This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Amifostine With IMRT for Submandibular and Sublingual Salivary Sparing During Head and Neck Cancer Treatment (NCT00409331), a non-randomized phase 2 study. The primary outcome is 12-month Clinically Relevant Salivary Flow (CRSF).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00409331 |
| Phase | Phase 2 |
| Condition | Head and Neck Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with head and neck cancer; its stated objectives refer to patients with head and neck squamous cell carcinoma (HNSCC). The salivary outcomes of interest were production by the submandibular and sublingual glands, considered collectively. The registry record reports enrollment of 3, but does not report an analyzed population or participant-level characteristics.
Intervention
The registered regimen combined intensity-modulated radiation therapy (IMRT) with amifostine. The arm description specifies IMRT at 2.0 to 2.2 Gy delivered in 30 fractions, with amifostine 500 mg in 2 divided doses given subcutaneously 30-60 minutes before IMRT. These are the registered treatment details; the record does not provide participant-level treatment exposure or adherence.
Comparator
There was no separate comparator arm in this non-randomized, single-group study. The registry record therefore does not support a direct comparison with IMRT alone, another treatment, or an untreated group. A comparison against an external or historical group is not reported in the registry record.
Primary question
The primary question was whether clinically relevant salivary flow from the submandibular and sublingual glands would be present at 12 months after radiation in the setting of amifostine plus IMRT. The registered definition treats production of 0.05 mL in a 5-minute collection period after radiation as clinically relevant salivary flow. The registry record says the study terminated early because of a change in sponsor and that no analysis was performed. It therefore does not report an answer to the primary question.
3. Trial Design
This was a phase II, non-randomized, unmasked, single-group study sponsored by M.D. Anderson Cancer Center. The registry record lists enrollment of 3 and one treatment arm, named IMRT + Amifostine. With no randomized allocation and no separate control arm, the design was intended to assess outcomes within the treated group rather than estimate a randomized treatment contrast.
The registered treatment paired IMRT with amifostine. The arm description gives an IMRT dose of 2.0 to 2.2 Gy delivered in 30 fractions and amifostine 500 mg in 2 divided doses subcutaneously 30-60 minutes before IMRT. The primary endpoint was bilateral 12-month clinically relevant salivary flow (CRSF) from the submandibular and sublingual glands collectively. The stated secondary objectives concerned parotid dose-volume and measured-flow relationships, mucositis, occipital scalp epilation, dysphagia assessed using the List Performance Status Scale, and amifostine safety.
The registry lists a study start of 2006-12 and primary completion of 2009-01. Its status is terminated, and the primary endpoint record states that the study terminated early because of a change in sponsor. The record does not report a detailed account of the termination, how much follow-up was completed, or whether each enrolled participant received the registered regimen. Those details are not reported in the registry record.
In general, a single-group design can describe outcomes among participants receiving a regimen, but it cannot by itself separate the treatment's contribution from other explanations for an outcome. Non-randomized allocation also does not provide the balance created by random assignment. Since no outcome analysis was performed, the posted record cannot establish even a within-group estimate of the primary endpoint.
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: Study terminated due to slow accrual and change in sponsor. Three patients registered, two removed prior to study beginning as not eligible.
Overall Study
| Stage | IMRT + Amifostine |
|---|---|
| STARTED | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | IMRT + Amifostine |
|---|---|
| Physician Decision | 1 |
Analysis population for the primary outcome, as defined in the registry: No analysis performed; study terminated early due to change in sponsor.
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.
| Characteristic | Unit | IMRT + Amifostine |
|---|---|---|
| Participants analysed | 1 | |
| Age Continuous | years | 48 (48 to 48) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 1 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as 12-month Clinically Relevant Salivary Flow (CRSF), measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was 12-month clinically relevant salivary flow (CRSF), defined as bilateral flow from the submandibular and sublingual salivary glands considered collectively. Saliva production was to be quantified using selective quantitative submandibular sialometry, with a total collection time of 5 minutes. The registry defines CRSF as production of 0.05 mL of saliva after radiation during that 5-minute collection period.
This endpoint uses a defined amount of collected saliva to classify whether production meets the registry's threshold for clinically relevant flow. In general, an operational threshold can make a biological measurement easier to interpret against a prespecified criterion, while the underlying continuous amount of saliva may carry detail that a threshold-based classification does not retain. The record does not report whether the analysis would also have summarized flow as a continuous measure, how bilateral measurements would have been combined beyond the stated collective endpoint, or how measurements below or above the threshold would have been handled in statistical summaries.
The planned assessment time was 12 months. The registry record reports no analysis performed and gives no observed flow values, participant-level measurements, or endpoint count. Consequently, the endpoint definition is available, but the result at the planned time point is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not report an estimate for 12-month CRSF. It explicitly states that no analysis was performed because the study terminated early after a change in sponsor. As a result, there is no posted proportion, mean, distribution, or other summary of salivary flow from which to assess the primary outcome. There is also no reported confidence interval or hypothesis-test result for that endpoint. The absence of an analysis is not evidence that the endpoint was met, nor is it evidence that it was not met.
Enrollment is listed as 3, but enrollment alone does not establish how many participants had an evaluable 12-month measurement. The analyzed population and the availability of endpoint measurements are not reported in the registry record. It is therefore not possible to infer outcome status from enrollment or to assess how much information the planned endpoint would have contributed. The registry lists one outcome measure and zero analyses; it does not post the participant-level data or summary statistics needed to independently evaluate the intended result.
The design also limits the kind of conclusion that could have followed from a within-group estimate. In general, without a separate comparison group, an outcome observed after a treatment regimen cannot distinguish the regimen's effect from changes that might occur for other reasons. This is especially relevant to causal interpretation: even a complete within-group result would describe outcomes in the study group, not establish what would have happened to comparable participants under another treatment. Here, the lack of an outcome analysis means that no such within-group description is available either.
The record's adverse-event information requires similar caution. For the IMRT + Amifostine group, the registry lists zero participants at risk and zero affected for serious and other adverse events; deaths are recorded as null. These entries do not supply an interpretable safety denominator or a participant-level account of events. They should not be read as demonstrating that no adverse events occurred. A safety estimate, event rate, or comparative safety conclusion is not reported in the registry record.
Planning illustrations based on an observed effect are not outcome findings and are not evidence of power achieved by this trial. The actual observed effect and planning outputs are not reported in the registry record. The record's termination and lack of analysis leave the primary efficacy question, the secondary objectives, and the safety objectives unresolved.
9. Statistical Methods Explained
What does a single-group design estimate?
In general, a single-group study follows participants receiving a treatment regimen and describes outcomes within that group. A suitable summary might describe a measured value or the proportion meeting a defined endpoint, depending on how the endpoint and analysis are specified. Such a summary can characterize the observed study group, but there is no concurrent untreated or alternative-treatment group to show what would have occurred under another approach.
This distinction separates description from causal comparison. A change from an earlier measurement, if one were reported, would not by itself show that the treatment caused the change. Other factors, including the natural course of illness, concurrent care, measurement variation, or changes in who remains available for follow-up, can contribute to an observed pattern. These are general considerations; the registry record does not report baseline results, follow-up completeness, or an analysis of change for this study.
Randomization is one way to support causal comparisons by assigning participants to groups in a way that can balance measured and unmeasured factors on average. This study is listed as non-randomized and single-group, so it has no randomized treatment contrast. The registry record does not report an external comparator or adjusted comparison. Accordingly, no comparative effect can be estimated from the posted design and results.
How should the endpoint definition be read?
The endpoint specifies a time point, glands of interest, measurement approach, and threshold. The planned time point is 12 months; the glands are the submandibular and sublingual glands collectively; and measurement is described as selective quantitative submandibular sialometry with a 5-minute collection. The threshold in the registry definition is 0.05 mL after radiation within that collection period.
In general, a threshold turns a quantitative measurement into a criterion that can be interpreted as meeting or not meeting a specified level. This may be useful for a clinically framed endpoint, but it can discard information about how far an individual measurement lies from the threshold. A complete analysis would ordinarily need to specify how measurements are summarized and how uncertainty is represented. The registry record does not report those statistical details or any observed endpoint measurements.
What do the planning assumptions mean?
The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. This is a planning exercise, not a description of the study's single-group design and not a report of an observed treatment comparison. The record does not report the underlying observed effect or numerical planning results.
In general, a sample-size calculation asks how much information a hypothetical design would need under specified assumptions. The calculation depends on the chosen effect, variability, significance threshold, allocation, and analysis method. Changing the target effect or assumptions changes the planning requirement. A planning illustration is not the same as observed power, which is not a useful substitute for reporting the estimate and its uncertainty after data collection. The record does not report a sample-size justification for the actual study or the statistical plan used to create the illustration.
The planning description distinguishes calculations reported as participants per arm from time-to-event calculations reported as total events. It does not make the two-arm assumptions applicable to this trial: the registered study is single-group and does not report a time-to-event primary endpoint. No new group size or event target can be inferred from the planning assumptions alone.
Why do uncertainty and model assumptions matter?
In general, a confidence interval describes a range of values compatible with the data under a statistical procedure and its assumptions. Its width reflects the precision of the estimate: less information or greater variability usually produces less precision. A point estimate without an uncertainty interval can conceal substantial uncertainty, while an interval does not correct design limitations or prove causation. No confidence interval is reported for this study's primary endpoint.
Statistical models also rely on assumptions about the outcome and how observations vary. For example, over-dispersion occurs when observed variability is greater than a model's assumed variability; if not addressed, uncertainty may be understated. This is a general concept, not a problem identified in this study. The registry record gives no fitted model, variance estimate, or analysis that would allow an assessment of over-dispersion or other model assumptions.
Because the record says no analysis was performed, there is no basis to evaluate a test statistic, model fit, adjustment, or sensitivity analysis. The statistical interpretation is therefore bounded by the design description, endpoint definition, and explicit absence of posted results. More detailed statistical methods are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry describes one primary endpoint and several secondary objectives. The secondary objectives include examining a parotid dose-volume histogram in relation to measured flow under specified dose conditions, observing mucositis at listed oral sites, observing occipital scalp epilation, assessing dysphagia with the List Performance Status Scale, and further evaluating amifostine safety. The registry record does not report results for these objectives.
When a study tests or estimates several outcomes, multiplicity can arise because examining many results increases the chance of at least one apparently unusual finding. In general, investigators may prespecify a hierarchy of outcomes, adjust statistical testing, or treat secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy for interpreting the secondary objectives, or a statistical analysis plan. Since no analysis was performed, there are no posted tests to assess for multiplicity.
Missing-data methods and analysis populations are also not reported in the registry record. The record does not state how unavailable 12-month measurements would have been handled, whether participants with incomplete follow-up would have been included in any particular analysis, or what rules would define an evaluable population. These omissions matter because incomplete outcome data can affect both the estimate and its precision, particularly when the reasons for missingness are related to the outcome.
The registry states that enrollment was 3, but it does not report how many participants contributed measurements at the primary time point. It also reports zero analyses. Therefore, no conclusion can be drawn about outcome completeness, missing-data assumptions, or the population used for an analysis.
11. What the Result Does, and Does Not, Mean
The registry record establishes the intended question and endpoint, but it does not establish the result. The study planned to assess 12-month CRSF after amifostine with IMRT, using a defined salivary-flow threshold and measurement procedure. Because the study terminated early and no analysis was performed, the posted record does not show whether participants met that threshold or how salivary flow changed or varied.
This lack of a result should not be interpreted as evidence for or against the regimen. A missing estimate is different from an estimate near zero, an estimate showing benefit, or an estimate showing harm. The registry does not report the outcome data or their uncertainty, so none of those interpretations is supported.
Nor could a result from this single-group design alone establish that the regimen caused an observed outcome. In general, a treatment effect requires a comparison that represents what would have happened to similar participants without that treatment or with an alternative. The study has no registered comparator arm, and no external comparison is reported. Thus, even if a within-group endpoint summary had been posted, its causal meaning would have been limited.
The safety information likewise does not establish the absence of harm. The adverse-event record lists zero at risk and zero affected for serious and other events, while deaths are null; it does not provide an interpretable denominator or analysis. The record does not support a safety rate or a conclusion that the regimen is safe or unsafe.
Overall, the appropriate interpretation is that the primary and secondary questions remain unanswered in the registry record. Planning calculations, where presented, describe hypothetical sample-size assumptions rather than trial findings or observed power. They do not replace outcome estimates, uncertainty intervals, or a complete accounting of participant follow-up.
12. Why This Trial Matters Statistically
This study illustrates why a clearly stated endpoint and an observed result are separate parts of statistical evidence. The registry defines a specific 12-month salivary-flow outcome, including the glands, collection method, and threshold. That degree of endpoint definition tells readers what the investigators intended to measure, but it cannot answer the clinical question without participant measurements and an analysis.
It also illustrates the limits of interpreting a single-group study. A within-group outcome can describe the participants who were measured, but it cannot directly compare the regimen with an alternative. When a trial has no control group, even a favorable-looking outcome may have explanations that cannot be distinguished from a treatment effect. The registry record reports no analysis in any case, so no within-group result is available to interpret.
Early termination is important for transparency because it clarifies why an intended analysis may be absent. The registry attributes termination to a change in sponsor. It does not report a detailed account of the decision, the status of follow-up, or whether the study could have completed its planned assessments. Those details would help readers understand the extent of missing information, but they are not reported in the registry record.
Finally, the planning assumptions are distinct from the trial's actual design. The illustration describes a two-arm planning scenario, while the registered study is single-group. This contrast is a reminder to interpret sample-size calculations in light of the assumptions they use and not to treat planning figures as observed findings. Here, the lack of an analysis means the central statistical contribution is the clear documentation of an unanswered question, rather than an estimate of treatment effect.
13. 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 for interpretation is that no outcome analysis was performed. The registry record therefore contains no estimate of 12-month CRSF, no measure of uncertainty, and no reported result for the secondary objectives. Enrollment is listed as 3, but the number with evaluable endpoint data is not reported in the registry record.
The design was non-randomized and single-group, with no separate comparator. This prevents a direct treatment contrast and limits causal interpretation even if an outcome summary were available. The record does not report a baseline salivary-flow summary, an external comparison, or an adjusted analysis that could address this limitation.
The study terminated early because of a change in sponsor. The record does not report the timing or extent of participant follow-up, the reasons for termination beyond the sponsor change, or whether participants completed the planned 12-month assessment. The handling of missing observations and the definition of analysis populations are also not reported in the registry record.
The adverse-event entries do not provide an interpretable safety assessment: the group record lists zero at risk and zero affected for serious and other events, with deaths recorded as null. Further participant-level safety information and an analysis are not reported. The registry also does not report a detailed statistical plan, multiplicity strategy, sample-size justification for the actual trial, or the analysis methods that would have been used for the endpoint. These limitations mean that neither effectiveness nor safety can be assessed from the posted results.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Amifostine With IMRT for Submandibular and Sublingual Salivary Sparing During Head and Neck Cancer Treatment — NCT00409331.
- Registry record last updated 2012-08-07; status last verified 2012-07.
- Results first posted 2010-01-18.
- 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.
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17. Record Summary
NCT00409331 is a phase II, non-randomized, unmasked, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 3 and evaluated a registered regimen of IMRT with amifostine for patients with head and neck cancer. The study start is listed as 2006-12, primary completion as 2009-01, and status as terminated.
The primary endpoint was bilateral 12-month CRSF from the submandibular and sublingual glands, measured using selective quantitative submandibular sialometry. The registry defines the threshold as 0.05 mL in a 5-minute collection period after radiation. Secondary objectives concerned parotid flow and dose, mucositis, scalp epilation, dysphagia, and safety.
The registry states that the study terminated early because of a change in sponsor and that no analysis was performed. It therefore reports no primary endpoint result or interpretable safety analysis.