Correlational Study on the Biomarkers Application to the Prediction and Diagnosis of Cardiovascular Diseases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Correlational Study on the Biomarkers Application to the Prediction and Diagnosis of Cardiovascular Diseases (NCT02179047), a registered phase not stated study. The primary outcome is Biomarker Titer of Patients With Coronary Artery Disease.

2. Clinical Question

3. Trial Design

NCT02179047 is recorded as a completed study sponsored by Taipei City Hospital. Its title describes a correlational study of biomarkers in the prediction and diagnosis of cardiovascular diseases, and the listed condition is stable angina. The registry records enrollment of 214 and gives a study start of 2014-06 and primary completion of 2016-05. The design classification is listed as other rather than as a randomized controlled trial.

The intervention entry is coronary angiography, categorized as a procedure. One group is described as patients with stable angina who received coronary angiography. The other group is labeled Placebo, while its description identifies healthy subjects. The registry explicitly notes that allocation is not stated and that the arms are not a like-for-like control comparison. These details matter when interpreting any group contrast: the record does not describe random assignment, and the groups differ in their stated clinical status.

The study summary names NGAL, Cystatin C, Galectin-3, Copeptin, MR-Pro ANP, and sST2 as biological indicators selected through a literature review. It does not provide a detailed protocol for how biomarker samples were collected, processed, or timed in relation to angiography. Those procedures are not reported in the registry record.

The registry lists three outcome measures and three analyses, but does not identify their details in the information available for this account. The primary endpoint is the titer of six biomarkers, described using a geometric mean and 95% confidence interval, with a timeframe of 6-12 months. The study is completed, but completion status alone does not establish that all planned measurements were collected or that all results were posted.

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 Biomarker Titer of Patients With Coronary Artery Disease, measured over 6-12 months.

The primary endpoint is titled Biomarker Titer of Patients With Coronary Artery Disease. Its description specifies the titers of NGAL, Cystatin C, Galectin-3, Copeptin, MR-Pro ANP, and sST2. The registry specifies a geometric mean and a 95% confidence interval as the summary format, gives the unit as tilter, and lists a 6-12 months timeframe. It does not provide numerical estimates for any of these biomarkers, nor does it clarify how the timeframe relates to each measurement.

A biomarker titer is a measurement of the amount or level of a biological indicator. In general, measuring candidate biomarkers can help researchers explore whether their levels differ across clinical groups or are associated with disease status. Such measurements may motivate further evaluation of prediction or diagnosis, but a biomarker level alone does not establish diagnostic accuracy or predictive usefulness. Those claims require appropriate performance measures and a clearly defined target and comparison.

A geometric mean is a summary commonly used for measurements that are positive and vary multiplicatively. In general, it is based on averaging on a logarithmic scale and converting the result back to the original scale. A confidence interval conveys uncertainty around an estimated quantity. The registry record does not report the actual geometric means or confidence limits, so the magnitude and precision of the endpoint estimates cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean describe?

The primary endpoint is summarized as a geometric mean. In general, this is useful for positive measurements whose variation is better understood in multiplicative terms than as equal-sized additive changes. The calculation is typically performed by transforming measurements to a logarithmic scale, averaging them there, and transforming the summary back to the original measurement scale. This can make the geometric mean less influenced by very high observations than an arithmetic mean, although it does not eliminate the need to examine the underlying data and assumptions.

The registry record does not say whether the biomarker measurements were transformed for analysis, how values below a detection limit were handled, or whether any values were excluded. The recorded unit is tilter, and the endpoint description names six biomarkers. Numerical estimates are not reported, so it is not possible to examine distributions, assess whether the chosen summary is appropriate for the observed measurements, or compare biomarker levels across groups.

How should a confidence interval be read?

A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. In general, it reflects the range of values reasonably compatible with the data and the statistical procedure. Its width gives information about precision: intervals that are wider indicate more uncertainty about the estimated quantity than narrower intervals. The interval does not show the probability that a particular hypothesis is true, and it does not remedy bias in the design or measurement process.

The endpoint specifies a 95% confidence interval, but no interval limits or point estimates are reported in the registry record. Therefore, the precision of the biomarker estimates cannot be judged. The record also does not identify whether intervals were calculated separately for each biomarker, for each group, or for a contrast between groups. That distinction affects what an interval can answer.

What can the study design support?

The study is described as correlational, with patients with stable angina who received coronary angiography and a group of healthy subjects. The record says allocation is not stated and that the groups are not a like-for-like control comparison. In general, a correlational study can describe associations, but a group difference does not by itself establish that one characteristic caused another. Differences between groups may arise from their clinical status or other factors, and the registry does not report an adjustment strategy.

Coronary angiography is listed as a procedure, not as a randomized treatment assigned against a placebo. The label Placebo for the healthy-subject group should therefore be read alongside the actual group description. The record does not give details of matching, recruitment, eligibility criteria, or baseline characteristics that would help evaluate comparability.

What do the planning assumptions mean?

The registry includes sample-size planning assumptions described as an illustration based on the observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study used those methods in its own design or analysis. The registry does not report a sample-size justification from the trial protocol.

Planning calculations estimate how many participants per arm might be needed under specified assumptions. Such illustrations depend on the effect size chosen, variability, allocation, and statistical model. They are not observed power and do not establish whether an analysis was adequately powered. The registry says time-to-event illustrations give the total number of events, while other illustrations give participants per arm. No numerical planning results are described in the record available for this account, so no planning estimate can be interpreted.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors may be too small and confidence intervals may be too narrow. Methods that accommodate over-dispersion can produce uncertainty estimates more consistent with the data. This is a general statistical consideration, not a method identified for this study: the registry record does not report the specific statistical models, distributional assumptions, or checks for over-dispersion.

More broadly, the record does not specify covariate adjustment, handling of repeated measurements, missing-value methods, or model diagnostics. It lists three analyses but does not describe them. Without those details and without numerical results, readers cannot reproduce the analysis or assess how sensitive the findings might be to modeling choices.

10. Multiplicity, Missing Data and Analysis Populations

The study summary names six biomarkers, while the registry lists three outcome measures and three analyses. It does not explain how the listed outcomes and analyses map to the biomarkers, or whether each biomarker was assessed in each group or at multiple measurement times. The analysis plan and the identity of the additional outcomes are not reported in the registry record.

Testing several biomarkers or several related outcomes creates a multiplicity issue: when many hypotheses are examined, the chance of at least one apparently unusual result can increase. In general, researchers may define a primary comparison in advance, adjust for multiple testing, or treat analyses as exploratory. The registry record does not report whether a multiplicity strategy was planned or used. No significance tests or numerical results are available to assess how multiplicity might affect interpretation.

The primary endpoint population field is blank. The registry record does not report the analysis population, the number of participants contributing measurements for each biomarker, or whether analyses followed an intention-to-treat, per-protocol, or other approach. It also does not describe missing-data amounts, reasons for missing measurements, or methods used to handle missingness. These omissions limit assessment of selection bias and whether the analyzed observations represent the enrolled groups.

The record reports enrollment of 214, while the adverse-event entries use group denominators of 187 and 20. The registry record does not explain how these figures relate to the primary biomarker analyses or why those safety denominators were used. They should not be treated as the primary endpoint sample sizes without an explicit connection in the record.

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 reports safety figures under groups labeled Intervention and Placebo. For serious adverse events, other adverse events, and deaths, the recorded number affected is 0 in each group. The listed at-risk denominators are 187 for Intervention and 20 for Placebo for each of these categories. No top serious adverse-event terms are listed.

These entries describe what was recorded in the registry; they do not establish that no adverse events occurred outside the period or scope of collection. The record does not report the safety surveillance methods, duration of follow-up for these outcomes, definitions used, or whether the figures reflect complete ascertainment. The group descriptions also matter: Intervention refers to patients with stable angina who received coronary angiography, while Placebo is described as healthy subjects. The names should not be interpreted as a randomized procedure-versus-placebo safety comparison.

Zero recorded affected participants is not proof of zero risk. It means that the registry lists no affected participants for the stated categories and denominators. The different group descriptions and the unreported safety methods limit what can be inferred from these entries, and the safety figures do not supply evidence about biomarker levels or diagnostic performance.

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

The record establishes that NCT02179047 was a completed correlational study sponsored by Taipei City Hospital, with stable angina listed as the condition and six biomarkers named in its summary. It identifies coronary angiography as the procedure and describes a healthy-subject group. It also defines a primary biomarker-titer endpoint using a geometric mean and 95% confidence interval, with a 6-12 months timeframe.

Those details explain the intended subject of the study, but they do not establish what the study found. Numerical titers, confidence limits, group contrasts, and association estimates are not reported in the registry record. Consequently, the posted information does not show whether biomarker values differed between groups, how precise any estimates were, or whether the biomarkers were associated with disease status.

The study title refers to prediction and diagnosis, but the endpoint information does not report diagnostic or predictive performance. A biomarker's measured level is distinct from evidence that it can classify patients accurately or predict a future outcome. The record does not describe a validated prediction model, diagnostic thresholds, or performance measures. It therefore cannot support a conclusion about those applications.

The design also limits causal interpretations. The registry states that allocation is not stated and that the arms are not a like-for-like control comparison. One group consists of patients with stable angina who received coronary angiography, and the group labeled Placebo consists of healthy subjects. Any contrast between these groups would need to be interpreted in light of that difference and the possibility of other confounding characteristics.

In short, the registry record describes a biomarker research question and basic study features, but does not provide the results or analytic detail required to judge the observed biomarker relationships, their precision, or their clinical relevance. The recorded safety counts are separate from the primary biomarker endpoint and do not resolve those uncertainties.

13. Why This Trial Matters Statistically

This study is statistically noteworthy because its stated aim connects biomarker measurement with prediction and diagnosis, while the primary endpoint is a set of biomarker titers. That distinction highlights an important principle: measuring a candidate marker is an early step in evaluating it, not a complete assessment of how well it can diagnose disease or predict outcomes. Those uses require clearly defined target outcomes and appropriate performance analyses.

The record also illustrates why the comparator description matters. Although one group is labeled Placebo, its description is healthy subjects, while the other group is patients with stable angina who received coronary angiography. The registry explicitly says the arms are not a like-for-like control comparison. Statistical contrasts between groups are most interpretable when the groups are comparable for the question being asked, or when relevant differences can be addressed through a clearly described design and analysis.

Precision is another central issue. The endpoint is specified as a geometric mean with a 95% confidence interval, a format that can communicate both the estimated biomarker level and its uncertainty. But the estimates and intervals are not reported in the registry record. Without them, readers cannot distinguish a precise estimate from an uncertain one or evaluate how well the data support the study question.

Finally, the record lists multiple biomarkers, outcomes, and analyses without describing the analysis plan or multiplicity approach. This makes it difficult to determine which findings would be primary and how exploratory comparisons should be interpreted. The case underscores why complete reporting of endpoint values, analytic populations, methods, and uncertainty is essential for evaluating biomarker research.

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 leaves important details of the study population and measurement process unspecified. The primary endpoint population field is blank, and eligibility criteria, recruitment methods, baseline characteristics, and matching are not reported. The information therefore does not show how participants were selected or how comparable the stable-angina and healthy-subject groups were beyond their descriptions.

The endpoint description identifies six biomarker titers and a 6-12 months timeframe, but does not explain the timing of individual measurements, the laboratory methods, assay characteristics, or handling of measurements outside an assay's range. The recorded unit is tilter. Numerical biomarker estimates and confidence limits are not reported, which prevents evaluation of magnitude and precision.

The record does not explain how its three outcome measures and three analyses relate to the six biomarkers. It does not report a statistical analysis plan, covariate adjustment, missing-data methods, or a multiplicity approach. It also does not describe diagnostic reference standards, thresholds, or predictive performance measures, despite the study title's focus on prediction and diagnosis.

The design information is limited: allocation is not stated, and the registry characterizes the groups as not being a like-for-like control comparison. The safety denominators are reported, but their relationship to enrollment and the primary biomarker population is not explained. These limitations prevent a detailed assessment of selection, confounding, measurement, and analysis. They are limitations of what is reported in the registry record and should not be mistaken for proof that unreported procedures were absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Correlational Study on the Biomarkers Application to the Prediction and Diagnosis of Cardiovascular Diseases — NCT02179047.
• Registry record last updated 2020-02-25; status last verified 2017-04.
• Results first posted 2020-02-25.
• 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

NCT02179047 is recorded as a completed correlational study sponsored by Taipei City Hospital, with stable angina listed as the condition. The registry gives enrollment of 214, a start of 2014-06, and primary completion of 2016-05. It describes coronary angiography in patients with stable angina and a group of healthy subjects labeled Placebo; allocation is not stated, and the record says the arms are not a like-for-like control comparison.

The primary endpoint concerns titers of NGAL, Cystatin C, Galectin-3, Copeptin, MR-Pro ANP, and sST2, summarized as a geometric mean with a 95% confidence interval over a 6-12 months timeframe. Numerical endpoint results and confidence limits are not reported in the registry record. Safety entries list 0 affected participants and 0 deaths in both groups, with denominators of 187 and 20. The record does not report enough outcome or analysis detail to assess biomarker associations, precision, or predictive and diagnostic performance.