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 Folinic Acid in Autism (NCT03771560), a na phase 2, phase 3 study. The primary outcome is Aberrant Behavior Checklist (ABC) - Parent Reported Change.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03771560 |
| Phase | Phase 2, Phase 3 |
| Condition | Autism Spectrum Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
Children with autism spectrum disorder (ASD). The registry lists an enrollment of 18, but it does not report the age range, participant characteristics, or the number included in the primary outcome analysis.
Intervention
Folinic acid given in pill form at a weight-based dose, twice daily. The trial is described as open-label, so participants and investigators were not masked to treatment.
Comparator
There was no separate control group. The registry identifies the study as single-group, with allocation listed as not applicable; it is not a randomized, like-for-like comparison.
Primary question
What change from baseline to Week 12 was recorded in the parent-reported Aberrant Behavior Checklist (ABC) total score during folinic acid use? The registry does not report the numerical change or its confidence interval.
The study’s stated focus was changes in urinary metabolites with folinic acid use in children with ASD. The registry summary also says investigators would measure behavioral and academic measures monthly at school, with reports from teachers and parents. The primary registered behavioral outcome was the parent-reported ABC change from baseline to Week 12. The listed secondary outcomes were parent-reported and teacher-reported change on the Social Responsiveness Scale (SRS), and parent-reported change on the Pediatric Quality of Life (PedsQL).
Those questions describe measurements during treatment, not a comparison of folinic acid with an untreated or alternative-treatment group. With a single group, a change from baseline can describe what happened among participants who were measured, but it cannot by itself separate treatment-associated change from other explanations, such as change over time, measurement variation, or expectations in an unmasked study. The registry does not report a numerical ABC change, a confidence interval, a p-value, or a detailed analysis population. Therefore, the primary question can be identified from the record, but its estimated answer and precision are not reported in the registry record.
3. Trial Design
NCT03771560, titled “Folinic Acid in Autism,” is listed as a completed study sponsored by the University of California, San Francisco. The registry records a Phase 2 and Phase 3 designation, an enrollment of 18, and a single-group model. Allocation is listed as not applicable. The intervention group is described as open-label: all subjects were to receive folinic acid twice daily, in pill form, at a weight-based dose. There is no separate comparator arm in the registered design.
The recorded study start date is 2018-02-15, and the primary completion date is 2018-06-30. The primary outcome is the parent-reported change in ABC score from baseline to Week 12. The registry also identifies SRS parent and teacher reports and PedsQL parent report as secondary outcomes. Its summary describes monthly measurement of behavioral and academic measures at school, with teacher and parent reports. Details of the academic measures are not reported in the registry record.
In a single-group study, the main descriptive contrast is between measurements taken at different times for participants in the same group. That differs from a randomized controlled comparison, where outcomes in separately assigned groups can be compared under the trial’s allocation process. Here, no randomized control comparison is reported, and the open-label design means participants and those collecting or reporting outcomes knew that folinic acid was being used. This design can document measured changes over the study period, but it does not provide a concurrent control group to account for changes that might occur without the intervention.
The registry status is completed, but completion does not itself establish that every planned measure was collected or that an analysis was completed as planned. The number contributing to the primary analysis, the analysis population definition, adherence details, and reasons for any missing measurements are not reported in the registry record. The record also does not report the protocol details needed to assess whether the registered outcome schedule or analysis plan changed.
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 | Folinic Acid Open-label |
|---|---|
| STARTED | 18 |
| COMPLETED | 12 |
| NOT COMPLETED | 6 |
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: Children with ASD enrolled in Oak Hill school and completed the entire study.
| Characteristic | Unit | Folinic Acid Open-label |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 12 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 16 (13 to 18) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 10 |
| 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 | 8 |
| Race (NIH/OMB): More than one race | Participants | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Aberrant Behavior Checklist (ABC) - Parent Reported Change, measured over Baseline to Week 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean change in the parent-reported Aberrant Behavior Checklist total score from baseline to Week 12. The ABC is described as a 58-question measure of aberrant behavior in children and young adults. Each question is scored from 0 (not a problem) to 3 (severe), and the total possible score range is 0 - 174. The registry states that a lower score indicates better performance.
A change score expresses how a participant’s measured value differs between two specified times. For this endpoint, the registered time points are baseline and Week 12. A group mean change would describe the average change among participants included in the analysis; it would not indicate that every participant changed by the same amount. The registry specifies a 95% confidence interval as the dispersion measure for this continuous outcome, but the numerical mean change and interval are not reported in the registry record.
Parent reporting provides a structured way to capture behavior observed by caregivers across the ABC’s questions. The total score converts those item responses into a single continuous measure that can be described using a mean and confidence interval. The instrument is relevant to the registered question because the study’s stated primary behavioral outcome is change in parent-reported ABC score. Its interpretation still depends on the score direction, the completeness and consistency of reports, the participants included, and the absence of a control group. The record does not state a threshold for a meaningful change, so the clinical importance of any numerical change cannot be determined from the registry description alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the primary outcome and its measurement period, but it does not report the numerical result. In particular, the mean ABC change from baseline to Week 12 and its 95% confidence interval are not reported in the registry record. A p-value, a participant-level distribution, and the number included in the primary analysis are also not reported. Consequently, the direction, size, and precision of the primary outcome estimate cannot be described from this record.
That absence matters because the endpoint is a change score, and the meaning of a change depends on both its direction and magnitude. The registry says that lower ABC scores indicate better performance, but it gives no observed mean change to interpret against that direction. It also does not report a threshold for a change considered important. No conclusion about the measured behavioral outcome’s magnitude or importance can be drawn from the endpoint description alone.
General statistical explanation: a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis that produced it. A narrow interval indicates greater statistical precision than a wide interval, but neither width alone nor a point estimate establishes that an effect is clinically important. In this study, the record names a 95% confidence interval as the dispersion measure, but without the interval’s limits there is no way to assess its precision.
The design further limits interpretation. This was a single-group open-label study, not a randomized comparison with a control group. A measured change between baseline and Week 12 would therefore describe change over time among those analyzed, rather than an isolated estimate of the effect of folinic acid relative to a comparator. Other influences on measurements over time cannot be separated from treatment-associated change by a single-group contrast alone. The registry does not report details that would allow an assessment of how those influences were addressed.
The registry records an enrollment of 18, while the adverse-event information uses its own at-risk counts. Enrollment should not be treated as the number analyzed for the primary endpoint: that analysis count is not reported. The record’s completed status likewise does not supply the missing outcome estimate. The safest statistical reading is therefore limited: the intended primary measure, scoring direction, and time frame are documented, but the outcome result and its uncertainty are not reported in the registry record.
9. Statistical Methods Explained
The registered primary outcome is continuous: it is the mean of a score change over time. Continuous outcomes can take a range of numerical values rather than representing only categories such as event versus no event. For this measure, each ABC item is scored on a 0-to-3 scale, and the total score is described as ranging from 0 - 174. The registry identifies a mean as the summary measure and a 95% confidence interval as the dispersion measure. It does not report the calculated mean change, the interval limits, or the method used to calculate them.
What does a mean change describe?
General statistical explanation: a mean change is an average of individual changes over the specified measurement period. The average can summarize a group while concealing variation: some participants may have larger changes, smaller changes, or changes in a different direction. The mean alone does not describe that spread. A confidence interval around the mean gives information about the statistical uncertainty of the estimate, but does not show every participant’s response. Without the estimated mean and confidence interval, neither the average change nor its precision can be assessed for this study.
How should a confidence interval be read?
General statistical explanation: a confidence interval is an interval estimate constructed using a statistical procedure. It reflects uncertainty associated with sampling and the model assumptions used for the analysis. It is not a range that contains every participant’s observed change, and it does not account automatically for design limitations, missing measurements, or bias in reporting. The registry specifies a 95% confidence interval for the ABC mean change, but the confidence interval’s numerical limits are not reported in the registry record.
What does the single-group design allow?
General statistical explanation: repeated measurements in one group can describe change between time points, but the baseline measurement is not a concurrent control condition. A before-and-after contrast does not by itself establish what would have happened over the same period without the intervention. In a randomized comparison, allocation to groups can support a different kind of contrast; no such comparison is reported for this study. The registry describes the trial as single-group and open-label, so its design should not be interpreted as a blinded, randomized treatment comparison.
Open-label measurement also affects how an outcome is understood. The ABC outcome is parent-reported, and the registry states that parents and teachers were involved in reporting behavioral or academic measures. General statistical explanation: knowledge of treatment assignment can influence expectations, reports, or the way measurements are collected. This possibility does not show that reporting was biased in this study; it is a design consideration that the record does not quantify. Information about efforts to standardize reporting or assess observer agreement is not reported in the registry record.
What can planning calculations say?
The planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a stated fraction of the observed effect. The same assumptions distinguish total event counts for time-to-event calculations from participants per arm for other calculations. These are assumptions for a planning illustration, not the trial’s reported design: the registered trial is single-group, with no like-for-like control comparison. Numerical planning estimates and the observed effect needed to interpret them are not reported in the registry record.
General statistical explanation: a sample-size calculation asks what number of participants would be needed under specified assumptions to target a chosen degree of statistical power for a particular effect. Such a calculation is conditional on its assumptions, including the effect size, variability, allocation, and analysis. A planning illustration based on an observed effect is not observed power and does not show that a completed study had a particular probability of detecting an effect. Because the numerical estimates and relevant observed effect are not reported in the registry record, no planning number can be interpreted from the registry entries.
What analysis details are unavailable?
The registry does not report the statistical test or model used for the ABC outcome, whether any adjustment was made, or how repeated measurements were handled in the analysis. It does not state whether the primary analysis used all enrolled participants, only participants with complete measurements, or another analysis population. The number of participants contributing to the primary result and the handling of missing values are not reported in the registry record. These details matter because they define the estimate’s target population and can affect the result’s uncertainty.
The registry lists five outcome measures and five analyses. It names the ABC as the primary outcome and lists SRS parent report, SRS teacher report, and PedsQL parent report as secondary outcomes. The result values, analysis details, and any adjustment for multiple outcome analyses are not reported in the registry record. Accordingly, the statistical methods that can be described are the registered outcome summary and planning assumptions; the analysis actually used to produce any result cannot be reconstructed from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and five analyses. The named primary outcome is parent-reported ABC change from baseline to Week 12. The named secondary outcomes are SRS parent-reported change, SRS teacher-reported change, and PedsQL parent-reported change. The record does not report numerical results for these outcomes or describe an adjustment for making multiple statistical comparisons. It also does not report whether any outcome was designated as exploratory or how the interpretation of multiple results was planned.
General statistical explanation: when several outcomes or comparisons are tested, the chance of observing at least one apparently unusual result can increase if each result is interpreted separately without accounting for multiplicity. Approaches to address this issue vary, and the appropriate approach depends on the study’s goals and analysis plan. No multiplicity procedure or rationale is reported in the registry record, so it is not possible to determine how the several registered analyses were handled statistically.
The record does not describe a missing-data strategy, reasons for missing observations, or the number of participants with a completed ABC assessment at Week 12. It does not define an analysis population or say how participants with incomplete measurements were treated. These omissions prevent assessment of whether missingness could have affected the estimated mean change or the confidence interval.
General statistical explanation: missing outcome data can reduce precision and may also affect interpretation if the people with recorded measurements differ in relevant ways from those without them. The impact depends on why data are missing and how the analysis handles them. A registry enrollment figure cannot substitute for an endpoint-specific analysis count. The registry’s completed status does not establish that all scheduled measurements were available or that all enrolled participants entered the primary analysis.
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 |
|---|---|---|---|
| Folinic Acid Open-label | 0 | 12 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Folinic Acid Open-label | 0 of 12 |
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 |
|---|---|
| Folinic Acid Open-label | 5 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Folinic Acid Open-label |
|---|---|---|
| Upset Stomach | Gastrointestinal disorders | 1 of 12 |
| Dry mouth | General disorders | 1 of 12 |
| Cold | Respiratory, thoracic and mediastinal disorders | 1 of 12 |
| Increased aggression | Psychiatric disorders | 1 of 12 |
| Blood in Stool | Gastrointestinal disorders | 1 of 12 |
The registry reports one group titled “Folinic Acid Open-label.” For serious adverse events, it lists 12 at risk and 0 affected. For other adverse events, it lists 12 at risk and 5 affected. It reports 0 deaths. No serious adverse event terms are listed among the top serious terms.
These figures should be read as the registry’s recorded counts, not as a comparative estimate. The study has no separate control group, so the adverse-event counts cannot be compared with a concurrent untreated or alternative-treatment group. The registry does not provide event descriptions for the other adverse events, timing, severity details, or information about whether participants experienced more than one event. It is therefore not possible to characterize those events further from the record.
General statistical explanation: an at-risk count identifies the group counted for a particular safety summary, while an affected count records the number reported as affected in that summary. Counts do not by themselves establish causation, and without a comparator they cannot show whether an event frequency differs from what would have occurred otherwise. The adverse-event at-risk count should not be assumed to equal enrollment or the number included in the primary outcome analysis; those relationships are not reported in the registry record.
The reported 0 serious adverse events and 0 deaths are the recorded values for this group. They do not establish that there was no risk, nor do they describe safety beyond the information captured in the registry. The record does not report additional detail needed for a fuller safety assessment.
12. What the Result Does, and Does Not, Mean
The registry documents a completed, open-label, single-group study of folinic acid in children with ASD, with parent-reported ABC change from baseline to Week 12 as the primary outcome. It specifies how the ABC is scored and states that a lower score indicates better performance. Those details identify what the primary outcome was intended to measure and how its direction should be read.
However, the numerical primary outcome result is not reported in the registry record. The mean change, its 95% confidence interval, the number analyzed, and a p-value are not reported. As a result, the record does not show whether the mean score changed, in which direction it changed, how precisely it was estimated, or how much participants varied in their changes. A registered measure is not itself an outcome result.
Even if a within-group change estimate were available, a single-group before-and-after measurement would describe change over time, not a randomized comparison of folinic acid with a control. General statistical explanation: change can reflect more than the intervention alone, including time-related variation, measurement variation, or influences on reporting. An open-label design also leaves participants and reporters aware of treatment. The record does not report a method for separating these possibilities from treatment-associated change.
The registry’s safety counts report 0 affected by serious adverse events, 5 affected by other adverse events, and 0 deaths, with 12 at risk in each adverse-event category. These are descriptive counts for the open-label group. They do not establish comparative risk, explain the types of other events, or show whether an event was caused by folinic acid.
Thus, the record supports a description of the study design, intended outcomes, scoring, and limited safety counts. It does not support a conclusion about the size, precision, or clinical importance of the primary outcome change. The missing outcome results and the lack of a control group are central limits on what can be inferred.
13. Why This Trial Matters Statistically
This study illustrates why a registered outcome definition and a reported outcome estimate serve different purposes. The registry identifies the ABC as the primary measure, describes its score range and direction, and specifies a baseline-to-Week 12 comparison. That information helps clarify what the investigators intended to measure. Without the mean change and confidence interval, however, the registered outcome cannot be used to assess the observed change or its statistical precision.
The design also makes the comparison being estimated important. A single-group study can describe change over time among its participants, but does not offer a concurrent control group. An open-label parent-reported endpoint introduces further interpretive considerations because reporters know treatment is being given. These features do not invalidate the measurement; they define the limits of the conclusions that a within-group change could support.
The record also demonstrates why analysis details matter. The number enrolled is recorded, but the number contributing to the primary endpoint is not reported. Missing-data methods, analysis-population definitions, and methods for handling multiple outcomes are also not reported. Without these details and the outcome estimates, readers cannot evaluate the reported precision or the robustness of an analysis.
Finally, planning illustrations based on an observed effect need to be distinguished from the study’s actual design and results. The listed assumptions describe a hypothetical two-arm planning calculation, whereas this trial is registered as single-group. A planning calculation does not supply the missing endpoint estimate and is not evidence of observed power. Keeping design, analysis, and result separate is essential for an accurate statistical reading of this record.
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 trial-specific limitations affect interpretation. The study is registered as single-group and open-label, with no separate control group. Therefore, any baseline-to-Week 12 change would be a within-group description rather than a randomized estimate comparing folinic acid with another condition. The record does not describe a method for distinguishing treatment-associated change from other changes over time.
The primary outcome is parent-reported, and the study summary also describes reports from teachers and parents. In an open-label study, reporters know that participants are receiving the intervention. The registry does not report procedures for standardizing reports, assessing consistency between reporters, or reducing the influence of expectations. These possibilities are limitations to consider, not evidence that reports were biased.
The primary outcome result is not reported in the registry record. The mean ABC change and 95% confidence interval are unavailable, as are the number included in the analysis and a numerical result for the listed secondary outcomes. The record also does not report the number of completed Week 12 assessments, a missing-data strategy, or reasons for missing measurements. These gaps prevent evaluation of the outcome estimate and its precision.
The registry identifies five outcome measures and five analyses, but does not report a multiplicity strategy. It does not report the statistical model or test used for the primary outcome, the analysis population, or whether adjustments were made. The recorded enrollment of 18 should not be treated as the endpoint analysis count. The detailed age range and participant characteristics are not reported in the registry record, limiting assessment of how broadly the study findings would apply even if the outcome results were available.
Finally, the safety record gives event counts but does not describe the other adverse events or provide a comparator. These data therefore offer limited descriptive safety information and cannot establish comparative risk or causality.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Folinic Acid in Autism — NCT03771560.
- Registry record last updated 2019-12-03; status last verified 2019-11.
- Results first posted 2019-12-03.
- 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
NCT03771560, “Folinic Acid in Autism,” is listed as completed and sponsored by the University of California, San Francisco. The registry identifies Phase 2 and Phase 3, enrollment of 18, and a single-group, open-label design. Folinic acid was to be given twice daily in pill form at a weight-based dose. The recorded start date is 2018-02-15, and the primary completion date is 2018-06-30.
The primary outcome is mean parent-reported ABC change from baseline to Week 12, with a 95% confidence interval specified. The ABC consists of 58 questions, has a total possible score range of 0 - 174, and lower scores indicate better performance. Named secondary outcomes are SRS parent report, SRS teacher report, and PedsQL parent report.
The registry does not report the numerical primary outcome result, its confidence interval, or the primary analysis count. Safety information lists 0 serious adverse events, 5 affected by other adverse events, and 0 deaths, with 12 at risk in each adverse-event category. Because the study has no control group and the outcome estimates are not reported in the registry record, the record describes the planned measurement and limited safety counts but does not permit assessment of the primary outcome’s magnitude or precision.