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 Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy (NCT03631641), a na phase 2 study. The primary outcome is Incidence Rate of Adenomas.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03631641 |
| Phase | Phase 2 |
| Condition | Colon Adenoma, Colon Carcinoma, Lynch Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | John Hays |
| Results posted | Yes |
2. Clinical Question
Population
Participants with Lynch syndrome and a history of surgery to remove part of the colon were eligible for the study. The listed conditions include colon adenoma, colon carcinoma, Lynch syndrome, and MLH1 and MSH2 gene mutations. The registry record does not report further eligibility details or a more specific description of the intended analysis population.
Intervention
The intervention was nivolumab, a biological treatment. The regimen description specifies intravenous administration over 60 minutes on day 1, repeated every 3 months for a total of 8 courses, provided there was no disease progression or unacceptable toxicity.
Comparator
This was a single-group study, not a randomized comparison. The primary-endpoint description refers to an incidence rate of 0.33 among Lynch patients not receiving nivolumab as the benchmark for comparison. The registry record does not describe an enrolled control group or provide further details about that benchmark population.
Primary question
The intended question was whether the incidence rate of colon adenomas at 3 years among participants receiving nivolumab differed from the rate of 0.33 cited for Lynch patients not receiving nivolumab. The registry record says the associated confidence intervals would be used for this assessment. Data were not obtained and analyzed because the study terminated early, so the intended comparison has no reported result.
3. Trial Design
This was a phase II study of nivolumab for prevention of colon adenomas in people with Lynch syndrome and a history of partial colectomy. The registry describes a single-group model and lists allocation as NA. Masking was none. These features mean the study was not a blinded, randomized comparison in which participants were assigned to nivolumab or a concurrent control treatment. The primary-endpoint description instead cites an incidence rate among Lynch patients not receiving nivolumab as a reference value.
The listed nivolumab regimen was intravenous administration over 60 minutes on day 1, with treatment repeating every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity. This describes the planned treatment schedule; it does not establish how much treatment any participant actually received. The registry record does not report treatment exposure or adherence.
The study started on 2018-10-04, and the listed primary completion date is 2021-01-25. Its status is terminated. Enrollment is listed as 3. The registry explains that primary-endpoint data were not obtained and analyzed because of early termination. Therefore, the design and planned question can be described, but an efficacy estimate from the intended endpoint cannot be drawn from the posted results.
The record lists 4 outcome measures and 0 analyses. It does not report a detailed statistical analysis plan, the reason for termination, a sample-size justification for the trial, or an interim-analysis plan. The planning assumptions attached to sample-size illustrations are not a substitute for the trial's own design justification.
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 | Treatment (Nivolumab) |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Data was not obtained and analyzed due to early study termination
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 | Treatment (Nivolumab) |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence Rate of Adenomas, measured over At 3 years.
| 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 the incidence rate of adenomas, with an assessment timeframe of 3 years. An incidence rate describes the occurrence of new events over a period of observation; in this study, the event of interest was an adenoma. As a general statistical concept, this type of endpoint can be useful when the question concerns how frequently new events arise during follow-up, rather than only whether any participant ever experiences an event.
The registry description says confidence intervals were intended to accompany the rate and be used to determine whether it differed significantly from 0.33, the rate cited for Lynch patients not receiving nivolumab. A confidence interval conveys the uncertainty around an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision. The registry record does not report the endpoint's unit, parameter, or dispersion measure, and no estimated rate or associated confidence interval is posted.
Most importantly, the record states that data were not obtained and analyzed because the study terminated early. The endpoint therefore has no reported estimate. This is missing outcome information, not a reported finding of zero adenomas or a rate of zero.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the primary endpoint was not analyzed. Although the study was intended to assess adenoma incidence at 3 years and compare the result with a benchmark of 0.33, the registry record states that data were not obtained and analyzed because of early termination. There is consequently no posted incidence-rate estimate, confidence interval, or statistical comparison with the benchmark. The direction, magnitude, and precision of any treatment-associated difference are not established by this record.
The benchmark does not function as a concurrent control group. The study is described as single-group, with allocation listed as NA and no masking. The primary-endpoint description refers to Lynch patients not receiving nivolumab, but the registry does not provide further details about that comparison population or how the benchmark was derived. As a general matter, comparisons with a reference rate can be affected by differences between the study participants and the reference population, as well as by differences in follow-up and outcome ascertainment. The record does not provide information to assess those issues for the cited rate.
Enrollment is listed as 3. This is a small enrollment, but no estimate of adenoma incidence can be reconstructed from enrollment alone. The registry does not report participant-level endpoint observations, follow-up time, or a set of analyzed outcomes. It would be inappropriate to treat the absence of an analysis as evidence that the incidence was low, high, or different from the benchmark.
The safety record reports 0 participants affected by serious adverse events among 3 at risk, 3 affected by other adverse events among 3 at risk, and 0 deaths. These counts describe the posted adverse-event categories; they do not supply the missing adenoma endpoint. Nor do they establish that all possible harms were measured or that the observed pattern would apply in a larger group. The record lists no serious adverse-event terms.
The study's terminated status and absence of endpoint analysis constrain what can be learned. The posted information documents the planned question, regimen, enrollment, and limited adverse-event counts, but it does not answer whether nivolumab changed adenoma incidence. Any sample-size illustration based on an observed effect should also be interpreted cautiously: the primary endpoint has no observed effect estimate in the record, and planning calculations are not observed power.
9. Statistical Methods Explained
What does an incidence rate represent?
As a general statistical concept, an incidence rate relates the number of new events to the amount of time participants are observed. It is suited to questions about the pace at which events occur during follow-up. The primary endpoint in this study was adenoma incidence at 3 years, but the registry record does not report the endpoint's unit or a calculated rate. It also states that the endpoint data were not obtained and analyzed because the study terminated early. The endpoint label and timeframe describe the intended measurement, not an observed result.
What would a confidence interval add?
A confidence interval gives a range of values compatible with an estimate under the statistical method used. In general, it helps readers judge precision; an estimate without an interval can obscure how much uncertainty remains. The registry says confidence intervals were intended for the adenoma incidence rate and would be used to determine whether it differed from the cited reference rate of 0.33. No interval is reported, so there is no basis for judging the precision of an adenoma-rate estimate or whether the intended comparison met a significance criterion.
How should the cited reference rate be understood?
The value 0.33 is described as the rate reported among Lynch patients not receiving nivolumab. It is a benchmark named in the endpoint description, not a second enrolled arm in this single-group study. In general, a comparison against an external reference may be informative, but it depends on whether the reference and study populations are sufficiently comparable and whether outcome definitions and observation conditions align. Details needed to assess those matters are not reported in the registry record. The record also does not give a fuller description of the reference population or an analysis procedure beyond stating the intended role of confidence intervals.
What does the design allow?
The study is identified as phase II, single group, with allocation listed as NA and masking as none. It therefore does not provide a randomized concurrent comparison. As a general principle, a single-group result cannot separate a treatment-associated pattern from differences in participants, follow-up, or other factors as effectively as a well-conducted randomized comparison can. Here, the missing endpoint analysis is an additional and decisive limitation: there is no primary outcome estimate to interpret, regardless of the design's other features.
What do the planning assumptions mean?
The registry includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are assumptions for illustrations, not a description of the trial's single-group design, and they are not reported as the trial's own design plan. The record does not provide a trial-specific sample-size justification. In general, a planning calculation asks how much information a future study might need under stated assumptions; it does not report what the current study observed.
Because no primary endpoint effect was obtained and analyzed, an illustration based on the observed effect cannot be interpreted as observed power for this trial. The record's sample-size assumptions also distinguish between total events for time-to-event illustrations and participants per arm for other illustrations. Those conventions do not establish an actual event count or participant allocation in this study. The planning values, if considered, should be read as hypothetical design aids, not as trial outcomes.
What can the adverse-event counts show?
The posted safety counts distinguish serious adverse events, other adverse events, and deaths. As a general principle, event counts and the number at risk describe what was recorded in the observed group; they do not by themselves identify cause, establish comparative safety, or resolve uncertainty about uncommon events. No serious-event terms are listed. The record does not report further detail about event definitions, ascertainment procedures, duration of safety follow-up, or how missing safety information was handled.
The record lists 4 outcome measures and 0 analyses. That count does not reveal whether outcomes were prespecified in a hierarchy, whether statistical tests were planned for each outcome, or whether any multiplicity adjustment was intended. Those details are not reported in the registry record. With no primary-endpoint analysis, inferential methods for the intended comparison cannot be evaluated from posted results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 4 outcome measures and 0 analyses. The primary outcome is adenoma incidence at 3 years, but the record does not provide analyzed data for it. It does not report a hierarchy of primary and secondary outcomes beyond identifying the primary endpoint, nor does it describe how multiplicity across outcomes would be handled. A multiplicity procedure, such as an adjustment to account for testing several outcomes, is not reported in the registry record. No claims about adjusted or unadjusted statistical significance can therefore be made.
The stated reason endpoint results are unavailable is early termination: data were not obtained and analyzed. The registry record does not report a missing-data method, imputation procedure, sensitivity analysis, or reasons at the participant level for unavailable endpoint information. It also does not describe analysis populations, such as a treated or evaluable population, or specify which participants would have been included in the primary analysis.
These omissions matter because missing outcome information is not interchangeable with a negative outcome. The absence of an adenoma-rate result does not indicate that no adenomas occurred. Without an analysis population, follow-up details, and a missing-data approach, readers cannot assess whether the intended endpoint could have been estimated or how any incomplete observations would have affected it. These analysis details are not reported in the registry record.
The record also does not report an interim-analysis plan or stopping boundaries. Early termination is recorded as the study status, but the statistical procedures behind that decision are not reported in the registry record. No inference about a planned statistical stopping rule should be drawn from the termination status alone.
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 |
|---|---|---|---|
| Treatment (Nivolumab) | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Nivolumab) | 0 of 3 |
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 |
|---|---|
| Treatment (Nivolumab) | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Nivolumab) |
|---|---|---|
| fatigue | General disorders | 2 of 3 |
| Glucose Intolerance | Metabolism and nutrition disorders | 2 of 3 |
| Platelet Count Decreased | Investigations | 2 of 3 |
| Skin Lesions | Skin and subcutaneous tissue disorders | 2 of 3 |
| Activated partial thromboplastin time prolonged | Investigations | 1 of 3 |
| Allergic reaction | Immune system disorders | 1 of 3 |
| Anemia | Blood and lymphatic system disorders | 1 of 3 |
| Bilateral skin lesions- arms and legs- 1 lesion | Skin and subcutaneous tissue disorders | 1 of 3 |
| Creatinine Increased | Investigations | 1 of 3 |
| decreased eGFR | Renal and urinary disorders | 1 of 3 |
The registry lists 3 at risk for serious adverse events, with 0 affected. For other adverse events, it lists 3 at risk and 3 affected. The death count is 0. The record does not list any serious adverse-event terms. These are descriptive counts for the posted treatment group, not a comparison with a control group.
The serious-event count should be read as no serious adverse events recorded among those listed as at risk, rather than as proof that serious harms cannot occur. The other-event count indicates that other adverse events were recorded for all participants listed as at risk; the record does not provide the terms, severity details, timing, or attribution needed to characterize them further. The registry's category label should not be used to infer details that are not listed.
As a general statistical point, a small observed group provides limited information about the range and frequency of possible adverse events. The posted counts do not establish comparative safety, and the registry record does not describe safety follow-up completeness or additional methods of adverse-event ascertainment.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase II study of nivolumab was conducted as a single-group study in participants with Lynch syndrome and a history of partial colectomy, and that the study was terminated. It records enrollment of 3 and a planned adenoma-incidence endpoint at 3 years. It also reports the stated treatment schedule and adverse-event counts.
It does not establish whether nivolumab changed adenoma incidence. The registry says endpoint data were not obtained and analyzed because of early termination. There is no posted rate, confidence interval, or comparison with the reference value of 0.33. Therefore, the record supports neither a conclusion that incidence was lower nor a conclusion that it was higher than the reference. Lack of an endpoint result is not evidence of no adenomas or of no effect.
The external reference value is not a concurrent control arm, and the registry does not give enough information to assess its comparability with the study group. Even if an outcome estimate had been available, the single-group design would require care in attributing any difference to the intervention. Here, the absence of outcome analysis prevents that assessment altogether.
The adverse-event figures are limited descriptive information: 0 serious adverse events among 3 at risk, 3 affected by other adverse events among 3 at risk, and 0 deaths. They do not establish the absence of risk, and they do not answer the adenoma-prevention question. The findings should be understood as a record of a terminated study with no analyzed primary endpoint, not as evidence for or against a treatment effect.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between a clinical question and an answer to that question. The registry describes a specific question: whether adenoma incidence at 3 years differed from a cited rate of 0.33 among Lynch patients not receiving nivolumab. It also states that confidence intervals were intended to inform the comparison. But the study terminated before endpoint data were obtained and analyzed, so the intended inferential result is unavailable.
That distinction matters statistically because design details do not substitute for outcome information. Knowing the phase, regimen, enrollment, endpoint, and reference rate does not make it possible to estimate an effect when no endpoint analysis is reported. Similarly, adverse-event counts cannot stand in for the primary outcome. They answer a different descriptive question and do not resolve whether adenoma incidence differed from the benchmark.
The record also demonstrates why comparator structure matters. The reference rate is external to this single-group study, not a concurrent randomized control group. General statistical reasoning requires attention to comparability when interpreting such benchmarks; relevant details are not reported in the registry record. The absence of a result compounds that limitation.
Finally, planning illustrations should remain conceptually separate from observed findings. Calculations under stated assumptions can support future-study planning, but they cannot restore missing endpoint data or establish observed power. The key statistical conclusion is therefore about information availability: the registry documents the intended analysis but does not provide the result needed to answer the primary question.
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 most consequential limitation is that the primary endpoint was not analyzed. The registry attributes this to early termination and reports no adenoma-incidence estimate or confidence interval. No conclusion about the intended comparison with 0.33 can be drawn from the posted outcome information.
The study was single group, with allocation listed as NA and masking as none. Its endpoint description relies on a reference rate among Lynch patients not receiving nivolumab rather than a concurrent control group. The registry record does not provide the reference population's details or enough information to assess comparability, outcome ascertainment, or follow-up alignment.
Enrollment is listed as 3, limiting the amount of information available even for the descriptive adverse-event counts. The record gives no participant-level endpoint observations, follow-up times, treatment exposure, adherence, or analysis-population definitions. The reason for termination and any statistical stopping plan are not reported in the registry record.
The record does not report a trial-specific sample-size justification, endpoint analysis method, multiplicity procedure, missing-data method, or sensitivity analysis. It lists 4 outcome measures and 0 analyses. The absence of these details restricts assessment of how outcomes would have been handled, while the absent endpoint results prevent assessment of effect size and precision. The adverse-event categories also lack detailed event terms apart from the statement that no serious adverse-event terms are listed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy — NCT03631641.
- Registry record last updated 2024-07-01; status last verified 2024-06.
- Results first posted 2024-07-01.
- 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
NCT03631641 is a phase II, single-group study of nivolumab for prevention of colon adenomas in participants with Lynch syndrome and a history of partial colectomy. Allocation is listed as NA, and masking as none. The regimen description specifies intravenous treatment over 60 minutes on day 1, repeated every 3 months for a total of 8 courses if there was no progression or unacceptable toxicity.
Enrollment is listed as 3. The study started on 2018-10-04, has a primary completion date of 2021-01-25, and is listed as terminated. The primary endpoint was adenoma incidence at 3 years, intended for comparison with the cited rate of 0.33. The registry states that data were not obtained and analyzed because of early termination.
The safety record lists 0 serious adverse events among 3 at risk, 3 affected by other adverse events among 3 at risk, and 0 deaths. The registry lists 4 outcome measures and 0 analyses.