Treatment Patterns And Outcomes In Patients Treated With Benefix Or Refacto/Refacto AF - A Swedish Cohort Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment Patterns And Outcomes In Patients Treated With Benefix Or Refacto/Refacto AF - A Swedish Cohort Study (NCT02740413), a registered phase not stated study. The primary outcome is Age of Participants at Disease Diagnosis.

2. Clinical Question

3. Trial Design

This is a Swedish cohort study intended to describe demographic and clinical characteristics, treatment patterns, and outcomes among patients with haemophilia treated with BeneFIX or ReFacto/ReFacto AF. The registry identifies two diagnosis-based categories: patients with haemophilia A and patients with haemophilia B. Those categories describe the clinical condition, not randomized treatment arms. Allocation is not stated, and the record explicitly does not support treating the categories as a like-for-like control comparison.

The registry lists enrollment as 86 and the study status as completed. The study start date is 2016-01-11, and the primary completion date is 2017-12-31. The sponsor is Pfizer. The outcome population definition refers to patients diagnosed with haemophilia A or B in ICD-10, registered in the MHR since 1977, and with at least one registered prescription of one of the named products since the respective product's market authorization. The registry wording does not provide a complete account of how records were selected or how any exclusions were handled.

The primary outcome is age at disease diagnosis. Secondary outcomes concern average annual cost of prescribed factor concentrate and dispensed replacement treatment, and average cost of replacement treatment related to invasive procedures. The record lists 28 outcome measures and 0 analyses. The posted information does not include numerical results for the primary age outcome or the cost outcomes, nor does it describe an inferential comparison between the diagnosis categories. Consequently, the study is best read as a registry-based descriptive study as represented in this record, not as evidence from a randomized comparison.

The registry record does not report a randomization method, allocation concealment, blinding, or a planned control group. It also does not report a detailed statistical analysis plan. These omissions limit what can be concluded about design choices and the intended handling of potential differences between the groups.

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: The study was a retrospective population-based register study. Detailed data on each participant diagnosed with haemophilia was retrieved from the Malmö Haemophilia Register (MHR) in January 2016 covering the period of January 2005 up to December 2015.

Overall Study

Analysis population for the primary outcome, as defined in the registry: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, "N"= number of participants evaluable for this outcome measure.

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: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in International Statistical Classification of Diseases and Related Health Problems (ICD-10), registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product

6. Primary Endpoint

The registry lists the primary outcome as Age of Participants at Disease Diagnosis, measured over At disease diagnosis within 11 years before the study start date (Day 1).

The primary endpoint is age at disease diagnosis, measured in years. The registry specifies the mean as the summary measure and the standard deviation as the measure of dispersion. Age at diagnosis can describe when the condition was first recorded or recognized in the defined registry population, and it offers a way to characterize that population. It is not itself a measure of treatment response or a comparison of the effects of the named products.

The stated timeframe is disease diagnosis within 11 years before the study start date, Day 1. The population definition refers to people with haemophilia A or B recorded in the MHR and at least one registered prescription of BeneFIX or ReFacto/ReFacto AF since market authorization of the respective product. Readers should therefore interpret the endpoint in the context of this defined registry population and timeframe, rather than as a measure for all people with haemophilia or for an unrestricted period.

The registry record identifies the planned type of summary but does not report the observed mean, standard deviation, or number of observations contributing to this endpoint. Without those results, the distribution and precision of age at diagnosis cannot be assessed. In general, the mean describes the average value, while the standard deviation describes variability around that average; neither alone establishes a treatment effect or explains why diagnosis occurred at a particular age.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure and specifies the mean and standard deviation. These are descriptive statistics. The mean represents the arithmetic average of the observed values. The standard deviation describes how dispersed values are around that average. A larger standard deviation indicates more spread in the observations, while a smaller one indicates values are more concentrated near the mean. Neither statistic is a measure of causal effect, and neither conveys the full shape of a distribution when values are skewed or contain influential extremes.

What does a mean describe?

For age at diagnosis, a mean would give a concise summary of the recorded ages in the endpoint population. It is useful for describing a central value, but it can be influenced by unusually low or high observations. It also depends on which records are included and how age at diagnosis was defined and captured. Those operational details are not reported in the registry record. The record states the measure and timeframe, but it does not provide the observed mean or the number of observations used to calculate it.

What does the standard deviation add?

The standard deviation complements the mean by describing variability among the observed ages. It is not the same as a confidence interval. A standard deviation describes variation among individual measurements; a confidence interval, when calculated, describes uncertainty around an estimated quantity under a statistical model. The registry record does not report a confidence interval for the primary outcome. It also does not report the numerical standard deviation, so the observed variation cannot be assessed.

In general, confidence intervals help readers judge how precisely an estimate is determined under the analysis assumptions. A narrow interval suggests less sampling uncertainty than a wide interval, although interval width does not address bias from selection, measurement, or missing data. An interval also does not on its own show whether an estimate is clinically important. Since no age estimate or confidence interval is reported in this registry record, those aspects of precision cannot be evaluated for the primary endpoint.

Why is this not a randomized comparison?

The registry describes a cohort and defines categories by haemophilia diagnosis. It does not state that treatment assignment was randomized; allocation is not stated. The record also cautions that the arms are not a like-for-like control comparison. In general, random assignment can help balance measured and unmeasured characteristics between treatment groups, while an observational cohort may retain differences related to disease, clinical history, prescribing, or data availability. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured confounding. The registry record reports 0 analyses, so it does not provide adjusted estimates or details of any such method.

The study aim is descriptive: it concerns characteristics, treatment patterns, and outcomes in the relevant registry populations. Descriptive statistics can show how recorded values are distributed in the cohort, but a descriptive result should not be interpreted as the effect of a product. A causal comparison would require a suitable design and clearly specified analyses that address the relevant sources of bias. Those details are not reported in the registry record.

How should planning calculations be read?

Planning illustrations based on an observed effect are not observed study results and are not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is the total number of events; other illustrations express participants per arm. These are planning conventions, not evidence that the study used those assumptions in its own design.

The registry record does not report an observed primary endpoint effect from which to assess such an illustration, nor does it report the trial's own sample-size justification. A planning estimate depends on its assumptions, including the effect size selected and the analysis model. If the underlying observed effect is unstable or not available, the illustration cannot be treated as a reliable prediction of the information needed for a future study. In particular, a planning calculation should not be described as proof that an existing study had adequate power.

Over-dispersion is a general statistical concern when observed variability exceeds what a model assumes. If a model understates variability, standard errors can be too small and confidence intervals or tests may appear more decisive than warranted. The primary endpoint is continuous and is specified with a standard deviation, but the registry record does not report a fitted model or any assessment of over-dispersion. This general concept therefore explains a possible modeling issue; it does not describe a reported feature of this analysis.

Finally, registry-based summaries depend on recording practices. In general, an estimate can be affected by incomplete records, inconsistent measurement, or the way eligibility is applied. The record describes the broad eligibility basis but does not report data validation, missing-data methods, or sensitivity analyses. These are important elements for interpreting a statistical result, and their absence means the methods cannot be fully reconstructed from the registry information.

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.

R code and output

arm <- c("Benefix/Refacto/Refacto AF: Haemophilia A", "Benefix/Refacto/Refacto AF: Haemophilia B")
n   <- c(28, 50)
m   <- c(5, 7)
sp  <- c(10.1, 10.7)
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  Benefix/Refacto/Refacto AF: Haemophilia A  28  5.000  10.100  1.084  8.916
CARM  Benefix/Refacto/Refacto AF: Haemophilia B  50  7.000  10.700  3.959  10.041

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 28 outcome measures and 0 analyses. The number of registered measures means there are several outcomes of interest, but it does not reveal which results were analyzed, whether they were treated as primary or secondary for inference, or how the chance of false-positive findings was considered. Multiplicity methods and any hierarchy among outcomes are not reported in the registry record. Without that information, a reader cannot determine whether any statistical testing adjusted for examining multiple outcomes.

The primary outcome is identified as age at disease diagnosis, with the mean and standard deviation specified. The record does not give the number of observations contributing to that endpoint, the amount of missing data, or the method used to handle missing values. It also does not report whether participants with incomplete registry information were excluded, whether values were imputed, or whether sensitivity analyses were conducted. These details matter because missingness can change the composition of the analyzed population and may affect a descriptive estimate.

The record's population definition refers to MHR registration and at least one registered prescription of a named product since its market authorization. However, the registry information does not report a full participant flow, outcome-specific analysis populations, or reasons for exclusion. It would therefore be inappropriate to assume that enrollment, eligibility, and the number contributing to each outcome are identical. The statistical analysis plan and any prespecified approach to multiplicity or missing data are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry's adverse-event summary lists the combined Benefix/Refacto/Refacto AF category with 86 at risk. It records 0 serious affected, 0 other affected, and 0 deaths, and no serious event terms are listed. These are the figures entered in the registry summary. They describe the reported counts in this category and should not be expanded into a claim that all possible adverse events were absent.

The record does not describe how adverse events were defined, collected, reviewed, or followed over time. It also does not provide event-level detail, exposure time, or a discussion of completeness. Without those details, the zero counts cannot be used to assess the sensitivity of event capture or to compare safety between products. The combined category also does not provide separate safety counts for BeneFIX and ReFacto/ReFacto AF.

In general, a recorded zero is an observation in a particular dataset and under its reporting process; it is not proof that the underlying risk is zero. These figures should be read as a limited registry summary rather than as a definitive estimate of safety.

13. What the Result Does, and Does Not, Mean

The record establishes the study's descriptive focus: characteristics, treatment patterns, and outcomes among Swedish registry patients with haemophilia A or B treated with BeneFIX or ReFacto/ReFacto AF. It identifies age at disease diagnosis as the primary endpoint, specifies a mean and standard deviation, and defines a population linked to MHR registration and product prescriptions. It also lists cost-related secondary outcomes and provides a limited adverse-event summary.

The record does not give the primary endpoint's mean or standard deviation, numerical results for the cost outcomes, or inferential analyses. Although 28 outcome measures are listed, 0 analyses are reported. The available information therefore cannot establish the observed age distribution, the size of any cost outcome, or the precision of estimates. Nor does the adverse-event summary establish the absence of unrecorded events.

The disease-defined groups are not a like-for-like control comparison, and allocation is not stated. The record does not provide a basis for attributing differences in outcomes to the products. Descriptive data from a registry can characterize the records captured, but they do not by themselves show that a treatment caused an outcome or that one product performs better than another.

General statistical interpretation also depends on the definition of the analysis population, missing-data handling, and methods used to account for uncertainty and multiple outcomes. Those details are not reported in the registry record. The findings should therefore be understood within the limits of the registered cohort description and the information actually reported, without extending them to people outside the defined population or to causal treatment claims.

14. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the role of registry cohorts in describing treatment patterns and clinical characteristics in a defined population. The registry population is based on MHR registration, diagnosis, and product-prescription criteria. Such definitions determine who is represented and set the boundaries for interpreting descriptive outcomes. The primary endpoint, age at disease diagnosis, provides a potentially useful population characteristic, but the registry record does not report its numerical summary.

The record also makes clear why design labels and group definitions matter. Haemophilia A and haemophilia B are disease categories, not randomized product groups. Allocation is not stated, and the record warns against treating the categories as like-for-like controls. This distinction prevents an unsupported causal reading of a descriptive comparison and highlights the importance of asking what a group actually represents before interpreting its statistics.

A further statistical lesson concerns the difference between registered outcomes and reported analyses. The record lists 28 outcome measures and 0 analyses. This makes clear that an outcome inventory is not itself a results report. Readers need estimates, denominators, uncertainty measures, and analytic methods to judge the empirical evidence. Without them, even a stated endpoint type and timeframe do not allow assessment of magnitude or precision.

Finally, the adverse-event counts show why registry summaries need context. Counts of 0 are meaningful as reported entries, but their interpretation depends on event definitions, observation, and completeness. Those details are not reported. The study therefore matters as an example of how registry-based evidence can be useful for descriptive purposes while still requiring caution about causal inference, missing information, and the limits of the posted analysis.

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 contains limited numerical outcome information. It specifies the primary endpoint as age at disease diagnosis, summarized by mean and standard deviation, but does not report the values or the number contributing to the estimate. The listed secondary outcomes concern treatment costs, but their numerical results are not reported in the record. Although 28 outcome measures are listed, 0 analyses are reported, so the available information does not permit evaluation of the planned or performed inferential methods.

The design information also limits interpretation. The study is a cohort study, allocation is not stated, and the diagnosis-defined groups are not a like-for-like control comparison. The record does not report a protocol for adjustment, a statistical analysis plan, or a sample-size justification. It does not describe how potential confounding, differences in clinical history, or differences in treatment patterns were handled.

The record does not provide an outcome-specific account of missingness, participant flow, or analysis populations. It does not say whether data were imputed, how incomplete records were treated, or whether sensitivity analyses were performed. The definition refers to MHR registration since 1977 and at least one registered prescription since product market authorization, but details of implementation and data validation are not reported.

For safety, the record presents counts but does not describe event definitions, surveillance, duration of observation, or completeness of reporting. The combined product category does not provide separate counts for each named product. These limitations do not negate the descriptive information in the record, but they constrain what can be concluded from it and make broad generalization or causal interpretation inappropriate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment Patterns And Outcomes In Patients Treated With Benefix Or Refacto/Refacto AF - A Swedish Cohort Study — NCT02740413.
• Registry record last updated 2025-07-16; status last verified 2025-07.
• Results first posted 2019-05-03.
• 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.

19. Record Summary

NCT02740413 is a completed Swedish cohort study sponsored by Pfizer. Its stated aim is to describe demographic and clinical characteristics, treatment patterns, and outcomes among patients with haemophilia A or B treated with BeneFIX or ReFacto/ReFacto AF. The registry lists enrollment of 86, a study start date of 2016-01-11, and a primary completion date of 2017-12-31.

The primary endpoint is age at disease diagnosis, in years, summarized by mean and standard deviation, with a stated timeframe of diagnosis within 11 years before the study start date. Secondary outcomes concern average annual cost of prescribed factor concentrate and dispensed replacement treatment, and average cost related to invasive procedures. The record lists 28 outcome measures and 0 analyses. It does not report the numerical primary or secondary outcome results. The adverse-event summary records 0 serious affected, 0 other affected, and 0 deaths in the listed combined product category.