Cardiovascular Complications of Sickle Cell Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cardiovascular Complications of Sickle Cell Disease (NCT01044901), a registered phase not stated study. The primary outcome is MRI Parameter - LVEDVi, mL/cm2 (Measured Using Method of Disks, Controls Serve as Normal Ranges).

2. Clinical Question

3. Trial Design

The registry record describes a completed research study sponsored by the University of Chicago. Its recorded start was 2009-03, and its primary completion was 2021-02. The stated enrollment is 51. The two described groups are patients with sickle cell disease and healthy volunteers; the record does not describe a randomized treatment assignment. Allocation is not stated, and the groups should not be read as a randomized comparison.

The sickle cell disease arm is described as 38 clinically stable Black patients with hemoglobin SS, SC, or β-thalassemia, demonstrated by high-performance liquid chromatographic separation or gel electrophoresis. The control arm is described as 13 healthy volunteers frequency matched to patients on age, sex, and race. Matching on those characteristics does not establish that the groups were similar in every other respect. The record does not report further details of recruitment, eligibility criteria, or matching procedures.

The study summary describes heart imaging exams and blood testing to investigate pulmonary hypertension and cardiovascular complications in sickle cell disease. Listed procedures include MRI, transthoracic echocardiography, tonometry, and EKG. The primary parameter was measured at baseline. The record also lists a secondary outcome concerning genome-wide gene expression and targeted genetic polymorphisms linked to a quantitative noninvasive-based pulmonary hypertension phenotype.

The record lists 20 outcome measures and 19 analyses. It does not report a statistical analysis plan, the rules used to select participants for each analysis, or the handling of missing measurements. These details matter when interpreting any comparison because the groups were not randomly assigned and the analysis procedures are not described.

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

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 MRI Parameter - LVEDVi, mL/cm2 (Measured Using Method of Disks, Controls Serve as Normal Ranges), measured over Parameter measured at baseline..

The primary endpoint is an MRI parameter labeled LVEDVi, reported in the record with the unit mL/cm2. It is described as measured using the method of disks, with controls serving as normal ranges. The measurement was taken at baseline. The registry record does not provide group means, standard deviations, a difference between groups, or a confidence interval for this endpoint.

In general, an endpoint is a predefined measure used to address a study question. A mean can describe the central value of a continuous measurement in a group, while a standard deviation describes the spread of individual measurements around that mean. Neither quantity alone establishes how precisely a difference between groups is estimated; that requires an uncertainty estimate for the comparison, such as a confidence interval.

The endpoint’s stated purpose is connected to characterizing cardiopulmonary complications and understanding pulmonary hypertension and diastolic dysfunction in sickle cell disease. MRI provides the named measurement method in the outcome description, but the registry record does not explain why this particular parameter was selected as the primary endpoint or how normal ranges were defined. The label and study objective therefore describe what was intended to be assessed, but do not by themselves show the observed values or support a conclusion about the size or precision of a group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing a measurement from a comparison. The primary outcome is a continuous MRI parameter summarized as a mean with standard deviation. A mean describes the group’s central value; the standard deviation describes variation among measurements within that group. To compare groups, analysts would ordinarily also report an estimated difference and an uncertainty interval. The numerical summaries and comparison estimate for this endpoint are not reported in the registry record, so the magnitude and precision of a difference cannot be described.

What does a confidence interval communicate?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, but it does not remove the possibility of bias from study design, measurement, or analysis choices. An interval for a group difference would help show which values are compatible with the observed data and analysis assumptions. No confidence interval for the primary outcome is reported in the registry record.

What can matching address?

The control volunteers were frequency matched to patients on age, sex, and race. In general, matching seeks to make groups more comparable on selected characteristics. Frequency matching describes similarity of group distributions rather than necessarily pairing each participant with a specific counterpart. It does not ensure balance on characteristics that were not matched, and it does not create randomized assignment. The registry record does not report the matching procedure in more detail or provide group-specific descriptions of those characteristics.

Why does the design affect interpretation?

The record describes a patient group and a healthy control group rather than a randomized intervention comparison. In general, randomization can help balance measured and unmeasured factors across treatment groups, while a nonrandomized comparison can retain differences related to how people entered the groups. Consequently, a difference in a measurement between these groups would be an association in the studied groups unless additional design and analysis information supported a stronger interpretation. Allocation is not stated, and the record does not report an adjustment strategy for potential confounding.

What does the planning illustration represent?

The planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It varies the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect. The record explicitly characterizes the illustration as separate from the trial’s own design. Its assumptions do not establish the protocol’s original sample-size justification, which is not reported in the registry record.

In general, a sample-size calculation estimates how many participants per arm would be needed under specified assumptions about variability, effect size, significance level, and power. Changing the effect to be detected changes the planning requirement. Such illustrations depend on their assumptions and should not be called observed power. The available record does not state a protocol-based target or explain how its planning assumptions relate to the original study design.

Why might over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and uncertainty can appear understated. The appropriate model depends on the outcome and its distribution. The primary endpoint is described as a continuous measure summarized with a mean and standard deviation; the registry record does not report a model or an assessment of distributional assumptions. Over-dispersion should therefore be understood as a general statistical issue, not as a documented feature of this study.

The record lists 20 outcome measures and 19 analyses. In general, testing or estimating many outcomes can raise multiplicity concerns, particularly when results are selected or interpreted without a prespecified approach. Possible approaches include defining a primary outcome in advance, adjusting inference, or treating other outcomes as exploratory. The registry record does not report whether any such approach was used, so its impact on interpretation cannot be determined.

Finally, sound interpretation depends on knowing who contributed data to each analysis, how missing observations were handled, and whether the analysis followed a prespecified plan. None of those details is reported in the registry record. The endpoint results themselves are also not reported. Statistical concepts can clarify what information would be useful, but they cannot recover absent estimates or establish findings that the record does not state.

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("Subjects With Sickle Cell Disease (SCD)", "Healthy Volunteers")
n   <- c(38, 13)
m   <- c(124, 78.7)
sp  <- c(26.8, 11.9)
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  Subjects With Sickle Cell Disease (SCD)  38  124.000  26.800  115.191  132.809
CARM  Healthy Volunteers  13  78.700  11.900  71.509  85.891

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 20 outcome measures and 19 analyses. This indicates that the study considered multiple measures or analyses, but the record does not describe their statistical hierarchy, whether secondary analyses were exploratory, or whether any multiplicity adjustment was applied. In general, when multiple outcomes or tests are considered, the chance of finding apparently notable results can be affected by the analysis strategy. A prespecified primary outcome can help focus interpretation, but the registry record does not report a plan for controlling multiplicity across the listed measures.

Missing-data handling is not reported in the registry record. There is no description of whether all enrolled participants had primary endpoint measurements, how incomplete tests were treated, or whether any imputation or other method was used. The analysis populations are also not described. Consequently, it is not possible to establish from this record which participants contributed to each outcome analysis or whether the reported enrollment corresponds to the analyzed population.

The record does not report the statistical analysis plan, an interim-analysis strategy, or a protocol-based sample-size justification. Those omissions limit assessment of whether analyses followed prespecified decisions. The planning illustration is explicitly separate from the trial’s own design and should not be mistaken for a documented protocol rationale. Because primary endpoint results are not reported in the registry record, neither multiplicity nor missingness can be evaluated against the actual outcome estimates.

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 record reports serious adverse events as zero affected among 38 at risk in the sickle cell disease group and zero affected among 13 at risk in the healthy-volunteer group. It also reports zero affected for the other adverse-event category among 38 at risk and among 13 at risk, respectively. No serious adverse event terms are listed.

Deaths are reported separately: 3 in the sickle cell disease group and 0 in the healthy-volunteer group. The record does not report causes, timing, or whether the deaths were considered related to study procedures. The death counts should not be conflated with the serious adverse-event counts, which are reported separately, or interpreted as evidence of a causal relationship.

These figures describe what the registry record reports for the listed groups; they do not, on their own, explain the circumstances of an event or establish comparative risk. The study involved measurement procedures, and the record does not provide further safety context or attribution details. The counts should therefore be read descriptively, with no inference about cause or relationship beyond what is explicitly recorded.

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

The record establishes the study’s broad purpose: to use cardiovascular imaging and other measurements to better understand cardiopulmonary complications associated with sickle cell disease. It identifies a primary baseline MRI parameter and describes a patient group and healthy controls. It also identifies a secondary genetic-expression outcome. These details clarify the subject of the research, but they do not show the observed primary outcome values.

The primary endpoint results, including group summaries and a between-group estimate, are not reported in the registry record. Therefore, it is not possible to state whether the groups differed, in which direction any difference went, how large it was, or how precisely it was estimated. The stated study objective is not evidence that the objective was achieved, and the endpoint’s name does not reveal its result.

Even if a numerical contrast were available, the design would need to guide its interpretation. The record describes healthy volunteers as controls and reports frequency matching on age, sex, and race. It does not describe randomized assignment. A comparison would therefore concern the observed groups and could not by itself establish that disease status caused any difference. Matching on selected characteristics cannot rule out differences on other factors.

The record’s status is completed, but completion is distinct from complete reporting of outcomes and methods. Information about analysis populations, missing data, multiplicity, and the statistical plan is not reported in the registry record. The serious adverse-event and death counts are descriptive registry entries and lack details about causes or attribution.

Accordingly, the reliable conclusion is about the study’s question and design, not a finding for or against a clinical effect. The information recorded does not permit a statistical conclusion about the primary MRI endpoint. It also does not provide a basis for medical advice or a conclusion about treatment, since the described study is a measurement comparison rather than a treatment trial.

14. Why This Trial Matters Statistically

This study is statistically interesting because it connects a clinical research question with quantitative cardiovascular measurements. MRI, echocardiography, tonometry, EKG, and blood testing are described as tools for examining cardiopulmonary complications in sickle cell disease. A continuous MRI endpoint can be summarized using a mean and standard deviation, while a carefully reported comparison would also communicate uncertainty around the contrast.

The comparison involves a patient group and healthy controls, with frequency matching on age, sex, and race. This gives readers a concrete example of the distinction between matching and randomization. Matching can address selected characteristics, but it does not make the groups equivalent in all respects or support the same causal interpretation as random assignment. Statistical adjustment may be relevant in such studies, but the record does not report an adjustment strategy.

The entry also illustrates why outcome reporting and methods reporting are essential companions to a study objective. The registry record lists the primary measurement and describes its intended role, yet does not report the endpoint’s group values or comparison estimate. It lists 20 outcome measures and 19 analyses, while leaving multiplicity procedures, analysis populations, and missing-data handling unreported. Without those details, readers cannot assess the precision or robustness of the primary finding.

Finally, planning calculations must be kept separate from observed results and from the original study design. The record describes a planning illustration based on the observed effect and specified assumptions, but explicitly distinguishes it from the trial’s own design. This is a useful reminder that a sample-size illustration is conditional on assumptions and is not observed power. In this case, the main statistical lesson is the importance of transparent reporting: design, analysis, uncertainty, and endpoint results are all needed to interpret a clinical comparison.

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 principal limitation for interpreting the primary question is that the endpoint’s numerical results are not reported in the registry record. No group means, standard deviations, estimated difference, confidence interval, or test result is given. The endpoint is identified as a baseline MRI parameter measured using the method of disks, but the record does not provide enough information to assess its observed distribution or the precision of a comparison.

The groups are not described as randomized, and allocation is not stated. Healthy volunteers were frequency matched to patients on age, sex, and race, but matching alone cannot address all potential group differences. The record does not give additional participant characteristics or an analysis strategy for confounding. The sickle cell disease group is described as clinically stable and as including specified hemoglobin types, which also limits interpretation to the population described rather than all people with sickle cell disease.

Important analytic details are absent: the statistical plan, analysis populations, missing-data handling, multiplicity procedures, and the rationale for the original sample size are not reported in the registry record. Although 20 outcome measures and 19 analyses are listed, the record does not explain how they relate to one another or whether inference was adjusted for multiple outcomes. The planning illustration is not a substitute for a documented design justification.

Safety reporting is also limited in context. Counts are given for serious events, other events, and deaths, but the record does not report causes or attribution. These limitations do not establish that a particular bias or problem occurred; they identify information needed for a fuller assessment that is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cardiovascular Complications of Sickle Cell Disease — NCT01044901.
• Registry record last updated 2022-02-23; status last verified 2022-02.
• Results first posted 2021-09-24.
• 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

The registry record describes a completed study titled “Cardiovascular Complications of Sickle Cell Disease,” sponsored by the University of Chicago. Its recorded start was 2009-03 and primary completion was 2021-02. Enrollment is listed as 51.

The study compared cardiovascular measurements in patients with sickle cell disease and healthy volunteers. The listed procedures include MRI, transthoracic echocardiography, tonometry, and EKG; the summary also describes blood testing. The primary outcome is a baseline MRI parameter labeled LVEDVi, measured using the method of disks, with controls serving as normal ranges. A secondary outcome concerns gene expression and targeted genetic polymorphisms linked to a noninvasive pulmonary hypertension phenotype.

The record lists 20 outcome measures and 19 analyses. Primary endpoint results and important analysis details, including missing-data handling and multiplicity procedures, are not reported in the registry record. Safety entries report zero serious adverse events in both groups, with deaths listed as 3 in the sickle cell disease group and 0 in the healthy-volunteer group; further context is not reported.