Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy (NCT03673176), a na na study. The primary outcome is Count of Patients With Grade 3 or Higher Adverse Events..

2. Clinical Question

The study is registered as NCT03673176 and is titled “Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy.” The registry record describes a proposed rationale: using precise target localization to reduce emphysematous lung volume, with the hope of reproducing benefits associated with surgical lung-volume reduction while reducing risk. That rationale is not itself evidence that the intervention improved lung function, symptoms, survival, or quality of life.

The registry lists secondary outcomes covering forced expiratory volume, diffusing capacity, six-minute walk distance, total lung capacity, residual volume, quality of life measured with the SF-36, and dyspnea measured with the Modified Borg scale. These outcomes could describe different aspects of respiratory function and patient experience. However, their result values are not reported in the registry record, so the clinical question about changes in these measures cannot be answered from the posted results.

3. Trial Design

This was a completed, single-group intervention study of stereotactic ablative radiation treatment for emphysema. The registry lists an enrollment of 9 and identifies Stanford University as the sponsor. The study start date is 2013-02-11, and the primary completion date is 2021-08-02. The phase is listed as NA. Allocation is also listed as NA, and masking is listed as NONE.

Because the study is single-group, the registry record does not describe a concurrent control group. It therefore cannot estimate a treatment effect by comparing outcomes in SABR recipients with outcomes in a comparable group assigned to another intervention. Any change from baseline, if it had been reported, would describe change within the treated group; without a control group, such change alone could not separate treatment effects from the course of disease, other care, measurement variation, or other influences.

The intervention is named Stereotactic Ablative Radiotherapy (SABR), and the arm description calls it experimental stereotactic ablative radiation treatment. The registry does not report details such as dose, treatment delivery schedule, target-selection criteria, or concurrent treatment. Those protocol details are not reported in the registry record and should not be inferred from the intervention name.

The primary endpoint is a count of participants with grade 3 or higher adverse events among participants who received SABR, with an 18 months timeframe. The description says adverse events will be based upon National Cancer Institute Common Terminology Criteria. The registry also lists nine secondary outcome measures, including lung-function measures, a walk test, quality of life, and dyspnea. It does not report the measurement schedule for those outcomes or their results.

The record marks the study completed, but completion status does not establish that all planned outcomes were measured or reported. The number of analyses listed is 0. The registry does not report a detailed statistical analysis plan, a sample-size justification, randomization procedures, interim analyses, or a missing-data strategy. These absences limit what can be concluded about how the study was intended to analyze outcome data.

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: 9 participants signed consent; 8 were allocated to the study arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received SABR

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: Participants who received SABR

6. Primary Endpoint

The registry lists the primary outcome as Count of Patients With Grade 3 or Higher Adverse Events., measured over 18 months.

The primary endpoint is the count of participants with at least one adverse event graded 3 or higher within the stated 18 months timeframe. The registry specifies that this endpoint applies to participants who received SABR and that adverse events will be based upon National Cancer Institute Common Terminology Criteria. The measure is a participant count, rather than a measure of event frequency or duration.

A participant count is useful for describing how many people experienced an event meeting a defined severity threshold. It focuses on whether participants experienced such an event, rather than how many separate events each person experienced. It can therefore offer a straightforward summary of a safety outcome, provided the event definition, observation period, and participant population are clear.

Severity grading gives clinical research teams a structured way to classify adverse events. The threshold in this endpoint is intended to identify events at or above a specified grade. The registry record, however, does not report the number of participants who met that primary endpoint. The separate serious adverse-event summary should not be treated as the primary endpoint result: serious-event classification and a grade threshold are not interchangeable definitions in the information recorded.

The endpoint is relevant to evaluating safety, but it does not measure whether SABR changed emphysema, lung function, exercise capacity, symptoms, or quality of life. Those topics appear among the secondary outcomes. Their results are not reported in the registry record. In the absence of a reported primary endpoint count, the stated endpoint can be described, but its observed result and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study observes outcomes among participants receiving an intervention, without a concurrent comparison group. It can describe what happened to those participants during the study, if outcome data are reported. It cannot, by design alone, show how those outcomes compare with what would have happened under another treatment or without the intervention.

That distinction is important when interpreting changes from baseline. A before-and-after change combines any effect of the intervention with changes that may have occurred over time for other reasons. These can include the natural course of illness, other care, changes in behavior, measurement variability, and differences in which participants contribute follow-up data. A concurrent comparison group can help distinguish treatment-associated change from these influences, but this study is listed as single-group and has no like-for-like control comparison.

Allocation is listed as NA, and the registry does not describe random assignment. Masking is listed as NONE. The record therefore does not support claims about randomized treatment allocation or masked outcome assessment. Details of the outcome assessment process beyond the named measures are not reported in the registry record.

What does a participant count tell the reader?

The primary endpoint is a count of participants meeting a severity criterion, rather than a continuous measurement such as lung-function volume. For this kind of endpoint, the count tells how many participants met the stated definition during the specified observation timeframe. The registry describes the endpoint as participants with grade 3 or higher adverse events, based on National Cancer Institute Common Terminology Criteria, within 18 months.

A count is not the same as the total number of event episodes. A participant may experience more than one event, but a participant-level endpoint counts that person as meeting the criterion rather than counting every episode separately. The primary endpoint result is not reported in the registry record, so neither the number of participants meeting the criterion nor its statistical precision is available.

In general, uncertainty intervals communicate how much statistical uncertainty surrounds an estimate. A confidence interval is an interval calculated using a statistical procedure intended to capture the target parameter at a stated rate over repeated use of that procedure. Its width is influenced by the information in the data and by the analysis method. No confidence interval for the primary endpoint is reported in the registry record.

How should adverse-event categories be distinguished?

The posted safety information separates serious adverse events from other adverse events. It reports 4 participants affected by serious adverse events and 3 participants affected by other adverse events, among 9 at risk. Those counts are not the primary endpoint result. The primary endpoint uses a grade threshold; the record does not state that its serious-event category is equivalent to that threshold.

The terms and percentages in the serious-event listing are also descriptive. They identify event categories recorded as serious and their listed percentages. The registry does not provide the event-level details needed to determine whether terms overlap within participants, how events were adjudicated, or whether any event was attributed to SABR. Nor does the listing establish comparative risk, because no control group is reported.

What is over-dispersion, and does it apply to these results?

In general, over-dispersion describes count data whose variability is greater than expected under a chosen statistical model. It can matter when analysts use a model that assumes a particular relationship between the mean and variance; if that assumption is too restrictive, standard errors and uncertainty assessments may be unreliable. Count outcomes can also reflect clustering, repeated events, or differences in participant risk, depending on the study and the data structure.

The registry record does not provide an analysis model for the primary endpoint or enough outcome data to assess over-dispersion. The primary measure is a participant count, not a reported rate of repeated event episodes. It would therefore be inappropriate to assert that over-dispersion was present or that a particular modeling approach was used.

What do sample-size planning assumptions mean?

In general, a sample-size calculation is a planning exercise that uses assumptions about a target effect, variability, significance level, power, allocation, and analysis method. It estimates the number of participants or events that might be needed for a planned study under those assumptions. Such a calculation is not an observed result and does not tell how persuasive the collected data are after the study is completed.

The registry record does not report a sample-size justification for this trial. A planning illustration described for the associated statistical material uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect specified as a fraction of the observed effect. Those are illustration assumptions, not documented design assumptions for this single-group study. The registry record does not report a two-arm design, and no numerical sample-size illustration is reported in the registry record described for this analysis.

Power is a prospective property of a design under stated assumptions, not a measure of whether a completed study found an effect. A calculation based on an observed effect after the fact is not observed power and should not be used to convert a non-significant or unreported result into evidence for or against an effect. Here, the primary endpoint result and the secondary outcome results are not reported, so no effect-based planning interpretation can be checked against reported outcome estimates.

What analyses are documented?

The registry lists 0 analyses. It does not report a detailed statistical analysis plan, inferential tests, adjustment methods, confidence intervals, or model specifications for the listed outcomes. The primary endpoint description specifies its measure and timeframe, but not the statistical procedure for analyzing it. The outcome definitions and available safety counts support descriptive interpretation only; they do not justify reconstructing 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 Ablative Radiotherapy")
n      <- c(8)
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  Stereotactic Ablative Radiotherapy  8  3  37.5  8.5  75.5  13.7  69.4  13.7  70.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine secondary outcome measures in addition to the primary safety endpoint. They cover forced expiratory volume, diffusing capacity for carbon dioxide, six-minute walk distance, total lung capacity, residual volume, SF-36 quality of life, and Modified Borg dyspnea. Considering multiple outcomes can raise a multiplicity issue: when many statistical tests are performed, the chance of at least one apparently notable finding can increase. In general, a prespecified testing strategy or an explicit distinction between confirmatory and exploratory outcomes helps readers interpret multiple results.

The registry record does not report a multiplicity adjustment, a hierarchy for testing the outcomes, or a statistical analysis plan that explains how multiple outcomes would be handled. It also does not report results or statistical tests for the listed secondary outcomes. It is therefore not possible to determine whether multiplicity was addressed in the analysis or to assess any outcome-specific finding.

Missing-data methods are also not reported in the registry record. There is no description of how missing baseline or follow-up measurements were handled, whether participants discontinued follow-up, or whether analyses used complete cases or another approach. The record does not report outcome-specific denominators beyond the stated safety counts. Without these details, the potential effects of missing measurements on any change-from-baseline estimate cannot be assessed.

The primary endpoint population is described as participants who received SABR. The registry does not report further analysis-population definitions, such as how eligibility, treatment receipt, or incomplete follow-up affected inclusion in each outcome analysis. The enrollment of 9 and the safety population at risk of 9 are reported, but those details do not establish the denominators for unreported efficacy or follow-up analyses. No imputation or sensitivity analysis is 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: copd exacerbation (22.2%), pneumonitis (11.1%), pleural effusion (11.1%), heart failure (11.1%), atrial fibrillation (11.1%).

The safety record lists 9 participants at risk in the SABR group. It reports 4 participants affected by serious adverse events and 3 affected by other adverse events. The serious-event terms include COPD exacerbation (22.2%), pneumonitis (11.1%), pleural effusion (11.1%), heart failure (11.1%), atrial fibrillation (11.1%), and pneumonia (11.1%). These are registry-listed descriptions and should be read as safety summaries, not as a controlled comparison.

The record also lists 4 deaths. It does not report the timing of these deaths, their cause, or their relationship to treatment or to particular adverse events. The deaths should not be assumed to be treatment-related, nor should they be assumed to fall within the primary endpoint timeframe.

The primary endpoint is the count of participants with grade 3 or higher adverse events within 18 months. The serious adverse-event count is not interchangeable with that endpoint, because the registry does not report that the categories use the same definition. The primary endpoint result itself is not reported in the registry record.

With a small participant group, descriptive safety counts provide limited precision, and the absence of a control group prevents a comparative estimate of excess risk. The registry information does not provide confidence intervals, event-level narratives, attribution, or a detailed accounting of participant overlap across event categories.

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

The record establishes that a study of SABR for emphysema was conducted and marked completed, with an enrollment of 9. It defines a primary safety endpoint focused on participants with grade 3 or higher adverse events within 18 months, and it lists adverse-event counts and terms. These details describe the study and its recorded safety information; they do not establish the result of the primary endpoint.

The registry record does not report the primary endpoint count. It also does not report results for the listed changes in lung function, diffusing capacity, walking distance, lung volumes, quality of life, or dyspnea. The study rationale includes the possibility that targeted radiation might reduce emphysematous lung volume and pursue benefits associated with surgical lung-volume reduction. A rationale or hypothesis is not an observed outcome. The registry record does not show whether those anticipated changes occurred.

The safety summary should not be interpreted as proving that SABR caused the listed events or deaths. Nor does the absence of a reported primary endpoint result establish that no such events occurred. The posted adverse-event information is descriptive and lacks a comparison group, treatment-attribution details, and an uncertainty estimate. The serious adverse-event category also cannot be substituted for the grade-based primary endpoint.

Because the study is single-group, it cannot provide a direct estimate of how outcomes would differ under another treatment or without SABR. An observed change within the treated group, if available, would not by itself distinguish intervention effects from time trends, other care, or measurement variability. No treatment-effect estimate or comparative conclusion is reported in the registry record.

The appropriate interpretation is therefore limited: the registry describes a completed, small, single-group study and reports selected safety counts, but it does not provide enough outcome results to evaluate the stated primary safety endpoint or the secondary clinical measures. The record cannot establish benefit, lack of benefit, or a comparative safety profile.

14. Why This Trial Matters Statistically

This study is statistically notable because its clinical rationale is ambitious while the registry record offers limited outcome information for evaluating it. The proposed approach uses stereotactic ablative radiation to reduce emphysematous lung volume, with the stated hope of pursuing benefits associated with surgical lung-volume reduction. Assessing such a proposal requires clear outcome definitions, observed results, and careful separation of descriptive findings from comparative evidence.

The single-group design can document experience among people receiving SABR, but it cannot directly answer what would have happened to similar participants under a different treatment or without the intervention. This is a central design limitation, not a statistical adjustment that can be repaired from the reported counts alone. A comparator is particularly relevant when outcomes can change over time or in response to other care.

The registry specifies a participant-level primary safety endpoint and a defined severity threshold, yet does not report its result. That illustrates why protocol-level endpoint descriptions and outcome reporting serve different purposes. A precise endpoint definition tells readers what was intended to be measured; it does not supply the observed estimate or its uncertainty.

The adverse-event summary also illustrates the need to keep safety classifications distinct. Serious adverse events, grade-based severity, other adverse events, and deaths are related safety concepts but are not interchangeable measures. Without timing, attribution, event-level details, and the primary endpoint result, readers cannot reconcile these categories or make a comparative safety judgment.

Finally, the study lists outcomes that span physiology, exercise capacity, quality of life, and dyspnea. These domains can contribute different information, but their results and the approach to multiple outcomes are not reported in the registry record. Statistical interpretation depends not only on the choice of outcome, but also on transparent reporting of the analysis population, missing data, uncertainty, and the prespecified analysis strategy.

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 principal limitation is the single-group design. Allocation is listed as NA, and there is no like-for-like control comparison. As a result, the record cannot estimate a comparative treatment effect or establish what outcomes would have occurred without SABR. The lack of masking, listed as NONE, is another design feature relevant to outcome assessment; the registry does not describe procedures used to limit assessment bias.

The enrollment was 9. A group of this size can offer only a limited basis for estimating the frequency of uncommon events or the distribution of clinical outcomes. The registry does not report uncertainty intervals for the posted safety counts. The absence of reported primary and secondary outcome results further prevents assessment of effect size, variability, and precision.

The primary safety endpoint is clearly described as a count of participants with grade 3 or higher adverse events within 18 months, but its observed count is not reported. The serious-event count and other adverse-event count do not resolve that omission. The record also lists 4 deaths without reporting timing, cause, or attribution. These data cannot be used to infer whether deaths were treatment-related or whether they met the primary endpoint definition.

Outcome reporting is incomplete in the registry record. Results are not reported for the listed lung-function, exercise, lung-volume, quality-of-life, and dyspnea measures. The registry does not report participant characteristics, detailed eligibility criteria, treatment delivery details, outcome-assessment schedules, handling of missing data, or analysis-population definitions. These omissions make it difficult to assess generalizability and to understand how complete or representative any outcome data would have been.

The record lists 0 analyses and does not report a detailed statistical analysis plan, sample-size justification, multiplicity strategy, interim analyses, or sensitivity analyses. The registry status is completed, but that status does not answer whether all intended measurements were obtained or why result fields are absent. These limitations constrain interpretation to the design description and the safety counts that are actually listed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy — NCT03673176.
• Registry record last updated 2024-07-11; status last verified 2024-06.
• Results first posted 2024-07-11.
• 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

NCT03673176 is a completed, single-group study sponsored by Stanford University, titled “Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy.” The registry lists an enrollment of 9, a start date of 2013-02-11, and a primary completion date of 2021-08-02. Allocation is NA, masking is NONE, and phase is NA.

The intervention is SABR. The primary endpoint is the count of participants with grade 3 or higher adverse events within 18 months, among participants who received SABR. Its result is not reported in the registry record. Safety information lists 4 participants affected by serious adverse events, 3 affected by other adverse events, and 4 deaths, with 9 participants at risk. Timing and attribution details for deaths are not reported.

Nine secondary outcomes are listed, spanning lung function, exercise, lung volumes, quality of life, and dyspnea; their results are not reported in the registry record. The single-group design has no like-for-like control comparison, and the record does not report a detailed statistical analysis plan or sample-size justification. These limits preclude conclusions about comparative effectiveness or safety.