Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (NCT02499679), a registered phase not stated study. The primary outcome is Percentage of Participants With Reclassification of CAD Management, Assessed as the Therapeutic Recommendations Made Based on Review of Coronary CTA Alone Versus CTA + FFRCT, When Available, by a Central Integration Core Laboratory..

2. Clinical Question

The registry’s stated objective was to evaluate the utility, clinical outcomes, and resource utilization of FFRCT-guided evaluation in clinically stable, symptomatic patients with coronary artery disease. The reclassification assessments were intended to examine the potential influence of FFRCT on downstream testing and clinical decision-making. The record says these assessments were not used to determine actual patient care.

The endpoint description distinguishes assessments made by a blinded independent review committee from assessments made by local physician teams. The primary endpoint is specifically described as reclassification between core-laboratory CCTA-alone management and CCTA-plus-FFRCT management. The registry record does not report a numerical primary-endpoint result or the associated confidence interval, so the frequency or precision of reclassification cannot be stated from the record.

3. Trial Design

ADVANCE is a registry evaluating FFRCT-guided assessment in patients with coronary artery disease. The registry record lists HeartFlow, Inc. as sponsor, enrollment of 4737, a start date of 2015-07, primary completion in 2019-02, and status as COMPLETED. These details describe the registry entry; they do not establish that all planned analyses or follow-up results are posted.

The eligible population is described as clinically stable, symptomatic patients diagnosed with coronary artery disease by cCTA. The record’s arm description begins with patients diagnosed with CAD by cCTA, but the description is truncated. Further details about the full eligibility criteria and the participant pathway are not reported in the registry record.

The record does not describe a randomized allocation, and the allocation method is not stated. The FFRCT threshold groups listed in the adverse-event information are not a like-for-like control comparison. They should not be interpreted as randomized arms or as evidence that differences between groups were caused by FFRCT status. A causal comparison of treatment strategies is not established by the information in the registry record.

The primary endpoint is management-plan reclassification at 90 days. The listed secondary outcomes include reclassification between an investigator’s cCTA-only plan and actual clinical management; invasive catheterization without obstructive disease; major adverse coronary events and their individual components at 90 days and one year; cumulative radiation exposure from cCTA; and resource utilization at 90 days, including a site-determined post-FFRCT treatment plan. The registry identifies nine outcome measures in total.

The record gives no detailed statistical analysis plan, participant flow, or analysis population definition. Results for the primary endpoint and secondary outcomes are not reported in the registry record. Consequently, completion status and enrollment alone do not indicate what the outcome estimates were or how precisely they were estimated.

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: The ADVANCE Registry screened a total of 5,083 patients, and 4,893 of them had coronary CTA submitted for FFRCT analysis. Of these submitted, 4,737 (96.80%) were of sufficient image quality for FFRCT analysis.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management.

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: There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results and data available.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Reclassification of CAD Management, Assessed as the Therapeutic Recommendations Made Based on Review of Coronary CTA Alone Versus CTA + FFRCT, When Available, by a Central Integration Core Laboratory., measured over at 90 days.

The primary endpoint is the percentage of participants whose coronary artery disease management is reclassified when therapeutic recommendations based on coronary CTA alone are compared with recommendations based on CTA plus FFRCT, when available. The assessment is specified at 90 days and refers to recommendations reviewed by a central integration core laboratory. The endpoint description also says the reclassification rate was assessed separately by a blinded independent review committee and local physician teams.

This measure is intended to capture whether adding FFRCT changes a proposed management classification relative to CTA alone. Such a measure can describe the incremental decision-making information associated with an added diagnostic assessment. It is not itself a measure of clinical benefit, harm, or diagnostic accuracy, and a reclassification does not establish that the revised recommendation improved patient outcomes. The record explicitly states that the assessments were intended to evaluate potential impact on downstream testing and clinical decision-making, but were not used to determine actual patient care.

For a percentage endpoint, the estimate depends on how many participants meet the endpoint definition and the analysis population used. The record names the endpoint and gives a 95% confidence interval as its dispersion measure, but no numerical estimate or interval is reported in the registry record. The denominator, endpoint classification rules, and handling of unavailable assessments are also not reported in the registry record. Without those details and the posted result, the magnitude and precision of reclassification cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish an observed estimate from its uncertainty, define who contributes to an analysis, and clarify what comparisons the design can support. For this registry, the primary endpoint is a percentage, while the record also lists event outcomes, resource use, and radiation exposure. The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint, but does not post its numerical estimate or interval.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method used. A narrower interval indicates greater precision than a wider interval, but neither width nor position can be assessed without the actual endpoints. A confidence interval is not a guarantee that the true value lies within a particular interval, nor does it by itself indicate whether a finding is clinically important. Since the primary estimate and interval are not reported in the registry record, its precision cannot be assessed.

What does a percentage endpoint require?

In general, a percentage is calculated from the number of participants meeting a defined outcome relative to a specified analysis denominator. For the reclassification endpoint, interpretation would depend on the operational definition of a reclassification, the population included, and whether assessments were available from the relevant reviewers. The registry describes the endpoint and review settings, but does not report the analysis denominator, classification details, or missing-assessment handling. No percentage can be reconstructed from the information in the record.

How does the design shape interpretation?

General statistical principle: randomized allocation can support a causal comparison when implemented and analyzed appropriately, while nonrandomized comparisons can be affected by differences between groups. In this record, allocation is not stated, and the threshold-based adverse-event groups are explicitly not a like-for-like control comparison. Their event counts are descriptive. They do not isolate the effect of a diagnostic strategy, and the registry record does not report an adjusted analysis that would account for potential differences between groups.

The primary endpoint compares management recommendations made using different diagnostic information. This is a decision-process endpoint. General principle: a change in classification can indicate that an additional measure altered a recommendation, but the change alone does not establish that the recommendation was correct or that subsequent clinical outcomes improved. The record itself distinguishes the potential impact being assessed from actual patient care, noting that the assessments were not used to determine care.

What do significance tests and power mean?

General principle: a significance test evaluates data against a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, and statistical significance does not establish clinical importance. No primary endpoint test result or p-value is reported in the registry record.

The record describes a sample-size planning illustration based on an 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 assumptions, not evidence that the trial was designed with those assumptions or that a particular power was achieved. The record does not report the protocol’s sample-size justification. Any sample-size figure derived under such assumptions is an illustration, not observed power. The stated sample-size convention is participants per arm for outcomes other than time-to-event outcomes, for which the convention is total events using the Schoenfeld method.

General principle: over-dispersion occurs when observed variability exceeds what a statistical model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The registry record does not report a model for the primary endpoint or indicate whether over-dispersion was assessed, so no claim about its presence or handling is possible.

Why do analysis choices matter?

Endpoint results can depend on which participants are included, how missing information is handled, and whether analyses are adjusted for other variables. These choices should be specified before interpreting estimates. The registry record does not report the primary analysis population, the missing-data approach, or the adjustment strategy. It also does not report interim analyses or a detailed statistical analysis plan.

The registry identifies multiple outcomes, including management reclassification, invasive catheterization without obstructive disease, major adverse coronary events, event components, radiation exposure, and resource utilization. General principle: examining multiple outcomes creates a multiplicity issue because the chance of at least one apparently unusual result can increase when many tests are conducted. Whether and how to address this depends on the prespecified objectives and analysis plan. That plan is not reported in the registry record; no adjustment should be presumed.

Finally, separate review assessments and site-level outcomes may reflect different measurement processes. General principle: differences in who classifies an outcome or how it is collected can affect comparability. The record notes review by a blinded independent committee and local physician teams, but does not give their numerical results or detailed adjudication procedures. Those missing details limit assessment of reproducibility and consistency.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Reclassification Rate by Core Lab")
n      <- c(4737)
events <- c(3169)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Reclassification Rate by Core Lab  4737  3169  66.9  65.5  68.2  65.5  68.2  65.5  68.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes, including reclassification, invasive catheterization without obstructive disease, major adverse coronary events and individual components at 90 days and one year, cumulative radiation exposure, and resource utilization. It identifies nine outcome measures in total. When several outcomes are assessed, multiplicity is a statistical concern: in general, the more tests conducted, the greater the chance of observing a nominally unusual result by chance. The registry record does not report whether a multiplicity adjustment was planned or used, how outcome priority was set beyond naming the primary endpoint, or whether analyses were confirmatory or exploratory.

Missing-data handling is not reported in the registry record. The record does not state how participants without a 90-day assessment, an evaluable management recommendation, or later follow-up were handled. It also does not provide endpoint-specific denominators or describe imputation, censoring, or sensitivity analyses. As a result, the extent to which incomplete data could affect estimates cannot be evaluated.

The primary analysis population is not reported in the registry record. The enrollment figure alone does not establish how many participants contributed to each outcome analysis, or whether all eligible participants were included. The record also does not report a detailed statistical analysis plan, interim-analysis procedures, or analysis adjustments. These omissions prevent a full assessment of whether outcome selection, missingness, and analysis populations were handled in a prespecified and consistent way.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (any cause) (0.6%), mi (0.2%), acs leading to urgent hospitalization and revascularization (0.1%).

The registry lists adverse-event information for two groups: “Patients Receiving cCTA and FFRCT >0.80” and “Patients Receiving cCTA and FFRCT≤0.80.” For serious events, each group is listed with 4737 at risk; serious-event counts are 12 and 43, respectively. For other events, the listed numbers at risk are 1591 and 3137, with 80 and 1036 events, respectively. The death counts are 7 and 28. These are posted counts, not evidence of a causal difference between groups.

The record identifies death (any cause) at 0.6%, MI at 0.2%, and ACS leading to urgent hospitalization and revascularization at 0.1% among the top serious-event terms. These terms and percentages should be read as safety reporting, not as a comparison of treatment effects. The record does not establish that the events were caused by a diagnostic test or by subsequent care.

The threshold groups are not a like-for-like control comparison, and their allocation method is not stated. The different numbers at risk listed for other events also mean those counts should not be treated as though they share a common denominator. The registry record does not report adjusted safety comparisons or further details about event attribution.

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

The registry record establishes that ADVANCE evaluated FFRCT-guided assessment in clinically stable, symptomatic patients with coronary artery disease and identified management-plan reclassification at 90 days as its primary endpoint. It also describes secondary outcomes covering clinical events, resource utilization, and radiation exposure. These details define the questions the registry set out to examine.

The record does not report the numerical primary-endpoint result, its 95% confidence interval, or the secondary-outcome results. Consequently, it does not allow a reader to determine the observed reclassification percentage, the precision of that estimate, or the recorded frequency of the named secondary outcomes. The completed status and enrollment of 4737 do not fill that gap.

Even if a reclassification estimate were available, it would describe a difference in management recommendations rather than establish a patient benefit. The record says the assessments were intended to evaluate potential impacts on downstream testing and clinical decisions, but were not used to determine actual patient care. A change in a proposed recommendation does not, on its own, show that the change was appropriate, that it altered care, or that it changed outcomes.

The adverse-event counts are also limited in what they can establish. The groups are defined by FFRCT thresholds and are not a like-for-like control comparison. Counts alone cannot identify the cause of events or support a causal contrast between diagnostic strategies. The record does not report adjusted analyses that would address group differences.

General statistical principle: estimates should be interpreted alongside their uncertainty, denominator, analysis population, and assumptions. Those details are not reported for the primary endpoint in the registry record. Therefore, the available information supports a description of the registry’s aims, design limitations, and posted safety counts, but not a conclusion about the effectiveness or lack of effectiveness of a treatment or diagnostic strategy.

14. Why This Trial Matters Statistically

This registry raises a practical statistical question about the role of additional diagnostic information in management decisions. Its primary endpoint focuses on whether recommendations based on cCTA alone are reclassified when FFRCT is also considered. That question is distinct from whether an intervention improves clinical outcomes, and the endpoint description makes the distinction important by stating that the assessments were not used to determine actual patient care.

Statistically, the record also illustrates why an endpoint label is not enough to interpret a result. The estimate needs a defined denominator, an analysis population, a clear classification rule, and an uncertainty measure. Although the record names a percentage endpoint and a 95% confidence interval, it does not post the estimate or interval. Precision therefore cannot be judged from the registry entry.

The registry includes outcomes across decision-making, clinical events, resource use, and radiation exposure. That breadth creates questions about how endpoints were prioritized, how missing follow-up was handled, and whether multiplicity was addressed. Those methods are not reported in the registry record. The information gap matters because outcome interpretation can depend on these choices, especially when several outcomes and follow-up times are considered.

Finally, the record’s threshold-based safety groups demonstrate why descriptive event counts should not be mistaken for controlled comparisons. Allocation is not stated, and the record indicates that the groups are not like-for-like controls. Clear separation between descriptive reporting and causal inference is essential when interpreting registry results.

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 does not report the primary endpoint estimate, its 95% confidence interval, or the results for the listed secondary outcomes. This prevents evaluation of the magnitude and precision of the principal measure and of the clinical-event and resource outcomes.

The allocation method is not stated, and the safety groups are not a like-for-like control comparison. The record therefore does not support interpreting differences between the FFRCT threshold groups as causal effects. No adjusted comparison is reported.

The primary endpoint is a management-recommendation measure. The record says the assessments were intended to evaluate potential influence on downstream testing and clinical decision-making, but were not used to determine actual patient care. It therefore does not directly report whether recommendations changed actual care or whether any change affected patient outcomes.

Endpoint-specific denominators, the primary analysis population, missing-data methods, and detailed endpoint classification procedures are not reported in the registry record. A detailed statistical analysis plan, multiplicity approach, and interim-analysis procedures are also not reported. The arm description is truncated, limiting the available description of study procedures and eligibility.

The adverse-event entries include different numbers at risk for other events across the two threshold groups, and the record does not provide adjusted analyses or further event-attribution details. These limitations constrain interpretation of the safety counts. Completion status and total enrollment do not resolve these reporting gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care — NCT02499679.
• Registry record last updated 2025-07-30; status last verified 2024-11.
• Results first posted 2025-07-30.
• 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 ADVANCE Registry evaluated FFRCT-guided assessment in clinically stable, symptomatic patients with coronary artery disease. The registry lists HeartFlow, Inc. as sponsor, enrollment of 4737, start date 2015-07, primary completion in 2019-02, and status COMPLETED.

The primary endpoint is the percentage of participants with reclassification of coronary artery disease management recommendations based on CTA alone versus CTA plus FFRCT when available, assessed at 90 days. Secondary outcomes include management reclassification, invasive catheterization without obstructive disease, major adverse coronary events and components, radiation exposure, and resource utilization.

The registry record does not report a numerical primary-endpoint result, its confidence interval, or the secondary-outcome analyses. Allocation is not stated, and the threshold-based adverse-event groups are not like-for-like controls. The record also does not report the analysis population, missing-data methods, or multiplicity plan.