Alternative in Beta Blocker Intolerance: The ABBI Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Alternative in Beta Blocker Intolerance: The ABBI Trial (NCT00893984), a na phase 4 study. The primary outcome is Number of Participants With Intolerance of Bystolic, Measured by Side Effect(s) That Lead to Discontinuance of Bystolic by the Patient and/or the Physician.

2. Clinical Question

The study concerned tolerance of nebivolol among patients described as unable to tolerate conventional beta blockers. Its stated hypothesis was that Bystolic would be tolerated by many such patients. That hypothesis is a rationale for the study, not a reported finding. A single-group design can describe what happened among participants receiving the intervention, but without a concurrent control group it cannot separate the observed course from other explanations or estimate a comparative treatment effect.

The record does not report detailed inclusion criteria, the number of participants who met each eligibility condition, or how previous intolerance was established. It also does not report whether participants had to stop a previous beta blocker for a particular symptom or how symptoms were assessed after starting nebivolol. These details matter to interpretation because the population and the definition of intolerance determine what the endpoint represents.

3. Trial Design

The ABBI trial is registered as a phase 4, single-group study of nebivolol. Allocation is recorded as not applicable, and masking is listed as none. These features mean the registry does not describe a randomized, masked comparison between nebivolol and another treatment. The enrollment recorded is 6. The trial status is terminated; the reason for termination is not reported in the registry record.

The intervention description specifies Bystolic (nebivolol), 5 mg per day for 30 days, titrated up to 10 mg at 2 weeks if necessary for blood pressure control. The primary outcome timeframe is 30 days. The record lists coronary artery disease as the condition and identifies the Minneapolis Heart Institute Foundation as sponsor. The recorded start is 2009-05 and primary completion is 2012-06.

The registry lists one intervention and a single-group model. It does not describe a concurrent control arm, a randomization procedure, or masked assessment. The study summary says side effects would be tracked and compared with previous beta blocker use, but the record does not report how that prior use was measured, which participants contributed such information, or how the comparison was analyzed. A retrospective or within-person comparison would not be equivalent to a randomized concurrent control, and the record does not give enough detail to characterize a specific comparison method.

The record lists four outcome measures, including the primary intolerance outcome and secondary outcomes concerning termination by reason, recurrence of the same symptom that led to stopping a previous beta blocker, and mild symptoms. It records zero analyses. Results for the primary endpoint and these secondary outcomes are not reported in the registry record. No protocol details about recruitment, follow-up completeness, or the reasons for termination are reported.

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 Number of Participants With Intolerance of Bystolic, Measured by Side Effect(s) That Lead to Discontinuance of Bystolic by the Patient and/or the Physician, measured over 30 Days.

The primary endpoint is the number of participants with intolerance of Bystolic, defined in the record by side effects that lead to discontinuance of Bystolic by the patient and/or the physician. Its timeframe is 30 days, and its unit is participants. This is a count outcome: it concerns how many people met the stated discontinuation criterion, rather than the severity of symptoms or a change in a continuous measurement.

Discontinuation is a practical way to operationalize treatment intolerance because it identifies side effects consequential enough to prompt stopping the intervention. However, the endpoint does not capture every symptom. A participant could experience a side effect without discontinuing, and the record does not specify how symptoms that did not lead to discontinuation were classified for the primary outcome. The listed secondary outcomes include mild symptoms and reasons for stopping, which address other aspects of tolerability, but their results are not reported in the registry record.

For a count endpoint, interpretation depends on both the event definition and the group of participants assessed. The registry record does not report the primary endpoint count, an analysis population, or whether all enrolled participants completed the 30-day assessment. As a result, the endpoint definition is available, but the observed frequency and its precision cannot be assessed from the reported primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a single-group study records outcomes among participants receiving an intervention without a concurrent control group. This design can describe event counts or symptom patterns in the treated group. It does not have the randomized comparison that helps balance measured and unmeasured factors between treatment groups. In the ABBI record, the study model is single group, allocation is not applicable, and masking is none. The record therefore does not describe a randomized or masked treatment comparison.

What does a count endpoint represent?

The primary outcome is a count of participants meeting a defined event criterion: side effects leading to discontinuation by the patient and/or physician during the 30-day timeframe. For an event count, the numerator is the number meeting that criterion, while interpretation also depends on how many participants were assessed. The registry record reports the enrolled group size but does not report the primary event count or the number included in the endpoint analysis. A group size alone cannot establish the event frequency.

Counts should be distinguished from event rates and from individual-level symptom descriptions. A count does not indicate how long symptoms lasted, their intensity, or whether more than one symptom occurred for a participant. The listed secondary outcomes address some related topics, including mild symptoms and reasons for termination, but the record does not report their results or detailed definitions. A reader should not treat the adverse-event counts as substitutes for the primary discontinuation endpoint.

Why does uncertainty matter?

In general, a point estimate describes the value calculated from the observed sample, while a confidence interval describes a range of values compatible with the data under the assumptions of the analysis. The interval helps convey precision; it is not a guarantee that the true value lies in that range. For a small group, estimates can be especially sensitive to the outcome of individual participants. In this record, no primary estimate or confidence interval is reported, so the uncertainty of the primary result cannot be evaluated.

For count outcomes, an analysis may use methods based on a binomial model when each participant contributes an event status over a defined period. Other approaches may be needed if the outcome is a count of repeated events, if follow-up differs, or if assumptions are not met. General methods cannot be assigned to this endpoint without knowing how the study handled incomplete follow-up and how the outcome was recorded. Those analysis details are not reported in the registry record.

What can a single-group comparison establish?

A concurrent control group helps distinguish outcomes associated with an intervention from outcomes that might have occurred without it or under another intervention. Without such a group, observed symptoms or discontinuations may reflect the intervention, the underlying condition, expectations, other care, or other factors. These are general limitations of uncontrolled comparisons, not findings about what occurred in this trial. The record's mention of comparison with previous beta blocker use does not specify a statistical method or provide results, so it cannot be interpreted as a formal comparative analysis.

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. Such planning illustrations are not the trial's own design justification, and they are not observed power. No numerical planning estimates are reported in the registry record. The record does not report a sample-size justification or statistical analysis plan for the trial.

More generally, a sample-size calculation depends on the outcome, the effect considered important, variability or event frequency, the significance threshold, power target, allocation, and analysis method. A planning illustration answers a hypothetical design question under specified assumptions; it does not show whether the study had adequate power after data collection. In particular, a calculation based on an observed effect should not be read as independent evidence that the effect is reliable. No such inference can be made for the primary ABBI outcome because its result is not reported.

The registry records zero analyses. It does not describe a model, adjustment strategy, confidence-interval method, handling of repeated measures, or analysis set. These details cannot be inferred from the endpoint wording or from the adverse-event counts. Any re-analysis would require sufficient posted summary information and should be identified as a recalculation rather than as the sponsor's analysis; no recalculated primary result is available from the information reported in the registry record.

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("Nebivolol")
n      <- c(6)
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  Nebivolol  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary intolerance endpoint and secondary measures concerning termination by reason, the same symptom that led to stopping a previous beta blocker, and mild symptoms. Considering multiple outcomes can raise a multiplicity issue because repeated testing can increase the chance of at least one apparently notable result. In general, investigators may specify one primary outcome, adjust analyses, or interpret secondary outcomes as exploratory. The registry record does not report a multiplicity strategy, a testing hierarchy, or results for the listed secondary outcomes.

The record reports zero analyses. It does not describe whether outcome analyses were planned, whether any adjustment for baseline characteristics was made, or how the primary and secondary outcomes would be summarized. A statistical analysis plan is not reported in the registry record. Accordingly, no claim can be made about whether multiplicity was addressed or what analysis was used.

Missing-data handling is also not reported in the registry record. The record does not say whether participants with incomplete follow-up were included, how missing endpoint status was treated, or whether any sensitivity analyses were planned. The enrollment figure does not establish how many participants had an evaluable 30-day outcome. The analysis population and the completeness of endpoint assessment are not reported, so it is not possible to determine whether the primary outcome denominator matched enrollment.

These omissions limit assessment of both bias and precision. In general, excluding participants with missing outcomes can distort a result if missingness is related to symptoms or treatment discontinuation. That is a general methodological concern, not evidence that such missingness occurred in this trial. The registry record does not provide enough information to determine how missing outcomes or multiplicity affected the findings.

12. 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 non-serious adverse event terms

The registry reports safety counts for the Nebivolol group. For serious adverse events, 0 participants are recorded as affected among 6 at risk. For other adverse events, 1 participant is recorded as affected among 6 at risk. No serious adverse-event terms are listed. These are the posted safety figures; the record does not provide descriptions of the other adverse event or its relationship to nebivolol.

In general, an adverse-event count describes events recorded during the specified safety collection, not necessarily events caused by the intervention. The registry record does not report the assessment rules or attribution method for these figures. The serious-event category should also be kept distinct from the primary intolerance endpoint, which requires side effects leading to discontinuation by the patient and/or physician within 30 days. The safety counts do not indicate whether the other adverse event led to discontinuation.

With a small enrolled group, zero recorded serious events does not establish that serious events cannot occur; it describes only what was recorded among those at risk in this study. These counts also do not provide a comparison with another treatment or an estimate of relative safety. No further event detail or uncertainty analysis is reported in the registry record.

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

The record identifies a clinically focused question: whether nebivolol would be tolerated by cardiovascular patients described as unable to tolerate conventional beta blockers. It defines intolerance through side effects that cause discontinuation within 30 days and lists additional symptom-related outcomes. These details clarify what the investigators intended to assess, but they are not evidence of the observed primary result.

The registry record does not report the number of participants meeting the primary endpoint. It therefore cannot establish the observed frequency of discontinuation due to side effects, how precisely that frequency was estimated, or whether participants commonly experienced mild symptoms. The posted serious and other adverse-event counts provide limited safety information, but they do not answer the primary endpoint question and do not establish causation.

The single-group design also limits what can be concluded comparatively. The record does not include a concurrent control group, and it does not report the method or results of the mentioned comparison with previous beta blocker use. The observed experience, even if fully reported, would not alone show whether outcomes differed from what would have occurred with another treatment or without nebivolol.

Thus, the trial record supports describing the intended population, intervention, timeframe, and endpoint, along with the limited safety counts that are posted. It does not support a conclusion that nebivolol was tolerated by a particular proportion of participants, nor a conclusion about comparative benefit or harm. The reason the study was terminated and the completeness of outcome follow-up are not reported in the registry record, further limiting interpretation.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical research: an endpoint can be clearly defined even when its result is not available in the registry record. Here, intolerance is operationalized as side effects leading to discontinuation, which is more specific than a general report of symptoms. Yet without the primary event count and analysis denominator, readers cannot quantify the endpoint or judge its precision.

It also shows why design labels matter. A single-group study can provide descriptive information about participants receiving an intervention, but it cannot provide the same comparative evidence as a randomized controlled design. The summary's mention of previous beta blocker use does not supply a substitute control unless the comparison method, outcome ascertainment, and analysis are described. Those details are not reported in the registry record.

The difference between safety events and the primary tolerability outcome is another useful statistical point. Serious and other adverse-event counts are recorded, but the primary outcome requires discontinuation due to side effects. Treating one outcome as though it answered the other would conflate different definitions. The posted counts should be interpreted according to their labels and not extended to conclusions they do not measure.

Finally, the registry status is terminated, while the reason for termination and the primary results are not reported. A status label does not explain study conduct or results. This record therefore demonstrates why outcome availability, analysis details, and transparent reporting are necessary alongside a study's question and design for readers to assess evidence.

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 most direct limitation is that the registry record does not report the primary endpoint result. It also does not report results for the secondary outcomes, so the intended assessment of mild symptoms, reasons for stopping, and recurrence of the same symptom cannot be evaluated. The record reports zero analyses, leaving no posted inferential analysis or precision estimate for the primary outcome.

The study enrolled 6 and used a single-group design. A small, uncontrolled study has limited ability to estimate event frequency precisely or distinguish intervention-associated events from other influences. Because there is no concurrent comparator, this record cannot support a randomized treatment comparison. The stated interest in prior beta blocker use is not accompanied by a reported method or result.

The status is terminated, but the reason is not reported in the registry record. It is also not reported whether all participants completed the 30-day endpoint assessment, what analysis population was used, how missing outcomes were handled, or whether any outcomes were changed or omitted. These gaps prevent assessment of follow-up completeness and potential selection effects.

Finally, the record gives limited clinical detail about eligibility, baseline characteristics, symptom assessment, and attribution of adverse events. Without these details, it is difficult to judge how broadly the study population represents patients with conventional beta blocker intolerance or how consistently outcomes were assessed. These are limits of the registry information and do not establish that any particular problem occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Alternative in Beta Blocker Intolerance: The ABBI Trial — NCT00893984.
• Registry record last updated 2019-08-06; status last verified 2019-07.
• Results first posted 2019-07-17.
• 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 ABBI trial is a phase 4, terminated, single-group study sponsored by the Minneapolis Heart Institute Foundation. The registry records an enrollment of 6, a start of 2009-05, and primary completion in 2012-06. It lists coronary artery disease as the condition, nebivolol as the intervention, no masking, and allocation as not applicable.

The intervention description specifies Bystolic at 5 mg per day for 30 days, titrated up to 10 mg at 2 weeks if necessary for blood pressure control. The primary endpoint is the number of participants with side effects leading to discontinuation by the patient and/or physician during 30 days. Its result is not reported in the registry record. The record lists four outcome measures and zero analyses.

Safety figures list 0 serious adverse events among 6 at risk and 1 other adverse event among 6 at risk in the Nebivolol group. No serious adverse-event terms are listed. The reason for termination, analysis population, missing-data handling, and method or result for the mentioned comparison with previous beta blocker use are not reported in the registry record.