Optimal Platelet Dose Strategy for Management of Thrombocytopenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimal Platelet Dose Strategy for Management of Thrombocytopenia (NCT00128713), a randomized phase 3 study. The primary outcome is At Least One Day With Grade 2 or Higher Bleeding.

2. Clinical Question

3. Trial Design

This was a randomized, phase 3, parallel-group trial of lower-, medium-, and higher-dose prophylactic platelet transfusion strategies. The registry lists 1351 participants enrolled and records the study as completed. The start is listed as 2004-07 and primary completion as 2008-01. Carelon Research is named as sponsor, and the official title identifies the study as a TMH CTN study.

Random allocation supports comparisons between assigned strategies by reducing systematic differences between groups at the point of assignment. The parallel design means participants were assigned to a strategy rather than being described as crossing through all strategies. The registry lists quadruple masking, but does not identify which groups of people were masked or explain how masking was maintained. Those details are not reported in the registry record.

The primary analyses are described as intention-to-treat. Under that approach, participants remain in the group to which they were randomized for analysis, regardless of whether they received transfusions that departed from the assigned strategy. This preserves the randomized comparison and estimates outcomes by assignment rather than by treatment actually received. The registry does not report the extent of departures from assigned dosing.

The primary outcome timeframe began at randomization and continued until the subject ended the study: 10 days after the most recent platelet transfusion, 30 days after the first platelet transfusion on study, or hospital discharge, whichever occurred first. Further detail on the setting, site structure, eligibility rules, and planned sample-size justification is 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

Analysis population for the primary outcome, as defined in the registry: These analyses were done on an intention-to-treat basis. That is, patients were counted in the treatment arm to which they were randomly assigned, even if they actually received transfusions that were not according to their assigned dosing strategy.

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 At Least One Day With Grade 2 or Higher Bleeding, measured over From randomization until the subject ends the study (10 days after most recent platelet transfusion, 30 days after first platelet transfusion on study, or hospital discharge, whichever occurs first).

The primary endpoint records whether a participant experienced at least one day with Grade 2 or higher bleeding during the study timeframe. It is a participant-level binary outcome: the result for an individual is classified by whether the defined bleeding occurred, rather than by the total number of bleeding days. The description specifies daily hemostatic assessment and documentation of red blood cell transfusions used to treat bleeding.

The Grade 2 threshold is defined as moderate bleeding that is not severe enough to warrant red blood cell transfusion. Combining Grade 2 and higher grades focuses the endpoint on bleeding that has crossed a prespecified severity threshold. A binary endpoint can make a comparison of the proportion of participants experiencing the event easier to interpret than a collection of separate bleeding episodes, but it does not convey the number, duration, location, or full intensity of events for each participant.

The timeframe ends at the earliest of the stated stopping conditions, so participants may have different observation durations. This is relevant when interpreting event proportions: the endpoint describes whether an event occurred within the defined study period, not a common fixed-duration risk. A single primary arm comparison and its estimates are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group comparison and describes the primary analysis population as intention-to-treat. These design features determine what a statistical comparison is intended to estimate. In an intention-to-treat analysis, outcomes are analyzed according to randomized assignment, not according to the treatment actually received. This preserves the comparison created by randomization, although it does not answer the separate question of outcomes among participants who followed the assigned strategy.

What does a binary endpoint capture?

The primary endpoint is whether a participant experienced at least one day with Grade 2 or higher bleeding during the specified timeframe. This turns the participant's observed experience into an event classification: the endpoint counts participants with the event, rather than counting every bleeding episode or every day of bleeding. A comparison of event proportions can be useful for expressing how commonly a defined outcome occurred in each arm. It necessarily leaves out details such as event duration, number of episodes, and the distribution of severity above the threshold.

The registry describes the primary outcome as having several categories or time points and does not reduce it to one comparison. Therefore, a single effect estimate cannot be inferred from the description alone. The arm-specific results, comparison method, and uncertainty around the primary contrast are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval expresses the uncertainty around an estimate under the statistical model used. A narrow interval indicates greater precision than a wide interval, while an interval that includes values consistent with no difference may leave the direction or size of an effect uncertain. A confidence interval is not a guarantee about the result for an individual participant. No primary confidence interval is reported in the registry record, so precision for the main comparison cannot be assessed from these details.

In general, a p-value describes how compatible the observed data are with a specified null model, assuming the analysis model and its assumptions. It does not measure the probability that the null hypothesis is true, nor does it measure clinical importance. The registry entries used for this analysis do not state a p-value for a single primary comparison or describe the statistical test used for that comparison.

What do the planning assumptions mean?

The sample-size assumptions describe an illustrative calculation based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The calculation is framed around detecting a stated fraction of the observed effect. Such calculations are planning illustrations: they indicate the sample size that would be associated with stated assumptions in a hypothetical design. They are not observed power and do not show the probability that this completed trial detected an effect. The registry does not report the trial's own sample-size justification or the planning assumptions used when the study was designed.

Over-dispersion is a general statistical issue that arises when observed variation exceeds what a simple model assumes. For event counts, ignoring extra variation can make uncertainty look smaller than it is. The primary endpoint is described as a participant-level event outcome, not as a count of recurrent episodes. The registry information does not report an over-dispersion assessment or a model for repeated bleeding events, so no such method can be attributed to the trial.

Why are several outcomes and analyses relevant?

The registry lists five outcome measures and 12 analyses. When multiple outcomes, time points, or pairwise comparisons are examined, the chance of finding at least one apparently noteworthy result can increase if every test is interpreted independently. General approaches to this issue include adjusting a significance threshold, controlling a family-wise error rate, or defining a hierarchy of outcomes and comparisons in advance. Which approach, if any, was used is not reported in the registry record.

The primary outcome and the secondary outcomes address different aspects of the study question. The listed secondary outcomes include platelet utilization, platelet transfusion episodes, bleeding severity if a suitable scale was validated and published by the time the trial ended, and highest grade of bleeding while on study. They should not be treated as interchangeable measures of a single effect. The registry does not provide enough statistical detail to establish how these measures were modeled, how missing values were handled, or how their results were prioritized.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and 12 analyses, including a primary bleeding outcome and secondary outcomes related to platelet use, transfusion episodes, and bleeding severity. Examining multiple outcomes or comparisons raises a general multiplicity concern: without an appropriate analysis plan, the interpretation of isolated statistical findings can become less reliable. Whether the trial used an adjustment, a prespecified hierarchy, or another method to address multiplicity is not reported in the registry record.

The primary analysis population is explicitly described as intention-to-treat. Participants were analyzed in the group to which they were randomized even if they received transfusions that did not follow their assigned strategy. This identifies the basis for group assignment in the primary analysis, but it does not say how missing endpoint assessments were handled, whether any participants were excluded from particular analyses, or whether additional analysis populations were used. Those details are not reported in the registry record.

The primary follow-up period ended according to the earliest of the stated study-ending conditions. The registry does not report the number of participants with complete endpoint assessments, the amount or pattern of missing data, or any imputation or sensitivity analyses. It is therefore not possible to assess from these details whether missingness could have affected the arm comparisons.

The registry does not report a statistical analysis plan, a prespecified order for testing outcomes, or interim analyses. None should be assumed. The stated intention-to-treat approach describes assignment for analysis; it does not establish the handling of every endpoint, multiplicity issue, or missing-data problem.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory distress (1.6%), veno-occlusive disease (1.3%), sepsis (1.1%), respiratory failure (0.9%), deep vein thrombosis (0.9%).

The registry reports serious and other adverse-event affected counts by dose group. For the lower-dose group, the serious affected count is 38 with 453 at risk, and the other affected count is 197 with 453 at risk. For the medium-dose group, the corresponding counts are 27 and 182, with 449 at risk. For the higher-dose group, they are 36 and 203, with 449 at risk. These are reported group counts; no additional comparison or rate has been calculated.

The registry also lists leading serious adverse-event terms with percentages: Respiratory Distress, 1.6%; Veno-Occlusive Disease, 1.3%; Sepsis, 1.1%; Respiratory Failure, 0.9%; Deep Vein Thrombosis, 0.9%; and Graft-Versus-Host Disease, 0.7%. The registry information does not specify in this summary whether these percentages use participants, events, or another denominator, so they should be read as listed rather than reinterpreted.

Adverse-event counts alone do not establish that a study strategy caused an event, and a difference in counts would not by itself establish a causal safety difference. Definitions, event-level detail, attribution procedures, and statistical comparisons are not reported in the registry record. Death counts are not reported in the registry record.

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

This trial addresses a practical statistical question: how bleeding outcomes compare when patients with thrombocytopenia are assigned to lower-, medium-, or higher-dose prophylactic platelet transfusion strategies. Randomization and intention-to-treat analysis are relevant because they define a comparison by assigned strategy, rather than by what participants ultimately received. The endpoint also specifies a clinically meaningful bleeding threshold and a defined follow-up period.

However, the registry information available for this analysis does not report a single primary arm comparison or its effect estimate. It therefore cannot establish from these details whether the groups differed, how large any difference was, or how precisely it was estimated. The trial's completed status and enrollment figure are not substitutes for outcome results. No conclusion about whether a strategy works or does not work follows from the design description alone.

The endpoint captures whether a participant experienced Grade 2 or higher bleeding, but it does not describe every dimension of bleeding burden. The secondary outcomes were intended to address other dimensions, including platelet utilization, transfusion frequency, and bleeding severity. The registry does not report enough results or methods to determine how those measures relate to one another or to the primary outcome.

The safety counts provide additional descriptive information, but they do not establish treatment causation. Their interpretation depends on event definitions, denominators, follow-up, and attribution methods. Those details are not reported in the registry record. Likewise, the absence of a listed death count should not be interpreted as evidence that no deaths occurred.

Overall, the record establishes the trial question, broad design, endpoint definition, and some safety counts. It does not provide the primary estimate, its uncertainty, or sufficient analysis detail to support a complete statistical interpretation of the efficacy comparison.

13. Why This Trial Matters Statistically

The trial is statistically notable for comparing three randomized dose strategies while defining the primary outcome around a participant-level bleeding threshold. That framing highlights a common challenge in clinical research: an endpoint can be easy to classify for analysis while still simplifying a more complex clinical experience. Whether a participant had any Grade 2 or higher bleeding does not describe how often bleeding occurred, how long it lasted, or how severity varied.

The intention-to-treat description is important because it makes the randomized assignment the basis of the primary analysis, even when received transfusions did not follow the assigned strategy. This preserves the interpretation of the comparison as one between assigned strategies. It also means that the analysis is not simply a comparison of participants who received each dose as intended.

The trial also illustrates why design details and results must be read separately. A randomized phase 3 design, masking, enrollment, and completion status describe how a study was structured; they do not reveal the size or precision of an outcome difference. Without a primary effect estimate and its uncertainty, readers cannot judge the evidence for the central comparison from the registry entries.

Finally, the multiple listed outcomes and analyses make transparent reporting of analysis choices important. The registry does not report whether multiplicity was addressed, how missing data were handled, or what statistical models were used. These omissions limit interpretation even when the clinical question and endpoint definitions are clear.

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 registry record does not report a single primary comparison, an arm-specific primary outcome result, an effect estimate, a confidence interval, or a p-value. This prevents assessment of the magnitude, direction, and precision of the principal comparison. The primary outcome is described as having several categories or time points and is not reduced to one comparison.

Important design and conduct details are also absent. The registry does not report detailed eligibility criteria, participant characteristics, dose amounts, transfusion rules, adherence to assigned strategies, or the extent of departures from assignment. Although quadruple masking is listed, the identities of those masked and the masking procedures are not reported in the registry record.

The record does not state how missing endpoint data were handled, how many participants had complete assessments, or whether sensitivity analyses were performed. It also does not report the statistical analysis plan, multiplicity procedures, interim analyses, or original sample-size justification. These gaps mean that the robustness of the outcome analysis cannot be assessed from the registry entries used.

The primary timeframe could end at different points for different participants, according to the stated stopping conditions. The registry does not provide participant-level follow-up or information needed to assess how variation in observation time affected the comparison. Safety reporting also lacks detail on event definitions, denominators for listed terms, and causal attribution. These limitations should be distinguished from evidence of an effect: the missing information restricts interpretation but does not itself indicate a particular result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Optimal Platelet Dose Strategy for Management of Thrombocytopenia — NCT00128713.
• Registry record last updated 2015-10-28; status last verified 2013-08.
• Results first posted 2009-07-16.
• 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.

18. Record Summary

The registry describes a completed randomized, phase 3, parallel-group trial comparing lower-, medium-, and higher-dose prophylactic platelet transfusion strategies in patients with thrombocytopenia. It lists 1351 participants enrolled, quadruple masking, and intention-to-treat primary analyses. The primary outcome was at least one day with Grade 2 or higher bleeding during a timeframe ending at the earliest of the stated study-ending conditions.

Secondary outcomes concerned platelet utilization, platelet transfusion episodes, bleeding severity, and highest grade of bleeding. The registry lists serious and other adverse-event affected counts by group and several leading serious adverse-event terms. A single primary comparison and its estimate are not reported in the registry record, nor are detailed methods for multiplicity, missing data, or outcome modeling. The design and endpoint can therefore be described, but the principal comparative result cannot be interpreted from these details.