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 Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy (NCT00528268), a non-randomized phase 1, phase 2 study. The primary outcome is Safety and Tolerability of Sodium Phenylbutyrate in Neonates and Infants With SMA.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00528268 |
| Phase | Phase 1, Phase 2 |
| Condition | Spinal Muscular Atrophy |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
Presymptomatic infants with spinal muscular atrophy (SMA), enrolled in separate cohorts for type I and type II SMA. The type I cohort criteria included age < 3 months, a sibling history of type I SMA, and SMN2 dosage < 3 copies. The type II cohort criteria included age < 6 months, a sibling history of type II SMA, and SMN2 dosage < 4 copies.
Intervention
Treatment with sodium phenylbutyrate. The registry describes the study as prospective and identifies the drug as its intervention.
Comparator
No randomized or like-for-like control group is described. Allocation was non-randomized, and the registry cautions that the arms are not a like-for-like control comparison.
Primary question
The primary outcome is titled safety and tolerability, but its description counts participants reaching developmental milestones such as sitting unsupported or walking independently during the study period. The registry does not report a numerical result or analysis for that outcome.
The study asks how sodium phenylbutyrate treatment is accompanied by safety observations and developmental milestones among presymptomatic infants in the two SMA cohorts. The cohorts have distinct eligibility criteria and planned follow-up durations: 18 months for type I infants and 24 months for type II infants. The primary outcome lists a timeframe of 24 months, so the record does not make clear how that single endpoint timeframe relates to the two cohort-specific study durations.
Because the allocation is non-randomized and there is no like-for-like control comparison, the central question is descriptive rather than a controlled estimate of treatment effect. The posted record does not report an analysis comparing developmental outcomes between treated infants and an untreated or randomized control group. It also does not give numerical milestone results. Consequently, the registry record cannot establish whether observed development differs from what would have occurred without treatment.
3. Trial Design
This is a prospective Phase I/II study of sodium phenylbutyrate in presymptomatic infants with spinal muscular atrophy. The registry identifies the design as parallel and non-randomized, with no masking. The study is described as single-center in its brief summary, and the sponsor is the University of Utah. Enrollment is listed as 22, and the record status is completed.
Participants were grouped into a type I SMA cohort and a type II SMA cohort. The type I cohort description specifies age < 3 months, a sibling history of type I SMA, and SMN2 dosage < 3 copies. The type II cohort description specifies age < 6 months, a sibling history of type II SMA, and SMN2 dosage < 4 copies. Both cohort descriptions specify treatment with sodium phenylbutyrate. These are different eligibility groups, not randomized treatment arms designed to be directly compared.
The brief summary states that type I infants would be followed for 18 months and type II infants for 24 months. The primary outcome timeframe is recorded as 24 months. The registry does not explain how outcome collection was aligned with the separate cohort durations or whether milestone observation windows differed by cohort.
The record lists a start date of 2007-07 and primary completion of 2013-12. It does not report the rationale for the planned enrollment, a sample-size justification, details of recruitment or treatment dosing, or a statistical analysis plan. The registry records one outcome measure and zero analyses. Completion status indicates that the study is recorded as completed; it does not by itself supply the missing numerical results for the primary outcome.
With no random allocation, no masking, and no like-for-like control comparison, differences between the cohorts would not isolate a treatment effect. The cohorts differ by SMA type and eligibility characteristics, so their outcomes should not be treated as a direct comparison of treatment strategies.
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 | Cohort 1 | Cohort 2 |
|---|---|---|
| STARTED | 6 | 8 |
| COMPLETED | 5 | 7 |
| NOT COMPLETED | 1 | 1 |
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.
| Characteristic | Unit | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 8 | 14 | |
| Age, Categorical: <=18 years | Participants | 6 | 8 | 14 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 2 | 5 | 7 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Tolerability of Sodium Phenylbutyrate in Neonates and Infants With SMA, measured over 24 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled Safety and Tolerability of Sodium Phenylbutyrate in Neonates and Infants With SMA. It is recorded as a count of participants, with a timeframe of 24 months. However, the outcome description specifies the number of participants able to achieve developmental milestones, including sitting unsupported or walking independently, during the study period. That description concerns developmental progress, while the title frames the endpoint as safety and tolerability. The registry record does not clarify this mismatch.
A participant count can describe how many people reached a defined milestone, but interpretation depends on a clear definition of the milestone, the time allowed to reach it, and the number of participants assessed. Those details, including separate milestone counts for the cohorts, are not reported in the registry record. The record also does not provide a numerical primary-outcome result or a statistical analysis of that result.
Milestone outcomes can be relevant in a study following infants over time because they describe observable developmental status. They do not, on their own, establish that an intervention caused a change. In this study, the non-randomized design and lack of a like-for-like control comparison further limit causal interpretation. The listed endpoint therefore signals an intended measure, but the posted record does not support an estimate of the treatment effect on milestone attainment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed, non-randomized study of sodium phenylbutyrate in presymptomatic infants with SMA. Its primary outcome is labeled as safety and tolerability, but the outcome description concerns participants reaching developmental milestones. No numerical result or analysis for that primary outcome is reported in the registry record. The record lists one outcome measure and zero analyses, so no estimate of milestone attainment or uncertainty around that estimate can be interpreted from the posted primary outcome information.
Safety information is posted separately by cohort. In cohort 1, 6 participants were at risk for serious adverse events and 6 were affected; for other adverse events, 6 participants were at risk and 6 were affected. In cohort 2, 8 participants were at risk for serious adverse events and 7 were affected; for other adverse events, 8 were at risk and 8 were affected. These are descriptive counts. They do not establish that the intervention caused the events, and the registry record does not report a control group suitable for estimating an excess risk attributable to treatment.
The listed serious-event terms include Fever at 66.7%, Upper Respiratory Infection at 50.0%, G-tube at 50.0%, Pneumonia at 33.3%, Lethargy at 25.0%, and GE Reflux at 16.7%. The record does not specify in this information the denominator or counting convention for these term percentages. They should therefore be read as registry-listed percentages, not assumed to represent percentages of participants with each event or rates over a particular follow-up period.
The enrollment entry is 22, whereas the safety entries give cohort-specific numbers at risk. The record does not explain the relationship between the enrollment total and those safety denominators. Nor does it explain whether the numbers reflect all enrolled participants, participants exposed to treatment, or another analysis population. This uncertainty prevents a fuller accounting of follow-up and outcome completeness.
The study has no randomization or masking, and the registry explicitly warns that the arms are not a like-for-like control comparison. The two cohorts also have different SMA types and eligibility criteria. Accordingly, the posted counts can describe recorded events in each cohort, but they cannot support an unconfounded comparison between cohorts or an estimate of treatment benefit relative to an untreated group. The record does not report confidence intervals, hypothesis tests, adjusted estimates, or a detailed statistical plan. Conclusions should remain limited to the descriptive information that is actually posted.
9. Statistical Methods Explained
The registry records a participant count as the primary outcome parameter. A count is a direct description of how many participants meet an outcome definition. For it to be interpretable, the definition, observation window, and number of participants assessed need to be clear. Here, the title refers to safety and tolerability, while the description refers to milestone attainment. The registry record does not resolve that difference or report numerical milestone counts.
What do the safety counts represent?
The adverse-event entries give numbers at risk and numbers affected for serious and other adverse events, separately for each cohort. In cohort 1, the serious-event figures are 6 at risk and 6 affected, and the other-event figures are also 6 at risk and 6 affected. In cohort 2, the corresponding serious-event figures are 8 at risk and 7 affected, while the other-event figures are 8 at risk and 8 affected. These figures are counts, not adjusted comparisons. They describe the entries in the registry and do not establish whether an event was caused by treatment.
General statistical explanation: when interpreting a count, the denominator defines the group in which events were observed. A participant count differs from an event count because one participant may experience more than one event. The registry entries do not state whether affected participants are counted once per category or how repeated events were handled. That counting convention is not reported in the registry record.
Why does the non-randomized design matter?
General statistical explanation: random allocation can help balance measured and unmeasured characteristics between treatment groups. Without randomization, group membership may be associated with prognosis or other characteristics. This study is recorded as non-randomized, and its cohort definitions differ by SMA type, age criteria, family history, and SMN2 dosage criteria. Therefore, contrasts between cohorts would combine treatment exposure with differences in who entered each cohort. The registry itself cautions that the arms are not a like-for-like control comparison.
There is no masking. General statistical explanation: knowledge of treatment assignment can influence assessment, reporting, or decisions about whether an outcome has occurred, particularly when outcomes require judgment. The record does not describe procedures to reduce that possibility. This does not establish that assessments were biased; it means the record does not describe masking that could limit such influence.
How should uncertainty be assessed?
General statistical explanation: a confidence interval expresses the range of estimates compatible with the data and the method used, and it communicates precision as well as the direction and size of an estimate. A p-value addresses compatibility with a specified null model under stated assumptions; it is not a measure of clinical importance or the probability that a hypothesis is true. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record. No primary-outcome estimate is posted from which to assess precision.
Small counts can be imprecise. General statistical explanation: with few observations, a single participant can have a substantial influence on a count or proportion, and estimates may vary considerably across samples. That is one reason to report uncertainty alongside descriptive estimates. The registry record does not provide uncertainty intervals for the posted safety counts or term percentages.
What do the planning assumptions mean?
The sample-size assumptions describe planning illustrations based on an observed effect, rather than the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. These assumptions do not establish that the trial was planned or conducted using those conditions. The registry does not report its own sample-size justification. A planning illustration is not observed power and does not show that a study had a particular probability of detecting an effect after its results were observed.
General statistical explanation: power calculations depend on assumptions about the outcome, target effect, variability, allocation, and analysis. Changing those assumptions changes the resulting planning estimate. For a non-randomized study without a like-for-like control comparison, an illustration built around equal allocation between arms should not be mistaken for evidence that the actual cohorts form a suitable controlled comparison.
The registry records zero analyses. It does not report the statistical methods used for the safety summaries, any adjustment for differences between participants, handling of missing observations, or a prespecified analysis population. Those omissions limit the ability to evaluate how the posted counts were assembled and how uncertainty should be quantified.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or an approach to multiplicity. Multiplicity concerns the increased chance of false-positive findings when many outcomes, comparisons, time points, or subgroup analyses are examined. General statistical explanation: prespecifying a primary analysis and accounting for multiple testing can help clarify which findings are confirmatory and which are exploratory. The absence of a reported plan does not establish that multiple testing occurred; it means the record does not describe how it would have been handled.
Missing data and the analysis population are also not described in the registry record. It does not report how many participants had primary-outcome assessments, whether every enrolled participant was followed for the stated duration, how incomplete follow-up was handled, or whether all treated participants were included in safety summaries. The enrollment entry is 22, while the cohort-specific safety entries give different numbers at risk; the reason for this difference is not reported in the registry record.
General statistical explanation: if participants with incomplete follow-up differ systematically from those with complete data, an analysis restricted to observed outcomes can be misleading. The possible direction and extent of such bias depend on why data are missing and on the analysis approach. Without reported follow-up completeness, missing-data methods, and analysis-population definitions, those issues cannot be assessed for this study.
The record does not report interim analyses, stopping rules, or whether outcome definitions changed during the study. Their presence or absence cannot be inferred from the listed results. These reporting gaps do not prove that the study lacked internal procedures, but they prevent readers from evaluating them from 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 |
|---|---|---|---|
| Cohort 1 | 6 | 6 | 100.0% |
| Cohort 2 | 7 | 8 | 87.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1 | 6 of 6 |
| Cohort 2 | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 |
|---|---|---|---|
| G-tube | Gastrointestinal disorders | 3 of 6 | 2 of 8 |
| Fever | General disorders | 4 of 6 | 1 of 8 |
| Upper Respiratory Infection | Infections and infestations | 3 of 6 | 0 of 8 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 2 of 6 | 1 of 8 |
| Increased Secretions | General disorders | 1 of 6 | 1 of 8 |
| Death | General disorders | 1 of 6 | 1 of 8 |
| Lethargy | General disorders | 0 of 6 | 2 of 8 |
| Daily Vomiting | Gastrointestinal disorders | 0 of 6 | 1 of 8 |
| GE Reflux | Gastrointestinal disorders | 1 of 6 | 0 of 8 |
| Anemia of Chronic Disease | Blood and lymphatic system disorders | 1 of 6 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 |
|---|---|---|---|
| Serous Otitis Media Bilateral | Infections and infestations | 4 of 6 | 3 of 8 |
| Flu symptoms | Infections and infestations | 2 of 6 | 5 of 8 |
| Upper Respiratory Infection | Infections and infestations | 2 of 6 | 3 of 8 |
| Rhinitis | Infections and infestations | 2 of 6 | 1 of 8 |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | 1 of 6 | 2 of 8 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 6 | 3 of 8 |
| Eye Infection | Infections and infestations | 1 of 6 | 1 of 8 |
| Constipation | Gastrointestinal disorders | 1 of 6 | 1 of 8 |
| Reflux | Gastrointestinal disorders | 0 of 6 | 2 of 8 |
| Sinus Infection | Infections and infestations | 0 of 6 | 2 of 8 |
Serious events with the highest arm-level rate: fever (66.7%), upper respiratory infection (50.0%), g-tube (50.0%), pneumonia (33.3%), lethargy (25.0%).
The registry reports serious and other adverse-event counts separately for cohort 1 and cohort 2. Cohort 1 has 6 participants at risk and 6 affected for serious events, and 6 at risk and 6 affected for other events. Cohort 2 has 8 at risk and 7 affected for serious events, and 8 at risk and 8 affected for other events. These are cohort-level descriptive entries; they are not a comparison against an untreated control group.
The listed serious-event terms and percentages are Fever at 66.7%, Upper Respiratory Infection at 50.0%, G-tube at 50.0%, Pneumonia at 33.3%, Lethargy at 25.0%, and GE Reflux at 16.7%. The registry information does not identify the denominator and counting convention for these term percentages. It is therefore not possible to tell from the record whether they refer to affected participants, events, or another basis. They should not be interpreted as incidence rates over a specified amount of person-time.
General statistical explanation: adverse-event counts describe what was recorded during observation; by themselves they do not establish causality. Interpretation also depends on exposure duration, event definitions, ascertainment, and the population included. Those details are not fully reported in the registry record. No deaths are listed in the adverse-event entries, but the record does not provide additional death information in those fields. The safety figures can be read as descriptive reports, not as evidence of a causal treatment effect or a comparative risk estimate.
12. What the Result Does, and Does Not, Mean
The registry record documents a prospective Phase I/II study of sodium phenylbutyrate in presymptomatic infants with type I and type II SMA. It identifies two non-randomized cohorts, describes their eligibility criteria, and reports safety counts and selected serious-event terms. It also identifies a primary outcome framed by its title as safety and tolerability, but described as a count of participants reaching developmental milestones during a 24-month timeframe.
The posted record does not report numerical results or an analysis for that primary outcome. It therefore does not show how many participants reached the listed milestones, how precisely any such count was estimated, or whether milestone attainment differed between groups. Although adverse-event summaries are present, the lack of a like-for-like control comparison prevents those summaries from establishing whether events were more or less common because of treatment.
The record also does not establish a causal treatment effect. Allocation was non-randomized and unmasked, and the cohort criteria differ. A comparison between the type I and type II cohorts would not isolate the effect of sodium phenylbutyrate because cohort membership is linked to SMA type and other eligibility characteristics. The record does not provide a suitable untreated or randomized control group for estimating what would have happened without treatment.
These limitations do not mean that the study has no descriptive value. The cohort definitions and safety entries document what the registry reports about this study. But a completed status is not a substitute for numerical primary-outcome results, a defined analysis population, or an uncertainty analysis. Conclusions about treatment effects, milestone outcomes, and comparative safety are not supported by the information reported in the registry record.
General statistical explanation: evidence about an intervention depends not only on the observed data but also on the design and the precision of the estimates. Counts without a clearly defined denominator, outcome analysis, or control comparison answer a narrower question than a randomized comparative estimate. The appropriate interpretation is therefore limited to the study description and descriptive safety entries, while recognizing that key outcome results and analysis details are not reported in the registry record.
13. Why This Trial Matters Statistically
This study matters statistically because it illustrates how a registry endpoint can be difficult to interpret when its title and description point to different concepts. The primary outcome title refers to safety and tolerability, while its description counts participants achieving developmental milestones. Without clarification, the intended primary estimand—the quantity the study sought to estimate—is not clear from the record. The lack of numerical results and the entry of zero analyses further limit assessment of the endpoint.
The record also makes the distinction between a treated cohort and a controlled comparison important. The study is non-randomized, has no masking, and the registry cautions that its arms are not a like-for-like control comparison. The two cohorts are defined by different SMA types and eligibility criteria. Treating their outcomes as a direct treatment comparison would confuse differences in cohort composition with potential treatment effects.
Safety summaries are useful as descriptions, but interpretation requires clarity about the denominator, event-counting rules, observation time, and analysis population. The registry gives numbers at risk and affected, and lists selected serious-event terms with percentages, but does not fully describe how the term percentages were constructed. The enrollment entry and cohort-level safety denominators also are not reconciled in the record.
More broadly, a completed trial record does not necessarily contain enough information to assess precision or bias. The record does not report primary-outcome estimates, confidence intervals, hypothesis tests, a sample-size justification, or a statistical analysis plan. General statistical explanation: design, endpoint definition, analysis choices, and transparent reporting jointly determine how much can be learned from results. In this case, the registry supports a description of the study and posted safety entries, but not a controlled estimate of treatment effect.
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.
Several limitations arise from the trial design and registry reporting. The study is non-randomized and unmasked, and the registry cautions that the arms are not a like-for-like control comparison. The type I and type II cohorts have different eligibility criteria, so comparing their outcomes would not provide a clean estimate of treatment effect. The single-center description may also limit how closely the enrolled population represents infants treated in other settings; the record does not report information that would quantify that issue.
The primary outcome has an apparent description mismatch: its title concerns safety and tolerability, while the description specifies milestone attainment. The outcome timeframe is listed as 24 months, whereas the brief summary gives a study duration of 18 months for type I infants and 24 months for type II infants. The registry does not explain how the endpoint was applied across those durations. It also does not report milestone results, outcome assessment details, or uncertainty estimates.
The registry records enrollment of 22, but the safety entries report cohort-specific numbers at risk without explaining their relationship to enrollment. It does not report the analysis population, completeness of follow-up, handling of missing data, or the denominator and counting method for the serious-event term percentages. These omissions make it difficult to assess whether the posted counts cover all enrolled or treated participants and how precisely they represent the study population.
The record does not report dosing details, a sample-size justification, a statistical analysis plan, multiplicity procedures, interim analyses, or stopping rules. These items are not assumed to be absent from the conduct of the study; they are not reported in the registry record. Together with the lack of a like-for-like control group and the absence of primary-outcome analyses, these limitations restrict the conclusions that can be drawn from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy — NCT00528268.
- Registry record last updated 2025-02-28; status last verified 2017-06.
- Results first posted 2015-07-03.
- 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 registry record describes a completed, prospective Phase I/II study of sodium phenylbutyrate in presymptomatic infants with SMA. It lists non-randomized allocation, no masking, a parallel model, enrollment of 22, and a single-center setting in the brief summary. Separate cohorts were defined for type I and type II SMA, with stated study durations of 18 months and 24 months, respectively.
The primary outcome is titled safety and tolerability but described as a count of participants achieving developmental milestones, with a 24-month timeframe. One outcome measure and zero analyses are listed; numerical primary-outcome results are not reported in the registry record. Safety counts and selected serious-event terms are posted by cohort, but the record does not provide a like-for-like control comparison or clarify the denominator for the term percentages.
Key design and analysis details—including a sample-size justification, statistical analysis plan, missing-data methods, and analysis population—are not reported in the registry record. The posted data therefore support a study description and limited descriptive safety reading, not a controlled estimate of treatment effect.