Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome (NCT00467831), a na phase 1, phase 2 study. The primary outcome is Survival at 2 Years.

2. Clinical Question

The study was intended to examine whether the five drugs used together could slow the course of pulmonary fibrosis associated with HPS. The record describes a pilot study rather than a controlled comparison. This distinction matters: without a concurrent comparator, a result in the treated group alone cannot establish how outcomes would have differed without the regimen.

The registry describes a population selected for HPS and serious pulmonary impairment. It does not report participant-level characteristics, such as the severity or duration of disease for those enrolled. The population therefore cannot be characterized beyond the eligibility description and the recorded enrollment.

The clinical question and the available primary outcome are not identical in scope. The stated aim concerns slowing pulmonary fibrosis, while the primary measure is survival after 24 months. The record does not report a primary measure of lung-function change or fibrosis progression. It also does not report a result for the survival measure. Thus, the record identifies what the study set out to assess but does not supply a result that answers the question about the regimen's effect.

3. Trial Design

The registry classifies this study as Phase 1 and Phase 2, single-group, with allocation recorded as NA and no masking. The listed group is the Multi-Drug Regimen. Enrollment is recorded as 3. There is no separate comparator group, so the study does not provide a randomized or concurrent controlled estimate of treatment effect.

The intervention combined pravastatin, losartan, zileuton, N-acetylcysteine and erythromycin. The arm description lists oral doses and schedules for each medicine. The study summary describes starting pravastatin on study day 2 and adding a new medicine every 3 days. It also describes continued treatment and scheduled assessments, including medical history, examination, blood and urine tests, lung-function tests, CT scans and bone-density scans. These are descriptions of the study plan; the registry does not establish that every planned procedure or treatment step was completed for each participant.

The record lists a start date of 2007-04 and a primary completion date of 2012-11. Its current status is terminated. The reason for termination is not reported in the registry record. A planned duration, actual treatment exposure, follow-up completion and participant flow are not reported in enough detail to determine how the study proceeded for each person.

The principal design limitation for interpretation is the absence of a control group. Outcomes in a single group can describe what happened among those enrolled, but they do not separate a possible treatment effect from the course of disease, changes in care, or other influences. In addition, the record does not report a statistical analysis or a primary outcome result. The design and registry information therefore support a description of the study's intent and structure, not an estimate of comparative efficacy.

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:

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 Survival at 2 Years, measured over 24 months.

The primary endpoint is titled Survival at 2 Years. Its stated measure is the number of subjects surviving after 24 months on study. This is a binary outcome at a defined follow-up point: each participant either meets the survival definition at that point or does not. The registry gives the unit as participants and identifies the measure as a number, rather than a rate, time-to-event estimate or measure of lung function.

In general, survival is used as an outcome because it is an important patient-level event and can be described without relying on a change in a laboratory or imaging measure. A survival endpoint at a defined follow-up point is different from time-to-event analysis. The latter uses information about when events occur and may account for differing follow-up; the record does not report such an analysis. The posted endpoint is specifically a count at 24 months.

The registry record does not report the number surviving at 24 months, the number with complete follow-up, or how missing survival status was handled. It also does not report a treatment-effect estimate, confidence interval or hypothesis test for this endpoint. As a result, the endpoint definition is available, but its observed result and statistical precision are not.

Survival also does not directly quantify lung-function change or the progression of fibrosis. The study's stated aim concerns the course of pulmonary fibrosis, but the primary outcome listed in the record is survival. No result for an additional lung-function endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome expressed as a number of participants: survival after 24 months on study. It also records no analyses for this outcome. The record therefore supplies an endpoint definition but not a statistical result. The methods discussion below distinguishes general statistical principles from methods actually documented for this study.

What does a binary outcome count describe?

In general, a binary outcome classifies each participant according to whether a specified event or status is present at the assessment point. Reporting a count can describe how many participants met the definition in the observed group. A count alone does not describe the probability of the outcome in a broader population unless the denominator, outcome ascertainment and analysis are also clear. For this study, the registry defines survival at 24 months as the outcome but does not report the observed survival count or the handling of participants without known status.

A count at a fixed follow-up point is not the same as a time-to-event analysis. A time-to-event method uses the timing of an event and can account for participants who have different lengths of follow-up, subject to its assumptions. The registry does not report a time-to-event estimate, such as a survival curve or hazard ratio. It would be inappropriate to assume that one was calculated simply because the endpoint concerns survival.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among participants who received the intervention. A controlled comparison is needed to directly contrast outcomes under different treatment strategies. Without a comparator, a result can be affected by the natural course of illness, participant selection, concurrent care and other factors. These influences cannot be separated from a treatment effect using a treated-group outcome alone.

This record identifies a single-group model, with allocation recorded as NA and masking as none. It does not list a control arm. No randomized allocation process or blinded outcome assessment is reported. The record consequently does not document a design that could produce a randomized contrast, and it does not report an adjusted analysis intended to address the absence of a comparator.

What does statistical precision mean?

In general, an estimate is more useful when its uncertainty is also described. A confidence interval indicates a range of values compatible with the observed data under the statistical method used; it is not a guarantee that the true value lies within that range. A narrow interval indicates greater precision than a wide interval, while a small dataset often yields imprecise estimates. No confidence interval or survival estimate is reported for this study, so its statistical precision cannot be assessed.

A hypothesis test, when planned and appropriate, assesses compatibility between data and a specified null hypothesis under stated assumptions. A p-value is not a measure of effect size, clinical importance or the probability that a treatment works. The registry lists no analysis for the primary endpoint and reports no p-value. It also does not report a statistical analysis plan, so the testing approach and assumptions are not available.

What does over-dispersion mean in general?

Over-dispersion is a feature of some count-data models: observed variability is greater than the model would expect under its assumed distribution. When present, ignoring it can make standard errors too small and intervals or tests too optimistic. This is a general issue for count outcomes, not a reported finding in this study. The endpoint is a participant count for a binary status, and no count model or dispersion estimate is reported in the registry record.

Do the planning assumptions describe this study's analysis?

The record includes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such assumptions describe a hypothetical planning exercise, not an analysis of the observed trial data. The record says that time-to-event illustrations use a total number of events, while other illustrations use participants per arm. The assumptions do not match the listed single-group design, which has no two-arm allocation. They should not be read as the study's actual sample-size justification or as observed power.

In general, a sample-size calculation depends on an assumed effect, outcome variability or event frequency, significance level, power target and design. A planning output answers a conditional question: what sample size would be required if those assumptions held? It does not show that a study had a particular probability of detecting an effect after the data were collected. The study's own sample-size justification is not reported in the registry record.

Overall, the registry documents the endpoint and broad design classifications but not the statistical analysis, precision estimates, missing-data method, or model specification. Statistical explanations about intervals, testing and count models are general concepts; they are not evidence that those procedures were used for this trial.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Multi-Drug Regimen")
n      <- c(2)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Multi-Drug Regimen  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, a multiplicity adjustment or a strategy for controlling the chance of false-positive findings across multiple tests. Since no primary endpoint result or hypothesis test is reported, multiplicity cannot be assessed from observed analyses. The absence of a reported adjustment does not establish whether one was planned or conducted outside the registry record.

Missing-data handling is also not reported in the registry record. The endpoint definition refers to survival after 24 months, but the record does not state how participants without recorded status at that point were classified or whether follow-up was complete. It does not provide participant-level follow-up, reasons for missing observations or sensitivity analyses. These details matter because an incomplete outcome record can affect the interpretation of a count or estimate.

The analysis population is not reported. The record does not specify whether the primary outcome was to be analyzed among all enrolled participants, those who started the regimen, those who completed treatment, or another defined group. It also does not report exclusions or withdrawals. The enrollment figure alone does not resolve which participants would enter an analysis.

In general, multiplicity concerns arise when multiple outcomes, time points or statistical tests are considered. Missing-data methods and analysis-population definitions likewise affect how results should be read. These are general considerations, not methods documented for this study. With no posted primary result or analysis description, the registry record does not permit an assessment of how these issues were addressed.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory failure (66.7%).

The registry lists safety information for the Multi-Drug Regimen group. For serious adverse events, it records 3 at risk and 2 affected. For other adverse events, it records 3 at risk and 3 affected. Respiratory failure is listed as the top serious adverse event term at 66.7%. These are the safety figures recorded; they are not a comparison with another group.

In general, an adverse event is an event observed during a study, and its occurrence alone does not show that a treatment caused it. Attribution requires information about timing, clinical review and other potential explanations. The registry record does not report attribution, event-level dates, duration, recurrence or participant-level detail. The percentage attached to respiratory failure is listed as a term frequency, but its denominator and calculation basis are not described in the registry record.

The counts for serious and other adverse events should be read as separate registry categories, not combined. The record does not clarify whether participants could appear in both categories or how event terms were grouped. The figures describe recorded events and affected participants; they do not by themselves establish the regimen's safety profile or permit a comparative risk assessment.

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

The registry record establishes that a pilot study of a five-drug regimen was registered for people with HPS and serious pulmonary impairment. It records a single-group design, enrollment of 3, a primary survival endpoint at 24 months and limited safety counts. It also records that the study was terminated. These registry entries describe the study structure and its registry entries, not the outcome of the intervention.

The record does not report how many participants survived after 24 months. It does not give an estimate of the regimen's effect on survival, a confidence interval, a p-value or an analysis comparing the regimen with another treatment. The stated primary endpoint therefore has no posted result to interpret. The record also does not report a primary result for lung-function change or fibrosis progression.

Even a complete outcome count from a single-group study would not, by itself, show what would have happened to comparable participants without the regimen. A control group or another credible comparative design is needed to distinguish a treatment effect from other influences. No such comparator is listed in this trial.

The safety entries report events among participants in the listed group. They do not establish that the regimen caused those events, and no comparative safety estimate is reported. The termination status also cannot be interpreted as evidence of harm or lack of benefit because its reason is not reported in the registry record.

Accordingly, the record supports a description of the study's intent, design, outcome definition and recorded safety information. It does not establish whether the regimen changed survival, pulmonary fibrosis or lung function. It also does not establish that the regimen was ineffective. Those conclusions would require outcome and analysis information that is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition, study design and availability of results all matter to statistical interpretation. The registry names survival after 24 months as the primary outcome, but does not report the observed result. A clearly stated endpoint cannot answer a treatment question without outcome data and an analysis describing the uncertainty around those data.

The single-group design is important because it limits what any observed outcome could establish. A treated-group description can be informative in a pilot study, particularly for documenting feasibility or the experience of participants, but this record does not report detailed feasibility outcomes or participant flow. Without a comparator, observed outcomes cannot be attributed to the regimen through a randomized contrast.

The small recorded enrollment also emphasizes the difference between a study's descriptive information and a stable estimate for a broader population. A count from a small group can be highly sensitive to each participant's outcome. That general principle does not permit an estimate of uncertainty in this case because the primary outcome count is absent.

The record's planning assumptions also show why design-specific interpretation is necessary. An illustration based on equal allocation between two arms does not describe the listed single-group design. Planning calculations are conditional exercises, not observed power and not evidence that the study was designed with a particular justification. The study's own sample-size justification is not reported in the registry record.

For clinical researchers, the central statistical lesson is to separate what a registry records from what an analysis demonstrates. The record identifies an intervention, population and endpoint, but does not post the primary result, analysis methods or reason for termination. Recognizing these gaps avoids treating a study's objective, completion status or safety listing as proof of an efficacy conclusion.

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 record contains limited information for evaluating this trial's conduct and results. It reports enrollment of 3 and identifies a single-group design, but does not provide participant-level characteristics, treatment exposure, adherence, withdrawals or follow-up completion. The reason for the terminated status is not reported in the registry record.

The primary endpoint is defined, but its observed result is absent. The registry does not report the number surviving after 24 months, outcome completeness, a statistical estimate or uncertainty interval. It also does not report a statistical analysis plan, missing-data method, analysis population or inferential analysis. Thus, neither the primary result nor the approach used to estimate it can be evaluated.

No comparator is listed, and the study is not randomized. Even if the outcome count were available, the design would not provide a direct randomized estimate of the regimen's effect relative to another strategy. The record also does not report a primary outcome measuring lung-function change or fibrosis progression, despite the study's stated aim of examining disease course.

The safety listing is also limited. It gives affected-participant counts and a leading serious event term, but does not provide timing, attribution, event duration, detailed severity, participant-level overlap or the basis for the listed percentage. The available figures therefore cannot establish causality or support a comparative safety assessment.

Finally, the planning assumptions describe a two-arm illustration, while the registered design is single-group. The illustration should not be taken as evidence of the trial's own design rationale. The registry record does not report the study's sample-size justification or explain the termination.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome — NCT00467831.
• Registry record last updated 2013-08-02; status last verified 2013-06.
• Results first posted 2013-08-02.
• 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

This Phase 1 and Phase 2 pilot study evaluated a planned multi-drug regimen for severe pulmonary fibrosis in Hermansky-Pudlak Syndrome. The listed drugs were pravastatin, losartan, zileuton, N-acetylcysteine and erythromycin. The intended population was people with HPS and serious loss of lung function due to pulmonary fibrosis.

The registry records a single-group design, no masking, allocation marked NA, enrollment of 3 and terminated status. It lists survival after 24 months as the primary outcome, measured as the number of participants surviving. No primary outcome result or statistical analysis is reported. The reason for termination is not reported in the registry record.

Safety entries list 2 participants affected by serious adverse events and 3 affected by other adverse events in the Multi-Drug Regimen group. Respiratory failure is the top serious adverse event term at 66.7%. These entries do not establish causation or comparative risk. Overall, the record describes the study and some safety information but does not provide the data needed to assess a treatment effect.