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 Open Lung Ventilation in ARDS: The PHARLAP Trial (NCT01667146), a randomized na study. The primary outcome is Number of Ventilator Free Days at Day 28 Post Randomisation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01667146 |
| Phase | NA |
| Condition | Acute Respiratory Distress Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 115 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Australian and New Zealand Intensive Care Research Centre |
| Results posted | Yes |
2. Clinical Question
Population
People with acute respiratory distress syndrome (ARDS) who required mechanical ventilation were the population of interest. ARDS is described in the registry record as lung injury that can impair oxygen delivery and carbon dioxide removal. The posted record gives an enrollment of 115 and lists the condition as Acute Respiratory Distress Syndrome.
Intervention
The intervention was the PHARLAP mechanical ventilation strategy. The record describes the broader approach as an open-lung strategy that includes permissive hypercapnia, alveolar recruitment and low airway pressure. The brief summary also refers to smaller ventilator breaths and occasional sustained deep breaths called recruitment manoeuvres.
Comparator
The comparator was a control-group mechanical ventilation strategy. The record does not give enough detail to specify the control ventilation protocol beyond its label.
Primary question
The primary outcome was the number of ventilator-free days at day 28 after randomisation. It counts days from day 1 through day 28 on which a participant was alive and received no invasive mechanical ventilation. The practical statistical question is how the outcome distributions in the two randomized groups compare. The registry record posts group medians and interquartile ranges, but does not report a two-group estimate or inferential analysis for this primary outcome.
3. Trial Design
The registry describes PHARLAP as a randomized, parallel-group trial with no masking. Participants were assigned to the PHARLAP ventilation group or the control-group ventilation strategy. The sponsor was the Australian and New Zealand Intensive Care Research Centre. The condition listed was acute respiratory distress syndrome, and the phase field is recorded as NA.
The registry lists an enrollment of 115. The reported primary-outcome groups contain 57 participants in the PHARLAP group and 56 in the control group. These are the group counts associated with the posted outcome, not a substitute for details about the analysis population or participant flow. The registry record does not report the method used to generate the random sequence, allocation concealment, eligibility criteria in detail, or the reasons for any exclusions or missing outcome data.
The recorded study start is 2012-10, and primary completion is recorded as 2017-10. The study status is terminated. The reason for termination and any consequences for recruitment or follow-up are not reported in the registry record. Although the brief summary discusses the trial as a larger study, the posted enrollment is 115; the registry record does not provide a complete explanation of the enrollment target or its relationship to the completed enrollment.
The record lists a primary endpoint and several secondary outcomes, including respiratory measures, inflammatory markers, safety events, rescue therapies, mortality, intensive care length of stay and acute kidney injury. It does not provide a detailed statistical analysis plan, analysis populations, or a full account of outcome-level results. Those absences limit how fully the design and analysis can be reconstructed from the registry record.
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
| Stage | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| STARTED | 58 | 57 |
| COMPLETED | 57 | 56 |
| NOT COMPLETED | 1 | 1 |
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.
| Characteristic | Unit | PHARLAP Intervention Arm | Control Group | Total |
|---|---|---|---|---|
| Participants analysed | 58 | 56 | 114 | |
| Age, Continuous | years | 54.2 (SD 14.0) | 53.2 (SD 14.4) | 53.7 (SD 14.2) |
| Sex: Female, Male: Female | Participants | 22 | 26 | 48 |
| Sex: Female, Male: Male | Participants | 36 | 30 | 66 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| APACHE II score | units on a scale | 23.2 (SD 6.8) | 22.3 (SD 7.7) | 22.8 (SD 7.2) |
| BMI | kg/m^2 | 31.3 (SD 10.1) | 30.3 (SD 7.2) | 30.8 (SD 8.6) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Ventilator Free Days at Day 28 Post Randomisation, measured over 28 days post randomisation.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is the number of ventilator-free days at day 28 after randomisation. It counts days from day 1 to day 28 on which a participant was alive and did not receive invasive mechanical ventilation. The registry describes values from 0, meaning no ventilator-free days, to 28, meaning no days on a ventilator. The endpoint therefore brings together survival and freedom from invasive ventilation over a fixed follow-up period.
The registry reports the outcome as a median with an interquartile range. A median describes the center of an outcome distribution without requiring the values to follow a symmetric or normal distribution. The interquartile range describes the middle half of the observed values, giving some information about spread. These summaries can be useful when outcomes are skewed or include many values at the limits of the scale.
The PHARLAP group had a median of 16.0 days, with an interquartile range from 0.0 to 21.0. The control group had a median of 14.5 days, with an interquartile range from 0.0 to 21.5. These summaries describe each group, but do not by themselves quantify the uncertainty in a between-group contrast. The registry record does not report a primary-outcome treatment-effect estimate, confidence interval, or inferential test. A comparison method suited to the outcome distribution could support a group-level inference, but the specific method used is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results are descriptive. The median number of ventilator-free days was 16.0 in the PHARLAP group and 14.5 in the control group. Their interquartile ranges were 0.0 to 21.0 and 0.0 to 21.5, respectively. These summaries show the center and spread of the observed outcome in each group, but they do not establish the size or precision of a treatment effect. No primary-outcome contrast, confidence interval, or p-value is reported in the registry record.
The interquartile ranges are broad and begin at 0.0 in both groups. This indicates that the middle half of each group’s observed values spans a wide range that includes the lower boundary. It also cautions against interpreting the medians as if they represented every participant’s experience. The endpoint combines being alive with not receiving invasive ventilation, so its value reflects more than one aspect of the clinical course. The registry record does not report separate primary-outcome summaries for those components.
The posted secondary comparisons provide estimates for barotrauma and mortality. For barotrauma, the risk-difference estimate for PHARLAP relative to control is 0.017, with a confidence interval from -0.059 to 0.093 and an unadjusted p-value of 0.662. For mortality at day 28, the risk-difference estimate is -0.022, with a confidence interval from -0.183 to 0.139 and an unadjusted p-value of 0.787. Both intervals include zero, so the estimates are compatible with a range of possible group differences, including no difference. The intervals are also wide, indicating limited precision. These secondary estimates do not fill the gap in the primary-outcome analysis.
The registry lists 3 participants with barotrauma in the PHARLAP group and 2 in the control group. It lists 14 deaths in the PHARLAP group and 15 in the control group at day 28. Counts alone do not show the uncertainty in a comparison, which is why the estimates and intervals matter. Conversely, a confidence interval that includes zero should not be treated as proof that the groups are identical: it indicates that the data do not pin down a single precise contrast.
The registry record reports no sponsor analyses for the secondary outcomes and no analysis for the primary outcome. The posted comparisons are unadjusted and should be read as exploratory rather than as a complete, prespecified body of evidence. They do not establish whether any observed difference is attributable to the ventilation strategy, and they do not support a clinical recommendation. The results describe a small set of reported outcomes and leave substantial uncertainty about both the primary contrast and the broader pattern of effects.
9. Statistical Methods Explained
Interpreting a trial result requires separating the way an outcome is summarized from the way groups are compared. The registry reports the primary endpoint as a median and interquartile range, while its posted binary secondary comparisons use risk differences with confidence intervals and unadjusted p-values. These summaries answer different questions and should not be treated as interchangeable.
What does the median and interquartile range describe?
The median is the central value when observations are ordered. The interquartile range runs from the lower quartile to the upper quartile and describes the middle half of the observed values. These summaries are often useful when an outcome is skewed or bounded, because they do not rely on the mean and standard deviation to describe its distribution. For ventilator-free days, the scale is bounded between 0 and 28 in the registry description. A median and interquartile range provide a useful group-level description, but do not directly provide a confidence interval for the difference between groups.
The PHARLAP median is 16.0, with an interquartile range of 0.0 to 21.0. The control median is 14.5, with an interquartile range of 0.0 to 21.5. The overlap between the reported ranges is not itself a formal test of a treatment effect. Nor can a valid uncertainty interval for a median difference be reconstructed from these summaries alone. The registry record does not report the analysis method, an estimate of the between-group contrast, or its uncertainty for the primary endpoint.
What does a risk difference represent?
A risk difference expresses the difference between the proportions of participants with an outcome in two groups. Its direction depends on the order used for the comparison; the posted comparisons label PHARLAP relative to control. A value of zero corresponds to equal proportions. For barotrauma, the posted estimate is 0.017, with a confidence interval from -0.059 to 0.093. For mortality at day 28, the estimate is -0.022, with a confidence interval from -0.183 to 0.139.
A confidence interval represents uncertainty around an estimated contrast under the statistical method used. It is not a range containing a known fixed proportion of individual outcomes, and it does not assign a probability to the true effect after the data have been observed. Both posted risk-difference intervals include zero and span values on either side of it. Their width signals that the estimates are not very precise. A narrow interval would generally indicate greater precision, while a wide interval allows more materially different effects to remain compatible with the data.
How should the p-values be read?
The unadjusted p-values are 0.662 for barotrauma and 0.787 for mortality. A p-value describes how compatible the observed data are with a specified null model under the test assumptions; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. These values do not replace the effect estimates and confidence intervals. The registry does not report the test specifications or a prespecified decision rule for these comparisons, so the p-values should not be read as a complete account of the analysis.
“Unadjusted” also matters because the registry lists multiple outcomes. When many outcomes are examined, chance alone can produce apparently notable findings. Without a reported multiplicity strategy, each unadjusted p-value should be interpreted cautiously and alongside the size and precision of its estimate. The registry record does not report an adjustment for multiple comparisons or identify a hierarchy for secondary outcomes.
Why do endpoint distributions matter?
General statistical principle: outcomes with skewed distributions or a bounded scale may be poorly represented by methods that assume a symmetric distribution. Medians and quantiles offer a descriptive alternative, while a comparison may require a method that accounts for the outcome’s shape, ties, boundaries or other features. The registry record does not report which primary-outcome method was used, and no sponsor-reported primary comparison is posted. It would therefore be inappropriate to infer a particular test or model from the form of the reported summaries.
General statistical principle: over-dispersion occurs when observed variation is greater than a model assumes. If a model underestimates variability, uncertainty intervals may be too narrow and tests may be too optimistic. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model for the primary endpoint or diagnostic checks, so there is no basis for claiming that over-dispersion was assessed or present in this trial.
What do the planning illustrations mean?
The sample-size illustrations are planning calculations based on the observed effects, not a report of the trial’s design justification and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; the effect considered is a stated fraction of the observed effect. The illustrations are conditional on those assumptions and on the estimated effect, which may be imprecise. Smaller assumed effects require larger planning samples in such calculations, but these illustrations do not establish that the trial was designed around those assumptions.
The trial’s sample-size justification, target enrollment rationale, and any formal power calculation are not reported in the registry record. A planning calculation based on an observed estimate should not be used to claim that the completed trial had a particular probability of detecting an effect. Power is a design property tied to assumptions made before observing results; it is not a retrospective measure of whether a study “worked.”
Finally, randomized assignment supports a comparison of groups in principle, but the interpretation also depends on follow-up, analysis populations, missingness, and adherence. Those details are not fully available in the registry record. The posted figures are therefore best read as descriptive summaries and unadjusted secondary comparisons, with their limits made explicit.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity, missing data and analysis populations affect how confidently a trial’s results can be interpreted. The registry record lists a primary endpoint and multiple secondary outcomes, but does not report a prespecified testing hierarchy, a multiplicity adjustment, or a detailed statistical analysis plan. Without that information, it is unclear which comparisons were intended to be confirmatory and how the analyses were meant to account for examining multiple outcomes. The posted secondary p-values are unadjusted, so they should be treated cautiously rather than as a set of definitive tests.
The primary endpoint is described, and group medians and interquartile ranges are posted, but the primary-outcome analysis itself is not reported. The record lists zero reported analyses. It does not state which analysis population was used, whether the analysis followed randomized assignment, how participants with incomplete follow-up were handled, or whether sensitivity analyses were planned. These details matter because exclusions or missing outcomes can affect the comparability created by randomization.
The registry enrollment is 115, while the primary-outcome group counts are 57 and 56. Those figures should not be used to infer why the counts differ from enrollment: participant flow, missing endpoint data, and the relationship between enrollment and analysis populations are not reported in the registry record. It is also not reported whether outcome data were complete for everyone assigned to a group. No assumption about missingness or imputation can be made from the posted summaries.
The record does not report interim analyses, stopping rules, or a reason for the terminated status. It also does not provide an explanation of whether termination affected the planned analyses or follow-up. These omissions do not prove that a particular issue occurred; they leave key safeguards and analysis decisions undocumented in the registry record. As a result, the primary result is limited to descriptive group summaries, and the secondary comparisons lack the context needed for a complete confirmatory interpretation.
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 |
|---|---|---|---|
| PHARLAP Ventilation Group | 23 | 58 | 39.7% |
| Control Group Ventilation | 15 | 56 | 26.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PHARLAP Ventilation Group | 14 of 57 |
| Control Group Ventilation | 17 of 56 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PHARLAP Ventilation Group | 9 of 58 |
| Control Group Ventilation | 4 of 56 |
Most frequent serious adverse event terms
| Event term | Organ system | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|---|
| Severe Hypotension | Cardiac disorders | 20 of 58 | 12 of 56 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 3 of 58 | 3 of 56 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|---|
| refractory acidosis | Metabolism and nutrition disorders | 9 of 58 | 4 of 56 |
Serious events with the highest arm-level rate: severe hypotension (34.5%), pneumothorax (5.4%).
The registry reports serious and other adverse-event counts separately by group. For serious events, 23 participants are listed as affected among 58 at risk in the PHARLAP group, and 15 among 56 at risk in the control group. For other adverse events, the listed counts are 9 among 58 at risk and 4 among 56 at risk, respectively. The record also lists deaths of 14 and 17 in the two groups. These are registry counts; the record does not provide enough detail to determine how event timing, recurrence, severity grading or attribution were handled.
The most frequent serious adverse-event terms listed are Severe Hypotension at 34.5% and Pneumothorax at 5.4%. The registry entry does not make the denominator or event-counting details for these term-specific percentages clear in the information available, so they should be interpreted as reported rather than converted into participant counts or compared with the group-level totals.
These safety figures are descriptive. They do not by themselves establish that an event was caused by a ventilation strategy, and counts from groups of this size can be imprecise. The registry record does not report adjusted safety comparisons or confidence intervals for these adverse-event summaries. Differences in counts should therefore not be treated as proof of a treatment-related safety effect or as evidence that an event risk is the same between groups.
12. What the Result Does, and Does Not, Mean
The posted results establish what the registry reports about the outcome summaries, not a definitive answer about the effect of the PHARLAP ventilation strategy. For the primary endpoint, the registry gives group medians and interquartile ranges for ventilator-free days at day 28. It does not report a primary between-group estimate or its uncertainty. The summaries can describe the observed groups, but they cannot alone support a precise estimate of the difference attributable to assignment.
The secondary comparisons provide estimates for barotrauma and mortality, but their confidence intervals are wide and include zero. This means that the posted data leave considerable uncertainty about the direction and size of those contrasts. The unadjusted p-values are not evidence that the groups are equivalent, and they do not rule out effects that the intervals still allow. Equally, the observed counts do not establish that the intervention caused any difference.
The trial was randomized and parallel-group, but the registry record does not report important details needed to assess the analyses fully, including the analysis populations, missing-data handling, outcome-level methods and a multiplicity plan. The study is marked terminated, but the reason and its implications are not reported in the registry record. These gaps limit interpretation without proving that the trial was conducted improperly.
The registry’s sample-size illustrations are hypothetical planning calculations based on observed effects and stated assumptions. They are not evidence of the trial’s original design assumptions, and they are not observed power. They should not be used to make claims about whether the trial was adequately powered without a documented design rationale and a prespecified effect of interest.
Overall, the record offers descriptive primary-outcome results and selected, unadjusted secondary comparisons, with substantial uncertainty and incomplete analysis context. It does not support a conclusion that one ventilation strategy is better or worse, and it does not establish equivalence. The statistical meaning is narrower: these are the posted group summaries and estimates, interpreted in light of their precision and the information that is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why endpoint summaries and between-group inference are not the same thing. The primary outcome is presented with medians and interquartile ranges, which describe the observed distributions, but no primary contrast or confidence interval is reported. Readers can see the group summaries, yet cannot assess the precision of a direct comparison from the registry entry alone. A treatment-effect estimate with an uncertainty interval would be needed to characterize the primary contrast more directly.
The outcome itself also illustrates a design choice with interpretive consequences. Ventilator-free days combines survival and freedom from invasive ventilation over a defined follow-up period. Such a composite-style measure can capture an important overall aspect of clinical course, but its meaning depends on the endpoint definition and on how outcomes at the limits of the scale are handled in analysis. The registry describes the scale but does not report the primary analysis method or further component-level results.
The secondary results demonstrate why point estimates should be read with their uncertainty. The risk-difference intervals allow a range of possible contrasts, while the unadjusted p-values do not quantify clinical importance or settle the direction of an effect. Multiple listed endpoints further reinforce the need for a reported testing hierarchy and prespecified analysis strategy. Neither is reported in the registry record.
Finally, the planning illustrations make a useful distinction between design assumptions and post hoc calculations. Illustrations based on observed effects can help show how strongly sample-size requirements depend on the effect assumed, but they cannot explain the trial’s original design or provide observed power. The trial’s design justification is not reported in the registry record. In combination, these features show why transparent reporting of the primary comparison, analysis population, missing-data approach and multiplicity plan is essential for turning trial summaries into a well-calibrated statistical conclusion.
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 are specific to the information posted for this trial. The primary outcome is summarized by group, but the registry does not provide a treatment-effect estimate, confidence interval or p-value. That prevents a direct assessment of the precision of the primary comparison. The endpoint description defines ventilator-free days, but the analysis method and the handling of participants who died or had incomplete follow-up are not reported in the registry record.
The registry lists an enrollment of 115, while the primary-outcome arm counts are 57 and 56. Participant flow and the analysis population are not described, so the relationship among enrollment, assignment, follow-up and the reported outcome counts cannot be determined from the record. Missing-data amounts, reasons for missingness, and any imputation or sensitivity analyses are not reported.
The study is marked terminated, but the reason for termination, whether recruitment or follow-up was affected, and any consequences for the planned analyses are not reported in the registry record. The record also does not give the sample-size justification, allocation-concealment method, detailed control protocol, or full statistical analysis plan. These omissions limit assessment of design and analysis decisions; they do not establish that a particular problem occurred.
Only selected secondary results are posted, and the reported comparisons are unadjusted. The registry does not report a multiplicity strategy, endpoint hierarchy, or sponsor-reported analyses for the posted secondary outcomes. The barotrauma and mortality intervals are wide, so their estimates are imprecise. The safety summaries also lack detailed event definitions, timing and attribution information in the record available. These limitations mean the secondary and safety findings should be treated as descriptive and incomplete rather than as a comprehensive account of outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open Lung Ventilation in ARDS: The PHARLAP Trial — NCT01667146.
- Registry record last updated 2024-07-18; status last verified 2024-02.
- Results first posted 2024-07-18.
- 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
The registry record describes NCT01667146 as a randomized, parallel-group, unmasked trial of PHARLAP mechanical ventilation versus control-group mechanical ventilation in acute respiratory distress syndrome. The sponsor is the Australian and New Zealand Intensive Care Research Centre. Enrollment is listed as 115; the recorded start is 2012-10, primary completion is 2017-10, and status is terminated.
The primary endpoint is ventilator-free days at day 28 after randomisation. The posted medians are 16.0 for PHARLAP and 14.5 for control, with interquartile ranges of 0.0 to 21.0 and 0.0 to 21.5. The registry does not report a primary between-group analysis. Selected secondary comparisons concern barotrauma and mortality; both are unadjusted and have confidence intervals that include zero. The record lists additional secondary outcomes, but their results are not reported in the registry record.
The registry does not report the reason for termination, the primary analysis method, analysis populations, missing-data handling, multiplicity procedures, or the sample-size justification. Accordingly, the posted results provide descriptive summaries and selected estimates, with limited information for a complete inferential assessment.