A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer (NCT02387996), a na phase 2 study. The primary outcome is Objective Response Rate Per BIRC Assessment.

2. Clinical Question

The study focused on objective response rate (ORR), a measure of the proportion of participants meeting specified tumor-response criteria. The registry describes the response as confirmed and based on the best overall response. It also lists progression-free survival, overall survival, and investigator-assessed ORR as secondary outcomes.

The central interpretive constraint is the single-group design. Without a concurrent control group, the record cannot provide a randomized comparison of nivolumab with another treatment or with no treatment. It can describe outcomes among the specified participants, but it cannot by itself establish what would have happened to comparable participants under a different treatment. The registry record does not report the primary ORR estimate or its confidence interval, so the magnitude and precision of the observed response cannot be assessed from the reported details.

3. Trial Design

This was a Phase II, single-arm clinical trial of nivolumab in participants with metastatic or unresectable urothelial cancer who had progressed or recurred following treatment with a platinum agent. The registry lists Bristol-Myers Squibb as sponsor and describes the intervention as nivolumab by intravenous infusion as specified. The study is marked completed. Its recorded enrollment is 270.

The design has no randomized allocation and no masking. The registry identifies a single-group model, with no control arm described. As a result, the study is structured to report outcomes in participants receiving nivolumab rather than estimate a between-group treatment contrast. The absence of a comparator is important when interpreting changes in disease status: a response observed during the study is a descriptive outcome, not a randomized estimate of the effect relative to another approach.

The primary efficacy analysis population is described as all treated participants, with treated participants from Japan enrolled after the main enrollment period excluded. The record does not state how many participants were excluded under this rule or provide a more detailed account of the analysis population.

The registry lists the study start as 2015-03-09 and primary completion as 2016-04-15. The primary outcome timeframe is from the date of first dose to objectively documented progression or subsequent therapy, whichever occurred first, assessed up to 14 months. Although the record identifies several secondary outcomes, it does not report their results or explain the analysis procedures used for them. Details of eligibility criteria beyond the disease and prior-treatment description 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: All treated participants. Treated participants from Japan enrolled after main enrollment period were excluded from primary efficacy analysis.

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: All Treated Participants

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate Per BIRC Assessment, measured over From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months).

The primary endpoint is objective response rate per blinded independent review committee assessment. It is defined as the number of participants with a best overall response of confirmed complete response or partial response divided by the number of all treated participants. The record gives the unit as percent of participants and specifies a 95% confidence interval. It describes the efficacy population as all treated participants, excluding treated participants from Japan enrolled after the main enrollment period.

Responses are classified using RECIST 1.1. A complete response means disappearance of all target lesions; pathological lymph nodes, whether target or non-target, must also have a short axis below 10 mm. A partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference. The endpoint therefore reduces tumor-assessment results to a binary participant-level outcome: whether a participant had a confirmed complete or partial response.

In general, an objective response endpoint provides a defined way to describe tumor shrinkage and can be assessed using prespecified imaging criteria. Independent review is intended to separate response assessment from the treating investigator’s assessment, though the registry record does not provide further details about review procedures. The record does not report the ORR estimate or confidence interval, so it is not possible to describe the observed response frequency or its statistical precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary outcome is binary at the participant level: a participant either met the confirmed complete- or partial-response definition or did not. The registry defines ORR as the number meeting either response category divided by the number of all treated participants. In general, a binary outcome can be summarized as a proportion, with the denominator specifying the population in which that proportion is calculated. Here, the primary efficacy population is described as all treated participants, subject to the stated exclusion of treated participants from Japan enrolled after the main enrollment period.

What does the confidence interval describe?

The endpoint specifies a 95% confidence interval. In general, a confidence interval communicates the statistical uncertainty around an estimated quantity. It is not a guarantee that the true value lies within a particular interval, and its width depends on the data and the method used to calculate it. Because neither the ORR estimate nor its confidence interval is reported in the registry record, the response frequency and its precision cannot be assessed. The record does not identify the interval calculation method.

Why does the single-group design matter?

In general, a single-group study can describe outcomes among the participants who received the intervention, but it does not provide a concurrent randomized comparison. A treatment contrast requires outcomes under different treatment conditions to be compared in a way that supports the intended inference. In this trial, the registry records no allocation and a single-group model. Thus, any response estimate would be a within-group description rather than a randomized estimate of the difference between treatments. Comparing it with a result from another study would not remove differences in populations, care, eligibility, or outcome assessment.

The study is unmasked according to the registry. The primary endpoint is nevertheless specified as assessed by a blinded independent review committee. In general, independent review can provide an assessment separate from investigators’ assessments, while masking of reviewers can reduce the possibility that knowledge of treatment influences outcome classification. The registry record does not provide procedural details about the committee, adjudication, or how disagreements were resolved.

How do the response criteria define the outcome?

RECIST 1.1 supplies the measurement framework named in the record. Complete response is defined by disappearance of target lesions, together with the specified lymph-node criterion. Partial response is defined by at least a 30% reduction in the sum of target-lesion diameters from baseline. Requiring a confirmed response distinguishes the endpoint from a response classification that has not met the stated confirmation requirement. The record does not provide participant-level measurements or counts by category, so the classifications cannot be independently reconstructed.

The registry labels the endpoint parameter as “NUMBER” while giving the unit as percent of participants. Its accompanying definition describes a proportion, but the record does not explain that parameter label. The actual numerical endpoint result is not reported in the registry record.

What can the secondary outcomes add?

The listed secondary outcomes are progression-free survival, overall survival, and investigator-assessed ORR. In general, time-to-event outcomes concern the time until a defined event, while investigator-assessed ORR uses response classifications made by investigators rather than the independent review committee. The registry record does not provide event definitions, estimates, confidence intervals, analysis methods, or results for these secondary outcomes. It is therefore not possible to compare their findings with the primary endpoint or assess their precision.

Statistical significance testing, adjustment for multiple outcomes, handling of censoring, missing assessments, and other analysis choices can affect how trial results should be interpreted. The registry record does not report the analysis procedures for these endpoints. General explanations of these methods cannot fill in the study-specific choices or substitute for the missing results.

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("Nivolumab 3 mg/kg")
n      <- c(265)
events <- c(52)
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  Nivolumab 3 mg/kg  265  52  19.6  15.0  24.9  15.3  24.8  15.3  24.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of ORR per blinded independent review committee assessment and secondary outcomes of progression-free survival, overall survival, and investigator-assessed ORR. It records ten outcome measures, but does not report results or analysis details for those measures. The relationship between the listed outcomes and the recorded count is not explained in the registry record.

When a study examines multiple outcomes or makes multiple statistical comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures may be used to control that risk, or outcomes may be interpreted according to a prespecified hierarchy. The registry record does not report whether multiplicity was addressed, whether outcomes were ranked, or whether confirmatory testing was planned. No particular approach should be inferred.

The primary efficacy population is described as all treated participants, with treated participants from Japan enrolled after the main enrollment period excluded. The record does not report the number of participants in that population, the number excluded under that rule, or how missing response assessments were handled. It also does not describe imputation, sensitivity analyses, or the treatment of participants who stopped assessment because of progression or subsequent therapy.

In general, missing outcome data can affect a response proportion if the probability of missingness is related to participants’ outcomes. The appropriate interpretation depends on the analysis population, missing-data assumptions, and any sensitivity analyses. Those study-specific details are not reported in the registry record. The primary endpoint’s timeframe ends at objectively documented progression or subsequent therapy, whichever occurs first, and is assessed up to 14 months; the record does not explain how these conditions were incorporated into the analysis.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malignant neoplasm progression (35.2%), urinary tract infection (6.3%), general physical health deterioration (4.4%), sepsis (4.4%), diarrhoea (2.6%).

The registry lists one nivolumab group with 270 participants at risk for serious adverse events and 199 affected, and 270 at risk for other adverse events and 245 affected. It also lists 225 deaths. These are registry counts; they do not establish that the reported events or deaths were caused by nivolumab. The record does not describe attribution procedures or provide a comparator group for estimating relative safety.

The selected serious-event terms are malignant neoplasm progression (35.2%), urinary tract infection (6.3%), general physical health deterioration (4.4%), sepsis (4.4%), diarrhoea (2.6%), and small intestinal obstruction (2.6%). The registry presents these as percentages, but the posted details do not give term-specific counts or explain how the percentages were calculated. These terms should be read as listed event categories, not as evidence of treatment causation.

In general, adverse-event counts describe how many participants were recorded as affected under the registry’s reporting framework. They do not by themselves convey event duration, severity beyond the stated category, timing, recurrence, or causal attribution. The record does not explain whether participants could contribute to more than one event category, so the listed categories should not be added together or treated as mutually exclusive.

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

The registry record describes a Phase II, single-group study of nivolumab and defines a primary endpoint based on confirmed tumor response assessed by a blinded independent review committee. It also identifies a treated-participant analysis population and several secondary outcomes. These registry entries explain what the study set out to assess, but they do not provide the numerical primary result.

The ORR estimate and its 95% confidence interval are not reported in the registry record. Without them, the posted information does not establish how many participants had a confirmed response as a proportion of the analysis population or how precisely that proportion was estimated. The absence of a reported estimate should not be interpreted as either a positive or a negative finding.

Even if a response estimate were available, a single-group study would describe outcomes in the treated population rather than establish a randomized contrast. The registry records no allocation and no comparator group. A causal interpretation or comparison with another treatment would require evidence beyond a response proportion from this study. The record also does not report the secondary-outcome results, so it cannot support conclusions about progression-free survival or overall survival.

The safety figures describe reported counts and selected serious-event percentages. They do not establish causation or comparative risk. The death count is listed without further details about cause or attribution. More generally, interpretation of safety requires the event definitions, follow-up, exposure context, and attribution information, which are not reported in the registry record.

In general, statistical evidence is best understood by considering the design, the outcome definition, the analysis population, the estimate, and its uncertainty together. In this record, the design and outcome definition are described, but the primary efficacy result and key analysis details are absent. The appropriate conclusion is limited to what the registry records about the study’s structure, endpoint, and listed safety information.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between a clearly defined endpoint and a reported result. The registry specifies ORR, the response categories, the RECIST 1.1 criteria, the assessment organization, the analysis population, and a 95% confidence interval as the measure of uncertainty. Those details make the intended outcome interpretable in principle. However, without the estimate and interval, the response frequency and its precision remain unknown from the registry record.

The single-group design is another important feature. It can provide a descriptive account of outcomes in participants receiving the intervention, but it does not offer the randomized contrast that would help separate treatment effects from other explanations. This matters whenever readers are tempted to treat an observed response as proof of comparative benefit. The design supports a narrower question than a randomized trial would answer.

The record also names both independent-review ORR and investigator-assessed ORR, along with progression-free and overall survival. In general, multiple outcome measures can capture different aspects of a study, but their interpretation depends on definitions, analysis plans, and attention to multiplicity. Those details and results are not reported in the registry record.

Finally, the efficacy population has a stated exclusion for certain treated participants from Japan, while the safety group is described with its own at-risk counts. Clear reporting of analysis populations is essential because denominators define what a proportion means. The record gives the population rule but not the final efficacy denominator or the number affected by the exclusion. Together, these features make the record useful for understanding the study framework, while limiting what can be concluded statistically about efficacy or comparative safety.

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.

The principal limitation for interpretation is that the registry record does not report the primary ORR estimate or its 95% confidence interval. It also does not report the outcome results for the listed secondary measures. Without those estimates, neither the frequency of response nor the precision of the primary result can be described.

The single-group design has no randomized comparator, so the record cannot estimate a treatment contrast. The registry also records no allocation and no masking, while describing the primary assessment as independent review. It does not provide further details on how that review was conducted or whether assessments were complete.

The efficacy population description excludes treated participants from Japan enrolled after the main enrollment period, but the number excluded and final analysis denominator are not reported. Missing-data handling, sensitivity analyses, and the treatment of unevaluable response assessments are not reported in the registry record. The relation between the listed endpoints and the recorded ten outcome measures is also not explained.

Safety interpretation is limited by the absence of a comparator and by missing details on event definitions, attribution, timing, and the circumstances surrounding the listed deaths. The selected serious-event percentages are not accompanied by term-specific counts in the registry record recorded. These limitations do not change what the registry states, but they restrict the strength and scope of statistical conclusions that can be drawn from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer — NCT02387996.
• Registry record last updated 2022-11-01; status last verified 2022-10.
• Results first posted 2017-05-24.
• 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

NCT02387996 is a completed Phase II, single-group study sponsored by Bristol-Myers Squibb. It evaluated nivolumab in participants with metastatic or unresectable urothelial cancer whose disease had progressed or recurred following platinum treatment. The registry records enrollment of 270, a study start date of 2015-03-09, and primary completion on 2016-04-15. Allocation is listed as not applicable, and masking as none.

The primary endpoint was ORR per blinded independent review committee assessment, defined using confirmed complete or partial response under RECIST 1.1. The primary analysis population is described as all treated participants, excluding treated participants from Japan enrolled after the main enrollment period. The registry does not report the primary estimate or its confidence interval. Listed secondary outcomes are progression-free survival, overall survival, and investigator-assessed ORR. Safety information includes serious and other adverse-event counts, a death count, and selected serious-event percentages; causal attribution is not reported.