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 Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available. (NCT02292446), a na phase 3 study. The primary outcome is Number of Participants With Adverse Events - All Grades.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02292446 |
| Phase | Phase 3 |
| Condition | Polycythemia Vera |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 161 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with polycythemia vera who were hydroxyurea resistant or intolerant and for whom no standard treatment alternative was available. The protocol was also intended for people who did not qualify for another clinical study for polycythemia vera.
Intervention
Ruxolitinib in an open-label expanded treatment protocol. The stated starting dose was 10 mg twice daily, with dose adjustment to an appropriate level within the stated limits.
Comparator
There was no comparator group. The registry classifies the study as single group, with allocation listed as NA.
Primary question
The primary endpoint was the number of participants with adverse events of all grades from baseline up to approximately 26 months. The protocol’s stated purpose was early access to ruxolitinib and evaluation of safety information in this population.
These design features make the main question descriptive: what safety information was recorded among participants receiving ruxolitinib in this protocol? The study does not set up a randomized comparison that could estimate how outcomes differed between ruxolitinib and another treatment or no treatment. The registry record lists changes in hematocrit, spleen length, and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score as secondary outcomes. It does not report their results in the material summarized by the record.
The enrolled population was specific to people with polycythemia vera facing the stated treatment constraints. The record describes 161 enrolled participants. Its findings should therefore be read in the context of that eligibility and access purpose, rather than as a direct comparison across treatments or as a result for all people with polycythemia vera.
3. Trial Design
The registry classifies NCT02292446 as a phase 3, open-label, multicenter, single-group expanded treatment protocol. It lists enrollment of 161 participants and status as completed. The study began on 2014-11-21, and primary completion was recorded as 2017-12-29. These dates describe the registry timeline, not necessarily each participant’s treatment or follow-up duration.
All participants were assigned to receive ruxolitinib; there was no separate control arm. The stated starting dose was 10 mg twice daily, with titration to the most appropriate dose. The dose was not to exceed 25 mg bid or be less than 5 mg once a day. Because the protocol was open-label, masking was listed as none. The registry does not report further details about how dose changes were made or how treatment exposure varied among participants.
The protocol’s stated purpose was to provide early access to ruxolitinib and evaluate safety information in people with polycythemia vera who were hydroxyurea resistant or intolerant, had no other standard treatment option, and did not qualify for another clinical study for polycythemia vera. That purpose differs from a randomized efficacy trial designed to compare treatment strategies. In a single-group study, outcomes can be described among those who received the intervention, but an untreated or active-control outcome cannot be estimated from the study itself.
The primary endpoint concerned participants with adverse events of all grades from baseline up to approximately 26 months. The registry also lists secondary outcomes concerning changes in hematocrit, spleen length, and symptom score. The record does not report the detailed eligibility criteria, follow-up schedule, dose-adjustment rules, or statistical analysis plan.
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: 161 patients were included in the ruxolitinib arm and 100% of the patient's received the treatment
Overall Study
| Stage | All Patients |
|---|---|
| STARTED | 161 |
| COMPLETED | 141 |
| NOT COMPLETED | 20 |
Reasons for not completing this period:
| Reason | All Patients |
|---|---|
| Adverse Event | 12 |
| Death | 1 |
| Disease progression | 2 |
| Subject/guardian decision | 2 |
| Withdrawal by Subject | 3 |
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 | All Patients |
|---|---|---|
| Participants analysed | 161 | |
| Age, Customized: <= 60 | participants | 52 |
| Age, Customized: >60 | participants | 109 |
| Sex: Female, Male: Female | Participants | 65 |
| Sex: Female, Male: Male | Participants | 96 |
| Race/Ethnicity, Customized: Caucasian | participants | 128 |
| Race/Ethnicity, Customized: Asian | participants | 3 |
| Race/Ethnicity, Customized: Other | participants | 30 |
| Number of participants resistant or intolerant to hydroxyurea (HU): Resistant to hydroxyurea | participants | 60 |
| Number of participants resistant or intolerant to hydroxyurea (HU): Intolerant to hydroxyurea | participants | 101 |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening: 1 phlebotomy | participants | 21 |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening: 2 phlebotomies | participants | 19 |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening: >=3 phlebotomies | participants | 74 |
| Number of participants' frequency of phlebotomy in 52 weeks prior to screening: Missing | participants | 47 |
| Number of participants' use of prior antineoplastic therapy: Prior Hydroxyurea use | participants | 160 |
| Number of participants' use of prior antineoplastic therapy: Prior other anti-neoplastic medications use | participants | 59 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events - All Grades, measured over Baseline up to approximately 26 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events of all grades, measured from baseline up to approximately 26 months. It is a participant-count endpoint: it concerns how many participants experienced an adverse event, not how many separate events each participant experienced. The record gives the endpoint’s unit as participants.
Safety protocols commonly track adverse events to characterize events that arise during a treatment period. Counting participants with events can give a direct description of how many people in the study were affected, while grades distinguish event severity when grading is recorded. This is a general explanation of the endpoint type, not a claim about the protocol’s unreported analysis choices.
The registry’s primary endpoint is stated as all-grade adverse events, while its posted safety summary separately lists participants with serious and other adverse events. The record does not provide a combined all-grade participant count in the information summarized, so the serious and other counts should not be treated as a complete all-grade total. Nor does the endpoint by itself establish whether an event was caused by ruxolitinib; the record’s event counts describe what was recorded during the stated timeframe.
The approximately 26-month timeframe is the endpoint’s stated window. The registry record does not specify how long each participant was followed, whether all participants contributed the same observation time, or how events after treatment discontinuation were handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry’s safety summary lists 161 participants at risk for serious adverse events and 26 participants affected. It also lists 161 participants at risk for other adverse events and 107 affected. These are descriptive counts within a single treatment group. They do not estimate a treatment difference, because the registry describes no comparator arm.
The record also lists 1 death. It does not report the cause of death or state whether the death was considered related to treatment. The serious-event terms listed include Anaemia, Pneumonia, and Squamous cell carcinoma, each reported as 1.2%; Bundle branch block bilateral, Pericarditis, and Ventricular extrasystoles are each reported as 0.6%. These percentages are reproduced as recorded; the summary does not supply further detail about event timing, recurrence, or participant-level overlap among terms.
Counts and percentages describe the observed study experience, not the probability of an event for every person with polycythemia vera. In general, estimates from a study sample are subject to uncertainty, and a single-group design cannot distinguish treatment effects from other explanations such as the underlying condition, other care, or chance. Those are general limitations of interpreting uncontrolled safety data, not findings about what caused any individual event in this study.
The registry lists changes in hematocrit, spleen length, and symptom score as secondary outcomes but does not report their results in the record summarized. It also lists no analyses in the registry record. Consequently, the posted information supports a description of the recorded safety counts, but does not support conclusions about change in those secondary outcomes or comparative treatment effects.
The adverse-event summary should be read alongside the study’s purpose and design. Participants entered an expanded treatment protocol in a context where the stated standard alternatives were unavailable to them. The observed counts are relevant to that group and study period; they should not be interpreted as a controlled estimate of excess risk or as proof for or against a treatment effect.
9. Statistical Methods Explained
The registry identifies a single-group, open-label protocol and reports participant counts for its safety summary. It does not report a detailed statistical analysis plan. The explanations below describe general statistical concepts relevant to interpreting this kind of record; they should not be taken as claims about methods that the investigators used.
What does a participant count describe?
A count of participants with an event records how many people experienced at least one event under the endpoint definition. It differs from a count of all event episodes: a participant with repeated events may still contribute once to a participant-based count. The registry gives the primary endpoint unit as participants. It does not describe rules for repeated events, event onset, or how events were classified for the all-grade endpoint.
A participant count also depends on who was observed and for how long. If participants have different follow-up durations, a simple count does not account for those differences in exposure time. Rates per unit of person-time or time-to-event analyses can address some follow-up differences, but the record does not report such measures or analyses for this endpoint. This is a general distinction, not a statement that unequal follow-up occurred.
What does an open-label, single-group design allow?
In an open-label study, participants and study personnel are not masked to the intervention. In a single-group design, all participants receive the study intervention and no concurrent control group is described. These features allow outcomes among treated participants to be recorded, but do not establish what would have happened to the same participants under a different treatment or without the intervention.
Random allocation in a controlled trial can help balance measured and unmeasured factors between groups on average. That design feature is not present in this registry record: allocation is listed as NA, and the model is single group. Therefore, an unadjusted comparison between treatment groups is not available. Changes observed over time, if reported, would also need careful interpretation because changes could reflect the intervention, the underlying condition, other care, measurement variation, or other influences. This is general reasoning about study design.
How should adverse-event categories be read?
Seriousness and grade are related but distinct concepts. Seriousness generally classifies an event according to consequences or regulatory criteria, whereas grade describes severity. The record’s primary endpoint refers to events of all grades, and its safety summary distinguishes serious events from other events. The registry summary does not provide definitions, grading criteria, adjudication procedures, or a complete breakdown linking all-grade events to the serious and other categories.
Event terms and percentages are descriptive. A percentage for a particular term does not on its own establish causality, duration, recurrence, or the number of events per affected participant. Without a control group and the necessary analysis details, the percentages should not be interpreted as comparative risks attributable to ruxolitinib.
What do planning calculations mean?
Sample-size calculations are planning illustrations, not observed power. The assumptions described for planning use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect expressed as a stated fraction of an observed effect. Those assumptions describe a hypothetical two-arm planning framework, whereas this protocol is single group. Any resulting arm-size illustration is therefore not the observed enrollment design and should not be read as evidence that the protocol had a particular power to detect an effect.
More generally, power is a design calculation conditional on assumptions about the effect, variability, significance level, and analysis. It is not a measure of whether a result is true, nor does it indicate the probability that a treatment works. The registry record does not report the protocol’s own sample-size justification or whether the planning assumptions were used in its design.
Confidence intervals, when reported, describe uncertainty around an estimate under the assumptions of the analysis; they do not repair the absence of a comparator or eliminate bias. The registry record summarized for this protocol does not report confidence intervals for the safety counts. Statistical precision and causal interpretation are separate issues: a precise count in a single group would still not establish a comparative treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary safety endpoint and secondary outcomes concerning hematocrit, spleen length, and symptom score. It does not report how the analysis handled multiple outcomes or multiple time points. When several outcomes or repeated comparisons are examined, the chance of at least one apparently notable result can increase. Statistical plans may address this through a prespecified hierarchy or adjustment, but the record does not state whether any such approach was used. No adjustment method should be inferred.
The record lists no analyses. That does not establish that no analyses were performed; it means analysis details are not reported in the registry record summarized. The record also does not give the statistical model, the method used to estimate event frequencies, or any approach to uncertainty for the primary endpoint.
Missing-data methods and the handling of incomplete follow-up are not reported in the registry record. The record does not state how participants who stopped treatment, missed visits, or had incomplete outcome information were handled. For a safety endpoint, these details matter because a person with shorter observation may have less opportunity for an event to be recorded. This is a general methodological concern, not a claim that any particular missingness occurred.
The analysis population is not specified in the endpoint description. Although the safety summary lists 161 participants at risk for each displayed category, the record does not explain whether all enrolled participants were included in every endpoint analysis or how the at-risk counts were defined. The registry record also does not report a prespecified handling of events after treatment discontinuation.
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 |
|---|---|---|---|
| All Patients | 26 | 161 | 16.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Patients | 1 of 161 |
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 |
|---|---|
| All Patients | 107 of 161 |
Most frequent serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 2 of 161 |
| Pneumonia | Infections and infestations | 2 of 161 |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 161 |
| Bundle branch block bilateral | Cardiac disorders | 1 of 161 |
| Pericarditis | Cardiac disorders | 1 of 161 |
| Ventricular extrasystoles | Cardiac disorders | 1 of 161 |
| Cataract | Eye disorders | 1 of 161 |
| Ascites | Gastrointestinal disorders | 1 of 161 |
| Diarrhoea | Gastrointestinal disorders | 1 of 161 |
| Retroperitoneal haematoma | Gastrointestinal disorders | 1 of 161 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 35 of 161 |
| Headache | Nervous system disorders | 27 of 161 |
| Diarrhoea | Gastrointestinal disorders | 15 of 161 |
| Constipation | Gastrointestinal disorders | 14 of 161 |
| Fatigue | General disorders | 14 of 161 |
| Weight increased | Investigations | 13 of 161 |
| Pruritus | Skin and subcutaneous tissue disorders | 13 of 161 |
| Asthenia | General disorders | 12 of 161 |
| Dizziness | Nervous system disorders | 12 of 161 |
| Thrombocytosis | Blood and lymphatic system disorders | 11 of 161 |
Serious events with the highest arm-level rate: anaemia (1.2%), pneumonia (1.2%), squamous cell carcinoma (1.2%), bundle branch block bilateral (0.6%), pericarditis (0.6%).
The registry lists 26 participants affected by serious adverse events among 161 at risk, and 107 participants affected by other adverse events among 161 at risk. It separately reports 1 death. These are counts in the study group, not comparisons with another treatment group. The record does not state whether the death was related to treatment or provide its cause.
The listed serious adverse-event terms and their reported percentages are Anaemia, Pneumonia, and Squamous cell carcinoma at 1.2% each; and Bundle branch block bilateral, Pericarditis, and Ventricular extrasystoles at 0.6% each. These are the terms identified in the registry summary, not a full clinical account of every event. The record does not provide event-level details, timing, duration, recurrence, or the degree of overlap among participants with different terms.
Serious adverse events should not be conflated with all-grade adverse events. The primary endpoint is described as participants with adverse events of all grades, while the displayed safety counts distinguish serious and other events. The record does not report a combined count for all grades in the information summarized. None of these descriptive counts establishes that ruxolitinib caused an event.
12. What the Result Does, and Does Not, Mean
The record documents a completed, open-label expanded treatment protocol in which 161 participants with polycythemia vera received ruxolitinib. Its stated purpose was early access and safety evaluation for people who were hydroxyurea resistant or intolerant and lacked the stated treatment alternatives. The safety summary reports serious and other adverse-event counts and lists selected serious-event terms and their percentages.
Those findings describe what was recorded in this participant group over the endpoint’s stated timeframe. They do not provide a randomized comparison, so they cannot show how the observed counts differ from outcomes under another treatment or no treatment. A count observed during treatment also does not by itself establish that the treatment caused the event. The record does not report the cause of the death.
The registry lists secondary outcomes related to hematocrit, spleen length, and symptom score, but their results are not reported in the registry record summarized. Therefore, the available information does not establish the direction or size of changes in those outcomes. Nor does it provide detailed estimates of uncertainty for the safety counts.
General statistical interpretation requires attention to both design and measurement. A single-group safety record can be informative about events recorded during treatment, but event definitions, follow-up completeness, analysis populations, and potential differences in observation time affect interpretation. Those details are not reported in the registry record. The findings apply most directly to the population and protocol described, and should not be treated as a comparative treatment effect or generalized without considering those limitations.
13. Why This Trial Matters Statistically
This protocol is statistically important as an example of a study whose purpose and design shape the conclusions that can be drawn. Its stated goal was early access to ruxolitinib and safety evaluation in a population with limited standard treatment alternatives. A single-group expanded treatment protocol can describe events among participants who receive the intervention, while not answering the same question as a randomized comparative trial.
That distinction matters when interpreting percentages and counts. A number of participants with events is meaningful as a description of the study experience, but it is not an estimate of excess events attributable to treatment. Without a control group, differences from an external expectation would be vulnerable to differences in population, follow-up, and event ascertainment. These are general reasons to distinguish descriptive safety evidence from comparative evidence.
The record also illustrates why endpoint definitions and reporting detail matter. The primary endpoint concerns all-grade adverse events, while the safety summary separately gives serious and other counts. The record does not explain the relationship between these categories in enough detail to combine or reinterpret them. It does not report analysis methods, missing-data procedures, or detailed results for the listed secondary outcomes.
For biostatistical reading, the central task is to keep the estimand aligned with the design: describe the recorded safety experience in the protocol population, and avoid treating it as a causal contrast. The protocol’s access purpose remains important context for understanding why a single-group design was used, but does not remove the limits on comparative inference.
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 lack of a comparator is the main design limitation for comparative interpretation. Since the registry describes a single group receiving ruxolitinib, the observed safety counts cannot be contrasted with outcomes under another intervention within this study. The record does not support estimation of a treatment difference or attribution of events to treatment.
The registry record does not report detailed eligibility criteria, participant characteristics, follow-up by participant, or the distribution of treatment exposure. Although the endpoint timeframe is stated as baseline up to approximately 26 months, the record does not specify whether each participant had the same observation period. The dose could be titrated within stated limits, but the record does not describe actual dose levels or duration at each dose.
Event ascertainment and analysis details are also not reported in the registry record. Definitions and grading procedures, event timing, handling of recurrent events, missing-data methods, and analysis populations are not specified. The all-grade primary endpoint is not accompanied by a combined count in the summarized safety information. The relationship between serious and other adverse events is not described in detail.
The record lists three secondary outcomes but does not report their results in the material summarized. It also does not report confidence intervals, the protocol’s sample-size justification, or a detailed statistical plan. These omissions limit assessment of precision and of how outcomes were analyzed. They do not imply that the information was never collected or analyzed; they are limits of what is reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available. — NCT02292446.
- Registry record last updated 2019-07-18; status last verified 2019-07.
- Results first posted 2019-04-02.
- 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
NCT02292446 is a completed phase 3, open-label, multicenter, single-group expanded treatment protocol of ruxolitinib in people with polycythemia vera who were hydroxyurea resistant or intolerant and had no available standard treatment alternative. Enrollment was 161. The stated starting dose was 10 mg twice daily, with titration within the specified dose limits.
The primary endpoint was the number of participants with adverse events of all grades from baseline up to approximately 26 months. The safety summary lists 26 participants with serious adverse events and 107 with other adverse events, each among 161 at risk, and reports 1 death. The registry also lists secondary outcomes concerning hematocrit, spleen length, and symptom score, but their results and detailed analysis methods are not reported in the registry record.
As a single-group study, the record describes safety observations but does not provide a randomized comparison or establish that events were caused by treatment.