receiving treatment. The percentage expresses the share of the analysis population meeting the endpoint, while its 95% confidence interval describes uncertainty around that estimated percentage.
The registry record does not report the endpoint percentage or confidence interval. It also does not report the number of participants with an evaluable SVR12 result. The endpoint definition is available, but its result and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies SVR12 as the primary endpoint, but it does not report the observed SVR12 percentage, its 95% confidence interval, or the number of participants contributing to that result. The primary efficacy finding therefore cannot be described from this record. Enrollment of 79 is not a substitute for the per-protocol denominator: the endpoint population excludes participants with important protocol deviations, and the analyzed count is not reported.
This distinction matters because an endpoint definition and a result are different kinds of information. Knowing that SVR12 was defined using HCV RNA below <15 IU/mL does not show how many participants met that definition. Without the observed percentage, there is no basis in the registry record for describing the magnitude of the result. Without a confidence interval, its statistical precision also cannot be assessed.
In general, a confidence interval indicates a range of values compatible with the observed data under the method used to calculate it. A narrower interval usually indicates greater precision than a wider interval, but neither width nor coverage can be assessed because the endpoint interval is not reported. The registry record also provides no primary-endpoint p-value or analysis output. No inferential claim about the endpoint can be reconstructed from the definition alone.
The design places an additional boundary on interpretation. This was a single-group study with no reported concurrent comparator. Any observed SVR12 percentage, if available elsewhere, would describe the outcome in the analyzed group; it would not by itself estimate a contrast against another treatment. Differences in participant characteristics, clinical setting, or other factors cannot be controlled through a randomized comparison in this design. The registry record does not report an adjusted comparison or a causal effect estimate.
The record lists 79 enrolled participants, four outcome measures, and no posted analyses. It separately reports safety counts for the treatment group. Those safety counts do not fill the gap in the primary efficacy result: adverse-event figures and SVR12 answer different questions. The registry record does not establish how the missing primary result relates to the safety population or whether the analysis population differs from the participants at risk for adverse events.
Planning calculations are also not efficacy findings. The described planning illustration uses an effect fraction and assumptions for a two-arm design, while this trial is single-group. Such calculations are planning illustrations, not observed power, and they do not establish what the trial found. Because the registry record does not report the observed SVR12 result, a reader should not treat planning assumptions or safety counts as evidence of the primary endpoint outcome.
9. Statistical Methods Explained
The registry record describes a percentage endpoint with a 95% confidence interval and identifies the per-protocol population. It does not report the method used to calculate the interval, the observed percentage, the endpoint denominator, or an inferential analysis. The explanations below distinguish general statistical concepts from methods documented for this particular study.
What does a percentage endpoint represent?
For a binary endpoint, each participant in the analysis population is classified according to whether the defined event occurred. The percentage is a summary of the participants who meet the endpoint relative to those included in that analysis. In this trial, the event is achieving SVR12 under the stated HCV RNA definition. The registry record does not state the number meeting that definition or the number assessed in the per-protocol population, so no endpoint percentage can be interpreted from the recorded information.
As a general concept, the denominator is essential to interpreting a percentage. A percentage based on a smaller analysis population can have different precision from the same percentage based on a larger one. Enrollment is not necessarily the analysis denominator, particularly when the endpoint is defined in a per-protocol population. Here, 79 participants were enrolled, but the per-protocol endpoint denominator is not reported. It would be inappropriate to substitute enrollment for that missing denominator.
What does a 95% confidence interval convey?
A confidence interval communicates uncertainty around an estimate under the statistical procedure used to construct it. In general, it helps readers distinguish a precisely estimated percentage from one with substantial uncertainty. The confidence level describes a property of the interval procedure over repeated use; it does not mean that a particular observed interval contains the true value with a probability assigned after seeing the data. The registry record identifies 95% confidence intervals as the endpoint's dispersion measure but does not provide the interval or state its calculation method.
Different statistical procedures can produce different intervals, especially when data are sparse or percentages are near the boundaries of their possible range. Since the registry record does not name the procedure or post the interval, it is not possible to assess whether the method suits the observed data or to reproduce the result. No alternative interval should be inferred from the endpoint description.
What is established about the analysis population?
The primary endpoint is specified for the per-protocol population. The record defines this population as excluding participants with important deviations from the protocol that may substantially affect the primary and key secondary efficacy endpoints. That description identifies a general selection principle, but it does not list the deviations, state how exclusions were adjudicated, or give the resulting analysis count. The registry record does not report whether a separate intention-to-treat analysis was performed.
As a general matter, per-protocol analyses can answer a question about outcomes among participants retained under the protocol's analysis rules. Exclusion can also affect how representative the analyzed group is of everyone who entered a study. Assessing that possibility requires details about exclusions and outcomes for participants omitted from the analysis, which are not reported in the registry record.
How should the planning illustration be understood?
The described planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes effects to detect as stated fractions of the observed effect. These assumptions characterize a planning calculation; they are not reported as the trial's own design justification or statistical analysis plan. The trial itself is single-group, so the two-arm assumptions do not describe its registered treatment allocation.
As a general concept, a sample-size calculation estimates the number of participants that would be needed under stated assumptions for a planned comparison. It depends on the assumed effect, variability or event rate, significance level, allocation, and analysis method. A calculation based on an observed effect is a retrospective planning illustration, not evidence that the trial was designed around that effect. Sample-size illustrations are not observed power and do not establish whether the trial's result is statistically persuasive.
The registry record does not report the numerical planning outputs or the observed primary effect needed to interpret them. The illustration's assumptions should not be converted into a claim about the trial's actual design, actual analysis, or primary result.
What can be inferred from the analysis record?
The record lists four outcome measures and no posted analyses. That means the registry information does not provide analysis results to inspect; it does not establish that no analyses were carried out outside the registry. It also does not report the statistical model, the approach to missing endpoint measurements, or any multiplicity procedure. General methods cannot be attributed to this study without documentation. The endpoint definition, population description, and confidence-interval label are useful design information, but they do not replace numerical findings or a statistical analysis plan.
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 |
|---|---|---|---|---|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | 70 | 68 | 97.1% | 90.1% to 99.7% | 90.2% to 99.2% | 90.2% to 99.1% |
R code and output
arm <- c("GZR 100 mg + EBR 50 mg + RBV for 12 Weeks")
n <- c(70)
events <- c(68)
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 GZR 100 mg + EBR 50 mg + RBV for 12 Weeks 70 68 97.1 90.1 99.7 90.2 99.2 90.2 99.111. Multiplicity, Missing Data and Analysis Populations
The registry record lists four outcome measures, including the primary SVR12 endpoint and a secondary outcome concerning SVR12 by prior direct-acting antiviral therapy. It does not report a multiplicity adjustment, a hierarchy for testing endpoints, or a statistical analysis plan. Whether the analyses were intended to support confirmatory claims, and how any multiple testing was to be handled, is not reported in the registry record.
As a general statistical concept, evaluating multiple outcomes or subgroups can increase the chance of finding an apparently notable result by chance if each is tested separately. Prespecified testing strategies can address that issue, but no such strategy is described in the registry record. No p-values or analysis results are posted, so there is no basis for assessing the consequences of multiplicity in the reported findings.
The record defines the primary efficacy population as per protocol and describes exclusions for important protocol deviations. It does not report how missing SVR12 measurements were handled, how many results were missing, whether participants were excluded for missing measurements, or whether sensitivity analyses were performed. It also does not report an intention-to-treat result. These omissions limit assessment of how missing outcomes or population selection may affect the primary endpoint.
The adverse-event figures use participants at risk in the listed treatment group, while the primary endpoint is defined for the per-protocol population. The relationship between those populations is not reported in the registry record. Their denominators should not be assumed to be interchangeable.
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 |
|---|---|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | 6 | 79 | 7.6% |
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 |
|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | 47 of 79 |
Most frequent serious adverse event terms
| Event term | Organ system | GZR 100 mg + EBR 50 mg + RBV for 12 Weeks |
|---|---|---|
| Appendicitis | Infections and infestations | 1 of 79 |
| Pharyngitis bacterial | Infections and infestations | 1 of 79 |
| Urinary tract infection | Infections and infestations | 1 of 79 |
| Laryngeal squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 79 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 1 of 79 |
| Inguinal hernia | Gastrointestinal disorders | 1 of 79 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GZR 100 mg + EBR 50 mg + RBV for 12 Weeks |
|---|---|---|
| Fatigue | General disorders | 22 of 79 |
| Headache | Nervous system disorders | 15 of 79 |
| Asthenia | General disorders | 12 of 79 |
| Nausea | Gastrointestinal disorders | 9 of 79 |
| Insomnia | Psychiatric disorders | 7 of 79 |
| Anaemia | Blood and lymphatic system disorders | 6 of 79 |
| Diarrhoea | Gastrointestinal disorders | 6 of 79 |
| Abdominal pain upper | Gastrointestinal disorders | 5 of 79 |
| Constipation | Gastrointestinal disorders | 5 of 79 |
| Vomiting | Gastrointestinal disorders | 4 of 79 |
Serious events with the highest arm-level rate: appendicitis (1.3%), pharyngitis bacterial (1.3%), urinary tract infection (1.3%), laryngeal squamous cell carcinoma (1.3%), chronic obstructive pulmonary disease (1.3%).
The registry record lists 79 participants at risk for serious adverse events in the treatment group and reports 6 affected. It also lists 79 participants at risk for other adverse events and reports 47 affected. These are separate registry summaries; they should not be added together, because the record does not say whether participants appear in both categories. The death count is not reported in the registry record.
The listed serious adverse-event terms are appendicitis, pharyngitis bacterial, urinary tract infection, laryngeal squamous cell carcinoma, chronic obstructive pulmonary disease, and inguinal hernia. Each term is reported as 1.3%. Those term-specific figures describe the registry entries; they do not establish that treatment caused an event, nor do they provide the full clinical context or timing for each event.
As a general concept, an adverse-event count describes events recorded during the specified safety observation, not necessarily events caused by treatment. A count of participants affected is also distinct from a count of all events, since a participant may experience more than one event. The registry record does not provide further detail needed to assess timing, severity beyond the serious classification, relatedness, or individual event histories.
13. What the Result Does, and Does Not, Mean
The registered question concerns SVR12 after a specified combination regimen in participants with chronic hepatitis C who failed prior direct-acting antiviral therapy. The endpoint definition is clear: HCV RNA below <15 IU/mL at the specified post-treatment assessment, measured in the per-protocol population. But the registry record does not report the SVR12 percentage, confidence interval, or analysis denominator. It therefore does not establish the observed primary efficacy result.
Even if a single-group SVR12 result were available, its interpretation would be descriptive of the participants analyzed under the study's rules. Without a concurrent comparator, the design does not estimate how outcomes would differ under another treatment or under no study treatment. As a general principle, an outcome observed after treatment is not by itself a randomized estimate of treatment effect. Other explanations for outcomes cannot be separated through this design alone.
The record does report safety counts, but these do not resolve the missing efficacy result. Nor do the listed serious adverse-event terms establish treatment causality. The registry information describes the recorded counts and percentages, not comparative safety or clinical explanations for individual events.
The trial's population and regimen also define the scope of its question: participants with genotype 1 infection who failed prior direct-acting antiviral therapy received the listed regimen for 12 weeks. The record does not support extending an efficacy interpretation to populations or regimens outside that description. Since the primary result and analysis details are not reported, a broader conclusion about benefit, lack of benefit, or comparative performance would go beyond the information in the registry record.
14. Why This Trial Matters Statistically
This study illustrates why a clearly named endpoint does not on its own communicate a clinical trial finding. SVR12 is defined with a measurement threshold and timing after treatment, and the record identifies a per-protocol population and a 95% confidence interval as the dispersion measure. Those features describe what was intended to be measured. The registry record does not include the percentage or interval needed to judge the observed result and its precision.
The single-group design is also important statistically. It can describe outcomes within the treated group, but it does not provide a randomized comparison with another regimen. Readers must distinguish a within-group endpoint rate from an estimate of a between-group treatment contrast. The latter is not part of the registered design.
For biostatisticians and clinical researchers, the record highlights the need to report analysis denominators, missing-data handling, analysis populations, and the method used for uncertainty intervals. These details make it possible to assess whether the endpoint definition was applied consistently and how much confidence to place in an estimate. The registry lists a per-protocol definition, but not the resulting population size or analysis method.
Finally, planning calculations have a different role from trial results. A two-arm planning illustration cannot turn a single-group study into a comparative trial, and it is not observed power. Keeping design assumptions, analysis methods, and observed results distinct prevents planning figures from being mistaken for evidence about the primary endpoint.
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 trial-specific limitation in the registry record is that it does not report the primary SVR12 result, its confidence interval, or its analysis denominator. As a result, neither the size of the observed endpoint percentage nor its precision can be assessed. The enrollment count of 79 does not establish how many participants entered the per-protocol analysis.
The single-group design has no concurrent comparator, and the allocation field is listed as NA. The record therefore does not support a randomized between-treatment contrast. It also does not report an adjusted analysis that could address differences against an external group. Any interpretation must remain within the descriptive scope of the registered group and endpoint.
Further details that would help assess the efficacy analysis are not reported in the registry record: the handling of missing SVR12 measurements, the exclusions used to form the per-protocol population, the confidence-interval method, and the statistical analysis plan. The record lists four outcome measures but no posted analyses, and does not state whether multiplicity procedures or interim analyses were used.
The safety record provides counts and serious-event terms but does not report a death count, event timing, relatedness assessments, or details linking each term to an individual participant. These limitations prevent a fuller assessment of the safety summaries. The registry description is also specific to the stated genotype, prior-treatment history, and regimen; it does not establish outcomes for populations or treatment strategies beyond that scope.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin in Participants With Chronic Hepatitis C Who Failed Prior Direct-Acting Antiviral Therapy (MK-5172-048) — NCT02105454.
- Registry record last updated 2018-09-24; status last verified 2018-08.
- Results first posted 2016-03-04.
- 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
NCT02105454 is a completed Phase II, single-group study of grazoprevir, elbasvir, and ribavirin in participants with chronic hepatitis C who failed prior direct-acting antiviral therapy. The registry lists 79 enrolled participants and a regimen of grazoprevir 100 mg once per day, elbasvir 50 mg once per day, and ribavirin 800 - 1400 mg daily in divided doses for 12 weeks.
The primary endpoint was the percentage achieving SVR12 in the per-protocol population, using HCV RNA below <15 IU/mL. The registry record does not report the endpoint percentage, confidence interval, or analysis denominator. It lists four outcome measures and no posted analyses. Safety entries report 6 participants affected by serious adverse events and 47 affected by other adverse events; the death count is not reported in the registry record.