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 Evaluation of Spectra Optia Red Blood Cell Exchange in Sickle Cell Patients (NCT01736657), a na na study. The primary outcome is Mean Ratio Actual Fraction of Cells Remaining (FCRa; as Measured by Post-Procedure % HbS) to the Predicted Fraction of Cells Remaining (FCRp; as Predicted by the Spectra Optia System FCR Algorithm Multiplied by the Pre-Procedure % HbS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01736657 |
| Phase | NA |
| Condition | Sickle Cell Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 73 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Terumo BCT |
| Results posted | Yes |
2. Clinical Question
Population
Patients with sickle cell disease undergoing red blood cell exchange. The registry reports 73 enrolled, while the primary efficacy analysis included an evaluable population of 60 patients. The record notes that 12 lead-in patients were excluded from efficacy analysis and included in safety analysis, and that 1 patient was consented but withdrawn prior.
Intervention
Red blood cell exchange using the Spectra Optia system. The study purpose includes evaluating the system’s exchange and depletion/exchange protocols. The listed intervention is a device-based red blood cell exchange procedure.
Comparator
There was no concurrent control group. The study is recorded as single-group, with no allocation and no masking. Its primary endpoint compares the actual fraction of cells remaining with the fraction predicted by the Spectra Optia system algorithm; this is a comparison with a prediction, not a randomized treatment comparison.
Primary question
In the evaluable population, how closely did the measured actual fraction of cells remaining correspond to the algorithm-predicted fraction? The endpoint is the mean ratio of actual to predicted fraction, assessed over the length of the procedure. The pre-defined range for this mean ratio was 0.75 to 1.25. The registry record does not report the observed mean ratio or its confidence interval, so the degree of agreement cannot be determined from the posted results.
3. Trial Design
The registry describes a completed, open-label, single-group evaluation of the Spectra Optia system for red blood cell exchange in patients with sickle cell disease. The intervention is listed as a device. The study purpose covers the system’s exchange and depletion/exchange protocols. No randomized allocation or masking is reported; the record specifies no allocation and no masking. There is no concurrent control arm, so the design evaluates procedural performance rather than estimating a between-group treatment effect.
The registry reports 73 enrolled. For the primary endpoint, the evaluable population comprised 60 patients. The record explains that 12 lead-in patients were undergoing operator training and that data from their procedures were excluded from efficacy analysis but included in the safety analysis, which included 72 patients. It also notes that 1 patient was consented but withdrawn prior. The record does not give further details about that withdrawal. These populations serve different purposes: the efficacy population is the basis for the primary endpoint, while the safety population is used for adverse-event reporting.
The primary endpoint was assessed over the length of the procedure. Other listed outcomes concern procedural success, achievement of the desired final hematocrit, and device-related serious adverse events. The registry record does not report results for these outcomes. It also does not report a detailed protocol description, the eligibility criteria, the precise procedures for determining evaluability, or the criteria used to define procedural success. Those details are important for understanding how the recorded populations and outcomes were operationalized.
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: Evaluable population includes 60 pts. Terumo Optia Trainer was present for Optia Operator support for 12 procedures, called "lead-in" procedures: these were not included in efficacy analysis, but were included in safety analysis (full analysis set).
Overall Study
| Stage | Red Blood Cell Exchange for Patients With Sickle Cell Disease |
|---|---|
| STARTED | 73 |
| COMPLETED | 72 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Red Blood Cell Exchange for Patients With Sickle Cell Disease |
|---|---|
| insufficient vascular access | 1 |
Analysis population for the primary outcome, as defined in the registry: 60 patients analyzed, 73 enrolled:12 patients were lead-in patients whereby Optia Operators completed their training and data from those procedures were not included in the efficacy analysis (60 pts), but were included in the safety analysis (72 patients); 1 patient was consented but withdrawn prior to procedure due to lack of vascular access.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Seventy-two patients were in safety analysis and 60 patients (evaluable popluation) were analyzed in the efficacy analysis. The 12 patients not in the efficacy analysis were "lead-in" patients and the RBCX procedures were conducted as the last phase in Operator training on the device.
| Characteristic | Unit | Red Blood Cell Exchange for Patients With Sickle Cell Disease |
|---|---|---|
| Participants analysed | 72 | |
| Age, Categorical: <=18 years | Participants | 26 |
| Age, Categorical: Between 18 and 65 years | Participants | 46 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 23.0 (SD 10.32) |
| Sex: Female, Male: Female | Participants | 29 |
| Sex: Female, Male: Male | Participants | 43 |
| Region of Enrollment: United States | participants | 72 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Ratio Actual Fraction of Cells Remaining (FCRa; as Measured by Post-Procedure % HbS) to the Predicted Fraction of Cells Remaining (FCRp; as Predicted by the Spectra Optia System FCR Algorithm Multiplied by the Pre-Procedure % HbS), measured over Length of the procedure.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | ratio |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean ratio of the actual fraction of cells remaining (FCRa) to the predicted fraction of cells remaining (FCRp). The actual value is based on post-procedure percentage HbS. The predicted value comes from the Spectra Optia system FCR algorithm multiplied by pre-procedure percentage HbS. The endpoint therefore assesses how the measured value relates to the system’s prediction in the evaluable population, rather than comparing outcomes between treatment groups.
A ratio expresses the measured quantity relative to the predicted quantity. In general, a mean ratio near the algorithm’s prediction would indicate closer average correspondence, while a ratio farther from that prediction would indicate a larger average discrepancy. This is a general interpretation of a ratio, not a statement about the trial’s result. The registry defined a range of 0.75 to 1.25 for the mean ratio in advance. That range provides a reference for interpreting the endpoint, but does not establish the observed result or its precision.
The registry specifies a 95% confidence interval as the dispersion measure and gives the timeframe as the length of the procedure. However, the observed mean and confidence interval are not reported in the registry record. Without them, it is not possible to assess whether the observed average fell within the defined range or how precisely it was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary question is whether the average measured fraction of cells remaining corresponded to the fraction predicted by the system algorithm. The endpoint was defined as the mean ratio of actual to predicted fraction in the evaluable population of 60 patients, with a pre-defined range of 0.75 to 1.25. The registry record does not report the observed mean ratio or its 95% confidence interval. Consequently, the posted results do not establish where the estimate fell relative to the defined range or how much uncertainty surrounded it.
A confidence interval describes the precision of an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. For an endpoint with a pre-defined range, both the estimate and its interval matter: an estimate alone would not show how compatible the data are with values around it, and an interval alone would not convey the point estimate. Since neither is reported for the primary endpoint, no conclusion about the degree of agreement or precision is supported by this record.
The design also limits what can be inferred. This was a single-group evaluation without a concurrent control group, random allocation, or masking. Its primary endpoint compares a measured value with an algorithmic prediction. That comparison can address correspondence between prediction and measurement, but it is not a randomized comparison of the device with another procedure, device, or standard of care. The registry record therefore does not support claims about comparative effectiveness or about what would have happened under an alternative approach.
The record lists other outcomes, including procedural success, achieving the desired final hematocrit, and device-related serious adverse events. Numerical results for the procedural outcomes are not reported in the registry record. For safety, it reports 0 serious adverse events among 72 patients at risk and 10 other adverse events among 72 patients at risk. These counts describe recorded events in the specified safety population; they do not by themselves establish whether events were caused by the device. Deaths are not reported in the registry record.
The study is marked completed, but completion status does not fill in missing outcome estimates. The registry record includes enrollment and population details, yet the absence of primary endpoint estimates prevents evaluation of the central efficacy question. Interpretation should therefore remain focused on the design and the limited results actually reported, not on an assumed favorable or unfavorable performance outcome.
9. Statistical Methods Explained
The primary endpoint is a continuous measure: a mean ratio of actual to predicted fraction of cells remaining. The registry specifies a 95% confidence interval and a pre-defined range for the mean ratio. The result would need to be interpreted in relation to both the prediction and that range. The observed estimate and interval, however, are not reported in the registry record.
What does the ratio represent?
The actual fraction is based on post-procedure percentage HbS. The predicted fraction is based on the Spectra Optia system FCR algorithm multiplied by pre-procedure percentage HbS. Dividing the actual measure by the predicted measure places the observed quantity on a scale relative to the prediction. In general, ratios are useful when the question concerns proportional agreement rather than an absolute difference. This is a general statistical explanation, not a claim that the study found agreement. A ratio can also be difficult to interpret without the underlying values and the distribution of individual observations. Those details are not reported in the registry record.
Why report a mean and a confidence interval?
The mean describes the average ratio in the analyzed population. It can summarize performance across patients, but it does not show how individual values vary. A confidence interval communicates uncertainty around the estimated mean under the analysis assumptions. In general, it should be read alongside the estimate and the pre-defined range, rather than as a separate pass-or-fail label. Here, the registry gives the intended confidence level but not the resulting mean or interval. The record also does not describe the analysis method used to construct the interval, so details such as distributional assumptions or any adjustments cannot be assessed.
What does the single-group design imply?
A single-group design can describe outcomes observed in the enrolled population, but it does not create a randomized comparison with another group. The endpoint’s predicted value is an algorithmic reference, not a concurrent control participant or control arm. In general, agreement with a prediction and comparative treatment effect are distinct questions. The reported design can address the former only to the extent that the observed endpoint and its uncertainty are available; it cannot establish a between-group effect. Allocation is listed as not applicable and masking as none.
How should the analysis populations be read?
The primary endpoint description identifies 60 patients in the evaluable population. The record states that 12 lead-in patients completed operator training and that their procedure data were not included in efficacy analysis, while they were included in safety analysis. The safety population is reported as 72 patients. The record also notes that 1 patient was consented but withdrawn prior. These labels should not be treated as interchangeable: the efficacy population is the population named for the primary endpoint, and the safety population is the population used for safety counts. The registry record does not provide complete definitions of the evaluable or full analysis populations, nor does it explain the withdrawal in further detail.
What can planning calculations tell readers?
Planning calculations are hypothetical illustrations of the sample size that might be needed under stated assumptions; they are not observed trial results and are not observed power. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects expressed as fractions of the observed effect. This approach is not aligned directly with the recorded single-group design, which has no two-arm allocation. Numeric planning results and the observed effect used for such illustrations are not reported in the registry record. No conclusion about the original study’s design justification can be drawn from those assumptions; the sample-size justification and any original planning calculations are not reported in the registry record.
In general, over-dispersion means that observed variability is greater than a model assumes. It can make standard errors and confidence intervals too optimistic if the analysis does not account for that extra variability. The registry record does not report an over-dispersion assessment or identify a statistical model addressing it. This general issue should not be mistaken for evidence that over-dispersion occurred in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, including the primary endpoint and secondary outcomes concerning procedural success, achievement of the desired final hematocrit, and device-related serious adverse events. It does not report analysis results for the primary endpoint or the procedural secondary outcomes. The record does not report a multiplicity strategy for handling several outcomes, such as an adjustment to control the chance of false-positive findings across multiple tests. Without analysis results and a stated strategy, the evidential role of any separate outcome cannot be evaluated.
The record identifies the evaluable population of 60 patients for the primary endpoint and a safety population of 72 patients. It states that 12 lead-in patients were excluded from efficacy analysis and included in safety analysis, and notes that 1 patient was consented but withdrawn prior. These descriptions clarify some population handling but do not fully define the analysis sets. Rules for missing endpoint data, incomplete procedures, or other exclusions are not reported in the registry record. The record also does not say whether any missing measurements were imputed, whether analyses were restricted to complete observations, or whether sensitivity analyses were performed.
The registry reports 0 analyses. This leaves the analysis methods, handling of uncertainty, and any adjustments or subgroup evaluations unreported in the registry record. The endpoint description specifies a mean and a 95% confidence interval, but the method used to calculate them is not stated. No interim analyses or sample-size justification are reported in the registry record. These omissions limit assessment of analysis choices and the robustness of the intended conclusions.
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 |
|---|---|---|---|
| Red Blood Cell Exchange for Patients With Sickle Cell Disease | 0 | 72 | 0.0% |
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 |
|---|---|
| Red Blood Cell Exchange for Patients With Sickle Cell Disease | 10 of 72 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Red Blood Cell Exchange for Patients With Sickle Cell Disease |
|---|---|---|
| Dizziness | Nervous system disorders | 6 of 72 |
| Nausea | Gastrointestinal disorders | 4 of 72 |
The safety population is reported as 72 patients. The registry records 0 serious adverse events among 72 patients at risk and 10 other adverse events among 72 patients at risk. These are event counts for the population and categories as listed in the record. They should not be interpreted as estimates of comparative risk, because there was no concurrent control group.
The record does not provide serious adverse event terms; specific event descriptions are not reported in the registry record. Deaths are also not reported in the registry record. A missing death entry should not be read as a reported count of zero. The record does not describe the nature, severity, timing, or relatedness of the other adverse events, nor does it state whether events were independently assessed. The count of other adverse events therefore cannot establish that they were caused by the device or procedure.
Safety findings are limited to the population and categories recorded. The lead-in procedures were included in the safety analysis, although they were excluded from efficacy analysis. This distinction matters when reading the safety count alongside the primary endpoint population. The counts describe what the registry reports; they do not establish the absence of unrecorded events or provide a comparison with another treatment approach.
12. What the Result Does, and Does Not, Mean
The registry record describes an evaluation of the Spectra Optia system in patients with sickle cell disease, using a primary endpoint that compares actual and algorithm-predicted fractions of cells remaining. It defines a mean-ratio range of 0.75 to 1.25 and names a 95% confidence interval as the dispersion measure. These details show what the study intended to assess, but the observed mean and interval are not reported in the registry record. As a result, the central performance question cannot be answered from the posted results.
The record does report safety counts: 0 serious adverse events among 72 patients at risk and 10 other adverse events among 72 patients at risk. Those counts should be interpreted as descriptive findings in the recorded safety population. They do not establish causation, comparative safety, or the absence of other events. Deaths are not reported in the registry record.
The single-group, open-label design also defines the limits of interpretation. There is no randomized comparator, and the algorithm-predicted quantity is not a control group. The study therefore does not provide a direct comparison with an alternative device or procedure. Nor does the record report enough analysis information to assess how the mean and confidence interval were calculated, how missing data were handled, or whether outcome multiplicity was addressed.
These limitations do not erase the value of the study’s stated question. A performance evaluation can be informative when its endpoint, population, and analysis are reported clearly. In this registry record, those design features are partly described, but the missing primary result prevents a determination of how closely the measured outcome matched the prediction. The appropriate interpretation is bounded by what is reported, without treating the absence of an estimate as evidence for either favorable or unfavorable performance.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between evaluating correspondence with a prediction and comparing outcomes between groups. Its primary endpoint is a ratio of measured to algorithm-predicted fraction of cells remaining. That framing makes the prediction itself central to interpretation: the question is not simply whether a procedure was completed, but how the measured value related to the system’s expectation.
The endpoint also illustrates why a point estimate and its uncertainty are both needed. The registry defines a range of 0.75 to 1.25 and specifies a 95% confidence interval, but reports neither the observed mean nor its interval. Without those results, readers cannot judge the estimated correspondence or its precision. This is a reporting limitation, not a finding that the endpoint failed or succeeded.
Population definitions matter as well. The primary endpoint uses an evaluable population of 60 patients, while safety counts use 72 patients. The record explains that lead-in procedures were excluded from efficacy analysis but included in safety analysis. Keeping these populations distinct prevents efficacy and safety counts from being treated as if they arose from the same analysis set.
Finally, the single-group design places a boundary around interpretation. A prediction-based reference can be relevant to procedural performance, but it does not substitute for a concurrent randomized comparator. The record can therefore frame a focused performance question while leaving comparative effects unanswered. Its statistical importance lies in showing how endpoint choice, analysis population, uncertainty, and design determine what conclusions a clinical study can support.
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 the observed primary endpoint mean or its 95% confidence interval. This prevents assessment of the central outcome against the pre-defined range of 0.75 to 1.25 and leaves its precision unknown. Results for the listed procedural secondary outcomes are also not reported in the registry record.
The study has no concurrent control group, and allocation is listed as not applicable. The record reports no masking. The primary endpoint compares measurement with an algorithmic prediction, so it does not provide a randomized comparison with another device or procedure. This design cannot answer comparative questions on its own.
The populations differ by purpose: the primary efficacy endpoint includes 60 evaluable patients, while the safety population includes 72 patients. The record says that 12 lead-in patients were excluded from efficacy analysis and included in safety analysis. It also notes that 1 patient was consented but withdrawn prior, without further explanation. The criteria defining evaluability and the full analysis set are not reported in the registry record.
Missing-data methods, the confidence-interval calculation method, and any sensitivity analyses are not reported in the registry record. Neither a multiplicity strategy nor interim-analysis details are reported. The registry gives no numerical results for the stated planning illustrations, and the study’s sample-size justification is not reported. Safety descriptions are also limited: serious adverse event terms and deaths are not reported in the registry record, and the nature and relatedness of other adverse events are not described.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Spectra Optia Red Blood Cell Exchange in Sickle Cell Patients — NCT01736657.
- Registry record last updated 2014-07-14; status last verified 2014-01.
- Results first posted 2014-07-14.
- 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
The record describes a completed, open-label, single-group evaluation of Spectra Optia red blood cell exchange in patients with sickle cell disease. The primary endpoint is the mean ratio of actual to algorithm-predicted fraction of cells remaining, assessed over the length of the procedure. The pre-defined range is 0.75 to 1.25.
The primary efficacy population is reported as 60 patients; the safety population is 72 patients, with 73 enrolled. Lead-in procedures were excluded from efficacy analysis and included in safety analysis. The primary endpoint estimate and confidence interval are not reported in the registry record. The safety record reports 0 serious adverse events and 10 other adverse events among 72 patients at risk; deaths are not reported in the registry record. The single-group design does not provide a concurrent treatment comparison.