Carotid Structure and Function in MPS Syndromes: A Multicenter Study of the Lysosomal Disease Network: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Carotid Structure and Function in MPS Syndromes: A Multicenter Study of the Lysosomal Disease Network (NCT01586871), a registered phase not stated study. The primary outcome is Carotid Intima-media Thickness, Measured in Millimeters.

2. Clinical Question

3. Trial Design

This was a multicenter observational study of carotid structure and function in mucopolysaccharidosis syndromes. The registry describes the study as having no treatment. Its stated aim was to evaluate the ease and convenience of a non-invasive artery-function measurement in people with MPS I, MPS II, and MPS VI compared with healthy control subjects. The registry lists an enrollment of 1147 and identifies the study status as completed.

The research questions concern comparisons between MPS patients and healthy controls, and between MPS VI patients and MPS I and II patients. These are observational comparisons, not randomized treatment contrasts. The registry record does not state an allocation method, and it does not give details on recruitment, eligibility criteria, participant characteristics, or how the control groups were selected. It therefore does not establish that the groups were similar in factors that might affect carotid measurements.

The primary measure was carotid intima-media thickness at baseline. The registry also lists carotid cross-sectional distensibility, carotid cross-sectional compliance, and carotid incremental elastic modulus as secondary outcomes. It does not describe the analysis populations, specify how measurements were handled, or report the results for these outcomes. The registry record reports zero analyses.

The study record lists a start date of 2012-03 and a primary completion date of 2016-08. Those dates describe the record’s study timeline; they do not provide information about measurement quality, follow-up completeness, or the timing of any individual participant’s assessment. The record also does not report a statistical analysis plan or sample-size justification. These omissions limit what can be concluded about how the planned questions were evaluated.

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 Carotid Intima-media Thickness, Measured in Millimeters, measured over Baseline.

Carotid intima-media thickness, or CIMT, measures the thickness of the inner two layers of the carotid artery: the intima and the media. The registry describes CIMT as a measure used to assess the extent of carotid atherosclerotic vascular disease. It notes that the measurement can identify thickening while patients are still asymptomatic. In this study, CIMT was measured in millimeters at baseline from the far wall of the left common carotid artery.

As a structural measurement, CIMT describes an artery feature rather than a clinical event or a direct measure of symptoms. Comparisons of CIMT can address whether the measured artery characteristic differs between the study groups, but interpretation depends on the observed values and the way the groups were analyzed. The registry record does not report those values, estimates of group differences, or measures of uncertainty.

The registry labels the primary outcome parameter as a median and its dispersion as a standard deviation. A median describes the center of a distribution, while standard deviation describes spread around a mean; the registry does not explain this combination or provide the underlying summary values. It also does not report a measurement protocol beyond the location and side of the artery. The listed secondary outcomes concern other aspects of carotid structure and function, but their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how measurements are summarized, how groups are compared, and how uncertainty is represented. The registry record names the primary outcome and its summary labels, but does not report a detailed statistical analysis plan. The distinctions below explain general statistical concepts relevant to interpreting this type of study; they are not claims about analyses performed in this study.

What does a group summary tell us?

A summary statistic condenses measurements across participants. A median identifies the middle of an ordered set of values and can be useful when a distribution is skewed or contains extreme observations. A mean is the arithmetic average and is often paired with a standard deviation, which describes the spread of individual values around that mean. A median and standard deviation describe different features of a distribution. The registry labels CIMT as a median with standard deviation for dispersion, but it does not explain that choice or report the values themselves. As a result, readers cannot inspect the distribution or assess how the reported summaries relate to the underlying measurements.

What would a comparison estimate?

A group comparison can be expressed as a difference in a measurement between groups. An estimate describes the observed contrast, while a confidence interval describes the range of values compatible with the data and the statistical procedure used. A narrower interval indicates greater precision than a wider interval, but precision is not the same as clinical importance. A p-value, when reported, describes how compatible the data are with a specified null model; it does not measure the size or importance of a difference. The registry record reports no comparison estimates, confidence intervals, or p-values for CIMT or the secondary outcomes.

Because this study is observational, group comparisons do not have the same interpretation as randomized treatment comparisons. In an observational study, participant characteristics may differ across groups and may be associated with the outcome. Statistical adjustment can address measured characteristics under stated assumptions, but cannot automatically remove bias from unmeasured or poorly measured factors. The registry record does not report whether adjusted comparisons were planned or performed, which variables were considered, or what model was used.

Why do distributions matter?

Some statistical methods rely on assumptions about the distribution of measurements or the variability around a model’s predictions. If the spread is greater than a model assumes, a method may understate uncertainty. This issue is often described as over-dispersion. General approaches can include using a model that allows more variability, robust uncertainty estimates, or methods suited to the observed distribution. Which approach is appropriate depends on the outcome and data structure. The registry record does not report distributional checks, over-dispersion assessments, or methods for addressing them.

For a continuous measure such as CIMT, analysts may examine the distribution, identify the summary that best describes its center and spread, and select a comparison method consistent with the data and study design. Such choices can affect estimates and uncertainty. The registry record does not report whether measurements were transformed, whether outliers were assessed, or which comparison procedures were used. No specific statistical method should be attributed to the study on the basis of the record alone.

How should planning calculations be read?

General sample-size calculations use assumptions about the outcome variability, the difference to be detected, the significance level, the allocation of participants, and the desired power. A planning calculation is not an observed result and is not a measure of the probability that a completed study has found a true effect. A calculation based on an observed effect is especially dependent on that estimate and should be read as an illustration under its stated assumptions. The registry record does not report a sample-size justification or the statistical plan used to determine enrollment.

Power is a property of a design under specified assumptions, not a retrospective verdict on whether a finding is true. When a result is uncertain, the estimate and its confidence interval are more informative about magnitude and precision than a statement about observed power. Since no outcome estimates or uncertainty measures are reported in the registry record, those interpretations cannot be made for this study.

What is not established by the registry entry?

The record does not report the data-analysis population, the treatment of missing measurements, the statistical software or model, or procedures for checking model assumptions. It also does not state whether analyses were prespecified or exploratory. These details matter because they explain how the raw measurements were converted into reported estimates and how much reliance to place on those estimates. In their absence, the study question and endpoint can be described, but the analysis cannot be independently evaluated from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary outcome and three secondary outcomes, and its stated questions involve more than one group comparison. When multiple outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is assessed separately at the same threshold. General approaches include identifying a primary comparison in advance, adjusting for multiple testing, or treating secondary findings as exploratory. The registry record does not report a multiplicity plan, so it is not possible to determine how multiple outcomes or comparisons were handled.

The record does not report a missing-data plan, the number of participants with usable measurements, or reasons measurements might be absent. Missingness can affect a comparison if the participants with measured outcomes differ systematically from those without them. General analyses may describe completeness, compare available participant characteristics, and use an approach suited to the likely missingness mechanism. No such procedures are reported in the registry record, and the enrollment figure alone does not establish how many participants contributed to each outcome.

The analysis populations are also not reported. The record does not specify whether all enrolled participants were eligible for each analysis, how group membership was defined for analysis, or whether any participants were excluded from outcome calculations. These omissions make it difficult to assess the relationship between the enrolled population and the population represented by any estimate. The registry reports zero analyses, so no outcome-specific analytic sample sizes or missing-data handling can be evaluated.

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 registry’s adverse-event entries list 33 MPS patients, 560 pediatric controls, and 554 adult controls as at risk. For each of those groups, the entries report zero serious adverse events, zero other adverse events, and zero deaths. These are the figures recorded for the listed groups; they do not explain the duration or completeness of safety surveillance.

This was an observational study with no treatment, according to the registry description. The adverse-event figures should therefore be read as registry reporting, not as a comparison of treatment safety. Zero reported events in an entry does not establish that no event occurred outside the recorded scope or that every participant was assessed in the same way. The record does not describe event definitions, collection procedures, reporting windows, or how missing safety information was handled. It also does not provide a narrative explaining the zero counts. These limitations prevent broader conclusions about safety or the completeness of adverse-event capture.

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

The registry record establishes that the study was designed to examine carotid structure and function in MPS I, MPS II, and MPS VI, with healthy controls as comparators. It identifies CIMT at baseline as the primary outcome and names additional measures of carotid distensibility, compliance, and elastic modulus. It also records a completed observational study with enrollment of 1147.

The record does not provide the numerical outcome findings. It therefore does not show whether CIMT or any secondary measure differed between groups, the size or direction of any contrast, or the precision of an estimate. The stated hypothesis that MPS patients would have poorer artery-health outcomes is not a finding. Without the analyses, the record cannot answer whether the proposed comparisons support that hypothesis.

Even if group differences were reported, the observational design would require care in interpreting them. A difference would describe the measured groups and would not, by itself, establish that MPS caused the difference. The record does not report participant characteristics or adjusted analyses that would clarify the role of other factors. It also does not report how many enrolled participants contributed usable measurements to each outcome.

CIMT is described as a measure of carotid atherosclerotic vascular disease, but the registry does not report clinical-event outcomes or explain how CIMT relates to later health outcomes in this study. The findings cannot be extended beyond the measured outcomes and study population on the basis of the registry entry. The available information supports describing the research question, design, and endpoint; it does not support a conclusion about the presence, absence, or clinical significance of a group difference.

13. Why This Trial Matters Statistically

This study is statistically notable for asking a measurement question in a population described as having heart-health complications, while using a non-invasive assessment of artery structure and function. In observational research, the quality and interpretation of a comparison depend not only on the outcome measurement but also on how groups are defined, how their characteristics differ, and how uncertainty is reported. The registry’s questions make those issues central: it proposes comparisons both between MPS patients and healthy controls and among MPS subgroups.

The endpoint also illustrates the difference between measuring a biological characteristic and reporting evidence about a group contrast. CIMT gives the study a defined structural measure, but an endpoint definition alone does not tell readers whether groups differed. Estimates, uncertainty, analysis methods, and participant accounting are needed to judge the strength and limits of a finding. Those results are not reported in the registry record.

The distinction between planning and evidence is important as well. Sample-size planning depends on assumptions and should not be confused with observed results or post hoc certainty. The registry record does not report a sample-size justification or statistical plan. Its enrollment figure cannot, on its own, establish how informative the outcome comparisons were, especially when outcome-specific analytic counts are not reported.

For clinical researchers and biostatisticians, the record demonstrates why transparent reporting of outcome values, comparison methods, missing data, and analysis populations matters. Without those elements, the study’s scientific question can be understood, but its empirical answer cannot be evaluated. The registry record is informative about the design and intended measurements, while leaving the statistical findings unavailable.

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 registry record does not report results for the primary or secondary outcomes. It gives no group-specific CIMT summaries, comparison estimates, confidence intervals, or p-values. As a result, the magnitude, direction, and precision of any observed differences cannot be assessed. The record reports zero analyses, further limiting the statistical interpretation.

Details needed to evaluate the observational comparisons are not reported in the registry record. These include participant eligibility and recruitment, demographic and clinical characteristics, the basis for selecting controls, and whether groups were comparable on factors related to carotid measurements. The record does not identify any adjustment strategy or explain how potential confounding was addressed. It also does not report the analysis populations or outcome-specific participant counts.

The registry describes CIMT as a median with standard deviation for dispersion but does not explain the summary choice or provide values. It gives the measurement location but does not report further details of the measurement protocol, quality control, or handling of repeated or unusable measurements. Missing-data procedures, multiplicity handling, model assumptions, and the statistical analysis plan are not reported in the registry record.

The study is observational and includes separate MPS and control groups; the record does not indicate random allocation or establish a like-for-like control comparison. The enrollment total and the group counts listed for adverse-event reporting do not provide a participant flow or confirm how many people contributed to each outcome. These limitations are specific to interpreting the information in the registry entry and constrain conclusions about both the study’s findings and their generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Carotid Structure and Function in MPS Syndromes: A Multicenter Study of the Lysosomal Disease Network — NCT01586871.
• Registry record last updated 2021-02-24; status last verified 2021-02.
• Results first posted 2021-02-03.
• 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.

18. Record Summary

The registry identifies NCT01586871 as a completed, multicenter observational study sponsored by the University of Minnesota. It lists enrollment of 1147, with a start date of 2012-03 and a primary completion date of 2016-08. The study concerned mucopolysaccharidoses and compared carotid artery measurements in people with MPS I, MPS II, and MPS VI with healthy controls, with an additional stated comparison among MPS subgroups.

The primary outcome was baseline carotid intima-media thickness, measured in millimeters from the far wall of the left common carotid artery. The record also lists carotid cross-sectional distensibility, carotid cross-sectional compliance, and carotid incremental elastic modulus as secondary outcomes. It reports zero analyses and does not provide numerical results, analysis methods, missing-data procedures, or a multiplicity plan. The adverse-event entries report zero serious events, zero other events, and zero deaths in each listed group. The registry describes the study question and measurements, but not the results needed to judge group differences.