Effects of Respiratory Muscle Training in Mechanically Ventilated Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Respiratory Muscle Training in Mechanically Ventilated Adults (NCT02469064), a randomized na study. The primary outcome is Weaning Time From Mechanical Ventilation.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, parallel-group trial, marked completed, with enrollment of 126. The two arms were respiratory muscle training and conventional physical therapy. In the experimental arm, respiratory muscle training was added to treatment; the comparison arm received conventional cardiopulmonary physical therapy. The registry does not report how the random sequence was generated, how allocation was concealed, or which participants, clinicians, or assessors were masked. The double-blind designation is recorded, but further detail about its implementation is not reported in the registry record.

The study dates listed are 2014-09 for the start and 2015-12 for primary completion. The record identifies respiratory muscle weakness as the condition and describes the target population as mechanically ventilated patients requiring ventilatory support for more than 48 hours in an intensive care unit in Cali. Additional eligibility criteria, recruitment procedures, and the number screened or excluded are not reported in the registry record.

The primary endpoint was weaning time, recorded in hours and summarized by the median and inter-quartile range. Maximum inspiratory pressure was a secondary outcome, reported as a mean with standard deviation. The registry lists two outcome measures and two analyses. The reported group counts differ by outcome: the primary endpoint includes 62 participants in the respiratory muscle training group and 64 in conventional physical therapy, while the secondary measure includes 48 and 54, respectively. Reasons for the different counts are not reported in the registry record.

The record does not report a protocol, a sample-size justification, a detailed statistical analysis plan, or an account of follow-up after extubation. It also does not state how the double-blind design was maintained in practice. These omissions limit what can be inferred about the planned analysis and the conduct of the trial beyond the information explicitly registered.

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: 126 patients were randomized, 3 of them did not comply with the protocol, being assigned to the experimental treatment and receiving conventional treatment. No patient requested to be withdrawn from the study, and no patient had any adverse effects

Overall Study

Reasons for not completing this period:

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 Weaning Time From Mechanical Ventilation, measured over Measured by the end of the period of mechanical ventilation, an average expected time of 4 days.

Weaning time from mechanical ventilation measures the elapsed time between the start of a specified ventilator-support mode and extubation. In this record, the starting point was pressure support at 10 centimeters of water or less, or continuous positive pressure in the airway mode; the endpoint was patient extubation. The outcome was recorded in hours and summarized using the median and inter-quartile range. The registry describes measurement by the end of the period of mechanical ventilation and gives an average expected time of 4 days.

This endpoint addresses a clinical process: how long patients remain on mechanical ventilatory support after reaching the stated point in the weaning process. A time-based endpoint can reflect both whether an event occurs and how long it takes to occur. For interpretation, the starting point and event definition matter because changing either can change the measured duration. In this study, the registry gives a specific operational definition, but it does not report further rules for cases in which extubation was delayed, ventilation resumed, or the endpoint was otherwise difficult to classify.

The median describes the middle of the observed distribution and is less sensitive than the mean to unusually long times. The inter-quartile range describes the central spread of observations. The group medians were both 5.0 hours, with ranges of 0.0 to 72.0 hours for respiratory muscle training and 0.0 to 59.0 hours for conventional physical therapy. The registry also reports a hazard ratio analysis. Because a hazard ratio concerns the relative rate of an event over time rather than a direct difference between medians, the summary measures need not express the result in the same way.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the trial as randomized, double-blind, and parallel-group. Randomization is intended, in general, to make treatment groups comparable on average at the start of a study, including for characteristics that may not have been measured. It does not guarantee exact balance in a particular trial. The registry does not describe the randomization procedure, allocation concealment, the masking procedures, or an analysis plan, so the practical details and safeguards cannot be evaluated from the record.

What does the median and inter-quartile range describe?

For the primary endpoint, the registry reports a median and inter-quartile range. The median is the middle value in an ordered set of observations. The inter-quartile range spans the central half of the observations and conveys spread without relying on a normal-distribution model. This can be useful for time measurements that are skewed or contain a long upper tail. The primary results also give the full observed ranges. Those ranges show the lowest and highest recorded values but do not, by themselves, indicate how observations are distributed between the extremes.

The two reported medians are 5.0 hours. Equal medians are a descriptive finding, not a complete comparison of the distributions. Two groups may share a median and still differ elsewhere in their distributions, including in the proportion of participants reaching an event over time. Conversely, a difference in a summary measure does not alone demonstrate that the difference is reliable or meaningful.

How should the hazard ratio be read?

The registry reports a hazard ratio of 0.82 and labels the analysis method “Mann Whitneey.” A hazard ratio generally compares event rates at a given time among participants who have not yet had the event, subject to the model and data assumptions. It is not a ratio of median times, nor does it directly state how many hours separate the groups. The registry’s analysis label and effect measure are not an especially transparent description of how the estimate was obtained. Further details, including the fitted model, treatment of censoring, and assumptions, are not reported in the registry record. Interpretation should therefore remain tied to the reported estimate and interval rather than assuming unreported analytic details.

The 95% confidence interval runs from 0.55 to 1.20. In general, a confidence interval expresses the precision of an estimate under a statistical procedure: repeated use of the same procedure would produce intervals with the stated coverage under its assumptions. It is not a range that assigns a probability to the true value after observing the data. For a hazard ratio, 1 represents no relative difference. Since the reported interval includes 1, the result is not statistically clear at the conventional two-sided 0.05 level; the registry reports p = 0.84. A high p-value is not the probability that the null hypothesis is true and does not establish equivalence.

What does the secondary mean difference express?

Maximum inspiratory pressure is reported as a mean with standard deviation. The mean is an arithmetic average; the standard deviation describes variability among observations around that average. The summary-statistic recalculation compares the two group means and gives a mean difference of -3.51 cmH20, with a 95% confidence interval from -8.543 to 1.523 and an unadjusted p-value of 0.172. The recalculated difference is expressed as conventional physical therapy minus respiratory muscle training, consistent with the group means used in the calculation. The confidence interval includes zero, the value representing no mean difference. This interval does not rule out differences in either direction.

The registry’s own secondary analysis reports a slope of 0.46, a 95% confidence interval from -3.75 to 4.78, and p = 0.48, using a two-sided t-test. A slope and a difference between final group means are not necessarily the same estimand. The record does not explain the relationship between this slope and the baseline and final measurements, or whether the analysis adjusts for baseline values. The two reported analyses therefore should not be treated as interchangeable versions of one result.

Why does over-dispersion matter in general?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model understates variability, its standard errors may be too small and its confidence intervals too narrow. For a time endpoint, skewness, tied values, censoring, and differences in follow-up can also affect which methods are appropriate. The registry does not provide enough detail to assess these issues for the primary analysis. The reported ranges suggest that the observed weaning times were not all identical, but the ranges alone cannot establish whether a particular model assumption was met.

How should planning illustrations be interpreted?

Sample-size calculations based on observed effects are planning illustrations, not observed power and not evidence that a treatment effect is real. In general, such calculations translate an assumed effect and design choices into a possible number of participants per arm. Their output depends on assumptions, including the target effect, allocation, significance level, and model. Here, the planning assumptions state a two-sided significance level of 0.05, equal allocation, and a normal approximation, with effects set to stated fractions of the observed effect. The registry’s own design justification is not reported in the registry record. The illustrations cannot establish whether the original trial was adequately planned or whether the observed estimate would recur in another study.

10. Analyses Reported by the Sponsor

For the primary endpoint, the registry reports the sponsor’s analysis as a hazard ratio of 0.82, with a 95% confidence interval from 0.55 to 1.20 and p = 0.84. The registry does not report a separate recalculated primary estimate from the posted summary statistics. The median and range summaries describe the observed group outcomes, while the hazard ratio is a time-to-event measure; these are different summaries and should not be expected to match numerically.

For maximum inspiratory pressure, the sponsor-reported analysis gives a slope of 0.46, with a 95% confidence interval from -3.75 to 4.78 and p = 0.48. The summary-statistic recalculation instead compares the posted group means and gives a mean difference of -3.51 cmH20, with a 95% confidence interval from -8.543 to 1.523 and an unadjusted p-value of 0.172. The estimates are not the same kind of quantity. The registry does not explain how the slope was defined or how baseline measurements entered that analysis, so a direct reconciliation is not possible from the record.

The sponsor-reported analyses and summary-statistic recalculation answer different statistical questions where their estimands differ. The recalculation is unadjusted and based on the posted summaries; it does not replace the registry’s reported analysis or establish which model was prespecified. The record does not provide enough detail to infer the underlying analysis procedure beyond the labels and results it reports.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, but it does not report a complete statistical analysis plan. In particular, a multiplicity strategy for interpreting the primary and secondary outcomes is not reported in the registry record. When several outcomes or comparisons are examined, the chance of a nominally noteworthy result arising by chance can increase. General approaches include prespecifying one primary endpoint, adjusting inference across selected comparisons, or treating secondary analyses as exploratory. The record does not say which approach was intended, so the reported secondary p-value should not be read as if an adjustment had been made.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint lists 62 participants in the respiratory muscle training group and 64 in conventional physical therapy, while the secondary outcome lists 48 and 54. These different counts do not, by themselves, identify why observations are absent or whether the groups were analyzed according to randomized assignment. Reasons could not be inferred from the counts, and the registry does not report whether missing measurements were excluded, imputed, or addressed in another way.

The record does not state whether the primary analysis followed an intention-to-treat principle, whether participants were analyzed as randomized, or how protocol deviations were handled. It also does not report a per-protocol analysis or a sensitivity analysis for missing data. These details matter because exclusions after randomization can affect the balance created by random assignment, and conclusions can depend on assumptions about unobserved outcomes.

In general, a credible interpretation of a trial result considers prespecification, outcome availability, analysis population, and the treatment of missing observations alongside the effect estimate and its uncertainty. The registry provides endpoint definitions and selected results, but it does not report enough information to assess these features fully. This does not establish that the analyses were inappropriate; it means that the relevant checks cannot be made from the registry record.

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.

The posted safety figures record zero serious adverse events, zero other adverse events, and zero deaths in the respiratory muscle training group, with 62 at risk for each adverse-event category. The conventional physical therapy group also has zero serious adverse events, zero other adverse events, and zero deaths, with 64 at risk for each category. These are the recorded figures for the groups and categories shown in the registry.

Zero recorded events should not be interpreted as proof that no adverse events occurred outside the registry’s recorded categories or observation period, nor as proof that either treatment has no risk. The registry does not report the method or duration of adverse-event surveillance, the definitions used for event classification, or details on ascertainment and reporting. It also does not provide event narratives or a description of how events were attributed to treatment. Those limits make the safety figures a summary of reported counts rather than a complete assessment of safety.

Because the record reports no events in the listed categories, it does not permit a comparison of event rates or an assessment of the range or severity of events. The absence of reported events should be read narrowly, alongside the unreported surveillance details, rather than as a general safety conclusion.

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

The primary result describes observed weaning times and a reported time-to-event comparison in this randomized trial. Both groups had a median of 5.0 hours. The reported hazard ratio and its confidence interval do not establish a statistically clear difference in the primary analysis. This is an interpretation of the estimates and their uncertainty, not proof that the two treatments are equivalent or that their effects are exactly the same.

A nonsignificant result can arise when the true difference is small, when the estimate is imprecise, or for other reasons. The confidence interval shows a range of values compatible with the data under the analysis assumptions; it does not settle which value is true. The registry does not report a clinically important threshold for weaning time, so the practical importance of possible differences within the interval cannot be judged from the record alone.

The secondary maximum inspiratory pressure result is a separate measurement and should not be used to claim a change in the primary endpoint. The sponsor-reported slope and the recalculation from group means are not directly interchangeable. The record does not give enough analysis detail to resolve their relationship. Their uncertainty also means they do not provide a definitive distinction between the groups.

The findings apply to the population and setting described in the registry, subject to the trial’s eligibility criteria, conduct, outcome measurement, and analysis. Further eligibility and analysis details are not reported in the registry record. The results do not, on their own, establish what would happen in other clinical settings or populations. Nor do the posted counts establish that adverse events are impossible; they indicate only that none were recorded in the listed categories for these groups.

Overall, the registry documents a randomized comparison and reports no statistically clear group difference on the primary analysis. That should be distinguished from a claim of no effect, a claim of equal effectiveness, or a recommendation about care. Those conclusions require additional evidence and, for equivalence, a prespecified equivalence framework that is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to compare a time-to-event endpoint with a group summary such as the median. The primary outcome is defined as time from a specified ventilator-support state to extubation, and the record presents both medians and a hazard ratio. Each captures a different aspect of time-to-event data. Reading them together requires attention to the endpoint definition, the analysis method, and the assumptions behind the hazard ratio.

The equal group medians do not make the reported time-to-event analysis redundant. Time-to-event methods can use information about when events occur across the follow-up period, while medians condense a distribution to one point. At the same time, the registry gives limited detail about censoring, model choice, and analysis assumptions. The difference between a concise effect estimate and a transparent account of the method is important for interpreting a trial.

The secondary outcome also illustrates why the analysis target matters. A comparison of posted means and a reported slope may describe different quantities, particularly when an outcome is measured at baseline and again later. Without a clear account of how those measurements were modeled, readers should not assume that two estimates answer the same question. Statistical transparency about the estimand, baseline handling, and analysis population helps make such results comparable and reproducible.

Finally, the different numbers of observations across the two outcomes highlight the role of outcome availability and missing-data reporting. Counts alone cannot explain why measurements are absent or how that absence affects inference. A statistical reading therefore attends not just to p-values, but also to effect measures, intervals, endpoint definitions, populations analyzed, and what the registry does not report.

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 registry record leaves important design and analysis details unspecified. It does not report the randomization procedure, allocation concealment, implementation of masking, or the detailed contents and delivery of either treatment. Although the design is marked double-blind, the record does not identify who was masked or how masking was maintained. These limits prevent a fuller assessment of possible bias in treatment delivery or outcome assessment.

For the primary endpoint, the registry gives a definition and reports a hazard ratio, but the analysis method is listed as “Mann Whitneey.” The fitted model, handling of censoring, and assumptions are not described. The relation between the reported hazard ratio and the group medians is therefore not fully documented. The endpoint timeframe also uses an average expected time of 4 days, while observed group summaries are reported in hours; the record does not clarify further details of the observation window.

The secondary outcome has fewer observations than the primary outcome, but reasons for the difference are not reported. The registry does not describe missing-data handling, the analysis population, adjustment for baseline maximum inspiratory pressure, or the definition of the sponsor-reported slope. As a result, the reported slope and the recalculation from group means cannot be reconciled confidently from the record.

A protocol, detailed statistical plan, sample-size justification, multiplicity strategy, and clinically important thresholds are not reported in the registry record. Follow-up and adverse-event ascertainment details are also not given. These omissions do not show that the trial procedures were inadequate, but they limit independent appraisal of prespecification, precision, missingness, and safety reporting. The single setting and population described also restrict how far the findings can be generalized, while further eligibility details are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Respiratory Muscle Training in Mechanically Ventilated Adults — NCT02469064.
• Registry record last updated 2023-01-12; status last verified 2023-01.
• Results first posted 2018-11-02.
• 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

NCT02469064 is a completed randomized, double-blind, parallel-group trial of respiratory muscle training in mechanically ventilated adults. Enrollment was 126. The study compared respiratory muscle training added to treatment with conventional cardiopulmonary physical therapy. The registry lists a start in 2014-09 and primary completion in 2015-12.

The primary endpoint was weaning time from mechanical ventilation, defined from the start of specified ventilator support to extubation and summarized by median and inter-quartile range. Both groups had a median of 5.0 hours. The reported hazard ratio was 0.82, with a 95% confidence interval from 0.55 to 1.20 and p = 0.84. Maximum inspiratory pressure was the posted secondary outcome. The registry reports a sponsor analysis and a distinct recalculation based on posted group means; neither provides a statistically clear separation.

The registry records zero serious adverse events, zero other adverse events, and zero deaths in both groups. Details on analysis populations, missing data, multiplicity, masking procedures, and adverse-event surveillance are not reported in the registry record.