Treatment of Critical Illness Polyneuromyopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Critical Illness Polyneuromyopathy (NCT01058421), a randomized na study. The primary outcome is The Primary Outcome Variable for This Study Will be the Short Form of the Continuous Scale Physical Functional Performance Test (CS-PFP) Called the PFP-10.

2. Clinical Question

The trial’s stated aim was to evaluate intensive physical therapy for patients recovering from acute respiratory failure, with particular attention to neuromuscular weakness and day-to-day function. The primary outcome was a functional-capacity score rather than a measure limited to pulmonary symptoms. Its activities include common tasks such as sweeping, moving clothes between appliances, and carrying groceries. The score is intended to represent a person’s capacity to perform activities of daily living and sustain activity.

The observed primary comparison was a mean score of 19.0 in the intensive physical therapy group and 20.9 in the standard-of-care group. The estimated mean difference, defined as intensive therapy minus standard of care, was -1.9 points. The confidence interval extends across values on either side of no difference, so the estimate is imprecise about the direction and size of the group difference. These results describe the posted comparison; they do not establish that one treatment is better or worse.

3. Trial Design

The registry record describes a randomized, single-masked, parallel-group trial. It lists 120 participants enrolled and identifies the study as completed. The two groups were intensive physical therapy treatment and standard-of-care physical therapy. The planned intensive intervention is described as daily intensive physical therapy over four weeks. No further treatment description is given for the standard-of-care group.

The study is listed as phase NA. The sponsor is the University of Colorado, Denver. The record gives a start of 2009-09 and a primary completion of 2014-05. These are registry dates, not a description of the timing of individual participants’ treatment or follow-up.

The primary endpoint was the PFP-10 score at 1 month. The outcome description says testing took place in a standardized physical therapy laboratory and that the physical therapist conducting the test was formally trained and blinded to group assignment. The record does not describe masking of participants or other study personnel, so the meaning of “single” masking beyond what is stated in the registry is not reported in the registry record.

The primary outcome account reports that 41 participants in the intensive treatment group and 48 in the standard-of-care group were analyzed. It also gives some detail about participants who completed testing or remained in a hospital or another facility, but the standard-of-care account is truncated. The record does not give a complete account of the analysis population, reasons for missing outcome measurements, or the handling of missing values.

The registry lists eight secondary outcomes, including ICU-free days, duration of mechanical ventilation, hospital and institution measures, and discharge home. The posted secondary results include an outcome for discharge home. No reported analyses are listed for the secondary 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: Deceased subjects were removed from starting period subject numbers for subsequent outcome periods in each cohort. All non-deceased subjects were included in period outcomes analysis and categorized as death in subsequent period, lost to follow-up, remained in hospital or other facility.

1 Month Outcomes

Reasons for not completing this period:

3 Month Outcomes

Reasons for not completing this period:

6 Month Outcomes

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 41 of 59 subjects were analyzed in the Intensive Treatment Group (20 completed outcomes testing + 5 remained in hospital + 16 remained in another facility = 41 subjects). 48 of 61 Standard of Care Group subjects were analyzed (19 completed outcomes testing + 12 remained in hospital + 17 remained in another facility = 48).

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 The Primary Outcome Variable for This Study Will be the Short Form of the Continuous Scale Physical Functional Performance Test (CS-PFP) Called the PFP-10, measured over 1 month.

The primary endpoint is the PFP-10, the short form of the Continuous Scale Physical Functional Performance Test. It measures a person’s ability to carry out activities of daily living through ten tasks, including sweeping a floor, moving clothes from a washer to a dryer, and carrying groceries. Tasks are assessed using time, time and weight, or distance. The test generates an overall score and scores for areas such as strength, flexibility, balance, coordination, and endurance.

The score ranges from 0 to 100, with higher values indicating better physical function. The registry says that participants who remained in hospital or a long-term care facility at assessment received a score of 0. This rule makes the endpoint reflect both performance on the tasks and the ability to be assessed outside those settings. It is important when interpreting the result: the score is not solely a test of physical performance among participants who completed the laboratory assessment.

The endpoint was assessed at 1 month. A standardized laboratory procedure and a trained assessor blinded to group assignment are described in the registry record. These features can help limit variation in how the test is administered and reduce the possibility that knowledge of treatment assignment influences scoring. The record does not give further details about adherence to the testing protocol or the reliability of measurements in this trial.

A mean score provides a group-level summary of a continuous measure. It does not show the full range of individual outcomes or how many participants experienced changes of particular sizes. The registry record does not report a threshold for a clinically important difference on this measure.

7. Results Posted in the Registry

• Intensive Physical Therapy Treatment Group: mean 19.00 versus 20.90 on control; difference -1.90 (95% CI -12.72 to 8.92), standardized effect d = -0.07; z-test p = 0.731.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Discharged to Home

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Intensive Physical Therapy Treatment Group: 50.8% (30/59) versus 49.2% (30/61) on control; risk difference 1.7 percentage points (95% CI -16.2 to 19.6), risk ratio 1.03 (0.72–1.48); unadjusted two-proportion z-test p = 0.855.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intensive Physical Therapy Treatment Group and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering time in intensive care, duration of mechanical ventilation, hospital and institution measures, and discharge home. These outcomes concern aspects of recovery and care use that are related to, but distinct from, the primary PFP-10 measure of physical function. The primary result is an imprecise comparison of functional scores; a secondary outcome cannot by itself resolve that uncertainty or replace the primary endpoint.

The posted secondary result for discharge home does not show a clear separation between groups: its estimate is close to zero, its confidence interval spans values in either direction, and its unadjusted p-value is 0.855. This is broadly consistent with the general uncertainty in the primary comparison, but the endpoints measure different things and have different scales. Similar-looking estimates across outcomes do not demonstrate that the interventions had the same effect on each aspect of recovery.

The record lists eight secondary outcomes, while reported analyses are not listed. Apart from discharge home, results for the listed secondary measures are not reported in the registry record. Therefore, the overall pattern across those other outcomes cannot be assessed from the posted results.

Unadjusted secondary results carry less weight when several outcomes are considered because examining multiple results creates more opportunities for apparently notable findings to occur by chance. This is a general statistical concern, not a claim that a particular result in this trial is false. The registry does not report a multiplicity strategy or a hierarchy specifying which secondary outcomes were confirmatory. Accordingly, the discharge-home result is best read as a secondary descriptive comparison rather than as independent confirmation of the primary result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• ICU-free Days
• ICU Length of Stay
• Mechanical Ventilation Duration
• Hospital Free Days
• Hospital Length of Stay
• Discharged to Home
• Institution Free Days
• Institution Free Days

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous, so the posted group summaries are means with standard errors. A mean summarizes the average score within a group. The standard error describes the estimated uncertainty in that group mean; it is not the spread of individual participants’ scores. The registry reports a mean of 19.0 with standard error 3.7 for the intensive physical therapy group, and a mean of 20.9 with standard error 4.1 for the standard-of-care group.

The comparison is expressed as a mean difference: the intensive-group mean minus the standard-of-care mean. The estimate is -1.9 points. This direction convention makes negative values correspond to a lower average score in the intensive group, while positive values would correspond to a higher average score. A mean difference is measured in the original outcome units, so this estimate is in PFP-10 score points.

A confidence interval gives a range of estimates compatible with the observed data under the method used to construct it. The primary comparison’s interval, -12.72 to 8.924, contains zero. Zero represents no difference between group means. Because the interval also contains values on either side of zero, it does not settle the direction of the difference. Its breadth indicates that the point estimate should not be treated as precise. The registry record does not state the confidence level or the method used to calculate this interval; the interval is commonly described as a 95% confidence interval in this interpretation.

The unadjusted p-value for the primary comparison is 0.731. A p-value assesses how compatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of a difference. The registry record does not report the statistical test or model used for the primary comparison. The reported p-value is unadjusted, and the record does not give details of any adjustment for other outcomes or analyses.

For a binary outcome such as discharge home, the posted summaries include the percentage in each group and a risk difference. A risk difference expresses the difference between the groups’ proportions, in percentage-point terms when proportions are expressed as percentages. The posted estimate is 0.017 as recorded, with an interval from -0.162 to 0.196 and an unadjusted p-value of 0.855. These values indicate substantial uncertainty around the estimated difference. The registry also reports relative measures for this outcome, but the record does not report adjusted analyses for it.

General statistical principle: confidence intervals and p-values answer related but distinct questions. A p-value summarizes compatibility with a null hypothesis under a model; a confidence interval shows a range of plausible effect estimates under its method. Neither replaces consideration of the outcome definition, missing data, analysis population, or design. For a continuous outcome, the scale and direction of the measure are essential to understanding what the estimate means.

General statistical principle: over-dispersion occurs when outcomes vary more than a statistical model assumes. If unaccounted for, this can make uncertainty appear smaller than it is. The registry record does not report whether over-dispersion was relevant or assessed for any analysis in this trial. Since the primary endpoint is continuous, the exact distributional and variance assumptions for its analysis cannot be established from the posted results.

The record reports the primary endpoint and one secondary result in detail, but it does not identify the statistical model, covariates, or treatment of repeated measurements, if any. The record also does not report a pre-specified hierarchy of endpoints, a multiplicity adjustment, or interim analyses. These details are not inferable from the reported means, confidence intervals, and p-values. Accordingly, the posted estimates can be described, but the full analysis strategy cannot be reconstructed from the registry record.

Planning sample sizes are a different kind of statistical quantity from the trial’s observed results. The planning illustrations use an effect based on the observed effect and state assumptions of a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. They show the participants per arm associated with specified target power and fractions of the observed effect. They do not establish what assumptions were used when the trial was originally designed.

11. Confidence Intervals and Precision

The primary mean difference is -1.9 PFP-10 points, and the confidence interval extends from -12.72 to 8.924 points. This interval includes zero, as well as estimates favoring either group. Its width is important: the observed point estimate is not precise enough to rule out differences that are appreciably larger in either direction. The interval should be considered alongside the point estimate rather than treating the point estimate as the only plausible result.

The group standard errors were 3.7 for intensive physical therapy and 4.1 for standard of care. Standard errors describe uncertainty in estimated group means, not the variation among individual scores. The registry does not report standard deviations for the primary outcome, and the standard errors alone do not describe the range of individual participant outcomes.

The reported analysis counts are 41 in the intensive group and 48 in the standard-of-care group. The enrollment count is 120. The smaller counts in the primary outcome account make the analysis population and missingness relevant when judging precision. The registry gives some information about participants who completed testing or remained in care settings, but it does not provide a complete account of the reasons for unavailable measurements or the methods used to address missing data.

The p-value of 0.731 is consistent with substantial uncertainty, but it does not quantify the range of possible mean differences. The confidence interval does that more directly. It also does not establish equivalence: no equivalence margin is reported, and the interval is not confined to a stated range of negligible differences. The registry record does not report a clinically important difference threshold for the PFP-10, so the clinical importance of the interval’s endpoints cannot be determined from this information alone.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations give participants per arm for 80% power and participants per arm for 90% power. These are not total sample sizes. The assumptions listed are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

For the primary outcome, planning for 100% of the observed effect corresponds to 3,018 participants per arm for 80% power and 4,040 participants per arm for 90% power. Planning for 75% of the observed effect corresponds to 5,365 participants per arm for 80% power and 7,182 participants per arm for 90% power. Planning for 50% of the observed effect corresponds to 12,071 participants per arm for 80% power and 16,160 participants per arm for 90% power.

In plain terms, a power target describes the probability of detecting a specified effect under the planning assumptions if that effect is present. The 80% and 90% columns represent different targets for that probability; the higher target requires a larger planned sample for the same effect. Smaller effects also require more participants because they are harder to distinguish from random variation. The figures are planning illustrations based on the observed effect, not observed power and not a retrospective measure of whether the trial succeeded.

For the discharge-home outcome, the same convention applies: the reported figures are participants per arm, not total events. The registry’s general note says that time-to-event planning displays use total events, but these posted outcomes are not identified as time-to-event outcomes. The registry record does not report the sample-size assumptions used for the original trial design.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.900; pooled standard deviation σ = 26.343.
2. n = 2 × (1.96 + 0.842)² × 26.343² / -1.900² = 3,017.6, rounded up to 3,018 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.9                      # observed difference in means
sigma <- 26.3432165361648                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1058421)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3,018 (80% power), 4,040 (90% power)
 75% of observed effect: n per arm = 5,365 (80% power), 7,182 (90% power)
 50% of observed effect: n per arm = 12,071 (80% power), 16,160 (90% power)
power.t.test: 3018.6 
Simulated power at n = 3,018 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan or explain how the primary and secondary outcomes were prioritized for formal inference. It lists eight secondary outcomes, but gives no multiplicity adjustment, testing hierarchy, or rule for interpreting results across the set. When multiple outcomes are assessed, the chance of at least one apparently unusual result can increase. Adjustments or pre-specified testing strategies can address that issue, but whether any were used in this trial is not reported in the registry record.

The record reports no listed secondary analyses, even though a result for discharge home is posted. It does not give a complete account of the statistical tests or models used, whether analyses were adjusted for baseline variables, or how any departures from the planned analyses were handled. Interim analyses and stopping rules are also not reported in the registry record.

Missing outcome information is relevant to the primary comparison. The registry says that 41 of 59 participants in the intensive treatment group and 48 of 61 participants in the standard-of-care group were analyzed. It describes completed testing and some participants who remained in hospital or another facility, but the standard-of-care description is incomplete. The record does not fully explain why other participants were not included in the reported primary outcome counts, whether all missingness had the same cause, or what methods were used to handle missing values.

The endpoint description states that participants still in hospital or a long-term care facility at the time of assessment received a score of 0. That is a defined part of the outcome, rather than an ordinary missing score, for those participants. The record does not make clear how participants with other unavailable assessments were treated. It also does not report whether the primary analysis followed an intention-to-treat principle or used another analysis population. These limitations constrain assessment of potential bias and reproducibility.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 59 participants at risk in the intensive physical therapy group and zero among 61 participants at risk in the standard-of-care group. It also reports one other, non-serious adverse event in each group, using the same respective denominators. No serious adverse-event terms are listed.

These counts describe the events posted in the registry record. They do not establish that no other events occurred, nor do they show that the groups have identical safety profiles. The record does not give details about event definitions, collection procedures, severity categories for the other events, or the period over which adverse events were collected. Death counts are not reported in the registry record.

With relatively few events recorded, event counts alone offer limited information about differences between groups. The serious adverse-event figures should therefore be read as a description of what was posted, not as proof of safety or as a comparison demonstrating a treatment effect. The registry’s adverse-event information does not change the interpretation of the primary functional outcome.

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

The posted primary result is a mean PFP-10 score of 19.0 in the intensive physical therapy group and 20.9 in the standard-of-care group at 1 month. The estimated mean difference is -1.9 points, with a confidence interval from -12.72 to 8.924 and an unadjusted p-value of 0.731. These statistics describe the observed comparison and its uncertainty. The interval includes no difference and estimates favoring either group.

This is not evidence that the treatments are equivalent. Equivalence requires an explicitly defined margin and an analysis designed to evaluate whether the uncertainty lies within that margin; such a margin is not reported in the registry record. Nor does a non-significant p-value prove that there is no effect. The result is better understood as an estimate that remains uncertain, rather than as a definitive answer in either direction.

The PFP-10 measures functional capacity through everyday tasks, and its scoring rule assigns 0 to participants who remained in hospital or a long-term care facility at assessment. Thus, the endpoint incorporates both task performance and the specified setting-based score. It does not capture every aspect of recovery, and the registry record does not report a threshold for a clinically important difference.

The secondary discharge-home result is also uncertain and is not a replacement for the primary outcome. The registry record lists other secondary outcomes but does not report their results in detail. It also does not report a multiplicity plan or full analysis methods. These limitations mean that the posted figures should be interpreted as registry-reported comparisons, not as a complete account of all possible analyses or outcomes.

Overall, the result does not establish that intensive physical therapy improves or worsens the measured function compared with standard of care. It also cannot rule out differences that the confidence interval permits. The conclusions apply to the outcomes and participants described in the registry record, and should not be extended to outcomes or populations that were not reported.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate, a confidence interval, and a p-value need to be read together. The mean difference gives the direction and scale of the observed contrast, while the confidence interval shows that the estimate remains uncertain. The p-value alone would not convey the range of differences compatible with the analysis, nor would it indicate whether any difference is clinically important.

The primary endpoint also illustrates how outcome construction shapes interpretation. The PFP-10 is based on practical activities, but the record assigns a score of 0 to participants still in hospital or a long-term care facility at assessment. That rule brings a feature of care status into a measure of physical function. Understanding the endpoint definition is necessary before treating the group means as a direct comparison of task performance alone.

The analysis counts also matter. The registry reports 120 enrolled participants but gives smaller counts for the primary outcome analysis. Without a full account of missing outcomes and the analysis population, readers cannot fully judge how representative the reported comparison is of all enrolled participants. This is a statistical reporting issue, not merely a matter of presentation.

Finally, the registry lists several secondary outcomes but does not report a multiplicity strategy or results for most of them. This highlights why secondary endpoints need to be interpreted in the context of a pre-specified analysis plan and why unadjusted findings should not be treated as independent confirmation. The record offers a useful view of the primary estimate, but important design and analysis details remain unavailable.

18. 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 primary outcome analysis includes 41 participants in the intensive group and 48 in the standard-of-care group, while total enrollment was 120. The record gives some reasons participants were assigned a score of 0 or completed outcome testing, but it does not provide a complete account of the primary analysis population or all unavailable assessments. Without fuller reporting, the effect of missing outcome data on the estimate cannot be evaluated.

The registry record does not describe the standard-of-care treatment beyond its label. It also does not specify what “single” masking means in practice, apart from stating that the assessor conducting the PFP-10 was blinded to group assignment. The record does not report adherence to the intensive intervention or the extent to which the groups’ care differed.

The statistical analysis is incompletely described. The test or model for the primary comparison, any adjustment variables, the approach to missing values, and the original sample-size justification are not reported in the registry record. Nor are interim analyses or a multiplicity strategy. These gaps limit assessment of whether the analyses followed a pre-specified plan.

The record lists eight secondary outcomes but reports detailed results for discharge home; other secondary results are not reported in the registry record. Adverse-event reporting is also limited to counts, without event-collection details or a reported timeframe. Finally, no clinically important difference threshold for the PFP-10 is reported. These limitations make it difficult to judge the clinical importance and completeness of the posted evidence.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Treatment of Critical Illness Polyneuromyopathy — NCT01058421.
• Registry record last updated 2017-04-27; status last verified 2017-03.
• Results first posted 2017-04-27.
• 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.

22. Record Summary

The registry record describes a completed, randomized, single-masked, parallel-group trial with 120 participants enrolled. It compared a four week course of daily intensive physical therapy with standard-of-care physical therapy for patients recovering from acute respiratory failure.

The primary endpoint was PFP-10 physical function at 1 month. The reported group means were 19.0 and 20.9, with a mean difference of -1.9 points, a confidence interval from -12.72 to 8.924, and an unadjusted p-value of 0.731. The estimate is imprecise and does not establish a difference between groups.

The record lists eight secondary outcomes and posts a result for discharge home. It does not report a complete secondary analysis plan, the original sample-size justification, or full details of missing outcome handling. Safety figures include zero serious adverse events in each group and one other event in each group; death counts are not reported in the registry record.