Arterial Function and Atherosclerosis in Essential Thrombocythemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Arterial Function and Atherosclerosis in Essential Thrombocythemia (NCT03828422), a registered phase not stated study. The primary outcome is Carotid Artery Stiffness (Expressed by Beta-stiffness Index ) in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period (From Baseline to Year 4)..

2. Clinical Question

The record describes two examinations: a first visit in 2014-2015 and a second visit planned for 2018-2019. Its primary outcome is the change in carotid artery beta-stiffness index from baseline to Year 4. The index is a continuous measure, so a comparison of change would need to account for both the measured values and their variation. The registry identifies the outcome as a mean with standard deviation, but it does not report the group means, changes, or a between-group estimate.

The study is framed as an observational comparison, not a test of an assigned therapy. Its question concerns differences in vascular measurements between the defined groups over time, rather than the effect of a randomized intervention. Even with matching on specified characteristics, the registry record does not establish that groups are equivalent on all factors that could affect vascular measurements. The reported aim and design therefore support describing the planned comparison, but not drawing a conclusion about whether stiffness progressed differently.

3. Trial Design

The registry describes a completed study with enrollment of 82. It identifies University Medical Centre Ljubljana as the sponsor. The start is recorded as 2014-01, and primary completion as 2021-08. The planned observation period for the primary outcome is described as four years, from baseline in 2014-2015 to Year 4 in 2018-2019. The record does not explain the timing between the planned visits and the primary completion date.

Participants were assigned to a patient group with JAK2 V617F-positive ET or to a control group. The control group was selected among healthy employees of the medical centre and their relatives; the record says it was matched with the patient group for age and sex distribution and classical cardiovascular disease risk factors. Allocation is not stated, and the record flags that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The record does not provide additional details about how matching was carried out or how the analysis would account for it.

The registry describes two visits for all subjects. Each visit was to include a structured questionnaire about personal and family medical history, cardiovascular risk factors and medication, a physical examination, a blood sample for laboratory tests, carotid ultrasound and measurement of coronary calcium. The intervention entry is imaging, classified as a diagnostic test; it is not a therapeutic intervention. JAK2 V617F allele burden was to be determined from genomic DNA in peripheral blood at both examinations.

The registry lists six outcome measures, but gives no analyses in its analysis count. The primary outcome concerns change in carotid beta-stiffness index. Numerical outcome values, participant flow between visits and details of the statistical analysis plan are not reported in the registry record. The stated total enrollment should not be assumed to equal the number with complete measurements for the primary outcome. The record does not provide a primary-outcome analysis population or say how incomplete follow-up was handled.

The official title refers to JAK2 V167F, while the study description and group definitions refer to JAK2 V617F. The registry does not explain this difference in wording. The description below uses V617F when discussing the patient group and mutation burden because those terms appear in the study details.

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.

Before assignment: had documented or clinically suspected atherosclerotic vascular disease

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.

Population: 4 participants did not particiapete at the second visit

6. Primary Endpoint

The registry lists the primary outcome as Carotid Artery Stiffness (Expressed by Beta-stiffness Index ) in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period (From Baseline to Year 4)., measured over From Baseline (in 2014-2015) to Year 4 (in 2018-2019).

The primary endpoint is the four-year change in carotid artery stiffness, expressed by the beta-stiffness index, in patients with JAK2 V617F-positive ET compared with healthy control subjects. The measure is based on echo-tracking ultrasound of the common carotid artery. Measurements were described as being taken two centimetres proximal to the bulb on both sides.

The registry gives a formula for the index using systolic and diastolic blood pressure and maximum and minimum arterial diameter. Conceptually, it relates pressure variation to the arterial wall's change in diameter. The record states that a larger beta-stiffness index indicates increased arterial stiffness and describes that as a worse outcome. The unit is listed as an index, and the outcome is defined as a continuous measure summarized by a mean and standard deviation.

Carotid stiffness is used as a vascular measurement to address the study's question about arterial function over time. The registry description states that values increase with age in the adult population, which makes age distribution relevant to a comparison between groups. The control group is described as matched on age and sex distribution and classical cardiovascular disease risk factors, but the registry does not provide the matching procedure or details of any adjustment in analysis.

The endpoint definition does not itself give the observed change. Group means, standard deviations, the between-group contrast, uncertainty intervals and a test result are not reported in the registry record. Consequently, the direction and precision of the primary comparison cannot be assessed from the record's outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

The beta-stiffness index is a continuous measure derived from carotid ultrasound and blood pressure measurements. The registry describes echo-tracking of the common carotid artery wall and gives a formula involving systolic and diastolic pressure and the artery's maximum and minimum diameter. In general, continuous outcomes can take a range of values rather than falling into categories such as present or absent. Summarizing them with a mean and standard deviation conveys the average level and the spread of measurements in a group.

The stated primary endpoint is change from baseline to Year 4, rather than a single measurement at one visit. A change score represents the difference between measurements over time for an individual or group. Comparing change between groups addresses whether their average trajectories differ over the stated follow-up. In general, a change comparison and a comparison of follow-up values answer related but not identical questions; the registry record does not report which statistical model or calculation was used.

Why does the comparison design matter?

In general, random allocation can help balance both known and unknown factors between groups, on average. This record does not state that allocation was randomized. Instead, patients with ET are compared with a control group selected from employees and relatives, with matching described for age and sex distribution and classical cardiovascular disease risk factors. Matching may address the characteristics used to select or pair participants, but it does not guarantee balance in other characteristics. Observational group differences can therefore reflect both the condition being studied and other differences between groups.

The record cautions that the arms are not a like-for-like control comparison. That caveat is important when interpreting an apparent contrast: matching on specified risk factors does not transform an observational comparison into a randomized experiment. The registry does not report whether the analysis accounted for matching, which factors were included in any adjustment, or whether any adjusted estimates were calculated. These analysis details are not reported in the registry record.

What do standard deviations and confidence intervals tell readers?

In general, a standard deviation describes how dispersed individual measurements are around a group mean. It is not the same as the uncertainty in the mean or in a difference between groups. The precision of an estimated group contrast is commonly conveyed with a confidence interval. Such an interval reflects sampling uncertainty under the assumptions of the analysis; its width is informative about how precisely the effect has been estimated. Neither the primary group means nor their standard deviations or confidence intervals are reported in the registry record.

A p-value, when reported, is a measure of how compatible the data are with a specified null model under the analysis assumptions. It does not measure the size or clinical importance of an effect. It also cannot replace an estimate and confidence interval, which convey direction, magnitude and precision. No primary-outcome p-value is reported in the registry record.

What can the sample-size assumptions establish?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. The assumed target effect is a stated fraction of the observed effect. In general, a planning calculation asks what sample size might be needed to detect an effect under stated assumptions. It is not a description of the actual analysis and does not show the probability that the completed study detected an effect. Such a probability is sometimes called observed power, but sample-size planning illustrations should not be interpreted that way.

The registry's stated assumptions also distinguish the reporting convention for time-to-event outcomes from that for other outcomes: time-to-event planning counts total events, while other planning counts participants per arm. The primary endpoint is continuous, not a time-to-event outcome. The calculated planning values are not reported in the registry record, and the actual primary-outcome sample available for analysis is also not reported. No design rationale or sample-size justification is reported in the registry record.

Why do follow-up and missing measurements matter?

A two-visit endpoint depends on measurements at both visits if change is to be calculated for each participant. In general, missing a baseline or follow-up measurement can reduce the data available for that calculation and may affect the comparison if missingness is related to health, participation or the measured outcome. Statistical methods can make different assumptions about missing data, and those assumptions affect interpretation. The registry does not report the amount or pattern of missing primary-outcome data, reasons for missingness, or a method for handling it.

Completion status does not establish completeness of follow-up for every outcome. The registry lists enrollment and describes the intended visits, but does not report a participant flow or the number included in the primary analysis. It also does not report whether analysis used only participants with measurements at both visits or another approach.

How should secondary aims be distinguished from findings?

The description includes an objective to examine whether JAK2 V617F allele burden correlates with vascular parameters. In general, a correlation describes the direction and strength of association between measured variables, but does not establish that one causes the other. No such estimate, uncertainty interval or test is reported in the registry record. The stated aim should therefore be read as an intended research question, not as a reported finding.

The record lists six outcome measures and zero analyses. The available information does not show how the outcomes were prioritized in analysis, how any correlations were assessed, or whether models were adjusted. Those details are not reported in the registry record. Without the numerical outcome estimates and the methods used to obtain them, readers can assess the measurement plan and design limitations but cannot reconstruct or validate the primary statistical conclusion.

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("Patients With Essential Thrombocythemia", "Control Group")
n   <- c(36, 38)
m   <- c(1.95, 0.22)
sp  <- c(2.18, 1.99)
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  Patients With Essential Thrombocythemia  36  1.950  2.180  1.212  2.688
CARM  Control Group  38  0.220  1.990  -0.434  0.874

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary measure of carotid beta-stiffness index change. It does not report a statistical analysis plan specifying how the outcome measures were prioritized, whether secondary outcomes were confirmatory or exploratory, or how multiple comparisons were handled. Multiplicity arises when several hypotheses are tested: in general, conducting many tests can increase the chance of at least one apparently notable result even when there is no corresponding underlying effect. The registry does not report whether any adjustment or other strategy was planned.

The analysis count is zero, and numerical analyses for the primary or other listed outcomes are not reported in the registry record. This leaves unavailable the estimates, uncertainty intervals and test results needed to assess the findings. It also leaves unreported whether there were interim analyses or any pre-specified stopping rules. No interim-analysis plan is reported in the registry record.

The record describes two examinations, with baseline in 2014-2015 and a second visit planned for 2018-2019. It does not report how many participants had usable measurements at both visits, whether measurements were missing, or why they might be missing. It also does not report how missing data were handled or what analysis population was used. In general, missing data can affect both precision and the interpretation of a change comparison, especially if availability of follow-up measurements is related to participant characteristics or outcome values.

Although enrollment is recorded as 82, the number enrolled should not be treated as the number analyzed for the primary endpoint. The safety groups have their own reported denominators, but those are not identified as the primary analysis population. A participant-flow account, outcome-specific denominators and the handling of incomplete observations are not reported in the registry record. Without that information, the completeness and representativeness of the analyzed measurements cannot be assessed.

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 reports serious adverse event counts separately for patients with essential thrombocythemia and the control group. For each group, the serious adverse event count is zero, and the reported number at risk is 36 for patients and 38 for controls. The registry also reports zero other adverse events in both groups, with the same group-specific numbers at risk, and zero deaths in either group.

These are safety figures as recorded in the registry. They should be read alongside the reported group-specific denominators, rather than treated as proof that no adverse events could occur. The record does not describe how adverse events were collected, the period over which they were monitored, or how completeness of reporting was assessed. It also does not explain why the safety denominators differ from the stated overall enrollment or how they relate to participants with primary-outcome measurements.

The intervention is described as imaging and other assessment procedures, not a therapeutic treatment. The posted safety counts do not provide an estimate of the effect of any treatment, and the registry record does not support a broader safety conclusion beyond the counts it reports. Zero events in the recorded categories mean that none were reported in those categories for the stated groups; they do not supply information about unrecorded events or outcomes outside the registry's reporting.

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

The study addresses a meaningful measurement question: whether carotid artery stiffness changed over a four-year observation period in patients with JAK2 V617F-positive ET compared with a control group. It also describes an interest in the relation between mutation allele burden and vascular measurements. The registry identifies the primary measure, the planned visit schedule and the imaging approach. These details explain what the study intended to assess.

They do not show what the study found. The registry record does not report primary-outcome values, changes in either group, a contrast between groups, or statistical uncertainty. It therefore does not establish the direction or magnitude of change, whether the groups differed, or how precisely any difference was estimated. The same limitation applies to the stated allele-burden question: numerical association results are not reported in the registry record.

The study is not described as randomized. The registry says the control group was matched for age and sex distribution and classical cardiovascular disease risk factors, but also cautions that the arms are not a like-for-like control comparison. In general, matching on selected characteristics cannot rule out all differences between observational groups. Any reported group contrast would need to be interpreted in light of that design and the analysis methods; those results and methods are not reported in the registry record.

The listed safety counts are separate from the primary efficacy question. They record zero serious adverse events, zero other adverse events and zero deaths in the stated groups, with group-specific denominators. These counts do not answer whether stiffness changed or whether the groups differed on the primary outcome. Nor do they provide evidence about treatment effects, since the study is described as an imaging and assessment study rather than a therapeutic comparison.

Overall, the record supports understanding the study's population, measurements and planned comparison, but not judging the outcome. Enrollment and completed status do not substitute for outcome estimates. Without reported results, it is not appropriate to conclude either that the groups had different trajectories or that their trajectories were similar.

14. Why This Trial Matters Statistically

This study is statistically notable for measuring a continuous vascular outcome at two visits in two observational groups. The primary endpoint is a change in carotid beta-stiffness index over a stated four-year period. A longitudinal measure can focus attention on change over time rather than on a single cross-sectional comparison, but interpreting that change depends on having measurements at both visits and a clearly described analysis.

The record also illustrates the difference between matching and randomization. The control group is described as matched to patients on age and sex distribution and classical cardiovascular disease risk factors, while allocation is not stated and the registry cautions that the arms are not a like-for-like control comparison. Statistically, matching addresses selected characteristics; it does not ensure balance in every factor that may matter. This makes the design and any adjustment strategy important to interpretation, yet the analysis methods are not reported in the registry record.

Another important feature is the separation between a defined endpoint and a reported result. The index, measurement location, ultrasound approach and direction of interpretation are described, but the outcome estimates and their precision are absent. That distinction matters for clinical researchers: a clear outcome definition makes it possible to understand what was intended to be measured, but it cannot establish the size, direction or uncertainty of an effect without results.

The study's secondary aim concerning mutation burden also raises a general statistical issue. Association analyses can describe whether two measured quantities vary together, but cannot by themselves establish causation. The registry does not report the correlation results or analytical details. More broadly, it lists multiple outcomes without reporting how multiplicity was handled. These omissions limit assessment of the strength and scope of the evidence, even though the measurement plan is described.

The registry is therefore useful for identifying the design questions readers should ask: who was compared, how measurements were made, whether follow-up data were complete, and how confounding and multiple outcomes were handled. The record does not provide enough outcome or analysis information to resolve those questions or quantify the primary 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 most important trial-specific limitation in interpreting this registry record is the absence of numerical results for the primary endpoint. No group means, standard deviations, changes, between-group estimate, confidence interval or p-value are reported. Without these, readers cannot evaluate the direction, magnitude or precision of the primary comparison.

The study is an observational comparison, and the registry does not state that allocation was randomized. Although the control group is described as matched for age and sex distribution and classical cardiovascular disease risk factors, the record itself cautions that the arms are not a like-for-like control comparison. Details of matching and any covariate adjustment are not reported. Residual differences between groups therefore cannot be assessed from the registry record.

Completeness of follow-up is also unclear. The intended assessments are described at baseline and Year 4, but the number of participants with measurements at both visits, outcome-specific denominators and reasons for missing measurements are not reported. The record does not state how missing data were handled or which participants were included in the primary analysis. Overall enrollment and the safety denominators do not resolve those questions.

The registry lists six outcomes but provides no analyses. The statistical plan, handling of multiple comparisons, and methods for the allele-burden association question are not reported. It is also not clear from the record how measurement variability, repeated observations or matching were incorporated in analysis. In general, these choices can affect estimates and uncertainty, but no particular method should be assumed.

Finally, the official title uses JAK2 V167F, whereas the study details describe JAK2 V617F. The record does not explain the difference. This wording inconsistency should be noted when identifying the mutation studied. These limitations concern what can be established from the registry record; they do not by themselves determine the quality of data or analyses that may exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Arterial Function and Atherosclerosis in Essential Thrombocythemia — NCT03828422.
• Registry record last updated 2021-11-04; status last verified 2021-10.
• Results first posted 2021-11-04.
• 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 sponsored by University Medical Centre Ljubljana, with enrollment of 82. The study compares patients with JAK2 V617F-positive essential thrombocythemia with a control group selected from healthy employees of the medical centre and their relatives. Matching is described for age and sex distribution and classical cardiovascular disease risk factors. The record does not state random allocation and cautions that the groups are not a like-for-like control comparison.

The primary outcome is four-year change in carotid artery beta-stiffness index, measured by echo-tracking ultrasound. The stated visits were baseline in 2014-2015 and Year 4 in 2018-2019. The registry also describes measurements of coronary calcium and JAK2 V617F allele burden, among other assessments.

Although the primary outcome and study aims are defined, numerical outcome results and statistical analyses are not reported in the registry record. The record lists six outcomes and zero analyses. Safety reporting lists zero serious adverse events, zero other adverse events and zero deaths in each group, with group-specific denominators. The official title's use of V167F differs from the V617F terminology in the study details; the registry does not explain that difference.