Dyslipidemia and Diabetic Retinopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dyslipidemia and Diabetic Retinopathy (NCT03403283), a registered phase not stated study. The primary outcome is Increase in Acid Sphingomyelinase (ASM) Expression and Activity in Bone Marrow-derived Endothelial Progenitor Cells (EPCs).

2. Clinical Question

3. Trial Design

NCT03403283, titled “Dyslipidemia and Diabetic Retinopathy,” is listed as completed. Its stated purpose is to determine whether the reparative cells of blood vessels called endothelial progenitor cells are defective in people with diabetes. The listed groups are people with diabetic retinopathy and healthy controls; the record describes the controls as age matched. The diabetic group descriptions include mild, moderate and severe non-proliferative retinopathy and proliferative retinopathy.

The registry lists 45 participants enrolled: 15 subjects with non-proliferative diabetic retinopathy, 15 with proliferative diabetic retinopathy, and 15 healthy controls. The intervention entries describe these populations rather than assigned treatments. Allocation is not stated, and the record explicitly cautions that the arms are not a like-for-like control comparison. The record does not describe a randomized intervention comparison.

The study start is listed as 2014-01, and primary completion as 2023-04-30. The primary outcome timeframe is described as three years. The endpoint is a continuous measure reported in nM/hr, with the parameter listed as a mean and dispersion as a standard deviation. No protocol details beyond those stated in the registry record should be inferred. In particular, the registry does not report a sample-size justification or a detailed statistical analysis plan.

Although the study status is completed, the record lists one outcome measure and no analyses. Completion status alone does not indicate that endpoint estimates or statistical tests are available in the registry record. The registered enrollment also does not establish how many participants contributed data to a particular outcome analysis.

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 Increase in Acid Sphingomyelinase (ASM) Expression and Activity in Bone Marrow-derived Endothelial Progenitor Cells (EPCs), measured over 3 years.

The primary endpoint is titled “Increase in Acid Sphingomyelinase (ASM) Expression and Activity in Bone Marrow-derived Endothelial Progenitor Cells (EPCs).” ASM activity is described as measured on a scale from 0 to 0.6, with 0.6 identified as worse and units of nM/hr. The endpoint parameter is a mean, with standard deviation specified as the measure of dispersion, and the timeframe is three years.

The registry describes collecting 150 cc of peripheral blood, about 8-10 tablespoons, from a vein in the arm of diabetic and control subjects. It frames EPCs as reparative cells of blood vessels and states that the study aims to determine whether these cells are defective in people with diabetes. This provides the biological rationale for examining ASM expression and activity in the cells.

As a general statistical point, a continuous endpoint can describe the average level of a measured quantity in each group, while its standard deviation describes variation among observations. The registry record does not report group means, standard deviations, participant-level data, or a between-group estimate. It also does not provide separate outcome values for expression and activity. The endpoint description therefore identifies what was intended to be measured, but does not show the observed result or how precisely any group difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as continuous, with the mean as its parameter and standard deviation as its dispersion measure. It does not report an analysis for that outcome. The explanations below describe general statistical concepts; they do not assert that a particular method was used in this study.

What does a mean describe?

General: A mean is an average across measured observations. It can summarize the central level of a continuous outcome in a group, but it does not show whether values cluster closely around that average or vary widely. For this endpoint, group means could describe the average ASM activity in each participant group if the values were reported. They are not reported in the registry record.

General: A mean can also be affected by unusually high or low observations. The standard deviation describes the spread of observations around the mean, but it is not the uncertainty of the mean itself. The standard deviation for this endpoint is specified in the registry as the dispersion measure, but no value is reported. Without the group means and their dispersion, the registry record does not allow readers to assess the observed distribution or compare the groups quantitatively.

How should a group comparison be read?

General: A comparison of group means concerns the size and direction of the estimated difference, together with its uncertainty. A confidence interval communicates uncertainty around an estimate under the assumptions of the analysis. A p-value measures how compatible the observed data are with a specified null hypothesis and model; it does not measure the probability that the null hypothesis is true, and it does not express the clinical importance of a result.

No between-group estimate, confidence interval or p-value is reported for the primary endpoint. It is therefore not possible to assess statistical precision or whether the data are compatible with a range of possible differences. A missing result should not be interpreted as a null finding. The registry record also does not report whether an adjusted comparison was planned or performed.

What does the design imply for interpretation?

General: Random allocation can help balance measured and unmeasured characteristics between groups, in expectation. This study is not described as a randomized comparison: allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. The diabetic and healthy-control groups are different populations by definition. A measured contrast could reflect the endpoint, other group differences, or both. The registry record does not report enough analysis details to determine whether any such factors were addressed.

The record describes the controls as age matched. Matching can be used to make groups more comparable on selected characteristics, but the registry does not report how matching was carried out, whether analysis accounted for it, or what other characteristics were measured. It would be inappropriate to assume a particular matching or adjustment procedure.

What do the planning assumptions mean?

General: Sample-size planning estimates how many observations may be needed to detect a specified effect under stated assumptions. The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not a report of the study's original design justification and not observed power.

Planning estimates depend on their assumptions. A smaller target effect generally requires more information to distinguish it from random variation, while the assumed variability also affects the required sample size. These are general relationships, not additional calculations for this study. The registry record does not report a sample-size justification, and no numerical planning output is stated in the registry record described for this analysis. An illustration based on an observed effect should not be taken as proof that the study was adequately powered or that a result is reliable.

Why can variability matter?

General: Standard statistical methods often rely on assumptions about how observations vary and how their distribution behaves. If a continuous measure has substantially greater variability than assumed, estimates may be less precise than anticipated. If observations are skewed, contain influential outliers, or are correlated within participants or groups, a simple model may not describe the data well. Over-dispersion, in general, means that variability exceeds what a model expects; it can make standard errors and inferences unreliable if not handled appropriately. The registry record does not describe the distribution of ASM values or indicate whether over-dispersion, outliers, or dependence were assessed.

The outcome is described as a mean and standard deviation, but these labels alone do not establish which inferential test or model was used. The analysis method, covariates, handling of subgroup comparisons, and approach to repeated measurements are not reported in the registry record. These omissions limit independent assessment of whether the analysis matched the data structure and study question.

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("Group 1", "Group 2")
n   <- c(30, 15)
m   <- c(0.2, 0.5)
sp  <- c(0.03, 0.04)
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  Group 1  30  0.200  0.030  0.189  0.211
CARM  Group 2  15  0.500  0.040  0.478  0.522

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report whether multiple hypotheses, subgroup comparisons, or repeated endpoint assessments were planned or conducted. No multiplicity adjustment is reported in the registry record. General: when several statistical tests are performed, the chance of at least one apparently notable result can increase; a prespecified strategy can help control or contextualize that issue. The number of tests and any such strategy cannot be inferred from the stated outcome count alone.

The registry does not report missing-data counts, reasons for missingness, or methods for handling missing values. Enrollment of 45 does not establish the number with a measured primary endpoint. General: missingness can affect an estimate when the likelihood of having a recorded value is related to participant characteristics or the outcome. Complete-case analysis, imputation, and other approaches make different assumptions; the record does not state which, if any, was used.

The analysis population is not reported in the registry record. It is not stated whether the endpoint analysis included all enrolled participants, only those with available blood samples, or another defined set. No participant flow for this outcome is reported. These omissions make it difficult to assess the relationship between enrollment and the data underlying any result, and there is no reported analysis to evaluate.

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 adverse-event record lists two groups, Group 1 and Group 2. For Group 1, 30 participants are listed as at risk for serious adverse events and 0 as affected; 30 are listed as at risk for other adverse events and 0 as affected; deaths are listed as 0. For Group 2, 15 participants are listed as at risk for serious adverse events and 0 as affected; 15 are listed as at risk for other adverse events and 0 as affected; deaths are listed as 0. No top serious-event terms are listed.

The registry record does not identify these generic group labels as the diabetic and control arms, so they should not be assigned to those populations based on the available description. The listed counts describe what the adverse-event fields contain; they do not establish that every participant was monitored in the same way or that no unrecorded events occurred. The record does not report additional detail about event definitions, surveillance, timing, or completeness. General: a zero count in a registry field is not, by itself, evidence of no risk. These figures should be read as the reported event counts, not as a standalone safety conclusion.

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

The registry record defines a biological question: whether endothelial progenitor cells are defective in people with diabetes, with the primary endpoint concerning ASM expression and activity. It identifies diabetic retinopathy groups and age-matched healthy controls, gives a continuous endpoint in nM/hr, and describes a three-year timeframe. Those details explain the intended comparison, but they do not provide its result.

No endpoint estimates or statistical analyses are reported in the registry record. There is no reported mean, standard deviation, group contrast, confidence interval or p-value. As a result, the posted record does not show whether ASM activity differed between groups, how large any difference was, or how precisely it was estimated. It also does not show whether expression and activity were analyzed separately.

Even if a numerical association were available, the stated comparison would not be a randomized treatment-effect estimate. The registry does not state allocation and cautions that the arms are not a like-for-like control comparison. General: comparisons between groups that differ in health status can be influenced by other characteristics. An observed association would not, by itself, establish that diabetes or retinopathy caused a change in ASM, or that ASM caused a clinical outcome.

The registry's completed status and enrollment count do not resolve these interpretive limits. The record does not report how many participants contributed primary endpoint data, how missing observations were handled, or which analysis population was used. Nor does it provide an analysis plan or sample-size justification. A planning illustration based on an observed effect is not the same as evidence of adequate design or observed power.

The appropriate reading is therefore narrow: the registry records a study objective, participant-group descriptions and a primary endpoint, while numerical findings and their uncertainty are not reported. This means the posted registry record cannot support a conclusion about the direction or magnitude of an ASM difference.

14. Why This Trial Matters Statistically

This study raises a statistical question about how to compare a continuous biological measurement across groups defined by diabetes and retinopathy status. A clear endpoint definition matters because readers need to know what was measured, in what units, over what timeframe, and how the outcome is summarized. The registry identifies a mean ASM measure, standard deviation, nM/hr units, and a three-year timeframe, giving a basic framework for understanding the intended endpoint.

The design also makes the distinction between association and intervention especially important. The groups are described as people with diabetic retinopathy and healthy controls, not as participants randomly assigned to treatments. The registry does not state allocation and cautions that the arms are not a like-for-like comparison. Statistical interpretation must therefore account for the possibility that differences between populations, apart from the measured endpoint, could influence a contrast.

Transparent reporting of estimates and uncertainty is central to evaluating such a comparison. Means and standard deviations could describe the observed groups, while an estimate with a confidence interval could show the magnitude and precision of a contrast. The registry record does not report these results or any analysis. This absence illustrates why a stated research question and completed status cannot replace outcome reporting.

Finally, enrollment and planning are not interchangeable with analyzable evidence. The record lists 45 enrolled participants, but does not report the endpoint analysis population or missing-data handling. Its planning assumptions are described as an illustration based on the observed effect, not as the trial's original design justification and not as observed power. Readers need to keep those distinctions in view when assessing what the registry can establish.

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 leaves several trial-specific limitations unresolved. Although enrollment is listed as 45 and the group descriptions specify 15 people with non-proliferative diabetic retinopathy, 15 with proliferative diabetic retinopathy and 15 healthy controls, the number contributing to the primary endpoint is not reported. Participant flow, reasons for unavailable measurements, and handling of missing values are also not reported.

The record describes the endpoint as an increase in ASM expression and activity, while its measurement description specifically details ASM activity on a 0 to 0.6 scale. It does not report separate outcome values for expression and activity or clarify how the endpoint title relates to the recorded measurement. The measurement scale is described, but no observed values or group summaries are reported.

Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. Although controls are described as age matched, the matching procedure, baseline characteristics, and any adjustment methods are not reported. The registry also does not identify how the generic safety groups map to the participant groups.

The analysis method, analysis population, multiplicity strategy, and sample-size justification are not reported in the registry record. No results are reported for the primary endpoint, and the record lists zero analyses. These limitations prevent assessment of the observed contrast, its precision, and the robustness of any statistical inference. They are limitations of what the registry record reports, rather than evidence that a particular analysis or procedure was or was not performed outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dyslipidemia and Diabetic Retinopathy — NCT03403283.
• Registry record last updated 2024-05-21; status last verified 2024-05.
• Results first posted 2024-05-21.
• 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

NCT03403283, “Dyslipidemia and Diabetic Retinopathy,” is listed as completed, with enrollment of 45. Its stated objective is to determine whether endothelial progenitor cells are defective in people with diabetes. The participant descriptions include non-proliferative and proliferative diabetic retinopathy groups and age-matched healthy controls. The primary endpoint concerns ASM expression and activity in EPCs, with activity described in nM/hr and a three-year timeframe.

The registry record does not report numerical primary endpoint results or analyses. The analysis population, missing-data methods, and statistical analysis plan are not reported. Adverse-event fields list zero affected participants and zero deaths for both generic groups, but the record does not identify those group labels as the clinical comparison arms.