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 Efficacy and Safety Study of Human-cl rhFVIII in PTPs With Severe Hemophilia A (NCT01125813), a na phase 3 study. The primary outcome is Efficacy Assessment After a Total of at Least 50 EDs Per Subject at the End of the Study at 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01125813 |
| Phase | Phase 3 |
| Condition | Severe Hemophilia A |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Octapharma |
| Results posted | Yes |
2. Clinical Question
Population
Previously treated patients with severe hemophilia A. The registry record reports enrollment of 32 participants. The primary endpoint population is described as all subjects who started prophylactic treatment; the number who started prophylaxis is not reported in the registry record.
Intervention
Human-cl rhFVIII, identified in the intervention listing as recombinant Factor VIII. The study description covers prophylactic treatment, treatment of bleeding episodes, and surgical prophylaxis. The primary endpoint concerns prophylactic treatment.
Comparator
There was no separate comparison group: the registry record describes a single-group study with allocation listed as NA. The study therefore does not provide a like-for-like control comparison.
Primary question
Among subjects who started prophylactic treatment, what was the frequency of spontaneous breakthrough bleeds per month after at least 50 Exposure Days and at least 6 months? The registry record states the measure and assessment period but does not report the observed mean or its standard deviation.
This question focuses on bleeding during prophylaxis, rather than on a comparison between randomized treatment assignments. The endpoint is a continuous summary of bleed frequency, expressed as bleeds per month. The registry record also identifies treatment of bleeding episodes and surgical prophylaxis in the study description, but these are not the stated primary endpoint.
Because the design is single-group, any observed bleed frequency would describe the participants assessed under the study treatment and conditions. It would not, by itself, quantify how that frequency differs from what would have occurred under another treatment or without treatment. The registry record does not report a comparator, a baseline bleed frequency, or a treatment-effect estimate for a between-group contrast. Those omissions limit the causal question that can be answered from the record.
3. Trial Design
This is a phase 3 study of human-cl rhFVIII in previously treated patients with severe hemophilia A. The registry record lists enrollment of 32 and identifies Octapharma as the sponsor. The study began in 2010-06, reached primary completion in 2012-01, and has COMPLETED status.
The design is listed as single group, with allocation recorded as NA and masking recorded as NONE. The registry identifies one intervention, recombinant Factor VIII, and one arm, Human Cl-rhFVIII. No separate control arm is described. The study therefore reports experience in a treated group rather than a randomized contrast between groups. Its design does not support interpreting a treated-versus-control effect from the registry record.
The study description says it will assess efficacy during prophylactic treatment, treatment of bleeding episodes, and surgical prophylaxis, as well as safety and immunogenicity. The primary endpoint is narrower: frequency of spontaneous breakthrough bleeds per month under prophylactic treatment. It is assessed after at least 50 Exposure Days and at least 6 months. The record states that all subjects who started prophylactic treatment were evaluated, but does not report how many started, completed, or contributed an endpoint measurement.
The record does not report the protocol’s sample-size justification, a statistical analysis plan, interim analyses, or the details of any masking procedures beyond the masking field being NONE. It lists two outcome measures and no analysis records. That does not establish what analyses were conducted outside the registry record; it means the record does not provide those analysis details. The design details are useful for understanding what comparisons are possible, but they do not supply the primary outcome estimate needed to judge the observed bleed frequency or its precision.
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: 36 participants were enrolled and screened. 4 were screen failures. Therefore, 32 of the 36 enrolled were exposed to investigation product.
Overall Study
| Stage | Human Cl-rhFVIII |
|---|---|
| STARTED | 36 |
| COMPLETED | 30 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Human Cl-rhFVIII |
|---|---|
| Death | 1 |
| Withdrawal by Subject | 1 |
| Screen Failures | 4 |
Analysis population for the primary outcome, as defined in the registry: All subjects who started prophylactic treatment were evaluated.
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 | Human Cl-rhFVIII |
|---|---|---|
| Participants analysed | 32 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 31 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 37.3 (SD 13.6) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 32 |
| Region of Enrollment: Austria | participants | 1 |
| Region of Enrollment: Bulgaria | participants | 8 |
| Region of Enrollment: Germany | participants | 8 |
| Region of Enrollment: United Kingdom | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Efficacy Assessment After a Total of at Least 50 EDs Per Subject at the End of the Study at 6 Months, measured over At least 50 Exposure Days and at least 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Bleeds per month |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the frequency of spontaneous breakthrough bleeds per month during prophylactic treatment. It is a continuous measure, summarized as a mean with a standard deviation. The stated population is all subjects who started prophylactic treatment. The assessment timeframe is after at least 50 Exposure Days and at least 6 months.
A monthly bleed frequency expresses the outcome on a time-based scale, which can make observations from different exposure durations easier to describe in a common unit. A mean gives a summary of the group’s measured frequency, while the standard deviation describes how spread out individual observations are around that mean. These are general interpretations of the chosen statistics; the registry record does not report the observed mean or standard deviation.
Spontaneous breakthrough bleeds are specified, distinguishing the endpoint from a count of all bleeding events regardless of cause. The endpoint is used to describe bleeding during prophylaxis, one of the study’s stated treatment settings. The registry record does not provide a definition of spontaneous bleeding, the event-adjudication method, or details on how follow-up time was handled for participants with different observation periods.
Without the endpoint estimate and its uncertainty, the record’s endpoint definition alone cannot show the frequency observed in the study or how precisely it was estimated. Nor does the measure, in this single-group design, establish a comparative treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically interpretable primary outcome: spontaneous breakthrough bleeds per month during prophylactic treatment. It also specifies a mean and standard deviation and describes the population as all subjects who started prophylaxis. However, it does not report the mean, standard deviation, or any confidence interval for this endpoint. Consequently, the posted record does not establish the observed bleed frequency or the precision of an estimate.
The distinction between an endpoint definition and an endpoint result matters. A clearly named measure tells readers what the study intended to assess, but it is not evidence of the value observed. The registry record gives an assessment period of at least 50 Exposure Days and at least 6 months; it does not give individual follow-up durations, the number contributing data, or the distribution of bleed counts. It is therefore not possible to assess whether observations were concentrated or variable, or whether the mean alone represents the data well.
The single-group design also constrains interpretation. A result from one treated group can describe that group’s experience, but it cannot isolate a treatment effect from other explanations without a suitable comparison. There is no separate comparator group listed, and no baseline bleed frequency or change-from-baseline estimate is reported. No unadjusted recalculation or comparison estimate is available in the registry record. The record’s stated study aims include efficacy, safety, and immunogenicity, but the listed primary endpoint addresses bleed frequency during prophylaxis.
The safety listing reports a serious-adverse-event affected count of 2 and an other-adverse-event affected count of 3 in the Human Cl-rhFVIII group, with 32 at risk for each listing. It also names Traumatic fracture and STATUS EPILEPTICUS among the top serious terms, each with a reported 3.1%. These entries describe reported safety counts and terms; they do not provide a comparison with an untreated group. The death count is not reported in the registry record.
Overall, the record supports a description of study structure, endpoint definition, assessment timeframe, and selected safety entries. It does not supply the primary efficacy estimate, its uncertainty, or a controlled comparison. A statistical conclusion about the magnitude or precision of the primary endpoint would go beyond what the registry record reports.
9. Statistical Methods Explained
The registry record characterizes the primary outcome as continuous, with a mean and standard deviation. These statistics answer different descriptive questions. The mean summarizes the average measured bleed frequency in the analyzed population. The standard deviation describes how much individual measurements vary around that average. Neither statistic, alone, establishes a treatment effect or shows how precisely the group mean has been estimated. The endpoint values are not reported in the registry record, so these quantities cannot be interpreted for this study.
What does a confidence interval add?
In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. It is not a range containing a known proportion of individual observations; the standard deviation is more directly related to individual spread. A narrow interval indicates greater statistical precision for the estimate, while a wide interval indicates less precision. The registry record does not report a confidence interval for the primary endpoint. Without an estimate and interval, readers cannot evaluate either the observed level of bleeding or the uncertainty around a group summary.
How does the single-group design affect statistical interpretation?
A single-group estimate is descriptive of the participants measured under the study conditions. To estimate a treatment contrast, a study ordinarily needs an appropriate comparison and a defined contrast between groups or conditions. Here, allocation is listed as NA and the design as single group; no separate control is listed. The record therefore does not support a randomized between-group comparison. Any difference from an external expectation would also depend on whether the external data were comparable, and no such comparison is reported.
The record does not give a baseline bleed frequency or a change-from-baseline analysis. Without these details, it is not possible to describe a within-participant change from baseline either. The stated primary endpoint is a frequency per month after a minimum exposure and follow-up period. The registry record does not explain how the analysis accounted for varying time under observation, recurrent events within a participant, or participants who did not complete the stated period.
Why can recurrent-event data need special care?
As a general statistical matter, bleed events can recur within a participant, so observations from the same person may be related rather than independent. A simple mean can describe the average frequency, but more detailed inference may require methods that account for repeated events, differences in observation time, and variation between participants. Over-dispersion is a general concern when event-count variability exceeds what a simple count model would expect. Accounting for it can affect estimated uncertainty. The registry record does not state which model, if any, was used, whether over-dispersion was assessed, or how recurrent events were handled. No particular model should be inferred from the reported endpoint type.
What can be said about sample-size calculations?
A planning illustration based on an observed effect is not the same as the trial’s original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrated quantity is participants per arm; time-to-event calculations are described in terms of total events using Schoenfeld. These are planning assumptions, not observed trial results and not observed power.
Because the registry record does not report the primary mean or a treatment contrast, it does not supply the observed effect needed to interpret an effect-based planning illustration. The trial itself is listed as single group, whereas the illustration assumes equal allocation between two arms. The illustration should therefore not be mistaken for the design used in this study. The protocol’s own sample-size justification is not reported in the registry record. A planning calculation cannot substitute for a reported endpoint estimate, confidence interval, or analysis plan.
What analyses are available in the record?
The registry lists two outcome measures and no analysis records. That is a statement about the analyses included in the registry record, not proof that no analysis was performed elsewhere. The sponsor’s own analysis would take precedence if a recalculation from posted summary statistics differed, but the record does not include the primary endpoint summary statistics needed for such a recalculation. No p-value, adjusted estimate, or comparative efficacy result is reported. In this setting, the appropriate statistical reading is to distinguish the specified outcome and design from results that the registry record does not report.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| Human Cl-rhFVIII | 32 | 0.188 | 0.307 | 0.077 to 0.299 |
R code and output
arm <- c("Human Cl-rhFVIII")
n <- c(32)
m <- c(0.188)
sp <- c(0.307)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM Human Cl-rhFVIII 32 0.188 0.307 0.077 0.29911. Multiplicity, Missing Data and Analysis Populations
The study listing includes two outcome measures, but the registry record does not report a multiplicity strategy. It does not say whether outcomes were organized into a hierarchy, whether testing was planned across outcomes, or whether any adjustment to account for multiple comparisons was used. The primary endpoint is identified by title, but that alone does not establish how other outcomes were treated statistically.
Missing-data methods are not reported in the registry record. The primary endpoint population is described as all subjects who started prophylactic treatment, but the number who started and the number with an observed endpoint are not reported. The record does not explain how missing measurements, withdrawal, incomplete follow-up, or varying observation time were handled. These details matter because an analysis can represent different populations depending on who contributed data and how incomplete observations were treated.
The registry does not provide an analysis population definition beyond the primary endpoint description, nor does it report a per-protocol or other analysis set for this outcome. Interim analyses are not reported in the registry record. The record also contains no analysis entries. This does not establish that no such decisions or analyses occurred; it means their details cannot be evaluated from the registry record.
As a result, the endpoint definition can be identified, but the handling of multiplicity and missing data, and the relationship between the intended and analyzed populations, remain unclear. Those uncertainties limit assessment of potential bias and of how broadly an endpoint result would apply, even if a result were otherwise available.
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 |
|---|---|---|---|
| Human Cl-rhFVIII | 2 | 32 | 6.2% |
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 |
|---|---|
| Human Cl-rhFVIII | 3 of 32 |
Most frequent serious adverse event terms
| Event term | Organ system | Human Cl-rhFVIII |
|---|---|---|
| Traumatic fracture | Injury, poisoning and procedural complications | 1 of 32 |
| STATUS EPILEPTICUS | Nervous system disorders | 1 of 32 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Human Cl-rhFVIII |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 3 of 32 |
| Headache | Nervous system disorders | 3 of 32 |
| Abdominal pain | Gastrointestinal disorders | 2 of 32 |
| Diarrhoea | Gastrointestinal disorders | 2 of 32 |
| Nausea | Gastrointestinal disorders | 2 of 32 |
| Pyrexia | General disorders | 2 of 32 |
| Contusion | Injury, poisoning and procedural complications | 2 of 32 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 32 |
| Paraesthesia | Nervous system disorders | 2 of 32 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 2 of 32 |
Serious events with the highest arm-level rate: traumatic fracture (3.1%), status epilepticus (3.1%).
The Human Cl-rhFVIII safety listing reports 32 at risk for serious adverse events and 2 in the serious-adverse-event affected count. It reports 32 at risk for other adverse events and 3 in the other-adverse-event affected count. These are separate registry entries; they should not be combined into a new total or treated as evidence that the categories are mutually exclusive.
The top serious terms are Traumatic fracture and STATUS EPILEPTICUS, each reported as 3.1%. The record does not explain in this listing how the term-level percentages relate to the affected count, nor does it provide further details such as timing, severity grading, attribution, or outcomes. The death count is not reported in the registry record.
These figures describe safety reporting within the study group. Because the design is single group and no control group is listed, they do not establish whether an event was more or less common than it would have been under another treatment or in the absence of treatment. Counts also do not by themselves describe the full clinical context or causal attribution. The safety entries should therefore be read as registry-reported observations, not as a comparative safety estimate.
13. What the Result Does, and Does Not, Mean
The registry record documents a phase 3, single-group study of human-cl rhFVIII in previously treated patients with severe hemophilia A. It identifies a primary endpoint focused on spontaneous breakthrough bleeds per month during prophylaxis, defines a minimum exposure and follow-up period, and provides selected safety entries. These registry entries establish what the study was designed to describe and give some context for the registry’s safety reporting.
The record does not report the primary endpoint mean, standard deviation, or confidence interval. It therefore does not show the observed bleed frequency or the precision of that estimate. A statistically careful interpretation cannot fill in those missing results from the endpoint title, study description, or enrollment information. Nor can it infer that the endpoint was favorable or unfavorable.
The design also does not provide a separate comparator. A single-group result, even if reported, would describe the observed group and would not by itself identify what changed because of treatment. No baseline result or controlled contrast is reported. The registry record therefore does not establish a comparative treatment effect.
The safety entries show reported counts and named serious-event terms, but they do not give a controlled comparison or the context needed to determine attribution. The count of deaths is not reported in the registry record. A listed event should not be interpreted as proof of a treatment-caused event, and the absence of a reported death count should not be read as a reported count of zero.
In short, the registry supports an account of design, intended endpoint, timeframe, and selected safety reporting. It does not provide enough outcome or analysis detail to quantify primary efficacy, assess its precision, or make a comparative conclusion. Those are limits of the information reported, not conclusions about what may appear in other study documents.
14. Why This Trial Matters Statistically
This study is statistically informative as an example of the difference between a defined endpoint and a reported result. The registry names a continuous primary measure, gives its unit, describes the population, and specifies an assessment period. Those details help readers understand what was intended to be summarized. Yet a statistical interpretation also requires the observed estimate and some account of uncertainty; neither is reported for the primary endpoint.
The single-group structure is equally important. A study can describe outcomes among treated participants without providing a controlled estimate of a treatment contrast. Recognizing that distinction prevents a descriptive result from being overstated as evidence about what would happen under another treatment or condition. The record lists allocation as NA and does not identify a control group, so comparative claims are not supported by its design description.
The record also illustrates why analysis-population and follow-up details matter for a frequency outcome. The endpoint is defined after at least 50 Exposure Days and at least 6 months, but the number contributing data and the handling of incomplete observation are not reported. For recurring events, time under observation and within-participant dependence can affect how an average and its uncertainty should be estimated. The methods used are not reported in the registry record.
Finally, safety counts and event terms require context. They describe registry entries, but without a comparator they do not estimate relative risk or establish causation. Statistical literacy means separating what is directly reported from what remains unknown, rather than filling gaps with assumptions.
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 main limitation for interpreting efficacy is that the registry record defines the primary endpoint but does not report its observed mean or standard deviation. It also provides no confidence interval, p-value, or comparative estimate for that outcome. Thus neither the measured frequency nor its statistical precision can be assessed from the record.
The single-group design has no listed comparator, and no baseline bleed frequency is reported. The record cannot support a randomized comparison or a documented change-from-baseline interpretation. Its endpoint population is described as all subjects who started prophylaxis, but the number who started and the number with endpoint data are not reported. The handling of missing observations, withdrawal, and variation in follow-up time is also not reported in the registry record.
The endpoint is a recurrent-event frequency, but the record does not describe event definitions, adjudication, observation-time adjustments, or the statistical model. It does not state whether dependence among repeated events or over-dispersion was assessed. The analysis plan, multiplicity approach, interim analyses, and protocol sample-size justification are not reported.
Safety information is limited to the listed affected counts and top serious terms. The record does not provide a control group, attribution details, or a reported death count. These limitations do not show that information is absent from all study documents; they identify what the registry record does not report and therefore what cannot be evaluated from it.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Human-cl rhFVIII in PTPs With Severe Hemophilia A — NCT01125813.
- Registry record last updated 2017-09-11; status last verified 2017-08.
- Results first posted 2013-04-22.
- 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.
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 NCT01125813, a completed phase 3, single-group study sponsored by Octapharma in previously treated patients with severe hemophilia A. It lists enrollment of 32, a start date of 2010-06, and primary completion in 2012-01. The intervention is recombinant Factor VIII, identified in the arm listing as Human Cl-rhFVIII. Allocation is listed as NA and masking as NONE.
The primary endpoint is mean spontaneous breakthrough bleeds per month during prophylactic treatment, assessed after at least 50 Exposure Days and at least 6 months. The endpoint population is described as all subjects who started prophylaxis. The observed mean, standard deviation, and confidence interval are not reported in the registry record. The listing includes serious- and other-adverse-event affected counts and two top serious terms, but no control group or reported death count. Analysis details, missing-data methods, and multiplicity procedures are not reported.