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Coronary Artery Disease Phase 3 Time-to-Event Analysis NCT00086450

FREEDOM: Complete Statistical Analysis of Coronary Revascularization in Multivessel Coronary Artery Disease with Diabetes

An independent statistical review of the randomized phase 3 FREEDOM trial comparing coronary artery bypass grafting with percutaneous coronary intervention in individuals with diabetes and multivessel coronary artery disease.

Trial period: 2004-04 to 2012-07  ·  Enrollment: 1900  ·  Primary endpoint: measured at Year 5
Scope of this record

This page separates reported trial results from statistical interpretation. Numerical results are restricted to the ClinicalTrials.gov record for NCT00086450. Where the registry does not provide a particular estimate, confidence interval, or design detail, it is not reported here.

Registry note: This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.

1. Trial at a Glance

FREEDOM was a randomized, parallel-group, unmasked phase 3 trial comparing percutaneous coronary intervention with coronary artery bypass grafting in individuals with diabetes and multivessel coronary artery disease. The registry reports a primary time-to-event composite endpoint measured at Year 5 and analyzed with a Cox proportional-hazards model.

1900
Enrollment
2 treatment arms
2
Arms
Parallel randomized design
7.9
Primary estimate
95% CI 3.3–12.5
0.005
Primary P-value
Superiority hypothesis
FeatureFREEDOM
Trial nameFREEDOM
PhasePhase 3
PopulationIndividuals with multivessel coronary artery disease and diabetes
ConditionsCardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Heart Diseases
DesignRandomized, parallel-group, unmasked
AllocationRandomized
Primary purposeTreatment
Enrollment1900
InterventionsCoronary Artery Bypass Graft (procedure); Percutaneous Coronary Intervention (device)
Trial statusUNKNOWN
Start2004-04
Primary completion2012-07
ClinicalTrials.govNCT00086450

2. Clinical Question

The statistical question is whether the two randomized revascularization strategies differ with respect to the registered composite endpoint of all-cause mortality, non-fatal myocardial infarction, and stroke, measured at Year 5.

Population

Individuals with multivessel coronary artery disease and diabetes, within the cardiovascular and coronary disease conditions specified in the registry.

Intervention

Percutaneous Coronary Intervention, described in the registry as a device intervention.

Comparator

Coronary Artery Bypass Graft, described in the registry as a procedure intervention.

Primary question

Under a superiority framework, does the randomized comparison of percutaneous coronary intervention versus coronary artery bypass grafting differ in the Year 5 composite endpoint?

3. Trial Design

01
Enroll1900 participants
02
Randomize2 parallel arms
03
TreatmentPCI or CABG
04
FollowTime-to-event outcomes
05
AnalyzeCox / log-rank methods
Allocation
Randomized allocation was used to assign participants to the two parallel treatment groups.
Design model
Parallel-group design with two arms.
Masking
None. The registry identifies the trial as unmasked.
Primary purpose
Treatment.
ARM A · 953 at risk for reported serious AEs

Percutaneous Coronary Intervention

  • Percutaneous Coronary Intervention
  • Registry intervention classification: device
ARM B · 947 at risk for reported serious AEs

Coronary Artery Bypass Graft

  • Coronary Artery Bypass Graft
  • Registry intervention classification: procedure

The serious-adverse-event denominators reported by arm are 953 for percutaneous coronary intervention and 947 for coronary artery bypass grafting. These sum to the total enrollment of 1900, but the ClinicalTrials.gov record does not provide a separate detailed analysis population definition beyond these affected/at-risk counts.

4. Endpoints

EndpointRegistry definition / time frameEndpoint typeStatistical approach
5-year Composite Endpoint of All-cause Mortality, Non-fatal Myocardial Infarction, and Stroke Measured at Year 5; registry definition notes median 3.8 years of follow-up. Time-to-event Cox proportional-hazards model
Major MACCE Rates, Including the First of One of the Following: Death, Myocardial Infarction, Stroke, or Repeat Revascularization Measured at Year 1 Time-to-event Cox proportional-hazards model
All-cause Mortality Measured at Year 5 Time-to-event Log-rank test
Rates of Individual MACCE Endpoints Measured at Day 30 Time-to-event Cox proportional-hazards model

The registry reports four outcome measures and four statistical analyses. One of the four analyses is identified as the primary endpoint analysis, while the other three are secondary analyses.

5. Primary Endpoint Result

The primary endpoint was the 5-year Composite Endpoint of All-cause Mortality, Non-fatal Myocardial Infarction, and Stroke, measured at Year 5. The registry identifies the endpoint as time-to-event and reports a Cox proportional-hazards regression comparing percutaneous coronary intervention with coronary artery bypass grafting.

Primary Cox proportional-hazards estimate

7.9

95% CI: 3.3–12.5   ·   P = 0.005

Comparison: Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft

Primary endpointComparisonEffect measureEstimate95% CIP-value
5-year Composite Endpoint of All-cause Mortality, Non-fatal Myocardial Infarction, and Stroke Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft Hazard ratio 7.9 3.3–12.5 0.005
Registry-field caution: the ClinicalTrials.gov record reports an effect measure of "Hazard ratio," an estimate of 7.9, and a 95% confidence interval of 3.3–12.5. This page reproduces those values exactly and does not recalculate, reinterpret, or substitute a different estimate from another source.
Clinical Biostats interpretation

What the estimate means: the registry reports a hazard ratio of 7.9 for percutaneous coronary intervention versus coronary artery bypass grafting for the primary composite endpoint. If interpreted literally as a hazard ratio, a value of 7.9 corresponds to an estimated instantaneous event hazard 7.9 times that of the comparator under the fitted model.

What it does not mean: a hazard ratio is not a percentage of participants experiencing the endpoint, not a probability that an individual patient will experience the endpoint, and not a statement that every participant has exactly the same relative hazard.

Precision: the reported 95% confidence interval extends from 3.3 to 12.5. It describes statistical uncertainty around the reported hazard-ratio estimate under the analysis framework; it does not describe the range of outcomes that individual participants could experience.

P-value: the reported P = 0.005 addresses evidence against the null hypothesis under the specified testing framework. It does not measure the size of the treatment effect and should not be interpreted as the probability that the null hypothesis is true.

Important caution: the registry supplies a Cox proportional-hazards analysis but does not provide enough information in the ClinicalTrials.gov record to independently assess the proportional-hazards assumption, censoring details, analysis population, or model specification. The reported estimate should therefore be understood as the registry's stated result rather than a reconstructed analysis.

6. Secondary Endpoint Results

Major MACCE Rates at Year 1

The registry reports a secondary time-to-event endpoint defined as Major MACCE Rates, Including the First of One of the Following: Death, Myocardial Infarction, Stroke, or Repeat Revascularization, measured at Year 1.

Hazard ratio

2.74

95% CI: 1.91–3.89   ·   P = 0.004

Comparison: Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft

The registry identifies Cox proportional-hazards regression as the analysis method and hazard ratio as the effect measure. The reported estimate is 2.74 with a 95% confidence interval of 1.91–3.89.

All-cause Mortality at Year 5

All-cause mortality was a secondary time-to-event endpoint measured at Year 5. The registry identifies the log-rank test as the reported statistical method and hazard ratio as the effect measure.

Hazard ratio

5.4

95% CI: not reported in the registry analysis data   ·   P = 0.049

Comparison: Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft

The ClinicalTrials.gov record does not provide lower and upper confidence limits for this secondary analysis. They are therefore not inferred from the point estimate or p-value.

Individual MACCE Endpoints at Day 30

The registry also reports a secondary endpoint, Rates of Individual MACCE Endpoints, measured at Day 30. The reported comparison used Cox proportional-hazards regression with a superiority hypothesis.

EndpointTime frameMethodEffect measureEstimate95% CIP-value
Rates of Individual MACCE Endpoints Day 30 Cox proportional-hazards model Hazard ratio Not reported in the ClinicalTrials.gov record Not reported in the ClinicalTrials.gov record 0.68

The registry supplies a P-value of 0.68 for this analysis but does not supply an estimate or confidence interval in the ClinicalTrials.gov record. No effect estimate is reconstructed from the p-value.

7. Statistical Methodology

Time-to-event analysis

The primary endpoint and all three reported secondary analyses are identified as time-to-event endpoints. This is important because the analysis concerns when an event occurs, rather than simply whether an event occurred by a fixed point.

Time-to-event methods can incorporate different lengths of follow-up and right-censoring. A participant who has not experienced the event at the end of their observed follow-up can still contribute information to the risk set up to the censoring time.

Conceptual survival function
S(t) = P(T > t)

The survival function represents the probability that the event time T exceeds time t. For a composite endpoint, the event is defined according to the registered composite outcome.

Cox proportional-hazards model

The registry identifies Cox proportional-hazards regression as the method for the primary endpoint, the Year 1 Major MACCE endpoint, and the Day 30 individual MACCE endpoint. The Cox model relates the hazard of an event to the treatment comparison without requiring a specific baseline hazard distribution.

Conceptual Cox model
h(t | X) = h0(t) exp(βX)

For a binary treatment indicator, the hazard ratio is represented by exp(β). The registry supplies the resulting hazard-ratio estimates but does not provide the underlying regression coefficient or full model specification.

Hazard ratio

The hazard ratio is a relative measure of the instantaneous event rate between groups within the Cox model. An HR below 1 indicates a lower estimated hazard for the numerator group relative to the comparator; an HR above 1 indicates a higher estimated hazard.

Because the registry comparison is explicitly Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft, the direction of every reported hazard ratio must be interpreted in that order. Reversing the comparison would invert the hazard ratio.

Log-rank test

The registry identifies the log-rank test for the secondary all-cause mortality endpoint measured at Year 5. The log-rank test compares the observed and expected event patterns across treatment groups over follow-up and is designed for time-to-event data.

Conceptual interpretation
Observed events  vs.  expected events under the null hypothesis

The log-rank framework evaluates whether the event-time distributions differ between groups. It is not itself a measure of effect size; the registry separately reports a hazard-ratio effect measure for this analysis.

Superiority hypothesis

The registry identifies the hypothesis type as superiority for the primary endpoint and each of the three reported secondary analyses. A superiority framework asks whether the randomized groups differ rather than whether one treatment stays within a prespecified non-inferiority margin.

8. Statistical Methods Explained

Why are these endpoints analyzed as time-to-event outcomes?

The registry defines the primary endpoint and secondary outcomes as time-to-event endpoints. This preserves information about the timing of events and permits participants with different observed follow-up times to contribute information appropriately. A simple binary comparison at Year 5 would discard some of that timing information.

What does a hazard ratio of 2.74 mean?

The reported Year 1 Major MACCE analysis has an HR of 2.74 for percutaneous coronary intervention versus coronary artery bypass grafting. Interpreted literally as a hazard ratio, the fitted model estimates an instantaneous event hazard 2.74 times that of the comparator over the modeled follow-up. It does not mean that 2.74 times as many participants necessarily experienced an event, nor does it imply a constant individual-level risk ratio.

Why is the confidence interval important?

The 95% confidence interval communicates the statistical precision of the estimated effect. For the primary endpoint, the reported interval is 3.3–12.5. A wide interval indicates more uncertainty about the exact magnitude than a narrow interval would. The interval is not a range containing 95% of individual patient effects.

Why doesn't the p-value measure effect size?

The primary P-value of 0.005 is evidence against the relevant null hypothesis under the stated analysis framework. It does not tell us whether the estimated effect is clinically large or small. Effect magnitude is described by the estimate itself, while the confidence interval adds information about precision.

Why can the log-rank test and Cox model appear in the same trial?

They address related but different statistical tasks. The log-rank test provides a hypothesis test comparing time-to-event experience between randomized groups, while the Cox model provides a model-based estimate of the relative hazard. The FREEDOM registry data use both methods across the reported endpoints.

What does randomization contribute statistically?

Randomization assigns participants to treatment groups without using observed baseline characteristics to determine assignment. Its principal statistical value is that, under appropriate conduct of the trial, treatment assignment is not systematically determined by prognostic factors at baseline. The comparison can therefore be interpreted as a randomized treatment comparison rather than simply an observational association.

What does an unmasked design change?

The registry specifies Masking: NONE. Consequently, patients and investigators were not blinded to the assigned surgical procedure. Knowledge of treatment assignment can affect aspects of care or behavior surrounding the intervention and follow-up, which is an important consideration when interpreting trial results.

9. Primary Endpoint: How to Read the Result

Estimate

The registry reports 7.9 as the primary hazard-ratio estimate for percutaneous coronary intervention versus coronary artery bypass grafting. Taken literally as the reported HR, this is a large relative difference in the estimated instantaneous hazard.

Confidence interval

The reported 95% CI is 3.3–12.5. The interval is entirely above 1, but the more important point for interpretation is that it shows substantial uncertainty about the exact magnitude of the estimated relative hazard.

P-value

The reported P = 0.005 is consistent with the registry's superiority hypothesis testing framework. It should be read as evidence relative to a null hypothesis, not as a measure of how important the treatment difference is.

Absolute effects

The registry analysis data do not provide event percentages for the primary composite endpoint. It would therefore be inappropriate to manufacture an absolute risk difference or number needed to treat from the reported hazard ratio alone.

10. Composite Endpoint Interpretation

The primary endpoint combines three clinically distinct events: all-cause mortality, non-fatal myocardial infarction, and stroke. A composite endpoint can increase the number of observed events and thereby provide more statistical information than any single component considered alone.

At the same time, a composite is not equivalent to any one of its components. A treatment effect on the composite can reflect different contributions from mortality, myocardial infarction, and stroke. The registry-reported primary analysis does not provide separate component-specific estimates for these three components, so the reported HR of 7.9 should be attributed only to the registered composite endpoint.

What the composite tells us

The primary statistical comparison concerns the first occurrence of the registered composite outcome under the time-to-event framework.

What it does not tell us

The primary composite estimate does not by itself identify which individual component drove the observed statistical difference.

11. Year 1 Major MACCE Analysis

The Year 1 secondary endpoint is defined as Major MACCE Rates, Including the First of One of the Following: Death, Myocardial Infarction, Stroke, or Repeat Revascularization.

FeatureReported result
EndpointMajor MACCE Rates, Including the First of One of the Following: Death, Myocardial Infarction, Stroke, or Repeat Revascularization
Time frameMeasured at Year 1
ComparisonPercutaneous Coronary Intervention vs Coronary Artery Bypass Graft
MethodCox proportional-hazards model
Effect measureHazard ratio
Estimate2.74
95% CI1.91–3.89
P-value0.004
HypothesisSuperiority

The endpoint is defined around the first occurrence of one of the listed MACCE components. That detail matters statistically: once the first qualifying event occurs, the participant has experienced the endpoint even if additional events subsequently occur.

12. Year 5 All-cause Mortality Analysis

All-cause mortality was evaluated as a secondary time-to-event endpoint measured at Year 5. The registry identifies the log-rank test as the reported method and gives a hazard ratio as the effect measure.

FeatureReported result
EndpointAll-cause Mortality
Time frameMeasured at Year 5
ComparisonPercutaneous Coronary Intervention vs Coronary Artery Bypass Graft
MethodLog-rank test
Effect measureHazard ratio
Estimate5.4
95% CINot reported in the ClinicalTrials.gov record
P-value0.049
HypothesisSuperiority

The combination of a log-rank test and a hazard-ratio effect measure illustrates why a test statistic and an effect estimate should not be treated as interchangeable. The p-value addresses statistical evidence under the null hypothesis, while the hazard ratio describes the reported relative effect.

13. Day 30 Individual MACCE Analysis

The registry reports a secondary analysis of Rates of Individual MACCE Endpoints, measured at Day 30. Cox proportional-hazards regression was used, with a superiority hypothesis.

Reported statistical evidence

P = 0.68

Cox proportional-hazards model   ·   Hazard ratio specified as the effect measure

The ClinicalTrials.gov record does not contain an estimate or confidence interval for this analysis.

A p-value of 0.68 should not be converted into an effect size. Because the ClinicalTrials.gov record does not include the hazard-ratio estimate or confidence interval, no quantitative magnitude of the Day 30 comparison is reported on this page.

14. Safety

The ClinicalTrials.gov record reports serious adverse events by treatment arm using affected participants over participants at risk. They do not provide a detailed list of individual serious adverse-event categories in the ClinicalTrials.gov record.

ArmSerious adverse events affectedAt risk
Percutaneous Coronary Intervention24953
Coronary Artery Bypass Graft42947

These counts should be kept distinct from the efficacy analyses. Serious adverse events are a safety measure, whereas the primary endpoint is a time-to-event composite of all-cause mortality, non-fatal myocardial infarction, and stroke.

Unmasked-design limitation: because the trial was not blinded, patients may have been treated differently on the basis of their surgical procedure. This is a registry-specified limitation and is particularly relevant when considering outcomes that may be affected by treatment behavior or differential care after assignment.

15. Censoring and Follow-up

The primary endpoint is a time-to-event outcome, and the registry definition specifies that it was measured at Year 5 while also noting median 3.8 years of follow-up. These are not interchangeable descriptions.

Year 5 time frame

The registered primary endpoint is explicitly described as being measured at Year 5.

Median follow-up

The registry definition posted on ClinicalTrials.gov for the primary endpoint states median 3.8 years of follow-up.

For a time-to-event analysis, participants do not necessarily contribute identical amounts of observed follow-up. The Cox and log-rank approaches are designed for this structure. The ClinicalTrials.gov record does not provide the detailed censoring rules, numbers censored, or reasons for censoring, so those features are not reconstructed here.

16. Randomization and Causal Interpretation

Randomized allocation is a central statistical feature of FREEDOM. Rather than assigning treatment according to clinician or patient preference, the registry identifies the allocation as RANDOMIZED.

Randomization supports a causal comparison because treatment assignment is established before the subsequent outcome experience. In a properly conducted randomized comparison, systematic differences in prognosis should be reduced by the allocation process rather than controlled only after the fact with a statistical model.

However, randomization does not make every aspect of a trial immune to bias. The registry explicitly identifies the trial as unmasked and notes the possibility that patients may have been treated differently on the basis of their surgical procedure. That limitation concerns conduct and interpretation after assignment rather than the mathematical definition of randomization itself.

Core statistical principle
Randomization → comparable treatment assignment → stronger basis for causal comparison

This does not mean that every post-randomization event is automatically unbiased; it means that treatment assignment itself is not chosen according to the participant's subsequent outcome.

17. Statistical Interpretation of Hazard Ratios

HR above 1

Because the reported comparison is Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft, an HR above 1 represents a higher estimated hazard for the first-listed group under the Cox model. The registry's reported primary estimate is 7.9, while the Year 1 Major MACCE estimate is 2.74 and the Year 5 all-cause mortality estimate is 5.4.

EndpointComparisonReported HR95% CIP-value
5-year composite of death, non-fatal MI, and strokePCI vs CABG7.93.3–12.50.005
Year 1 Major MACCEPCI vs CABG2.741.91–3.890.004
Year 5 all-cause mortalityPCI vs CABG5.4Not reported0.049
Day 30 individual MACCE endpointsPCI vs CABGNot reportedNot reported0.68

These estimates should not be combined into a single overall treatment effect. They correspond to different endpoints and time frames, and the ClinicalTrials.gov record reports them as separate analyses.

Relative effect is not absolute risk

A hazard ratio does not tell us how many additional or fewer participants experienced an event. For that, absolute event probabilities or cumulative incidence estimates are needed. The registry-reported primary analysis data do not provide those quantities, so this page does not derive them from the hazard ratios.

Hazard ratio is not a risk ratio

A risk ratio compares probabilities over a specified period. A hazard ratio compares instantaneous event rates within a time-to-event model. The two measures can differ substantially, particularly when event risk changes over time.

Hazard ratio is not necessarily constant in reality

The Cox proportional-hazards model uses a proportional-hazards framework. The ClinicalTrials.gov record does not include diagnostics for that assumption, so this page does not claim that proportional hazards were empirically demonstrated. The reported HR should be understood as the effect measure generated by the registry's Cox analysis.

18. P-values and Confidence Intervals

P-value

A p-value quantifies how incompatible the observed data are with a specified null hypothesis under the assumed statistical model and testing procedure. It is not a measure of effect magnitude.

Confidence interval

A confidence interval describes uncertainty around an estimated parameter under the corresponding statistical framework. It is not the range of effects that individual patients experience.

For the primary endpoint, the registry reports both an estimate and a 95% confidence interval: 7.9 (95% CI 3.3–12.5). That combination is substantially more informative than the p-value alone because it communicates both the direction and magnitude of the reported effect and the uncertainty around it.

For the Year 5 all-cause mortality analysis, the registry reports an estimate of 5.4 and a p-value of 0.049, but no confidence limits are reported in the ClinicalTrials.gov record provided. The absence of a registry-reported confidence interval prevents a precision assessment comparable to the primary endpoint.

19. Limitations

20. Why This Trial Matters Statistically

FREEDOM provides a compact teaching example of how randomized clinical-trial statistics can combine allocation, composite endpoints, survival analysis, hazard ratios, confidence intervals, and hypothesis testing.

ConceptHow it appears in FREEDOM
RandomizationThe registry identifies allocation as randomized.
Parallel designTwo treatment arms are analyzed as parallel groups.
Time-to-event endpointThe primary endpoint and reported secondary outcomes are identified as time-to-event measures.
Composite endpointThe primary endpoint combines all-cause mortality, non-fatal myocardial infarction, and stroke.
Cox modelUsed for the primary endpoint and selected secondary endpoints.
Hazard ratioUsed as the reported effect measure for the primary and selected secondary analyses.
Log-rank testUsed for the Year 5 all-cause mortality analysis.
Confidence intervalThe primary estimate is accompanied by a 95% CI of 3.3–12.5.
P-valueReported for all four statistical analyses reported in the ClinicalTrials.gov record.
Superiority testingThe registry identifies superiority as the hypothesis type for the reported analyses.
Unmasked trialNo masking was used, and the registry explicitly identifies this as a limitation.

The main statistical lesson is that a clinical-trial result is not one number. The endpoint definition determines what is being measured; the time frame determines when it is measured; the analysis method determines how the comparison is estimated; and the confidence interval and p-value provide different information about uncertainty and statistical evidence.

21. Clinical Interpretation vs Statistical Interpretation

Statistical interpretation

The registry reports a randomized comparison with a superiority hypothesis and time-to-event analyses using Cox proportional-hazards regression and the log-rank test. The primary endpoint has a reported hazard-ratio estimate of 7.9 with a 95% CI of 3.3–12.5 and P = 0.005.

Clinical interpretation

The primary endpoint combines death, non-fatal myocardial infarction, and stroke. Secondary analyses address Major MACCE at Year 1, all-cause mortality at Year 5, and individual MACCE endpoints at Day 30. The registry also reports serious adverse events by treatment arm.

Keeping these two levels separate is important. Statistical evidence describes the strength, direction, and uncertainty of the observed randomized comparison. Clinical interpretation additionally depends on the endpoint's components, timing, safety, trial conduct, and the context in which the intervention is used.

22. Trial Timeline

2004-04

Trial start

The registry lists April 2004 as the trial start.

Phase 3 · 1900 enrolled

Randomized comparison

The trial enrolled 1900 participants and compared percutaneous coronary intervention with coronary artery bypass grafting in a parallel randomized design.

Day 30

Early MACCE analysis

The registry reports a secondary analysis of individual MACCE endpoints at Day 30, with P = 0.68.

Year 1

Major MACCE analysis

The registry reports a secondary Major MACCE analysis with HR 2.74, 95% CI 1.91–3.89, and P = 0.004.

Year 5

Primary and mortality analyses

The primary composite endpoint was measured at Year 5, alongside the secondary all-cause mortality analysis.

2012-07

Primary completion

The registry lists July 2012 as the primary completion date.

23. What Can and Cannot Be Concluded From the Registry Data

QuestionWhat the ClinicalTrials.gov record supports
Was the trial randomized?Yes. Allocation is listed as randomized.
Was the trial masked?No. Masking is listed as none.
What was the primary endpoint?5-year Composite Endpoint of All-cause Mortality, Non-fatal Myocardial Infarction, and Stroke, measured at Year 5.
What was the primary statistical method?Cox proportional-hazards model.
What was the primary effect measure?Hazard ratio.
What was the primary estimate?7.9.
What was the primary 95% CI?3.3–12.5.
What was the primary P-value?0.005.
Was a formal comparison reported for secondary endpoints?Yes. The ClinicalTrials.gov record contains three secondary statistical analyses.
Are all secondary effect estimates available?No. The Day 30 analysis does not supply an estimate or confidence interval in the ClinicalTrials.gov record.
Are detailed baseline characteristics reported?No. They are not part of the ClinicalTrials.gov record.
Are subgroup results reported?No. They are not part of the ClinicalTrials.gov record.
Are detailed censoring rules reported?No. They are not part of the ClinicalTrials.gov record.

This distinction prevents an analysis page from filling gaps with plausible but unverified trial details. The statistical interpretation can be detailed without manufacturing numbers that are absent from the registry data.

24. Related Tutorials

Learn more about the methods used in this trial:

25. Related Calculators

26. Sources

Continue with Clinical Biostats

Explore the statistical methods behind randomized clinical trials, survival analysis, and time-to-event endpoints through focused tutorials and practical calculators.

27. Record Summary

FREEDOM is a useful statistical teaching case because it combines randomized allocation, a parallel-group design, an unmasked intervention comparison, a composite time-to-event primary endpoint, Cox proportional-hazards regression, a log-rank analysis, hazard-ratio effect measures, confidence intervals, and superiority hypothesis testing. The registry reports a primary estimate of 7.9 with a 95% CI of 3.3–12.5 and P = 0.005, together with secondary analyses at Year 1, Year 5, and Day 30.

The most important interpretive discipline is to keep the endpoint, time frame, effect measure, and analysis method connected. The primary HR applies to the registered composite of all-cause mortality, non-fatal myocardial infarction, and stroke; the Year 1 HR applies to Major MACCE; the Year 5 mortality analysis is a separate secondary analysis; and the Day 30 analysis reports a p-value without a registry-reported effect estimate. These results should therefore be interpreted separately rather than collapsed into a single summary statistic.

Clinical Biostats methodology: A rigorous trial-results page should distinguish what the registry actually reports from what statistical theory allows us to explain. The purpose of the analysis is not to fill missing fields with assumptions, but to show how the reported design, endpoint definitions, effect measures, confidence intervals, and hypothesis tests fit together.