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 Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD) (NCT01410227), a non-randomized phase 3 study. The primary outcome is Percentage of Participants With Treatment Success for Treated Bleeding Episodes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01410227 |
| Phase | Phase 3 |
| Condition | Von Willebrand Disease |
| Allocation | Non-Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 49 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Baxalta now part of Shire |
| Results posted | Yes |
2. Clinical Question
The study asked whether recombinant von Willebrand factor (rVWF), alone or with recombinant factor VIII (rFVIII), could be used to treat bleeding episodes in people with severe hereditary von Willebrand disease (VWD). The broader study purpose also included assessment of pharmacokinetics and safety. Its primary efficacy question was framed around participants’ ratings of control across bleeding episodes treated with study product, rather than a direct comparison of randomized treatment groups.
Population
Participants diagnosed with VWD. The study description focuses on severe hereditary VWD; the treatment-only arm could include participants independent of VWD subtype.
Intervention
Study treatment of bleeding episodes with recombinant von Willebrand factor, with or without recombinant factor VIII, during the treatment period.
Comparator
The study was non-randomized and had a crossover model. The registry record does not establish a randomized, like-for-like control comparison for the primary efficacy question.
Primary question
What percentage of participants met the study’s definition of treatment success for treated bleeding episodes during the stated treatment period?
The primary endpoint required an efficacy rating for a participant’s treated bleeding episodes. Treatment success was defined using the participant’s mean efficacy rating, with a score below 2.5. The rating reflected the extent of bleeding control and whether additional VWF was required. This makes the endpoint a participant-level summary of episode ratings, not simply a count of episodes rated successful.
The registry record reports enrollment of 49 participants and describes several study arms with different pharmacokinetic assessments and treatment arrangements. It does not report the percentage meeting the primary endpoint, the number of participants included in that endpoint analysis, or an uncertainty interval for the result. Therefore, the clinical question can be described, but the registry record does not allow the primary efficacy finding to be stated.
3. Trial Design
This was a completed phase 3 study with non-randomized allocation, no masking, and a crossover model. Enrollment was 49. The recorded study start was 2011-11-01, and primary completion was 2014-02-01. The study concerned pharmacokinetics, safety, and efficacy of rVWF:rFVIII and rVWF for treatment of bleeding episodes in VWD.
The registry describes distinct groups rather than a single uniform comparison. The PK 80 arm had a pharmacokinetic assessment using 80 IU/kg rVWF followed by a 12-month treatment period, with a minimum of 22 subjects with severe VWD. The PK 50 arm included 14 subjects with type 3 VWD, two single-blinded pharmacokinetic assessments using 50 IU/kg rVWF plus rFVIII or placebo, and a 12-month treatment period. The PK 50 Only arm had a pharmacokinetic assessment using 50 IU/kg rVWF and no treatment of bleeding episodes, with a minimum of 7 subjects with type 3 VWD. The Treatment Only arm treated bleeding episodes for a total of 12 months and could include up to 7 subjects independent of VWD subtype.
These group descriptions indicate that participants did not all follow the same study pathway. Some underwent pharmacokinetic assessments, and some were eligible for treatment of bleeding episodes under the described schedule. The crossover label and the single-blinded assessments in one arm do not make the overall study a randomized trial. Allocation is explicitly recorded as non-randomized, and masking as none. The registry record does not report enough detail to reconstruct the sequence of all treatment periods or to establish a balanced comparison between study products.
The registry lists rVWF, placebo, and rFVIII as interventions. Their presence in the intervention list does not by itself define a control group for the primary efficacy outcome. The study arms had differing eligibility, objectives, and treatment exposure, so comparisons between them would require careful interpretation. A randomized comparator, allocation concealment, and a protocol-level account of the crossover sequence are not reported in the registry record.
The study status is completed. Completion status means the registry lists the study as finished; it does not establish that every planned outcome was reported or that the primary endpoint result is available in the 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: 49 participants provided informed consent and were screened for the study, of which 37 were exposed to study product. Reasons for discontinuation were 6 screen failures, consent withdrawn by 3 participants, 1 physician decision, 1 participant received high doses of rFVIII for oral procedure and arm for which 1 participant was eligible was closed.
Overall Study
| Stage | Arm 1: PK50 + Treatment | Arm 2: PK50 Only | Arm 3: PK80 + Treatment | Arm 4: Treatment Only |
|---|---|---|---|---|
| STARTED | 8 | 8 | 15 | 6 |
| COMPLETED | 4 | 8 | 13 | 5 |
| NOT COMPLETED | 4 | 0 | 2 | 1 |
Reasons for not completing this period:
| Reason | Arm 1: PK50 + Treatment | Arm 2: PK50 Only | Arm 3: PK80 + Treatment | Arm 4: Treatment Only |
|---|---|---|---|---|
| Adverse Event | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 3 | 0 | 1 | 0 |
| Pregnancy | 0 | 0 | 0 | 1 |
| Met Excl. Criteria After Starting Study | 0 | 0 | 1 | 0 |
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: Baseline consists of all participants in study \[N=37\] so is a total of the four arms described in Participant Flow (Arm 1: PK50 + Treatment \[N=8\]; Arm 2: PK50 Only \[N=8\]; Arm 3: PK80 + Treatment \[N=15\]; Arm 4: Treatment Only \[N=6\]).
| Characteristic | Unit | All Subjects Treated With Study Product |
|---|---|---|
| Participants analysed | 37 | |
| Age, Continuous | Years | 37 (18 to 64) |
| Sex: Female, Male: Female | Participants | 20 |
| Sex: Female, Male: Male | Participants | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Treatment Success for Treated Bleeding Episodes, measured over For 12 months after first infusion of rVWF:rFVIII or rVWF.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 90% Confidence Interval |
| Unit | Percent of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with treatment success for treated bleeding episodes. It summarizes the efficacy ratings for a participant’s bleeding episodes treated with study product over the stated 12-month period after the first infusion. The definition uses the participant’s mean efficacy rating score, with treatment success set at a score below 2.5.
Ratings represented the degree of bleeding control and treatment requirements. An excellent rating corresponded to no more than the estimated number of infusions required and no additional VWF. A good rating allowed some additional infusions relative to the estimate, depending on bleed severity, but still required no additional VWF. Moderate ratings reflected a larger infusion requirement, while a rating of none represented severe uncontrolled bleeding or no change in bleeding intensity, with additional VWF required. The endpoint therefore combines clinical judgment about control with information about treatment burden.
A participant-level percentage can be useful when the question concerns how many participants achieved an overall level of control, rather than how many individual episodes received a favorable rating. However, it condenses variation among episodes: a participant with multiple episodes contributes a summary rating rather than a separate participant for each episode. Interpretation depends on how episode ratings were collected and summarized.
The stated endpoint population included participants with an available primary efficacy rating, prospectively excluding gastrointestinal bleeds, in the Full Analysis Set. The registry record does not report the primary endpoint percentage, its 90% confidence interval, or the number of participants contributing to that result. The endpoint definition is reported, but its observed finding is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the primary endpoint definition but no primary endpoint result. It does not report the percentage of participants classified as having treatment success, the corresponding 90% confidence interval, or the number analyzed for that endpoint. Consequently, the posted record does not support a statement about the observed frequency of success or the precision of that estimate. The endpoint’s wording should not be mistaken for a reported finding.
The study’s non-randomized design also matters when interpreting any comparisons across its groups. The arms differed in pharmacokinetic assessments, eligibility, and whether bleeding episodes were treated. The registry lists a crossover model, but allocation was non-randomized and masking was recorded as none. Any differences between groups could therefore reflect differences in who entered each group, their study pathway, or their treatment exposure, as well as the treatments themselves. The registry record does not report an adjusted comparison that would address such differences.
The primary endpoint is participant-level and based on ratings of treated episodes. It uses a threshold on the mean efficacy rating, so it converts a graded measure into a treatment-success classification. This can make the result easier to describe as a percentage, while concealing variation in scores near the threshold and differences in the number or severity of episodes contributing to each participant’s mean. The recorded endpoint also prospectively excludes gastrointestinal bleeds. The resulting outcome is therefore specific to the included bleeding episodes, not an all-bleed summary.
The record lists 67 outcome measures and 1 analysis. The registry does not explain how the analysis relates to the full set of outcomes, whether other analyses were conducted, or whether any outcome-selection procedure was used. The statistical analysis plan, missing-data procedures, and multiplicity strategy are not reported in the registry record. This limits the ability to judge how the endpoint was selected, how uncertainty was handled, and whether the reported analysis was prespecified.
Safety figures are reported for a Safety Analysis Set of 37 participants. The record lists 7 affected participants among 37 at risk for serious adverse events and 14 among 37 at risk for other adverse events. The listed serious-event terms each have a reported percentage of 2.7%. These are descriptive safety summaries; they do not provide a randomized comparison or establish that a particular treatment caused an event. The death count is not reported in the registry record.
Any sample-size figures associated with planning illustrations should be read as hypothetical planning calculations, not as observed trial findings or observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. Those assumptions are not a substitute for the trial’s own design rationale, which is not reported in the registry record.
9. Statistical Methods Explained
The primary endpoint is a proportion: participants meeting the study’s definition of treatment success divided by the participants eligible for the endpoint analysis. A proportion describes how common a classification was in the analyzed group. It does not, on its own, describe the size of a treatment effect relative to a control group. The registry record does not report the primary proportion or its uncertainty interval, so neither the estimate nor its precision can be interpreted from the record.
What does a confidence interval communicate?
A confidence interval expresses uncertainty around an estimate under the statistical model used to construct it. A narrower interval indicates greater precision under that model; a wider interval indicates less precision. It is not a range that guarantees where the true value lies, and it does not correct biases in study design, outcome measurement, or missing data. The primary endpoint specifies a 90% confidence interval, but its bounds are not reported in the registry record. There is therefore no basis in this record for describing the width or location of that interval.
What does the participant-level endpoint summarize?
Each participant’s efficacy rating was based on treated bleeding episodes, and success depended on a mean score below 2.5. Turning a graded scale into a binary success classification makes the result readable as a percentage, but it discards detail about how far participants’ scores were from the threshold. It also means that episodes are not necessarily independent observations in the endpoint: multiple episodes may contribute to the same participant-level summary. An analysis that instead treated every episode as independent could understate uncertainty if observations from the same participant are correlated. The registry record does not report an episode-level analysis or its statistical handling.
The categories themselves combine infusion requirements, estimated treatment needs, control of bleeding, and whether additional VWF was required. This makes the rating clinically interpretable as a measure of control and treatment burden. It also means that reproducibility depends on consistent application of the rating definitions and the estimates used to judge required infusions. The registry record states the score definitions but does not report information on assessor training, agreement between assessors, or adjudication.
Why does the study design affect comparisons?
Random allocation can help balance measured and unmeasured participant characteristics across treatment groups. This study is recorded as non-randomized, so comparisons among its arms cannot rely on randomization to support that balance. The arms also had different study arrangements, including pharmacokinetic-only participation and treatment of bleeding episodes. A comparison of outcomes across such groups could be affected by eligibility and treatment-pathway differences. The crossover label describes the general model, but the registry record does not report the full sequence, washout arrangements, or a primary analysis accounting for period or sequence effects. These details are not reported in the registry record.
Masking is recorded as none for the study. In an outcome based on efficacy ratings, knowledge of treatment can potentially influence reporting or assessment. This is a general methodological concern, not evidence that ratings in this study were biased. The record does not describe safeguards that may have been used to standardize or independently assess ratings.
How should the planning calculations be read?
The sample-size assumptions describe a planning illustration rather than the trial’s own design justification. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It sets the effect to detect as a stated fraction of the observed effect. Such calculations are hypothetical: they describe the sample size implied by chosen assumptions, not the probability that the completed study detected an effect. They are not observed power. The registry record does not report the trial’s sample-size justification or the assumptions used by the investigators to plan enrollment.
For a binary outcome, planning calculations depend on the assumed event proportions and the effect considered important, in addition to the chosen error rate and allocation. Changing those assumptions changes the required sample size. If an assumed effect is taken from an observed estimate, the illustration is conditional on that estimate and its uncertainty. It should not be interpreted as evidence that the study was adequately powered or that the observed endpoint result is reliable. The primary endpoint result itself is not reported in the registry record.
Why can over-dispersion matter?
Over-dispersion is a general statistical issue that arises when observed variability is greater than a model expects. For repeated bleeding episodes, participants may differ in their tendency to experience episodes or in their responses, so the episode outcomes can be more variable than a simple model assumes. A model that ignores this extra variability may produce confidence intervals that are too narrow. The registry record does not report an episode-count model or evidence that over-dispersion was assessed for this trial; this is a general consideration, not a description of an analysis known to have been used.
For a participant-level binary endpoint, the relevant uncertainty also depends on how many participants were analyzed and how success was defined and recorded. For episode-level secondary outcomes, the within-participant structure would need attention if multiple episodes contributed per person. The registry’s outcome list includes measures such as efficacy ratings and the number of infusions or units per bleeding episode, but it does not give the methods used for their statistical analysis.
The record lists 67 outcome measures and 1 analysis, without explaining the analysis family, model, covariates, confidence-interval method, or handling of repeated observations. These statistical details are not reported in the registry record. General methodological explanations can clarify what such choices mean, but they cannot establish which choices the investigators made.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Full Analysis Set | 18 | 18 | 100.0% | 81.5% to 100.0% | 82.4% to 100.0% | 82.4% to 99.9% |
R code and output
arm <- c("Full Analysis Set")
n <- c(18)
events <- c(18)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Full Analysis Set 18 18 100.0 81.5 100.0 82.4 100.0 82.4 99.911. Multiplicity, Missing Data and Analysis Populations
The registry lists 67 outcome measures and 1 analysis. A large set of outcomes can raise multiplicity concerns: when many statistical questions are examined, the chance of at least one apparently notable result can increase if each is treated as a separate confirmatory test. Statistical plans can address this by defining a primary outcome, specifying a testing order, or adjusting interpretation for multiple comparisons. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or whether secondary outcomes were considered confirmatory.
The primary outcome is defined as the percentage of participants with treatment success, and the endpoint population includes participants with an available primary efficacy rating in the Full Analysis Set. The description also says that gastrointestinal bleeds are prospectively excluded from the primary efficacy rating. It does not report how participants without an available rating were handled, how many were missing, or whether sensitivity analyses were conducted. These missing-data procedures are not reported in the registry record.
Missingness can affect interpretation when the availability of an outcome is related to participants’ health, treatment experience, or likelihood of success. General approaches include describing missingness, using prespecified assumptions, and testing whether conclusions change under alternative assumptions. The registry record does not specify whether such approaches were used. The number analyzed for the primary endpoint is also not reported in the registry record.
The Safety Analysis Set is stated to include 37 participants, but the endpoint-analysis population and the relationship between analysis populations are not described. The registry record does not report whether all enrolled participants were included in each outcome analysis, or how exclusions and withdrawals were handled. Conclusions about missing data or multiplicity should therefore remain limited to what the record states, rather than assuming a particular analysis plan.
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 |
|---|---|---|---|
| Safety Analysis Set | 7 | 37 | 18.9% |
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 |
|---|---|
| Safety Analysis Set | 14 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | Safety Analysis Set |
|---|---|---|
| Constipation | Gastrointestinal disorders | 1 of 37 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 37 |
| Haemorrhoids | Gastrointestinal disorders | 1 of 37 |
| Mesenteric haematoma | Gastrointestinal disorders | 1 of 37 |
| Chest discomfort | General disorders | 1 of 37 |
| Osteomyelitis | Infections and infestations | 1 of 37 |
| Heart rate increased | Infections and infestations | 1 of 37 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 1 of 37 |
| Uterine polyp | Reproductive system and breast disorders | 1 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Safety Analysis Set |
|---|---|---|
| Headache | Nervous system disorders | 4 of 37 |
| Iron deficiency anaemia | Blood and lymphatic system disorders | 3 of 37 |
| Vomiting | Gastrointestinal disorders | 3 of 37 |
| Upper respiratory tract infection | Infections and infestations | 3 of 37 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 3 of 37 |
| Anaemia | Blood and lymphatic system disorders | 2 of 37 |
| Vertigo | Ear and labyrinth disorders | 2 of 37 |
| Nausea | Gastrointestinal disorders | 2 of 37 |
| Infusion site paraesthesia | General disorders | 2 of 37 |
| Contusion | Injury, poisoning and procedural complications | 2 of 37 |
Serious events with the highest arm-level rate: constipation (2.7%), gastrointestinal haemorrhage (2.7%), haemorrhoids (2.7%), mesenteric haematoma (2.7%), chest discomfort (2.7%).
The registry reports safety findings for a Safety Analysis Set of 37 participants. For serious adverse events, it lists 7 affected participants among 37 at risk. For other adverse events, it lists 14 affected participants among 37 at risk. These are participant counts in the registry’s safety categories; the figures do not show how many events each participant experienced.
The listed serious adverse-event terms are constipation, gastrointestinal haemorrhage, haemorrhoids, mesenteric haematoma, chest discomfort, and osteomyelitis. Each term has a reported percentage of 2.7%. The record does not state whether participants could contribute to more than one term, so these percentages should not be added or treated as mutually exclusive categories.
Adverse-event summaries describe events recorded during the study and do not by themselves establish causation. Because the study was non-randomized, these figures are not a randomized comparison of safety between treatments. The registry record does not report a death count. It also does not provide enough information in these figures to interpret event timing, exposure duration by treatment, or differences in risk across the study arms.
13. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 3 study of rVWF, with or without rFVIII, was completed and that its stated aims included pharmacokinetics, safety, and treatment of bleeding episodes in VWD. It also gives the primary efficacy definition, study-arm descriptions, and selected safety counts. These registry entries describe the study and the outcomes it intended to assess.
The record does not report the primary efficacy percentage or its 90% confidence interval. It therefore does not show how many participants met the success definition or how precisely that percentage was estimated. Without the endpoint result, no conclusion about the observed frequency of treatment success can be drawn from this registry record. A detailed endpoint definition is not a substitute for its result.
The design also limits what a between-group comparison could establish. Allocation was non-randomized, masking was recorded as none, and the arms differed in their pharmacokinetic assessments and treatment arrangements. Those features do not erase the descriptive value of the study, but they mean that an observed difference across groups would not automatically be attributable to treatment. The registry record does not report a randomized, like-for-like comparison for the primary question.
The safety summaries show that serious and other adverse events were recorded in the Safety Analysis Set, with specific serious-event terms listed. The figures do not establish that study treatment caused those events, and they do not provide a randomized comparison of adverse-event risk. The listed percentages should be read as reported for their respective terms, without assuming that categories are exclusive.
More generally, statistical interpretation requires the estimate, its uncertainty, the analyzed population, and sufficient information about the analysis plan. The registry record lacks the primary result and does not report key details about missing data, multiplicity, or the investigators’ statistical methods. Accordingly, the available record supports a description of the study design and endpoint, but not a quantitative conclusion about primary efficacy or a causal comparison between treatments.
14. Why This Trial Matters Statistically
This study illustrates why a clearly stated endpoint and a reported endpoint result are different parts of a clinical-trial record. The primary outcome is defined in detail: it uses participant-level mean ratings of treated bleeding episodes and a threshold for treatment success. That definition allows readers to understand what the study intended to measure. But the registry record does not report the resulting percentage or its confidence interval, so the central efficacy estimate cannot be evaluated from this record.
The study also makes visible the distinction between an intervention list and a valid control comparison. rVWF, placebo, and rFVIII are listed, but the study is non-randomized and includes arms with different purposes and treatment pathways. A control-like intervention does not by itself make the primary analysis a randomized comparison. Interpretation depends on allocation and on whether groups are sufficiently comparable, not simply on the presence of multiple named interventions.
Its endpoint brings together episode ratings, treatment burden, and participant-level classification. That approach is understandable for summarizing experience across bleeding episodes, while also raising statistical questions about repeated observations, score thresholds, and the information lost when a graded measure is converted to success or not. These are general issues to consider when reading outcomes built from multiple events per participant.
Finally, the registry lists many outcome measures but gives little information about multiplicity, missing data, and analysis methods. This shows why outcome definitions alone cannot establish how robust a result is. A statistical interpretation needs transparent reporting of the estimate, uncertainty, analysis population, and methods. Here, the record supplies useful design and endpoint context, but leaves the primary efficacy finding unavailable.
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 registry record does not report the primary endpoint result, the 90% confidence interval, or the number of participants included in the primary efficacy analysis. It is therefore not possible to assess the observed efficacy estimate or its precision from the record. The stated endpoint population includes participants with an available rating and prospectively excludes gastrointestinal bleeds, but the record does not report the impact of that exclusion or the number of ratings unavailable.
Allocation was non-randomized, and the study arms had different eligibility and assessment arrangements. This limits straightforward comparisons among arms, particularly if participants differed in clinical or study characteristics. Masking was recorded as none. The registry record does not report an analysis that adjusts for potential group differences, nor does it describe the sequence and other details needed to assess crossover-period effects.
The primary outcome depends on ratings of bleeding control and treatment requirements. The registry gives the rating categories, but does not report who assigned ratings, how consistency was maintained, whether ratings were independently reviewed, or how disagreements were handled. These unreported details matter because judgment is part of the endpoint definition.
The record lists 67 outcome measures and 1 analysis, but does not report a multiplicity plan, the statistical model, covariate adjustment, missing-data approach, or sensitivity analyses. It also does not report the trial’s own sample-size justification. These are limitations of what can be learned from the registry record and should not be interpreted as evidence that the study did or did not use any particular method.
The safety figures are descriptive and do not provide randomized treatment-specific comparisons. The death count is not reported in the registry record. The listed serious-event percentages do not establish whether event categories overlap or how exposure and timing relate to each event.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD) — NCT01410227.
- Registry record last updated 2021-05-19; status last verified 2021-04.
- Results first posted 2016-04-21.
- 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
This completed phase 3 study enrolled 49 participants and examined pharmacokinetics, safety, and efficacy of rVWF:rFVIII and rVWF for bleeding episodes in VWD. The design was non-randomized, unmasked, and described as a crossover model. Study arms included pharmacokinetic assessments and treatment periods with differing eligibility and arrangements.
The primary endpoint was the percentage of participants meeting a participant-level treatment-success definition based on mean efficacy ratings for treated bleeding episodes. Its stated timeframe was 12 months after first infusion, and the primary efficacy rating prospectively excluded gastrointestinal bleeds. The registry record does not report the primary endpoint result or its 90% confidence interval.
For the Safety Analysis Set, the record lists 7 participants with serious adverse events and 14 with other adverse events, each among 37 at risk. Six serious-event terms are listed at 2.7% each. The record lists 67 outcome measures and 1 analysis; details of multiplicity, missing-data handling, and the statistical analysis plan are not reported in the registry record.