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 MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID (NCT00794508), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00794508 |
| Phase | Phase 2 |
| Condition | Severe Combined Immunodeficiency |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Donald B. Kohn, M.D. |
| Results posted | Yes |
2. Clinical Question
Population
Children with ADA-deficient severe combined immunodeficiency (ADA-SCID) were the population of interest. The registry summary describes eligibility for patients without a matched sibling donor who met entry criteria, including adequate organ function and absence of active infections. The number enrolled was 10.
Intervention
The intervention was ADA gene transfer. The registry describes collecting bone marrow, isolating CD34+ cells, transferring the human ADA gene to those cells using an MND-ADA gamma-retroviral vector, giving busulfan to make space in the marrow, and reinfusing the gene-modified cells. The primary outcome description specifies 90 mg/m2 busulfan.
Comparator
There was no comparator arm: the registry identifies a single-group model and allocation as NA. Consequently, the record does not offer a like-for-like control group for comparing adverse-event counts or other outcomes.
Primary question
The primary question was whether adverse events occurred during the safety assessment of the procedure. The primary outcome was the number of participants with adverse events, with a timeframe of 2 years. The registry lists two secondary outcomes: participants with greater than 1% of gene-modified cells in peripheral blood and participants reaching the normal range of ADA enzyme activity.
3. Trial Design
This was a phase 2, single-group trial listed as completed. The registry reports enrollment of 10 and gives a start date of 2008-11 and a primary completion date of 2014-12. The listed condition is severe combined immunodeficiency. The trial title and summary specify ADA-deficient SCID in children.
The intervention was retroviral-mediated ADA gene transfer to CD34+ cells isolated from bone marrow. The primary outcome description frames the safety assessment around bone marrow harvesting, cell isolation, ex vivo gene transduction, busulfan administration, and reinfusion of autologous gene-modified cells. It gives the busulfan dose as 90 mg/m2.
The registry lists no masking and no randomized allocation. With only one group, the design describes outcomes among participants who received the intervention; it does not provide a concurrent untreated or alternative-treatment group. The posted adverse-event counts therefore describe events in this trial group rather than a comparative estimate of risk.
The registry record does not report a sample-size justification, a detailed statistical analysis plan, or a comparator-based design. A planning illustration using equal allocation between two arms is not a description of this single-group design. Any such illustration is planning only, not observed power or evidence from a second group. The record also does not report the reasons for choosing the enrollment target of 10.
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 | Gamma-retroviral-mediated ADA Gene Transfer |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
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: Pre-treatment
| Characteristic | Unit | Experimental Retroviral-mediated ADA Gene Transfer |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 10 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 4 |
| 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 | 1 |
| Race (NIH/OMB): White | Participants | 7 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events, assessed over a timeframe of 2 years. It is a participant-count outcome: it records how many people experienced an event, rather than the total number of event episodes or an event rate over person-time. The registry’s primary outcome description says the endpoint was intended to examine safety across the procedures and treatment involved in the trial.
Counting participants with events can provide a direct descriptive account of how many people in the study group experienced harms during the stated assessment period. It is important, however, to distinguish this measure from the number, severity, timing, or duration of events. Those details are not fully represented by a participant count. The record separately presents serious and other adverse-event counts, and lists infection requiring hospitalization among the top serious terms.
Because the trial has no comparator group, the endpoint cannot by itself establish how the observed count differs from what would have occurred under another treatment or without this intervention. The registry record does not report an adjusted estimate or a statistical comparison for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports 10 participants at risk for serious adverse events, with 5 affected, and 10 at risk for other adverse events, with 9 affected. These are counts within the single trial group. The record also lists infection requiring hospitalization as a top serious term at 50.0%. The primary outcome timeframe is 2 years.
These counts describe what was recorded among participants in the study; they are not a comparison against another group. Without a control group, the data cannot separate events associated with the intervention and its procedures from events that might also occur because of the underlying condition, other care, or other circumstances. A single-group count is therefore descriptive rather than a controlled estimate of treatment effect.
The denominator matters when reading the counts. The record gives 10 participants at risk in each adverse-event category. Counts summarize participants, not event episodes; one participant may have experienced more than one event, and the posted summary does not give the total number of episodes. The record does not describe event timing, duration, or follow-up completeness in enough detail to interpret the counts as rates over time.
The primary outcome is broad, while the record also highlights a serious-event term. A broad adverse-event measure and a particular serious-event category answer different descriptive questions. The listed 50.0% for infection requiring hospitalization should be read as the registry’s reported figure for that term; additional detail about its denominator and event-level context is not reported in the registry record.
No inferential analyses are reported in the registry record. There are no posted confidence intervals, hypothesis tests, or adjusted estimates for these adverse-event counts. A confidence interval, as a general statistical concept, communicates the uncertainty around an estimate under the assumptions of the analysis; without a reported interval or analysis, the precision of these counts cannot be quantified from the record. The small enrollment also means each participant represents an appreciable part of the group, so the counts alone should not be treated as precise estimates of event frequency in a broader population.
The registry lists two secondary outcomes concerning gene-modified cells in peripheral blood and ADA enzyme activity. Results for these secondary outcomes are not reported in the registry record. Thus, the adverse-event summary does not answer those secondary questions, and the record does not permit a combined judgment about safety and those biological outcomes.
9. Statistical Methods Explained
What does a participant count describe?
The primary outcome is a count of participants who experienced adverse events. This kind of endpoint summarizes how many people in the study group had at least one event during the specified assessment period. It does not count every episode separately, and it does not indicate whether affected participants had one event or several. The registry reports counts separately for serious and other adverse events, each with 10 participants at risk.
As a general statistical principle, counts are easiest to interpret alongside their denominators and the rules used to define and collect events. Here, the denominators are reported, but definitions beyond the named categories, event-collection procedures, and participant-level details are not reported in the registry record. The count should therefore be interpreted as the registry’s summary, not as a complete description of every event.
What can a single-group design estimate?
A single-group design can describe outcomes among participants who received the intervention. It cannot directly estimate a contrast with a concurrent control group because none is listed. In a randomized comparison, differences between groups can support an estimate of a relative treatment effect, subject to the analysis and its assumptions. That comparison is unavailable in this trial record. The adverse-event counts should not be interpreted as showing how event frequency compares with another treatment or with no intervention.
In general, a confidence interval describes uncertainty around an estimated quantity under a specified statistical model. The registry record does not report confidence intervals or a statistical model for these outcomes. No precision estimate should be inferred from the counts alone. The absence of an interval does not mean that the result is exact; it means that interval-based uncertainty is not reported.
Why does the denominator matter?
A participant count gains context from the number of participants at risk. The registry reports 10 at risk for serious adverse events and 10 at risk for other adverse events. The two categories should be kept distinct: they are separate summaries, not counts to combine into a new total. The registry does not state whether the same participants appear in both categories, and no combined count should be inferred.
Counts also differ from rates that account for time at risk. A rate needs information about how long participants were observed and how events accrued. The primary outcome has a 2 years timeframe, but person-time and event timing are not reported in the registry record. Accordingly, the reported counts cannot be converted into event rates without adding information that is absent from the record.
What does the planning information mean?
General sample-size planning asks how many participants would be needed to detect a specified effect under stated assumptions. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as a fraction of an observed effect. It also distinguishes total events for time-to-event planning from participants per arm for other outcomes. These are planning assumptions, not the design of this single-group trial. The registry record does not report a trial-specific sample-size justification, and planning illustrations are not observed power or trial results.
The equal-allocation, two-arm framework does not match the listed single-group design. It should not be read as evidence that this study had two arms or as a basis for a controlled comparison. No calculated planning values are described in the registry record.
What analyses are reported?
The registry reports no analyses for the outcomes. It does not report a hypothesis test, an adjusted model, a prespecified approach to handling repeated events, or a statistical comparison. The figures available for adverse events are descriptive participant counts and the listed serious-event term. Without an analysis plan and results, readers cannot determine whether any inferential procedures were intended or how they would have handled multiple outcomes, missing observations, or differences in follow-up.
Over-dispersion is a general issue for count models when variability exceeds what a chosen model assumes. It can matter when analyzing event counts, especially when event episodes vary substantially across participants. The primary outcome is a participant count, and no count-model analysis is reported; therefore, over-dispersion cannot be evaluated from the registry summary. More broadly, the methods needed to assess uncertainty depend on the precise outcome definition and analysis model, neither of which is fully documented in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures: the primary measure of participants with adverse events and two secondary measures. The secondary outcomes concern participants with greater than 1% of gene-modified cells in peripheral blood and participants reaching the normal range of ADA enzyme activity. Results for those secondary outcomes are not reported in the registry record.
When a study evaluates multiple outcomes, testing each one can increase the chance of at least one apparently noteworthy result if each is assessed separately. Statistical methods for addressing this issue are general options, not evidence that a particular method was used in this trial. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or inferential analyses. With no posted tests, the impact of multiplicity cannot be evaluated from the record.
The record reports 10 participants enrolled and 10 at risk in each of the serious and other adverse-event summaries. It does not report a detailed analysis population, participant flow, exclusions from outcome summaries, or the amount and handling of missing outcome data. It is therefore not possible to establish from the registry record whether all enrolled participants contributed data to every outcome or whether follow-up was complete for every participant.
For the adverse-event summaries, the reported at-risk denominators provide context for the counts. They do not, on their own, explain how missing observations were handled or whether participants had differing observation periods. A missing-data plan and a definition of analysis populations are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Retroviral-mediated ADA Gene Transfer | 5 | 10 | 50.0% |
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 |
|---|---|
| Retroviral-mediated ADA Gene Transfer | 9 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Retroviral-mediated ADA Gene Transfer |
|---|---|---|
| Infection requiring hospitalization | Immune system disorders | 5 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Retroviral-mediated ADA Gene Transfer |
|---|---|---|
| neutropenia | Blood and lymphatic system disorders | 9 of 10 |
Serious events with the highest arm-level rate: infection requiring hospitalization (50.0%).
The registry reports 5 participants affected by serious adverse events among 10 at risk. For other adverse events, it reports 9 affected among 10 at risk. These are participant counts in the trial group, not counts of event episodes. Participants may have experienced multiple events; the summary does not report how many total episodes occurred.
The top serious-event term is infection requiring hospitalization, listed at 50.0%. The record does not provide further event-level detail in the posted summary, including timing, duration, or whether the term occurred more than once in a participant. The listed percentage should be interpreted as the registry’s reported figure for that term, not as a comparative estimate.
Serious and other adverse-event categories are presented separately. They should not be added together because the registry does not report whether the same participants are represented in both categories. The single-group design also means these counts do not establish how the event experience compares with another group or whether each event was caused by the intervention. The registry record does not report an adverse-event analysis beyond these descriptive summaries.
12. What the Result Does, and Does Not, Mean
The posted data describe adverse events in a group of 10 participants enrolled in a single-group phase 2 trial of ADA gene transfer. The registry reports serious adverse events in 5 of 10 participants at risk and other adverse events in 9 of 10 participants at risk. It lists infection requiring hospitalization at 50.0% among the top serious-event terms. These are the main numerical safety results reported in the record.
The results do not, by themselves, establish a causal relationship between the intervention and an event. Nor do they show whether the event counts are higher or lower than under another treatment, because no comparator group is listed. The registry summary does not provide the detail needed to assess event timing, event episodes, or variation in follow-up.
The trial also listed secondary outcomes related to gene-modified cells and ADA enzyme activity, but their results are not reported in the registry record. The adverse-event counts do not answer those questions. No inferential analyses or precision estimates are reported, so the uncertainty around the counts is not quantified.
In general, a small study can identify and describe events among its participants, but its counts may be imprecise as estimates for a broader group. That general point does not convert these results into a prediction for an individual or another population. The record supports a limited descriptive reading: these events were recorded in this study group under the registry’s categories. It does not support a controlled treatment-effect conclusion or a comprehensive assessment of all outcomes.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between describing outcomes and comparing treatments. Its single-group design allows the registry to report what happened among participants who received ADA gene transfer, but it does not supply a concurrent reference group. The adverse-event counts are therefore descriptive rather than comparative.
The record also illustrates why denominators and outcome definitions matter. It reports the numbers at risk for serious and other adverse events, while the primary endpoint counts participants with events. That differs from counting every event episode or calculating a rate over time. The registry summary does not provide enough detail to reconstruct those other measures, and the categories should not be combined without knowing whether participants overlap.
Another statistical issue is the gap between an outcome being listed and its result being reported. The registry identifies two secondary outcomes, but their results are not reported in the registry record. Nor are analyses, confidence intervals, or a multiplicity plan reported. A complete interpretation must distinguish the existence of planned or listed outcomes from evidence about their results.
Finally, planning assumptions are not trial findings. A two-arm planning framework does not change the registry’s single-group design, and planning calculations are not observed power. These distinctions help prevent descriptive counts, secondary outcome listings, and planning illustrations from being mistaken for comparative evidence.
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 principal limitation for interpreting the adverse-event results is the absence of a comparator group. The registry identifies a single-group model and no randomized allocation, so the record does not support a direct comparison with another treatment or a control condition. The reported counts describe participants in this trial group only.
Enrollment was 10. Counts from a group of this size provide limited information about how precisely the same event experience would characterize a broader population. The registry does not report confidence intervals or another uncertainty analysis. It also does not report details on event timing, event episodes, participant-level overlap between serious and other events, or variation in follow-up.
The primary outcome description gives a 2 years timeframe, but the record does not provide a detailed account of completeness of follow-up or missing-data handling. Analysis populations, exclusions, and the handling of missing outcome information are not reported in the registry record. Consequently, the reported denominators cannot resolve those questions.
The registry lists two secondary outcomes but does not report their results. It also does not report an analysis plan, inferential analyses, or a strategy for multiplicity. A trial-specific sample-size justification is not reported. The planning description uses assumptions for equal allocation between two arms, which do not correspond to the listed single-group trial design and should not be treated as the trial’s own justification or as observed power.
These limitations concern what can be concluded from the registry record; they do not establish that unreported procedures or analyses did or did not occur outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID — NCT00794508.
- Registry record last updated 2021-04-23; status last verified 2021-04.
- Results first posted 2016-05-30.
- 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
NCT00794508 is a completed phase 2, single-group trial titled MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID. The registry reports enrollment of 10, a start date of 2008-11, and a primary completion date of 2014-12. The intervention was retroviral-mediated ADA gene transfer to bone-marrow CD34+ cells.
The primary outcome was the number of participants with adverse events over 2 years. The registry reports serious adverse events in 5 of 10 participants at risk and other adverse events in 9 of 10 at risk; infection requiring hospitalization is listed at 50.0% among the top serious-event terms. Two secondary outcomes are listed, but their results are not reported in the registry record. No comparator group, statistical analyses, sample-size justification, multiplicity plan, or missing-data approach is reported.