Imaging Biomarkers in Crohn's Associated Spondyloarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imaging Biomarkers in Crohn's Associated Spondyloarthritis (NCT02709694), a registered phase not stated study. The primary outcome is Number of Participants With MRI Positivity- Global Assessment Positive.

2. Clinical Question

3. Trial Design

NCT02709694, titled “Imaging Biomarkers in Crohn's Associated Spondyloarthritis,” is listed as completed. The record names Hospital for Special Surgery, New York, as sponsor, gives a start date of 2016-04 and a primary completion date of 2019-01, and lists enrollment of 33. Crohn's disease and spondyloarthritis are the conditions named in the registry.

The registry lists “No intervention” and does not describe a randomized treatment comparison. Allocation is not stated. The study is therefore not represented in the record as a trial comparing assigned interventions, and the data should not be interpreted as estimating a treatment effect. The primary endpoint is an assessment of MRI positivity at one study visit.

MRI scans were independently read and scored by 2 expert rheumatologists and 1 newly trained rheumatologist reader. Readers were blinded to clinical information. They evaluated bone marrow edema and structural lesions, including erosion, fat metaplasia, backfill and ankylosis. The MRI global assessment used the contextual signature of active and structural sacroiliac-joint lesions; positivity required agreement of at least 2 of 3 readers.

The registry lists secondary outcomes covering axial spondyloarthritis based on European Spondyloarthropathy Study Group guidelines, current and historical peripheral arthritis, BASDAI, BASMI, ASDAS-CRP, CRP, and duration of Crohn's disease. It does not report results for these outcomes in the information described by the record. Further details about recruitment, follow-up beyond the stated study visit, protocol procedures, or statistical planning 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

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 Number of Participants With MRI Positivity- Global Assessment Positive, measured over one study visit.

The primary endpoint is the number of participants whose MRI was classified as positive for sacroiliitis by global assessment. It is a count outcome: the endpoint asks how many participants met the specified positivity rule, rather than measuring a change from baseline or comparing treatment groups. The assessment was based on MRI evidence considered in context, including active bone marrow edema and structural lesions such as erosion, fat metaplasia, backfill and ankylosis.

Three rheumatologist readers independently assessed the scans, with two described as experts and one as newly trained. They were blinded to clinical information. The endpoint counted an MRI as positive when at least 2 of 3 readers agreed. This majority rule provides a consistent operational definition for translating reader assessments into a participant-level classification. It also means that the endpoint reflects the global judgment and agreement rule, not a separately reported estimate for each lesion or reader.

In general, a binary classification can make an imaging question easier to interpret as a frequency: positive versus not positive under the chosen definition. It can also conceal variation in the degree or location of imaging findings. The registry record does not report the observed number classified as positive, the number classified as negative, or an uncertainty interval. Thus, although the endpoint and its reading rule are described, its observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being counted?

The primary endpoint is a count of participants classified as MRI-positive for sacroiliitis. The classification is binary at the participant level: each assessed scan meets or does not meet the stated global-assessment rule. The registry describes the endpoint as “Number of Participants With MRI Positivity- Global Assessment Positive” and gives its timeframe as one study visit. The observed count is not reported in the registry record.

In general, a count endpoint answers a frequency question. Its interpretation depends on knowing both the number meeting the criterion and the population in which the criterion was assessed. A count by itself does not convey the frequency unless the relevant denominator is also known. The record lists enrollment of 33 but does not report the primary analysis denominator or whether all enrolled participants had evaluable MRI assessments. No calculation based on enrollment alone should be substituted for an observed endpoint result.

How does the MRI classification work?

The record says MRIs were independently read and scored by 2 expert rheumatologists and 1 newly trained rheumatologist reader, blinded to clinical information. Scoring considered bone marrow edema and structural lesions, including erosion, fat metaplasia, backfill and ankylosis. The method was described as validated and originally derived from the Spondyloarthritis Research Consortium of Canada SIJ module. The global assessment considered the contextual signature of active and structural sacroiliac-joint lesions. A scan was defined as positive when at least 2 of 3 readers agreed.

In general, blinding is intended to limit influence from information outside the image assessment. Independent reading allows each reader to evaluate the scan without relying on another reader's classification. A majority rule offers a prespecified way to produce a participant-level classification when readers may differ. These features describe the assessment process; they do not, on their own, show how reproducible the readings were. The registry record does not report individual reader classifications or a quantitative measure of inter-reader agreement.

What can a confidence interval tell a reader?

In general, a confidence interval expresses uncertainty around an estimated quantity. For a proportion or count-based frequency, it indicates how much uncertainty remains about the underlying frequency given the observed data and the method used to calculate the interval. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. An interval does not remove limitations in how participants were selected or how outcomes were measured.

The registry record does not report a primary endpoint estimate or confidence interval. It is therefore not possible to describe the precision of the MRI positivity result. Nor does the record state a model, interval method, or hypothesis test for the primary outcome. Any statistical method beyond the documented reading rule is not reported in the registry record.

What does over-dispersion mean in general?

Over-dispersion is a general issue for some statistical models of counts. It occurs when the observed variability is greater than the model assumes. If a model fails to account for that extra variability, uncertainty estimates may be too small and tests may appear more decisive than the data warrant. Whether over-dispersion is relevant depends on the outcome scale and analysis model. The registry record does not report a model for the primary count, so it does not establish whether over-dispersion was assessed or relevant to the analysis.

What do the planning assumptions represent?

In general, sample-size calculations are planning tools that describe the amount of information a hypothetical design might need under stated assumptions. They are not observed results and do not measure the probability that a completed study produced a statistically significant finding. The planning description associated with the record specifies 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. For time-to-event calculations, it describes total events; for other calculations, it describes participants per arm.

Those assumptions do not describe a randomized comparison in this registry: “No intervention” is listed and allocation is not stated. The registry record does not report a design rationale, sample-size justification, or the observed effect needed to interpret such planning illustrations. Therefore, any planning calculation should be understood only under its stated hypothetical assumptions, not as an observed-power analysis or evidence that the study was designed around a particular effect. The sponsor's own statistical analysis, if any, is not reported in 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("Any Back Pain", "No Back Pain")
n      <- c(19, 14)
events <- c(4, 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  Any Back Pain  19  4  21.1  6.1  45.6  8.5  43.3  8.7  43.7
ARM  No Back Pain  14  0  0.0  0.0  23.2  0.0  21.5  0.2  21.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 55 outcome measures and 0 analyses. It names multiple secondary outcomes, including axial spondyloarthritis under European Spondyloarthropathy Study Group guidelines, current and historical peripheral arthritis, BASDAI, BASMI, ASDAS-CRP, CRP, and duration of Crohn's disease. Results for these measures are not reported in the registry record.

When a study examines multiple outcomes, multiplicity can matter because repeated statistical testing can increase the chance of at least one apparently notable result arising by chance. In general, a statistical plan may address this by defining a primary outcome, specifying a hierarchy, or adjusting inference across tests. The registry record does not report whether any such approach was used. The existence of a named primary endpoint does not establish how other outcomes were handled in analysis.

The record does not report a missing-data method, the number of participants with evaluable MRI, or how incomplete assessments were treated. It also does not identify an analysis population for the primary endpoint or state whether the reported enrollment and analysis populations differed. These details affect the denominator and interpretation of a frequency outcome, so they should not be inferred from enrollment alone.

No statistical analysis plan, prespecified hypothesis-testing procedure, or imputation approach is reported in the registry record. The listed count of 0 analyses should not be expanded into a claim about analyses that may have been conducted outside the registry; it describes what the registry lists. With no endpoint results or analysis details reported, neither multiplicity control nor the consequences of missing data can be evaluated.

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.

The registry lists an adverse-event group titled “Adult Subjects With Crohn's Disease.” In that group, the record gives 33 participants at risk for serious adverse events and 0 affected by serious adverse events. It also gives 33 at risk for other adverse events and 0 affected, with 0 deaths. These are the event figures recorded in the registry.

In general, “at risk” identifies the group considered for the adverse-event summary, while “affected” is the number recorded with the event category. A zero in the posted results means no events of that category are listed for the stated group in this registry record. It does not establish that an event could not have occurred, that every possible event was captured, or that the intervention was safe: no intervention is listed, and registry reporting has limits.

The record does not list serious adverse-event terms, and it does not provide detail on collection procedures, observation duration for safety, or the handling of participants with incomplete follow-up. These figures should therefore be read as the registry's reported counts, not as a comprehensive safety assessment or a comparison between treatments.

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

The scientific question is whether MRI can identify sacroiliac-joint inflammation or structural changes in people with Crohn's disease, including in the context of possible spondyloarthritis. The record describes a global MRI assessment that considered active and structural lesions and used agreement among readers to define positivity. This is useful for understanding how the study operationalized its imaging question.

The registry record does not report the number of participants classified as MRI-positive. It therefore does not establish the frequency of positive MRI assessments in this study. It also does not report an effect estimate, uncertainty interval, or analysis result for the primary endpoint. An endpoint definition is not itself an outcome finding. The lack of a posted count cannot be interpreted as zero positive scans.

The study is not listed as a treatment comparison. It has no intervention in the registry, and allocation is not stated. Thus, the record cannot show that a treatment caused an imaging change or altered a clinical outcome. The primary outcome is an imaging classification at one study visit, not a change over time or a comparison of assigned treatments.

Nor does the endpoint definition establish that MRI positivity corresponds to symptoms, future disease, or patient-reported impact. The registry rationale discusses questions about MRI findings and clinical symptoms, and secondary measures include disease activity and patient-reported instruments, but their results are not reported. The association between imaging and those outcomes cannot be assessed from the record.

In general, imaging findings can be studied as markers of disease processes, but clinical meaning depends on the observed data and their relationship to relevant clinical outcomes. Here, the registry provides a reading method and lists outcome domains, but not the results needed to assess those relationships. The appropriate interpretation is consequently limited to what was planned to be measured and how the primary imaging classification was defined.

14. Why This Trial Matters Statistically

This study is statistically notable for treating MRI interpretation as a defined measurement process rather than an unstructured judgment. The record specifies independent reading, blinding to clinical information, the imaging features considered, and a participant-level majority rule for positivity. These details help readers understand what the primary endpoint means and what information was intended to contribute to the classification.

The majority rule is important because imaging interpretation can involve reader disagreement. In general, a prespecified agreement rule makes the transformation from individual reads to an endpoint more transparent. At the same time, the final classification can depend on that rule. Without reader-level results or an agreement statistic, the registry record does not show how often the readers differed or how robust the classification was to reader variation.

The clinical motivation spans imaging and clinical outcomes: the record raises questions about sacroiliitis, axial inflammation, symptoms, and patient-reported measures. The listed secondary outcomes include several clinical and laboratory domains. Statistically, linking these domains would require reported results and a clear analysis strategy. Neither is available in the registry record, so the relationships cannot be evaluated.

The record also illustrates why an outcome definition and an outcome result are distinct. Although the primary outcome is described in detail, its observed count and uncertainty are not reported. The record lists 55 outcome measures and 0 analyses, making it especially important not to infer findings from the list of planned or named measures. The study's statistical contribution cannot be judged from its measurement definitions alone; the results and analysis details would be needed to determine the evidence and its precision.

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 most direct limitation for interpreting this study is that the registry record does not report the primary endpoint count. Without the observed result, denominator, and uncertainty estimate, the frequency and precision of MRI positivity cannot be assessed. Enrollment of 33 does not establish the number with evaluable scans or the primary analysis population.

The record describes a reader-based classification but does not report reader-specific assessments, disagreement frequency, or an inter-reader reliability statistic. The majority rule is explicit, yet the reliability of the classification cannot be quantified from the reported information. The record also does not give further MRI acquisition details or specify how incomplete or technically inadequate scans were handled.

Clinical and secondary-outcome results are not reported in the registry record. This prevents assessment of how imaging findings relate to axial spondyloarthritis classification, peripheral arthritis, disease activity, CRP, or Crohn's disease duration. The registry lists 55 outcome measures and 0 analyses, but does not describe multiplicity handling, a statistical analysis plan, or missing-data procedures.

The registry lists no intervention and does not state allocation. Therefore, the study should not be interpreted as a randomized treatment comparison, and the record cannot support a causal treatment claim. The record also describes the primary assessment at one study visit, so it does not supply evidence about change over time. Further recruitment, eligibility, and follow-up details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Imaging Biomarkers in Crohn's Associated Spondyloarthritis — NCT02709694.
• Registry record last updated 2021-10-25; status last verified 2021-09.
• Results first posted 2021-10-25.
• 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

NCT02709694, “Imaging Biomarkers in Crohn's Associated Spondyloarthritis,” is listed as completed and sponsored by Hospital for Special Surgery, New York. The registry gives a start date of 2016-04, a primary completion date of 2019-01, and enrollment of 33. Crohn's disease and spondyloarthritis are the listed conditions.

No intervention is listed. The primary outcome is the number of participants with MRI positivity for sacroiliitis by global assessment at one study visit. MRIs were independently read by 2 expert rheumatologists and 1 newly trained rheumatologist reader, blinded to clinical information. Positivity required agreement of at least 2 of 3 readers.

The registry does not report the primary outcome result or statistical analyses. It lists 55 outcome measures and 0 analyses. In the adverse-event listing, 0 serious events, 0 other adverse events, and 0 deaths are recorded for the group described. The record does not report the analysis population, missing-data approach, multiplicity handling, or statistical analysis plan.