Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis (NCT03793439), a na phase 1 study. The primary outcome is Number of Participants With 50% Reduction in Corticosteroid Requirement.

2. Clinical Question

3. Trial Design

This completed Phase 1 study is a hypothesis-generating pilot of tofacitinib in corticosteroid-dependent pulmonary sarcoidosis. Oregon Health and Science University is listed as the sponsor. The registry record lists a start date of 2019-05-15, a primary completion date of 2020-06-24, and enrollment of 5 participants.

The design is single-group and open-label, with no masking and allocation recorded as NA. All participants are described as receiving tofacitinib 5mg twice daily from week 0 to week 16. A corticosteroid taper is described as starting at week 16, alongside spirometry, RNA sequencing and laboratory evaluations. A one-year open-label extension is also listed among the interventions, but the registry record does not describe whether participants entered that extension or how it related to the primary endpoint.

The study's stated purpose is to determine whether further research is warranted to assess tofacitinib as a steroid-sparing treatment. That purpose is exploratory: the design does not include a concurrent control group, so it cannot separate changes during treatment from changes that might occur over time or for other reasons. The registry record does not report a protocol, a sample-size justification, or a detailed statistical analysis plan. It also does not report outcome results or analysis populations. The single-group pilot design and the small enrollment are important context when interpreting any outcome information; in this record, the primary endpoint result itself is not reported.

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

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: 5 participants were analyzed for baseline characteristics. The overall number of baseline participants did not differ from the number assigned to arms and entire study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With 50% Reduction in Corticosteroid Requirement, measured over 16 weeks.

The primary endpoint counts participants who achieve a 50% reduction in corticosteroid requirement by week 16 while avoiding a specified decline in pulmonary function. The definition requires the reduction in corticosteroid requirement and no decline greater than 15% in FVC, FEV1 or DLCO relative to baseline. It is therefore a combined clinical criterion: a participant must meet the steroid-reduction target and the lung-function condition to count as meeting the endpoint.

A steroid-reduction endpoint is relevant to the study's stated steroid-sparing question because it measures a change in corticosteroid requirement rather than only a change in a laboratory measure. The pulmonary-function condition is included to distinguish a reduction in steroid use accompanied by preserved measured lung function from a reduction accompanied by a substantial decline in those measures. This is a description of the endpoint's role, not evidence that participants achieved it.

The registry record specifies a participant count and a 16-week timeframe, but does not report the number meeting the endpoint. It also does not report the participant-level corticosteroid changes or pulmonary-function measurements underlying the classification. Without those results, the endpoint definition can be explained, but the frequency of endpoint achievement and its precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives the primary endpoint as a count of participants meeting a defined criterion. A count is a direct description of how many people in the study meet the endpoint, rather than a measurement of the size of an average change. The criterion combines a corticosteroid-reduction target with a pulmonary-function safeguard. The timepoint is week 16.

What a participant count can show

For a binary outcome, each participant is classified as meeting or not meeting the endpoint according to its definition. The total count describes the observed study group. If an accompanying proportion or interval estimate is available, it can help readers understand how uncertain an estimate of the underlying frequency may be. General statistical principle: a confidence interval represents a range of values compatible with the observed data under the method's assumptions; it is not a guarantee that the true value lies in that range. The registry record does not report a primary endpoint count or an interval estimate, so neither the observed frequency nor its precision can be evaluated from this record.

Why the study design matters

A single-group study has no concurrent control group. The study can describe what happened among its participants, but it cannot use a between-group contrast to account for changes that might occur without the intervention. Open-label status means masking is absent; participants and study personnel are not described as blinded to treatment. For an endpoint involving corticosteroid requirement, decisions and assessments may be affected by study procedures and clinical judgment. This is a general consideration, not a claim that bias occurred in this study. The registry record does not report procedures intended to reduce or assess such influences.

Allocation is recorded as NA, which is consistent with the listed single-group model rather than a randomized allocation between treatment groups. There is no like-for-like treatment comparison to interpret. Therefore, concepts such as a randomized treatment contrast or an adjusted between-arm estimate do not apply to the design as registered.

Interpreting pulmonary-function criteria

The endpoint uses FVC, FEV1 and DLCO relative to baseline, with a decline greater than 15% serving as the stated pulmonary-function threshold. Combining this safeguard with steroid reduction makes the outcome more specific than steroid reduction alone: a participant must satisfy both parts of the definition. General statistical principle: combining conditions can change how frequently an endpoint is met, because a participant who satisfies one condition but not the other does not meet the combined endpoint. The registry record does not provide separate results for the steroid-reduction and pulmonary-function components.

Precision and small pilot studies

Precision describes how much uncertainty surrounds an estimate. With enrollment of 5, the study has little information for estimating a stable frequency beyond its own participants. This does not make the study's observations meaningless; it means that any observed count would need cautious interpretation, especially when considering other patients or settings. General statistical principle: small samples tend to yield less precise estimates, and a small change in the observed count can have a large influence on an estimated frequency. No confidence interval or precision analysis is reported in the registry record.

The record does not report a sample-size justification or a planned power calculation. Any planning illustration based on an observed effect would be a hypothetical design aid, not observed power and not evidence that the study was adequately sized. Because the endpoint result is absent, the registry record also does not support a planning interpretation based on an observed primary effect.

Multiplicity and analysis choices

The record lists a primary endpoint and a secondary RNA-sequencing outcome. When a study evaluates multiple outcomes or multiple analyses, the chance of at least one apparently notable result can increase if those tests are considered together without an appropriate strategy. General statistical principle: multiplicity methods address the interpretation of repeated statistical testing. The registry record does not report a multiplicity strategy, specific tests, model choices, or an analysis plan. It would be inappropriate to infer that adjustment was or was not performed beyond what the record states.

Likewise, the record does not describe an intention-to-treat population, a per-protocol population, handling of missing observations, or rules for classifying participants with unavailable measurements. These choices matter because the endpoint requires both corticosteroid and pulmonary-function information. Without reporting on missing data and analysis populations, readers cannot determine how incomplete measurements would have affected endpoint classification.

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("Open Label")
n      <- c(5)
events <- c(3)
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  Open Label  5  3  60.0  14.7  94.7  23.1  88.2  22.3  88.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and a secondary outcome based on RNA sequencing, and it reports two outcome measures overall. It does not report a multiplicity strategy, planned hypothesis tests, or a detailed statistical analysis plan. General statistical principle: evaluating several outcomes or analyses can complicate interpretation because repeated testing can increase the chance of apparently noteworthy findings. The record does not allow assessment of whether or how that issue was addressed.

Missing-data procedures are not reported in the registry record. The primary endpoint depends on both corticosteroid requirement and pulmonary-function measurements relative to baseline. The record does not specify how participants with missing steroid or lung-function information would be classified, whether measurements would be imputed, or what follow-up was available for each participant.

Analysis populations are also not reported in the registry record. It does not state whether the primary endpoint was analyzed among all enrolled participants or under another population definition. Enrollment was 5, but the record does not provide a participant flow, an analyzed denominator, or reasons for any exclusions or missing observations. The outcome findings needed to see how these issues affected the reported result are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: peripheral motor neuropathy (20.0%), skin infection (20.0%).

The open-label safety group has 5 participants at risk. The registry record lists serious adverse events in 2 participants, other adverse events in 4 participants, and 0 deaths. It also lists peripheral motor neuropathy and skin infection among the serious adverse-event terms, each reported as 20.0%.

These are descriptive counts from a small group, not comparative safety estimates. The registry record does not report event timing, duration, outcomes, participant-level overlap between categories, or attribution to tofacitinib. The term-specific percentages should be read as registry-recorded frequencies, not as evidence that the treatment caused those events. The absence of deaths in this group does not establish the absence of other safety concerns, and the counts alone cannot characterize risk in a broader population.

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

The record documents a completed Phase 1, open-label pilot in which 5 participants were enrolled and the primary question concerned a 50% reduction in corticosteroid requirement by week 16 without a specified pulmonary-function decline. It also records limited adverse-event counts. These registry entries describe the study's design and its registered outcome framework.

The primary endpoint result is not reported in the registry record. Therefore, the record does not show how many participants met the endpoint, whether the endpoint was achieved by any participant, or how precisely its frequency could be estimated. The secondary RNA-sequencing result is also not reported. Completion status is not a substitute for outcome data.

The single-group, open-label design cannot provide a randomized comparison with another treatment or with no study treatment. Any change observed within the group would not, by itself, establish that tofacitinib caused that change. The small enrollment further limits the amount of information available for estimating outcomes beyond these participants. These are design and precision considerations, not judgments about treatment efficacy.

The registry record's stated aim is to determine whether further research is warranted. Without reported endpoint results, it is not possible to assess that aim from the registered outcomes. The safety counts can be described, but they do not establish causality or characterize safety in a broader population. The appropriate interpretation is limited to what the record documents: the pilot design, the endpoint definition, the enrolled group size, and the recorded safety figures, while the main outcome findings remain unreported.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a pilot can frame a clinically relevant endpoint while leaving important interpretive questions dependent on complete outcome reporting. The primary outcome is not a laboratory marker alone: it requires a corticosteroid reduction alongside a pulmonary-function condition. That combination makes the endpoint's definition central to understanding what a reported count would mean.

The single-group design also illustrates a key distinction between describing an outcome and estimating a treatment effect. A count among participants receiving open-label treatment can describe what occurred in that group. Without a concurrent control group, it cannot establish how the outcome compares with what would have happened under another condition. A pilot can be hypothesis-generating, but a treatment effect cannot be inferred from its design alone.

Enrollment of 5 emphasizes the importance of precision and restraint in interpretation. Small pilot groups can help motivate later research, but estimates based on few participants are uncertain and may not generalize. Here, the registry record does not report the primary outcome count, so even the observed endpoint frequency cannot be assessed.

The case also demonstrates why registration status and outcome reporting are distinct. The study is marked completed, yet the primary and secondary findings are not reported in the registry record. For statistical interpretation, a clearly specified endpoint is useful, but it must be accompanied by results, analysis details and information about missing data and analysis populations to support a complete reading.

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 main limitation for interpreting this trial from its registry record is that the primary endpoint result is not reported. The record therefore does not show the number of participants who achieved the required corticosteroid reduction without the specified pulmonary-function decline. The secondary RNA-sequencing result is also not reported.

The study is a single-group, open-label pilot with enrollment of 5 participants and no concurrent control group. It cannot provide a randomized treatment comparison, and its small enrollment limits precision and generalizability. The registry record does not provide a fuller description of participant characteristics or eligibility criteria, so the population represented by the enrolled group cannot be characterized in detail.

The record does not report a statistical analysis plan, sample-size justification, analysis population, missing-data procedures, or multiplicity strategy. It also does not provide participant flow or separate results for the corticosteroid-reduction and pulmonary-function components of the combined endpoint. These omissions make it difficult to evaluate the analysis choices that would shape interpretation even if an endpoint count were available.

The listed one-year open-label extension is not accompanied by results or details about participant entry in the registry record. Safety reporting is also limited: counts and two serious-event terms are listed, but timing, outcomes, attribution and participant-level overlap are not reported. These limitations restrict the conclusions that can be drawn from the registry record; they do not establish what the unreported results would show.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis — NCT03793439.
• Registry record last updated 2022-02-18; status last verified 2021-12.
• Results first posted 2022-02-18.
• 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.

19. Record Summary

NCT03793439 is a completed Phase 1, open-label, single-group pilot sponsored by Oregon Health and Science University. It enrolled 5 participants and studied tofacitinib in corticosteroid-dependent pulmonary sarcoidosis. The listed primary endpoint is the number of participants with a 50% reduction in corticosteroid requirement by week 16 without a decline greater than 15% in FVC, FEV1 or DLCO relative to baseline.

The registry record does not report the primary or secondary outcome results, a statistical analysis plan, missing-data procedures, or analysis populations. Safety figures list 2 participants with serious adverse events, 4 with other adverse events, and 0 deaths; peripheral motor neuropathy and skin infection are each listed at 20.0%. The single-group design does not provide a randomized comparison.