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 NSAID Effects on Clinical and Imaging Breast Biomarkers (NCT01761877), a non-randomized phase 2 study. The primary outcome is Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01761877 |
| Phase | Phase 2 |
| Condition | Inflammation, Cancer, Pain |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 114 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Stony Brook University |
| Results posted | Yes |
2. Clinical Question
Population
Women taking aromatase inhibitors for adjuvant therapy for breast cancer. The registry describes breast-density measurements and pain and stiffness associated with regular aromatase-inhibitor use as study interests. Enrollment was 114, but the registry does not report the number of participants contributing primary endpoint data in each group. It notes that breast-density data were unavailable for 4 participants in the observation group because of MRI intolerance.
Intervention
The intervention was sulindac, identified in the registry as Clinoril. The intervention group description specifies 150 mg twice daily for 12 months, with up to 4 MRI within 12 months. The registry states that the study aimed to determine whether daily sulindac decreased breast density and whether it reduced pain and stiffness associated with regular aromatase-inhibitor use.
Comparator
The observational group continued aromatase-inhibitor treatment and was monitored with MRI and standard-of-care tests every 6 months for up to 12 months. This was a non-randomized comparison, so the observational group should not be treated as a like-for-like control. Differences between groups could reflect factors other than sulindac; the registry does not report adjustment for all possible sources of group difference.
Primary question
The primary endpoint concerned change in breast density, measured as a fat-to-water ratio by MRI, from baseline to 12 months. The registry describes adjusted estimates of relative change in percent breast density. It does not report the group estimates, the between-group contrast, or confidence intervals for this endpoint. Therefore, the clinical question is identifiable from the record, but the size and precision of the posted primary result cannot be assessed from the recorded details.
3. Trial Design
The registry lists this as a Phase 2, completed, parallel study sponsored by Stony Brook University. Its recorded start is 2012-12 and its primary completion date is 2019-02-07. Enrollment is listed as 114. The study used non-randomized allocation and no masking. These design features matter when interpreting any comparison: the groups were not formed by random assignment, and participants and study personnel were not masked to group assignment.
The intervention group description says women taking aromatase inhibitors for adjuvant breast-cancer therapy received 150 mg of sulindac twice daily for 12 months. They could receive up to 4 MRI within 12 months. The observational group continued their treatment and was monitored with MRI and standard-of-care tests every 6 months for up to 12 months. The registry does not report how participants entered each group or whether the groups were similar at baseline.
The registry describes two study purposes: assessing whether daily sulindac decreases breast density, a risk factor for breast-cancer development, and assessing pain and stiffness associated with regular aromatase-inhibitor use. The primary endpoint was change in breast density measured by MRI. Muscle and joint pain and stiffness is listed as a secondary outcome. The record lists 3 outcome measures and 3 analyses, but does not report the full analysis plan or outcome results in the registry record for this interpretation.
Non-randomized allocation limits causal interpretation because measured and unmeasured differences between groups may affect outcomes. The distinct MRI-monitoring schedules also mean that the planned observation process was not identical between groups. The registry record does not report whether those differences were addressed analytically.
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: Patients assigned to receive sulindac were required to complete a NSAID washout period.
Overall Study
| Stage | Sulindac (Clinoril) | Observational |
|---|---|---|
| STARTED | 58 | 56 |
| COMPLETED | 43 | 40 |
| NOT COMPLETED | 15 | 16 |
Reasons for not completing this period:
| Reason | Sulindac (Clinoril) | Observational |
|---|---|---|
| Adverse Event | 7 | 0 |
| Withdrawal by Subject | 6 | 4 |
| Stopped taking AI Aromatase Inhibitor | 1 | 5 |
| Death | 0 | 1 |
| MRI intolerant | 1 | 6 |
Analysis population for the primary outcome, as defined in the registry: Breast density data were unavailable for 4 participants in the observation group due to MRI intolerance. This reduced the sample size for the outcome of change in breast density for the observation arm compared to the secondary endpoints.
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: For baseline analyses for the sulindac arm, we included only those participants who remained in the study after the NSAID washout and who started the intervention with sulindac (n=50). For the baseline analyses for the observation arm, we included those participants who either completed their baseline MRI and/or questionnaires for the secondary arthralgia endpoints (n=50).
| Characteristic | Unit | Sulindac (Clinoril) | Observational | Total |
|---|---|---|---|---|
| Participants analysed | 50 | 50 | 100 | |
| Age, Continuous | years | 62.6 (SD 5.5) | 64.2 (SD 6.6) | 63.4 (SD 6.1) |
| Sex: Female, Male: Female | Participants | 50 | 50 | 100 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White, Non-Hispanic | Participants | 44 | 46 | 90 |
| Race/Ethnicity, Customized: Black, Non-Hispanic | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Hispanic | Participants | 3 | 3 | 6 |
| Race/Ethnicity, Customized: Asian, Non-Hispanic | Participants | 2 | 1 | 3 |
| Region of Enrollment: United States | Participants | 50 | 50 | 100 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Breast Density Measured as Fat to Water Ratio by Magnetic Resonance Imaging, measured over Baseline and 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change in breast density |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in breast density measured as a fat-to-water ratio by MRI, with assessment at baseline and 12 months. The registry describes the reported measure as adjusted estimates of relative change in percent breast density. It identifies the outcome as a continuous measure summarized by a mean and a 95% confidence interval.
Breast density is included because the registry describes it as a risk factor for breast-cancer development. MRI provides the imaging measurement used for this endpoint; the registry does not report additional details about image processing, reader procedures, or how the fat-to-water ratio was converted to percent breast density. Nor does it state a threshold for a change that would be considered clinically meaningful.
For interpretation, the endpoint’s estimate would indicate the direction and size of the measured change, while its confidence interval would show the statistical precision of that estimate under the analysis used. The registry record does not report the primary endpoint estimates or confidence intervals, so neither the magnitude nor precision of the recorded primary outcome can be described. It also does not report a numerical contrast between the sulindac and observational groups.
The record notes that MRI intolerance left breast-density data unavailable for 4 participants in the observation group, reducing the sample size for this outcome relative to the secondary endpoints. That missingness is relevant because the endpoint depends on MRI measurement being available at the required assessment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary outcome, its measurement method, assessment timing, and summary format, but the primary result values are not reported in the registry record. In particular, no adjusted estimate of relative change in percent breast density, confidence interval, or numerical comparison between the study groups is included in the registry record for this interpretation. The direction, magnitude, and precision of the primary result therefore cannot be characterized.
The study was non-randomized and unmasked. Consequently, a difference between the groups, if reported, would not by itself establish that sulindac caused the difference. Group assignment may be related to participant characteristics or other factors that also influence breast density or symptoms. The registry record does not report baseline characteristics or the details of any adjustment beyond describing the primary endpoint estimates as adjusted.
The primary endpoint was measured at baseline and 12 months, while the intervention description specifies sulindac for 12 months. The observation group had MRI and standard-of-care tests every 6 months for up to 12 months; the intervention group could receive up to 4 MRI within 12 months. Different monitoring schedules may affect the opportunity to obtain measurements. The record does not explain how this difference was handled in the analysis.
The registry reports that breast-density data were unavailable for 4 participants in the observation group because of MRI intolerance. It does not report whether missingness was related to participant characteristics or outcome values, what methods were used to handle missing data, or whether sensitivity analyses were performed. Thus, the effect of missing measurements on the primary estimate cannot be judged from the recorded details.
The record lists muscle and joint pain and stiffness as a secondary outcome, but does not report its results. It also lists serious and other adverse-event counts, which should be read as registry-reported safety summaries rather than as a randomized comparison. Overall, the record establishes what the trial set out to measure and describes some design constraints, but it does not give enough outcome information to assess the primary result or its uncertainty.
9. Statistical Methods Explained
The registry describes the primary outcome as a continuous measure summarized by a mean, with a 95% confidence interval. It also says the estimates are adjusted and concern relative change in percent breast density. The record does not report the adjustment variables, model specification, or the numerical estimates. The following explanations are general statistical context, not a description of unreported methods used in this study.
What does a confidence interval communicate?
In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis. A narrower interval indicates greater precision under that analysis, while a wider interval indicates less precision. A confidence interval is not a guarantee that the true value lies within the particular interval, and it does not resolve possible bias from non-randomized group assignment, measurement differences, or missing data. Because the registry record does not report the endpoint interval, its precision cannot be evaluated.
What does adjustment mean?
In general, an adjusted estimate accounts for selected variables through a statistical model. Adjustment can address measured differences included in the model, but does not automatically eliminate confounding. Its interpretation depends on which variables were used, how they were measured, and how the model was specified. The registry characterizes the primary estimates as adjusted but does not report the adjustment variables or analysis details. It is therefore not possible to determine which differences were accounted for or whether the adjustment was adequate for the comparison.
Why does non-randomized allocation matter?
In general, random assignment helps make treatment groups comparable on average, including for factors that are not measured. With non-randomized allocation, group membership may be associated with participant characteristics, care decisions, or other factors that influence outcomes. Statistical adjustment may reduce some measured differences, but its ability to do so depends on the information collected and the analysis. The record does not report how allocation occurred, group baseline characteristics, or enough model detail to assess the extent to which confounding was addressed. A group contrast should therefore be interpreted as an association unless stronger design and analysis evidence supports a causal interpretation.
How should the imaging schedule be considered?
In general, outcome measurement schedules can influence whether measurements are available and when changes are observed. The intervention description allows up to 4 MRI within 12 months, while the observational group is described as having MRI and standard-of-care tests every 6 months for up to 12 months. The registry does not report whether actual imaging frequency differed, whether all scans were used for the endpoint, or how timing and repeated measurements were handled. These details matter when comparing an outcome measured through imaging.
What can planning calculations say?
In general, sample-size calculations describe the number of participants per arm that a future study might plan for under specified assumptions. They do not measure the power actually achieved by a completed study. The planning assumptions described for this trial use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect set as a stated fraction of the observed effect. The record does not report the resulting planning values in the registry record for this interpretation. Any such values are illustrations based on assumptions, not observed power and not evidence that the study was designed with those assumptions.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model understates variability, its uncertainty estimates may be too small and its intervals may be too narrow. The registry record does not report whether over-dispersion was relevant to this trial’s analyses or whether it was assessed. This general consideration cannot be used to infer that the trial’s estimates were affected.
The registry lists 3 outcome measures and 3 analyses, but does not report the full statistical analysis plan, model diagnostics, or detailed results. No specific testing procedure or adjustment for multiple comparisons can be inferred from those counts alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and 3 analyses. These counts do not reveal which outcomes were tested together, which were considered primary or secondary beyond the named breast-density primary endpoint and the listed muscle and joint pain and stiffness secondary outcome, or whether any multiplicity adjustment was planned. The statistical plan for multiple comparisons is not reported in the registry record. Without that information and the outcome results, the risk of interpreting chance findings among multiple analyses cannot be assessed.
For the primary breast-density endpoint, the registry specifically notes that MRI intolerance left data unavailable for 4 participants in the observation group. It says this reduced the sample size for that outcome in the observation arm compared with the secondary endpoints. The record does not report missingness in the intervention arm for this endpoint, the number analyzed by group, the analysis population, or the method used to handle missing observations. It also does not report sensitivity analyses to assess how assumptions about missing data might affect the result.
In general, missing-data methods rely on assumptions about why measurements are absent. If the chance of a missing measurement is related to participant characteristics or the outcome itself, an analysis restricted to available measurements may not represent the intended population. The record does not report enough information to determine whether that concern applies or how it was addressed.
The record does not report whether analyses followed an intention-to-treat principle, included all enrolled participants, or used another analysis population. It also does not report how participants with incomplete follow-up were handled. These omissions limit assessment of the analysis population and the impact of missing data.
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 |
|---|---|---|---|
| Sulindac (Clinoril) | 3 | 50 | 6.0% |
| Observational | 1 | 50 | 2.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sulindac (Clinoril) | 0 of 50 |
| Observational | 1 of 50 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sulindac (Clinoril) | 25 of 50 |
| Observational | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Sulindac (Clinoril) | Observational |
|---|---|---|---|
| Intraparenchymal Hemorrhage associated with cerebral amyloid angiopathy | Nervous system disorders | 1 of 50 | 0 of 50 |
| Transient Pancreatitis of Unclear Etiology | Gastrointestinal disorders | 1 of 50 | 0 of 50 |
| B cell Lymphoma | Blood and lymphatic system disorders | 1 of 50 | 0 of 50 |
| Antral Gastritis | Gastrointestinal disorders | 1 of 50 | 0 of 50 |
| death | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 50 | 1 of 50 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sulindac (Clinoril) | Observational |
|---|---|---|---|
| hypertension | Vascular disorders | 7 of 50 | 0 of 0 |
| upset stomach or pain | Gastrointestinal disorders | 6 of 50 | 0 of 0 |
| rash | Skin and subcutaneous tissue disorders | 3 of 50 | 0 of 0 |
| headache | Nervous system disorders | 3 of 50 | 0 of 0 |
| hyperglycemia | Metabolism and nutrition disorders | 3 of 50 | 0 of 0 |
| insomnia | Psychiatric disorders | 3 of 50 | 0 of 0 |
Serious events with the highest arm-level rate: intraparenchymal hemorrhage associated with cerebral amyloid angiopathy (2.0%), transient pancreatitis of unclear etiology (2.0%), b cell lymphoma (2.0%), antral gastritis (2.0%), death (2.0%).
The registry reports serious adverse-event figures for the sulindac and observational groups separately. For the sulindac group, it lists 3 participants affected among 50 at risk for serious events, and 25 affected among 50 at risk for other events. For the observational group, it lists 1 participant affected among 50 at risk for serious events; the other-event fields list 0 at risk and 0 affected. The recorded deaths are 0 in the sulindac group and 1 in the observational group.
The registry also lists serious-event terms with 2.0% beside each: intraparenchymal hemorrhage associated with cerebral amyloid angiopathy, transient pancreatitis of unclear etiology, B cell lymphoma, antral gastritis, and death. The record does not give enough detail to determine from these terms alone how they relate to the group-level counts or whether any event was considered related to treatment.
These are registry summaries, not estimates from a randomized safety comparison. The study was non-randomized, and the record does not report the criteria for event attribution, duration of safety follow-up, or a formal comparative analysis. The counts should not be interpreted as establishing that sulindac caused or prevented an event.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed Phase 2, non-randomized study that examined breast density by MRI among women taking aromatase inhibitors for adjuvant breast-cancer therapy. It also describes an interest in pain and stiffness associated with regular aromatase-inhibitor use. The primary outcome was defined as change in breast density from baseline to 12 months, summarized through adjusted estimates of relative change in percent breast density.
Those design and endpoint details explain what the study set out to examine, but they do not establish what the study found. The numerical primary endpoint results, confidence intervals, and between-group contrast are not reported in the registry record. The secondary pain and stiffness results are also not reported in the registry record. It is therefore not possible to describe the direction, size, or precision of either outcome result.
Even if a numerical contrast were available, non-randomized allocation would limit causal interpretation. The observational group is not a like-for-like control by design, and the registry does not report enough about baseline characteristics or adjustment methods to judge how comparable the groups were. The different MRI-monitoring descriptions and missing breast-density data in the observation group also matter when assessing the endpoint.
The serious and other adverse-event counts are descriptive registry entries. They do not by themselves establish a treatment-related safety effect, and the record does not report a formal comparative safety analysis. The study’s stated purpose and its registry status should not be mistaken for evidence of a particular benefit or harm. The most defensible reading is that the record specifies a clinical question and study structure, while leaving the main outcome estimates and important analysis details unreported.
13. Why This Trial Matters Statistically
This trial illustrates why a clinical question, a design description, and a numerical result must be distinguished. The registry identifies a measurable primary endpoint—change in MRI breast density—and describes the study groups and assessment period. But without the endpoint estimates and confidence intervals, readers cannot assess the observed magnitude or statistical precision. Knowing what was measured does not substitute for knowing the result.
It also illustrates the importance of allocation. A non-randomized study can describe outcomes in groups receiving different care, but group differences may reflect factors beyond the intervention. The registry characterizes the primary estimates as adjusted, yet does not report the adjustment variables or model details. Readers therefore cannot judge how much the analysis addressed possible confounding.
Measurement availability is another statistical issue. The record notes missing MRI breast-density data for 4 participants in the observation group because of MRI intolerance. That is specific to the primary endpoint and may make its analysis population different from those for secondary endpoints. The missing-data method and sensitivity analyses are not reported, so the robustness of the primary result cannot be assessed.
Finally, the safety counts show why descriptive figures need context. They are not a randomized comparison, and the registry does not report attribution or a formal comparative analysis. Across the endpoint, design, missing-data, and safety information, the record supports careful description of what was planned and recorded, but not a quantitative conclusion about the study’s findings.
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 interpretation is that the registry record does not report the primary outcome estimates or confidence intervals. Without these, the observed size and precision of change in breast density cannot be assessed. Results for the listed secondary outcome of muscle and joint pain and stiffness are also not reported in the registry record for this interpretation.
Non-randomized allocation and lack of masking are additional design constraints. The record does not describe how participants entered the sulindac or observational group, report baseline characteristics, or specify the adjustment variables used for the primary estimates. Consequently, the degree of comparability between groups and the handling of potential confounding cannot be evaluated.
The intervention and observational group descriptions differ in their MRI-monitoring schedules. The registry does not report whether actual imaging followed those schedules, how MRI timing was incorporated into the analysis, or whether measurement procedures were standardized across groups. It also does not report image-reading procedures or the clinical importance threshold for a breast-density change.
Missing primary endpoint data are explicitly noted for 4 participants in the observation group because of MRI intolerance. The record does not describe missing-data methods, analysis populations, or sensitivity analyses. The statistical plan for multiplicity and the detailed model specification are also not reported in the registry record. These omissions make it difficult to judge the robustness and scope of any result, even apart from the absence of numerical outcome estimates.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: NSAID Effects on Clinical and Imaging Breast Biomarkers — NCT01761877.
- Registry record last updated 2023-02-10; status last verified 2023-01.
- Results first posted 2023-02-10.
- 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
The registry lists NCT01761877, “NSAID Effects on Clinical and Imaging Breast Biomarkers,” as a completed Phase 2, parallel, non-randomized, unmasked study sponsored by Stony Brook University. Enrollment is listed as 114. The recorded start is 2012-12, and the primary completion date is 2019-02-07.
Women taking aromatase inhibitors for adjuvant breast-cancer therapy were described in a sulindac group receiving 150 mg twice daily for 12 months and an observational group continuing treatment with MRI and standard-of-care monitoring. The primary endpoint was change in breast density measured by MRI from baseline to 12 months. Muscle and joint pain and stiffness is listed as a secondary outcome.
The registry notes missing breast-density data for 4 participants in the observation group because of MRI intolerance. Numerical primary endpoint results, confidence intervals, detailed analysis methods, and secondary outcome results are not reported in the registry record.