The PEARL 8.0 Post-Approval Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The PEARL 8.0 Post-Approval Study (NCT01845103), a registered phase not stated study. The primary outcome is Mortality.

2. Clinical Question

3. Trial Design

The PEARL 8.0 Post-Approval Study is identified as a prospective single-arm study of the Cardiogenesis PEARL 8.0 Handpiece Delivery System. Its official title describes the handpiece for transmyocardial revascularization with the Cardiogenesis Holmium:YAG Laser System. The registry lists Class IV Angina as the condition and Cardiogenesis Corporation, a wholly-owned subsidiary of CryoLife, Inc., as the sponsor.

The record lists a start date of 2013-09 and primary completion of 2014-12. Its status is TERMINATED, and enrollment is 1. These entries describe the registry record; they do not establish why the study was terminated or whether the planned enrollment was reached. The reason for termination and the intended enrollment target are not reported in the registry record.

The brief summary states that the purpose was to assess 30 day mortality against a historical rate plus a non-inferiority margin. This is a one-group framing rather than a randomized comparison. The record does not identify a concurrent control arm or state an allocation method. The historical comparator's numerical rate and the non-inferiority margin are not reported in the registry record.

Mortality is the primary outcome, and Major Adverse Coronary and Cerebrovascular Events (MACCE) is listed as a secondary outcome. The record lists two outcome measures but no analyses. It does not report the protocol's analysis population, sample-size justification, planned statistical model, follow-up completeness, interim analyses, or detailed endpoint definitions. The design information therefore establishes the intended question and the basic single-arm structure, but not the operational or inferential details needed to reconstruct a full analysis plan.

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.

Overall Study

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 Mortality, measured over 30 day.

The primary endpoint is mortality, measured as the percentage of participants, at 30 day. A mortality endpoint records whether participants died within the stated observation timeframe; as a percentage, it expresses the number with the event relative to the relevant participant group. The registry record does not provide a numerical mortality result or further specify the event definition, assessment procedure, or analysis population.

In general, a mortality endpoint can provide a direct description of deaths during a defined follow-up period. Here the stated objective was not simply to report mortality: the brief summary says the study aimed to show that the treated-group 30 day mortality rate was less than a historical rate plus a non-inferiority margin. Such a comparison requires the historical benchmark and margin to be specified, as well as an analysis capable of estimating the rate with appropriate uncertainty. Those numerical specifications and analysis details are not reported in the registry record.

The endpoint's interpretation also depends on the amount of observed information and the completeness of follow-up. Enrollment is 1, but the record does not post the primary outcome result or the participant's outcome status. It is therefore not possible to infer the observed 30 day mortality percentage from the enrollment entry alone. The registry lists MACCE as a secondary outcome, but does not provide a posted analysis for it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage endpoint: mortality, expressed as the percentage of participants, at 30 day. A binary endpoint classifies each participant according to whether an event occurred within a specified period. In general, the event proportion is a descriptive summary, while a statistical analysis may also quantify uncertainty or compare the proportion with a reference value. The registry record supplies the endpoint label and timeframe but no primary mortality result, estimate of uncertainty, or inferential analysis.

What does the stated non-inferiority objective mean?

In general, a non-inferiority question asks whether an outcome under an intervention is not unacceptably worse than a comparator, according to a prespecified margin. The brief summary states a specific form of the intended question: whether treated-patient 30 day mortality was less than a historical rate plus a non-inferiority margin. To assess that question, an analysis needs a defined historical rate, a defined margin, and an estimate of the study rate with uncertainty. The historical rate and margin are not reported in the registry record. Nor does the record include the primary outcome estimate or an analysis result, so the stated objective cannot be evaluated from the posted information.

Why does the single-arm design matter?

In general, a single-arm study observes outcomes in an intervention group without a concurrent control group. A comparison with a historical rate can be informative, but it relies on the relevance and comparability of the historical benchmark. Changes in participant characteristics, clinical practice, follow-up, or event definitions can make a historical rate differ from the rate that would have been observed in a concurrent control group. These are general methodological considerations. The registry does not report the historical source, its population, or procedures for ensuring comparability, so it is not possible to assess those features for this study.

The registry's skip information also notes that this is not a randomized comparison and that allocation is not stated. That warning is consistent with the single-arm description: there are no like-for-like randomized arms to compare. The one listed PEARL 8.0 group should not be interpreted as a treatment arm in a randomized contrast.

What do uncertainty and precision mean?

In general, an estimate summarizes the observed data, and a confidence interval communicates uncertainty around that estimate under a specified statistical method. A narrow interval indicates greater precision than a wide interval, while an interval spanning values that would lead to different conclusions can leave the result unresolved. A p-value, when reported, describes the compatibility of the data with a specified null model; it is not a measure of clinical importance or the probability that a hypothesis is true. The registry reports no confidence interval or p-value for mortality, and the analysis count is 0.

Enrollment of 1 means the record lists only one participant. With very little observed information, binary event-rate estimates are generally imprecise, particularly when the event status or follow-up is not posted. That general point does not permit a mortality estimate to be calculated: the record does not state whether the participant died within 30 day. No rate should be inferred from enrollment or from the separate serious adverse-event listing.

How should planning illustrations be understood?

General sample-size calculations can illustrate how the required number of participants changes under chosen assumptions about significance level, allocation, and the effect to detect. The planning assumptions associated with this study are two-sided significance level 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 explicitly planning-illustration assumptions, not a report of the study's own design. The record describes a single-arm study, so the equal-allocation, two-arm assumption does not describe the observed study structure. No trial-specific sample-size justification is reported in the registry record.

A planning calculation based on an observed effect is not an observed power calculation and does not establish that the study was adequately designed or that a result is reliable. The registry does not report the underlying observed primary effect needed to interpret such an illustration. Any planning number should be understood as conditional on its stated assumptions, rather than as a count of participants actually studied or evidence about the endpoint.

What cannot be reconstructed?

The record does not report the statistical model or test for the primary outcome, the confidence level or interval method, the analysis population, handling of missing outcome data, or whether any interim analysis was planned. The protocol's sample-size justification is also not reported in the registry record. These omissions prevent reconstruction of the planned analysis. General statistical principles can describe what such methods are used for, but they cannot establish which methods this study used.

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("PEARL 8.0")
n      <- c(1)
events <- c(0)
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  PEARL 8.0  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists mortality as the primary outcome and MACCE as a secondary outcome, and it records two outcome measures. It also reports zero analyses. No multiplicity strategy is reported in the registry record. In general, multiplicity arises when several outcomes, timepoints, or statistical tests are considered; without a stated approach, the control of false-positive findings across tests cannot be assessed. There are no posted analyses on which to evaluate that issue.

The record does not report an analysis population, the number of participants with outcome data, or the completeness of 30 day follow-up. It also does not describe how missing outcomes would be handled. Enrollment of 1 does not establish that the primary endpoint was observed or that follow-up was complete. The record's serious and other adverse-event entries do not substitute for a mortality outcome status.

In general, missing outcome data can affect both the estimated event proportion and its uncertainty, with the implications depending on why data are missing and how the analysis handles them. No missing-data assumptions or procedures are reported in the registry record, so none can be attributed to this study. Likewise, the record does not state whether all enrolled participants were included in an intended analysis or whether any exclusions were planned. With no posted analyses, the available information cannot establish the analysis population or the treatment of missing observations.

12. 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: serious adverse event required hospitalization (100.0%).

The serious adverse-event entry for PEARL 8.0 lists one participant at risk and one affected. The leading serious term is “Serious Adverse Event required hospitalization,” reported as 100.0%. The separate other-adverse-event entry lists one participant at risk and zero affected. These are the registry's safety figures and categories; they should be read separately rather than added together or interpreted as a mortality result.

In general, a percentage for an adverse-event term describes the share of the relevant at-risk group recorded with that term, subject to the registry's definitions and reporting conventions. With the listed group size of 1, the 100.0% figure corresponds to the sole participant in that at-risk group being recorded as affected for the serious term. It does not indicate how common the event would be in a larger population or establish a comparative risk.

The registry does not give further clinical detail about the hospitalization event, its timing, relationship to the device or procedure, or outcome. Deaths are listed as null, and no primary mortality analysis is posted. The serious-event entry therefore cannot be used to infer a death or the 30 day mortality endpoint.

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

The record establishes that a prospective single-arm post-approval study was intended to assess the PEARL 8.0 Handpiece Delivery System in the context of transmyocardial revascularization with the Cardiogenesis Holmium:YAG Laser System. Its stated primary question concerned 30 day mortality relative to a historical rate plus a non-inferiority margin. The record lists enrollment of 1, a TERMINATED status, and no posted analyses.

Those details do not establish whether the primary endpoint occurred, what the observed mortality rate was, or whether the stated objective was met. Neither a historical benchmark nor a margin is reported, and no effect estimate, confidence interval, or p-value is posted. The intended question and the outcome result are distinct: registering an endpoint does not demonstrate a finding.

The safety figures describe one participant at risk for serious adverse events and one affected, with “Serious Adverse Event required hospitalization” at 100.0%. The other-adverse-event entry lists one at risk and zero affected. These entries should not be treated as a comparative safety assessment, nor do they answer the mortality question. The record does not report the event details needed to interpret clinical context or relationship to the intervention.

In general, conclusions about whether a treatment changes an outcome require interpretable outcome data and an appropriate analysis. A single-arm study that invokes a historical comparator also depends on the relevance of that benchmark and the prespecified margin. The registry does not report enough information to assess those components. It is therefore not possible to conclude from this record that the intervention did or did not meet the stated objective, or to generalize the listed safety entries beyond the recorded group.

The defensible conclusion is narrow: the registry documents the study's intended question, listed enrollment and status, one reported serious-event term, and an absence of posted outcome analyses. It does not provide evidence sufficient to estimate the primary mortality result or resolve the non-inferiority question.

14. Why This Trial Matters Statistically

This record illustrates why a registered research question and a reported statistical result are not interchangeable. The study states a specific intended comparison for 30 day mortality, but the registry lists no analyses. Without an outcome estimate and its uncertainty, readers cannot determine how the observed data relate to the historical benchmark or non-inferiority margin.

The single-arm design makes the comparator especially important. In general, a historical rate is not the same as a concurrent randomized control: its meaning depends on how well the reference population, outcome definitions, and observation conditions correspond to the study. The registry does not report the historical rate or the margin, leaving the central comparison unspecified in numerical terms.

Enrollment of 1 also highlights the distinction between recording an event and estimating a stable event rate. A single participant's outcome cannot, by itself, characterize a broader population precisely. Yet the record does not post the primary outcome status, so even a descriptive 30 day mortality result cannot be stated. The listed serious adverse-event figure is a separate safety entry, not a substitute for the endpoint analysis.

These features matter for statistical reading because they constrain what can be learned from an otherwise clearly named endpoint. The record supports a description of the study's intent and reporting status, but not an effect estimate, comparative conclusion, or assessment of statistical precision. Recognizing that boundary prevents an outcome label, event percentage, or planning illustration from being mistaken for evidence answering the study question.

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 main limitation of the registry information is the absence of a posted primary-outcome analysis. Mortality at 30 day is named, but no mortality result, estimate of uncertainty, or inferential finding is reported. The analysis count is 0, so the stated objective cannot be assessed from posted analyses.

Enrollment is 1, and the status is TERMINATED. The registry does not report why the study was terminated, whether the listed enrollment was the intended target, or the protocol's sample-size justification. It also does not report the primary outcome status or completeness of follow-up. These omissions prevent determination of whether the endpoint was observed for the participant.

The study's summary invokes a historical mortality rate and a non-inferiority margin, but neither is reported numerically. The historical source, population, and definition are also not reported in the registry record. Without these details, the comparator and threshold underlying the central question cannot be evaluated. The record does not state an analysis method or provide confidence intervals, p-values, or an analysis population.

The record lists MACCE as a secondary outcome but gives no analysis for it. It does not report a multiplicity approach, missing-data plan, interim analyses, or detailed endpoint definitions. These items should be treated as unknown, rather than assumed absent from the study protocol. The serious adverse-event listing is limited to one participant at risk and one affected for a hospitalization-required term; it provides no further event context or comparative safety assessment.

Finally, the single-arm structure does not provide a concurrent control comparison. General concerns about historical comparisons apply, but the available record does not establish whether any particular source of bias occurred. The limitations are therefore both statistical and documentary: the registry does not contain enough outcome or methods information to reconstruct the intended analysis or interpret its result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The PEARL 8.0 Post-Approval Study — NCT01845103.
• Registry record last updated 2016-10-06; status last verified 2016-08.
• Results first posted 2015-09-30.
• 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 PEARL 8.0 Post-Approval Study is described as a prospective single-arm study of the Cardiogenesis PEARL 8.0 Handpiece Delivery System with the Cardiogenesis Holmium:YAG Laser System for TMR. The condition is Class IV Angina. The registry lists Cardiogenesis Corporation, a wholly-owned subsidiary of CryoLife, Inc., as sponsor; a start date of 2013-09; primary completion of 2014-12; status TERMINATED; and enrollment of 1.

Mortality, measured as the percentage of participants at 30 day, is the primary outcome. The summary states an intended comparison with a historical rate plus a non-inferiority margin. MACCE is listed as a secondary outcome. The record reports no analyses, and the numerical historical rate, margin, primary outcome result, and statistical plan are not reported in the registry record.

The serious-event listing records one participant at risk and one affected for “Serious Adverse Event required hospitalization,” reported as 100.0%. The separate other-event listing records one at risk and zero affected. These entries do not provide a primary mortality result.