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
PRAISE is a cardiovascular study in patients with atrial fibrillation evaluating pulmonary vein reconnection following ablation index-guided ablation. The study is registered as a non-randomized, parallel-design treatment study with no masking and two arms.
| Feature | PRAISE |
|---|---|
| Trial name | PRAISE |
| ClinicalTrials.gov identifier | NCT02628730 |
| Condition | Atrial Fibrillation |
| Therapeutic area | Cardiovascular |
| Phase | NA |
| Allocation | NON_RANDOMIZED |
| Design model | PARALLEL |
| Masking | NONE |
| Primary purpose | TREATMENT |
| Enrollment | 40 |
| Arms | 2 |
| Lead sponsor | Liverpool Heart and Chest Hospital NHS Foundation Trust |
| Status | UNKNOWN |
2. Clinical Question
The central statistical question is whether the study's ablation strategy is associated with the occurrence of pulmonary vein reconnection when patients are reassessed at a repeat electrophysiology study 8-10 weeks after the initial intervention.
Population
Patients with atrial fibrillation enrolled in the PRAISE study.
Intervention
PVI using the ThermoCool® SmartTouch® Catheter.
Comparator
RFA ablation data comparison.
Primary question
What proportion of patients have pulmonary vein reconnection at repeat electrophysiology study 8-10 weeks after ablation?
The registry describes the allocation as NON_RANDOMIZED. That distinction is central to interpretation: the study does not have the same treatment-comparison framework as a randomized controlled trial. Any observed difference between its two arms must therefore be interpreted in light of the possibility that the groups differ systematically in characteristics related to the intervention or outcome.
3. Trial Design
PVI using ThermoCool® SmartTouch® Catheter
- Device intervention
- PVI using ThermoCool® SmartTouch® Catheter
RFA ablation data comparison
- Device-related comparison
- RFA ablation data comparison
The registry identifies two parallel arms but does not provide arm-specific enrollment counts in the available record. Consequently, the overall enrollment of 40.0 should not be interpreted as an equal allocation between the two arms.
4. Primary Endpoint
| Endpoint | Definition | Time frame | Type |
|---|---|---|---|
| Primary endpoint | The proportion of patients with PV reconnection seen at repeat EP study | 8-10 weeks | Binary |
The endpoint is binary because each patient can be classified according to whether pulmonary vein reconnection is observed at the repeat electrophysiology study. The quantity of direct interest is therefore a proportion, rather than a continuous measurement or a time-to-event outcome.
5. Planned Analysis
The registered endpoint will be measured as the proportion of patients with pulmonary vein reconnection at the repeat EP study during the 8-10 week assessment window. For a binary endpoint, the fundamental descriptive analysis is the number of patients meeting the endpoint divided by the number of patients assessed.
where x is the number of patients with PV reconnection and n is the number of patients assessed at the repeat EP study.
If the two study arms are compared, the corresponding analysis would examine the observed proportion in each arm and quantify the between-arm difference using an appropriate measure of association or effect. Depending on the number of patients and the observed event counts, an exact method may be preferable to a large-sample approximation.
Because the allocation is explicitly non-randomized, the statistical comparison is not equivalent to a randomized treatment effect. A difference in observed proportions can reflect differences in the groups that existed before treatment as well as differences associated with the intervention itself.
Confidence intervals for a proportion
A confidence interval around each proportion is important because the observed proportion is estimated from a finite number of patients. With an enrollment of 40.0, even a seemingly large or small observed proportion can have substantial statistical uncertainty, particularly if the number assessed is smaller than the total enrollment.
The proportion summarizes the observed frequency of PV reconnection. A confidence interval describes uncertainty around that estimated frequency; it does not describe the range of outcomes that an individual patient might experience.
6. Statistical Methodology
Analysis of a binary endpoint
The registered primary endpoint has two possible states: PV reconnection observed or PV reconnection not observed at repeat EP study. This makes the endpoint naturally suited to binomial methods.
The simplest analysis reports the number and percentage of patients with reconnection. If the two arms are compared, the analysis can be framed around an absolute difference in proportions, a relative measure such as a risk ratio, or an odds ratio. The choice should be specified before looking at the observed results because these measures answer different questions.
Why the proportion is the central estimand
For this endpoint, the most direct estimand is the probability of PV reconnection within the defined assessment window. Unlike a hazard ratio, the proportion does not require a time-to-event model. Unlike a mean, it does not assume that the outcome is measured on a continuous scale.
An absolute difference describes how many percentage points the observed proportions differ between two groups.
Why randomization matters
Randomization is designed to make treatment groups comparable, on average, with respect to measured and unmeasured baseline characteristics. PRAISE is registered as non-randomized, so that protection is not reported by the study design.
This does not make the binary endpoint statistically unusable. It changes what can be concluded from a comparison. A difference in proportions can be estimated, but causal interpretation requires consideration of confounding and other sources of systematic group differences.
Confidence intervals versus p-values
A p-value, if a formal hypothesis test is performed, addresses compatibility of the observed data with a specified null hypothesis. It does not quantify the magnitude of the treatment effect. A confidence interval is more informative about the precision and range of plausible values for the estimated effect under the statistical model.
Small-sample considerations
The total enrollment is 40.0. With a study of this size, asymptotic approximations for binary data may be unreliable when event counts are sparse. Exact or otherwise small-sample-appropriate methods can therefore be relevant, particularly for arm-level comparisons.
7. Statistical Methods Explained
What makes the primary endpoint binary?
The registry asks whether PV reconnection is seen at repeat EP study. Each assessed patient therefore contributes a yes/no outcome. Binary endpoints are naturally summarized using counts and proportions.
Why report the proportion rather than only the number of events?
The number of patients with PV reconnection cannot be interpreted without knowing how many patients were assessed. A proportion places the event count on a common denominator and directly estimates the frequency of reconnection within the study population.
What does an absolute difference in proportions mean?
If one arm has proportion p1 and another has proportion p2, the absolute difference is p1 − p2. It describes the separation between the two observed probabilities in percentage-point terms.
Why are confidence intervals important with 40.0 enrolled patients?
A proportion estimated from a small sample can be imprecise. The confidence interval makes that uncertainty visible instead of presenting the observed proportion as if it were known without error.
Why does non-randomized allocation change interpretation?
In a randomized study, random assignment provides the principal mechanism for balancing prognostic factors between groups. In a non-randomized study, differences between groups can be related to how patients were allocated rather than solely to the intervention. Statistical adjustment can address measured differences, but it cannot automatically remove unmeasured confounding.
Would a survival analysis be appropriate for the primary endpoint?
Not for the endpoint as registered. The primary endpoint is a binary assessment at a specified 8-10 week time frame. A time-to-event analysis would require a different endpoint definition in which the timing of an event is itself part of the analysis.
8. Interpretation of the Planned Analysis
The primary endpoint estimates the proportion of assessed patients in whom PV reconnection is observed at repeat EP study during the 8-10 week assessment window.
The proportion alone does not establish why reconnection occurred, whether an observed difference between arms is causal, or whether a particular observed proportion would generalize to patients outside the study population.
Because allocation is non-randomized and masking is absent, interpretation of any between-arm difference must distinguish the descriptive comparison from a causal treatment effect.
The endpoint is defined specifically at 8-10 weeks. A proportion measured at that assessment is not interchangeable with a proportion measured at another follow-up interval because the timing of assessment is part of the endpoint definition.
9. Important Limitations and Interpretation Issues
- Non-randomized allocation: the study is registered as NON_RANDOMIZED, so differences between the two arms may reflect baseline or other systematic differences as well as intervention-related differences.
- No masking: the registry identifies the study as having no masking. For an endpoint assessed at repeat EP study, the potential for assessment-related bias should therefore be considered in interpreting comparisons.
- Small enrollment: the registry reports enrollment of 40.0, which limits precision for estimates of a binary endpoint and can make conventional large-sample approximations less reliable.
- Assessment window: the primary endpoint is defined at 8-10 weeks, so conclusions apply to that specified assessment period rather than to an unspecified duration of follow-up.
- Unknown status: the ClinicalTrials.gov record lists the overall study status as UNKNOWN.
- No posted statistical analyses: the registry contains the registered primary endpoint but no posted statistical analyses or numerical outcome estimates.
- Arm-level enrollment: the record identifies 2 arms but does not report arm-specific enrollment counts in the available ClinicalTrials.gov record.
10. Why This Trial Matters Statistically
PRAISE is a useful teaching example because the statistical structure is fundamentally different from that of a large randomized time-to-event trial. Its primary endpoint is binary, the assessment occurs within a defined 8-10 week window, and allocation is non-randomized. Those features determine what statistical questions can appropriately be asked.
| Concept | How it appears in PRAISE |
|---|---|
| Binary endpoint | The primary endpoint is the proportion of patients with PV reconnection at repeat EP study. |
| Proportion | The primary descriptive quantity is the frequency of reconnection among assessed patients. |
| Fixed assessment window | The primary endpoint is evaluated at 8-10 weeks. |
| Non-randomized allocation | The registry identifies allocation as NON_RANDOMIZED. |
| Parallel design | The registry identifies the design model as PARALLEL with 2 arms. |
| Unmasked design | The registry identifies masking as NONE. |
| Small-sample inference | Enrollment of 40 makes precision and appropriate small-sample methods important considerations. |
| Confidence intervals | Interval estimation would quantify uncertainty around observed proportions or between-arm effects. |
| Causal interpretation | Any between-arm comparison must account for the absence of randomization. |
11. Related Tutorials
Learn more about the methods used in this trial:
12. Related Statistical Calculators
13. Sources
- ClinicalTrials.gov: PRAISE (NCT02628730).
- Linked publication: PubMed record for PMID 30354288.
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14. Record Summary
PRAISE is a cardiovascular study of atrial fibrillation with 40.0 enrolled patients, 2 parallel arms, non-randomized allocation, and no masking. Its registered primary endpoint is the proportion of patients with PV reconnection seen at repeat EP study at 8-10 weeks. Statistically, this is a binary endpoint for which proportions and corresponding measures of uncertainty provide the natural starting point for analysis. The non-randomized design is equally important: an observed difference between the two arms would be a descriptive association unless the analysis adequately addresses the possibility of confounding.