ALS and Airway Clearance (ALSAC) Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ALS and Airway Clearance (ALSAC) Therapy (NCT04947436), a randomized na study. The primary outcome is Respiratory Complications Severity.

2. Clinical Question

The trial addresses a practical comparison of airway-clearance approaches in ALS, a condition associated in this record with respiratory muscle weakness. Its brief summary describes a six-month study period, clinic visits at baseline and at 3 and 6 months, and monthly home visits by a respiratory therapist. The registry also lists Patient Global Impression of Change as a secondary outcome.

The central statistical question is whether the posted outcome summaries can distinguish the groups. They do not, by themselves, establish a comparative effect: the registry record contains no inferential comparison, and the outcome's score direction is described inconsistently. It also does not make clear whether the reported means represent change from baseline or scores at a particular visit. These details limit how confidently the group summaries can be interpreted as evidence about relative changes in respiratory complications.

3. Trial Design

ALS and Airway Clearance (ALSAC) Therapy was a randomized, single-masked, parallel-group study. The registry lists an enrollment of 28 and marks the study as completed. It identifies The University of Texas Health Science Center at San Antonio as the sponsor. The phase is listed as not applicable. The registry record gives a start date of 2012-01-25 and a primary completion date of 2016-09-21.

Participants were assigned among three intervention groups: HFCWO alone, MIE alone, or HFCWO together with MIE. The study summary describes all three as respiratory therapy interventions for airway-clearance assistance. The record gives planned allocation proportions of 50% to the combined-device group, 30% to HFCWO alone and 20% to MIE alone. It does not report the randomization sequence or how allocation was concealed.

The planned study period was six months. The brief summary describes clinic visits at baseline and at 3 and 6 months, as well as 6 monthly home visits by a respiratory therapist. These statements describe the study schedule; the registry record does not report how many participants completed each visit or whether the visit schedule was followed as planned. Arm descriptions are blank, so additional details about how the devices were administered are not reported in the registry record.

The primary outcome is titled Respiratory Complications Severity, with a timeframe of baseline to 6 months. The record states that a 9-item instrument would record change over that period. However, it does not provide a statistical analysis plan or explain whether the posted means are baseline-to-follow-up changes, endpoint scores, or another summary. The group-level outcome counts are 3 for HFCWO, 2 for MIE and 5 for the combined intervention; the registry record does not explain how these counts relate to enrollment or define the analysis population behind them.

Randomization can help reduce systematic differences between groups, but it does not remove uncertainty, especially when the posted group counts are small. The record does not report masking details, protocol deviations, or a sample-size justification. Those features therefore cannot be used to assess how the trial was planned or conducted beyond the design information stated in the registry.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Half (50%) of patients were randomized to the group with two devices, while 30% to only the HFCWO device and 20% to only the Mechanical Insufflation/exsufflation device.

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 Respiratory Complications Severity, measured over Baseline to 6 months.

The primary endpoint is titled Respiratory Complications Severity. The registry describes a 9-item instrument intended to record change from baseline to 6 months in respiratory complications, on a scale described as ranging from 0-9. The listed unit is a score on a scale, and the endpoint is summarized using a mean and standard deviation. The clinical aim is to represent the burden of respiratory complications over the study period, rather than a single isolated symptom.

The registry's description contains an important inconsistency about score direction. It says the scale runs from best, defined as no complications, to worst, defined as death due to respiratory complications, but also says a score of 9 indicates no complications. Those descriptions do not establish which end of the numeric scale reflects better status. The registry record does not clarify the scoring convention, so the posted means cannot safely be interpreted as indicating more or fewer complications based on their numeric direction alone.

The endpoint is potentially relevant because it is intended to summarize respiratory complications during a period in which participants received airway-clearance therapy. However, the registry record does not describe the instrument's validation, the specific items, or how the items are combined into a score. It also does not clarify whether the reported group means are changes from baseline or scores at follow-up. These omissions matter: an endpoint's clinical meaning depends on both what it measures and how the score is constructed and interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with distinguishing a descriptive summary from an estimate of a difference. A mean describes the average score among the observations included in a group summary. A standard deviation describes how spread out those observations are around their mean. Neither quantity alone answers whether randomized groups differ beyond what could plausibly arise from sampling variation. That requires a comparison estimate and an account of its uncertainty, such as a confidence interval, or a suitable hypothesis test. No such primary-outcome comparison is reported in the registry record.

What the means and standard deviations describe

For a continuous outcome, the mean is often useful because it compresses a set of measurements into a readily compared summary. The standard deviation adds information about observed variability. Here, the record reports a mean and standard deviation in each intervention group, alongside the group count. These summaries make the observed outcome values visible at a basic level, but they do not show the distribution of individual observations. In very small groups, a single observation can have considerable influence on the mean, and the standard deviation itself is estimated with substantial uncertainty.

A standard deviation of 0.0 is not evidence that the underlying outcome has no variability. It means that the values included in that particular summary had no recorded spread at the precision reported. The MIE summary is based on a count of 2, so the observation is particularly limited as a guide to variation in a wider population. The registry does not provide individual-level data or confidence intervals that could show the uncertainty around the group summaries.

Why a comparison needs an effect estimate

A trial comparison should define the contrast of interest, such as the mean difference between two randomized groups, or an overall comparison across all groups. The estimate gives the size and direction of the observed contrast under a clearly defined outcome scale. A confidence interval describes the range of effect values compatible with the data and the analysis assumptions. In general, wider intervals indicate less precision. A p-value, when reported, addresses compatibility with a specified null hypothesis; it does not measure the size or clinical importance of an effect.

The registry has no posted analysis for the primary outcome. It supplies no between-group estimate, confidence interval, or p-value to interpret. The reported means therefore should not be converted into a claim about treatment benefit or harm. In addition, the endpoint score direction is unresolved, and the record does not specify whether the summaries are change scores or follow-up scores. Those are necessary interpretive details before a difference in means can be assigned a clinical direction.

Three groups and multiplicity

With three randomized groups, an analysis might address an overall group difference, selected pairwise comparisons, or a prespecified contrast. Each approach answers a different question. If multiple comparisons are examined, the analysis plan should explain how the risk of false-positive findings is handled or why particular comparisons were selected. In general, multiplicity refers to the increased chance of finding an apparently noteworthy result when many outcomes, groups, time points, or comparisons are tested. The registry record does not report a statistical plan, prespecified contrasts, or any multiplicity approach. Since no primary-outcome tests are posted, there is no reported multiplicity-adjusted or unadjusted result to interpret.

The record lists Patient Global Impression of Change as a secondary outcome and reports two outcome measures overall. It does not provide a statistical analysis of the secondary outcome. The existence of multiple outcomes makes it important to know which result was designated primary and how secondary analyses were intended to be treated; the registry identifies the primary endpoint but does not report the analysis strategy.

Planning calculations are not trial results

Planning illustrations based on an observed effect are conceptually different from observed power. In general, a sample-size calculation asks how many participants per arm might be needed to detect a target effect under stated assumptions, such as a two-sided significance level, equal allocation, and a normal approximation. The record describes planning assumptions using a two-sided significance level of 0.05 and equal allocation between two arms, with the target effect expressed as a fraction of an observed effect. Such illustrations are not evidence that the completed trial had adequate power, and they do not replace an analysis of the trial data.

The registry's planning description also distinguishes calculations for time-to-event outcomes, which use a total number of events, from other outcomes, which use participants per arm. Respiratory Complications Severity is a continuous outcome, and the record indicates that values were missing or not estimable for a two-arm comparison. Without a reported effect estimate suitable for that calculation, no numerical planning conclusion can be drawn in the registry record. Any sample-size illustration should be read as hypothetical planning rather than as an observed trial finding.

Dispersion and distributional assumptions

Many analyses of continuous outcomes use methods that rely on assumptions about the distribution of observations or model residuals. In general, unusually variable data, skewed distributions, or outliers can make simple mean-based methods less reliable, particularly in small samples. Over-dispersion is most commonly discussed for count outcomes, where observed variability exceeds what a chosen model expects; it is not a diagnosis that can be made from these group means and standard deviations alone. The registry does not report individual scores, distribution plots, model diagnostics, or a statistical model. It is therefore not possible to assess distributional assumptions or determine whether an alternative analysis would have been appropriate.

Overall, the registry permits a limited descriptive reading of the posted group summaries. It does not provide enough analysis detail to quantify comparative uncertainty, assess model assumptions, or interpret the result as a statistically established difference. The score-direction and outcome-timepoint ambiguities further limit interpretation, independent of the choice of statistical method.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies Respiratory Complications Severity as the primary outcome and Patient Global Impression of Change as a secondary outcome. It reports two outcome measures overall, but does not report an analysis for either outcome. A statistical analysis plan, prespecified comparisons, or a method for handling multiple outcomes and comparisons is not reported in the registry record. Consequently, the record does not show whether the three groups were intended to be compared through an overall test, selected pairwise contrasts, or another approach.

Missing-data handling is also not reported. The primary-outcome summaries are accompanied by counts of 3 for HFCWO, 2 for MIE and 5 for the combined intervention, while overall enrollment is 28. The record does not explain the relationship between these counts and enrollment, identify reasons that outcome information may be unavailable, or state whether missing values were imputed or otherwise handled. It does not report the number of participants with measurements at baseline and at follow-up visits.

Analysis populations are not described. The registry does not say whether the summaries follow an intention-to-treat approach, include participants according to treatment received, or use another population definition. Randomization describes assignment, but without a stated analysis population and accounting of outcome availability, readers cannot determine how the posted summaries relate to the randomized groups as a whole.

In general, multiplicity and missing-data decisions can affect the interpretation of estimates and uncertainty. These issues are not resolved by the group means and standard deviations. Since no inferential analyses are posted, there is no reported test result whose multiplicity adjustment or missing-data assumptions can be evaluated.

11. 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.

The registry lists serious adverse event counts and other adverse event counts for each intervention group. For HFCWO, the record lists 0 participants affected by serious adverse events and 0 affected by other adverse events, with 7 at risk in each category. For MIE, it lists 0 affected in each category, with 10 at risk. For the combined HFCWO and MIE group, it lists 0 affected in each category, with 11 at risk. These are the posted counts; they do not provide event rates or comparative safety estimates.

The record separately lists 1 death in each intervention group. It does not state whether these deaths were related to the devices, caused by respiratory complications, or otherwise judged to be associated with the intervention. A death count should not be interpreted as an adverse-event attribution without that information. The registry's primary endpoint description mentions death due to respiratory complications as part of its scale wording, but it does not connect that endpoint description to the listed death counts.

Zero affected participants in the posted adverse-event categories does not establish that risk is absent. Safety estimates are uncertain when group counts are small, and the registry record does not provide event narratives, timing, severity details, exposure duration, or causal assessments. It also does not explain how the “at risk” counts relate to enrollment or the outcome analysis counts. These safety figures are therefore best read as registry-reported counts, not as a complete comparative assessment of safety.

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

The registry record shows that a randomized, single-masked, parallel-group trial compared HFCWO alone, MIE alone, and the two devices together for airway-clearance assistance in people with ALS. It reports group means and standard deviations for the primary outcome, along with small group counts. The study was marked completed, and its brief summary describes a six-month period with clinic and home visits.

The posted statistics do not establish which intervention group had better respiratory-complication outcomes. No statistical comparison, uncertainty interval, or p-value is reported, and the score direction is internally inconsistent in the endpoint description. The record also does not clarify whether the means represent baseline-to-follow-up change or another outcome summary. These limitations prevent a confident interpretation of the numerical ordering of the group means.

The result does not establish that the interventions are equivalent. A lack of a posted comparison is not evidence that there is no difference; it means the registry record does not provide the analysis needed to assess one. Nor do the descriptive summaries show that any intervention works or does not work. They are observations from a small set of reported outcome summaries whose relationship to the enrolled population is unexplained.

The safety counts likewise have a limited interpretation. The record reports no affected participants in the serious or other adverse-event categories, alongside one death listed in each group, but does not provide causal attribution or enough detail to compare safety. Those counts should not be translated into a conclusion about comparative risk.

In general, trial results are most informative when outcome definitions, analysis populations, effect estimates, and uncertainty are clearly reported. Here, key details are absent, including the statistical plan, missing-data handling, and the connection between enrollment and the outcome counts. The registry supports a description of what was posted, not a firm inference about comparative efficacy or safety.

13. Why This Trial Matters Statistically

This trial is statistically notable because it sets up a three-group randomized comparison but posts only descriptive primary-outcome summaries. That distinction illustrates why group averages alone are not enough to answer a comparative question. An estimate of the difference between groups, accompanied by uncertainty, is needed to judge how precise a contrast is and what range of effects is compatible with the data. The registry record does not report such estimates.

The reported outcome counts are small in relation to the listed enrollment, and the registry does not explain why. This makes transparent reporting of analysis populations and missing outcomes especially important. Without a clear account of who contributed measurements and why other enrolled participants are not represented in the summaries, readers cannot assess whether the data describe the randomized groups or a selected subset.

The endpoint description also demonstrates why operational definitions matter. The same scale description identifies no complications as best and death due to respiratory complications as worst, while stating that a score of 9 indicates no complications. A statistical summary is only interpretable when readers know what higher and lower values mean. If direction is ambiguous, even the sign of a group difference cannot be translated reliably into a clinical interpretation.

Finally, the safety summaries distinguish reported counts from conclusions about risk. The record lists zero affected participants in the adverse-event categories and one death in each group, but does not report attribution or comparative estimates. This is an example of why event counts require context and why absence of a detailed analysis should not be mistaken for evidence of no risk.

For clinical researchers and biostatisticians, the record underscores the value of aligning outcome definitions, analysis plans, participant accounting, and reporting. Those elements determine whether a completed randomized study can yield a precise and interpretable answer to its research question.

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.

Several limitations specific to this trial record constrain interpretation. First, the endpoint's score direction is contradictory: the scale is described as ranging from no complications to death due to respiratory complications, while a score of 9 is also said to indicate no complications. The registry does not resolve this conflict. The reported means therefore cannot be translated reliably into better or worse respiratory status.

Second, the registry describes the primary endpoint as change from baseline to 6 months, but does not clarify whether the posted means are changes, follow-up values, or another summary. The instrument's 9 items and scoring procedure are not detailed, and its validation is not reported in the registry record. This leaves uncertainty about what the reported score captures and how it should be interpreted.

Third, the primary-outcome counts are 3, 2 and 5 across the groups, despite listed enrollment of 28. The record does not explain this difference, define the analysis population, report completion at each visit, or describe missing-data handling. It is not possible to determine whether the summaries reflect all available observations or a selected subset.

Fourth, no inferential analysis is posted. There are no reported confidence intervals, p-values, adjusted estimates, model details, or multiplicity procedures. The registry does not report a sample-size justification, interim analyses, or statistical analysis plan. These omissions prevent assessment of the intended analysis and the precision of any group contrast.

Finally, the safety information is limited to counts. The registry does not report timing, event descriptions, causal assessments, or how deaths relate to the interventions. Arm descriptions are blank, and the record does not detail device-use procedures beyond naming the interventions. These gaps limit assessment of implementation, outcome ascertainment, and safety context.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ALS and Airway Clearance (ALSAC) Therapy — NCT04947436.
• Registry record last updated 2021-11-04; status last verified 2021-10.
• Results first posted 2021-11-04.
• 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.

18. Record Summary

NCT04947436, titled ALS and Airway Clearance (ALSAC) Therapy, is a completed randomized, single-masked, parallel-group study sponsored by The University of Texas Health Science Center at San Antonio. The registry lists enrollment of 28 and compares HFCWO, MIE, and their combined use in participants with amyotrophic lateral sclerosis and respiratory muscle weakness. The described study period is six months, with clinic visits at baseline and at 3 and 6 months and monthly home visits by a respiratory therapist.

The primary outcome is Respiratory Complications Severity, described as a baseline-to-6-month measure. The registry posts group means and standard deviations, but not a comparative analysis. Outcome counts are small relative to enrollment, and the relationship between them is not explained. The endpoint's score direction is internally inconsistent, and the record does not clarify whether the summaries are changes or follow-up scores.

Patient Global Impression of Change is listed as a secondary outcome, but no analysis is posted. Serious and other adverse-event counts are reported as zero affected participants in each group, with one death listed per group; attribution is not reported. Overall, the record permits limited descriptive reporting but does not establish a comparative statistical result.