A Study to Evaluate the Potential Role of Mesenchymal Stem Cells in the Treatment of Idiopathic Pulmonary Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Potential Role of Mesenchymal Stem Cells in the Treatment of Idiopathic Pulmonary Fibrosis (NCT01385644), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Demonstrated Acute Adverse Events Following Infusion.

2. Clinical Question

3. Trial Design

This was a Phase I study of placental MSC infusions for idiopathic pulmonary fibrosis. The registry lists the study as completed, with a start date of 2010-10 and a primary completion date of 2013-05. Enrollment was 8. The record describes the allocation as nonrandomized, masking as none, and the model as single-group.

Two dose descriptions are listed: 1*10^6 MSC / kg and 2*10^6 MSC / kg. The primary outcome population states that data from 8 participants were analyzed, 4 from each group. Although the record lists these dose groups, it does not describe a randomized comparison or a separate control intervention. The groups therefore cannot be treated as equivalent to randomized treatment and control arms. The method used to assign participants to dose groups is not reported in the registry record.

The primary objective was to establish the feasibility and safety of infusions from related or unrelated HLA identical or HLA mismatched donors. Secondary objectives concerned changes in lung function, 6 minute walk distance, gas exchange, and radiological appearance over a six month evaluation period. Listed secondary outcomes include percentage change in FVC, 6 minute walk distance, and DLCO compared with baseline. Numerical secondary-outcome results are not reported in the registry record.

Other design details, including eligibility criteria, the infusion schedule, dose-selection rationale, and the statistical analysis plan, are not reported in the registry record. The record does not establish how the two dose groups were formed or whether the study was intended to support a formal comparison between them.

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: All patients meet all inclusion criteria and none of the exclusion criteria.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data from 8 participants was analyzed. (4 from each group)

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.

Population: All participants meet all inclusion criteria and none of the exclusion criteria

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Demonstrated Acute Adverse Events Following Infusion, measured over 4 hours post-infusion.

The primary outcome is the number of participants who demonstrated acute adverse events following infusion, assessed at 4 hours post-infusion. The event definition includes development of anaphylaxis and/or a 25% increase or decrease from baseline in hemodynamic measurements. The outcome is a participant count, rather than a measure of the severity or duration of an event.

This endpoint fits the stated primary objective of establishing the feasibility and safety of MSC infusions. In general, a prespecified observation window and event definition help make safety monitoring more consistent: readers can see which events count and when they were assessed. The registry record does not report further details about event adjudication, the specific hemodynamic measurements, or whether events were independently reviewed.

The record identifies the analyzed population as 8 participants, with 4 from each dose group, but does not report the primary endpoint result. It therefore does not establish how many participants met the acute-event definition. The separate adverse-event entries do not supply a numerical result for this specifically defined primary outcome, and should not be substituted for it.

The secondary outcomes address changes from baseline in FVC, 6 minute walk distance, and DLCO. The stated secondary objectives also include gas exchange and radiological appearance. Results for these outcomes, and their analysis details, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a nonrandomized study with a single-group model and no masking. It lists two dose groups, but does not describe a randomized allocation process or a concurrent control intervention. This distinction matters statistically: an observed difference between the dose groups is not automatically attributable to dose when assignment was not randomized. The record does not report how participants entered either group or whether relevant baseline characteristics were comparable.

What does the primary outcome count?

The primary outcome is a count of participants meeting a defined acute adverse-event criterion at 4 hours post-infusion. It is not a count of all events, an event rate over person-time, or a measure of long-term safety. The definition includes anaphylaxis and/or a 25% increase or decrease from baseline in hemodynamic measurements. The registry record does not report how those measurements were selected, how the event definition was applied when information was incomplete, or whether an independent group reviewed events.

For a binary outcome recorded for each participant, a basic summary can describe how many participants experienced the event and how many were assessed. In general, such counts are easier to interpret when accompanied by an uncertainty interval. With sparse observations, however, estimates and intervals can be unstable or broad. The registry record does not report a numerical result for the defined primary outcome, an uncertainty interval, or a formal statistical comparison.

Why does nonrandomized allocation matter?

Random allocation is intended to make groups comparable, on average, with respect to both measured and unmeasured characteristics. Without it, differences between groups may be associated with factors other than the assigned dose. This concern applies even when group sizes are the same. Here, the registry record identifies the study as nonrandomized and warns that the arms are not a like-for-like control comparison. Any contrast between the dose groups should therefore be treated as descriptive rather than as a causal estimate of dose effect.

Masking can also affect measurement and reporting, particularly when outcomes require judgment. The record states that masking was none. It does not report whether the acute-event criteria were assessed by blinded reviewers or whether outcome ascertainment used additional safeguards. No further inference about these procedures is possible from the registry record.

What can a confidence interval or test tell a reader?

In general, a confidence interval conveys uncertainty around an estimated quantity under the statistical model used. It does not establish that a result is clinically important, nor does it remove biases caused by nonrandom allocation, missing data, or measurement choices. A p-value, in general, assesses how compatible the observed data are with a specified null model; it is not the probability that a treatment effect is true. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record, so no such inference can be made from the posted primary-outcome information.

For sparse binary data, standard large-sample approximations may perform poorly. Exact or other methods designed for small samples can sometimes be considered, but the registry record does not report which method, if any, was used for the outcome. It also does not report an adjusted analysis. No method should be assumed simply because the outcome is binary.

How should planning calculations be read?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is stated as a fraction of the observed effect. These are planning assumptions, not evidence that a future study would achieve a particular result. Sample-size illustrations are not observed power, and they do not repair limitations in the original design. The registry record does not report the trial's own sample-size justification or design rationale.

The record also distinguishes planning outputs for time-to-event outcomes, expressed as total events, from other outcomes, expressed as participants per arm. No time-to-event primary outcome is identified in the registry record described for this study. The numerical planning results themselves are not reported in the registry record. General interpretation of any planning illustration depends on its assumed effect, allocation, significance level, and approximation; it should not be confused with a result observed in this trial.

What analysis details remain unknown?

The record lists 4 outcome measures and 0 analyses. This describes what is listed in the registry record; it does not establish that no analysis was conducted. The statistical plan, model specifications, handling of repeated measurements, and multiplicity procedures are not reported in the registry record. Nor are confidence intervals, p-values, or adjusted estimates for the primary outcome reported. These omissions limit the ability to reconstruct or evaluate the analysis.

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("1*10^6 MSC / kg", "2*10^6 MSC / kg")
n      <- c(4, 4)
events <- c(0, 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  1*10^6 MSC / kg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  2*10^6 MSC / kg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures, including the primary acute adverse-event outcome and secondary measures of change in FVC, 6 minute walk distance, and DLCO. The stated secondary objectives also refer to gas exchange and radiological appearance. The record lists 0 analyses, but that does not show that no analyses were conducted; it means the registry record does not provide listed analysis details for interpretation.

When a study examines multiple outcomes or multiple time points, the chance of at least one apparently unusual result can increase. In general, a prespecified hierarchy or multiplicity adjustment can help readers understand how multiple statistical questions were handled. Whether such a strategy was used, which outcomes were designated primary at analysis, and whether there were additional analyses are not reported in the registry record. No adjustment should be presumed.

The primary outcome population states that data from 8 participants were analyzed, with 4 from each group. The record does not describe missing-data frequency for other outcomes, reasons for missing observations, imputation, or sensitivity analyses. It also does not report whether all enrolled participants were included in every analysis or define an intention-to-treat or per-protocol population. Thus, the reported primary population count cannot establish how missing data were handled across outcomes.

Interim analyses, stopping rules, and monitoring procedures are not reported in the registry record. Without these details, readers cannot assess whether analysis timing or selective reporting affected the posted results.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small bowel obstruction (25.0%).

The adverse-event entries list 1 participant with a serious adverse event among 4 at risk in the 1*10^6 MSC / kg group, and 0 among 4 at risk in the 2*10^6 MSC / kg group. These are descriptive counts. They do not establish that the doses differ in safety, particularly because allocation was nonrandomized and the record says the arms are not a like-for-like control comparison.

The record lists Small Bowel Obstruction as a serious adverse-event term with 25.0%. The denominator and the precise context for this percentage are not reported in the registry record, so it should not be interpreted as a participant-level risk or compared directly with the group counts. The serious-event entries also do not show whether the listed participants had other events, or how event timing and relatedness were assessed.

The primary endpoint has a specific acute definition and a 4 hours post-infusion assessment time. The serious-event summaries are not interchangeable with that endpoint: the registry record does not report the primary endpoint result. Death counts are not reported in the registry record. The adverse-event information is therefore limited to the listed entries and should be read as descriptive safety reporting, not as a comparative safety estimate.

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

The study addresses an early-phase question: whether placental MSC infusions could be assessed for feasibility and safety in people with idiopathic pulmonary fibrosis. The registry lists two dose groups and describes a primary acute adverse-event outcome. It also identifies secondary aims involving lung function, walking distance, gas exchange, and radiological appearance.

The posted record does not report the numerical result for the primary outcome or the numerical results for the listed secondary outcomes. Consequently, it cannot establish how many participants met the acute-event definition or whether the measured secondary outcomes changed. The separate adverse-event counts provide limited descriptive information, but they are not a substitute for the primary outcome result.

The design also limits interpretation of any apparent difference between dose groups. Allocation was nonrandomized, masking was absent, and the record cautions that the arms are not a like-for-like control comparison. This prevents a clean causal interpretation of group differences. The small analyzed population further means that the observed counts cannot provide a precise characterization of uncommon events.

In general, an early-phase study can describe feasibility and identify observations that may warrant further study, but its findings do not by themselves establish comparative efficacy or safety. The registry record does not report a randomized control comparison, a formal estimate with uncertainty, or the primary endpoint result. Accordingly, the available information supports a narrow account of the study design and listed adverse-event entries, not a conclusion about whether the intervention improves IPF outcomes or about its overall safety.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the limits of interpreting early-phase, nonrandomized data. The registry identifies a Phase I study with two dose descriptions, a small analyzed population, and a stated acute safety endpoint. Those features make clear why the design and reporting context matter as much as the observed counts.

When allocation is nonrandomized, group comparisons can be affected by differences in who received each dose. Equal group sizes do not remove that concern. The registry itself cautions that the arms are not a like-for-like control comparison, so a dose contrast should not be treated as a randomized estimate. This distinction is important when reading any descriptive figures.

The record also illustrates the value of complete outcome reporting. It defines the primary event and assessment time, but does not report the primary outcome count. Without that result, readers cannot judge the main stated safety outcome, calculate an effect estimate, or assess its precision. Listed secondary objectives likewise do not provide evidence of observed changes when numerical results are absent.

In general, confidence intervals and clear analysis methods help convey uncertainty, while transparent reporting of missing data and outcome selection helps readers assess potential bias. These details are not reported in the registry record. Their absence does not establish that analyses were not performed, but it constrains what can be independently interpreted.

The study therefore matters as a reminder to distinguish an objective from a result, a count from a comparative estimate, and a planning illustration from observed evidence. Its registry record permits a careful description of the design and selected safety entries, while leaving key results and analysis details unavailable.

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.

Several limitations specific to this study constrain interpretation. The registry record describes a nonrandomized allocation and explicitly warns that the dose groups are not a like-for-like control comparison. The method used to assign participants to dose groups is not reported in the registry record. Differences between the groups cannot therefore be attributed to dose alone.

The analyzed population is small: the primary outcome description reports data from 8 participants, with 4 from each group. Sparse observations limit the precision of descriptive estimates and make uncommon events difficult to characterize. The record does not report confidence intervals for the primary outcome, and the primary outcome result itself is not reported.

Masking was none. The record does not describe blinded outcome assessment, event adjudication, or other procedures that might reduce measurement or reporting bias. The acute primary outcome is assessed at 4 hours post-infusion, so it does not by itself describe later safety. The separate serious-event entries do not fill that gap or establish longer-term risk.

Results for secondary outcomes are not reported in the registry record, despite the stated objectives concerning lung function, 6 minute walk distance, gas exchange, and radiological appearance over a six month evaluation period. Eligibility criteria, baseline characteristics, dose assignment procedures, missing-data handling, analysis methods, and multiplicity procedures are also not reported in the registry record.

Finally, the registry does not report the study's own sample-size justification or a complete statistical analysis plan. These limitations mean readers cannot determine whether all planned outcomes were reported, how uncertainty was quantified, or how the observed safety entries relate to the full intended analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Potential Role of Mesenchymal Stem Cells in the Treatment of Idiopathic Pulmonary Fibrosis — NCT01385644.
• Registry record last updated 2015-12-29; status last verified 2015-11.
• Results first posted 2015-12-29.
• 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 completed Phase I study evaluated placental MSC infusions for idiopathic pulmonary fibrosis. The registry records nonrandomized allocation, no masking, a single-group model, and enrollment of 8. Two dose groups are listed: 1*10^6 MSC / kg and 2*10^6 MSC / kg. The primary outcome counts participants with acute adverse events at 4 hours post-infusion, using a definition that includes anaphylaxis and/or a 25% change from baseline in hemodynamic measurements.

The primary outcome population states that data from 8 participants were analyzed, with 4 from each group, but the numerical primary outcome result is not reported in the registry record. The adverse-event entries list 1 serious adverse-event participant in the lower-dose group and 0 in the higher-dose group; the registry cautions that the groups are not a like-for-like control comparison. Numerical secondary-outcome results and key analysis details are not reported in the registry record.