Sickle Cell Trait and the Risk of Venous Thromboembolism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sickle Cell Trait and the Risk of Venous Thromboembolism (NCT01148940), a registered phase not stated study. The primary outcome is D-Dimer Levels Than in Black Women With Hb AA and White Women With Hb AA..

2. Clinical Question

The study rationale in the registry record is that D-dimer is often elevated during pregnancy and postpartum, and that elevated levels may be relevant to thrombotic risk. The record describes D-dimer as a surrogate marker rather than a direct measure of venous thromboembolism. It also notes that blood group was of interest. No results are reported to establish whether the intended group differences were present. In particular, the absence of recruited participants with sickle cell trait means the primary comparison involving that group could not be assessed using the registered study population.

3. Trial Design

The registry record describes an observational comparison of pregnant and postpartum women in groups defined by race and hemoglobin status. The planned groups were white women with Hb AA, black women with Hb AA, and black women with HbAS, or sickle cell trait. The main measure was D-dimer, recorded on a continuous scale. There is no treatment allocation described for this comparison, and the record says allocation was not stated. It also cautions that the arms are not a like-for-like control comparison. The study is not described as randomized.

The record lists enrollment of 34 and gives a study start of 2010-07 and primary completion of 2011-06. Its status is TERMINATED. The registry record does not report why the study was terminated. The primary-outcome description says that no women with sickle cell trait were recruited. The adverse-event groups list 7 women with HbAA in the white group and 27 women with HbAA in the black group; the sickle-cell-trait group lists 0 at risk. These group counts describe the posted adverse-event record and do not supply an analysis of the primary endpoint.

The stated measurement timeframe was from the date of delivery until 4-5 weeks postpartum. The registry summary also describes interest in whether D-dimer levels might be reflected in a greater incidence of postpartum thrombosis, the prevalence of symptomatic venous thrombosis, and possible effects of blood group. The record does not provide outcome estimates or analyses for these aims. Details such as recruitment procedures, the timing and number of blood draws, the allocation process, and the planned statistical analysis are not reported in the registry record. Any planning illustrations based on the observed effect are not the trial's design or a record of the enrollment target.

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

Analysis population for the primary outcome, as defined in the registry: did not recruit any women with sickle cell trait

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 D-Dimer Levels Than in Black Women With Hb AA and White Women With Hb AA., measured over Date of delivery until 4-5 weeks postpartum..

The primary endpoint is D-dimer level, measured as a continuous quantity in micrograms/ml. The registry record describes the summary measure as a mean with a 95% confidence interval. Measurement was intended during the period from delivery until 4-5 weeks postpartum. D-dimer is described in the record as a surrogate marker of venous thromboembolism and as a measure that can be elevated during pregnancy and postpartum. The study rationale treats higher levels as potentially relevant to hypercoagulability and thrombotic risk, but a surrogate measure is not itself a clinical event such as diagnosed venous thrombosis.

The record states that D-dimer levels >1.0 mg/ml may be predictive of increased thrombotic risk. This is part of the rationale; it is not a reported result from the study. The intended comparison was the mean level among black women with sickle cell trait against the mean levels among black and white women with Hb AA. The primary-outcome description states that no women with sickle cell trait were recruited, and no primary-outcome estimates are reported in the registry record. It is therefore not possible to interpret a group contrast, its precision, or its statistical significance from the posted results.

General statistical context: a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. Its width depends on features such as the amount and variability of data and the method used. Although the registry record specifies a 95% confidence interval as the intended dispersion measure, it reports no interval for D-dimer. The record also does not specify how repeated measurements, if any, would have been summarized or analyzed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a continuous endpoint and names the mean and a 95% confidence interval as the summary format. It does not report an analysis for that endpoint. The statistical points below explain the concepts relevant to the registered question; they do not describe methods that the study is known to have used.

What does a continuous endpoint mean?

A continuous measure can take values along a scale rather than being limited to categories such as event or no event. D-dimer is specified as a continuous measure in the registry record. Comparing group means is one way to describe average levels, but it does not show the distribution of individual measurements. Two groups can have different distributions even when their means are similar, or similar means despite different variability. A complete report would ordinarily make clear how the measurements were summarized and what analysis was used. Those details are not reported in the registry record.

What does a confidence interval contribute?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under a specified method and its assumptions. A narrower interval generally indicates greater precision than a wider interval, while an interval that spans a broad range leaves more uncertainty about the underlying value. A confidence interval does not show that every value inside it is equally plausible, and it does not account automatically for bias, measurement problems, or an unsuitable analysis model. The registry record names a 95% confidence interval as the dispersion measure, but no D-dimer estimate or interval is reported.

Why does the group structure matter?

The intended comparison involved three groups: black women with HbAS, black women with Hb AA, and white women with Hb AA. A group comparison can be described with separate estimates and contrasts, but the interpretation depends on how participants entered each group and whether the groups differ in relevant ways. The registry record says the comparison was not randomized, that allocation was not stated, and that the arms are not a like-for-like control comparison. This means the design description does not support an assumption that the groups were made comparable by random assignment. The registry record does not report adjustment variables or an adjusted analysis plan.

Because no women with sickle cell trait were recruited, the intended comparison involving HbAS cannot be calculated from this study population. The two Hb AA groups are listed in the adverse-event record, but no primary-outcome means or contrast between them is reported. A comparison limited to the available Hb AA groups would not answer the main question about sickle cell trait.

What role does the surrogate measure play?

The registry record treats D-dimer as a surrogate marker related to venous thromboembolism, and explains that elevated levels may be relevant to thrombotic risk. General statistical explanation: a surrogate is a measure used in place of a clinical outcome for a particular research purpose. A change in a surrogate does not automatically imply a change in the clinical outcome. The relationship between the surrogate and the clinical event needs evidence and depends on the setting. The study summary mentions investigating thrombosis and symptomatic venous thrombosis, but the registry record reports no analysis results for those outcomes.

What do the planning assumptions mean?

The stated sample-size assumptions describe a planning illustration based on the observed effect, not the study's original design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects to detect expressed as fractions of the observed effect. In general, such a calculation asks how many participants per arm would be needed under those assumptions to attain a chosen power for a specified effect. It is conditional on the assumed effect and model. If the observed effect is imprecise or unstable, a planning calculation based on it can also be unstable. These figures are planning illustrations, never observed power; the registry record does not report the study's own sample-size justification.

General statistical explanation: power is a design property under specified assumptions about the effect, variability, analysis, and significance level. It is not a measure of whether a result is true, and it cannot be inferred from a non-significant result. When there are no reported endpoint estimates or tests, observed power cannot describe the evidence from this study. No statistical test, model, transformation, covariate adjustment, handling of repeated measurements, or diagnostic procedure is reported in the registry record.

Why can variation and over-dispersion matter?

General statistical explanation: the variability of a continuous outcome affects the precision of a mean and the ability to distinguish group estimates. When data vary more than a model assumes, standard errors may be too small if that extra variation is ignored; this is one reason analysts assess whether a model adequately represents the data. This concept is sometimes discussed as over-dispersion, particularly for data modeled as counts. The registry record does not report the observed distribution or variability of D-dimer, nor does it describe a model that would allow assessment of over-dispersion. It would be inappropriate to assert that over-dispersion occurred in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, D-dimer levels, and zero analyses. It does not report statistical test results or an analysis plan. The broader study summary also mentions thrombosis occurrence, symptomatic venous thrombosis, and blood group. Whether these were formally specified outcomes, exploratory aims, or planned analyses with defined hypotheses is not reported in the registry record.

General statistical context: multiplicity arises when several hypotheses or outcomes are tested. As the number of tests grows, the chance of at least one apparently unusual result can increase if no adjustment or other strategy is used. An analysis plan may identify a primary comparison, distinguish confirmatory from exploratory analyses, or specify how multiplicity will be handled. The registry record does not report a multiplicity strategy, planned contrasts, or any adjustment for multiple comparisons. The intended three-group question could involve more than one contrast, but the record does not state how comparisons were to be organized.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not explain whether all enrolled participants were expected to contribute endpoint data, how incomplete measurements would be handled, or which participants would be included in each analysis. It does not report the number of D-dimer measurements available or any reasons for missing measurements. The absence of recruited women with sickle cell trait is a documented limitation of the intended comparison, not a missing-data method. No imputation, complete-case approach, or sensitivity analysis is described.

The record does not report whether interim analyses were planned. It also does not report a statistical analysis plan, a rationale for enrollment, or procedures for accounting for repeated measurements. These gaps prevent assessment of whether the registered questions, analysis choices, and reported results align. Because no outcome analysis is posted, there is no basis for evaluating multiplicity-adjusted or unadjusted inference.

11. 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 adverse-event record lists 7 white women with HbAA and 27 black women with HbAA as at risk. For each of these groups, serious adverse events were 0, other adverse events were 0, and deaths were 0. The black women with SCT group lists 0 at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. The record lists no serious adverse-event terms.

These figures should be read as counts in the posted safety record, not as evidence that an event could not occur. In particular, the SCT group had no participants at risk in this record, so its zero event count does not provide safety information about participants with sickle cell trait. Zero recorded events in the HbAA groups also does not establish absence of risk. The registry record does not describe the adverse-event definitions, the completeness of event ascertainment, or the detailed observation period for safety reporting. It also does not provide comparative safety analyses. No treatment intervention is identified as tested in the main study comparison, so these counts should not be interpreted as a treatment safety comparison.

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

The registry record documents a study intended to examine D-dimer levels in pregnant and postpartum women across groups defined by race and hemoglobin status. It also describes interest in thrombosis, symptomatic venous thrombosis, and blood group. The main statistical outcome was a continuous D-dimer measure summarized as a mean with a 95% confidence interval. The record reports no estimates, confidence intervals, or analysis results for that outcome.

The most important qualification is that the primary-outcome description says no women with sickle cell trait were recruited. The study therefore cannot provide the intended direct comparison between black women with HbAS and the Hb AA groups. The listed enrollment of 34 and the adverse-event counts for the two HbAA groups do not resolve that gap. They do not establish what D-dimer levels were, whether groups differed, or whether thrombosis occurred at different rates.

The record's discussion of D-dimer as a surrogate marker should also be kept distinct from evidence about clinical events. Even if D-dimer had been measured and analyzed, a difference in this marker would not by itself establish a difference in venous thromboembolism. The registry record contains no reported results from which to assess either marker levels or clinical outcomes.

The study is marked TERMINATED, but the reason is not reported in the registry record. The record does not report whether termination followed a recruitment difficulty, a scientific finding, or another circumstance; no explanation should be inferred. It mentions a future prophylactic-anticoagulation trial as a possible next step if increased risk were supported, but does not describe that treatment as part of the present study.

General statistical context: an unavailable estimate is not evidence of no effect, and the absence of a recruited comparison group is not evidence that the groups are equivalent. The appropriate conclusion is limited to what the registry record documents: the intended comparison was not completed with an SCT group, and no primary-outcome analysis is reported. The posted data cannot establish benefit, lack of benefit, or a clinical risk difference.

13. Why This Trial Matters Statistically

This study illustrates why the difference between a research question and an answer matters. The registered question concerns whether D-dimer levels differ between women with sickle cell trait and women with Hb AA. The registry record gives a rationale for asking that question and identifies a continuous primary measure, but it also states that no women with sickle cell trait were recruited. Without the group central to the comparison, the intended contrast cannot be estimated.

The record also distinguishes a surrogate measure from a clinical outcome. D-dimer is presented as potentially relevant to thrombotic risk, while the broader summary discusses postpartum thrombosis and symptomatic venous thrombosis. Those are related but not interchangeable questions. Statistical interpretation needs to keep the measured endpoint separate from the clinical event it may be intended to represent. The record contains no results that would allow either question to be answered.

From a design perspective, the nonrandomized group structure and the statement that the arms are not like-for-like controls matter. Group differences can reflect factors other than the characteristic being studied, and the registry record does not report an adjustment plan that could be assessed. These details are important when evaluating what an observational comparison could support, even if endpoint estimates were available.

Finally, a terminated study with no posted primary analysis shows why transparent reporting of enrollment, missing groups, outcomes, and analysis methods is essential. The record includes enrollment and adverse-event counts, but not a reason for termination or a sample-size justification. Planning illustrations based on an observed effect should not be mistaken for the original trial design or for observed power. The statistical value of the record is therefore chiefly in clarifying the intended question and the limits of the information available, rather than in offering an estimate of the proposed association.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation specific to this study is the absence of recruited women with sickle cell trait, as stated in the primary-outcome description. The HbAS group was central to the intended comparison, so the study population described in the registry record cannot answer the main question as planned. The record is marked TERMINATED, but the reason for termination is not reported in the registry record.

No D-dimer results, confidence intervals, or statistical tests are reported. The record therefore does not permit evaluation of effect size, precision, or statistical compatibility with a null hypothesis. Although the adverse-event groups list 7 white women with HbAA and 27 black women with HbAA, those counts do not substitute for primary-outcome data. The SCT adverse-event group lists 0 at risk, leaving no safety observations for that group in the posted record.

The study is not described as randomized, and allocation is not stated. The registry record cautions that the arms are not a like-for-like control comparison. It does not report adjustment factors, a statistical model, measurement procedures, or how any repeated measurements were handled. Recruitment methods and the reason the SCT group was not enrolled are also not reported in the registry record.

Other limitations of interpretation include the absence of a reported analysis plan, sample-size justification, missing-data approach, analysis populations, multiplicity strategy, and interim-analysis information. The registry summary mentions thrombosis, symptomatic venous thrombosis, and blood group, but no corresponding results are reported. The stated follow-up timeframe for the primary measure is from delivery until 4-5 weeks postpartum; additional details about endpoint ascertainment and completeness are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sickle Cell Trait and the Risk of Venous Thromboembolism — NCT01148940.
• Registry record last updated 2020-12-17; status last verified 2020-12.
• Results first posted 2020-01-02.
• 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

The registry record for NCT01148940, titled “Sickle Cell Trait and the Risk of Venous Thromboembolism,” lists Albert Einstein College of Medicine as sponsor and Thrombosis as the condition. It records enrollment of 34, a study start of 2010-07, primary completion of 2011-06, and status TERMINATED.

The intended primary outcome was mean D-dimer level in micrograms/ml, with a 95% confidence interval, measured from delivery until 4-5 weeks postpartum. Planned groups were white women with Hb AA, black women with Hb AA, and black women with HbAS. The primary-outcome description states that no women with sickle cell trait were recruited. The record reports zero analyses and no primary-outcome estimates.

Safety counts list 7 white women with HbAA and 27 black women with HbAA at risk, with zero serious adverse events, other adverse events, and deaths in each group. The SCT group lists 0 at risk. The reason for termination, statistical analysis plan, sample-size justification, and missing-data procedures are not reported in the registry record.