The Value of CT Fractional Flow Reserve: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Value of CT Fractional Flow Reserve (NCT03026283), a registered phase not stated study. The primary outcome is Comparison of CCTA Alone to FFR-CT After CCTA.

2. Clinical Question

The study asks whether adding CT-derived fractional flow reserve (CT-FFR) to coronary computed tomography angiography (CCTA) helps distinguish physiologically significant coronary narrowing from narrowing that is not significant by invasive fractional flow reserve (FFR). Its focus is diagnostic performance, not a randomized comparison of treatment strategies.

Those measures address different aspects of diagnostic classification. The registry’s stated aim is to evaluate the incremental diagnostic benefit of CT-FFR in triaging this chest-pain population. It also describes correlating invasive FFR and short-term clinical outcomes with each diagnostic approach. The record does not report the resulting estimates, so the size or precision of any incremental diagnostic value cannot be stated.

3. Trial Design

This is a prospective, single-center observational clinical trial sponsored by Northwell Health. The registry lists an enrollment of 586 and a status of completed. The recorded start is 2017-01, and primary completion is recorded as 2018-06. These registry dates and enrollment information describe the study record; they do not establish which participants contributed to each analysis.

Patients undergo CCTA as part of routine care. The study description says that consenting patients with coronary stenosis of 30% to 90%, based on the cardiologist’s reading, receive CT-FFR. The intervention is named HeartFlow CT-FFR. The listed arm description says patients who consent receive CT-FFR and medically acceptable care according to the study protocol, accepted standards of care and the patient’s condition.

The diagnostic comparison is CCTA alone versus CT-FFR after CCTA, with invasive FFR used as the reference standard. The primary endpoint population is specified as patients who received both FFR-CT and diagnostic catheterization. This is not a randomized treatment comparison: the registry states that allocation is not stated and that the arms are not a like-for-like control comparison. The outcome categories for safety are patients referred for cardiac intervention, stress testing, or optimal medical care; these are care dispositions, not randomized arms.

The registry describes a timeframe of up to 1 year from study initiation to enroll all study patients and obtain invasive and noninvasive FFR. It does not report how many participants had each diagnostic test, the number included in each endpoint analysis, or the reasons some participants may not have contributed to a particular analysis. Detailed eligibility criteria, recruitment procedures and the statistical plan are not reported in the registry record.

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: To participate, patients were required to complete the CCTA, and on exam have no Cardiac stenting or bypasses as determined by medical history provided by the patient and review of CCTA scan.

Only the first 6 of 8 groups are shown.

CCTA Diagnosis

Reasons for not completing this period:

Optimal Medical Care/FFR-CT Diagnosis

Reasons for not completing this period:

Optimal Care/Stress Test/ICA

Reasons for not completing this period:

Optimal Care/ICA Diagnostic Cath

Analysis population for the primary outcome, as defined in the registry: All patients who received FFR-CT and Diagnostic Catheterization.

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: The initial enrollment number was 586. However, 14 patients did not receive CCTA, and three additional patients became screen failures, due to medical conditions revealed on the CCTA screen. Therefore the total reported is 569.

6. Primary Endpoint

The registry lists the primary outcome as Comparison of CCTA Alone to FFR-CT After CCTA, measured over Up to 1 year from the study initiation will be required to enroll all study patients and obstain invasive and noninvasive FFR..

The primary endpoint evaluates sensitivity, specificity, positive predictive value and negative predictive value for CT-FFR after CCTA compared with CCTA alone, using invasive FFR as the gold standard. These are diagnostic-performance measures: sensitivity describes how often a method identifies disease when the reference standard indicates disease, while specificity describes how often it identifies its absence. Positive and negative predictive values describe the relationship between a test classification and the reference standard among positive and negative classifications, respectively.

The comparison is intended to address whether CT-FFR adds information beyond the CCTA assessment. A reference standard is needed because the diagnostic methods being compared do not themselves determine whether a coronary narrowing is physiologically significant. In this record, invasive FFR serves that role.

The listed endpoint unit is percent, and its stated dispersion is a 95% confidence interval. The specified population is patients who received FFR-CT and diagnostic catheterization. That population definition matters: the endpoint does not automatically describe every enrolled participant or every patient undergoing CCTA.

The timeframe says up to 1 year from study initiation would be required to enroll all study patients and obtain invasive and noninvasive FFR. The registry record contains no primary endpoint estimates or confidence limits. Therefore, it is not possible to describe the observed diagnostic performance, its precision, or the magnitude of any difference between CCTA alone and CT-FFR after CCTA from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies diagnostic-performance measures and a reference standard, but it does not report the numerical analyses or a detailed statistical analysis plan. The concepts below explain how these measures are generally interpreted; they should not be taken as confirmation of specific analytic choices beyond those named in the record.

What does sensitivity and specificity measure?

When a diagnostic method is evaluated against a reference standard, sensitivity and specificity describe two different types of classification. Sensitivity concerns how often the method gives a positive classification among cases classified as positive by the reference standard. Specificity concerns how often the method gives a negative classification among cases classified as negative by the reference standard. A method can perform differently on these two dimensions, so neither measure alone fully describes diagnostic performance.

Here, invasive FFR is named as the gold standard. The primary objective is to evaluate these measures for CCTA alone and for CT-FFR after CCTA. The registry does not report the underlying classification counts, estimates or confidence intervals, so the measures cannot be reconstructed or interpreted numerically from the record.

What do predictive values add?

Positive predictive value concerns the proportion of positive test classifications that agree with a positive reference-standard classification. Negative predictive value concerns the proportion of negative test classifications that agree with a negative reference-standard classification. These values answer questions about the meaning of a test result within the population being assessed. Unlike sensitivity and specificity, predictive values depend on how common reference-standard-positive cases are in the population under study. Consequently, predictive values from a selected group that received catheterization may not carry over directly to a different clinical population.

The study’s stated population for the primary endpoint includes patients who received both FFR-CT and diagnostic catheterization. That restriction is relevant to predictive-value interpretation because the registry does not establish that this group represents all CCTA patients or all people with chest pain.

How should the confidence interval be read?

A confidence interval is a statistical expression of uncertainty around an estimate. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. Its interpretation depends on the estimate, the analysis and the data. The registry specifies a 95% confidence interval as the endpoint’s dispersion, but does not report the interval limits or the underlying diagnostic-performance estimates. The precision of the study’s primary results therefore cannot be assessed from the record.

What does the comparison establish?

The named comparison is CCTA alone versus CT-FFR after CCTA, using invasive FFR as the reference standard. This is a comparison of diagnostic classifications, not a randomized comparison of clinical outcomes under alternative assigned interventions. The registry describes an observational design, and it does not state that participants were allocated at random. The comparison can address diagnostic performance as defined by the endpoint, but it does not by itself establish the effects of a testing strategy on later health outcomes.

The registry also refers to correlating short-term clinical outcomes at 90 days with each diagnostic modality. The record does not report the analysis methods or results for that relationship. Association between a test result and a later outcome would not, by itself, establish that the test caused the outcome or that using the test changes outcomes.

How does observer reliability differ from accuracy?

The listed secondary measures include inter-observer reliability for all cases and for cases meeting at least mild, moderate or severe disease thresholds on CCTA. Inter-observer reliability generally concerns the consistency of assessments made by different observers. It is distinct from diagnostic accuracy: observers can agree with one another without necessarily agreeing with the reference standard. The registry does not state the reliability statistic, the observer procedures or the results, so the strength and meaning of any agreement cannot be determined.

What can be inferred from planning illustrations?

Any sample-size calculations associated with the posted results are planning illustrations computed from an observed effect, not a report of the trial’s original design rationale. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such calculations describe hypothetical planning requirements under their assumptions; they are not observed power and do not show that the trial was designed around those assumptions. The registry record does not report the original sample-size justification or a protocol-based statistical plan.

Because the endpoint results are not reported in the registry record, a planning illustration cannot substitute for estimates of diagnostic performance or their uncertainty. It also cannot resolve the implications of the selected endpoint population, missing data or the nonrandomized study design.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven secondary outcome measures. They include inter-observer reliability for all cases, for cases with at least mild disease, for cases with at least moderate disease, and for cases with severe disease diagnosed on the official read. It also lists return visits and reasons for return. The record lists two analyses, but does not describe their statistical methods in detail.

When a study examines multiple outcomes or multiple related analyses, the chance of finding at least one apparently unusual result can increase if each is interpreted without accounting for the broader set of comparisons. This is a general statistical concern, not a claim about a particular result in this study. The registry does not report whether any multiplicity adjustment, hierarchy of endpoints or prespecified testing order was used.

The record does not describe how missing observations were handled, whether incomplete diagnostic workups were excluded, or how participants without both CT-FFR and diagnostic catheterization were treated in analyses. It also does not report analysis-population definitions beyond the primary endpoint population of patients who received both tests. The enrollment figure should therefore not be assumed to be the denominator for every outcome.

Further details on exclusions, missingness, imputation, protocol deviations and analysis populations are not reported in the registry record. Without them, it is difficult to assess the potential effects of incomplete follow-up or selection into the primary diagnostic analysis.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: percutaneous coronary intevention (1.4%).

The registry reports safety counts under three referral categories: patients referred for cardiac intervention, stress testing, and optimal medical care. In the cardiac-intervention category, 101 were at risk for serious adverse events, with 1 affected; 101 were at risk for other adverse events, with 0 affected; deaths were 2. In the stress-testing category, 73 were at risk for serious adverse events, with 1 affected; 73 were at risk for other adverse events, with 2 affected; deaths were 0. In the optimal-medical-care category, 398 were at risk for serious adverse events, with 0 affected; 398 were at risk for other adverse events, with 2 affected; deaths were 0.

The registry also lists Percutaneous Coronary Intevention at 1.4% among the leading serious adverse event terms. These figures are descriptive counts in the recorded referral categories. The record does not explain whether categories overlap, how events were attributed, or how the listed term relates to the category-level counts. The counts should not be read as evidence that CT-FFR or any particular care pathway caused an event. The categories are not randomized comparison groups, and the registry does not report a causal safety analysis.

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

The registry record establishes what the study set out to evaluate: whether CT-FFR after CCTA improves diagnostic classification relative to CCTA alone, using invasive FFR as the reference standard. It also describes a prospective, single-center observational design, a primary endpoint population requiring both CT-FFR and diagnostic catheterization, and several secondary outcomes. These details help define the question and the population to which an eventual diagnostic estimate would apply.

The record does not report the primary estimates, confidence intervals or secondary outcome results. It therefore does not show the observed sensitivity, specificity, positive predictive value or negative predictive value for either diagnostic approach. Without those estimates, readers cannot assess the direction, magnitude or precision of the diagnostic comparison. Enrollment and completion status do not fill that gap.

Even if diagnostic performance estimates were available, they would address agreement with the named reference standard in the analyzed population. They would not by themselves establish that using CT-FFR changes clinical decisions, improves clinical outcomes, or causes a difference in safety. The observational design and absence of random allocation also mean that outcomes across referral categories cannot be treated as a randomized comparison of care strategies.

The endpoint population is defined by receipt of both CT-FFR and diagnostic catheterization. That selection may limit how directly its findings apply to people who undergo CCTA but do not receive both additional assessments. The record does not report how participants were selected for catheterization or whether the analyzed group differed from other enrolled participants.

Accordingly, the study question is clinically specific, but the registry record alone supports no conclusion about the comparative diagnostic results or their clinical consequences. Those conclusions require the actual analyses, uncertainty estimates and relevant details of participant selection and missing data.

13. Why This Trial Matters Statistically

This trial matters statistically because it frames an incremental diagnostic question. CCTA and CT-FFR are not treated as interchangeable measurements: the study asks whether CT-FFR adds diagnostic information after CCTA, and it names invasive FFR as the reference standard. Comparing both diagnostic approaches against the same reference standard is central to interpreting the stated aim.

The choice of performance measures also matters. Sensitivity and specificity describe classification relative to the reference standard, whereas positive and negative predictive values describe the meaning of classifications within the tested population. Predictive values can vary with the composition of that population. The primary endpoint’s restriction to patients receiving both CT-FFR and diagnostic catheterization is therefore part of the statistical interpretation, not merely an administrative detail.

The observational design provides a different kind of evidence from a randomized trial. It can examine diagnostic performance and associations, but care dispositions are not randomized groups. Referral categories may reflect clinical findings and decisions, so their outcomes should not be interpreted as causal treatment comparisons.

The registry also identifies observer reliability and return visits as secondary topics. Reliability is distinct from accuracy, while return visits concern subsequent care. Each requires its own outcome definition and analysis. The record does not report results or a multiplicity plan, which limits assessment of the full set of intended analyses.

Finally, the registry’s endpoint definitions and design details are informative, but estimates and uncertainty are necessary to judge evidence. Without the primary results and their confidence intervals, the central diagnostic question remains unanswered in the registry record.

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 principal limitation for interpretation is that the registry record does not report the primary diagnostic estimates or their confidence intervals. Although it specifies the measures and reference standard, it does not provide the results needed to assess performance or precision.

The study is prospective and observational, with a single center named in its official title. Its findings, if reported, would need to be interpreted in light of that setting and the defined patient group. The endpoint population consists of patients who received both FFR-CT and diagnostic catheterization, while enrollment describes the broader study. The record does not report the number included in the primary analysis or the selection process leading to catheterization.

The registry summary describes eligible stenosis as > 30% and < 90%, while the study description also refers to 30% to 90% stenosis based on the cardiologist’s reading. The record does not explain how these threshold descriptions were operationalized or how borderline readings were handled. It also does not report detailed eligibility criteria, missing-data procedures, exclusions or analysis-population definitions.

Allocation is not stated, and the listed referral categories are not like-for-like randomized groups. Consequently, comparisons among those categories cannot establish causal effects of different care. The registry does not report adjustment methods, event adjudication procedures, or a statistical analysis plan. It also does not report whether multiplicity was addressed across the secondary outcomes and analyses. These omissions limit assessment of potential bias, uncertainty and the interpretation of any eventual findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Value of CT Fractional Flow Reserve — NCT03026283.
• Registry record last updated 2023-05-30; status last verified 2023-05.
• Results first posted 2020-06-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes The Value of CT Fractional Flow Reserve as a completed, prospective, single-center observational trial sponsored by Northwell Health. It lists enrollment of 586, with a start of 2017-01 and primary completion of 2018-06. The study concerns outpatient low to intermediate risk chest pain and CCTA findings of coronary stenosis.

The primary objective is to compare CCTA alone with CT-FFR after CCTA for sensitivity, specificity, positive predictive value and negative predictive value, using invasive FFR as the reference standard. The listed endpoint population is patients who received both FFR-CT and diagnostic catheterization. Secondary outcomes include inter-observer reliability and return visits.

The record lists safety counts by referral category but does not report primary diagnostic estimates, confidence intervals, secondary results, missing-data methods, or a detailed statistical plan. Allocation is not stated; the care categories are not randomized comparison groups. The registry therefore defines the study question and some outcome populations, but does not provide the results needed to evaluate diagnostic performance.