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 a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients (NCT00157157), a na phase 3 study. The primary outcome is Factor VIII Inhibitor Development.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00157157 |
| Phase | Phase 3 |
| Condition | Hemophilia A |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 66 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Baxalta now part of Shire |
| Results posted | Yes |
2. Clinical Question
Population
Previously untreated patients with hemophilia A were eligible for the study. The primary-outcome population was participants who received at least 1 infusion of rAHF-PFM. The registry record lists 66 enrolled participants, but does not state how many received an infusion or contributed to the primary analysis.
Intervention
Participants received recombinant antihemophilic factor manufactured and formulated without added human or animal proteins, identified as rAHF-PFM. The registry record describes a single study arm and does not provide a separate untreated or active-comparator group.
Comparator
There was no randomized comparator. Allocation is recorded as not applicable, and the study is described as single-group and unmasked. Consequently, the study does not provide a like-for-like comparison of rAHF-PFM with another treatment or with no treatment.
Primary question
The primary question was what percentage of treated participants developed factor VIII inhibitors during the study period. Follow-up was to last at least 75 exposure days or 3 years, whichever came first. The numerical percentage and its 95% confidence interval are not reported in the registry record.
This question addresses an immune response to factor VIII in participants who had not previously been treated with factor VIII. The registry also lists outcomes concerning bleeding episodes, hemostasis, treatment use, recovery, and surgical outcomes. Those outcomes give broader context about the study’s aims, but the listed outcome names do not supply numerical results.
Because the trial had one group, its primary endpoint is descriptive: it records the observed proportion of treated participants who developed inhibitors. It cannot, by itself, establish how that proportion compares with what would have occurred under another treatment or in the absence of treatment. That distinction matters when interpreting both the primary outcome and the safety listings.
3. Trial Design
The registry record describes a completed Phase 3, single-group study of rAHF-PFM in previously untreated patients with hemophilia A. It lists 66 participants as enrolled. The intervention was a recombinant antihemophilic factor manufactured and formulated without added human or animal proteins. The sponsor is recorded as Baxalta now part of Shire.
The study began on 2004-04-01, and primary completion is recorded as 2009-09-11. The registry status is completed. These dates describe the study record; they do not give each participant’s follow-up duration. The primary endpoint timeframe was assessed during a study period that was to be at least 75 exposure days or 3 years, whichever came first.
Allocation is recorded as not applicable, masking as none, and the model as single group. The arm description identifies one arm containing eligible enrolled participants. There is therefore no randomized treatment contrast in this record. An outcome observed in this group cannot be interpreted as the difference caused by rAHF-PFM relative to a concurrent control.
The primary outcome was factor VIII inhibitor development, expressed as the percentage of treated participants who developed inhibitors. Its analysis population is specified as participants who received at least 1 infusion of rAHF-PFM. The registry lists a 95% confidence interval as the dispersion measure, but the numerical estimate and interval are not reported in the registry record.
The record lists 14 outcome measures and 3 analyses. It identifies secondary outcomes involving treated bleeding episodes, hemostasis assessments, annualized bleeding, weekly product use, in vivo incremental recovery, and surgical outcomes. The specific results for these measures, the detailed analysis procedures, and the reasons for selecting this design are not reported in the registry record. A protocol rationale, sample-size justification, or interim-analysis plan is also not reported in the registry record.
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: Participants screened for maximum 21 days. Study was not randomized; it was an open-label evaluation. Prior to initial infusion, a minimum washout period of 3 days was required. 11 participants who enrolled did not receive any rAHF-PFM infusions (3 withdrew consent, 6 screen failures, 1 non-compliance with screening, 1 pre-existing low hemoglobin)
Overall Study
| Stage | Previously Untreated Patients (PUPs) |
|---|---|
| STARTED | 55 |
| COMPLETED | 44 |
| NOT COMPLETED | 11 |
Reasons for not completing this period:
| Reason | Previously Untreated Patients (PUPs) |
|---|---|
| Withdrawal by Subject | 6 |
| Physician Decision | 1 |
| Lost to Follow-up | 1 |
| Enrolled in another study | 1 |
| Met exclusion criteria | 1 |
| Inclusion not met- baseline FVIII value | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants who received at least 1 infusion of rAHF-PFM
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 | PUPs |
|---|---|---|
| Participants analysed | 55 | |
| Age, Customized: <6 months | Participants | 21 |
| Age, Customized: 6-12 months | Participants | 26 |
| Age, Customized: ≥13 months | Participants | 8 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 55 |
6. Primary Endpoint
The registry lists the primary outcome as Factor VIII Inhibitor Development, measured over Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of treated participants who developed factor VIII inhibitors. The registry defines the relevant population as participants who received at least 1 infusion of rAHF-PFM and gives the assessment period as at least 75 exposure days or 3 years, whichever came first.
In general, a percentage summarizes how often a defined outcome occurred in a specified group. The accompanying 95% confidence interval is intended to convey uncertainty around that estimate: a narrower interval indicates greater statistical precision, while a wider interval indicates greater uncertainty. The interval does not remove limitations arising from the study design, the participants observed, or the way follow-up and outcomes were recorded.
Inhibitor development is used as a clinically relevant immunogenicity outcome: it records whether participants developed antibodies that inhibit factor VIII. The registry states that the purpose of the study was to evaluate efficacy and safety, and its primary endpoint focuses on inhibitor development. The record also lists separate secondary outcomes relating to bleeding, hemostasis, recovery, utilization, and surgery.
The registry record does not report the primary percentage, the confidence limits, or the number of participants included in this endpoint analysis. It is therefore not possible to describe the observed primary result or its precision from this record alone. The serious-adverse-event listing includes a Factor VIII inhibition term, but that safety listing is not a substitute for the primary endpoint estimate and does not provide its confidence interval.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study asks a focused descriptive question about factor VIII inhibitor development among previously untreated patients who received rAHF-PFM. The record identifies the endpoint, the analysis population, and the intended follow-up timeframe. It does not give the numerical primary estimate, confidence interval, or primary-analysis denominator. The key result and its precision are therefore not reported in the registry record.
The study’s single-group design shapes what can be inferred. It can describe outcomes observed among participants in the treated group, but it does not create a randomized comparison with another treatment. Without a like-for-like control group, differences attributable specifically to the intervention cannot be separated from other explanations, such as characteristics of the enrolled participants, their clinical course, or how outcomes were assessed. This is a general limitation of interpreting uncontrolled treatment groups, not evidence that any particular alternative explanation occurred in this study.
The registry records 66 enrolled participants, but enrollment alone does not establish how many received at least 1 infusion, reached the intended follow-up, or were included in the primary analysis. The primary outcome population is defined by receipt of an infusion, while the reported enrollment count covers those enrolled. The number analyzed and the handling of incomplete follow-up are not reported in the registry record. Those details are important for understanding how much information supports the endpoint.
A confidence interval, in general, communicates the statistical uncertainty around an estimate. The registry names a 95% confidence interval as the dispersion measure, but without the estimate and interval, neither the observed proportion nor its precision can be assessed. Even when reported, a confidence interval describes uncertainty under the analysis assumptions; it does not correct for selection, missing outcomes, or the lack of a comparator.
The serious-adverse-event listings include Factor VIII inhibition at 29.1%, as well as Coagulopathy, Mouth injury, and Pyrexia at 3.6% each, and Bacteraemia and Bronchial hyperreactivity at 1.8% each. These are safety listings and should not be treated as a complete account of all outcomes or as the primary endpoint estimate. The record also gives affected-participant counts for serious and other adverse events, but does not provide details that would establish how those listed terms relate to the primary endpoint population.
Interpretation should therefore stay close to what the registry records: a completed single-group study, a defined inhibitor-development endpoint, several additional outcome areas, and adverse-event summaries. The record does not report the primary numerical result, a comparative treatment effect, or enough analysis detail to assess missing data, adjustments, or the statistical plan. These gaps limit conclusions about the magnitude and precision of the primary finding.
9. Statistical Methods Explained
What does a single-group design estimate?
In general, a single-group study describes outcomes observed among participants who received the intervention. The primary endpoint in this record is a percentage of treated participants who developed factor VIII inhibitors. Such an estimate is a summary of the study group, not a comparison between treatment strategies. A randomized comparison would use groups assigned to different strategies to estimate a contrast; this record does not describe such a comparison.
The registry records allocation as not applicable, masking as none, and the model as single group. Those design features mean that readers should not interpret the outcome as a randomized treatment effect. Open-label status can also matter generally because knowledge of treatment may affect reporting, clinical decisions, or outcome assessment. The record does not describe how those possibilities were addressed.
What does the confidence interval contribute?
In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. It is used to express uncertainty around an estimate, rather than to guarantee that the true value lies within a particular range. An interval’s width reflects statistical precision: narrower intervals indicate more precision, and wider intervals indicate less.
The registry identifies a 95% confidence interval for the primary endpoint. However, the numerical endpoint estimate and its interval are not reported in the registry record. Without them, readers cannot judge either the observed percentage or the precision of that percentage. The interval would not, by itself, establish a treatment effect, because the design has no randomized comparator.
Why does the analysis population matter?
The primary analysis population is specified as participants who received at least 1 infusion. This is narrower than the registry’s enrollment figure unless every enrolled participant received an infusion, and that is not reported in the registry record. In general, defining the population clarifies whose outcomes contribute to an endpoint. It also means that readers need to know how many participants met the definition and how many had outcome information available.
The number of participants analyzed for inhibitor development, the number with missing endpoint data, and the treatment of participants with incomplete follow-up are not reported in the registry record. These details affect how an observed percentage should be understood. For example, if follow-up or outcome availability differs across participants, the estimate may describe only those with recorded outcomes rather than everyone who entered the study. Whether that occurred in this study is not reported in the registry record.
How should the follow-up timeframe be understood?
The primary endpoint was assessed during a study period that was to be at least 75 exposure days or 3 years, whichever came first. This defines the intended endpoint timeframe in terms of exposure or elapsed time. It does not state that every participant completed the same duration of follow-up. Participant-level exposure, follow-up distributions, and timing of inhibitor development are not reported in the registry record.
In general, when participants have different observation times, a simple percentage and a time-to-event analysis answer different questions. A percentage describes the share meeting an outcome within a defined observation scheme; a time-to-event method accounts for when the event occurs and how long participants are observed. The registry does not specify a time-to-event method for the primary endpoint, so the statistical approach beyond the listed percentage and confidence interval is not reported in the registry record.
What do the other outcomes add?
The registry lists secondary outcomes concerning bleeding episodes treated with 1 to ≥4 infusions, assessment of hemostasis for bleeding episodes, annualized bleeding, weekly rAHF-PFM utilization, in vivo incremental recovery, intra-operative and postoperative hemostasis, and blood loss during surgical procedures. In general, outcomes from multiple domains can describe different aspects of a study, but each requires its own definition, analysis population, and interpretation. The titles alone do not provide estimates or methods for those outcomes.
The record lists 14 outcome measures and 3 analyses. It does not report how the analyses were assigned to outcomes, which results were confirmatory, or whether any adjustment was used for multiple testing. A multiplicity adjustment is a method that accounts for the increased chance of false-positive findings when several hypotheses are tested. Whether an adjustment was planned or used is not reported in the registry record.
How should planning illustrations be read?
Planning illustrations are distinct from the trial’s observed results and from its original design justification. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events using the Schoenfeld method; other illustrations give participants per arm.
These assumptions describe hypothetical planning calculations, not the design of this single-group trial. The record does not report that the original study used these assumptions, and the illustrations should not be interpreted as observed power. In general, such calculations explore what sample size might be needed under chosen assumptions. They do not change the amount of information actually collected, establish that the original study was adequately powered, or supply the missing primary estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures and 3 analyses, including the primary inhibitor-development endpoint and secondary measures concerning bleeding, hemostasis, utilization, recovery, and surgery. With multiple outcomes, general statistical practice distinguishes a prespecified primary question from additional analyses, because testing many hypotheses can increase the chance of at least one apparently notable result by chance. An adjustment can address that issue, but no multiplicity procedure is reported in the registry record.
The registry record does not report a detailed statistical analysis plan, the hierarchy of secondary outcomes, or which analyses were confirmatory. It also does not report whether analyses were adjusted for baseline characteristics or other factors. No adjustment should be assumed from the outcome list alone.
The primary analysis population is defined as participants who received at least 1 infusion. The number in that population, the number with primary outcome data, and the handling of missing or incomplete observations are not reported in the registry record. In general, missing outcomes can affect an estimate if participants with and without recorded outcomes differ in relevant ways. The record does not state whether any imputation, censoring, or sensitivity analysis was used.
The record lists a confidence interval for the primary percentage, but the numerical estimate and interval are absent. It also does not describe interim analyses, stopping rules, or a sample-size justification for the original trial. These omissions prevent a full assessment of how the analysis was planned and how incomplete data or multiple outcomes were handled.
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 |
|---|---|---|---|
| PUPs | 28 | 55 | 50.9% |
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 |
|---|---|
| PUPs | 52 of 55 |
Most frequent serious adverse event terms
| Event term | Organ system | PUPs |
|---|---|---|
| Factor VIII inhibition | Blood and lymphatic system disorders | 16 of 55 |
| Coagulopathy | Blood and lymphatic system disorders | 2 of 55 |
| Mouth injury | Injury, poisoning and procedural complications | 2 of 55 |
| Pyrexia | General disorders | 2 of 55 |
| Bacteraemia | Infections and infestations | 1 of 55 |
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | 1 of 55 |
| Bronchitis | Infections and infestations | 1 of 55 |
| Catheter bacteraemia | Infections and infestations | 1 of 55 |
| Catheter related infection | Infections and infestations | 1 of 55 |
| Catheter site haematoma | General disorders | 1 of 55 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PUPs |
|---|---|---|
| Pyrexia | General disorders | 39 of 55 |
| Nasopharyngitis | Infections and infestations | 28 of 55 |
| Cough | Respiratory, thoracic and mediastinal disorders | 23 of 55 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 22 of 55 |
| Diarrhea | Gastrointestinal disorders | 20 of 55 |
| Ear infection | Infections and infestations | 20 of 55 |
| Vomiting | Gastrointestinal disorders | 17 of 55 |
| Upper respiratory tract infection | Infections and infestations | 16 of 55 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 15 of 55 |
| Rash | Skin and subcutaneous tissue disorders | 13 of 55 |
Serious events with the highest arm-level rate: factor viii inhibition (29.1%), coagulopathy (3.6%), mouth injury (3.6%), pyrexia (3.6%), bacteraemia (1.8%).
The registry lists 55 participants at risk and 28 affected for serious adverse events in the PUPs group. It separately lists 55 at risk and 52 affected for other adverse events. These are participant counts, not counts of individual event episodes. The record does not give additional detail about the event definitions, timing, severity grades, or relationships to treatment for these summaries.
The most prominent listed serious-event term is Factor VIII inhibition at 29.1%. Other listed terms are Coagulopathy, Mouth injury, and Pyrexia at 3.6% each, and Bacteraemia and Bronchial hyperreactivity at 1.8% each. These percentages should be read as registry safety listings; the record does not explain their calculation denominator in the information.
Factor VIII inhibition also appears as the primary outcome, but the safety listing does not replace the primary endpoint result. The primary percentage and its 95% confidence interval are not reported in the registry record. Safety summaries also do not establish that an event was caused by treatment. The record does not provide a comparison group for estimating relative safety, and the listed terms are not a complete account of all possible clinical outcomes.
12. What the Result Does, and Does Not, Mean
The registry describes a completed single-group Phase 3 study of rAHF-PFM in previously untreated patients with hemophilia A. It identifies inhibitor development as the primary endpoint and specifies the population and intended follow-up timeframe. These details make the study question clear, but the registry does not report the numerical primary estimate or its 95% confidence interval.
That missing result prevents readers from determining the recorded percentage of treated participants who developed factor VIII inhibitors, or how precise that estimate was. The adverse-event listing includes Factor VIII inhibition at 29.1%, but that safety summary is not an adequate substitute for the primary outcome result. The record does not report enough information to reconcile the two summaries or establish that they use the same definition and analysis population.
The single-group design can describe outcomes among enrolled and treated participants, but it cannot establish a randomized comparison with another treatment. Even a complete outcome estimate would not, on its own, show what would have happened under a different treatment strategy. The absence of a comparator also limits conclusions about whether differences in outcomes are attributable to the intervention.
The registry lists secondary outcomes spanning bleeding, hemostasis, product use, recovery, and surgery, but their numerical findings and detailed analysis methods are not reported in the registry record. The record also does not report the number contributing to the primary analysis, missing-data methods, multiplicity procedures, interim analyses, or the original sample-size justification.
The result therefore supports a limited statistical reading: the trial was designed to assess inhibitor development and other outcomes in a previously untreated population, but the available registry entries do not establish the primary outcome’s observed magnitude or precision. They also do not establish comparative efficacy or safety. Those are limits of what can be concluded from the registry record, not claims about results that are absent from it.
13. Why This Trial Matters Statistically
This study raises statistical questions that are important when evaluating a treatment in a previously untreated population. Its primary endpoint concerns inhibitor development, and its population is defined as participants who received at least 1 infusion. The endpoint and population definitions are essential: a percentage is meaningful only when readers know which participants and which outcome it summarizes.
The study also illustrates why design and precision must be considered together. A confidence interval can describe uncertainty around an estimate, but the registry does not report the numerical primary estimate or interval. And even a precise estimate from one group would remain descriptive in the absence of a concurrent randomized comparator. Precision and causal comparison are different properties of evidence.
Follow-up is framed around exposure days or elapsed time, with the intended period stated as at least 75 exposure days or 3 years, whichever came first. In general, exposure-based follow-up can be relevant when participants accrue treatment experience at different rates. To interpret an endpoint fully, however, readers also need information about actual follow-up, endpoint ascertainment, and the number analyzed. Those details are not reported in the registry record.
The record lists a range of secondary outcomes, which reflect several clinical domains beyond inhibitor development. Such breadth makes clear why outcome definitions, analysis populations, and multiplicity methods matter. The record does not report how multiple analyses were prioritized or adjusted.
Finally, the study demonstrates the difference between planning illustrations and evidence collected in a trial. Hypothetical sample-size calculations cannot replace the observed result or validate a design retrospectively. The registry record’s omissions make these distinctions especially important when interpreting what the study can and cannot establish.
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 main limitation for statistical interpretation is that the primary endpoint’s numerical percentage and 95% confidence interval are not reported in the registry record. The primary-analysis denominator is also not reported, although the record defines that population as participants who received at least 1 infusion. Enrollment of 66 does not establish how many participants received treatment or contributed outcome data.
The single-group design has no randomized comparator. It can describe outcomes in the study group but cannot provide a like-for-like estimate of differences relative to another treatment. Masking is recorded as none, and the record does not describe procedures used to limit possible effects of unmasked outcome assessment.
The intended primary timeframe is at least 75 exposure days or 3 years, whichever came first, but actual participant-level follow-up and exposure are not reported in the registry record. The number of participants with incomplete follow-up, the handling of missing endpoint data, and any sensitivity analyses are also not reported.
The record lists 14 outcome measures and 3 analyses, but does not state the analysis hierarchy, multiplicity approach, detailed statistical methods, or which outcomes were confirmatory. Interim analyses, stopping rules, and the original sample-size justification are not reported in the registry record. The planning assumptions described for hypothetical illustrations should not be treated as the trial’s original design rationale.
Safety summaries include participant counts and selected serious-event terms, but further details about event definitions, timing, causality, and denominators are not reported. The registry information therefore does not support a complete assessment of outcome ascertainment, analysis conduct, or comparative benefit and harm.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients — NCT00157157.
- Registry record last updated 2021-05-24; status last verified 2021-04.
- Results first posted 2011-07-15.
- 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.
18. Record Summary
The registry record describes NCT00157157, a completed Phase 3, single-group study of rAHF-PFM in previously untreated patients with hemophilia A. It lists 66 enrolled participants, no masking, and allocation recorded as not applicable. The sponsor is recorded as Baxalta now part of Shire.
The primary endpoint was the percentage of treated participants who developed factor VIII inhibitors. The endpoint population was participants who received at least 1 infusion, with assessment during a period intended to be at least 75 exposure days or 3 years, whichever came first. The registry lists a 95% confidence interval but does not report the numerical endpoint result or interval.
Secondary outcomes cover bleeding, hemostasis, product use, recovery, and surgery. The record lists 14 outcome measures and 3 analyses. It also reports serious and other adverse-event participant counts and selected serious-event terms. The detailed statistical plan, missing-data handling, multiplicity approach, and primary-analysis denominator are not reported in the registry record.