FAME II - Fractional Flow Reserve (FFR) Guided Percutaneous Coronary Intervention (PCI) Plus Optimal Medical Treatment (OMT) Verses OMT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for FAME II - Fractional Flow Reserve (FFR) Guided Percutaneous Coronary Intervention (PCI) Plus Optimal Medical Treatment (OMT) Verses OMT (NCT01132495), a randomized na study. The primary outcome is Major Adverse Cardiac Event Rate (MACE).

2. Clinical Question

3. Trial Design

FAME II is recorded as a randomized, parallel-group trial with no masking. Its official title describes a comparison of fractional flow reserve-guided percutaneous coronary intervention plus optimal medical treatment against optimal medical treatment alone in patients with stable coronary artery disease. The registry lists enrollment of 1170 and identifies Abbott Medical Devices as the sponsor. The listed status is completed; the recorded start is 2010-05 and primary completion is 2014-01.

The primary outcome analysis was designed for Cohort A, whose arm descriptions are PCI plus OMT and OMT alone. The registry also describes Cohort B as FFR > 0.80, with treatment according to local practice. The record does not explain how participants were assigned to Cohort B, or whether Cohort B was randomized. The primary comparison should therefore be understood as the Cohort A comparison, not as a comparison across every listed cohort.

Randomization is intended to make treatment groups comparable at the start of a trial, on average, so that outcome differences can be interpreted in relation to the assigned strategies. In an unmasked trial, participants and clinicians are not blinded to treatment assignment. That can matter for outcomes involving clinical decisions, such as hospitalization leading to revascularization, because knowledge of treatment may influence care or outcome assessment. The registry record does not report allocation concealment, detailed randomization procedures, outcome adjudication, or safeguards against bias.

The phase is recorded as NA. The brief summary describes clinical outcomes, safety, and cost-effectiveness as overall aims, but the registry’s primary outcome entry concerns MACE. Further design details, including a statistical analysis plan and sample-size justification, 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: Participants were randomized to Cohort A if at least one stenoses had an FFR value of \<=0.80. Participants with FFR \>0.80 were treated according to local practice and were randomized to study follow-up / no study follow-up in Cohort B. Therefore, participants are either in cohort A or cohort B (not both).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary outcome analysis was designed for Cohort A only.

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 Major Adverse Cardiac Event Rate (MACE), measured over 24 Month.

The primary endpoint is the percentage of participants with a major adverse cardiac event at 24 Month. The registry defines MACE as a composite of all-cause death, documented myocardial infarction, or unplanned hospitalization leading to urgent revascularization. This combines distinct outcomes into a single endpoint: a participant can meet the composite by experiencing any listed component.

As a general statistical concept, composite endpoints can capture several clinically important ways an intervention might affect participants and can provide a broader summary than any component alone. They also require careful interpretation. Components can differ in severity, frequency, and susceptibility to clinical judgment, so a composite result does not by itself show which component contributed most. The registry record does not report component-specific primary outcome results.

The endpoint is described as a percentage of subjects with SAEs, while the primary outcome definition specifies MACE. The registry record does not further explain this wording. It also does not report an analyzed percentage, a between-group estimate, a confidence interval, or a significance test for the primary endpoint. Consequently, the endpoint definition is available, but the magnitude and precision of the primary comparison are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization, endpoints, and uncertainty each answer different questions. The registry describes FAME II as randomized, parallel, and unmasked. The primary outcome is a binary participant-level measure: whether a participant had a MACE as defined in the record. The record lists the outcome as a percentage, but does not report analyzed percentages or a treatment-effect estimate.

What randomization contributes

As a general statistical principle, random assignment aims to balance known and unknown prognostic characteristics between groups at the time of assignment. This supports a comparison based on assigned treatment, provided the analysis and follow-up preserve the benefits of randomization. The registry record does not report the allocation sequence method, concealment procedures, or the primary analysis population in more detail than identifying Cohort A.

The record states that there was no masking. In general, lack of masking can affect behavior, care decisions, or outcome assessment, particularly when an endpoint includes decisions about hospitalization and revascularization. Randomization does not eliminate those risks. The registry record does not report whether MACE events were adjudicated by a committee unaware of treatment assignment or how decisions about urgent revascularization were standardized.

How to understand a binary endpoint

A binary endpoint classifies each participant according to whether an event occurred during the stated assessment period. A group percentage summarizes the frequency of participants meeting that definition. A comparison of percentages can be expressed in different ways, such as a difference or a relative measure, but the registry record does not report a primary comparison in any form. No such estimate should be inferred from the serious adverse event counts, which are separately recorded.

MACE is a composite: all-cause death, documented MI, or unplanned hospitalization leading to urgent revascularization. General interpretation of a composite requires attention to its component outcomes. If components differ in clinical importance or frequency, the overall composite can reflect them unequally. The record does not provide component-specific primary outcome results, so the contribution of each component cannot be assessed.

What uncertainty measures would tell readers

In general, a confidence interval describes statistical uncertainty around an estimate under the assumptions of the analysis. Its width is informative about precision; it is not a guarantee that the true effect lies within its bounds. A p-value, when reported, addresses compatibility of the observed data with a specified null hypothesis under a statistical model. It does not measure the probability that a treatment is effective, nor does it describe the size or clinical importance of an effect. The registry record reports neither a confidence interval nor a p-value for the primary comparison.

For binary outcomes, analyses can also depend on how follow-up time and missing outcome status are handled. The registry record gives a 24 Month timeframe, but does not state whether the analysis used a complete-case approach, imputation, a time-to-event method, or another procedure. These methods can answer different questions and rely on different assumptions. The statistical analysis plan and handling of missing data are not reported in the registry record.

Why over-dispersion is not the main issue described

As a general concept, over-dispersion arises when count data vary more than a chosen model expects, which can make standard errors too small if the extra variation is ignored. The primary endpoint is described as the percentage of participants with a binary event, not as a count outcome model. The registry record does not report a model or analysis that would allow readers to assess whether over-dispersion was relevant. It is therefore not appropriate to assume a particular model or adjustment.

Planning illustrations and observed evidence

The registry’s sample-size assumptions describe planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are explicitly planning illustrations, not observed power. The stated approach distinguishes total events for time-to-event outcomes from participants per arm for other outcomes. No numerical planning outputs or primary observed effect are reported in the registry record. A planning illustration cannot replace a treatment-effect estimate or establish what the trial observed.

In short, the registry gives enough information to identify the broad design and endpoint, but not enough to reproduce or evaluate the primary analysis. The exact statistical model, covariate adjustment, estimand, confidence interval method, and analysis population beyond Cohort A are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry names Overall MACE as a secondary outcome and records two outcome measures, but no analyzed results are listed. It records zero analyses. The primary outcome is specified for Cohort A, but the registry record does not describe a broader hierarchy of hypotheses, a multiplicity adjustment, or rules for interpreting multiple outcomes. These details are not reported in the registry record.

Multiplicity matters in general when several outcomes or comparisons are tested: conducting more tests can increase the chance of finding a nominally unusual result even when there is no underlying effect. Adjustment methods and pre-specified testing strategies can address that concern, but readers cannot determine what approach was used from this entry. No adjustment should be assumed.

The registry record does not explain missing outcome data, loss to follow-up, withdrawals, or censoring. It also does not state whether the primary analysis followed intention-to-treat principles, used another population, or applied a particular imputation method. Those choices can affect both the analysis population and the interpretation of a randomized comparison. They are not reported in the registry record.

The primary endpoint analysis is stated to be designed for Cohort A only. The record does not provide additional details about the exact membership of the analysis population or how participants with unavailable endpoint information were treated. Therefore, the analysis set and missing-data assumptions cannot be independently assessed from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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

Serious events with the highest arm-level rate: non urgent revacularization (32.7%), unplanned hospitalization with urgent revascularization (13.4%), death or mi (12.2%), myocardial infarction (9.3%), death (3.9%).

The registry lists serious adverse event figures by cohort. For Cohort A, PCI plus OMT has 447 participants at risk and 137 affected; OMT alone has 441 at risk and 324 affected. Cohort B follow-up has 166 at risk and 55 affected, and Cohort B with no follow-up re-consented has 116 at risk and 28 affected. These are registry-listed safety entries, not a substitute for the primary MACE analysis.

The record also lists serious event terms and percentages: Non Urgent Revacularization, 32.7%; Unplanned Hospitalization with Urgent Revascularization, 13.4%; Death or MI, 12.2%; Myocardial Infarction, 9.3%; Death, 3.9%; and Cerebrovascular Event, 2.2%. The registry record does not make clear in this entry whether these terms refer to unique participants, events, or a particular denominator, so they should be read as listed rather than converted into comparative risks.

These figures do not establish causation or a treatment effect. The record does not report attribution to study treatment, exposure time, statistical comparisons, or a detailed account of overlap among event terms. Serious adverse events should also be distinguished from MACE: the primary endpoint has its own stated composite definition and its analysis is not reported in the registry record.

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

The registry record establishes that FAME II was designed to compare FFR-guided PCI plus OMT with OMT alone in Cohort A, among patients with stable coronary artery disease. It identifies randomization, a parallel design, no masking, and a primary MACE endpoint assessed at 24 Month. These details define the clinical question, but they do not tell readers what the primary comparison found.

The record does not report the primary outcome event percentages, effect estimate, confidence interval, or p-value. Consequently, it cannot show how the groups differed, how precise any difference was, or whether a result was compatible with a range of clinically meaningful effects. The completed status does not fill in those missing statistical results.

The serious adverse event counts and listed event terms offer descriptive safety information, but the entry does not provide the context needed for a comparative safety analysis. They do not identify treatment attribution, clarify event overlap, or report an adjusted estimate. They should not be treated as proof that one strategy is safer or less safe.

More generally, a trial result is an estimate tied to a population, outcome definition, follow-up period, and analysis method. Even a reported statistical difference would need to be interpreted alongside its uncertainty, outcome components, and study limitations. Here, the statistical comparison itself is not reported in the registry record, so neither benefit nor lack of benefit can be inferred from the listed design information or safety entries.

The record supports a precise description of the intended randomized question and the limits of the posted results. It does not support a clinical recommendation, a claim that treatment works or fails, or a conclusion about the balance of benefits and harms.

13. Why This Trial Matters Statistically

FAME II illustrates an important distinction in clinical trial reporting: a registered design and a stated endpoint are not the same as a reported analysis. The record identifies a randomized comparison and defines a composite outcome, giving readers a clear outline of the question the trial was intended to address. Yet the primary outcome comparison is not available in the registry record.

That distinction matters statistically because conclusions depend on estimates and their uncertainty, not on trial labels alone. Without outcome percentages, a treatment-effect estimate, or an interval describing precision, readers cannot judge the magnitude or reliability of the primary comparison. A completed trial status and a large enrollment figure do not independently supply that evidence.

The trial also highlights why composite outcomes require transparent reporting. MACE combines death, documented MI, and urgent revascularization after unplanned hospitalization. These components may represent different kinds of events, and a composite summary alone would not show their separate contributions. Component results would help readers understand what shaped an overall comparison, but they are not reported for the primary outcome in this entry.

The unmasked design is also relevant to statistical interpretation. Randomization helps address baseline differences, while lack of masking can leave room for differences in care or outcome assessment, especially for endpoints that include clinical decisions. Information on adjudication and analysis procedures would help readers assess these issues; it is not reported in the registry record.

Finally, the safety entries demonstrate the value of explaining denominators, event definitions, attribution, and overlap. Without that context, listed counts and percentages cannot be treated as a complete comparative safety analysis. The statistical lesson is not a conclusion about either treatment strategy, but the importance of complete, interpretable results alongside a clear trial design.

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 contains no analyzed primary outcome comparison, despite specifying MACE at 24 Month as the primary endpoint. It provides no Cohort A event percentages, effect estimate, confidence interval, or p-value. The primary outcome results and their precision are therefore unavailable for interpretation.

The endpoint is defined as a composite of all-cause death, documented MI, or unplanned hospitalization leading to urgent revascularization, but primary component-specific results are not reported. The endpoint entry’s wording refers to a percentage of subjects with SAEs; the record does not explain that wording in relation to its MACE definition.

Several methods needed to assess possible bias and robustness are not reported in the registry record. These include allocation concealment, outcome adjudication, the statistical model, covariate adjustment, the analysis population beyond the statement that the primary analysis was designed for Cohort A, multiplicity handling, and missing-data methods. The record also does not explain Cohort B’s relationship to the randomized comparison.

Safety information is limited to listed serious adverse event counts and terms. The record does not specify event attribution, exposure time, overlap among terms, or the denominators behind the listed percentages. These entries cannot replace a comparative safety analysis.

The registry identifies the trial as completed and gives enrollment and timing, but these details do not resolve the absence of analyzed outcomes. The statistical analysis plan and sample-size justification are not reported in the registry record. The available information therefore supports description of the intended design, not an independent assessment of the trial’s primary findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: FAME II - Fractional Flow Reserve (FFR) Guided Percutaneous Coronary Intervention (PCI) Plus Optimal Medical Treatment (OMT) Verses OMT — NCT01132495.
• Registry record last updated 2019-09-16; status last verified 2019-08.
• Results first posted 2016-12-09.
• 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

FAME II is recorded as a completed, randomized, parallel-group, unmasked trial sponsored by Abbott Medical Devices. It enrolled 1170 participants with coronary artery disease. The stated primary question concerned Cohort A: FFR-guided PCI plus OMT compared with OMT alone. The primary endpoint was MACE at 24 Month, defined as all-cause death, documented MI, or unplanned hospitalization leading to urgent revascularization.

The record lists serious adverse event counts for Cohort A and Cohort B groups, along with serious event terms and percentages. It names Overall MACE as a secondary outcome. However, it reports zero analyses and does not include a primary outcome estimate, confidence interval, or p-value. Details of the analysis plan, multiplicity, and missing-data handling are not reported in the registry record. The registry information therefore describes the intended comparison and selected safety entries, but does not report the primary statistical result.