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 Multiple Ascending Dose of BMS-911543 (NCT01236352), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01236352 |
| Phase | Phase 1, Phase 2 |
| Condition | Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 98 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with symptomatic intermediate-1, intermediate-2 or high-risk myelofibrosis. The primary safety population was all treated participants. The registry record lists an enrollment of 98, but the posted adverse-event figures are organized by dose cohort and do not provide a single overall count for the primary endpoint.
Intervention
Participants received BMS-911543 in non-randomized dose cohorts. The Phase 1 cohorts included doses from 5 mg through 320 mg, and the Phase 2 cohorts included 120 mg and 200 mg. The stated regimen was a capsule by mouth twice daily for 12 months or longer depending on response.
Comparator
There was no randomized control group in the registry record. The dose cohorts are not like-for-like control groups: enrollment into them was non-randomized, and the record does not describe them as a comparative treatment design. Differences in their counts should therefore not be interpreted as randomized dose effects.
Primary question
The primary endpoint counted participants with adverse events. Safety assessments used medical review of adverse-event reports and results from vital-sign measurements, ECGs, physical examinations and clinical laboratory tests, evaluated using NCI CTCAE v.4.0. The registry record also lists pharmacokinetic, pharmacodynamic and efficacy aims, but does not provide efficacy results or analysis entries.
In practical statistical terms, this was an early-phase investigation of safety and tolerability across dose cohorts, alongside characterization of drug exposure and biological measures. The record states that the study was intended to determine whether BMS-911543 was safe and tolerable enough to permit further clinical testing at a maximum tolerated dose or a clinically active dose, and to assess whether it would demonstrate efficacy. The posted information does not establish a treatment effect: there is no randomized comparator, and no inferential analysis results are recorded.
3. Trial Design
The registry identifies this as a Phase 1/2, parallel-model study with non-randomized allocation and no masking. Its stated title describes a multiple ascending dose study. The trial began on 2011-04-07, had primary completion on 2015-11-19, and is listed as terminated. The reason for termination is not reported in the registry record.
Phase 1 used dose cohorts of 5 mg, 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, 160 mg, 200 mg, 240 mg and 320 mg. Phase 2 included cohorts at 120 mg and 200 mg. The planned regimen in each cohort was BMS-911543 by mouth twice daily for 12 months or longer, depending on response. These are separate dose cohorts, not randomized arms intended to provide controlled comparisons. The registry record does not report the rules used to assign participants to dose cohorts or the criteria for dose escalation.
Enrollment is listed as 98. That registry total should not be treated as a denominator for each dose-specific result: the posted adverse-event counts have cohort-specific denominators, and no total treated population count is given alongside the primary outcome. The adverse-event figures list Phase 1 groups through 240 mg and Phase 2 groups at 120 mg and 200 mg; they do not list a 320 mg Phase 1 group.
The primary endpoint covered adverse events from written consent until 30 days after dosing or study participation ended, unless the last scheduled visit occurred later. It was assessed up to 4.5 years. Other listed outcomes included JAK/STAT pathway activity, circulating CD34+ cells, plasma cytokines and several pharmacokinetic measures for BMS-911543 and its metabolite. Results for those outcomes 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.
Before assignment: 98 participants were enrolled and 84 participants were treated. 14 participants did not enter treatment period (13 no longer met study criteria and 1 due to other reasons). 42 entered Phase 1 and 42 entered Phase 2
Only the first 6 of 11 groups are shown.
Overall Study
| Stage | 5 mg Phase I | 10 mg Phase I | 20 mg Phase I | 40 mg Phase I | 80 mg Phase I | 120 mg Phase I |
|---|---|---|---|---|---|---|
| STARTED | 4 | 4 | 4 | 4 | 4 | 4 |
| COMPLETED | 0 | 0 | 0 | 1 | 0 | 0 |
| NOT COMPLETED | 4 | 4 | 4 | 3 | 4 | 4 |
Reasons for not completing this period:
| Reason | 5 mg Phase I | 10 mg Phase I | 20 mg Phase I | 40 mg Phase I | 80 mg Phase I | 120 mg Phase I |
|---|---|---|---|---|---|---|
| Death | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
| Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 |
| Study drug toxicity | 0 | 0 | 0 | 0 | 0 | 1 |
| Disease progression | 1 | 2 | 1 | 2 | 2 | 2 |
| Poor/Non-compliance | 1 | 0 | 0 | 0 | 0 | 0 |
| Maximum clinical benefit | 1 | 1 | 1 | 0 | 2 | 0 |
| Subject request to discontinue treatment | 0 | 0 | 1 | 1 | 0 | 1 |
| Subject to receive drug via EAP | 1 | 1 | 1 | 0 | 0 | 0 |
| Patient moving to allogeneic transplant | 0 | 0 | 0 | 0 | 0 | 0 |
| Relapse of Splenomegaly and symptoms | 0 | 0 | 0 | 0 | 0 | 0 |
| Lack of response to drug | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All treated participants
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
Only the first 6 of 12 groups are shown.
| Characteristic | Unit | 5 mg Phase I | 10 mg Phase I | 20 mg Phase I | 40 mg Phase I | 80 mg Phase I | 120 mg Phase I |
|---|---|---|---|---|---|---|---|
| Participants analysed | 4 | 4 | 4 | 4 | 4 | 4 | |
| Age, Continuous | Years | 76.8 (SD 4.50) | 56.5 (SD 3.70) | 70.5 (SD 4.80) | 64.0 (SD 7.70) | 69.8 (SD 9.54) | 63.3 (SD 12.97) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 2 | 2 | 2 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 2 | 2 | 2 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 3 | 3 | 3 | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 1 | 1 | 1 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 4 | 4 | 4 | 4 | 4 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with adverse events, measured as a participant count in all treated participants. It is a safety endpoint: it records whether participants experienced adverse events during the specified observation period, rather than measuring a change in myelofibrosis symptoms or a clinical benefit.
The safety review drew on adverse-event reports and findings from vital-sign measurements, ECGs, physical examinations and clinical laboratory tests. Events were evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. The observation window began at written consent and continued until 30 days after dosing or study participation ended, unless a later last scheduled visit extended it; the record states that assessment was up to 4.5 years.
Participant counts are useful for describing how many people in a cohort were affected. They do not, by themselves, describe the number of separate events, their duration, severity distribution, timing or relationship to treatment. Nor does a count establish that the drug caused an event. The registry record's cohort-specific serious and other adverse-event counts offer safety descriptions, but it does not report an overall primary-endpoint analysis or a comparison with a control group. The primary endpoint is therefore best read as descriptive monitoring within this non-randomized study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results are cohort-specific counts, not estimates from a randomized comparison. For serious adverse events, the record gives both a number at risk and a number affected in each listed cohort. The figures vary across cohorts: for example, the 5 mg Phase I group lists 3 affected among 4 at risk, while the 40 mg Phase I group lists 1 among 4 at risk. The 120 mg Phase II group lists 9 among 22 at risk, and the 200 mg Phase II group lists 10 among 20 at risk. These are descriptions of the reported groups, not evidence that one dose caused more or fewer events than another.
For other adverse events, each listed group reports the same count affected as the count at risk. That pattern is descriptive and does not convey event severity, the number of events per participant, or their clinical importance. Death counts are also listed by cohort. They are counts, not an attribution analysis: the registry record does not state whether a death was considered related to treatment, nor does it provide causes of death in these cohort summaries.
The serious-event terms listed most often include Spleen disorder, Abdominal pain and Back pain, each at 33.3%; Cellulitis, Lung infection and Abscess limb are each listed at 25.0%. These percentages should be read as the registry's posted term-level summaries. The record does not provide the event-specific denominators or additional detail needed to interpret them as comparative risks across dose cohorts.
Precision is limited by the modest cohort-specific counts and by the lack of a randomized comparator. A count in a small cohort can change noticeably with only a few participants, so apparent differences between groups are particularly uncertain. No confidence intervals, hypothesis tests or adjusted estimates are included in the registry record. The record also contains no analysis entries. Consequently, there is no reported inferential basis for ranking doses by safety, estimating a dose-response relationship, or drawing a treatment-effect conclusion.
The study's stated purpose included assessing efficacy, but the posted information in this record does not include efficacy outcome results. The listed pharmacokinetic and pharmacodynamic outcomes likewise have no results reported in the registry record. The safety counts therefore do not answer those other questions. In particular, they cannot establish whether BMS-911543 improved myelofibrosis outcomes or whether any observed adverse event pattern is specific to the drug rather than the underlying condition or other circumstances.
The study is listed as terminated, but the reason is not reported in the registry record. Termination alone does not explain the safety findings or indicate why the study ended. The results should be interpreted within the limits of the recorded population, cohort structure and available outcomes, without inferring unreported design decisions or causes.
9. Statistical Methods Explained
The registry record identifies a participant-count endpoint and supplies cohort-level counts for serious adverse events, other adverse events and deaths. It does not describe a statistical analysis plan, provide analysis entries, or report confidence intervals or hypothesis tests. The concepts below are general explanations of how such data can be interpreted; they are not claims about analyses performed in this study.
What does a participant count represent?
A count of participants with an event answers how many people in a defined group experienced at least one event under the endpoint definition. It is distinct from a count of all event episodes. One participant may experience more than one event, but a participant-count endpoint counts that person once for the relevant outcome. The posted cohort figures should be read according to their labels: the serious-event results include participants at risk and participants affected, while other-event results are also given as participant counts.
Counts need a meaningful denominator to be interpreted as a frequency within a group. The registry record gives cohort-specific at-risk counts for the adverse-event figures. The overall enrollment figure is not an appropriate substitute for those cohort denominators, and it should not be combined with them to construct an unreported result. Even when a denominator is available, a frequency is descriptive: it does not by itself show that an intervention caused the event.
Why is a randomized comparator important?
In general, random allocation helps make groups comparable on average with respect to both measured and unmeasured characteristics. This study is explicitly non-randomized and has no masking. Dose cohorts may differ in who entered them, when they entered, how long they were observed, or other characteristics; the registry record does not report enough detail to assess these possibilities. Therefore, comparing raw counts across cohorts cannot isolate a dose effect. A higher or lower count may reflect differences between groups or exposure and observation patterns, as well as chance.
Masking is also absent. In general, knowledge of treatment assignment can affect some aspects of event reporting or assessment, although the record does not establish that this happened. Safety assessments included clinical review and several types of measurements, but the registry does not describe any blinded adjudication procedure.
What would uncertainty estimates add?
In general, a confidence interval expresses the range of effect estimates that are reasonably compatible with the data under a specified statistical model and repeated-sampling procedure. It communicates precision, not the probability that a particular treatment effect is true. Intervals are often wide when groups are small or events are sparse. No confidence intervals are reported for these cohort counts, so their sampling uncertainty cannot be quantified from the registry information alone.
A hypothesis test would address a specified contrast under assumptions about the data and analysis. Here, the registry record contains no analysis entries or reported tests, and the non-randomized cohorts are not like-for-like controls. It would be misleading to invent a test or use one to imply a causal comparison that the design does not support.
How should multiple outcomes be understood?
The record lists safety, pharmacokinetic, pharmacodynamic and efficacy aims, along with multiple pharmacokinetic measures. In general, testing many outcomes can increase the chance of finding at least one apparently notable result by chance if results are selected or interpreted without accounting for multiplicity. A prespecified hierarchy, adjustment strategy or clear distinction between exploratory and confirmatory outcomes can help manage that issue. Such details are not reported in the registry record, and no outcome analyses are available to assess how multiplicity was handled.
What can sample-size planning illustrations say?
In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance threshold, allocation and statistical method. It does not establish the study's actual power after data collection, and a calculation based on an observed effect is especially not a measure of observed power. No trial-specific sample-size justification or planning assumptions are reported in the registry record. The record also does not state that the reported cohort sizes were chosen to support formal comparisons.
Overall, the appropriate statistical reading is descriptive: report the posted cohort counts and their definitions, recognize that the denominators are cohort-specific, and avoid treating unadjusted differences between non-randomized dose groups as causal estimates. More detailed conclusions would require analysis methods and results that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary safety outcome and numerous secondary outcomes, including pathway activity, circulating CD34+ cells, cytokines and pharmacokinetic measures. It does not report a multiplicity plan, such as a hierarchy of outcomes, an adjustment procedure or a distinction between confirmatory and exploratory tests. Because no analysis entries or inferential results are recorded, it is not possible to determine whether or how multiple testing was addressed.
Missing-data methods are also not reported in the registry record. The posted adverse-event figures identify participants at risk and affected in each listed group, but do not explain whether all treated participants had complete follow-up, how incomplete observation was handled, or whether participants who discontinued contributed data through the end of the stated safety window. The record describes the endpoint's observation period but does not specify rules for censoring, imputation or sensitivity analyses.
The primary endpoint population is described as all treated participants. That is a stated safety population, not evidence that every enrolled participant was treated or that outcome information was complete for everyone. The registry record does not provide a flow of participants through screening, treatment, follow-up and analysis, nor does it define analysis populations for the secondary outcomes. Those details are important because differences in follow-up or inclusion can affect descriptive counts.
In general, multiplicity and missingness matter because they affect how confidently results can be interpreted. When outcomes are numerous, selective emphasis can overstate evidence; when follow-up is incomplete, observed counts may not reflect the experience of all participants. Without the relevant prespecified methods and analysis results, the posted safety counts should be treated as cohort descriptions rather than as a complete inferential assessment.
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 |
|---|---|---|---|
| 5 mg Phase I | 3 | 4 | 75.0% |
| 10 mg Phase I | 2 | 4 | 50.0% |
| 20 mg Phase I | 2 | 4 | 50.0% |
| 40 mg Phase I | 1 | 4 | 25.0% |
| 80 mg Phase I | 4 | 4 | 100.0% |
| 120 mg Phase I | 2 | 4 | 50.0% |
| 160 mg Phase I | 6 | 8 | 75.0% |
| 200 mg Phase I | 2 | 7 | 28.6% |
| 240 mg Phase I | 1 | 3 | 33.3% |
| 120 mg Phase II | 9 | 22 | 40.9% |
| 200 mg Phase II | 10 | 20 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 5 mg Phase I | 1 of 4 |
| 10 mg Phase I | 0 of 4 |
| 20 mg Phase I | 0 of 4 |
| 40 mg Phase I | 0 of 4 |
| 80 mg Phase I | 1 of 4 |
| 120 mg Phase I | 1 of 4 |
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 |
|---|---|
| 5 mg Phase I | 4 of 4 |
| 10 mg Phase I | 4 of 4 |
| 20 mg Phase I | 4 of 4 |
| 40 mg Phase I | 4 of 4 |
| 80 mg Phase I | 4 of 4 |
| 120 mg Phase I | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | 5 mg Phase I | 10 mg Phase I | 20 mg Phase I | 40 mg Phase I | 80 mg Phase I | 120 mg Phase I |
|---|---|---|---|---|---|---|---|
| Spleen disorder | Blood and lymphatic system disorders | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 | 1 of 4 | 1 of 4 |
| Abdominal pain | Gastrointestinal disorders | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 |
| Disease progression | General disorders | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 4 |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 4 | 1 of 4 |
| Cellulitis | Infections and infestations | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 |
| Lung infection | Infections and infestations | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 |
| Abscess limb | Infections and infestations | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 4 |
| Appendicitis | Infections and infestations | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 |
| Diverticulitis | Infections and infestations | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 4 |
| Sepsis | Infections and infestations | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 5 mg Phase I | 10 mg Phase I | 20 mg Phase I | 40 mg Phase I | 80 mg Phase I | 120 mg Phase I |
|---|---|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 4 | 0 of 4 | 3 of 4 | 2 of 4 | 1 of 4 | 4 of 4 |
| Fatigue | General disorders | 1 of 4 | 3 of 4 | 3 of 4 | 0 of 4 | 2 of 4 | 1 of 4 |
| Nausea | Gastrointestinal disorders | 0 of 4 | 1 of 4 | 2 of 4 | 2 of 4 | 1 of 4 | 2 of 4 |
| Diarrhoea | Gastrointestinal disorders | 0 of 4 | 1 of 4 | 3 of 4 | 2 of 4 | 0 of 4 | 2 of 4 |
| Contusion | Injury, poisoning and procedural complications | 1 of 4 | 0 of 4 | 2 of 4 | 1 of 4 | 2 of 4 | 2 of 4 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 4 | 0 of 4 | 0 of 4 | 2 of 4 | 1 of 4 | 2 of 4 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 4 | 0 of 4 | 1 of 4 | 2 of 4 | 1 of 4 | 1 of 4 |
| Abdominal Pain | Gastrointestinal disorders | 2 of 4 | 1 of 4 | 2 of 4 | 0 of 4 | 1 of 4 | 0 of 4 |
| Constipation | Gastrointestinal disorders | 0 of 4 | 0 of 4 | 1 of 4 | 2 of 4 | 2 of 4 | 0 of 4 |
| Night sweats | Skin and subcutaneous tissue disorders | 1 of 4 | 0 of 4 | 2 of 4 | 0 of 4 | 0 of 4 | 2 of 4 |
Serious events with the highest arm-level rate: spleen disorder (33.3%), abdominal pain (33.3%), back pain (33.3%), cellulitis (25.0%), lung infection (25.0%).
The serious adverse-event figures report, for each listed dose cohort, the number at risk and the number affected. For example, the 160 mg Phase I group lists 6 affected among 8 at risk, and the 120 mg Phase II group lists 9 affected among 22 at risk. The record also reports other adverse events: in each listed group, the count affected matches the count at risk. These are participant counts, not counts of separate event episodes.
Deaths are given as a separate count by cohort. The record does not say whether any death was attributed to BMS-911543 or provide causes for these counts, so they should not be interpreted as treatment-related deaths. The serious-event term summaries list Spleen disorder, Abdominal pain and Back pain at 33.3% each; Cellulitis, Lung infection and Abscess limb are listed at 25.0% each. The registry record does not include enough detail to establish comparative risks for these terms across cohorts.
As a general statistical caution, raw counts from small, non-randomized groups are imprecise and do not establish causation. Follow-up duration and cohort composition may also differ; the registry record does not provide enough information to assess those factors. These safety figures describe what was recorded in the listed groups, not a controlled comparison of doses.
12. What the Result Does, and Does Not, Mean
The record documents a Phase 1/2 investigation of BMS-911543 in people with symptomatic myelofibrosis and provides descriptive safety counts for several dose cohorts. It identifies adverse events as the primary endpoint, defines a safety observation period, and states that assessments were based on clinical review and several types of measurements. Those details help readers understand the intended scope of safety monitoring.
The posted data do not establish that BMS-911543 caused the reported events, nor do they establish that a particular dose is safer or riskier than another. Allocation was non-randomized, masking was absent, and there was no like-for-like control group. Differences among cohort counts cannot be treated as causal dose comparisons. The counts also do not reveal event duration, repeated episodes, attribution to treatment or the full pattern of severity for every event.
The study's stated aims included efficacy and biological and pharmacokinetic outcomes, but their results are not reported in the registry record. The safety data therefore do not answer whether the drug changed disease outcomes or biological measures. The record's terminated status does not explain why the study ended; the reason is not reported.
In general, early-phase safety findings can help describe events observed during exposure and motivate further investigation, but interpreting them depends on study design, exposure, follow-up and complete outcome reporting. For this study, the available information supports a descriptive account of recorded cohort counts. It does not support treatment recommendations, a conclusion of benefit or lack of benefit, or a definitive estimate of comparative safety.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between dose exploration and controlled comparison. The registry describes a multiple ascending dose study, but its non-randomized parallel cohorts do not provide the protections of random assignment. Cohort-specific adverse-event counts can describe what was observed, yet they cannot by themselves distinguish dose effects from differences in the people enrolled, their follow-up or other factors.
The endpoint also illustrates why outcome definitions matter. A count of participants with an adverse event is not the same as a count of all events, a measure of severity, or an estimate of treatment-attributable harm. Reading the denominator alongside the count is essential, but even a count with a denominator does not resolve confounding or uncertainty. The registry record does not report confidence intervals or formal comparisons to quantify those uncertainties.
Finally, the contrast between broad stated aims and the available results is important for evidence interpretation. The study sought safety, efficacy, pharmacokinetic and pharmacodynamic information, while the registry record gives adverse-event counts and lists other outcomes without reporting their results. This makes clear why a registry entry should be read according to the outcomes and analyses actually recorded, rather than the full set of questions a trial intended to investigate. The missing details about analysis methods, multiplicity and missing data further limit what can be inferred.
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.
Several limitations are specific to the information recorded for this trial. First, allocation was non-randomized, masking was absent, and no control group is listed. Dose-cohort differences therefore cannot be interpreted as unbiased treatment comparisons. Second, the cohort sizes for the posted safety figures are limited, making descriptive counts sensitive to a small number of participants; confidence intervals and other precision measures are not reported.
Third, the registry record does not provide a participant-flow account, cohort assignment rules, duration of follow-up by group or missing-data methods. Although the primary endpoint has a stated assessment window, the available information does not show how much observation each participant contributed. Fourth, death counts are listed without causes or treatment attribution, and the record does not provide detailed event-level information such as timing, duration or repeated episodes.
The serious-event summaries include term-level percentages, but the event-specific denominators and the basis for comparing those terms across cohorts are not reported. The posted adverse-event group figures do not list a 320 mg Phase I group, despite that dose appearing in the planned Phase 1 cohort descriptions. The reason for the discrepancy in listed cohort coverage is not reported in the registry record.
Finally, efficacy, pharmacokinetic and pharmacodynamic results are absent, as are statistical analysis entries and details on multiplicity. The study is listed as terminated, but its reason for termination is not reported. These limitations constrain interpretation to the descriptive information actually recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Multiple Ascending Dose of BMS-911543 — NCT01236352.
- Registry record last updated 2019-07-31; status last verified 2019-07.
- Results first posted 2019-05-21.
- 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
NCT01236352 is a Phase 1/2, non-randomized, unmasked, parallel-model study of BMS-911543 in people with myelofibrosis. The registry lists enrollment of 98, a start date of 2011-04-07, primary completion on 2015-11-19 and status as terminated. The reason for termination is not reported in the registry record.
The primary endpoint counted participants with adverse events among all treated participants, with assessment from written consent through the post-discontinuation period and up to 4.5 years. Posted safety results give serious-event, other-event and death counts by several dose cohorts. The record lists additional efficacy, pharmacokinetic and pharmacodynamic outcomes but does not report their results, and it contains no analysis entries. These data support descriptive safety interpretation, not a controlled comparison of doses or a conclusion about efficacy.