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 High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study (NCT00288626), a na phase 2 study. The primary outcome is Event-Free Survival Probability During the 5 Years After Transplant.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00288626 |
| Phase | Phase 2 |
| Condition | Relapsing-Remitting Multiple Sclerosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants with relapsing-remitting multiple sclerosis and a poor prognosis, as described in the official title. The primary outcome population is defined as participants who received high-dose immunosuppressive therapy and autologous CD34+ hematopoietic stem cell transplant. The registry record lists enrollment as 25; the number included in the primary endpoint analysis is not reported in the registry record.
Intervention
The treatment strategy combined high-dose immunosuppressive therapy with autologous hematopoietic cell transplantation. The arm description says that CD34+ selected peripheral blood stem cell grafts were used, followed by carmustine, etoposide, cytarabine, and melphalan, as well as rabbit antithymocyte globulin. G-CSF and prednisone are also listed as interventions.
Comparator
There was no separate control arm. The registry describes a single-group study, with allocation listed as not applicable and no masking. Consequently, the record does not provide a randomized comparison with another treatment or a control condition.
Primary question
The primary endpoint asks for the probability of remaining alive without specified disease activity during the 5 years after transplant. Disease activity includes neurological function loss, relapse, or new MRI lesions, as defined in the endpoint description. The numerical probability and its 90% confidence interval are not reported in the registry record.
This is a within-group question about event-free survival following the combined treatment strategy. It is not a comparative estimate of how outcomes differ between treatment options. Without a control group, the registry results cannot separate the course associated with the treatment from other influences on event-free survival. The study purpose was to assess the treatment in multiple sclerosis, but the record's stated primary endpoint is specifically the probability of remaining free of death and the listed disease-activity events. That endpoint gives a broader picture than survival alone because it also counts specified neurological and MRI events. The registry record does not report the endpoint estimate, event count, or confidence interval, so the magnitude and precision of the primary result cannot be described from the record.
3. Trial Design
HALT MS is a Phase II study registered as NCT00288626. The registry lists a single-group model, allocation as not applicable, and no masking. The record lists enrollment as 25. The study is marked completed; its recorded start is 2006-07 and its primary completion is 2015-11. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID).
The intervention was a treatment sequence rather than a comparison of separate arms. The arm description states that participants received CD34+ selected autologous peripheral blood stem cell grafts, followed by high-dose treatment with carmustine, etoposide, cytarabine, and melphalan, as well as rabbit antithymocyte globulin. The registry also lists G-CSF and prednisone, and autologous hematopoietic stem cell transplant, among the interventions. The brief summary explains that the participant's own blood-forming stem cells were collected before chemotherapy and returned afterward. It describes the transplant as intended to prevent very prolonged periods of low blood cell counts after high-dose chemotherapy.
Because there is no concurrent comparator arm, this design can describe outcomes among treated participants but cannot estimate a randomized treatment contrast. The absence of masking is also part of the recorded design. It should not be assumed that an unmasked design necessarily changed any particular outcome; rather, it means the record does not describe masking as a design feature.
The record lists 20 outcome measures, including event-free survival, overall survival, mortality outcomes, morbidity, and times to neutrophil and platelet engraftment. It lists zero analysis entries. A protocol description of the sample-size justification, planned interim analyses, and a detailed statistical analysis plan is not reported in the registry record. These omissions limit assessment of whether the recorded outcomes and methods followed a prespecified plan.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | HDIT and HCT |
|---|---|
| STARTED | 24 |
| COMPLETED | 17 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | HDIT and HCT |
|---|---|
| Death | 3 |
| Withdrawal by Subject | 4 |
Analysis population for the primary outcome, as defined in the registry: Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT).
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: Participants who received High-Dose Immunosuppressive Therapy (HDIT)and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
| Characteristic | Unit | HDIT and HCT |
|---|---|---|
| Participants analysed | 24 | |
| Age, Continuous | years | 36.5 (SD 7.7) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 8 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 23 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 23 |
| Race (NIH/OMB): More than one race | Participants | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 24 |
| Expanded Disability Status Scale (EDSS) at Baseline | units on a scale | 4.4 (SD .64) |
| Number of Gadolinium-Enhanced Lesions at Baseline | Lesions per scan | 2.3 (SD 5.8) |
| T1 Lesion Volume at Baseline | milliliters | 1.2 (SD 2.7) |
| T2 Lesion Volume at Baseline | milliliters | 11.1 (SD 13.7) |
| Normalized Brain Volume at Screening | liters | 1.6 (SD 0.1) |
6. Primary Endpoint
The registry lists the primary outcome as Event-Free Survival Probability During the 5 Years After Transplant, measured over 5 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 90% Confidence Interval |
| Unit | Probability |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the probability of event-free survival during the 5 years after transplant. Event-free survival combines being alive with remaining free of the disease-activity criteria specified in the registry record. Those criteria are loss of neurological function, relapse, or new lesions on MRI. Neurological function loss is defined as a change in pretransplant EDSS of > 0.5. Relapse requires a new or worsening neurological sign and corresponding symptom localized to central nervous system white matter, resulting in neurological deficit or disability and lasting over 48 hours. New MRI lesions are defined as 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant.
This endpoint is used to capture more than mortality alone: a participant can experience an event through specified disease activity even if alive. That makes it relevant to a study asking about both survival and disease control, while also making the endpoint dependent on the stated clinical and imaging definitions. The estimate is described as a Kaplan-Meier survival probability, with a 90% confidence interval based on Greenwood's formula for the standard error. In general, a confidence interval conveys uncertainty around an estimated quantity; its width reflects the precision supported by the data and method. The numerical estimate, interval limits, and event count for this primary endpoint are not reported in the registry record, so neither the observed level of event-free survival nor its precision can be assessed from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies event-free survival during the 5 years after transplant as the primary endpoint and specifies how events are defined. However, the numerical event-free survival estimate and its 90% confidence interval are not reported in the registry record. The primary result therefore cannot be characterized as a particular probability, and its statistical precision cannot be judged. The record's endpoint definition alone does not reveal how many participants experienced an event or when events occurred.
The planned endpoint is a time-to-event measure. Kaplan-Meier estimation is generally used to estimate the probability of remaining event-free over time while accounting for participants whose follow-up ends before an event is observed. A Kaplan-Meier estimate depends on the observed event and censoring histories. In general, censoring means that a participant's event status is not observed beyond a certain point; it does not establish that an event never occurred. The registry record does not report the event times, censoring details, numbers at risk over follow-up, or the endpoint estimate needed to evaluate those features.
The 90% confidence interval is described as based on Greenwood's formula for the standard error. In general, a confidence interval indicates a range of values compatible with the estimate and its sampling uncertainty under the method's assumptions. It is not a guarantee that the true value lies within the particular interval, and it does not itself establish whether an outcome is clinically important. Since neither interval limit is reported in the registry record, no statement about interval width or precision is possible.
The design also determines the scope of interpretation. This is a single-group study, not a randomized comparison. Any observed endpoint would describe outcomes among participants receiving the treatment strategy, rather than a contrast against an untreated or alternatively treated group. It would not, by itself, show what would have happened to the same participants under another approach. The record does not provide a control estimate or a treatment-effect contrast.
The registry reports 25 enrolled participants, but the primary population is defined as participants who received the therapy and transplant. The number analyzed for the primary endpoint is not reported in the registry record. Enrollment should not automatically be treated as the endpoint analysis population. Also, the record lists zero analysis entries, so additional model output or analysis detail is not available in the registry record. Taken together, the endpoint definition is clear, but the posted record does not contain the numerical primary result necessary to interpret the observed event-free survival or its uncertainty.
9. Statistical Methods Explained
The statistical approach named for the primary endpoint is Kaplan-Meier estimation. In general, this method estimates the probability of remaining free of an event over follow-up. It uses the timing of events and accommodates participants who have incomplete follow-up by the time the analysis is conducted. Participants with no observed event before their follow-up ends contribute information up to that point; the method does not treat them as known to remain event-free indefinitely.
The registry defines the event as death or disease activity meeting at least one of the stated criteria. The criteria include a specified change in EDSS, relapse with the required neurological features and duration, or the specified MRI lesions. A composite endpoint of this kind combines different event types into a single event-free survival measure. In general, a composite can summarize several clinically relevant outcomes, but interpretation depends on which components occur and how often. The component-specific event counts are not reported in the registry record.
The endpoint's time frame is the 5 years after transplant. A time-to-event estimate reflects not only whether events occurred but also when they occurred during follow-up. The registry record does not report a numerical Kaplan-Meier estimate, event counts, event times, censoring counts, or numbers at risk at particular times. Therefore, the overall time pattern and the contribution of individual follow-up intervals cannot be evaluated from the registry record.
The record specifies a 90% confidence interval and says that its standard error is based on Greenwood's formula. In general, Greenwood's formula estimates uncertainty for a Kaplan-Meier survival probability using the information in the event and risk sets over time. A confidence interval communicates sampling uncertainty around the estimated probability. The confidence level describes a property of the interval procedure under its assumptions; it is not the probability that the particular interval contains the true value. Because the limits are not reported, it is not possible to comment on the interval's width or the precision of this study's estimate.
For a time-to-event outcome, censoring is important because follow-up may end without an observed event. Kaplan-Meier estimation relies on assumptions about how censoring relates to event risk. In general, if censoring is informative—for example, if the chance of follow-up ending is related to the participant's underlying event risk—the estimate may not represent the intended population probability. The registry record does not describe censoring patterns or provide information to assess this assumption.
The study's single-group structure affects what the statistical results can establish. A one-group Kaplan-Meier estimate describes the event-free survival observed among the analysis population under the study conditions. It does not estimate a difference between treatment and control, and it does not remove confounding or other influences on outcomes. Since allocation is listed as not applicable and the model is single group, no like-for-like randomized comparison is described.
The record lists enrollment as 25, while the primary population is participants who received high-dose immunosuppressive therapy and autologous transplant. The number analyzed for the primary endpoint is not reported in the registry record. In general, the analysis population matters because exclusions, incomplete treatment, and loss to follow-up can affect who contributes to an estimate. No specific reasons for differences between enrollment and analysis, if any, are reported in the registry record.
A planning illustration is described as using the observed effect, 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. The illustrations are planning calculations, not observed power. They are not a description of the trial's original design justification, and the protocol's sample-size justification is not reported in the registry record. Because this trial is a single-group study and no numerical observed effect is reported in the registry record, those assumptions should not be interpreted as establishing a randomized comparison or as evidence about the trial's achieved power.
In general, power is a prospective design concept: it concerns the probability that a planned statistical procedure will detect a specified effect under stated assumptions. A calculation based on an observed effect is not an independent measure of how informative the completed study was. The uncertainty in an observed estimate is better assessed from the estimate, its confidence interval, and the underlying event and follow-up information. Those primary numerical results are not reported in the registry record.
The record lists zero analysis entries. It does not report whether interim analyses were planned or conducted, the handling of missing outcome data, or a detailed prespecified statistical plan. These details are needed to evaluate analysis choices and their relationship to the protocol. General explanations of Kaplan-Meier estimation and confidence intervals describe statistical concepts, not undisclosed procedures or results for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures, including the primary event-free survival endpoint and secondary outcomes covering survival, mortality, morbidity, and engraftment. Considering several outcomes can raise a multiplicity issue: in general, the more statistical questions assessed, the greater the chance of at least one apparently notable result arising by chance if each is interpreted separately. Whether and how to address multiplicity depends on the planned inferential goals. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes.
The record lists zero analysis entries. A detailed statistical analysis plan, including any planned interim analyses, is not reported in the registry record. It is therefore not possible to determine from the record whether additional analyses were planned, whether reported outcomes reflect prespecified analyses, or how any multiplicity was handled.
Missing-data procedures are also not reported in the registry record. For the time-to-event endpoint, incomplete follow-up may be represented through censoring, but the record does not provide censoring counts, reasons, or procedures for other missing information. It does not state how participants with unavailable endpoint assessments were handled. These omissions make it difficult to assess the extent to which the analysis population and follow-up may affect the endpoint estimate.
The primary outcome population is defined as participants who received the high-dose therapy and transplant, but the number analyzed is not reported in the registry record. The record's enrollment figure does not establish the number contributing to that analysis. The adverse-event risk groups and primary endpoint population should also not be assumed to be identical without a reported linkage. These population details matter when assessing how broadly the outcome estimate applies.
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 |
|---|---|---|---|
| HDIT and HCT | 16 | 25 | 64.0% |
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 |
|---|---|
| HDIT and HCT | 25 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | HDIT and HCT |
|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | 3 of 25 |
| Multiple sclerosis | Nervous system disorders | 3 of 25 |
| Leukopenia | Blood and lymphatic system disorders | 2 of 25 |
| Pyrexia | General disorders | 2 of 25 |
| Hypokalaemia | Metabolism and nutrition disorders | 2 of 25 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 2 of 25 |
| Hemiparesis | Nervous system disorders | 2 of 25 |
| Suicide attempt | Psychiatric disorders | 2 of 25 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 2 of 25 |
| Atrioventricular block | Cardiac disorders | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HDIT and HCT |
|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | 25 of 25 |
| Neutropenia | Blood and lymphatic system disorders | 23 of 25 |
| Leukopenia | Blood and lymphatic system disorders | 22 of 25 |
| Thrombocytopenia | Blood and lymphatic system disorders | 19 of 25 |
| Nausea | Gastrointestinal disorders | 10 of 25 |
| Herpes zoster | Infections and infestations | 7 of 25 |
| Urinary tract infection | Infections and infestations | 7 of 25 |
| Cytomegalovirus infection | Infections and infestations | 6 of 25 |
| Diarrhoea | Gastrointestinal disorders | 5 of 25 |
| Sinusitis | Infections and infestations | 5 of 25 |
Serious events with the highest arm-level rate: lymphopenia (12.0%), multiple sclerosis (12.0%), leukopenia (8.0%), pyrexia (8.0%), hypokalaemia (8.0%).
The registry lists 25 participants at risk for serious adverse events and 16 affected in the HDIT and HCT group. For other adverse events, it lists 25 at risk and 25 affected. These are registry counts for the listed group; they should not be read as a comparison with another treatment arm, since the study is single group and has no control arm.
The most frequently listed serious adverse event terms are lymphopenia and multiple sclerosis, each at 12.0%. Leukopenia, pyrexia, hypokalaemia, and pain in extremity are each listed at 8.0%. These percentages describe the terms in the registry's serious-event listing. They do not provide a complete description of severity, duration, recurrence, timing, or causal attribution for each participant. The record does not report those details in the registry record for this analysis.
The deaths field is null. A null entry does not establish that no deaths occurred; the number of deaths is not reported in the registry record. The record also lists survival and mortality among the secondary outcomes, but numerical results for those outcomes are not reported. The adverse-event counts and term percentages should therefore be read as safety reporting, not as proof for or against a causal relationship between the treatment and an event, and not as a comparison of relative safety.
12. What the Result Does, and Does Not, Mean
The registry record gives a defined primary question: the probability of event-free survival during the 5 years after transplant among participants who received high-dose immunosuppressive therapy and autologous CD34+ stem cell transplant. It describes event-free survival as survival without death or the specified neurological or MRI disease activity. That definition makes clear what the endpoint was intended to capture.
The numerical primary estimate and its 90% confidence interval are not reported in the registry record. As a result, the record does not allow the observed event-free survival probability, its precision, or its time pattern to be stated. It also does not report the primary event count or the number analyzed. The presence of an endpoint definition is not itself evidence of a particular outcome.
The study's single-group design means that any outcome would describe the treated group rather than a randomized treatment contrast. In general, an outcome observed after treatment cannot alone establish what would have occurred in the absence of treatment or under an alternative treatment. The registry record does not include a comparator arm, and no causal treatment effect can be inferred from a within-group result alone.
The safety listing reports serious and other adverse-event counts for the HDIT and HCT group and gives percentages for selected serious-event terms. These data are useful descriptions of events recorded in the registry, but they do not by themselves establish whether the treatment caused those events. The record does not provide enough detail to evaluate timing, duration, individual event courses, or comparative safety. The deaths field is null rather than a reported numerical count.
Thus, the record documents the study question, the treatment sequence, the design, and some safety reporting, but it does not report the numerical primary outcome needed to assess the observed event-free survival. It should not be interpreted as demonstrating either benefit or lack of benefit. The limitations are about what can be concluded from the registry record, not a recommendation about treatment.
13. Why This Trial Matters Statistically
This trial is statistically notable for asking a time-to-event question in a single-group Phase II study. Event-free survival combines mortality with defined neurological and imaging events, so the endpoint captures more than survival alone. Its clinical interpretation depends on both the specified event definitions and the way follow-up contributes to the Kaplan-Meier estimate.
The record also illustrates the distinction between describing outcomes and estimating a treatment contrast. A single-group design can characterize what happened in the study population, but it does not provide a randomized comparison. This distinction is essential when interpreting outcomes after a complex treatment strategy, because an observed course in treated participants is not the same quantity as a difference attributable to treatment.
Precision is another central issue. The primary endpoint specifies a 90% confidence interval based on Greenwood's formula, but the numerical estimate and interval are not reported in the registry record. Without them, readers cannot assess how uncertain the primary estimate was. The absence of the analysis population size, event counts, and follow-up detail further limits scrutiny of the time-to-event result.
The registry includes a range of secondary outcomes and adverse-event reporting, making clear why prespecification and multiplicity procedures matter in clinical research. Those procedures are not reported in the registry record. The study therefore offers a useful case for reading design features, endpoint definitions, risk-group counts, and missing outcome estimates separately rather than treating a registry entry as a complete statistical report.
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 most consequential limitation for interpreting outcomes in the registry record is that the primary event-free survival estimate and its confidence interval are not reported. Although the endpoint and its method are described, no numerical result, event count, or time-specific risk information is available. This prevents direct assessment of the estimated probability and its precision.
The design is single group, with allocation not applicable and no masking. There is no concurrent comparator, so the record cannot support a randomized treatment contrast. The absence of a control group also means that background disease course and other influences cannot be separated from outcomes observed after the treatment strategy.
Enrollment is reported as 25, but the number of participants included in the primary endpoint analysis is not reported in the registry record. The endpoint population is described as those who received the therapy and transplant; the relationship between that population and enrollment is not detailed. The record does not report missing-data procedures, censoring patterns, reasons for loss to follow-up, or the numbers at risk over time.
The record lists 20 outcome measures and zero analysis entries. Multiplicity handling, analysis hierarchy, interim analysis plans, and the detailed statistical analysis plan are not reported in the registry record. The secondary outcome definitions and numerical results are not included in the registry record for this analysis, so those outcomes cannot be evaluated in detail.
Safety reporting gives counts for serious and other adverse events and percentages for selected serious-event terms, but the deaths field is null. The record does not report timing, duration, recurrence, or attribution details for these events. These limitations restrict what can be concluded from the registry information and should not be mistaken for evidence that unreported events or analyses did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study — NCT00288626.
- Registry record last updated 2017-09-19; status last verified 2017-08.
- Results first posted 2017-04-04.
- 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
NCT00288626 is a completed Phase II, single-group study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The registry lists enrollment as 25, a start date of 2006-07, and primary completion in 2015-11. It studied high-dose immunosuppressive therapy followed by autologous CD34+ hematopoietic stem cell transplant for relapsing-remitting multiple sclerosis.
The primary endpoint was event-free survival probability during the 5 years after transplant, estimated using Kaplan-Meier methods with a 90% confidence interval based on Greenwood's formula. The registry record defines the event criteria, but its numerical primary estimate and interval are not reported. No randomized comparator is described. The record lists 20 outcome measures and zero analysis entries; details on multiplicity, missing data, and the statistical analysis plan are not reported. Safety listings include serious and other adverse-event counts, while the number of deaths is not reported in the registry record.