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 to Collect Blood Biomarker Samples From Participants With Chronic Hepatitis B (CHB) Who Received Treatment With Pegasys (Peginterferon Alfa-2a) ± Nucleoside/Nucleotide Analogue (NCT01855997), a registered phase not stated study. The primary outcome is Single Nucleotide Polymorphisms (SNPs) Associated With HBeAg Seroconversion or Hepatitis B Surface Antigen (HBsAg) Clearance ≥24 Weeks Post-Treatment in HBeAg-Positive East Asian (CN) Population: Additive Model.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01855997 |
| Phase | Phase not stated |
| Condition | Hepatitis B, Chronic |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 1669 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The primary analysis population was HBeAg-positive participants of East Asian genetic background in the CN population. Their genetic data had to pass a protocol-specified quality check and share a common East Asian background relative to HapMap version 3.0 reference individuals. The broader study enrolled adults with chronic hepatitis B who had completed at least 24 weeks of a Peg-IFN alfa-2a-containing regimen and at least 24 weeks of post-treatment follow-up. Participants could come from Roche clinical studies or general medical practice.
Intervention
This was not a study assigning a new treatment. Participants had already received Peg-IFN alfa-2a, with or without nucleoside analogue therapy. The study collected blood biomarker samples and medical-record information; some participants could contribute previously collected repository DNA rather than a new blood sample.
Comparator
The registry record does not identify a randomized or like-for-like control group. Treatment history was part of the participant background, not a comparison assigned by this sample-collection study. The primary analysis examined genetic markers in relation to treatment-response outcomes rather than comparing treatment arms.
Primary question
Among the defined HBeAg-positive East Asian population, were single nucleotide polymorphisms associated with HBeAg seroconversion or HBsAg clearance at least 24 weeks after treatment? The primary outcome description specifies logistic regression adjusted for covariates, with markers coded under an additive inheritance model. The registry record does not report the individual marker estimates or which markers met the stated significance thresholds.
3. Trial Design
NCT01855997 is described as a Phase IV blood-sample collection study, not as a randomized treatment trial. Its purpose was exploratory evaluation of associations between genetic variation and treatment response among people with chronic hepatitis B who had already completed treatment. The registry lists an enrollment of 1669 and a completed status. The recorded start date is 2013-08-20, and the primary completion date is 2014-11-28.
Eligible participants had received at least 24 weeks of a regimen containing pegylated interferon alfa-2a and completed at least 24 weeks of follow-up after treatment. Their treatment could also have included a nucleoside or nucleotide analogue. Recruitment could occur through Roche-supported or sponsored historical or ongoing studies, or through general medical practice. Follow-up for participants who chose to join was to follow the applicable ongoing study or the participant’s usual medical practice.
Study procedures included blood sample collection and medical-record capture. A new blood collection was not applicable to participants who had already consented to and donated Roche Clinical Repository DNA samples. The record also describes combining genetic data from the GV28555 study or available repository samples with data from other applicable studies.
The study’s overall enrollment should not be read as the size of the primary genetic analysis. That analysis was restricted to HBeAg-positive participants in the CN population who passed a genetic quality check and met the East Asian genetic-background criterion. The number who met those criteria is not reported in the registry record. There was no randomized allocation or treatment-control comparison identified in the record, and the allocation method is not stated.
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
| Stage | Adult Participants Treated With Peg-IFN |
|---|---|
| STARTED | 1669 |
| COMPLETED | 1669 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: HBeAg-Positive CN Population: All HBeAg-positive participants whose genetic data passed a protocol-specified quality check and shared common East Asian genetic background as compared to haplotype map (HapMap) version 3.0 reference individuals.
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.
Population: All Enrolled Population: All participants for whom genotype data were available.
| Characteristic | Unit | Adult Participants Treated With Peg-IFN |
|---|---|---|
| Participants analysed | 1669 | |
| Age, Continuous | years | 39.09 (SD 0.270) |
| Sex: Female, Male: Female | Participants | 471 |
| Sex: Female, Male: Male | Participants | 1198 |
| HBeAg Status: Positive | participants | 932 |
| HBeAg Status: Negative | participants | 676 |
| HBeAg Status: Not Known | participants | 61 |
6. Primary Endpoint
The registry lists the primary outcome as Single Nucleotide Polymorphisms (SNPs) Associated With HBeAg Seroconversion or Hepatitis B Surface Antigen (HBsAg) Clearance ≥24 Weeks Post-Treatment in HBeAg-Positive East Asian (CN) Population: Additive Model, measured over Single blood sample ≥24 weeks post-treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | beta coefficient |
| Endpoint classification | not reduced to a single comparison |
The primary outcome concerns associations between single nucleotide polymorphisms (SNPs) and either HBeAg seroconversion or HBsAg clearance, measured at least 24 weeks after treatment in the HBeAg-positive East Asian CN population. HBeAg seroconversion was defined as loss of HBeAg together with detection of anti-HBe. HBsAg clearance was defined as loss of HBsAg, with or without detection of anti-HBs. The outcome unit is a beta coefficient.
The endpoint is used to investigate whether genetic markers are associated with the chance of these response outcomes. In general, a beta coefficient describes the direction and magnitude of an association on the model’s scale; the registry states that larger beta coefficients correspond to greater likelihood of treatment response. It does not give the individual coefficients or their uncertainty in the information available for this account, so the size and precision of any particular marker association cannot be described.
The registry describes a genome-wide association study using logistic regression adjusted for covariates, with SNPs coded according to an additive model of inheritance. This is an exploratory association endpoint, not a direct randomized estimate of the effect of Peg-IFN or of adding a nucleos(t)ide analogue. The endpoint’s timing is a single blood sample at least 24 weeks after treatment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry frames the primary analysis as a search for genetic associations with hepatitis B treatment-response outcomes. Its target is not a treatment comparison. Participants had previously completed Peg-IFN alfa-2a-containing therapy, and this study collected samples and records to investigate how SNPs related to response. Because treatment was not assigned within this study and the record identifies no randomized control group, the analysis should be read as observational association evidence.
The primary analysis population was narrower than the overall study enrollment. It consisted of HBeAg-positive participants in the CN population whose genetic data passed a protocol-specified quality check and whose genetic background met the stated East Asian criterion. The registry enrollment is 1669, but the number in this specific analysis population is not reported in the registry record. The enrollment figure therefore should not be treated as the denominator for the primary genetic analysis.
The outcome description defines two response measures: HBeAg seroconversion and HBsAg clearance. It states that logistic regression adjusted for covariates was used, and that markers were evaluated with additive coding. However, the individual SNP results, beta coefficients, confidence intervals, p-values, and counts of participants with each response are not reported in the registry record. Consequently, no particular association’s direction, magnitude, or precision can be assessed from this record. The record also does not identify which SNPs met either of its stated thresholds.
The registry specifies p < 10^-5 as suggestive and p < 5x10^-8 as genome-wide significant. These are threshold definitions, not evidence that any marker crossed either threshold. A threshold alone does not show how large an association is, how uncertain it is, or whether it is clinically meaningful. Those assessments require the marker-specific estimates and supporting results, which are not reported in the registry record.
The outcome timing—at least 24 weeks after treatment—describes when the response status was assessed for this analysis. It does not establish when each participant began treatment, how treatment histories differed, or whether follow-up was uniform across recruitment sources. Those details are not reported in the registry record. Likewise, covariate adjustment is noted, but the covariates and model diagnostics are not listed.
Overall, the record describes an exploratory genetic-association objective and its broad analytic approach, but does not report results sufficient to judge the evidence for any individual SNP. The study’s completed status and enrollment do not substitute for those estimates. No treatment benefit or lack of benefit can be inferred from the information recorded for this analysis.
9. Statistical Methods Explained
What does an additive genetic model mean?
The registry says that SNP markers were coded according to an additive model of inheritance. In general, this model represents genetic-marker categories in an ordered way so that the fitted association reflects a stepwise change across marker copies. It is a modeling choice about how genotype information enters the analysis; it does not establish that the biological relationship is truly additive. The registry does not report the marker-specific coding details or any alternative genetic models that may have been assessed.
Why use logistic regression?
The response outcomes are described as binary: participants either met the stated definition of HBeAg seroconversion or they did not, and likewise for HBsAg clearance. In general, logistic regression models the relationship between one or more predictors and the probability of a binary outcome. Here the predictor of interest was a SNP, and the registry states that the analysis adjusted for covariates. Adjustment can account statistically for measured characteristics included in the model, but it cannot remove bias from unmeasured factors or incorrect model assumptions. The covariates used, the fitted estimates, and the model checks are not reported in the registry record.
What does a beta coefficient describe?
The primary outcome is expressed as a beta coefficient. In general, a coefficient describes the direction and size of a modeled relationship on the model’s scale. The registry says that larger beta coefficients correspond to greater likelihood of treatment response. A coefficient should be interpreted together with its uncertainty and the model definition; neither the coefficients nor their uncertainty are reported in the registry record. It is therefore not possible to characterize a particular marker’s estimated association or precision from the record alone.
How should the significance thresholds be read?
The registry identifies p < 10^-5 as suggestive and p < 5x10^-8 as genome-wide significant. In general, a p-value measures how compatible data are with a specified statistical model under a null hypothesis; it is not the probability that the null hypothesis is true, nor does it measure the clinical importance of an association. Genome-wide studies examine many markers, so thresholds are used to distinguish levels of statistical evidence in that broad search. The record’s threshold definitions do not disclose whether any marker reached them. Marker-specific p-values and estimates are not reported in the registry record.
Why does multiplicity matter in a genome-wide analysis?
In general, testing many genetic markers increases the chance that some may appear associated by chance alone. A threshold designed for a genome-wide search can help address that multiplicity, but a threshold does not by itself convey effect size, uncertainty, replication, or relevance to clinical decisions. The registry states two thresholds and labels their intended interpretation, but does not report the number of markers tested, a complete list of results, or any confirmation analysis. It is not possible to reconstruct the analysis-wide evidence from the threshold definitions alone.
What can covariate adjustment accomplish?
In general, adjustment estimates a marker association conditional on the covariates included in a model. It may help account for measured differences that relate to both the marker and outcome. Adjustment does not make an observational analysis equivalent to a randomized comparison, and it does not guarantee that all sources of bias are controlled. The registry confirms that covariates were used but does not report their identities, selection rationale, missing-data handling, or the adjusted estimates.
How should planning illustrations be understood?
The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated effect to detect is a fraction of the observed effect. In general, such calculations illustrate the sample size associated with specified assumptions; they are not observed power and do not establish that the study was designed around those assumptions. The assumptions are not the same as a randomized trial design, and no numerical planning results are reported in the registry record.
For time-to-event calculations, the record says the illustrations use total events; other calculations use participants per arm. The primary genetic-association endpoint is not a randomized two-arm treatment comparison, so those generic planning assumptions should not be interpreted as defining this study’s allocation or primary analysis. The registry does not report a sample-size justification for the genetic analysis.
10. Multiplicity, Missing Data and Analysis Populations
The primary objective uses a genome-wide association approach, so multiplicity is relevant: many marker-outcome associations may be examined. The registry defines p < 10^-5 as suggestive and p < 5x10^-8 as genome-wide significant. It does not report the number of markers tested, a complete set of marker results, or which markers met either threshold. The stated cutoffs should therefore be understood as analysis criteria, not as evidence that a finding crossed them.
The record describes logistic regression adjusted for covariates, but does not name those covariates or report how they were selected. It also does not report whether additional outcomes or subgroup analyses were considered in relation to multiplicity, or whether there were interim analyses. Those details are not reported in the registry record.
For missing data, the registry does not explain how missing response status, covariate values, or genetic data were handled. It specifies a genetic quality-check requirement for the primary population, but does not give the number excluded or describe the quality-control procedures. The number of participants in the analysis population is not reported in the registry record.
The population description identifies HBeAg-positive participants with an East Asian genetic background who passed the stated quality check. The record does not provide a full participant flow or the number contributing to each outcome analysis. The overall enrollment should not be used as a substitute for those analysis denominators. The covariate-adjusted model and eligibility criteria are stated, but details needed to assess missingness, exclusions, and analysis-population sensitivity are not reported in the registry record.
11. 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 |
|---|---|---|---|
| Adult Participants Treated With Peg-IFN | 0 | 1105 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adult Participants Treated With Peg-IFN | 0 of 1105 |
The adverse-event record lists 1105 participants at risk for serious adverse events and 0 affected by a serious adverse event. It also lists 1105 at risk for other adverse events and 0 affected by an other adverse event. No serious adverse-event terms are listed. These are the counts recorded in the registry, not evidence that no events occurred outside the categories, populations, or reporting period captured by those entries.
The death count is recorded as null, which means it is not reported in the registry record; it should not be read as zero. The record does not specify an adverse-event observation window in the information available for this account. It also does not provide details about event collection, severity definitions, or how adverse events were attributed.
This was a blood-sample collection study involving participants who had already completed treatment, rather than a randomized comparison of treatment safety. The adverse-event entries therefore do not provide a comparative estimate for Peg-IFN alfa-2a or nucleoside analogue therapy. The registry’s event counts should be interpreted within the study’s stated collection context and with the missing reporting details in mind.
12. What the Result Does, and Does Not, Mean
The record describes a completed biomarker study that sought to evaluate whether SNPs were associated with hepatitis B treatment-response outcomes after Peg-IFN alfa-2a-containing therapy. It gives definitions for HBeAg seroconversion and HBsAg clearance, identifies a restricted primary genetic-analysis population, and specifies adjusted logistic regression with additive SNP coding. These details explain the type of question and broad analytic approach.
The record does not report the individual SNP beta coefficients, confidence intervals, p-values, or outcome counts. It also does not report which markers met the suggestive or genome-wide significance thresholds. As a result, the strength, direction, and precision of any specific association cannot be judged from the record. The absence of reported estimates is not evidence that associations were absent.
Even if a marker association were reported, an observational genetic association in participants with prior treatment would not, by itself, show that a treatment caused the response or that a treatment should be selected on the basis of that marker. The study did not assign treatment or establish a randomized comparator. Association estimates can also depend on population definition, measured covariates, genetic quality control, and the completeness of the outcome data.
The overall enrollment of 1669 describes the study record, not necessarily the number in the primary genetic analysis. The analysis population required HBeAg positivity, the specified East Asian genetic background, and passing the genetic quality check. Its size and outcome-specific denominators are not reported in the registry record.
The safety entries are also limited: the registry lists zero affected participants for the recorded serious and other adverse-event categories, while the death count is not reported. These entries should not be extended beyond their recorded scope or interpreted as comparative treatment-safety evidence.
13. Why This Trial Matters Statistically
This study is statistically distinctive because its main question concerns genetic associations within a population defined by both clinical status and genetic background. Such restrictions can make an analysis population different from the full enrolled study population. Here, the primary population required HBeAg positivity, an East Asian genetic background relative to a reference, and genetic data passing a quality check. Distinguishing that analytic population from the overall enrollment is essential when interpreting results and denominators.
The study also illustrates the separation between treatment research and biomarker research. Participants had completed Peg-IFN alfa-2a-containing treatment before entering this sample-collection study. The analysis asks whether markers are associated with response outcomes; it does not compare assigned treatment strategies. That distinction limits causal interpretation and prevents the study design from serving as a randomized treatment-effect comparison.
Genome-wide analysis raises an important multiplicity issue because many markers may be evaluated. The registry explicitly labels p < 10^-5 as suggestive and p < 5x10^-8 as genome-wide significant. Those definitions help readers understand the intended evidence thresholds, but without marker-level estimates and results they do not establish that a particular association was found. Statistical significance and the magnitude or practical importance of an association are separate questions.
The record further shows why complete reporting matters for interpretation. Without the analysis-population size, participant flow, covariate definitions, marker-level estimates, and uncertainty measures, readers cannot assess the precision or robustness of individual findings. A clearly stated method and endpoint definition are useful, but they cannot replace the results needed to evaluate the evidence.
14. 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 describes the study objective and broad analysis method but does not report the primary marker-level results. The beta coefficients, confidence intervals, p-values, and marker-specific outcome counts are not reported in the registry record. The record therefore does not allow assessment of the magnitude, direction, or precision of individual SNP associations, or whether any met the stated thresholds.
The primary population is restricted to HBeAg-positive participants in the CN population with the specified East Asian genetic background and genetic quality-check status. The number meeting these criteria is not reported in the registry record, nor are the outcome-specific analysis denominators or participant flow. The overall enrollment of 1669 cannot be assumed to describe those analysis populations.
The registry says that covariates were included in logistic regression but does not identify them or report the model specification in detail. Missing-data methods, genetic quality-control procedures, and sensitivity analyses are not reported in the registry record. The number of markers assessed and any replication or confirmation analysis are also not reported.
Participants were recruited from Roche clinical studies or general practice, and follow-up was to accord with the ongoing study or medical practice. The record does not describe how follow-up differed across sources or provide details sufficient to evaluate consistency of outcome ascertainment. Because treatment was not assigned in this study and no randomized control group is identified, the design supports an association question rather than a causal treatment comparison.
The registry’s safety entries do not include an observation window in the information, and the death count is not reported. These reporting gaps limit interpretation of the adverse-event counts as well as the genetic analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Collect Blood Biomarker Samples From Participants With Chronic Hepatitis B (CHB) Who Received Treatment With Pegasys (Peginterferon Alfa-2a) ± Nucleoside/Nucleotide Analogue — NCT01855997.
- Registry record last updated 2017-04-05; status last verified 2017-03.
- Results first posted 2016-04-08.
- 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.
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18. Record Summary
NCT01855997 is a completed Phase IV study of blood biomarker collection in people with chronic hepatitis B who had completed at least 24 weeks of Peg-IFN alfa-2a-containing treatment and at least 24 weeks of post-treatment follow-up. The registry lists enrollment of 1669, a start date of 2013-08-20, and a primary completion date of 2014-11-28.
The primary objective was to explore associations between SNPs and HBeAg seroconversion or HBsAg clearance in HBeAg-positive participants of East Asian genetic background who passed a genetic quality check. The record describes adjusted logistic regression and additive marker coding, but does not report marker-specific estimates or which markers met the stated significance thresholds.
The study was not a randomized treatment comparison. The primary analysis population size, covariate details, missing-data methods, and individual genetic results are not reported in the registry record. The safety record lists 0 affected participants for serious and other adverse events among 1105 at risk in each category; the death count is not reported.