Exploratory Multi-centre Trial In Patients With ET Treated With XAGRID®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exploratory Multi-centre Trial In Patients With ET Treated With XAGRID® (NCT01352585), a registered phase not stated study. The primary outcome is Number of Patients With Platelet Count ≤600x10^9/L After 12 Months.

2. Clinical Question

The study is explicitly described as exploratory and hypothesis-generating. Its focus is whether JAK2 (V617F) mutation status is associated with treatment response in patients with ET treated with anagrelide hydrochloride. Because the registry describes an observational study and does not state that mutation status was assigned, the comparison is about response across existing status groups, not about the effect of assigning a mutation or a treatment.

The primary outcome uses a platelet-count threshold at a specified follow-up time. It does not, by itself, describe the full course of platelet counts, the time taken to reach the threshold, or how long a response was maintained. The record also lists laboratory measures and a second platelet-count threshold as secondary outcomes, but does not provide results for them. Consequently, the posted information establishes the question and its measurement framework, but does not show whether the groups differed in the observed response.

3. Trial Design

The registry describes NCT01352585 as an exploratory, observational, multicentre study of patients with essential thrombocythemia treated with XAGRID® (anagrelide hydrochloride). Its stated purpose was to investigate the impact of JAK2 (V617F) mutation status on treatment response. The study is marked completed. The recorded study start is 2011-07-19, the primary completion date is 2013-09-19, and enrollment is 47.

The comparison is organized by JAK2 status: positive participants and negative participants. The registry does not describe these as randomized treatment groups, and the allocation field is not stated. Both groups therefore should be read as observational status groups, not as a treatment and control pair. The arm descriptions do not add details about the groups. Baseline characteristics, treatment schedules, dose changes, adherence, and other co-interventions are not reported in the registry record.

The primary outcome is the number of patients with a platelet count of ≤600x10^9/L after 12 months. The description defines that threshold as at least a partial response. The primary analysis population is the Full Analysis Set in each JAK2 status group with a viable platelet sample during the 12-month follow-up window; the record says 35 patients in the Full Analysis Set had a viable laboratory sample for this outcome. It does not state the group-specific number contributing to the primary outcome.

The registry lists several additional laboratory outcomes, including platelet, red blood cell, white blood cell, differential white blood cell, hemoglobin, and hematocrit measures. It also lists the number of patients with a platelet count of ≤400x10^9/L after 12 months. The record does not provide their numerical results. It lists zero outcome analyses, so estimates, statistical comparisons, and analysis details are not posted. The protocol's statistical plan, sample-size justification, and approach to interim analyses are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 35 patients in the FAS had a viable laboratory sample.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Platelet Count ≤600x10^9/L After 12 Months, measured over 1 year.

The primary endpoint is the number of patients with a platelet count of ≤600x10^9/L after 12 months. The registry defines reaching this threshold as at least a partial response. It is a binary participant-level outcome: each assessed participant either meets the stated threshold at the follow-up measurement or does not. The reported endpoint is a count of participants, rather than a continuous summary of platelet values.

A threshold can make a clinical response criterion easier to interpret than a collection of raw laboratory values. It also reduces a range of measurements to a yes-or-no classification at the specified assessment time. That simplification comes with a trade-off: people with counts just on either side of the cutoff are classified differently, even if their measured values are close. The endpoint also does not describe changes between baseline and follow-up, the pattern of measurements over time, or whether the threshold was sustained.

The endpoint is assessed after 12 months, while the primary timeframe is also described as 1 year. The defined population consists of Full Analysis Set participants in each JAK2 status group who had a viable platelet sample during the follow-up window. The record says 35 patients in the Full Analysis Set had a viable laboratory sample, but does not report how many met the threshold in either group. It also does not provide a group-specific denominator for the endpoint or an estimate comparing the groups. The registry record therefore identifies the response rule and assessment time, but not the observed response counts or their precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary outcome is a participant count based on a binary classification. At the 12-month assessment, a participant with a platelet count of ≤600x10^9/L meets the registry's definition of at least a partial response; a participant who does not meet that cutoff does not. The endpoint is therefore not a mean platelet count or a measure of change from baseline. It compresses a laboratory value into a response category and reports the number meeting the criterion.

As a general statistical point, binary outcomes can be described using counts and proportions. A count needs a clear denominator to show how common the outcome was among the assessed group. A proportion also needs an uncertainty measure when the aim is to judge how precisely the underlying response frequency is estimated. The registry record gives an overall count of Full Analysis Set participants with a viable laboratory sample for this outcome, but does not give the number meeting the cutoff or the group-specific denominators. It does not post a confidence interval or other uncertainty measure.

What does a confidence interval communicate? In general, a confidence interval describes the range of effect estimates compatible with the data under the method used. A narrow interval indicates greater precision than a wide interval, while an interval that spans effects in different directions may leave the direction uncertain. A confidence interval is not a guarantee that the true value lies inside its limits. No confidence interval for this primary outcome is reported in the registry record, so its precision cannot be evaluated from the posted results.

What does the group comparison represent? The groups are defined by JAK2 status, with positive and negative participants considered separately. This is an observational comparison, not a randomized allocation to treatments. In general, randomization can help balance measured and unmeasured baseline factors across treatment groups, whereas an observational comparison can retain differences related to who is in each group. The registry does not report baseline characteristics or an adjusted analysis for this endpoint. Any association, if estimated, would not by itself establish that JAK2 status caused a difference in response.

What analyses are reported? The registry lists zero outcome analyses. It does not report a test statistic, p-value, effect estimate, model, or analysis plan for the primary outcome. A p-value, in general, measures how compatible observed data are with a specified null model under its assumptions; it does not measure the size or clinical importance of an effect. Without a posted analysis, there is no p-value to interpret and no basis for claiming statistical significance or lack of significance.

How should planning calculations be understood? The registry's sample-size assumptions describe planning illustrations based on an observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event calculations, the stated quantity is the total number of events using the Schoenfeld method; for other calculations, it is participants per arm. These assumptions describe an illustration, not an observed trial outcome, and do not establish that the study had a particular power. Sample-size calculations are planning aids and are never observed power. The registry record does not report a trial-specific sample-size justification.

Does count variability matter? In general, over-dispersion occurs when count data vary more than a model assumes. It can make standard errors too small if an unsuitable model is used. That issue is relevant to some count outcomes, but the primary endpoint is a participant count based on whether a threshold was met, not a recurrent-event count. The registry record does not identify an analysis model, so it is not possible to assess model assumptions or whether any dispersion adjustment was considered.

What does the completion status tell readers? Completion means the registry marks the study as completed; it does not supply an endpoint estimate or establish that the planned analysis was conducted. The record includes enrollment, the primary completion date, the response definition, and the population description. It does not include the numerical primary result, a statistical comparison, or the methods needed to reproduce such an analysis. Statistical interpretation must therefore remain focused on the design and the information that is actually posted.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("JAK2 Positive Participants", "JAK2 Negative Participants")
n      <- c(14, 21)
events <- c(12, 14)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  JAK2 Positive Participants  14  12  85.7  57.2  98.2  60.1  96.0  59.5  95.7
ARM  JAK2 Negative Participants  21  14  66.7  43.0  85.4  45.4  82.8  45.1  82.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary platelet-response endpoint and several secondary laboratory outcomes. These include a second platelet threshold at 12 months, platelet count, red blood cell count, white blood cell count, differential white blood cell measures, hemoglobin concentration, and hematocrit. Examining multiple outcomes can create multiplicity: when several questions are tested, the chance of at least one apparently noteworthy result can increase. In general, a prespecified hierarchy or adjustment method can address this concern. The registry record does not report whether any multiplicity strategy was planned or used.

Missingness is relevant to the primary endpoint because the analysis population is restricted to participants with a viable platelet sample during the 12-month follow-up window. The record states that 35 patients in the Full Analysis Set had a viable laboratory sample for this outcome. It does not report how many eligible participants lacked a viable sample, why samples were unavailable or not viable, or whether missingness differed by JAK2 status. The group-specific denominators are not reported.

The registry record also does not describe imputation, sensitivity analyses, or another method for handling missing measurements. Without those details, readers cannot assess whether the observed sample could differ systematically from participants without an available result. Nor can they determine how missing values might affect a group comparison.

Zero outcome analyses are listed, and numerical results for the primary and secondary outcomes are not reported in the registry record. A statistical analysis plan, the handling of repeated or multiple laboratory measurements, and any interim-analysis approach are not reported in the registry record. These gaps prevent an assessment of which analyses were conducted and how selective reporting or missing observations might affect interpretation.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry's safety figures are organized by JAK2 status. For JAK2-positive participants, the record lists 23 at risk for serious adverse events and 0 serious adverse events; for JAK2-negative participants, it lists 24 at risk and 0 serious adverse events. These entries mean that the posted safety data record no serious adverse events in either group. They should not be read as proof that serious harms are impossible or that all potential harms were fully captured.

For other adverse events, the registry lists 6 events among the 23 JAK2-positive participants at risk and 9 among the 24 JAK2-negative participants at risk. These are counts, not percentages, and no comparative statistical analysis or uncertainty estimate is reported. The counts alone do not establish that the groups had different risks. The registry's serious-adverse-event term list is empty, and death counts are not reported in the registry record.

Safety interpretation also depends on definitions, observation time, collection procedures, and completeness of reporting. Those details are not reported in the registry record. The listed counts describe only the posted safety entries; they do not establish causality or provide a complete account of tolerability.

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

The record documents an exploratory observational study asking whether JAK2 (V617F) status is related to platelet response among patients with ET treated with anagrelide hydrochloride. It defines the primary response as a platelet count of ≤600x10^9/L after 12 months and identifies the Full Analysis Set with a viable platelet sample as the outcome population. These details clarify what the study intended to measure.

The record does not report the primary response counts, a group comparison, an effect estimate, or a confidence interval. It therefore cannot show whether the response differed between JAK2-positive and JAK2-negative participants, how large any difference was, or how precisely it was estimated. The recorded enrollment and sample information do not fill that gap. No result should be inferred from the endpoint definition or study completion status.

The observational design also limits causal interpretation. Mutation-status groups are not randomized treatment arms, and the registry does not report baseline characteristics or adjusted analyses. Even a reported association could not automatically be attributed to mutation status without considering other group differences and the analysis used. The study's hypothesis-generating purpose is important context: its question may inform further research, but the posted record does not provide a confirmatory statistical result.

The safety entries list zero serious adverse events in each status group and other adverse-event counts of 6 and 9. They do not include comparative estimates, uncertainty, or enough detail to judge the completeness of event capture. These entries should be read as registry counts, not as a comprehensive assessment of safety.

In short, the record shows how the primary endpoint was defined and which patients were intended to contribute, but it does not report the primary finding. It neither supports a claim of benefit nor a claim of no effect. It leaves the response association, its precision, and its robustness unquantified.

14. Why This Trial Matters Statistically

This study raises a statistically meaningful design question: whether an observed treatment-response pattern differs according to JAK2 (V617F) status among patients with ET receiving anagrelide hydrochloride. Separating groups by a biological characteristic can be useful for generating hypotheses about variation in outcomes. The study's exploratory, hypothesis-generating framing appropriately signals that the question is investigative rather than a randomized treatment comparison.

The record also illustrates why endpoint definitions and analysis populations matter. The primary endpoint uses a clear platelet-count cutoff after 12 months, and the registry specifies that a viable platelet sample is needed for inclusion in the relevant Full Analysis Set. Such definitions help readers understand what qualifies as response and who contributes to its assessment. At the same time, the absent group-specific denominators and outcome counts prevent an evaluation of the response frequencies and their precision.

Observational comparisons require particular care. JAK2 status defines the groups, but the record does not show that other participant characteristics were balanced or statistically controlled. The label of a group difference, even if one were posted, would not by itself establish a causal explanation. Reporting baseline information, the analysis approach, and uncertainty would be important for evaluating the strength of an association.

The registry record also makes transparent the distinction between a completed study and a fully interpretable posted result. Completion and enrollment describe the study's status and scope; they do not substitute for outcome estimates. With zero outcome analyses listed, the central response question remains unanswered in the posted record. This makes the study statistically relevant as a clearly stated exploratory question, while underscoring how essential complete outcome reporting is for readers to assess evidence.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. First, the registry describes an observational comparison by JAK2 status, not a randomized comparison. Allocation is not stated, and the arms are not a like-for-like control comparison. The record does not report baseline characteristics, so it is not possible to assess the degree to which the groups differed in other ways.

Second, the registry does not post the primary outcome counts, group-specific denominators, effect estimates, confidence intervals, p-values, or analysis methods. It lists zero outcome analyses. As a result, neither the direction nor the magnitude nor the precision of the primary comparison can be evaluated. The endpoint definition alone does not establish a result.

Third, the primary analysis population depends on a viable platelet sample during the 12-month follow-up window. The record states that 35 Full Analysis Set patients had a viable laboratory sample, but does not explain why samples might be unavailable or not viable, whether missingness differed by JAK2 status, or how missing measurements were handled. The protocol's statistical plan, sample-size justification, and interim-analysis approach are not reported in the registry record.

Finally, the record lists several secondary laboratory outcomes but does not provide their numerical results or describe any multiplicity strategy. Safety counts are posted, but the event definitions, ascertainment details, observation periods, and comparative analyses are not reported in the registry record. These limitations mean the posted information is insufficient to evaluate the primary association, assess robustness, or make a comprehensive comparison of safety between status groups.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Exploratory Multi-centre Trial In Patients With ET Treated With XAGRID® — NCT01352585.
• Registry record last updated 2021-07-30; status last verified 2021-07.
• Results first posted 2014-07-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01352585 is a completed exploratory, observational, multicentre study of patients with essential thrombocythemia treated with anagrelide hydrochloride (XAGRID®). Its stated aim was to investigate whether JAK2 (V617F) mutation status was associated with treatment response. The registry records enrollment of 47, a start date of 2011-07-19, and a primary completion date of 2013-09-19.

The primary outcome is the number of patients with a platelet count of ≤600x10^9/L after 12 months, defined as at least a partial response. The Full Analysis Set participants in each status group needed a viable platelet sample; the record states that 35 patients had such a sample. The registry does not report primary or secondary outcome results and lists zero outcome analyses. Safety entries list zero serious adverse events in both groups and other adverse-event counts of 6 for JAK2-positive participants and 9 for JAK2-negative participants. The posted information establishes the study question and outcome definitions, but not the response comparison or its precision.