An Observational Study On The Safety And Tolerability Of Prolonged Thrombosis Prophylaxis With Fragmin®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study On The Safety And Tolerability Of Prolonged Thrombosis Prophylaxis With Fragmin® (NCT01046903), a registered phase not stated study. The primary outcome is Physician's Assessment of Efficacy of Treatment.

2. Clinical Question

This is a descriptive question rather than a conventional randomized-trial question about whether one treatment outperforms another. The registry describes an observational study intended to observe use of Fragmin® in a high-risk orthopedic population after surgery. Its primary outcome asks how physicians rated treatment efficacy on a scale ranging from excellent to poor. That measure captures a clinical judgment, but the record does not report how the ratings were distributed or provide a treatment-effect estimate.

The study also names safety, tolerability, and compliance as objectives. Those objectives are relevant to prolonged prophylaxis, but the registry material available for interpretation does not give detailed compliance or tolerability results. Nor does it describe a comparison group that would permit separating treatment-related outcomes from the course of recovery, underlying patient risks, or other care. The record supports a description of what was assessed and which safety counts were posted; it does not establish a causal treatment benefit or harm.

3. Trial Design

The registry identifies NCT01046903 as a completed observational study sponsored by Pfizer. Its title concerns safety and tolerability of prolonged thrombosis prophylaxis with Fragmin® in patients undergoing major orthopedic surgery. The study start is recorded as 2010-03, and primary completion as 2011-02. Enrollment is listed as 503. The condition named is Venous Thromboembolism.

The intervention is Fragmin® (Dalteparin Sodium), classified as a drug. The registry summary says the objective was to observe safety, tolerability, and compliance in use of Fragmin® for prolonged thromboprophylaxis in post-surgery high-risk orthopedic patients. The record does not report the dose, the exact duration of prophylaxis, or detailed eligibility criteria. An allocation method is not stated. Because the study is observational and the record does not identify a comparable control group, the posted safety group should not be interpreted as one side of a randomized treatment comparison.

The primary outcome is Physician's Assessment of Efficacy of Treatment. It is defined as a participant count associated with a physician assessment on a five point categorical scale: excellent, very good, good, fair, or poor. The stated timeframe is baseline up to Week 5. Its analysis population, the Full Analysis Set, includes participants who received at least 1 dose of study medication. The enrollment figure should not automatically be substituted for the endpoint population because the record does not state that all enrolled participants entered that analysis set.

The registry lists 10 outcome measures but no analyses. The posted record does not describe the statistical analysis plan, a sample-size justification, interim analyses, or adjustments for confounding. It also does not give a detailed account of treatment exposure or follow-up completeness. These omissions limit the ability to reconstruct how observations were collected and analyzed, and they make the record more suitable for descriptive reading than for comparative-effectiveness conclusions.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) included all those participants who received at least 1 dose of the study medication.

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.

6. Primary Endpoint

The registry lists the primary outcome as Physician's Assessment of Efficacy of Treatment, measured over Baseline up to Week 5.

The primary endpoint is the physician's assessment of treatment efficacy, recorded as a participant count and evaluated from baseline up to Week 5. Physicians used a five point categorical scale: excellent, very good, good, fair, or poor. The stated Full Analysis Set includes all participants who received at least 1 dose of study medication.

This kind of endpoint is used to capture an overall clinical judgment rather than a single laboratory measurement or a narrowly defined event. Such judgments can bring together several aspects of a patient's observed course, but the registry does not specify which considerations physicians were instructed to weigh. It also does not report whether assessments were standardized across clinicians, whether assessors were blinded, or how disagreements were handled. Those details are not reported in the registry record.

The categories are ordered in a natural direction, but they are not necessarily equally spaced. A move from poor to fair cannot be assumed to represent the same amount of change as a move from very good to excellent. For that reason, counts within each category would be important for understanding the distribution. The registry information available for this interpretation describes the measure but does not provide its category results. No inference about the frequency of favorable or unfavorable assessments can therefore be made from the endpoint definition alone.

As a general measurement point, a physician rating can be informative while still depending on judgment and assessment practice. It should be interpreted as the outcome that was defined, not as a direct measure of prevention of venous thromboembolism unless the record specifies that link. The endpoint name and scale do not, on their own, establish treatment effectiveness.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is categorical, so its most direct descriptive presentation would show how many participants fell into each physician-rating category. The endpoint description defines five ordered responses, from excellent to poor, but the registry record does not report the counts for those responses. It also lists the outcome unit as participants and the parameter as a number. That indicates a count-based endpoint, not a continuous score or a time-to-event measure.

As a general statistical point, categorical data can be summarized by counts and, when the denominator is known, proportions. The denominator matters because a count alone does not indicate how common an outcome was among the people eligible for the analysis. Here, the endpoint population is defined as the Full Analysis Set: participants who received at least 1 dose. The registry enrollment figure is 503, but the record does not state that every enrolled participant was included in the endpoint analysis. The enrolled total should not be assumed to be the endpoint denominator.

The five categories have an order, but that does not guarantee equal spacing between them. Treating the responses as if they were measurements on an evenly spaced numerical scale would require an assumption that the registry does not state. A category-by-category description preserves the original meaning of the responses. A collapsed favorable-versus-unfavorable result would require a prespecified rule about which categories belong in each group; no such rule is reported. Nor does the record give a threshold defining a successful assessment.

What would a confidence interval add?

As a general explanation, a confidence interval communicates uncertainty around an estimate. It is not simply a measure of whether an estimate is clinically important, and it does not remove bias from study design or measurement. For a count or proportion, the interval depends on the analysis method and assumptions as well as on the observed data. No confidence interval for the primary endpoint or posted safety counts is reported in the registry record, so the precision of those quantities cannot be evaluated from the counts alone.

Why does the study design matter for inference?

An observational study describes outcomes arising during care without a randomized allocation specified in the record. In a randomized comparison, treatment groups are formed under a design intended to support a causal contrast. Here, allocation is not stated, and no like-for-like control group is identified. Differences in patient risk, treatment decisions, follow-up, and other care may shape observed outcomes. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjustment strategy or covariates. Even an adjusted analysis cannot automatically remove bias from factors that were not measured or modeled.

The record lists no analyses. Therefore, no modeling approach, hypothesis test, confidence interval method, or missing-data procedure can be attributed to the study from the registry information. In particular, it would be inappropriate to infer that a specific analysis was performed simply because the endpoint is categorical. The relevant analysis choices depend on the intended question, the way observations were recorded, and the availability of complete outcome data.

How should the safety counts be read?

The safety record gives a group labelled Dalteparin Sodium, with 503 at risk in the serious category and 26 affected; it also gives 503 at risk and 46 affected in the other adverse-event category. These are counts associated with binary event outcomes, not a randomized comparison. The serious-event terms are accompanied by percentages as listed in the registry. The record does not state whether the terms are mutually exclusive, whether repeated events in a participant are counted once or more than once, or how event attribution was determined. Accordingly, the figures should be read as registry-recorded safety summaries rather than as a complete causal account.

General methods for binary outcomes often rely on assumptions about independent observations and consistent event definitions. If outcomes cluster within participants or sites, or if participants have multiple events, methods that assume independent observations may understate uncertainty. Over-dispersion is a general concern when observed variability exceeds what a chosen model expects; however, the registry does not report a model or enough detail to determine whether that issue applies to its analyses. No model-based uncertainty estimate is reported.

Time-to-event methods answer a different question: they account for when an event occurs and may handle varying follow-up under specified assumptions. The primary physician-rating outcome is not described as time-to-event, and the safety record does not provide event times. Therefore, event timing, censoring, and a time-to-event comparison cannot be reconstructed from the stated information.

The planning illustrations use general design assumptions: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. For time-to-event tables, the stated convention is total events; for other tables, it is participants per arm. These are planning conventions, not observed trial results. They do not demonstrate observed power, establish a protocol target, or supply evidence of a treatment effect. The study's own sample-size justification and statistical plan are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures, but no analyses. It does not identify a hierarchy of primary and secondary hypotheses beyond naming Physician's Assessment of Efficacy of Treatment as the primary outcome. It also does not report whether multiple testing was planned, whether any adjustment was used, or how the multiplicity of outcomes was handled. Without an analysis plan and posted analysis results, it is not possible to assess how the number of outcomes may have affected interpretation.

Missing outcome data can affect both the estimated category distribution and its precision. The Full Analysis Set is defined as participants who received at least 1 dose, but the record does not state how many members of that set had an assessment at each time, whether any assessments were missing, or how missing observations were treated. It does not report imputation, complete-case analysis, sensitivity analysis, or reasons for missingness. These details are not reported in the registry record.

As a general statistical point, missingness is not only a matter of how many values are absent. The reasons values are missing may be related to a participant's health, treatment experience, or outcome, and those patterns can affect the validity of an analysis. A complete-case result may be misleading if the people with recorded outcomes differ systematically from those without them. Methods for addressing missingness require assumptions that should be stated and evaluated; none are described in the available registry information.

The record does not report interim analyses, stopping rules, or a statistical analysis plan. These omissions prevent assessment of whether the analysis was prespecified or whether analytic decisions were made after outcomes were observed. That uncertainty should not be filled by assuming a particular procedure. The most defensible reading is limited to the endpoint definition and safety counts actually recorded.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypokalaemia (0.8%), urinary tract infection (0.6%), lymphoedema (0.6%), subileus (0.4%), periprosthetic fracture (0.4%).

The registry safety record lists the Dalteparin Sodium group with 503 at risk and 26 affected in the serious adverse-event category. For other adverse events, it lists 503 at risk and 46 affected. These are separate entries, and the registry record does not explain whether an individual could appear in both categories. The counts should not be added together or treated as a count of unique participants.

The listed serious adverse-event terms and percentages are Hypokalaemia, 0.8%; Urinary tract infection, 0.6%; Lymphoedema, 0.6%; Subileus, 0.4%; Periprosthetic fracture, 0.4%; and Pulmonary embolism, 0.4%. These are selected terms, not a complete narrative of all safety findings. The record does not explain the selection rule for the terms, how events were attributed, or whether repeated events were counted separately.

As a general interpretation point, an adverse event occurring during treatment is not automatically caused by treatment. In an observational study without a like-for-like control group, these counts cannot show whether event frequency differs from what would have occurred under another treatment or without treatment. The deaths field has no reported value; deaths are therefore not reported in the registry record. The listed counts describe recorded safety observations, not a causal estimate.

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

The study provides a registry description of an observational effort to examine safety, tolerability, and compliance during prolonged thromboprophylaxis with Fragmin® in high-risk patients after major orthopedic surgery. It identifies a physician-rated primary endpoint and posts safety counts for a Dalteparin Sodium group. This information is useful for understanding what the study set out to observe and which outcomes appear in the registry record.

The record does not provide the distribution of physician ratings, an estimated treatment effect, confidence intervals, or inferential analyses. It therefore does not establish how often physicians rated treatment excellent, very good, good, fair, or poor, nor how precise any such distribution would be. The listed adverse-event counts and serious-event terms are descriptive. Without a suitable comparison and methods addressing differences among patients, they cannot establish that treatment caused or prevented an event.

The observational design is central to interpretation. Treatment allocation is not stated, and a like-for-like comparator is not identified. Patient characteristics and clinical decisions may be associated with both treatment exposure and outcomes. Even detailed statistical modeling would depend on measured information and assumptions, and the registry record does not report adjusted analyses.

The findings should also be understood within the limits of the recorded information. The record does not report the exact dose or duration, detailed compliance results, missing-data handling, an analysis plan, or the endpoint category counts. The enrollment figure is not necessarily the denominator for the primary endpoint, whose population is defined as participants receiving at least 1 dose.

As a general distinction, a study can be valuable for describing treatment use and observed events without answering a causal comparative question. The registry information supports that descriptive role. It does not, by itself, prove that Fragmin® works or does not work, or establish that the treatment is safe or unsafe. Interpretation should remain bounded by the outcomes and design information that are actually recorded.

13. Why This Trial Matters Statistically

This study is statistically instructive because its stated aim and its design call for descriptive interpretation. The registry describes an observational study of prolonged thromboprophylaxis, not a randomized comparison. That distinction shapes what the counts can answer: they can describe recorded outcomes in the Dalteparin Sodium group, but they do not provide a direct estimate of how outcomes would differ under an alternative strategy.

The primary endpoint also illustrates the importance of matching analysis to measurement. A physician's assessment on an ordered categorical scale is not the same as a continuous measurement, and the categories need not be equally spaced. Preserving category-specific results would avoid imposing a numerical interpretation not specified in the record. Yet the registry describes the scale without reporting its outcome distribution, leaving the central endpoint question unanswered by the available results.

The safety record highlights the difference between counts and comparative evidence. Counts can be clinically important signals, but their meaning depends on definitions, follow-up, event ascertainment, and a denominator. They do not by themselves establish causation or quantify a treatment contrast. The absence of reported uncertainty estimates further limits judgments about precision.

Finally, the registry lists 10 outcome measures but no analyses, and it does not report a statistical plan, missing-data procedures, multiplicity handling, or a sample-size justification. These details matter because transparent analysis choices help readers evaluate how outcomes were selected and interpreted. The planning illustrations use stated hypothetical assumptions and should not be confused with the study's actual design or observed statistical power. This record is a useful case in separating a study's objectives, its design, its descriptive findings, and the stronger claims that would require additional evidence.

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.

Several trial-specific limitations follow from the registry record. The study is observational, allocation is not stated, and no like-for-like control group is identified. That prevents a direct treatment contrast and leaves open the possibility that patient characteristics, clinical decisions, or other care influenced the recorded outcomes. The registry does not report adjustment methods that might address measured differences.

The primary outcome is described but its results are not reported in the registry record. The record does not provide counts in the physician-rating categories, an effect estimate, or uncertainty intervals. It also does not state how physicians were trained, whether the assessments were standardized, or whether assessors were blinded. These gaps limit evaluation of measurement consistency as well as interpretation of the endpoint itself.

For safety, the registry lists affected counts and selected serious adverse-event terms, but it does not explain event attribution, selection of listed terms, repeat-event handling, or overlap between event categories. The deaths field has no reported value. Detailed compliance and tolerability results are also not reported in the registry record, despite being named as study objectives.

The dose, exact duration of treatment, detailed eligibility criteria, follow-up completeness, and missing-data procedures are not reported. Although enrollment is listed as 503, the primary endpoint population is defined by receipt of at least 1 dose, and its analyzed denominator is not stated. The record lists 10 outcome measures but no analyses, and gives no statistical plan, interim-analysis information, multiplicity approach, or study-specific sample-size justification. These limitations restrict both reproducibility and the strength of conclusions that can be drawn.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Observational Study On The Safety And Tolerability Of Prolonged Thrombosis Prophylaxis With Fragmin® — NCT01046903.
• Registry record last updated 2012-02-27; status last verified 2012-02.
• Results first posted 2012-02-13.
• 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.

18. Record Summary

NCT01046903 is a completed observational study sponsored by Pfizer, with enrollment listed as 503. The registry records a start of 2010-03 and primary completion of 2011-02. Its stated objective was to observe safety, tolerability, and compliance with Fragmin® (Dalteparin Sodium) for prolonged thromboprophylaxis in post-surgery high-risk orthopedic patients.

The primary outcome is Physician's Assessment of Efficacy of Treatment, rated on a five point scale from excellent to poor, from baseline up to Week 5. The Full Analysis Set includes participants who received at least 1 dose. The registry record does not report the primary category results or analyses. It lists safety counts of 26 affected in the serious adverse-event category and 46 in the other adverse-event category, with 503 at risk in each listing. The record does not identify a like-for-like control group, so these counts are descriptive rather than comparative evidence.