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 Open Label Ruxolitinib (INCB018424) in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (NCT00509899), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00509899 |
| Phase | Phase 1, Phase 2 |
| Condition | Myelofibrosis, Polycythemia Vera, Thrombocytosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 154 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Incyte Corporation |
| Results posted | Yes |
2. Clinical Question
Population
Patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or essential thrombocythemia myelofibrosis. The safety population included patients who received at least one dose of study medication.
Intervention
Oral ruxolitinib, with starting doses that varied according to when participants entered the study. The listed starting regimens included 10 mg twice a day, 15 mg twice a day, 25 mg twice a day, 50 mg twice a day, 25 mg once a day, 50 mg once a day, 100 mg once a day or 200 mg once a day.
Comparator
There was no separate control group. The registry describes a single-group, open-label study, and the dose groups are not a randomized comparison.
Primary question
How many participants experienced adverse events during the study period? The primary outcome is a participant count, with treatment-emergent and treatment-related events defined in the registry record.
The study’s stated purpose was to assess the safety, tolerability and effectiveness of ruxolitinib in the specified myelofibrosis populations. The registry lists secondary outcomes concerning spleen palpation length, spleen volume, myelofibrosis symptoms, health-related quality of life, body weight and ECOG performance status. These outcomes describe additional areas of interest, but their result values are not reported in the registry record.
The central statistical question is descriptive rather than a treatment-versus-control comparison: what adverse events were recorded among participants receiving ruxolitinib, and how should counts be understood in a study without random allocation? Such data can describe observed safety experience in the enrolled group. On their own, they do not establish what would have happened to the same participants under a different treatment or no treatment.
3. Trial Design
This was a Phase 1/2, open-label, single-group study of oral ruxolitinib. The registry reports an enrollment of 154 and describes patients with primary myelofibrosis, post-polycythemia vera myelofibrosis and essential thrombocythemia myelofibrosis. There was no randomized allocation and no masked treatment assignment. All participants received oral ruxolitinib; therefore, the study does not provide a concurrent untreated or active-control group for estimating a comparative treatment effect.
Starting dose depended on the period in which a participant entered the study. The listed regimens were 10 mg twice a day, 15 mg twice a day, 25 mg twice a day, 50 mg twice a day, 25 mg once a day, 50 mg once a day, 100 mg once a day and 200 mg once a day. The record says doses were titrated based on efficacy and, but the remaining description is not reported in the registry record. Dose groups therefore should not be interpreted as randomized arms or as directly comparable treatment groups.
The primary outcome was the number of participants with adverse events, assessed from baseline to the interim clinical cut-off date of 31 December 2009. The registry reports a median time on study of 14.8 months, with a range of 26 days to 29.7 months. It also reports total ruxolitinib exposure of 269 patient-years as of March 1, 2011. These different follow-up and exposure summaries matter when interpreting event counts: participants may have contributed different amounts of observation time.
The study is marked completed. The registry record does not report a detailed allocation procedure, a control group, or the full dose-titration rule. A sample-size justification and a full statistical analysis plan 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: This was a non-randomized dose-ranging study. Participants were enrolled into the currently available cohort based on the timeframe when they entered the study.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | 10 mg Bid | 15 mg Bid | 25 mg Bid | 50 mg Bid | 25 mg qd | 50 mg qd |
|---|---|---|---|---|---|---|
| STARTED | 30 | 35 | 47 | 5 | 6 | 22 |
| COMPLETED | 14 | 26 | 27 | 1 | 1 | 12 |
| NOT COMPLETED | 16 | 9 | 20 | 4 | 5 | 10 |
Reasons for not completing this period:
| Reason | 10 mg Bid | 15 mg Bid | 25 mg Bid | 50 mg Bid | 25 mg qd | 50 mg qd |
|---|---|---|---|---|---|---|
| Progressive disease | 1 | 3 | 5 | 1 | 0 | 1 |
| Unacceptable Toxicity | 1 | 0 | 0 | 2 | 0 | 0 |
| Withdrawal by Subject | 6 | 2 | 3 | 0 | 3 | 2 |
| Physician Decision | 4 | 2 | 7 | 0 | 1 | 4 |
| Intercurrent Illness | 1 | 0 | 0 | 1 | 0 | 1 |
| Death | 2 | 2 | 3 | 0 | 1 | 1 |
| Lack of Efficacy | 1 | 0 | 2 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety population included all patients who received at least 1 dose of study medication.
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.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | 10 mg Bid | 15 mg Bid | 25 mg Bid | 50 mg Bid | 25 mg qd | 50 mg qd |
|---|---|---|---|---|---|---|---|
| Participants analysed | 30 | 35 | 47 | 5 | 6 | 22 | |
| Age, Continuous | years | 61.6 (SD 8.29) | 63.8 (SD 9.57) | 63.9 (SD 9.06) | 63.0 (SD 8.37) | 57.3 (SD 9.89) | 66.3 (SD 6.66) |
| Sex: Female, Male: Female | Participants | 12 | 12 | 16 | 2 | 1 | 12 |
| Sex: Female, Male: Male | Participants | 18 | 23 | 31 | 3 | 5 | 10 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 0 | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: White | Participants | 28 | 35 | 45 | 5 | 6 | 20 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 0 | 1 | 0 | 0 | 1 |
| Disease sub-type: Primary myelofibrosis | Participants | 12 | 19 | 23 | 3 | 5 | 14 |
| Disease sub-type: Post-polycythemia vera-myelofibrosis | Participants | 13 | 10 | 15 | 2 | 1 | 4 |
| Disease sub-type: Post-essential thrombocythemia-myelofibrosis | Participants | 5 | 6 | 9 | 0 | 0 | 4 |
| Body Mass Index (BMI) | kg/m^2 | 25.8 (SD 3.8) | 25.3 (SD 4.4) | 26.2 (SD 5.9) | 24.8 (SD 2.9) | 24.7 (SD 2.9) | 25.3 (SD 4.5) |
| Palpable spleen length below the costal margin | cm | 19.11 (SD 8.2) | 18.47 (SD 5.7) | 17.13 (SD 8.9) | 13.0 (SD 10.1) | 19.58 (SD 10.5) | 20.0 (SD 7.3) |
| JAK2 V617F mutation status: Negative | participants | 1 | 5 | 5 | 1 | 4 | 7 |
| JAK2 V617F mutation status: Positive | participants | 22 | 29 | 39 | 2 | 2 | 15 |
| JAK2 V617F mutation status: Unknown | participants | 7 | 1 | 3 | 2 | 0 | 0 |
| Eastern Cooperative Oncology Group Performance Status: 0 | participants | 7 | 0 | 9 | 2 | 1 | 5 |
| Eastern Cooperative Oncology Group Performance Status: 1 | participants | 19 | 32 | 33 | 3 | 4 | 14 |
| Eastern Cooperative Oncology Group Performance Status: 2 | participants | 4 | 3 | 5 | 0 | 1 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over From Baseline to the interim clinical cut-off date (31 December 2009). The median time on study was 14.8 months, with a range of 26 days to 29.7 months. As of March 1, 2011 the total exposure to ruxolitinib was 269 patient-years..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events. It is a count of participants, rather than a measure of the number of separate event episodes or an event rate per unit of follow-up. The safety population included all patients who received at least one dose of study medication.
The registry distinguishes treatment-emergent events, which occurred after the first drug administration or worsened from baseline, from treatment-related events. Treatment-related events were those with definite, probable, possible or missing causality. A serious adverse event was defined by specified medical consequences, including death, life-threatening illness, inpatient hospitalization or its prolongation, persistent or significant disability, congenital anomaly or birth defect, or a medical event requiring intervention to prevent one of those outcomes. Severe or life-threatening intensity was based on NCI-CTCAE v3.0.
Safety counts are used to describe the types and extent of adverse events observed during treatment. General statistical context: a participant count is easy to interpret, but it does not by itself account for differences in follow-up duration. Nor can it separate effects of treatment from the underlying illness, other exposures or chance. The registry’s follow-up summaries help describe observation time, but an exposure-adjusted event rate is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results give participant counts by dose group for serious adverse events and for other adverse events. In the 10 mg Bid group, 8 of 30 participants were recorded with serious adverse events and 29 of 30 with other adverse events. In the 15 mg Bid group, the corresponding counts were 17 of 35 and 35 of 35. In the 25 mg Bid group, they were 21 of 47 and 47 of 47. In the 50 mg Bid group, they were 2 of 5 and 5 of 5. In the All QD group, they were 23 of 37 and 36 of 37. These are descriptive counts within groups, not estimates from a randomized comparison.
The registry lists anaemia and pneumonia as top serious adverse event terms, each at 20.0%. Splenomegaly is listed at 8.6%, pyrexia at 6.4%, myocardial infarction at 5.4% and asthenia at 5.4%. These percentages describe the listed terms as recorded; the registry record does not provide additional detail about the denominator or the method used to derive each percentage. Death counts are not reported in the registry record.
Counts require caution because follow-up was not identical for every participant. The median time on study was 14.8 months, with a range of 26 days to 29.7 months. Total exposure to ruxolitinib was 269 patient-years as of March 1, 2011. A count accumulated over longer observation can be larger simply because there was more time in which an event could be recorded. The posted counts are not exposure-adjusted rates.
The dose groups also cannot be read as a dose-response experiment. Starting doses depended on entry period, doses were titrated, and the study had no random allocation. Differences in counts between groups could reflect group size, length of observation, participant characteristics, dose changes or other factors; the registry record does not establish their contributions. The results describe adverse events among participants in this study, but do not identify the cause of each event or compare risk against a control group.
The listed secondary outcomes concern spleen measures, symptoms, quality of life, body weight and ECOG performance status. Their result values are not reported in the registry record, so no conclusion about changes in those measures can be drawn from the posted information. Likewise, inferential estimates such as confidence intervals or p-values are not reported in the registry record. The safety findings should therefore be read as descriptive evidence with limited comparative precision, not as a causal estimate.
9. Statistical Methods Explained
In general, a single-group safety study summarizes events observed among participants exposed to the study treatment. Here, the primary endpoint is a participant count. The registry record identifies the safety population as all patients who received at least one dose. This definition means that the endpoint concerns treated participants rather than everyone who might have been screened or considered for enrollment. The number of enrolled participants is 154, but the record does not give further detail about screening or exclusions.
What does a participant count represent?
A count of participants with an event differs from a count of event episodes. A participant may experience more than one event, but a participant-level count records whether a person was affected, not how many episodes occurred. The primary outcome title specifies the number of participants with adverse events. The registry’s dose-group results separately report counts for serious adverse events and other adverse events. The record does not provide a fuller account of how repeat events were handled in those group summaries.
The event definitions also determine what is counted. Treatment-emergent events occurred after first drug administration or worsened from baseline. Treatment-related events included events with definite, probable, possible or missing causality. Seriousness is based on medical consequences, whereas severity or intensity is based on NCI-CTCAE v3.0. In general, seriousness and severity are distinct concepts: an event can be medically serious because of its consequences, while intensity describes how severe it is. The registry record supplies these definitions but does not report a complete cross-tabulation of seriousness, intensity and causality.
Why does follow-up matter?
General statistical context: raw participant counts do not adjust for how long participants were observed. Participants with longer follow-up have more opportunity for an event to be detected. The registry reports a median time on study of 14.8 months, a range of 26 days to 29.7 months, and total exposure of 269 patient-years as of March 1, 2011. These summaries signal that observation time varied. They do not, by themselves, convert the posted counts into event rates or make group follow-up comparable. An exposure-adjusted rate and its uncertainty are not reported in the registry record.
Confidence intervals are a general way to express the precision of an estimated quantity: they show a range of values compatible with the data under a specified statistical model. A confidence interval for a participant proportion or event rate is not reported in the registry record. Without such an interval, the posted counts alone do not quantify sampling uncertainty. Even an interval would not resolve the absence of a randomized control group or remove possible differences between dose groups.
What can dose groups show?
In general, comparing event counts across groups can be informative only when the groups and observation periods are understood. This study was single-group and not randomized. Participants began with different listed regimens according to when they entered, and doses were titrated based on efficacy and a further criterion that is not reported in the registry record. The dose-group labels therefore do not establish fixed, independently assigned treatment levels. Differences in counts are descriptive and cannot be attributed to dose from these data alone.
The planning assumptions in the registry describe an illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For time-to-event outcomes, that illustration uses a total number of events; for other outcomes, it expresses participants per arm. These are planning assumptions, not the design used in this single-group study. Planning illustrations are not observed power, and the numerical sample-size illustrations are not reported in the registry record. The trial’s own sample-size justification is not reported in the registry record.
General statistical context: over-dispersion matters when variability in count data is greater than a simple model assumes. A model that underestimates variability can make uncertainty look smaller than it is. The registry record does not report a count model, an over-dispersion assessment or a model-based analysis for this endpoint, so none should be inferred.
What inferential results are available?
The registry includes adverse-event counts and a list of secondary outcome measures, but it does not report p-values, confidence intervals or adjusted effect estimates for the outcomes described. The secondary outcomes include percentage reductions in spleen measures, changes in symptom score, health-related quality of life, body weight and ECOG performance status. Their result values are not reported in the registry record. There is therefore no basis in the posted information for reconstructing an efficacy analysis or assessing its precision.
General statistical context: a p-value is a measure of how compatible data are with a specified null model; it is not the probability that a treatment works or that the null hypothesis is true. An effect estimate and confidence interval are usually more informative about magnitude and precision than a p-value alone. Neither form of inferential result is reported for these outcomes in the registry record. The available safety counts should be interpreted descriptively, with the design and variable follow-up kept in view.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures, including the primary adverse-event outcome and secondary measures of spleen response, symptoms, health-related quality of life, body weight and ECOG performance status. Considering multiple outcomes creates a general multiplicity issue: if many statistical tests are conducted, the chance of at least one apparently unusual result can increase. Whether and how that issue was addressed is not reported in the registry record. Adjustments for multiple testing, a prespecified hierarchy of outcomes and an analysis plan are not reported in the registry record.
The registry gives secondary outcome titles and time points, including Week 24 for symptom score, health-related quality of life and ECOG performance status. Their result values and analysis details are not reported in the registry record. It is therefore not possible to assess whether all listed outcomes were analyzed, how missing measurements were handled, or whether analyses followed a prespecified plan. The primary safety outcome is described over a stated period, but missing-data procedures for adverse-event reporting are not reported in the registry record.
The safety population included all patients who received at least one dose. The registry record does not report a separate intention-to-treat population, per-protocol population, or rules for excluding participants from particular outcome analyses. Nor does it report how participants who discontinued treatment or had incomplete follow-up contributed to each summary. These omissions limit assessment of the analysis populations and the potential influence of missing data.
General statistical context: missingness can affect conclusions when the likelihood of an unrecorded outcome is related to a participant’s health, treatment or follow-up. Simply knowing that a result is missing does not establish the direction or size of any resulting bias. No missing-data assumptions or sensitivity analyses are reported in the registry record. The statistical analysis plan, interim analysis procedures and multiplicity strategy are also not reported in the registry record.
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 |
|---|---|---|---|
| 10 mg Bid | 8 | 30 | 26.7% |
| 15 mg Bid | 17 | 35 | 48.6% |
| 25 mg Bid | 21 | 47 | 44.7% |
| 50 mg Bid | 2 | 5 | 40.0% |
| All QD | 23 | 37 | 62.2% |
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 |
|---|---|
| 10 mg Bid | 29 of 30 |
| 15 mg Bid | 35 of 35 |
| 25 mg Bid | 47 of 47 |
| 50 mg Bid | 5 of 5 |
| All QD | 36 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | 10 mg Bid | 15 mg Bid | 25 mg Bid | 50 mg Bid | All QD |
|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 2 of 30 | 0 of 35 | 3 of 47 | 1 of 5 | 5 of 37 |
| Splenomegaly | Blood and lymphatic system disorders | 1 of 30 | 3 of 35 | 2 of 47 | 0 of 5 | 0 of 37 |
| Anaemia | Blood and lymphatic system disorders | 0 of 30 | 0 of 35 | 1 of 47 | 1 of 5 | 3 of 37 |
| Pyrexia | General disorders | 0 of 30 | 0 of 35 | 3 of 47 | 0 of 5 | 2 of 37 |
| Asthenia | General disorders | 0 of 30 | 0 of 35 | 1 of 47 | 0 of 5 | 2 of 37 |
| Cellulitis | Infections and infestations | 0 of 30 | 1 of 35 | 0 of 47 | 0 of 5 | 2 of 37 |
| Sepsis | Infections and infestations | 0 of 30 | 0 of 35 | 2 of 47 | 0 of 5 | 1 of 37 |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 30 | 0 of 35 | 1 of 47 | 0 of 5 | 2 of 37 |
| Myocardial infarction | Cardiac disorders | 0 of 30 | 0 of 35 | 0 of 47 | 0 of 5 | 2 of 37 |
| Diarrhoea | Gastrointestinal disorders | 0 of 30 | 0 of 35 | 1 of 47 | 0 of 5 | 1 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 10 mg Bid | 15 mg Bid | 25 mg Bid | 50 mg Bid | All QD |
|---|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 14 of 30 | 14 of 35 | 27 of 47 | 0 of 5 | 18 of 37 |
| Thrombocytopenia | Blood and lymphatic system disorders | 12 of 30 | 11 of 35 | 29 of 47 | 4 of 5 | 14 of 37 |
| Diarrhoea | Gastrointestinal disorders | 8 of 30 | 12 of 35 | 15 of 47 | 1 of 5 | 6 of 37 |
| Fatigue | General disorders | 7 of 30 | 10 of 35 | 11 of 47 | 1 of 5 | 7 of 37 |
| Cardiac murmur | Investigations | 6 of 30 | 7 of 35 | 7 of 47 | 0 of 5 | 7 of 37 |
| Headache | Nervous system disorders | 6 of 30 | 6 of 35 | 5 of 47 | 3 of 5 | 6 of 37 |
| Weight increased | Investigations | 3 of 30 | 4 of 35 | 9 of 47 | 1 of 5 | 8 of 37 |
| Nausea | Gastrointestinal disorders | 7 of 30 | 4 of 35 | 6 of 47 | 1 of 5 | 6 of 37 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 3 of 30 | 4 of 35 | 11 of 47 | 1 of 5 | 5 of 37 |
| Edema peripheral | General disorders | 2 of 30 | 8 of 35 | 10 of 47 | 3 of 5 | 0 of 37 |
Serious events with the highest arm-level rate: anaemia (20.0%), pneumonia (20.0%), splenomegaly (8.6%), pyrexia (6.4%), myocardial infarction (5.4%).
The safety summaries give the number of participants at risk and the number recorded with serious adverse events and other adverse events in each dose group. The reported serious-event counts are 8 of 30 for 10 mg Bid, 17 of 35 for 15 mg Bid, 21 of 47 for 25 mg Bid, 2 of 5 for 50 mg Bid and 23 of 37 for All QD. The corresponding other-event counts are 29 of 30, 35 of 35, 47 of 47, 5 of 5 and 36 of 37. These figures are counts within nonrandomized dose groups, not treatment-versus-control effects.
The registry lists anaemia and pneumonia at 20.0% each among the top serious adverse event terms; it also lists splenomegaly at 8.6%, pyrexia at 6.4%, myocardial infarction at 5.4% and asthenia at 5.4%. Death counts are not reported in the registry record. The record defines serious adverse events by medical consequences and defines severe or life-threatening intensity separately using NCI-CTCAE v3.0.
General statistical context: these counts do not account for differing follow-up. The reported time on study ranged from 26 days to 29.7 months, and total exposure was 269 patient-years as of March 1, 2011. The counts are not exposure-adjusted rates, and the registry record does not report uncertainty intervals for them. Group differences should not be interpreted as evidence that one dose caused more or fewer events.
12. What the Result Does, and Does Not, Mean
The results describe adverse events recorded among participants who received oral ruxolitinib in an open-label, single-group study. They provide counts by the listed dose groups and identify several serious adverse event terms. This is useful descriptive information about the study’s safety experience, interpreted alongside the registry’s event definitions and follow-up summaries.
The counts do not estimate a comparative effect against placebo, usual care or another treatment, because no control group was included. The study was not randomized, and participants entered under different starting-dose regimens according to the time period of entry. Dose titration further means that a starting-dose label should not be treated as a fixed exposure assignment. The registry record does not establish that observed differences between dose groups were caused by dose.
General statistical context: observed events in a clinical study can reflect treatment, underlying disease, other factors or chance. A single-group design cannot isolate those explanations in the way a suitable randomized comparison may help to do. Counts also depend on the amount of follow-up and the way events are classified. Follow-up varied, and exposure-adjusted rates are not reported in the registry record.
The registry’s secondary outcomes cover spleen measures, symptoms, quality of life, body weight and performance status, but their results are not reported in the registry record. The posted information therefore does not support conclusions about changes in those outcomes. Inferential results such as confidence intervals and p-values are also not reported in the registry record, limiting assessment of statistical precision.
These findings should be understood as a record of events observed in the study population, not as proof of a causal relationship for each event or a comparison of risks with another treatment. They also do not determine how results would apply to patients outside the populations and study conditions described in the registry.
13. Why This Trial Matters Statistically
This trial illustrates why study design shapes the questions that statistical results can answer. A single-group study can document adverse events during treatment, but it cannot make a randomized comparison with an alternative. The dose groups may look like separate arms, yet the registry states that allocation was not randomized and that starting dose depended on entry period. Their counts are therefore descriptive rather than direct estimates of comparative safety.
The record also illustrates the importance of keeping counts distinct from rates. Participants had different observed time on study, ranging from 26 days to 29.7 months, while total exposure was reported as 269 patient-years. A raw count does not account for that variation. Exposure adjustment could address time at risk in some analyses, but no exposure-adjusted adverse-event rate is reported in the registry record.
Endpoint definitions matter as well. The record distinguishes treatment-emergent events, treatment-related events, serious events and severe or life-threatening intensity. These categories answer different questions and should not be treated as interchangeable. Their interpretation depends on the stated definitions and the level of detail available in the results.
Finally, the study shows why outcome listings and outcome results must be distinguished. Several secondary measures are named, but their results are not reported in the registry record. Without estimates, uncertainty measures and analysis details, readers cannot assess their magnitude or precision. The available information supports a descriptive reading of the posted safety counts, while leaving comparative and inferential questions unresolved.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main design limitation is the absence of a randomized control group. The study is open-label and single-group, so it cannot estimate how adverse-event experience differed from an alternative treatment or no study treatment. The dose groups are not like-for-like randomized arms: starting regimens depended on the time of entry, and doses were titrated. The remaining detail about the titration rule is not reported in the registry record.
Follow-up varied across participants. The registry reports a median time on study of 14.8 months and a range of 26 days to 29.7 months. Raw counts do not account for that variation, and exposure-adjusted rates are not reported in the registry record. The record also does not report confidence intervals or other measures of uncertainty for the adverse-event counts.
The outcome information is incomplete for statistical interpretation. Although secondary outcomes are listed, their results are not reported in the registry record. A detailed statistical analysis plan, sample-size justification, interim analysis procedures, missing-data methods, multiplicity strategy and analysis populations beyond the stated safety population are not reported in the registry record.
The registry defines adverse-event categories but does not provide all details needed to assess event-level handling, such as how repeat events were represented in the group summaries. Death counts are not reported in the registry record. The percentages listed for top serious adverse event terms are not accompanied by additional denominator or derivation detail in the information available. Together, these limitations support a descriptive, cautious interpretation rather than a comparative or causal conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open Label Ruxolitinib (INCB018424) in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis — NCT00509899.
- Registry record last updated 2018-03-12; status last verified 2018-02.
- Results first posted 2012-08-02.
- 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
NCT00509899 is a completed Phase 1/2, open-label, single-group study of oral ruxolitinib in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or essential thrombocythemia myelofibrosis. Enrollment was 154. Starting doses varied according to entry period, and the registry describes dose titration.
The primary outcome was the number of participants with adverse events. The safety population included patients who received at least one dose. The registry reports serious and other adverse-event counts by dose group, along with selected serious-event terms and percentages. Time on study had a median of 14.8 months and a range of 26 days to 29.7 months; total exposure was 269 patient-years as of March 1, 2011.
The study had no randomized control group. Secondary outcomes are listed, but their results and inferential estimates are not reported in the registry record. The posted safety counts are descriptive and do not establish comparative treatment effects.