Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus (NCT00504348), a na phase 2, phase 3 study. The primary outcome is Overall Survival.

2. Clinical Question

The clinical question concerns survival and safety in a specific population with inflammatory muscle disease and interstitial pneumonitis. The registry lists progression-free survival as a secondary outcome, but does not report its result. The study is open-label, with no masking, and its record lists phases 2 and 3. These features describe how the investigation was organized; they do not establish whether the treatment changed survival or how its outcomes compare with those of historical controls.

3. Trial Design

The registry describes an open-label clinical trial of tacrolimus combined with corticosteroids in people with polymyositis or dermatomyositis and interstitial pneumonitis. It identifies a prospective investigation group and classifies the model as single-group. Allocation is recorded as NA, and masking as none. Enrollment is listed as 25. The sponsor is Tokyo Medical and Dental University, and the phases are listed as phase 2 and phase 3.

The treatment description specifies that tacrolimus was to be initiated at 0.075mg/kg/day, adjusted to maintain whole blood trough levels between 5 and 10 ng/mL for 52 weeks. All participants were to receive glucocorticoids, with starting doses equivalent to between 0.6 and 1.0 mg/kg/day of prednisolone. The registry description of the glucocorticoid regimen is truncated, so further details are not reported in the registry record.

The official title describes comparison with corticosteroid-treated historical controls. That is not the same design as a randomized comparison with a concurrent control group. The registry specifically flags that the study is not a randomized comparison and that its arms are not a like-for-like control comparison. Details about how the historical controls were selected, measured, or analyzed are not reported in the registry record.

The study began in 2007-07 and its primary completion date is 2011-01; its status is completed. These dates describe the registry timeline, not the availability of outcome estimates. The record lists overall survival as the primary outcome at 52 weeks and progression-free survival as a secondary outcome. It records 2 outcome measures and 0 analyses. An analysis plan, details of participant follow-up, and the methods used to compare any historical controls are not reported in 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

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 Overall Survival, measured over 52 weeks.

Overall survival is the primary endpoint. The registry defines it as the time from the start of protocol treatment until death due to any cause. Participants who were still alive were censored at the date they were last known to be alive. The stated timeframe is 52 weeks, and the outcome is described as a percentage of participants.

Overall survival is used in clinical research because it captures death from any cause rather than requiring attribution to a particular disease or treatment. General statistical explanation: when a participant is alive at the end of observed follow-up, or is no longer observed before an event, the exact time to death is unknown. Censoring records the period during which survival is known without treating the participant as though death occurred at the last contact. The interpretation of a survival estimate therefore depends on how follow-up and censoring were handled.

The registry identifies a 95% confidence interval as the measure of uncertainty for this outcome. General statistical explanation: a confidence interval conveys the precision of an estimate under the method used to calculate it; a wider interval indicates greater uncertainty. However, neither the overall-survival percentage nor its confidence interval is reported in the registry record. The record therefore does not allow readers to assess the estimated survival level or its precision.

Progression-free survival is listed as a secondary outcome, but its definition, estimate, and uncertainty are not reported in the registry record. No inference about that outcome can be drawn from its listing alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies a percentage outcome, a 95% confidence interval, and the definition of overall survival, but does not report the estimate, interval limits, or analysis details. The following concepts are general explanations rather than claims about methods used in this study.

What does a confidence interval convey?

General: a confidence interval describes uncertainty around an estimated quantity under the calculation method and assumptions used. For an overall-survival percentage, the estimate communicates the observed survival level at the stated timeframe, while the interval communicates how precisely that level has been estimated. An interval should be read together with its estimate, not as a separate result. Because neither is reported in the registry record, the precision of the primary outcome cannot be assessed.

The registry specifies a 95% confidence interval as the dispersion measure for overall survival. It does not name the method used to calculate that interval. Different methods can make different assumptions about follow-up and the pattern of censoring. It would therefore be inappropriate to assume a particular interval calculation from the endpoint description alone.

How does censoring matter?

General: in time-to-event analysis, censoring indicates that an event time is not observed during the available follow-up. A participant may be known to be alive through the last recorded contact without the record containing a later status. The registry says participants still alive were censored at the date they were last known to be alive. This defines the recorded endpoint rule, but the record does not describe the amount of follow-up for each participant, losses to follow-up, or checks made to establish vital status.

Censoring does not mean that a participant experienced the event at the censoring time. It also does not, by itself, guarantee an unbiased estimate. General statistical interpretation depends on whether the censoring process is appropriately handled and on assumptions about how censoring relates to the outcome. The registry does not report enough analysis detail to evaluate those assumptions.

What can be inferred from a single-group design?

General: an outcome measured in a single group can describe what happened among participants who received the study regimen. Without a suitable concurrent comparison group, it cannot by itself distinguish a treatment effect from the course of the disease, other care, or differences in the characteristics of the people studied. A historical control may offer context, but interpretation depends on how those controls were selected and whether their outcome definitions, follow-up, and care are comparable.

The registry's official title refers to corticosteroid-treated historical controls, while its model is listed as single-group and its record cautions that the arms are not a like-for-like control comparison. Control-group characteristics and comparative analysis methods are not reported in the registry record. No comparative effect estimate or significance test is reported. A treatment effect should not be inferred from the existence of a historical comparison in the title.

How should the sample-size illustrations be read?

General: a sample-size calculation asks what study size might be needed under specified assumptions about an effect, significance level, allocation, and statistical method. It is a planning exercise, not an outcome of the completed study. The registry describes an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also says that the effect to detect is a stated fraction of an observed effect. The corresponding illustration values are not reported in the registry record.

The registry explicitly characterizes these calculations as planning illustrations computed from an observed effect, not as the trial's own design. They should not be presented as observed power. The record does not report the original study's sample-size justification, assumptions, or statistical plan. In particular, the presence of a planning illustration does not show that the study was designed prospectively around that calculation.

What does the posted analysis record establish?

The registry lists 2 outcome measures and 0 analyses. It provides no reported overall-survival estimate, no confidence interval limits, and no progression-free survival result. The record does not identify statistical tests, adjustment methods, or a prespecified analysis plan. These omissions limit the scope of statistical interpretation: the endpoint definitions can be described, but the numerical outcome findings and the methods behind them cannot be independently assessed from the registry record.

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("Prospective Investigation Group")
n      <- c(25)
events <- c(22)
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  Prospective Investigation Group  25  22  88.0  68.8  97.5  70.0  95.8  69.8  95.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists overall survival as the primary outcome and progression-free survival as a secondary outcome. It records 2 outcome measures and 0 analyses. It does not report a statistical analysis plan, a hierarchy among outcomes, or any method for handling multiple comparisons. Whether multiplicity was considered is not reported in the registry record.

General statistical explanation: when an analysis examines multiple outcomes or makes multiple statistical comparisons, the chance of finding an apparently notable result can change. An analysis plan may specify how outcomes are prioritized or how uncertainty is handled. Without that plan and the analyses, readers cannot determine whether any multiplicity adjustment was intended or needed. No adjustment should be assumed.

The primary endpoint description specifies censoring for participants still alive, but the registry does not report the number or pattern of censored observations, losses to follow-up, or missing endpoint information. How missing data were handled beyond the stated censoring rule is not reported in the registry record. The record also does not describe an analysis population, such as whether outcome analyses included all enrolled participants or a defined subset.

These gaps matter because the reported endpoint and the population used to estimate it determine what a result would represent. Since the primary estimate and its confidence interval are not reported, and analysis-population details are absent, readers cannot assess the impact of missing observations or determine whether the outcome analysis followed an intention-to-treat or other approach.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: interstitial lung disease (24.0%), zoster (4.0%), nocardiosis (4.0%), cytomegalovirus pneumonitis (4.0%), pneumocystis jiroveci pneumonia (4.0%).

The registry's safety record lists a prospective investigation group with 25 participants at risk for other adverse events and 25 affected. For serious adverse events, it lists 25 at risk and 11 affected. The record also lists 4 deaths. These are posted counts; the registry does not report event timing, participant-level overlap among event categories, or details of attribution.

The serious adverse-event terms include interstitial lung disease at 24.0%, and zoster, nocardiosis, cytomegalovirus pneumonitis, Pneumocystis jiroveci pneumonia, and thrombocytopenia at 4.0% each. These percentages describe the listed event terms; they should not be treated as proof that an event was caused by treatment. The registry record does not report a comparative safety analysis or a detailed account of how adverse events were collected and attributed.

General statistical explanation: adverse-event counts and percentages are descriptive unless the record also provides a suitable comparison and analysis. Event categories may overlap, and a participant may experience more than one event. The posted figures therefore should not be added or interpreted as a count of distinct participants. A comparison with historical controls would require details about how events were defined and collected in both groups; those details are not reported in the registry record.

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

The record describes a study of tacrolimus with corticosteroids in people with polymyositis or dermatomyositis and interstitial pneumonitis. It specifies overall survival at 52 weeks as the primary outcome and provides a definition based on death from any cause, with censoring for participants known to be alive at last contact. It also lists progression-free survival as a secondary outcome and includes adverse-event counts and terms.

Those descriptions do not supply the main primary result. The overall-survival percentage and its 95% confidence interval are not reported in the registry record. The progression-free survival result and statistical analyses are also not reported. Without those outcome results, it is not possible to describe the observed survival level, the precision of the estimate, or a comparative treatment effect from this record.

The study is open-label and single-group, with no masking and allocation recorded as NA. Although its official title refers to corticosteroid-treated historical controls, the registry cautions that the comparison is not randomized and is not like-for-like. This design can provide information about outcomes observed in the prospective group, but differences from historical controls may reflect factors other than treatment. The registry does not report enough information to assess the comparability of those controls.

The posted safety counts and listed event terms are descriptive. They do not establish whether the events were caused by tacrolimus, corticosteroids, the underlying disease, or other factors. Nor do they provide a comparative safety estimate.

General statistical explanation: a finding of no reported result is not evidence of no effect. It means the registry record does not contain the result needed to assess the effect. Similarly, a sample-size illustration does not establish the study's observed power or demonstrate that the study was adequately designed for its primary question. Conclusions should remain limited to the trial's recorded design, endpoint definitions, and posted safety information.

14. Why This Trial Matters Statistically

This trial is statistically important to interpret with care because its stated clinical question involves a combination treatment and a comparison against historical controls, while the registry classifies the prospective study as single-group. The design label and the registry's caution that the groups are not a like-for-like comparison make clear that the study should not be read as a randomized treatment comparison.

The primary endpoint is overall survival at 52 weeks, a clinically direct time-to-event outcome. Its definition identifies the event and the censoring rule, and the registry names a 95% confidence interval as the dispersion measure. Yet the survival estimate and interval are not reported in the registry record. This illustrates an important statistical distinction: specifying an outcome and its uncertainty measure is not the same as reporting an interpretable result.

The record also illustrates why comparator quality matters. Historical controls may provide context, but statistical adjustment cannot necessarily remove bias from differences in participant selection, care, follow-up, or measurement. The registry does not describe the historical group or comparative methods sufficiently to judge those issues. The design therefore limits causal interpretation, independently of whether a numerical outcome estimate might be available elsewhere.

Finally, the sample-size assumptions are explicitly described as planning illustrations rather than the trial's own design. Keeping planning calculations separate from observed findings avoids treating a hypothetical calculation as evidence of precision or power achieved in the completed study. With outcome analyses unreported, the registry supports a description of the study design and safety entries, but not an assessment of the primary survival result.

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 primary limitation for statistical interpretation is that the registry does not report the overall-survival estimate or its 95% confidence interval. It also does not report the progression-free survival result, despite listing it as a secondary outcome. As a result, the stated outcomes cannot be evaluated for magnitude or precision from the registry record.

The study is identified as open-label and single-group, and allocation is recorded as NA. The title refers to corticosteroid-treated historical controls, but the record cautions that the comparison is not randomized and the groups are not like-for-like. Selection and time-related differences could affect such a comparison. Information about the historical controls, their baseline characteristics, outcome definitions, follow-up, and analysis is not reported in the registry record.

The registry lists 0 analyses and does not report the statistical analysis plan, specific survival-analysis methods, missing-data procedures, analysis population, or handling of multiple outcomes. It gives a censoring definition, but information about follow-up completeness and censoring patterns is not reported. These omissions prevent assessment of whether the analysis addressed the assumptions relevant to its endpoint.

The safety record lists adverse-event counts and terms, but details of event timing, attribution, ascertainment, and comparative analysis are not reported. The treatment description is also truncated after the glucocorticoid starting-dose information, so further regimen details are not reported in the registry record. The registry's sample-size assumptions are for planning illustrations, not the trial's own design; the original sample-size justification is not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus — NCT00504348.
• Registry record last updated 2020-03-24; status last verified 2020-03.
• Results first posted 2020-03-24.
• 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

The registry record describes an open-label, single-group study of tacrolimus with corticosteroids in polymyositis or dermatomyositis patients with interstitial pneumonitis. It lists phases 2 and 3, enrollment of 25, and a completed status. The study began in 2007-07, with primary completion in 2011-01.

Tacrolimus was to start at 0.075mg/kg/day, adjusted to maintain whole blood trough levels between 5 and 10 ng/mL for 52 weeks. Glucocorticoid starting doses were equivalent to between 0.6 and 1.0 mg/kg/day of prednisolone. The primary outcome is overall survival at 52 weeks; progression-free survival is listed as secondary.

The registry does not report the primary survival estimate, its 95% confidence interval, the secondary outcome result, or statistical analyses. It describes a historical-control comparison in the title but cautions that it is not randomized or like-for-like. Safety entries include 11 affected by serious adverse events, 25 affected by other adverse events, and 4 deaths; listed serious-event terms include interstitial lung disease at 24.0% and several terms at 4.0%.