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 Evaluating B-Domain Deleted Recombinant Factor VIII (BDDrFVIII, ReFacto AF) in Patients With Hemophilia A Undergoing Elective Major Surgery (NCT00243659), a non-randomized phase 3 study. The primary outcome is Number of Patients Who Achieved Hemostatic Efficacy After Surgery.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00243659 |
| Phase | Phase 3 |
| Condition | Hemophilia A |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wyeth is now a wholly owned subsidiary of Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Patients with severe or moderately severe Hemophilia A undergoing elective major surgery. The primary analysis population is described as efficacy evaluable at visit three; the number in that population is not reported in the registry record.
Intervention
ReFacto AF administered by bolus injections or continuous infusion. The record does not report the specific dosing schedules or the criteria used to choose the administration method.
Comparator
The record describes the two administration approaches in parallel, non-randomized groups. It does not describe a randomized control group, and the groups should not be treated as a like-for-like comparison.
Primary question
How many patients achieved hemostatic efficacy after surgery, as judged by the investigator and/or surgeon using an ordinal assessment? The endpoint description names Excellent, Good, Moderate, and None, but the registry does not report the resulting patient counts or clarify which categories constitute achievement.
The study focuses on hemostasis around elective major surgery in patients with Hemophilia A. Its brief summary frames the question as examining the efficacy and safety of ReFacto AF when administered by bolus injections or continuous infusion. The primary outcome is a count of patients who achieved hemostatic efficacy after surgery, with efficacy assessed at the end of surgery according to the outcome description. The listed timeframe is 6 weeks, and the relationship between that timeframe and the end-of-surgery assessment is not clarified in the registry record.
The clinical question is descriptive as well as comparative: the record identifies two administration approaches, but the non-randomized allocation does not establish that patients receiving each approach were comparable at baseline. The record does not report arm descriptions, participant characteristics by group, or criteria for choosing bolus injection versus continuous infusion. Consequently, differences between groups, if reported elsewhere, could reflect patient or treatment-selection differences as well as the administration approach. The posted registry information does not include primary outcome counts, estimates of uncertainty, or a statistical comparison. It therefore does not establish the size or precision of any difference in hemostatic efficacy.
3. Trial Design
This is a phase 3, open-label, multicenter study with a parallel model and non-randomized allocation. The registry lists enrollment as 30 and the study status as completed. The recorded start is 2006-04 and primary completion is 2008-06. The listed condition is Hemophilia A, and the title and summary describe patients undergoing elective major surgery. The summary specifies severe and moderately severe disease.
The study examines ReFacto AF administered either by bolus injections (BI) or continuous infusion (CI). The intervention is classified as biological. Although the record identifies these administration approaches, it leaves both arm descriptions blank. Dosing details, treatment assignment procedures, eligibility criteria beyond the population description, and the reasons for selecting an administration approach are not reported in the registry record. The enrollment figure should not be interpreted as the number analyzed for the primary outcome; the analyzed population size is not reported.
Open-label means that masking is listed as none. In general, knowledge of the treatment approach can influence care, assessment, or reporting, particularly when an outcome depends on investigator or surgeon judgment. Non-randomized allocation also means that treatment groups may differ in ways related to their assignment. These features limit the strength of direct comparisons between the groups. The record itself flags that the arms are not a like-for-like control comparison.
The registry lists a secondary outcome, the number of patients who achieved hemostatic efficacy at hospital discharge, and reports two outcome measures overall. It does not describe the timing or methods for all assessments, the statistical analysis plan, or how safety follow-up was structured. Wyeth is listed as sponsor; the record notes that Wyeth is now a wholly owned subsidiary of Pfizer. The record does not report whether any interim analyses were planned or conducted, or how the enrollment target was determined.
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: Patients were screened for a maximum of 42 days.
Overall Study
| Stage | Bolus Injection | Continuous Infusion |
|---|---|---|
| STARTED | 22 | 8 |
| COMPLETED | 20 | 5 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Bolus Injection | Continuous Infusion |
|---|---|---|
| Withdrawal by Subject | 1 | 1 |
| Protocol Violation | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: The analysis population is the efficacy evaluable at visit three.
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 | Bolus Injection | Continuous Infusion | Total |
|---|---|---|---|---|
| Participants analysed | 22 | 8 | 30 | |
| Age Continuous | years | 35.05 (SD 9.51) | 38.13 (SD 8.54) | 35.87 (SD 9.22) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0.0 |
| Sex: Female, Male: Male | Participants | 22 | 8 | 30.0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients Who Achieved Hemostatic Efficacy After Surgery, measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | patients |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of patients who achieved hemostatic efficacy after surgery. The outcome description says the investigator and/or surgeon assessed efficacy at the end of surgery using an ordinal scale with the categories Excellent, Good, Moderate, and None. It describes Excellent as hemostasis comparable to that in non-hemophilic patients, and Good as prolonged time to hemostasis with somewhat increased bleeding compared with non-hemophilic patients. The descriptions of Moderate and None are not reported in the registry record. The listed timeframe is 6 weeks, but the record does not explain how that timeframe relates to the end-of-surgery assessment.
A count of patients with an outcome can communicate how many participants were judged to have achieved a specified clinical status. It is most interpretable alongside the number assessed, the definition of success, and a measure of uncertainty. Those details are important because the endpoint uses an ordered clinical judgment rather than a reported laboratory threshold. The registry does not specify whether only Excellent, Excellent or Good, or another grouping constitutes “achieved” hemostatic efficacy. Nor does it provide the primary outcome count, denominator, or an estimate with a confidence interval. Accordingly, the endpoint's intended clinical construct is identifiable, but its operational success threshold and observed result cannot be established from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary outcome and the study's intended comparison, but it does not report primary endpoint results. There are no posted counts of patients achieving hemostatic efficacy, no denominators for the primary analysis, and no reported treatment-effect estimate or confidence interval. No p-value or other inferential result is reported. The clinical effect and its precision therefore cannot be evaluated from this record. The absence of an analysis entry is not evidence that the outcome was zero or that no analysis was performed outside the registry.
Interpretation also depends on how “achieved” was defined. The scale lists Excellent, Good, Moderate, and None, while the description gives definitions for Excellent and Good. The registry does not say which categories were counted as achievement. Without that threshold, even a count alone would be difficult to interpret consistently. The record also gives a 6 weeks timeframe while describing efficacy at the end of surgery; it does not clarify whether the assessment was made at surgery, during follow-up, or at both times.
The design warrants caution about any comparison between bolus injection and continuous infusion. Allocation was non-randomized, and masking was absent. In general, non-randomized treatment groups can differ because of clinical decisions or other factors associated with treatment selection. An observed difference would not automatically isolate an effect of administration method. Open-label assessment may also be vulnerable to differences in expectations or judgment, especially for a clinician-assessed endpoint. The registry does not report adjustment methods or baseline comparisons that could help assess these concerns.
The adverse-event record lists 4 affected for serious adverse events in the Bolus Injection group and 1 in the Continuous Infusion group. It lists 19 and 7 affected, respectively, for other adverse events. The numbers at risk are not reported, so these counts cannot be interpreted as rates or compared as risks. Death counts are not reported in the registry record. The record also lists serious adverse-event terms with percentages, including Fever and Hemorrhage at 12.5%, Cough increased at 12.5%, Factor VIII inhibition at 9.1%, and Accidental injury and Cellulitis at 4.5%. The relevant denominators and the attribution of those percentages to a specific group are not reported, so those percentages should not be treated as group-specific rates.
Overall, the posted information describes the question, design, and some safety counts, but does not establish the primary efficacy result. The completed status does not substitute for outcome estimates. A reader cannot infer either benefit or lack of benefit, or compare the two administration approaches reliably, from the missing primary results and incomplete denominators.
9. Statistical Methods Explained
The registry describes the primary outcome as a number of patients, which is a count rather than a continuous measurement. For a count to be interpretable as a proportion or risk, the number assessed in the relevant group must also be known. In general, a count without its denominator does not show how common the outcome was among participants at risk or assessed. The record does not report the primary outcome counts or denominators, so neither a proportion nor a between-group estimate can be recovered from the registry information.
What does the ordinal assessment capture?
The outcome is based on an ordinal scale: Excellent, Good, Moderate, or None. Ordinal categories have a meaningful order, but the distance between adjacent categories is not necessarily equal. A shift from None to Moderate need not represent the same clinical change as a shift from Good to Excellent. Analysts can report the category distribution, or define a clinically motivated threshold and analyze the resulting count. Those approaches answer different questions. The registry names the scale and gives partial category descriptions, but does not specify the threshold used to classify patients as having achieved efficacy. It also does not report the distribution across categories.
The assessment is attributed to the investigator and/or surgeon. In general, clinician judgment can be appropriate for a clinical outcome, but its reproducibility depends on clear criteria and consistent application. Open-label assessment can introduce the possibility that expectations affect ratings. Blinded review or standardized assessment rules can reduce some sources of measurement bias, but masking is listed as none and the registry does not describe additional safeguards. This is a methodological concern, not evidence that assessments were biased in this study.
What can a comparison estimate?
A treatment comparison generally contrasts outcomes between groups using a defined estimand, such as a difference in proportions or a relative measure. An estimate should be accompanied by a confidence interval, which expresses the range of values compatible with the data under the statistical model and assumptions. A narrow interval indicates greater precision than a wide interval; an interval alone does not correct bias from study design or measurement. The registry record does not report an estimate or confidence interval for the primary endpoint. There is therefore no basis for describing the magnitude or precision of a comparison.
Random allocation is commonly used to balance measured and unmeasured prognostic factors on average. This study is listed as non-randomized. In general, differences in patient condition, surgical circumstances, or clinical decisions could affect which administration method was used and could also relate to the outcome. An adjusted analysis can address measured differences when the relevant variables are collected and the model is suitable, but it cannot guarantee removal of unmeasured confounding. No adjustment strategy or covariate set is reported in the registry record. The non-randomized design means that any contrast should be read as an association unless stronger design or analysis details support a causal interpretation.
How should the adverse-event counts be read?
The registry lists affected counts for serious and other adverse events separately by administration group. Without numbers at risk, exposure time, or clear event definitions and collection procedures, the counts do not provide rates. Counts may also depend on how long participants were followed and how events were collected. The record does not report those details. The listed serious-event terms and percentages should be interpreted cautiously because their denominators and group attribution are not stated. A percentage is meaningful only when its underlying population and calculation are clear.
What do the planning assumptions mean?
The record includes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The illustration describes detecting a stated fraction of the observed effect. These are planning assumptions, not evidence about how participants were allocated or how the trial was designed. In particular, the equal-allocation assumption does not establish equal enrollment in the actual groups. Sample-size illustrations are not observed power and do not show that the study had adequate precision. The primary result needed to interpret an observed-effect-based illustration is not reported in the registry record, and the record does not report the trial's own sample-size justification or statistical plan.
For count outcomes, statistical methods should reflect both the event definition and the denominator. For clustered, repeated, or highly variable count data, over-dispersion can make a simple model underestimate uncertainty; methods that allow extra variation may be more appropriate. This is a general consideration, not a claim about the data in this study. The record does not report a model for the primary endpoint, an over-dispersion assessment, or any model diagnostics. Because the endpoint is described as a patient count in two groups rather than a repeated event count, the appropriate analysis would depend on the precise outcome definition and available denominators, which are not fully described.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary outcome of patients achieving hemostatic efficacy after surgery and a secondary outcome of patients achieving hemostatic efficacy at hospital discharge. It does not report a multiplicity procedure or explain how interpretation would account for examining more than one outcome. In general, evaluating multiple outcomes can increase the chance of emphasizing a result that appears notable by chance. Prespecifying a primary endpoint and controlling or describing multiplicity can make interpretation clearer. The registry identifies a primary outcome, but its analysis plan is not reported.
Missing-data methods are not reported in the registry record. The record does not give the number assessed for the primary endpoint, reasons for missing assessments, or how missing outcomes were handled. These details matter because a count of successful outcomes can be affected by who is included in the analysis and how unavailable assessments are treated. No imputation method, sensitivity analysis, or participant-flow accounting is described.
The primary analysis population is described as “efficacy evaluable at visit three.” The number in that population and the criteria for being efficacy evaluable are not reported. This population may differ from the enrollment figure, but the record does not provide enough information to characterize that difference. It also does not report whether all enrolled participants were included in the safety summaries or how the analysis populations were defined for secondary outcomes. These omissions limit assessment of selection into the analysis and the completeness of outcome reporting.
11. What the Result Does, and Does Not, Mean
The registry record establishes that the study was completed and that it was designed to examine ReFacto AF administered by bolus injections or continuous infusion in patients with Hemophilia A undergoing elective major surgery. It also identifies a clinician-assessed primary endpoint and reports some adverse-event affected counts. Those details describe the study's scope; they do not establish the primary outcome result.
The record does not report how many patients achieved hemostatic efficacy, how many were assessed, or the uncertainty around any estimate. It does not define clearly which ordinal categories count as success. As a result, the posted information cannot show the frequency of achieving the endpoint or the precision of an efficacy estimate. It also cannot establish whether the two administration approaches differed.
The design limits causal interpretation of any simple group contrast. Allocation was non-randomized, and treatment masking was absent. General statistical reasoning indicates that treatment selection and clinician assessment can influence observed comparisons. The registry does not report enough information about baseline characteristics, assignment decisions, adjustment, or assessment safeguards to evaluate how those issues were addressed.
The adverse-event counts are counts of affected participants, not rates, because numbers at risk are not reported. The listed event percentages lack stated denominators and group attribution. They therefore do not support a reliable comparison of safety between the groups. Missing primary results should not be interpreted as a null result, and the completed status should not be treated as evidence of a particular outcome. The information in the registry record is insufficient to conclude either that an administration approach performed better or that no difference existed.
12. Why This Trial Matters Statistically
This study raises several important statistical issues for clinical research. First, its primary endpoint combines a clinically meaningful judgment with a count-based result. A clear operational definition is essential: readers need to know which ordinal categories count as success and how assessments are made. Without that definition, the endpoint may not be reproducible across assessors or comparable across studies.
Second, the non-randomized design affects what a comparison can mean. Differences between bolus injection and continuous infusion groups could reflect differences in the patients or circumstances that led to treatment selection. Statistical adjustment can address measured factors under appropriate assumptions, but it cannot by itself make non-randomized groups equivalent. The record does not report an adjustment strategy, making it especially important not to read the groups as a randomized comparison.
Third, reporting counts without denominators restricts interpretation. A count does not establish the frequency of an outcome unless the number assessed or at risk is also clear. This applies to the primary endpoint and to the adverse-event summaries. Uncertainty estimates and transparent analysis populations would further show how precisely results are estimated and who contributes to them.
Finally, registry completeness matters. The study status is completed, yet the primary efficacy results and key analysis details are not reported in the registry record. Clear outcome definitions, participant flow, denominators, missing-data handling, and analysis methods allow readers to distinguish an unreported result from a null finding and to assess both precision and potential bias.
13. 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.
Several trial-specific limitations restrict interpretation of the registry information. The primary outcome is described as a number of patients achieving hemostatic efficacy, but the result and analysis denominator are not reported. The record also does not identify which categories on the Excellent, Good, Moderate, or None scale qualify as achievement. This leaves the endpoint's success threshold uncertain.
The outcome description places assessment at the end of surgery, while the listed timeframe is 6 weeks. The registry does not explain how those timing statements fit together. The analysis population is described as efficacy evaluable at visit three, but its size and eligibility criteria are not reported. Participant flow, missing assessments, and reasons for exclusion from the efficacy-evaluable population are also not reported.
The arms are non-randomized and open-label, and their descriptions are blank. The record does not provide group-specific baseline characteristics, dosing details, treatment-selection criteria, or an adjustment plan. These omissions make it difficult to assess comparability, measurement procedures, and the potential for confounding. No primary estimate, confidence interval, or analysis method is reported.
Safety reporting is incomplete for comparative interpretation: numbers at risk and death counts are not reported, and the denominators and group attribution for listed serious-event percentages are unclear. The registry does not report missing-data procedures, multiplicity handling, interim analyses, or the trial's sample-size justification. These are limitations of what is reported in the registry record and do not establish what may have been documented elsewhere.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Study Evaluating B-Domain Deleted Recombinant Factor VIII (BDDrFVIII, ReFacto AF) in Patients With Hemophilia A Undergoing Elective Major Surgery — NCT00243659.
- Registry record last updated 2011-06-03; status last verified 2011-06.
- Results first posted 2009-07-20.
- 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.
17. Record Summary
NCT00243659 is a completed phase 3, open-label, multicenter, non-randomized parallel study of ReFacto AF in patients with severe or moderately severe Hemophilia A undergoing elective major surgery. The study examined bolus injections and continuous infusion. Enrollment is listed as 30; the recorded start is 2006-04 and primary completion is 2008-06.
The primary endpoint is the number of patients achieving hemostatic efficacy after surgery, assessed by the investigator and/or surgeon on an ordinal scale. A secondary outcome concerns achievement at hospital discharge. The primary result, analysis denominator, and statistical analysis details are not reported in the registry record. The record lists adverse-event affected counts by group but does not report numbers at risk. Its non-randomized, unmasked design limits direct comparisons between administration groups.