SIMT Stereotactic Radiosurgery Outcomes Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SIMT Stereotactic Radiosurgery Outcomes Study (NCT02886572), a na na study. The primary outcome is Number of Participants Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score.

2. Clinical Question

The clinical question is therefore descriptive: among the participants in this single-arm study, how many outlived the survival expectation associated with their GPA score? The registry describes the study purpose as assessing the effectiveness and efficiency of SIMT SRS in participants with four or more brain metastases. However, the registered primary outcome is specifically a count based on survival relative to GPA prediction. The record does not give the number meeting that outcome, or a comparison with participants receiving another treatment or no treatment.

The GPA incorporates age, Karnofsky Performance Score, extracranial metastases, and number of brain metastases. The registry describes each factor as receiving a score of 0, 0.5, or 1.0, with the GPA calculated as their sum. It gives GPA categories and corresponding median survival values as background for the prediction. These reference values explain the basis of the outcome; they are not results observed in this study. Since the registry record does not report the primary outcome count, it does not establish how participants’ observed survival compared with those GPA expectations.

3. Trial Design

This was a prospective, single-arm study at Duke University, listed as completed. The registry record gives an enrollment of 40 and describes the study population as adults with brain metastases. The official title narrows the target population to adults with 4 or more brain metastases. The study began on 2017-01-25, and its primary completion date is listed as 2021-04-30. Phase is listed as NA.

All participants in the treatment arm were assigned stereotactic radiosurgery. The arm description says the treatment followed RTOG Stereotactic Radiotherapy Guidelines. The study title specifies single-isocenter, multi-target stereotactic radiosurgery, abbreviated SIMT SRS. Masking is listed as none. Allocation is listed as NA, and the model is single-group. There is no randomized comparison or control arm in the registry record, so outcomes cannot be interpreted as a direct contrast between SIMT SRS and another treatment group.

The primary outcome is the count of participants who lived longer than predicted according to GPA score, with a timeframe of up to 24 months after SRS. The registry also lists secondary outcomes concerning local brain recurrence within 1 year, neurologic death within 1 year, a new brain metastasis at a different site 1 year after treatment, and Grade 3, 4, or 5 neurologic adverse events attributable to SIMT SRS. These are registered outcome questions; their results are not reported in the registry record.

The registry identifies five outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. The planning illustrations associated with the posted results should not be mistaken for the study’s design: the registry’s stated assumptions use equal allocation between two arms, whereas this trial is recorded as single-arm. Those illustrations are not evidence that the study was designed as a two-arm trial, and they are not observed power.

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:

Analysis population for the primary outcome, as defined in the registry: Participants who completed the 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 Who Live Longer Than Predicted According to the Graded Prognostic Assessment (GPA) Score, measured over Up to 24 months after SRS.

The primary endpoint is a count: the number of participants who lived longer than predicted according to their Graded Prognostic Assessment score. The registry gives a timeframe of up to 24 months after SRS and says the primary population consists of participants who completed the study. The number of participants who completed the study is not reported in the registry record.

The GPA is used to set a prognostic reference for survival. As described in the registry, it combines age, Karnofsky Performance Score, extracranial metastases, and the number of brain metastases. The four factors are scored and summed to form GPA groups. The record lists median survival values for those groups as the basis for the prediction. Comparing observed survival with a prognostic expectation gives the endpoint its meaning: it asks whether participants exceeded the survival expectation associated with their GPA, rather than measuring a treatment-versus-control difference.

This endpoint should not be read as a complete account of treatment benefit or harm. It is a count based on survival relative to a prognostic score. It does not, by itself, establish why an individual lived longer or shorter than predicted, nor does it isolate the effect of SRS from other influences. No primary endpoint count, estimate, or uncertainty interval is reported in the registry record, so the posted record does not show how many participants met the endpoint or how precisely that count was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main outcome is a count of participants who live longer than their GPA-based prediction. A count conveys how many people met a defined outcome, but interpretation also depends on the population included, the observation period, and the rule used to decide whether survival exceeded prediction. The registry gives the timeframe as up to 24 months after SRS and identifies the primary population as participants who completed the study. It does not report the number completing the study or the primary count. No rate or proportion should be inferred from the enrollment figure alone.

GPA is a prognostic score described in the registry as incorporating age, Karnofsky Performance Score, extracranial metastases, and number of brain metastases. The record says each factor receives a score of 0, 0.5, or 1.0, and that the scores are summed. It lists GPA groupings with median survival values: GPA 0-1 with 2.6 months, GPA 1.5-2.5 with 3.8 months, GPA 3 with 6.9 months, and GPA 3.5-4.0 with 11 months. These values are the reference expectations described by the registry. They are not observed survival results from this study. A comparison with prognostic expectations can be informative descriptively, but it is not the same as estimating a causal treatment effect against a control group.

For an outcome expressed as a count, the number of events and the denominator both matter. A count without a clearly reported denominator does not show the fraction of the population meeting the outcome. Here, the primary endpoint’s denominator is especially important because the registry says it applies to participants who completed the study, while the number completing is not reported. The record also does not describe how incomplete follow-up or missing survival information was handled. Missingness can affect both the count and the population to which it applies; no particular handling method should be assumed.

Uncertainty is also important. In general, a confidence interval describes a range of values compatible with the observed data under a statistical method and its assumptions. It helps distinguish a precise estimate from one that is uncertain. The primary endpoint’s estimate and confidence interval are not reported in the registry record, so its precision cannot be judged. The record lists zero analyses and does not provide a p-value or a statistical model for the primary outcome.

For binary outcomes, an analysis may report the number with an event and the number assessed, with an interval around an estimated event rate. Such an interval reflects sampling uncertainty; it does not account automatically for bias from missing data, selection, or outcome measurement. The registry’s secondary outcomes are framed as counts, including recurrence, neurologic death, new metastasis, and neurologic adverse events. Their results and uncertainty estimates are not reported in the registry record. The safety counts are also not accompanied by intervals or a detailed analysis method.

The sample-size planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe planning for stated fractions of an observed effect. For time-to-event outcomes, the illustrations use total events; for other outcomes, they use participants per arm. These are assumptions for planning illustrations, not a description of the actual single-arm study design. They are not observed power. A planning calculation depends on its assumed effect and design; it cannot substitute for an observed estimate, and it should not be interpreted as evidence that the trial had a particular probability of detecting an effect.

Over-dispersion is a general concern when count outcomes vary more than a model’s assumed distribution allows. If ignored, uncertainty may be understated. That concept does not establish that over-dispersion occurred in this study: the registry does not report a count model, dispersion estimate, or analysis method. Similarly, a time-to-event method can account for the timing of events and censoring, but the registry record does not identify such a method for the primary endpoint. The endpoint’s timeframe alone is not enough to infer an analysis approach.

Multiplicity arises when several outcomes or statistical tests are considered. In general, examining multiple outcomes can increase the chance that at least one result appears notable by chance, depending on the testing strategy. The registry lists five outcome measures, but it does not report whether or how multiplicity was addressed. No adjustment or hierarchy should be assumed. The record also does not report prespecified covariate adjustment, subgroup analyses, or interim analyses. These omissions limit what can be concluded about the statistical procedures behind any unreported analyses.

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("Stereotactic Radiosurgery")
n      <- c(32)
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  Stereotactic Radiosurgery  32  22  68.8  50.0  83.9  51.4  82.0  51.3  82.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures: the primary GPA-relative survival count and secondary outcomes concerning local recurrence, neurologic death, a new brain metastasis at a different site, and Grade 3, 4, or 5 neurologic adverse events attributable to SIMT SRS. The record does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment for testing several outcomes. It is therefore not possible to determine how the study treated the risk of chance findings across multiple endpoints. No statistical analysis plan is reported in the registry record.

The primary endpoint description specifies participants who completed the study. The number completing is not reported, and the record does not explain how missing follow-up or incomplete outcome information was handled. It does not state whether an analysis population was defined as all enrolled participants, all treated participants, or another group. The study is single-arm, but the registry does not describe an analysis set or how participants with unavailable data were included.

These omissions matter because the population used for analysis affects the denominator and the interpretation of a count. Missingness may also introduce bias if the availability of an outcome is related to the outcome itself or to participant characteristics. These are general concerns, not claims about what occurred in this study. The registry record does not provide enough information to assess missingness, exclusions, or the analysis population. Its listing of zero analyses does not establish that no analyses were conducted; it means results of analyses 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety summary lists 0 serious adverse events among 40 at risk in the stereotactic radiosurgery group. It also lists 16 other adverse events among 40 at risk and 39 deaths. These are counts as recorded in the safety summary. The record does not provide detailed event descriptions, timing, or an explanation of how the categories were defined. It lists no serious adverse-event terms in the top serious terms field.

The serious adverse-event count and the other adverse-event count should be kept distinct. The registry does not report whether the other events were related to treatment, their severity, or whether participants experienced more than one event. The count of deaths should not be treated as a count of neurologic deaths: the secondary outcome specifies neurologic death within 1 year, while the safety summary does not give cause or timing for the deaths. The relationship between those counts is not reported in the registry record.

A zero count in the reported serious-event summary does not establish that treatment carries no risk. It is a count in the recorded study group, without a comparator or a reported uncertainty estimate. The safety information is therefore descriptive and should not be interpreted as a controlled estimate of relative safety.

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

The registry record establishes that a prospective, single-arm study evaluated stereotactic radiosurgery in adults with 4 or more brain metastases. Its primary outcome was whether participants lived longer than predicted by GPA score, assessed up to 24 months after SRS. This framing makes the outcome a comparison with a prognostic expectation, not a comparison between randomized treatment groups.

The registry does not report the primary outcome count, an estimate of uncertainty, or the results of the listed secondary outcomes. As a result, the posted record does not establish how many participants outlived GPA prediction, how often recurrence or new metastases occurred, or how many experienced the specified neurologic outcomes. Those results are not reported in the registry record. The presence of registered outcomes is not evidence that the outcomes were observed at any particular frequency.

The safety summary reports 0 serious adverse events, 16 other adverse events, and 39 deaths. These counts do not provide a treatment comparison, and the registry does not give the details needed to interpret the deaths by cause or timing. In particular, they do not answer the secondary question about neurologic death within 1 year. Nor do the counts alone establish whether an adverse event was attributable to SRS.

The design cannot distinguish outcomes associated with the treatment from outcomes that might have occurred for other reasons, because there is no comparator arm. The GPA reference values provide prognostic context but do not remove that limitation. The record also lacks the statistical analysis details and missing-data information needed to judge how the primary population and endpoint were analyzed.

Thus the record is useful for understanding the intended population, treatment, outcome definitions, and some safety counts. It does not provide a complete results-based assessment of the primary question. No conclusion that SIMT SRS does or does not improve survival, prevent recurrence, or produce a particular level of harm follows from the information reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a single-arm outcome description and a comparative treatment effect. The registry asks whether survival exceeded a GPA-based expectation, which can place outcomes in a prognostic context. But there is no concurrent control group, so the design cannot directly show what would have happened to similar participants under another treatment or without the intervention.

The primary endpoint also shows why a prognostic benchmark and an observed result must be kept separate. The registry provides GPA factors and survival expectations to explain how “longer than predicted” is defined. Those expectations are background information, not study findings. Without the reported count of participants meeting the endpoint and its uncertainty, the reader cannot assess the primary result from the record.

The study’s outcome list spans survival relative to prognosis, recurrence, new metastases, neurologic death, and neurologic adverse events. Considering several outcomes may give a broader view of what investigators intended to track, but it also raises questions about analysis plans and multiplicity. Those plans are not reported in the registry record. The missing analysis and missingness details therefore matter to statistical interpretation, not just to presentation.

The safety summary further illustrates the limits of aggregate counts. Counts of serious and other adverse events and deaths are descriptive, but without event timing, causes, or a comparison group they do not establish treatment attribution or comparative risk. The record makes the study question and design visible, while the absent primary and secondary results leave the central outcome questions unanswered in the registry record.

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 important trial-specific limitation is the absence of a comparator arm. The registry classifies the study as single-group and single-arm, with allocation listed as NA. Any outcomes among participants treated with SRS are therefore descriptive and cannot be contrasted directly with outcomes under another management strategy. Masking is listed as none.

The registered primary outcome is survival longer than predicted according to GPA, rather than a comparative survival endpoint. The GPA reference categories and median survival values are reported, but the primary outcome count is not. The record also does not report the number of participants who completed the study, although the primary outcome population is described as participants who completed it. This makes the analysis denominator unclear from the registry record.

Results for the primary and listed secondary outcomes are not reported in the registry record. The record lists zero analyses and does not provide estimates, confidence intervals, p-values, or a statistical analysis plan. It also does not describe how missing outcome information was handled, whether participants were excluded from analyses, or whether outcomes were adjudicated in a particular way.

The safety summary gives aggregate counts but does not report event timing, causes of death, detailed adverse-event terms, or a treatment-relatedness assessment. The 39 deaths cannot be matched to the registered neurologic-death outcome from the information reported. The registry’s enrollment is 40, but that figure does not establish the number included in each outcome analysis or the number completing the study.

Finally, the population is defined as adults with 4 or more brain metastases, so the record’s stated scope is specific to that group. The study title and arm description identify SIMT SRS and stereotactic radiosurgery, but the registry information does not provide additional treatment-delivery details beyond the guideline reference. These reporting limits constrain interpretation of both outcome estimates and applicability beyond the population described.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: SIMT Stereotactic Radiosurgery Outcomes Study — NCT02886572.
• Registry record last updated 2022-06-01; status last verified 2022-05.
• Results first posted 2022-04-08.
• 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

NCT02886572 is the registry record for the SIMT Stereotactic Radiosurgery Outcomes Study, sponsored by Duke University. It is listed as completed, prospective, single-arm, and single-group, with enrollment of 40. The study began on 2017-01-25, and primary completion is listed as 2021-04-30. Phase is recorded as NA.

The study concerns adults with 4 or more brain metastases treated with single-isocenter, multi-target stereotactic radiosurgery. Its primary outcome counts participants who lived longer than predicted according to GPA score, up to 24 months after SRS. Four secondary outcome questions concern local recurrence, neurologic death, new metastasis at a different site, and serious neurologic adverse events.

The registry record does not report the primary or secondary outcome results or a statistical analysis plan. Its safety summary lists 0 serious adverse events, 16 other adverse events, and 39 deaths. These figures are descriptive and do not provide a controlled comparison.