This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Response to Diaphragmatic Pacing in Subjects With Pompe Disease (NCT02354651), a registered phase not stated study. The primary outcome is Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02354651 |
| Phase | Phase not stated |
| Condition | Pompe Disease |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Florida |
| Results posted | Yes |
2. Clinical Question
Population
People with Pompe disease eligible for diaphragm pacing. The registry record lists enrollment of 9 and describes testing in patients receiving a NeuRx Diaphragm pacer.
Intervention
Diaphragm conditioning via phrenic nerve stimulation. The study description focuses on spontaneous breathing with the diaphragm pacer turned on, with breathing support adjusted according to tolerance.
Comparator
No like-for-like control comparison is described. The registry record does not state allocation, and the study is not described as a randomized comparison.
Primary question
How does off-ventilator spontaneous breathing, measured in hours per day, compare between baseline and Day 180 in the context of paced ventilation?
The stated aim is to evaluate the duration and pattern of spontaneous respiratory function versus paced ventilation respiratory function. The primary outcome is specifically titled Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180. Its description says an initial trial of unassisted breathing is conducted with the pacer turned on; the duration is increased to tolerance using a protocol. For patients unable initially to complete at least 30-minute bouts of paced spontaneous breathing, trials focus on breathing with reduced mechanical-ventilator support.
This is a question about respiratory function over time in a group receiving pacing, not a question answered by a randomized treatment-versus-control contrast. The registry record does not report an outcome estimate or an analysis comparing baseline with Day 180. It therefore does not establish the size or direction of any change in spontaneous breathing, nor does it quantify how paced and spontaneous ventilation compare in practice.
3. Trial Design
The study, titled “Response to Diaphragmatic Pacing in Subjects With Pompe Disease,” is listed as completed. The registry record lists University of Florida as sponsor, a start date of 2013-05, primary completion in 2022-06, and enrollment of 9. Pompe Disease is the listed condition. The description concerns people with Pompe disease who have received the NeuRx Diaphragm pacer.
The listed intervention is diaphragm conditioning via phrenic nerve stimulation. The described group is “Patients With Pompe Disease Eligible for Diaphragm Pacing.” Its description lists breathing-pattern tests, phrenic nerve stimulation, maximal inspiratory pressure, forced expiration, and electromyography. The registry record does not describe a randomized allocation. It indicates that the arms are not a like-for-like control comparison and that allocation is not stated. Thus, the study should not be read as a randomized trial with a comparable untreated control group.
The primary outcome is off-ventilator spontaneous breathing at baseline and Day 180, measured in hours per day. The registry describes ventilator-chip data averaged to generate these measures. The listed secondary outcomes are maximal inspiratory pressure at baseline and Day 180, change in resting breathing pattern, and diaphragm electromyogram at Day 180. There are 8 outcome measures listed, but the registry record reports 0 analyses.
The design information establishes the intended clinical measurements and the planned time points, but it does not establish how many enrolled participants contributed data at each time point. The registry record does not report participant flow, the timing or duration of pacing exposure for each participant, or the analysis population for the secondary outcomes. It also does not report a protocol-level statistical analysis plan, a sample-size justification, or details of interim analyses. Those features should not be inferred from the completion status or the listed outcomes.
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: Subjects were eligible to receive a diaphragmatic pacemaker as part of their clinical care. Some subjects who enrolled decided not to include pacing as part of their clinical care (n=2), or were found to have medical conditions that made them ineligible (n=1).
Overall Study
| Stage | Patients With Pompe Disease Eligible for Diaphragm Pacing |
|---|---|
| STARTED | 9 |
| COMPLETED | 6 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Patients With Pompe Disease Eligible for Diaphragm Pacing |
|---|---|
| Withdrawal by Subject | 2 |
| Physician Decision | 1 |
Analysis population for the primary outcome, as defined in the registry: Full sample
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.
Population: Participants who underwent implantation of a diaphragm pacing system.
| Characteristic | Unit | Pompe Subjects Receiving NeuDx DPS |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 3 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 24.5 (3 to 53) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Ventilator-Free Breathing | hours of unassisted ventilation per day | 0.52 (0 to 1.5) |
6. Primary Endpoint
The registry lists the primary outcome as Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180, measured over Baseline, Day 180.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | hours per day |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180. It is measured in hours per day and summarized as a mean with a full range. The registry record describes an initial trial of unassisted breathing while the diaphragm pacer is turned on. The duration of paced spontaneous breathing is increased to tolerance. If a patient cannot initially complete at least 30-minute bouts, the focus shifts to breathing with reduced mechanical-ventilator support. The measures are generated from ventilator-chip data for spontaneous breathing that has been averaged.
This endpoint is relevant to the stated study aim because it quantifies the duration of spontaneous breathing in the context of pacing, rather than reporting only a physiological test value. Comparing the same measure at baseline and Day 180 could describe whether recorded breathing duration changed over that interval among participants with measurements at both times. The registry record does not report the observed means, ranges, participant counts at either time point, or a calculated change. It therefore does not show the size, direction, or precision of any change.
The mean gives a central summary, while the full range describes the span of the recorded values. General statistical interpretation: the range can show whether observations vary widely, but it does not by itself indicate the shape of the distribution or the uncertainty around the mean. The registry record does not report confidence intervals for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a clinically focused measurement plan, but it does not post numerical primary-outcome results. The stated endpoint is mean off-ventilator spontaneous breathing in hours per day at baseline and Day 180, with a full range. No observed means, ranges, changes, confidence intervals, or p-values are reported in the registry record. The record also lists 0 analyses. As a result, there is no posted estimate from which to describe the direction or magnitude of change, or the statistical precision of an estimate.
The primary outcome is defined for the full sample, but that label does not establish that all enrolled participants contributed measurements at both time points. The registry record does not report the number of participants with endpoint data at baseline or Day 180, how missing measurements were handled, or whether a within-participant comparison was conducted. A baseline-to-Day 180 comparison would depend on data availability and the analysis method; the registry record does not report those details.
The absence of an identified like-for-like control group also shapes interpretation. A change over time in a group receiving pacing would not, on its own, isolate the effect of pacing from other changes over the same period. The registry record does not state allocation and does not describe a randomized comparison. It is therefore not possible to interpret a hypothetical before-and-after difference as a controlled causal effect.
Three secondary outcomes are named: maximal inspiratory pressure at baseline and Day 180, change in resting breathing pattern, and diaphragm electromyogram at Day 180. The record lists 8 outcome measures overall, but it does not post their numerical results or analyses. No conclusions about these secondary measures can be drawn from their names alone.
The adverse-event record is separate from the respiratory endpoint. It lists serious and other adverse-event counts for Pompe Subjects Receiving NeuRx DPS, along with several serious-event terms. Those entries describe reported safety events, but do not provide a comparison group or enough context to attribute events to pacing. In particular, the registry record does not report event timing, exposure duration, or a causal assessment.
Planning illustrations based on an observed effect are not trial findings and are not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. These assumptions do not establish that the trial used a two-arm randomized design. No numerical planning result or observed effect estimate is reported in the registry record, so the illustrations cannot fill the gap in clinical outcome results.
9. Statistical Methods Explained
The registry record identifies a mean as the primary endpoint parameter and a full range as its dispersion summary. The measurement is off-ventilator spontaneous breathing in hours per day, assessed at baseline and Day 180. The record states that ventilator-chip data for spontaneous breathing are averaged to generate the measures. It does not specify a statistical test, a model, an adjustment set, or a method for calculating uncertainty.
What does a mean describe?
General statistical explanation: a mean is a measure of the center of a set of observations. It is useful for expressing an average duration, but it can be influenced by unusually high or low values. In a small group, individual observations can have substantial influence on the mean. The registry lists enrollment of 9, but it does not report the number with usable primary-outcome data. Therefore, the available information does not establish how many observations contributed to any endpoint summary.
What does the full range add?
General statistical explanation: the full range describes the lowest and highest observed values and gives a direct sense of the span of the data. It is sensitive to extreme observations and does not show how values are distributed between those endpoints. A range is not a confidence interval: it describes observed data, whereas a confidence interval is an estimate of uncertainty around a population quantity under a statistical method. No confidence interval is reported for the primary endpoint in the registry record.
The mean and range would be complementary descriptions if numerical results were available. Together, they could indicate the average recorded duration and how far apart the smallest and largest values were. They would not, alone, establish a treatment effect, account for missing observations, or quantify the uncertainty in a baseline-to-Day 180 comparison.
How should repeated measurements be considered?
General statistical explanation: when measurements are taken from the same participants at different times, the observations are related. An analysis of within-participant change can account for that relationship, while a comparison that treats time points as independent may not. The registry record lists baseline and Day 180 for the primary endpoint, but does not report the analysis method or confirm which participants had measurements at both times. It is therefore not possible to say whether a paired method, a repeated-measures model, or another approach was used.
The outcome description also permits breathing trials to proceed differently according to tolerance and ability to complete paced spontaneous-breathing bouts. That is part of the measurement context, not evidence about the statistical method. The registry record does not report how the protocol’s different breathing-support conditions were represented in the endpoint analysis, or whether any adjustments were planned for them.
What can planning calculations tell readers?
The registry record describes sample-size figures as planning illustrations computed from the observed effect, not as the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are assumptions for illustrations. They do not demonstrate that the study itself had two comparable arms, used equal allocation, or used that calculation to set enrollment.
General statistical explanation: a sample-size calculation estimates how many observations may be needed under specified assumptions to detect a target effect with a chosen level of statistical power. Its result depends on the target effect, variability, significance level, allocation, and analysis assumptions. A planning illustration is not observed power and is not a measurement of how informative the completed study was. The registry record does not report the numerical observed effect underlying the illustrations, a trial-specific sample-size justification, or the trial’s actual statistical analysis plan.
The normal approximation is an assumption in the planning illustrations, not a reported diagnostic of the endpoint data. General statistical explanation: a normal approximation may be used to simplify calculations, but its relevance depends on the outcome distribution and the analysis. With a small dataset or a highly variable duration measure, distributional features and outlying values may matter. No distributional summaries beyond the stated mean and full range are reported in the registry record.
Why does over-dispersion matter in general?
General statistical explanation: over-dispersion means that the observed variability is greater than a model expects. If a model assumes less variability than the data contain, uncertainty can be understated and inferential results may be too optimistic. This concept matters when selecting and checking statistical models, but the registry record does not identify a model for these outcomes, report a dispersion estimate, or indicate that over-dispersion was assessed. It should not be assumed to have occurred in this study.
Overall, the information available supports describing the intended endpoint and the stated planning assumptions, but not reconstructing an inferential analysis. No outcome estimates, confidence intervals, p-values, analysis methods, or model diagnostics are reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 8 outcome measures, including the primary spontaneous-breathing measure and secondary measures of maximal inspiratory pressure, resting breathing pattern, and diaphragm electromyogram. It reports 0 analyses. No numerical results or statistical tests are posted for these outcomes.
Multiplicity arises when several outcomes or comparisons are tested: the chance of at least one apparently notable result can increase as the number of tests grows. General statistical explanation: a prespecified testing hierarchy or an adjustment procedure can address that issue, but the appropriate approach depends on the study question and analysis plan. The registry record does not report a multiplicity strategy, adjustment method, or testing hierarchy. The outcome labels alone do not establish which comparisons, if any, were designated for formal hypothesis testing.
Missing-data handling is also not reported in the registry record. Enrollment is listed as 9, and the primary outcome is described for the full sample, but the record does not state how many participants had primary measurements at baseline or Day 180. It does not describe reasons for unavailable measurements, imputation, exclusions, or sensitivity analyses. The endpoint description’s breathing protocol does not establish how incomplete or unusable ventilator-chip data were handled.
The analysis population for the primary outcome is not defined beyond the “Full sample” description. The registry record does not report whether analyses used all enrolled participants, only participants with paired measurements, or another population. It also does not report analysis populations for the secondary outcomes. These omissions prevent assessment of how missing observations or participant selection may have affected the results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pompe Subjects Receiving NeuRx DPS | 3 | 6 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pompe Subjects Receiving NeuRx DPS | 0 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pompe Subjects Receiving NeuRx DPS | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Pompe Subjects Receiving NeuRx DPS |
|---|---|---|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
| Scoliosis requiring spinal fusion | Musculoskeletal and connective tissue disorders | 1 of 6 |
| Seizures | Nervous system disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pompe Subjects Receiving NeuRx DPS |
|---|---|---|
| Breakage of pacemaker external wires | Product Issues | 5 of 6 |
| Skin irritation | Skin and subcutaneous tissue disorders | 3 of 6 |
| Respiratory infection | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
| Cholecystitis | Hepatobiliary disorders | 1 of 6 |
| Diarrhea | Gastrointestinal disorders | 1 of 6 |
| Occipital pressure ulcer | Skin and subcutaneous tissue disorders | 1 of 6 |
| Damaged infusion port | Product Issues | 1 of 6 |
| Sinusitis | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
Serious events with the highest arm-level rate: pneumonia (33.3%), scoliosis requiring spinal fusion (16.7%), seizures (16.7%).
The registry record lists an adverse-event group titled Pompe Subjects Receiving NeuRx DPS. For that group, the record lists 6 at risk for serious adverse events and 3 affected; it lists 6 at risk for other adverse events and 6 affected. Deaths are listed as 0. These are registry counts, not a randomized comparison of event rates between treatment groups.
The most frequently listed serious-event terms are pneumonia at 33.3%, scoliosis requiring spinal fusion at 16.7%, and seizures at 16.7%. The registry record does not state whether the listed terms refer to distinct participants, how events were timed in relation to pacing, or whether the same participant could contribute more than one term. It does not report exposure duration or a causal assessment for these events.
These entries should be read as reported safety information, not as proof that the intervention caused an event or that an event was unrelated to it. The record does not provide a comparable control group or additional context for interpreting differences in risk.
12. What the Result Does, and Does Not, Mean
The study addresses a meaningful measurement question: whether spontaneous breathing duration, recorded while the diaphragm pacer is on, is assessed at baseline and Day 180 in people with Pompe disease. Its description also outlines breathing trials that can progress according to tolerance and the ability to complete paced spontaneous-breathing bouts. These details define what the investigators intended to measure.
The registry record does not report numerical primary-outcome results. There is no posted mean or range at either time point, no reported change, and no confidence interval or p-value. Consequently, the record does not show whether breathing duration increased, decreased, or remained similar, nor how precisely any estimate was determined. The secondary outcome names likewise do not establish their results.
The design information also limits causal interpretation. Allocation is not stated, and the record says the arms are not a like-for-like control comparison. A comparison across time in participants receiving pacing, if one were available, could describe change but would not by itself separate the contribution of pacing from other factors that vary over time. No controlled causal estimate is reported.
The adverse-event entries add descriptive safety information, including counts, deaths, and selected serious-event terms. Without event timing, exposure details, causal assessments, or a comparable control group, those entries do not establish whether pacing caused or prevented any event.
The appropriate conclusion is therefore about the scope of the registry record: it documents a completed study, its stated endpoint and other outcomes, and some adverse-event counts, but does not report analyses that answer the primary clinical question. Planning illustrations based on an observed effect are not a substitute for outcome estimates and do not represent observed power.
13. Why This Trial Matters Statistically
This study is statistically notable for the distinction between a clearly described measurement plan and the absence of posted endpoint analyses. The primary outcome is a duration measure, expressed as hours per day, at baseline and Day 180. The record explains how spontaneous breathing was to be assessed in the context of pacing and reduced mechanical-ventilator support. Yet no numerical endpoint summaries or analyses are reported. That gap matters: a study’s measurement plan explains what it intended to learn, while results are needed to estimate what was observed and how uncertain that estimate is.
The design also illustrates why the comparison structure must be made explicit. The registry record does not state allocation and says the arms are not a like-for-like control comparison. Without a suitable concurrent comparator, a before-and-after change cannot on its own distinguish intervention-related change from other changes during follow-up. The registry information supports describing the intended time points but not assigning a causal interpretation to an unreported difference.
Several methods details would be important for understanding any eventual estimate: the number with measurements at each time point, how repeated observations were analyzed, how missing data were handled, and how multiple outcomes were addressed. Those details are not reported in the registry record. They influence how precisely estimates can be interpreted and whether the analysis aligns with the study question.
The planning assumptions also need to be kept separate from the completed study’s evidence. The record describes normal-approximation sample-size illustrations based on an observed effect, with equal allocation between two arms. That is a planning framework, not proof that the study used that design or achieved a particular level of power. Taken together, the record highlights the importance of publishing analysis methods and numerical results alongside outcome definitions.
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 main limitation for statistical interpretation is that the registry record reports 0 analyses and no numerical results for the primary or secondary outcomes. The primary endpoint is defined, but observed means, ranges, changes, and uncertainty estimates are not reported. No conclusion about the direction or size of respiratory change can be drawn from the endpoint definition alone.
Enrollment is listed as 9, while the primary outcome is described for the full sample. The registry record does not state how many participants contributed usable measurements at baseline or Day 180. It does not report participant flow, missing-data reasons, the analysis population, or methods for handling unavailable data. This makes it impossible to assess completeness of outcome data or whether analyzed participants differed from those enrolled.
The record does not describe a randomized allocation or a like-for-like control comparison; allocation is not stated. That prevents a controlled comparison from being identified in the registry information and limits causal interpretation of any time-related change. The record also does not report the statistical model or test, a trial-specific sample-size rationale, interim analyses, multiplicity handling, or sensitivity analyses.
The endpoint description includes tolerance-based breathing trials and a reduced-support pathway for patients unable initially to complete at least 30-minute bouts of paced spontaneous breathing. The registry record does not report how these different conditions were handled in analysis. The adverse-event information is also limited: event timing, exposure duration, causal assessments, and a comparable control group are not reported in the registry record. These limits restrict interpretation of both respiratory outcomes and safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Response to Diaphragmatic Pacing in Subjects With Pompe Disease — NCT02354651.
- Registry record last updated 2023-08-01; status last verified 2023-07.
- Results first posted 2023-06-05.
- 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.
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18. Record Summary
NCT02354651 is a completed University of Florida study titled “Response to Diaphragmatic Pacing in Subjects With Pompe Disease.” The registry lists enrollment of 9, a start date of 2013-05, and primary completion in 2022-06. The stated intervention is diaphragm conditioning via phrenic nerve stimulation.
The primary endpoint is off-ventilator spontaneous breathing at baseline and Day 180, measured in hours per day and summarized as a mean with a full range. The record lists 8 outcome measures and 0 analyses. Numerical primary and secondary outcome results are not reported in the registry record. Allocation is not stated, and the described arms are not a like-for-like control comparison.
The safety record lists 6 at risk and 3 affected for serious adverse events, 6 at risk and 6 affected for other adverse events, and 0 deaths. Serious-event terms include pneumonia at 33.3%, scoliosis requiring spinal fusion at 16.7%, and seizures at 16.7%. The registry record does not report causal assessments.