Phase I Clinical Trial of GRID Therapy in Pediatric Osteosarcoma of the Extremity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I Clinical Trial of GRID Therapy in Pediatric Osteosarcoma of the Extremity (NCT03139318), a na na study. The primary outcome is Number of Participants With Toxicities Associated With GRID Radiotherapy.

2. Clinical Question

The clinical question is about toxicity, not comparative efficacy. The objective names three dose levels, but the registry record does not report dose-specific participant counts or outcomes. It also does not report a primary endpoint analysis. Consequently, the record describes what the study set out to assess, but it does not establish how toxicity varied by dose or provide a basis for comparing dose levels.

3. Trial Design

The registry identifies this as a Phase I clinical trial of GRID therapy in pediatric osteosarcoma of the extremity. Phase is listed as NA, however, so the registry record does not specify a phase classification beyond the study title. The model is sequential, allocation is NA, and masking is NONE. One participant was enrolled.

The sole intervention is GRID radiotherapy, listed as a radiation intervention. The study objective is to evaluate the toxicity profile using dose levels of 10Gy, 15 Gy and 20Gy. The arm description says that patients will be treated with GRID radiotherapy. It does not give a dose-assignment sequence, escalation rule, or participant-level dose information. Those details are not reported in the registry record.

The record names the University of Arkansas as sponsor. The study start date is 2017-07-25, the primary completion date is 2018-08-29, and the status is TERMINATED. The reason for termination and the date on which the study was terminated are not reported in the registry record. The record does not explain whether termination was related to enrollment, safety, logistics, or another reason.

Because there is no described comparator and enrollment was 1, the design does not support a between-group treatment comparison. The record also does not report the intended sample size, recruitment target, or a statistical analysis plan. The sequential model alone does not establish how dose decisions were to be made or whether any formal stopping rules were used.

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 Toxicities Associated With GRID Radiotherapy, measured over An average of 12 months.

The primary endpoint is the number of participants with toxicities associated with GRID radiotherapy. Its timeframe is described as an average of 12 months. The endpoint description defines dose-limiting toxicity as a treatment-related adverse event of Grade 3 or higher. Thus, the endpoint focuses on a count of participants meeting a toxicity definition, rather than on a continuous measurement or time-to-event outcome.

In general, a toxicity endpoint is used in an early-phase study to characterize harms observed during treatment and follow-up. A prespecified threshold such as the one described can distinguish events considered dose-limiting from less severe events, provided that event severity and treatment relationship are assessed and recorded. The registry record does not report how those assessments were made, how the timeframe was applied to the participant, or whether any participant met the endpoint definition.

The registry record lists one primary outcome measure but reports no analyses. It therefore does not report a primary endpoint count or a dose-specific toxicity result. The adverse-event counts elsewhere in the record are not, on their own, a reported result for the defined dose-limiting toxicity endpoint: the adverse-event summary does not give the required event grade and treatment relationship for each event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a binary primary outcome: participants either meet the stated toxicity endpoint or do not. The endpoint is expressed as a count of participants with toxicities associated with GRID radiotherapy. Its clinical definition is a treatment-related adverse event of Grade 3 or higher, with a timeframe described as an average of 12 months. No primary endpoint count or statistical analysis is reported.

What does a binary endpoint represent?

General statistical context: a binary endpoint records whether an event or condition is present for each participant. Analysts can summarize such an outcome by counting participants who meet the definition and relating that count to the number assessed. That summary is only meaningful when the event definition, observation period, and assessment population are clear. Here, the definition is stated, but the registry record does not report a primary endpoint result or explain the participant-level assessment.

The term “treatment-related” matters because it makes attribution part of the endpoint definition. Severity also matters because the threshold is Grade 3 or higher. A record that only reports whether any adverse event occurred does not provide all the information needed to determine whether this endpoint was met. The posted adverse-event summary does not identify the grade and treatment relationship of the other event, so it cannot substitute for a reported dose-limiting toxicity analysis.

What can a count tell us?

General statistical context: event counts are direct descriptions of what was observed, while estimates of event frequency attempt to extend that description beyond the participants observed. When the number of participants is very small, such an estimate is imprecise and sensitive to the experience of each participant. The enrollment of 1 therefore limits what can be learned about the frequency or variability of toxicity. It also prevents a meaningful assessment of how outcomes might differ across the listed dose levels.

A confidence interval is a statistical range used to communicate uncertainty around an estimate. Its width depends on the data and the method used. The registry record does not report a primary endpoint estimate or confidence interval, so there is no interval-based precision result to interpret. No p-value or other inferential result for the primary endpoint is reported either. The absence of these results should not be filled by deriving an analysis from the safety counts: the safety summary does not include the grade and relationship information needed for the defined endpoint.

What does the sequential model establish?

The model is listed as SEQUENTIAL. General statistical context: a sequential design may involve decisions made as observations accrue, but the label alone does not describe the decision rules. The registry record does not report a stopping boundary, dose-escalation rule, interim analysis plan, or other sequential procedure. It would therefore be speculative to describe how participants were assigned among dose levels, how safety findings affected enrollment, or whether a formal interim review occurred.

Allocation is listed as NA, and no comparator is described. Thus, there is no randomized contrast to interpret and no basis for calculating a treatment difference from the registry record. Masking is listed as NONE; the record does not explain who knew the treatment assignment or whether any outcome assessments were blinded. These design details should not be expanded beyond what is stated.

How should planning illustrations be read?

The planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe detecting a stated fraction of an observed effect. These are planning assumptions, not evidence that the trial itself used a two-arm design or had those planned characteristics. The registry record describes no comparator arm, reports no primary endpoint analysis, and does not report the effect on which such illustrations would be based. Any sample-size illustrations are therefore not an observed power calculation and do not establish the study's own sample-size justification.

General statistical context: over-dispersion is relevant when observed variation in counts is greater than a model assumes. Accounting for it can affect uncertainty estimates in settings where the data and model warrant that approach. The primary outcome is described as a binary participant count, and the record supplies no analysis or dispersion estimate. There is no basis in the registry record to say that over-dispersion was assessed or that a particular model was used.

The statistical analysis plan, including the estimator, confidence-interval method, handling of incomplete follow-up, and any model adjustments, is not reported in the registry record. No recalculated endpoint analysis is available in the registry record reported, because the required primary endpoint count and event details are absent. The most defensible statistical reading is therefore descriptive: distinguish the stated endpoint from the posted general safety counts and avoid treating either as a comparative or dose-response 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("GRID Radiotherapy")
n      <- c(1)
events <- c(1)
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  GRID Radiotherapy  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and reports no analyses. It does not report a multiplicity plan, such as how conclusions would be adjusted when evaluating multiple outcomes, dose levels, or statistical tests. The study objective names dose levels of 10Gy, 15 Gy and 20Gy, but no dose-specific endpoint results or comparisons are reported. It is therefore not possible to determine whether multiple dose evaluations were planned as formal statistical tests or how any such tests would have been interpreted.

General statistical context: multiplicity arises when several hypotheses or outcomes are examined; without a plan, the chance of a misleading positive finding can increase across repeated tests. This matters when interpreting a set of comparisons, but the registry record does not show a set of primary endpoint tests to assess. No adjustment method or hierarchy of outcomes is reported.

Missing-data methods are also not reported in the registry record. The record does not say whether the participant completed the average 12-month timeframe, whether any assessments were missing, or how incomplete follow-up would have been handled. It does not identify an analysis population, such as participants who received treatment or participants with evaluable outcome data. Enrollment of 1 is not by itself evidence that all endpoint information was available.

Without those details and a reported endpoint analysis, the posted safety counts should not be treated as a substitute analysis population or as proof that there was no missing outcome information. The registry record does not report imputation, exclusions, or sensitivity analyses.

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 non-serious adverse event terms

The registry safety summary lists the GRID Radiotherapy group with 1 participant at risk for serious adverse events and 0 affected. For other adverse events, it lists 1 participant at risk and 1 affected. Deaths are listed as 0 among 1 participant at risk. No serious-event terms are listed in the registry record.

These figures are participant counts in the posted safety summary. The serious-event count, the other adverse-event count, and the death count are separate categories; they should not be added together to create a total because the record does not describe how event categories overlap. The summary does not provide event grades or treatment relationships for the other adverse event. It therefore does not show whether that event met the primary endpoint definition of a treatment-related adverse event of Grade 3 or higher.

General statistical context: safety counts describe reported observations in the participants at risk; they do not establish how frequently events would occur in a larger group. In this record, the denominator is 1, so the counts offer very limited information about safety beyond that participant's reported experience.

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

The registry record establishes that the study was intended to evaluate the toxicity profile of GRID radiotherapy in pediatric osteosarcoma of the extremity, with the objective naming dose levels of 10Gy, 15 Gy and 20Gy. It reports enrollment of 1 participant and a primary endpoint defined as a treatment-related adverse event of Grade 3 or higher. It also reports 0 serious adverse events, 1 other adverse event, and 0 deaths in the posted safety summary.

It does not report whether the enrolled participant experienced the defined dose-limiting toxicity. The other adverse event cannot be classified as a primary endpoint event from the information in the safety summary, because grade and treatment relationship are not stated there. The record also does not report which dose the participant received or provide separate outcomes for the named dose levels.

There is no reported primary endpoint analysis, estimate of toxicity frequency, confidence interval, or comparison with another treatment. Since no comparator is described and only 1 participant was enrolled, the record cannot support a comparative conclusion or a robust estimate of how toxicity varies across participants. The absence of a reported serious adverse event in this summary does not establish that serious toxicity cannot occur.

The status is TERMINATED, but the reason is not reported in the registry record. It should not be interpreted as evidence of a particular safety finding, lack of efficacy, or other cause. The registry entries support a description of the study's objective, design labels, enrollment, endpoint definition, and posted safety counts. They do not establish that GRID radiotherapy is effective or ineffective, or provide a clinical recommendation.

14. Why This Trial Matters Statistically

This record illustrates why design descriptions, endpoint definitions, and outcome results need to be read separately. The study objective specifies a toxicity question and names dose levels, while the primary endpoint has a narrower definition based on severity and treatment relationship. The posted safety counts describe adverse-event categories, but they do not provide enough detail to determine whether the defined endpoint was met.

Enrollment of 1 and the absence of a reported primary endpoint analysis sharply limit statistical interpretation. There is no reported dose-specific result, comparator, uncertainty estimate, or test of a hypothesis. The status TERMINATED is relevant to understanding the study's recorded history, but the registry record does not give a reason for termination. Careful reporting of these distinctions prevents a small set of descriptive counts from being mistaken for a comparative or dose-response finding.

General statistical context: early-phase toxicity questions often depend on clear event definitions, consistent follow-up, and transparent reporting of who was assessed. Those elements allow readers to distinguish observed events from estimates and to understand the limits of precision. In this record, the toxicity definition is stated, but the primary endpoint result and several analysis details are not reported. The statistical value of the record is therefore primarily in clarifying what was planned and identifying what remains unknown, rather than in supporting a broad inference about toxicity.

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 central limitation is the enrollment of 1 participant, which leaves little information for describing variability or estimating event frequency. The registry record reports no primary endpoint analysis, so the planned dose-limiting toxicity outcome cannot be evaluated from the posted results. It also does not say which dose level the participant received, despite the objective naming 10Gy, 15 Gy and 20Gy.

No comparator is described, allocation is listed as NA, and the record does not provide a basis for a treatment comparison. The model is listed as sequential, but its decision rules and any dose-escalation or stopping procedures are not reported in the registry record. The statistical analysis plan, sample-size justification, and interim analyses are also not reported.

The safety summary gives counts but does not provide the grade or treatment relationship of the other adverse event. It therefore cannot be used to classify that event against the primary endpoint definition. The record does not report participant-level follow-up, missing outcome information, or an analysis population. The reason for termination is not reported in the registry record, so the study status cannot be attributed to a particular event or decision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase I Clinical Trial of GRID Therapy in Pediatric Osteosarcoma of the Extremity — NCT03139318.
• Registry record last updated 2022-07-20; status last verified 2022-06.
• Results first posted 2022-07-12.
• 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

NCT03139318 is a University of Arkansas-sponsored study titled “Phase I Clinical Trial of GRID Therapy in Pediatric Osteosarcoma of the Extremity.” The record lists a sequential model, allocation NA, masking NONE, and 1 enrolled participant. Its objective was to evaluate toxicity at dose levels of 10Gy, 15 Gy and 20Gy. The primary endpoint was the number of participants with toxicities associated with GRID radiotherapy, with dose-limiting toxicity defined as a treatment-related adverse event of Grade 3 or higher.

The study started on 2017-07-25, reached primary completion on 2018-08-29, and is listed as TERMINATED. The safety summary reports 0 serious adverse events, 1 other adverse event, and 0 deaths among 1 participant at risk. No primary endpoint analysis is reported. The reason for termination, dose received, and dose-specific toxicity results are not reported in the registry record.