Stress CMR Perfusion Imaging in the United States (SPINS) Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Stress CMR Perfusion Imaging in the United States (SPINS) Study (NCT03192891), a registered phase not stated study. The primary outcome is Cardiovascular Mortality.

2. Clinical Question

The registry’s rationale describes earlier single-center evidence on diagnostic accuracy and clinical event rates, while noting limitations in the broader prognostic evidence. SPINS was registered as a Society for Cardiovascular Magnetic Resonance registry study intended to contribute large-scale, multicenter, real-world evidence. That rationale describes why such a registry was considered useful; it is not itself a result demonstrating the performance of stress CMR in this cohort. The record does not establish a causal comparison between imaging strategies or report the diagnostic accuracy of the test in this study.

3. Trial Design

SPINS is identified as a registry study sponsored by the Society for Cardiovascular Magnetic Resonance. Its registered intervention is stress cardiac magnetic resonance perfusion imaging, classified as a diagnostic test. The registry lists myocardial ischemia as the condition and reports enrollment of 2349. The study status is completed. The recorded start date is 2016-12-01, and the primary completion date is 2019-11-30.

The record describes a retrospective assessment of outcomes from the date of the first index cardiac magnetic resonance imaging study, dated Jan-2008, through at least 4 years following the last index CMR or through study completion in Nov-2019. The outcome timeframe also includes the phrase “Between 12/1/2016 to 11/30/2019.” These dates describe the registry’s stated assessment period; the record does not explain further how the different date references relate to individual participants.

The registry’s summary presents the study as addressing a need for large-scale, multicenter, real-world evidence. The number and characteristics of participating sites are not reported in the registry record. Nor does the record specify a randomized allocation process. Allocation is not stated, and the registry cautions that arms are not a like-for-like control comparison. Accordingly, the study should be read as a registry assessment, not as a randomized comparison of stress CMR against a control strategy.

Cardiovascular mortality is the primary outcome. Listed secondary outcomes include cardiac hospitalizations, late coronary arterial bypass surgery, and incremental cost-effectiveness ratio in dollar per quality-adjusted life year. The record lists 5 outcome measures, but it does not report a primary outcome analysis or results for the listed secondary outcomes. It also does not provide a detailed account of recruitment, follow-up completeness, or participant-level analysis procedures.

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: Inclusion Criteria: all of the following at time of imaging: 1. male or female at age 35-85 years, 2. presence of either symptoms suspicious of ischemia, or abnormal electrocardiography with a suspicion of coronary artery disease 3. at least 2 of the following risk factors: patient age \> 50 for male, 60 for female, diabetes, hypertension, hypercholesterolemia, family history of premature coronary disease, Body mass index\> 30, peripheral artery disease, any hx of coronary artery disease.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: total cohort at risk

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 Cardiovascular Mortality, measured over Between 12/1/2016 to 11/30/2019, the outcome were retrospectively assessed from the date of the first index cardiac magnetic resonance imaging study (Jan-2008) to at least 4 years following the last index CMR or through study completion (Nov-2019)..

The primary endpoint is cardiovascular mortality, measured as the count of participants. The registry defines it as patient mortality due to cardiac or vascular events and identifies the population as the total cohort at risk. This endpoint captures deaths attributed to cardiovascular causes rather than all-cause mortality, as described in the record.

Mortality is a clinically consequential outcome and can be used in prognostic research to describe events observed after an index test. In general, counting participants with an event gives an outcome measure that can be interpreted as a number of people experiencing the defined event within the population and assessment period. The count alone, however, does not describe when events occurred, how follow-up differed between participants, or the precision of a rate or comparative effect estimate.

The stated assessment was retrospective, extending from the first index cardiac magnetic resonance imaging study to at least 4 years after the last index CMR or through study completion. The registry record does not provide a primary endpoint result, a time-to-event estimate, a confidence interval, or a comparison against a control group. It also does not report the specific procedures used to determine whether a death met the cardiovascular definition. The separate safety field lists 255 deaths, but the record does not establish that this count is the reported result for the primary cardiovascular mortality endpoint. Those entries should not be conflated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a count of participants with cardiovascular mortality. This is a binary event outcome at the participant level: a participant either meets the endpoint definition or does not, within the outcome assessment. The record defines the event as mortality due to cardiac or vascular events. It does not report an analyzed event count for this endpoint, however, so the endpoint definition should not be mistaken for a result.

What does a confidence interval express?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate, while a wider interval indicates more uncertainty. The registry record does not report a confidence interval for cardiovascular mortality, or a confidence interval for any comparative primary outcome estimate. There is therefore no interval-based precision assessment available for the primary endpoint.

Why does the comparison matter?

In general, interpreting a treatment or diagnostic strategy’s effect requires a clearly defined contrast. A randomized comparison can help make groups comparable by design, while observational comparisons may require careful adjustment for differences between groups. The record does not describe randomized allocation; allocation is not stated. It also cautions that the arms are not a like-for-like control comparison. No adjusted analysis or model specification is reported. Thus, even if outcome counts were available, the registry entries do not provide a basis for attributing a difference to the imaging strategy.

How should the planning illustrations be read?

The stated sample-size assumptions describe planning illustrations computed from the observed effect, not the study’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event tables, the stated convention is to give the total number of events; for other tables, it is participants per arm. These are planning assumptions, not observed findings or evidence that the study had a particular probability of detecting an effect. The registry record does not report a numerical planning result in the study details, and no such result should be read as observed power.

In general, a sample-size calculation depends on choices such as the target effect, significance level, allocation, and statistical model. Changing those assumptions can change the planning requirement. An illustration based on an observed effect is especially dependent on how that effect was estimated; it does not replace a prospective justification for the actual study design. No prospective sample-size justification is reported in the registry record.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability is greater than expected under a model’s assumptions. If it is not accounted for, standard errors and confidence intervals can be too small, making results appear more precise than they are. This is a general consideration for count data, not a reported feature of SPINS. The registry record does not identify a count model, report a dispersion estimate, or describe an over-dispersion assessment. The primary endpoint itself is described as a participant count, not as a reported rate model.

Time-to-event methods can be useful when the timing of events and differing follow-up durations matter. In general, those methods use information about when participants experience an event or are last known to be event-free. The registry’s outcome timeframe refers to retrospective follow-up through at least 4 years after the last index CMR or through study completion, but it does not report a time-to-event model, an event-time estimate, or handling of censoring. The timeframe alone does not establish that such a model was used.

The registry record lists 0 analyses. No primary outcome test, regression model, adjustment set, test statistic, p-value, or confidence interval is reported. Consequently, the available record supports a description of the planned endpoint and the general meaning of statistical methods, but not a reconstruction or evaluation of an unreported 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("Stress CMR and Stable Chest Pain")
n      <- c(2294)
events <- c(74)
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  Stress CMR and Stable Chest Pain  2294  74  3.2  2.5  4.0  2.6  4.0  2.6  4.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists cardiovascular mortality as the primary outcome and names cardiac hospitalizations, late coronary arterial bypass surgery, and incremental cost-effectiveness ratio in dollar per quality-adjusted life year among the secondary outcomes. It reports 5 outcome measures overall. The record does not describe a multiplicity plan: it does not state whether testing across outcomes was adjusted, whether outcomes were ordered hierarchically, or how any family of statistical tests was defined. No outcome analyses are listed, so the consequences of any multiplicity approach cannot be evaluated from the posted record.

Missing-data methods are not reported in the registry record. The record does not describe how incomplete follow-up, unavailable outcome status, or missing covariates were handled, and it does not report the extent of missingness. Absence of a description is not evidence that data were complete or that a particular method was used.

The primary population is described as the total cohort at risk. The record does not provide a detailed definition of that analysis population, eligibility rules for inclusion in each analysis, or an account of exclusions. It reports enrollment of 2349, while the safety record gives 2294 at risk for the listed group; the relationship between these counts is not explained. No intention-to-treat or per-protocol population is described, and no analysis population should be inferred from those labels.

These omissions limit assessment of how the reported cohort would translate into endpoint-specific denominators and how robust results might be to missing information or multiple comparisons. Since no primary analysis is posted, the impact of these issues on an effect estimate cannot be quantified.

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 safety record lists one group, Stress CMR and Stable Chest Pain, with 2294 participants at risk. It reports 0 serious adverse events and 0 other adverse events in the corresponding event fields, and separately lists 255 deaths. These entries should be read according to their distinct fields rather than combined into a single measure. In particular, 0 serious adverse events does not mean that no deaths were recorded: the same safety record separately lists deaths.

The registry does not give serious adverse event terms, since no top serious terms are listed. It also does not explain the relationship between the death count and the primary cardiovascular mortality endpoint. The primary endpoint is defined as mortality due to cardiac or vascular events, whereas the safety field is simply labeled deaths. Without a stated linkage or cause-specific breakdown, the 255 deaths cannot be assumed to represent cardiovascular deaths or the primary endpoint result.

These entries do not provide event rates, comparative safety estimates, or information about timing, severity beyond the serious-event field, or attribution. The registry record also cautions that the arms are not a like-for-like control comparison. Therefore, the figures describe the posted safety fields but do not establish a relative safety effect or explain why the event fields contain the reported values.

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

The registry record establishes that SPINS was a completed registry study of stress CMR perfusion imaging, with cardiovascular mortality specified as the primary endpoint. It also gives the enrollment figure, the retrospective outcome timeframe, and selected safety fields. These details describe the study and the information recorded; they are not, by themselves, an analysis of whether the test predicts outcomes or changes outcomes.

The primary endpoint result is not reported in the registry record. There is no primary estimate, uncertainty interval, or comparison result to quantify. The 255 deaths listed in the safety record should not be substituted for a cardiovascular mortality result, because the record does not state that they are the same outcome. Likewise, the 0 serious and 0 other adverse-event entries do not imply that no deaths occurred.

The registry’s stated rationale emphasizes the need for broader real-world evidence beyond earlier studies described as limited in size, setting, and design. That motivation does not establish that this registry resolves those limitations. The number and characteristics of sites are not reported in the registry record, and the record does not provide an analysis showing how representative the cohort was.

In general, a registry can help describe clinical outcomes in recorded practice. But an observational record without a clearly comparable control group cannot, on its own, establish a causal effect. The registry cautions that its arms are not a like-for-like control comparison, and allocation is not stated. No conclusion that stress CMR improved outcomes, worsened outcomes, or had a particular diagnostic performance follows from the information reported.

The appropriate interpretation is therefore descriptive and bounded: the record identifies the study question and outcome framework, but does not report the main outcome analysis required to answer the prognostic question quantitatively.

14. Why This Trial Matters Statistically

SPINS is statistically relevant because it frames a diagnostic imaging question in terms of longer-term clinical outcomes rather than diagnostic accuracy alone. The registry’s stated rationale is that prior evidence had limitations related to study size, single-center settings, academic-center predominance, and lack of real-world design. The registry was intended to contribute large-scale, multicenter, real-world evidence. Those statements explain the motivation for the study, but the registry entries do not establish how fully the study achieved that aim.

The endpoint also highlights a distinction important in clinical research: a test’s diagnostic performance and its association with later outcomes are different questions. Cardiovascular mortality was selected as the primary endpoint, while cardiac hospitalizations, late coronary arterial bypass surgery, and a cost-effectiveness measure were listed as secondary outcomes. The record does not post the analyses needed to evaluate those questions.

For biostatistical interpretation, the study’s nonrandomized registry context matters. The record does not state an allocation process and explicitly warns that arms are not a like-for-like control comparison. That limits causal interpretation and underscores why descriptions of cohort outcomes should be separated from claims about effects of a diagnostic strategy.

The record also illustrates the importance of transparent reporting: definitions, denominators, missing-data handling, statistical models, uncertainty, and multiplicity decisions all shape interpretation. Several of these details are not reported in the registry record, and no analyses are listed. Consequently, the statistical importance lies as much in identifying what cannot be concluded as in understanding the intended endpoint and study rationale.

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 registry record leaves important aspects of the study design and analysis unspecified. Although its rationale describes a large-scale, multicenter, real-world registry, the number of sites and their characteristics are not reported. The recruitment process, eligibility details, and cohort composition are also not described beyond the condition and the total enrollment figure.

The record does not describe a randomized allocation process, and allocation is not stated. It cautions that the arms are not a like-for-like control comparison. Without a suitable comparison and a reported adjustment strategy, causal interpretation is limited. No analysis is listed, so there is no reported method to evaluate confounding, follow-up differences, or other sources of bias.

The outcome timeframe has retrospective elements, including the date of the first index CMR and follow-up through at least 4 years after the last index CMR or through study completion. The record does not explain how follow-up duration was handled in analysis, how cardiovascular cause of death was determined, or whether censoring occurred. It also does not connect the 255 deaths in the safety field to the primary cardiovascular mortality endpoint.

Missing-data handling, analysis populations, multiplicity procedures, and the primary outcome result are not reported in the registry record. The enrollment figure of 2349 and the safety group’s 2294 participants at risk are both recorded, but their relationship is not explained. These reporting gaps prevent assessment of endpoint-specific denominators, precision, and robustness. They do not show that a particular bias or data problem occurred; they mean the record does not provide enough information to evaluate those possibilities.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Stress CMR Perfusion Imaging in the United States (SPINS) Study — NCT03192891.
• Registry record last updated 2025-12-30; status last verified 2025-01.
• Results first posted 2025-01-31.
• 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

SPINS is a completed Society for Cardiovascular Magnetic Resonance registry study of stress CMR perfusion imaging, listed for myocardial ischemia. The record reports enrollment of 2349, a start date of 2016-12-01, and primary completion on 2019-11-30. Cardiovascular mortality, defined as mortality due to cardiac or vascular events, is the primary endpoint. The stated assessment was retrospective from the first index CMR through at least 4 years after the last index CMR or through study completion.

Secondary outcomes include cardiac hospitalizations, late coronary arterial bypass surgery, and incremental cost-effectiveness ratio in dollar per quality-adjusted life year. The safety record lists 2294 at risk, 0 serious adverse events, 0 other adverse events, and 255 deaths for Stress CMR and Stable Chest Pain. The primary outcome result and statistical analyses are not reported in the registry record. Allocation is not stated, and the record cautions that arms are not a like-for-like control comparison.