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 Sulfasalazine in Preventing Acute Diarrhea in Patients With Cancer Who Are Undergoing Pelvic Radiation Therapy (NCT01198145), a randomized phase 3 study. The primary outcome is Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01198145 |
| Phase | Phase 3 |
| Condition | Diarrhea, Gastrointestinal Complications, Unspecified Adult Solid Tumor, Protocol Specific |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 87 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alliance for Clinical Trials in Oncology |
| Results posted | Yes |
2. Clinical Question
Population
Patients with cancer undergoing pelvic radiation therapy were eligible for this study. The registry lists diarrhea, gastrointestinal complications, and unspecified adult solid tumor, protocol specific, among the conditions studied. Enrollment was 87. The primary endpoint description notes that two patients in Arm I and one patient in Arm II were excluded from baseline and endpoint analyses because of cancellations and protocol violations.
Intervention
Arm I received oral sulfasalazine twice daily during radiotherapy and for 4 weeks after radiotherapy was completed. The study rationale was that sulfasalazine might relieve diarrhea in patients receiving pelvic radiation therapy; the trial’s stated purpose was to study its use in preventing acute diarrhea.
Comparator
Arm II received oral placebo twice daily during radiotherapy and for 4 weeks after radiotherapy was completed. The study was randomized, double-masked, and used a parallel-group design.
Primary question
The primary question was whether the distributions of maximum diarrhea severity differed between the sulfasalazine and placebo arms during radiotherapy and up to 6 weeks after radiotherapy. Severity was graded using the Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE v4.0). The registry states that a two-sided Wilcoxon rank-sum test would be used. The primary endpoint results are not reported in the registry record, so the record does not establish how the observed severity distributions compared.
3. Trial Design
This was a phase III, randomized, double-masked, parallel-group study of sulfasalazine versus placebo. The listed sponsor was the Alliance for Clinical Trials in Oncology. The trial enrolled 87 participants and is marked completed in the registry record. The listed start was 2011-04, and the primary completion date was 2013-07-22.
The two arms differed in the assigned oral medication. Participants in Arm I received sulfasalazine twice daily during radiotherapy and for 4 weeks after radiotherapy was completed. Participants in Arm II received oral placebo on the same schedule. The record describes both arms as receiving their assigned medication during radiotherapy and for the stated post-radiotherapy period.
The primary outcome was the maximum severity of diarrhea toxicity during radiotherapy and up to 6 weeks after radiotherapy. Assessments were recorded during radiotherapy and for 6 weeks following it. Each participant’s worst graded diarrhea was the endpoint value. Severity categories ranged from Grade 0, none, through Grade 4, life-threatening, with mild, moderate, and severe grades in between.
The endpoint description identifies three participants who were not included in baseline or endpoint analyses: two from Arm I and one from Arm II. The stated reasons were cancellations and protocol violations. The registry record does not report the allocation sequence method, concealment procedures, or further details about masking. It also does not report a planned sample-size justification, the numbers randomized to each arm, or the complete analysis populations beyond the endpoint exclusions described.
The registry lists secondary outcomes covering bowel symptoms, CTCAE-graded diarrhea toxicity, bowel-function questionnaire responses, antidiarrheal medication use, quality of life, and fatigue. These listed outcomes describe the scope of assessment, but their numerical results 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
| Stage | Arm I: Sulfasalazine | Arm II: Placebo |
|---|---|---|
| STARTED | 44 | 43 |
| COMPLETED | 43 | 42 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Arm I: Sulfasalazine | Arm II: Placebo |
|---|---|---|
| Withdrawal by Subject | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Two patients in Arm I and one patient from Arm II were not included in the baseline analysis nor the endpoint analyses due to cancellations and protocol violations.
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: Two patients in Arm I and one patient from Arm II were not included in the baseline analysis nor the endpoint analyses due to cancellations and protocol violations.
| Characteristic | Unit | Arm I: Sulfasalazine | Arm II: Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 42 | 42 | 84 | |
| Age, Continuous | years | 59 (37 to 84) | 56.5 (37 to 81) | 58 (37 to 84) |
| Sex: Female, Male: Female | Participants | 15 | 18 | 33 |
| Sex: Female, Male: Male | Participants | 27 | 24 | 51 |
| Region of Enrollment: United States | participants | 42 | 42 | 84 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT), measured over During radiation therapy and up to 6 weeks post radiation therapy.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was each participant’s maximum diarrhea severity during radiotherapy and up to 6 weeks after radiotherapy. The study used CTCAE v4.0 grades: Grade 0 indicated none, Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening diarrhea. Assessments were recorded during radiotherapy and for 6 weeks after it, and the endpoint retained the worst grade recorded for each participant.
Using the maximum grade focuses on whether a participant experienced a more severe episode, rather than describing only a single assessment or an average across assessments. It also turns observations made over the treatment and follow-up period into an ordered outcome for each participant. This can be useful when the clinical question concerns the most severe toxicity experienced over time. As a general statistical point, reducing repeated assessments to a maximum does not describe when symptoms occurred, how long they lasted, or how often they recurred. Those features would require other summaries or outcomes.
The registry specifies a two-sided Wilcoxon rank-sum test to compare the distributions of maximum grades between the treatment arms. The actual grade counts and the test result are not reported in the registry record. Consequently, the direction, magnitude, and precision of any difference in the primary endpoint cannot be assessed from the recorded results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question the trial set out to answer and the planned primary comparison, but it does not report the primary endpoint results. In particular, it gives no counts of participants at each maximum diarrhea grade, no arm-specific distribution, and no result from the stated Wilcoxon rank-sum test. There is therefore no posted primary estimate or confidence interval from which to describe the size or precision of an observed difference.
The endpoint was ordinal: the grades run from no diarrhea to life-threatening diarrhea. For this kind of outcome, the distribution across severity categories matters. A comparison may reflect differences in the overall ordering of grades, but without the actual category counts or test result, it is not possible to say how the distributions compared in this trial. The registry’s purpose statement and rationale describe the question being studied; they are not evidence of an outcome.
Several secondary outcomes are listed, including rectal bleeding, abdominal cramping, tenesmus, constipation, diarrhea severity summaries, bowel-function questionnaire responses, antidiarrheal medication use, quality of life, and fatigue. Listing an outcome does not establish that a result was favorable, unfavorable, or statistically distinguishable between arms. Numerical results for those outcomes are not reported in the registry record.
The adverse-event record includes serious-event counts by arm and a list of serious-event terms with percentages. Those safety figures are separate from the primary diarrhea-severity endpoint. They do not substitute for the missing primary outcome distributions or test result. The serious-event counts also do not provide a comparative estimate of the primary endpoint.
Statistical interpretation depends on more than whether a test is named in a protocol description. A reader would ordinarily need the observed arm-specific outcomes, an effect estimate suited to the outcome, and information about uncertainty to assess how precisely the trial answers its question. These primary-result details are not reported in the registry record. The results therefore remain indeterminate from this record: it documents the planned comparison, but not the observed primary outcome or its statistical uncertainty.
Any planning illustration based on an observed effect should not be confused with observed power or with a trial result. A planning calculation is hypothetical and depends on its assumptions; it cannot fill in outcome information missing from the registry record. The record does not report the trial’s own sample-size justification, so the adequacy of the planned enrollment for the primary comparison cannot be judged from the stated information.
9. Statistical Methods Explained
The primary endpoint was an ordered categorical measure: each participant was represented by the worst CTCAE v4.0 diarrhea grade recorded during radiotherapy and up to 6 weeks afterward. The grades distinguish levels of severity, from Grade 0, none, to Grade 4, life-threatening. Such grades have a natural order, but the distance between adjacent categories is not necessarily equal. For example, a change between neighboring grades should not automatically be treated as the same-sized change everywhere on the scale.
The registry states that a two-sided Wilcoxon rank-sum test would compare the equality of the distributions of maximum diarrhea severity in the two arms. In general, this test pools observations from the groups, ranks them, and compares the rank patterns between groups. It is often used for outcomes that are ordered or measured on a continuous scale when a comparison based on ranks is appropriate. For an ordinal grade, ranks preserve ordering without requiring the grades to behave like equally spaced measurements.
A two-sided test evaluates departures in either direction: the distributions could differ with higher severity tending toward either arm. The test does not, by itself, express the size of a clinically meaningful difference. A p-value, if reported, would summarize how compatible the data are with the test’s null hypothesis under its assumptions; it would not be the probability that the null hypothesis is true. The registry does not report a p-value, a test statistic, or the outcome counts needed to evaluate the primary comparison.
A confidence interval is a general way to express the uncertainty around an estimated effect. Its interpretation depends on the estimate and method used, and its width reflects the precision of the data under that method. The primary result and a confidence interval for it are not reported in the registry record. Without an estimate and its uncertainty, the magnitude and precision of the treatment-arm contrast cannot be described.
The endpoint uses the maximum grade over repeated assessments. As a general statistical consideration, a maximum captures the most severe recorded grade, but it discards information about the timing, duration, and recurrence of symptoms. Participants with the same maximum may have had different patterns over the assessment period. The registry also lists other outcomes that address different aspects of symptoms and function, but their results are not reported in the record.
For a result to be interpreted fully, readers would also need to know how observations were handled when assessments were missing, whether the analysis followed randomized assignment, and whether any adjustments were made for the several outcomes examined. These details are not reported in the registry record. The primary endpoint description does identify participants excluded from baseline and endpoint analyses because of cancellations and protocol violations, but it does not describe any broader missing-data procedure.
As general statistical context, missing outcome data can affect an analysis if the availability of measurements is related to the outcome or differs between groups. The impact depends on why data are missing and how the analysis handles them. No imputation method, sensitivity analysis, or other missing-data approach is reported in the registry record. It would therefore be inappropriate to assume that missing observations were treated in a particular way.
Multiplicity is another general concern when a study examines multiple outcomes or comparisons. Repeated testing can increase the chance of finding at least one apparently unusual result under a setting where all null hypotheses hold. A prespecified hierarchy or adjustment can address some multiplicity concerns, but neither such a procedure nor a broader statistical analysis plan is reported in the registry record. The primary endpoint is identified, but no multiplicity strategy is stated.
Finally, planning calculations and observed results answer different questions. A sample-size illustration uses assumptions about the effect to be detected and the chosen error rate; it is not evidence about what occurred in the trial. The registry does not report the trial’s own sample-size justification. Any planning illustration should be understood as a planning exercise, not as observed power or as a substitute for the primary outcome results.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary endpoint and lists several secondary outcomes, including multiple symptom measures, bowel-function questionnaire responses, medication use, quality of life, and fatigue. It does not report whether the analyses were arranged in a prespecified testing hierarchy, whether multiplicity adjustments were planned, or how interpretation across the outcomes was intended to be controlled. These procedures are not reported in the registry record.
The primary endpoint description says that two participants in Arm I and one participant in Arm II were excluded from baseline and endpoint analyses because of cancellations and protocol violations. This is the specific endpoint-population information recorded. The registry does not otherwise describe the analysis population, such as whether participants were analyzed according to randomized assignment, nor does it provide a full account of participants with missing assessments.
No method for handling missing endpoint measurements is reported in the registry record. The record also does not report imputation, sensitivity analyses, or reasons for missingness beyond the cancellations and protocol violations identified for the excluded participants. As a general matter, missingness can affect estimated group comparisons, and its potential impact depends on why observations are unavailable and how the analysis handles them. The record does not provide enough information to assess that issue.
The primary endpoint results themselves are not reported, so no assessment of the consequences of exclusions or missing observations can be made from observed grade distributions. The absence of a reported multiplicity strategy also means that the interpretation of any collection of secondary findings cannot be reconstructed from this record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm I: Sulfasalazine | 1 | 43 | 2.3% |
| Arm II: Placebo | 2 | 42 | 4.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm I: Sulfasalazine | 42 of 43 |
| Arm II: Placebo | 40 of 42 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm I: Sulfasalazine | Arm II: Placebo |
|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 0 of 43 | 1 of 42 |
| Abdominal pain | Gastrointestinal disorders | 1 of 43 | 0 of 42 |
| Constipation | Gastrointestinal disorders | 0 of 43 | 1 of 42 |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | 0 of 43 | 1 of 42 |
| Tenesmus | Gastrointestinal disorders | 0 of 43 | 1 of 42 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm I: Sulfasalazine | Arm II: Placebo |
|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 33 of 43 | 32 of 42 |
| Abdominal pain | Gastrointestinal disorders | 15 of 43 | 22 of 42 |
| Tenesmus | Gastrointestinal disorders | 17 of 43 | 16 of 42 |
| Anemia | Blood and lymphatic system disorders | 15 of 43 | 17 of 42 |
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | 17 of 43 | 15 of 42 |
| Constipation | Gastrointestinal disorders | 15 of 43 | 15 of 42 |
| White blood cell decreased | Investigations | 8 of 43 | 18 of 42 |
| Platelet count decreased | Investigations | 4 of 43 | 8 of 42 |
| Neutrophil count decreased | Investigations | 4 of 43 | 6 of 42 |
| Lymphocyte count decreased | Investigations | 2 of 43 | 7 of 42 |
Serious events with the highest arm-level rate: anemia (2.4%), constipation (2.4%), gastrointestinal disorders - other, specify (2.4%), tenesmus (2.4%), abdominal pain (2.3%).
The registry’s serious-adverse-event figures list 1 affected participant among 43 at risk in Arm I, sulfasalazine, and 2 affected participants among 42 at risk in Arm II, placebo. These are the posted serious-event counts; they should be read as safety summaries, not as the primary diarrhea-severity outcome. The registry record does not provide a comparative statistical analysis or uncertainty estimate for these counts.
The record also lists serious-event terms with percentages: Anemia, 2.4%; Constipation, 2.4%; Gastrointestinal disorders - Other, specify, 2.4%; Tenesmus, 2.4%; and Abdominal pain, 2.3%. The record does not identify an arm alongside each term in this list, so these percentages cannot be assigned to a particular treatment arm on the basis of the recorded information.
The safety summary includes separate columns for other adverse events, with 42 affected participants among 43 at risk in Arm I and 40 among 42 at risk in Arm II. These figures are distinct from the serious-event counts. Deaths are not reported in the registry record. The safety data do not, on their own, establish a treatment effect or replace the missing primary endpoint results.
12. What the Result Does, and Does Not, Mean
The trial was designed to compare sulfasalazine with placebo for prevention of acute diarrhea in patients receiving pelvic radiotherapy. Its primary outcome was the maximum CTCAE v4.0 diarrhea grade over radiotherapy and follow-up through 6 weeks after radiotherapy. The registry record names a two-sided Wilcoxon rank-sum test for comparing the arm-specific distributions.
What the record does not establish is how those distributions differed. It does not report the number of participants in each severity grade by arm, the test result, an effect estimate, or a confidence interval for the primary endpoint. The record therefore cannot support a conclusion about the direction, size, or precision of the primary comparison. The study rationale and planned analysis are not outcome findings.
The secondary outcome list shows that the study intended to assess additional bowel symptoms, symptom severity, medication use, quality of life, and fatigue. However, outcome names alone do not show what participants experienced or whether outcomes differed between groups. Numerical results for these secondary outcomes are not reported in the registry record.
The serious-adverse-event figures are reported separately and describe the number of affected participants in each arm. They should not be treated as a measure of the primary endpoint or as a complete account of the comparative balance of benefits and harms. The registry provides no statistical comparison or uncertainty estimate for these safety counts, and deaths are not reported in the registry record.
In general, a randomized comparison is interpreted by examining the outcome data, the estimated contrast, and the uncertainty around it, alongside the study’s analysis procedures and limitations. Here, the record describes the design and intended endpoint but lacks the primary results and important analysis details. Thus, it documents what the trial set out to test, not whether the posted data show a difference between sulfasalazine and placebo.
13. Why This Trial Matters Statistically
This trial raises a useful statistical question about how to compare ordered toxicity grades collected repeatedly over a treatment and follow-up period. The endpoint reduces each participant’s recorded diarrhea assessments to a maximum CTCAE grade. That summary is directly focused on worst severity, while necessarily leaving out timing, duration, and recurrence. Recognizing what a summary captures—and what it omits—is central to interpreting clinical outcomes.
The planned Wilcoxon rank-sum test is consistent with comparing ordered distributions without treating the grades as equally spaced numerical measurements. This illustrates why the scale of an outcome matters when choosing an analysis. A test can be named and appropriate in principle, but meaningful interpretation still requires the observed grade distributions and an estimate of the comparison’s uncertainty.
The record also illustrates the distinction between a registered research question and a reported result. It gives a phase III randomized design, an identified primary endpoint, and an intended test, but does not report the primary outcome findings. Without those findings, readers cannot judge the magnitude or precision of the comparison from this record. The missing outcome data also prevent a direct assessment of how the exclusions affected the analysis.
Finally, the record lists multiple secondary outcomes and includes separate safety summaries. These components address different questions and should not be conflated with the primary endpoint. Their presence makes clear why outcome definitions, analysis populations, missing-data procedures, and multiplicity plans matter for interpreting a trial. Several of those details are not reported in the registry record, limiting what can be concluded statistically.
14. 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 main limitation for interpreting this trial from the registry record is that the primary endpoint results are not reported. There are no arm-specific counts for maximum diarrhea grades, no result from the stated Wilcoxon rank-sum test, and no effect estimate or confidence interval. Consequently, neither the direction nor the precision of the primary comparison can be assessed.
The primary endpoint description notes that two participants in Arm I and one participant in Arm II were excluded from baseline and endpoint analyses because of cancellations and protocol violations. The record does not provide further details about these exclusions, the full analysis populations, or how missing assessments were handled. It also does not describe sensitivity analyses that might show how the primary comparison changes under different assumptions about missing observations.
The registry lists several secondary outcomes, but their numerical results are not reported in the registry record. It does not report a multiplicity plan or statistical analysis plan that would clarify how those outcomes were to be interpreted together. The lack of these details limits assessment of the full analysis strategy.
The record also does not report the trial’s own sample-size justification, the allocation procedure, or further operational details about masking. Enrollment is reported as 87, but the record does not state the numbers randomized to each arm for the primary analysis. Safety-group counts should not be assumed to define the primary analysis population.
These limitations concern what can be learned from the registry record; they do not establish that the trial lacked procedures or analyses that are simply not recorded there. The record supports description of the study design and planned endpoint, but not a complete statistical appraisal of its primary findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sulfasalazine in Preventing Acute Diarrhea in Patients With Cancer Who Are Undergoing Pelvic Radiation Therapy — NCT01198145.
- Registry record last updated 2020-05-12; status last verified 2020-04.
- Results first posted 2017-04-04.
- 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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18. Record Summary
NCT01198145 is a completed phase III randomized, double-masked, parallel-group study sponsored by the Alliance for Clinical Trials in Oncology. Enrollment was 87. The listed start was 2011-04, and primary completion was 2013-07-22. Participants received oral sulfasalazine or placebo twice daily during radiotherapy and for 4 weeks afterward.
The primary endpoint was each participant’s maximum CTCAE v4.0 diarrhea grade during radiotherapy and up to 6 weeks afterward. The registry states that a two-sided Wilcoxon rank-sum test would compare the distributions. It identifies two Arm I participants and one Arm II participant excluded from baseline and endpoint analyses because of cancellations and protocol violations.
Primary and secondary outcome results, a sample-size justification, missing-data procedures, and a multiplicity strategy are not reported in the registry record. Serious-adverse-event counts are recorded separately, but do not supply the missing primary outcome comparison.