Amifostine to Protect the Rectum During External Beam Radiotherapy for Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Amifostine to Protect the Rectum During External Beam Radiotherapy for Prostate Cancer (NCT00040365), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With a Good Toxicity Outcome Who Experienced an Acute Rectal Toxicity and Received Topical Administrations of Amifostine in Conjunction With High Dose, 3D Conformal Radiotherapy for Prostate Cancer..

2. Clinical Question

3. Trial Design

The registry describes a completed Phase II study of amifostine as a rectal protector during external beam radiotherapy for prostate cancer. It lists a planned enrollment of 30 and identifies the study as non-randomized, unmasked, and single-group. These design features matter when interpreting the reported aims: the record does not describe random allocation or a concurrent control group against which toxicity could be compared.

Participants received radiation therapy and topical rectal amifostine. The dose description distinguishes the first 18 patients, who received 1000 mg, from the last 12, who received 2000 mg. It does not report random assignment between these dose regimens, nor does it provide a comparative estimate between them. The registry description states that amifostine was administered before each radiation treatment and gives 33-39 doses. Radiation was described as a course delivered 5 consecutive days for 8 weeks.

The primary outcome concerns acute rectal toxicity at week 5 and week 7, with a good outcome defined by remaining below grade 2 at both assessments. The registry also lists secondary outcomes concerning late rectal toxicity, adverse events, bowel assessment, quality of life, and proctoscopic examinations. The posted record lists six outcome measures, but it does not include numerical primary results or statistical analysis results.

The record gives a study start of 2002-06, primary completion of 2010-05, and status of completed. These entries describe registry milestones; they do not establish when results were analyzed or whether every planned assessment was completed. Further details about the protocol, participant flow, and analysis plan are not reported in the registry record.

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: Number of participants 29 versus 30 = One patient was taken off study due to tumor progression prior to the follow up period.

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 Percentage of Participants With a Good Toxicity Outcome Who Experienced an Acute Rectal Toxicity and Received Topical Administrations of Amifostine in Conjunction With High Dose, 3D Conformal Radiotherapy for Prostate Cancer., measured over RTOG Acute was used on week 5 and 7.

The primary endpoint is the percentage of participants with a good acute rectal toxicity outcome while receiving topical amifostine together with high-dose, 3D conformal radiotherapy for prostate cancer. The definition requires less than grade 2 toxicity at both week 5 and week 7. Toxicity is assessed using the Radiation Therapy Oncology Group acute radiation morbidity scoring scheme and Rectal Mucosal Toxicity response criteria; the registry says the physician assigns a grade based on symptoms reported by the patient.

A binary percentage endpoint classifies each assessed participant according to whether the defined event occurred. In general, this can make a clinical outcome easier to interpret as the proportion meeting a prespecified threshold, rather than as a change in a continuous score. Requiring the criterion at both assessment times means the endpoint represents meeting the definition on both occasions, not merely at one of them. This is the endpoint’s stated construction, not evidence that the threshold is clinically definitive in every setting.

The registry record does not report the observed percentage, its denominator as analyzed, or a confidence interval. It therefore does not allow readers to judge the estimated frequency or its precision. The population note states 29 versus 30 and explains that one patient was taken off study because of tumor progression before the follow-up period; the record does not clarify further how that note maps to the primary endpoint analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A clinical endpoint turns observations into a quantity that can be interpreted in relation to a study question. In this study, the primary endpoint is a percentage, and the event is a good acute toxicity outcome as defined in the registry. Each participant’s status depends on whether toxicity was less than grade 2 at both week 5 and week 7. The result would ordinarily be the number meeting that definition relative to the number assessed, expressed as a percentage. The registry record does not report that result, so no estimate can be interpreted for this study.

In general, a percentage summarizes the frequency of a binary outcome in the analyzed population. It does not describe every individual’s symptom trajectory, and it can conceal differences in how close participants were to the threshold. A participant just below the grade threshold and one with no recorded toxicity can both meet the same binary definition. The registry’s endpoint rules tell readers how the classification was intended to work, but the posted information does not provide the underlying participant-level observations.

A confidence interval is a way to express the statistical uncertainty around an estimate. In general, a wider interval indicates less precision, while a narrower interval indicates more precision under the assumptions of the method. Confidence intervals do not guarantee that the true value lies within a particular interval, and they do not resolve design limitations such as the absence of a control group. No confidence interval for the primary percentage is reported in the registry record.

A statistical test, when used, addresses a specified comparison or hypothesis. The question and design determine what such a test can answer. A single-group percentage can be described, but a test of a treatment contrast requires a comparator or a specified reference value. The registry lists no analyses, and it does not report a hypothesis test for the primary endpoint. The statistical plan, including whether a reference value or other inferential procedure was intended, is not reported in the registry record.

The study’s non-randomized design has implications for inference. Random allocation, in general, aims to reduce systematic differences between groups at the start of a comparison. This study is listed as single-group and non-randomized, so the registry record does not offer a randomized contrast. Observed toxicity during treatment may be described, but an uncontrolled observation cannot establish how outcomes would have differed under another treatment strategy.

The dose description also requires care. The first 18 patients received 1000 mg and the last 12 received 2000 mg. This is an enrollment-ordered description, not a report of random dose allocation. General comparisons between non-randomized groups can be affected by differences in who entered each group or by changes over the enrollment period. The registry does not report a dose comparison, adjustment method, or analysis plan, so readers should not infer a dose-response relationship from the dose sequence alone.

The record includes a sample-size planning illustration based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s own design: the trial is listed as a single-group study. Such planning calculations are hypothetical illustrations of sample requirements under assumptions. They are not observed power, do not change the number of participants actually enrolled, and do not show that a trial result is statistically significant. The registry record does not report a protocol-based sample-size justification.

For binary outcomes, uncertainty depends in part on the number of participants and the number with the event. In general, limited information yields less precise estimates, particularly when outcomes are uncommon or the denominator is small. This general principle cannot supply the missing precision estimate for this study: the registry does not report the primary event count or an analyzed denominator. The enrollment of 30 is not a substitute for those outcome-specific details.

Outcome grading also involves measurement choices. Here, the registry says that the physician assigns the grade based on patient-reported symptoms and names the assessment criteria. General measurement considerations include whether assessments are applied consistently and whether the person grading outcomes is aware of treatment. Masking is listed as none, but the registry does not describe how this might have influenced grading or whether any assessment procedures addressed that issue. No additional claims about measurement reliability can be made from the posted information.

Finally, endpoint timing shapes what the result would represent. Assessments at week 5 and week 7 contribute to a definition requiring a good outcome at both points. This is distinct from a summary of all symptoms throughout treatment, and it is also distinct from the secondary late-toxicity outcomes listed in the record. In general, separate endpoints can answer different clinical questions and may require separate analysis choices. The registry does not report the statistical procedures used for the primary or secondary outcomes.

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("Amifostine")
n      <- c(29)
events <- c(6)
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  Amifostine  29  6  20.7  8.0  39.7  9.8  38.4  9.9  38.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary acute rectal toxicity endpoint and secondary outcomes concerning late toxicity, adverse events, bowel assessment, quality of life, and proctoscopic examinations. When a study evaluates several outcomes, general statistical practice distinguishes the prespecified primary question from additional outcomes. Testing or interpreting many outcomes can increase the chance of apparently notable findings arising by chance, depending on the analysis strategy. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed statistical plan. It is therefore not possible to determine how the study addressed multiplicity.

The registry lists no analyses. It does not provide an analysis population definition, a missing-data method, or information about the number and reasons for unavailable endpoint assessments. The primary-outcome population note reports 29 versus 30 and explains that one patient was removed from study due to tumor progression before the follow-up period. The record does not say whether this patient was included in the primary endpoint denominator or how other missing observations, if any, were handled.

In general, missing outcome data can affect an estimate when the people with unrecorded outcomes differ from those whose outcomes are observed. A complete-case percentage describes those with available assessments, whereas other methods may make different assumptions about missing outcomes. Without a reported method and denominator, readers cannot establish which interpretation applies. The registry record also does not report sensitivity analyses that might show how conclusions vary under alternative assumptions about missing data.

The record does not state whether the primary endpoint was analyzed according to a prespecified intention-to-treat or other population rule. Such analysis-population details are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: proctitis (3.3%).

The registry’s adverse-event summary lists 30 participants at risk for serious adverse events and 1 affected. It separately lists 30 at risk for other adverse events and 30 affected. These are separate categories in the record and should not be added together to create a total. The registry also lists Proctitis at 3.3% among the top serious adverse-event terms.

These entries describe recorded event counts in the study group; they do not provide a comparison with a control group. In general, an at-risk count is the population assessed for the event category, while the affected count describes participants recorded as having an event. A count alone does not indicate the event’s duration, severity beyond its classification, or whether it was caused by a particular treatment. The listed serious term should not be interpreted as evidence of a comparative risk.

The record does not provide further detail in the registry record about event definitions, timing, relatedness assessments, or the full distribution of adverse-event types and grades. Nor does it report a comparative safety analysis. These figures therefore support a limited description of the registry’s recorded counts and serious term, not an estimate of excess risk or a conclusion about safety relative to another approach.

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

The record documents a Phase II study intended to evaluate topical amifostine during external beam radiotherapy for prostate cancer. It specifies an acute rectal toxicity endpoint, the time points used for that endpoint, and a threshold defining a good outcome. It also records the single-group, non-randomized design and describes the dose regimens used across enrollment. These registry entries help readers understand what the study set out to assess.

However, the primary outcome value is not reported in the registry record. There is no percentage of participants meeting the acute toxicity definition, no confidence interval, and no reported analysis result. As a result, the posted information does not quantify the observed outcome or its precision. It cannot establish whether the study met a particular target or whether a statistical comparison was significant.

The design also limits what can be inferred even if an outcome percentage were available. A single-group study can describe the toxicity observed among enrolled participants, but the registry does not provide a concurrent control group or a randomized comparison. The observed outcome would therefore not, by itself, establish what would have happened under radiation without amifostine or under another treatment strategy.

The registry lists additional outcomes and adverse-event counts, but these do not fill the gap in the primary result. The adverse-event figures describe recorded counts in the study group, not comparative risks. The population note indicates 29 versus 30 and identifies a removal due to tumor progression before follow-up; the record does not fully explain the primary analysis population or missing-data handling. This affects how confidently any percentage could be understood, even if reported.

The appropriate reading is therefore limited: the registry describes the intended evaluation and some safety reporting, but it does not report the primary efficacy-related endpoint result or the analysis needed to judge its uncertainty. It neither demonstrates a comparative treatment effect nor provides grounds for a clinical recommendation.

14. Why This Trial Matters Statistically

This study illustrates why a clearly described endpoint is not the same as a reported result. The registry defines a good acute rectal toxicity outcome through a grade threshold at week 5 and week 7, making the intended classification understandable. But without the observed percentage, denominator, and uncertainty interval, the outcome cannot be quantitatively interpreted. For statistical readers, this distinction separates a protocol-level question from evidence about the participants’ observed outcomes.

The study also highlights how design determines the scope of inference. A single-group, non-randomized study can provide descriptive information about outcomes under the treatment regimen used. It does not create the same basis for causal comparison as a randomized controlled design. This matters when the stated aim concerns whether an intervention reduces side effects: a reduction is inherently comparative, while the registry record does not list a concurrent control group.

The ordered dose description is another useful statistical consideration. The first 18 patients received 1000 mg and the last 12 received 2000 mg. Because the record does not describe random allocation, any apparent difference by dose could be entangled with enrollment order or participant composition. A dose sequence should not be treated as a controlled dose comparison without supporting design and analysis information.

Finally, the record shows why population and missing-data descriptions matter for a percentage endpoint. The primary population note reports 29 versus 30 and attributes the difference to tumor progression before follow-up, while the actual primary result and analysis denominator are absent. Statistical interpretation depends not only on the endpoint definition but also on who contributed data and how unavailable assessments were handled. Those details are not reported 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.

Important limitations specific to this study include the absence of a reported primary outcome value and uncertainty estimate. The registry defines acute toxicity at week 5 and week 7 but does not provide the percentage meeting that definition, a confidence interval, or an analysis result. Readers therefore cannot assess the observed frequency or its precision from the posted record.

The study is listed as single-group and non-randomized, with no like-for-like control comparison. Consequently, the record does not support an estimate of the difference attributable to amifostine relative to radiation without amifostine. The dose regimen also changed across enrollment: the first 18 patients received 1000 mg and the last 12 received 2000 mg. The registry does not describe random assignment or a comparative dose analysis, limiting interpretation of any dose-specific pattern.

The primary population note gives 29 versus 30 and states that one patient was taken off study due to tumor progression before the follow-up period. The record does not specify the final primary-analysis denominator, handling of missing assessments, or whether the same population contributed at both time points. The statistical analysis plan and any sensitivity analyses are not reported in the registry record.

Masking is listed as none. The record does not explain whether this affected toxicity grading or what steps, if any, were used to support consistent assessment. It also does not provide detail about the multiplicity strategy across listed outcomes. These limits concern the interpretation of the registry information; they do not establish that particular sources of bias or missingness occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Amifostine to Protect the Rectum During External Beam Radiotherapy for Prostate Cancer — NCT00040365.
• Registry record last updated 2012-04-30; status last verified 2012-04.
• Results first posted 2012-03-29.
• 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

The registry record describes a completed Phase II, non-randomized, unmasked, single-group study of topical amifostine during external beam radiotherapy for prostate cancer. Planned enrollment was 30. The first 18 patients received 1000 mg and the last 12 received 2000 mg. The primary endpoint is the percentage with a good acute rectal toxicity outcome, defined as less than grade 2 at both week 5 and week 7.

The primary result and its statistical uncertainty are not reported in the registry record. The record lists six outcome measures and no analyses. Its population note reports 29 versus 30 and explains that one patient was taken off study due to tumor progression before follow-up. Adverse-event entries list 1 affected among 30 at risk for serious events and 30 affected among 30 at risk for other events; Proctitis is listed at 3.3% among the top serious terms.