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 Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON) (NCT01267422), a na na study. The primary outcome is The Best Corrected Visual Acuity(BCVA).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01267422 |
| Phase | NA |
| Condition | Leber Hereditary Optic Neuropathy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bin Li |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with Leber hereditary optic neuropathy (LHON) and the 11778 LHON mutation. The registry record lists enrollment of 9 participants. Further eligibility details, such as age ranges or disease duration, are not reported in the registry record.
Intervention
The intervention was rAAV2-ND4, described in the official title as a single intravitreal injection. The arm description also identifies an injection. Details about dose, administration procedures, or other care are not reported in the registry record.
Comparator
This was a single-group study, with no control arm described. Allocation is listed as NA and masking as none. The record therefore does not describe a randomized comparison with a control treatment or untreated group.
Primary question
The primary outcome was best corrected visual acuity (BCVA), measured in logMAR, with assessment up to 3 years. The stated analytic question was whether BCVA changed between the before-treatment and after-treatment measurements. Lower logMAR represents a better outcome. Numerical measurements and the result of the comparison are not reported in the registry record.
3. Trial Design
The registry record describes a completed, single-group study of rAAV2-ND4 for LHON. Enrollment was 9. The condition is listed as Leber Hereditary Optic Neuropathy, and the brief summary specifies treatment of LHON with the 11778 mutation. The official title describes a single intravitreal injection. The intervention arm is named rAAV2-ND4 and its description is “injection.”
There is no randomized allocation or like-for-like control comparison described: allocation is NA and the study model is single group. Masking is listed as none. The phase is listed as NA. These registry entries do not establish what procedures or oversight may have been used beyond the details recorded. Further protocol information, including eligibility criteria, dose, recruitment approach, and treatment administration details, is not reported in the registry record.
The study start is recorded as 2011-04, primary completion as 2015-11, and status as completed. The primary outcome was BCVA in logMAR, assessed up to 3 years. Secondary outcomes included intraocular pressure, neutralizing antibody assay, average retinal nerve fiber layer thickness measured by optical coherence tomography, and computerized visual field measures called mean deviation and visual field index. The record lists 7 outcome measures, but does not provide numerical results for the primary endpoint in the information reported.
Because this is a single-group, before-and-after design, the stated comparison concerns measurements from the same participants over time, rather than outcomes between independent treatment groups. Without a separate control group, changes over time cannot be distinguished from other influences using a randomized between-group contrast. The registry record does not report further design details that would clarify how the study addressed such influences.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: All patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 36 months.
Intravitreal rAAV2-ND4 Injection
| Stage | Participants Receiving Treatment in Left Eye | Participants Receiving Treatment in Right Eye |
|---|---|---|
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
Safety and Efficacy Study
| Stage | Participants Receiving Treatment in Left Eye | Participants Receiving Treatment in Right Eye |
|---|---|---|
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The data are expressed as mean±standard error. Comparisons before and after treatment of the BCVA were analyzed using the paired t-test.A probability (P) value of less than 0.05 was considered statistically significant.Lower logMAR represents a better outcome.
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 | All Study Participants |
|---|---|---|
| Participants analysed | 9 | |
| Age, Continuous | years | 15 (7.65 to 30.79) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 9 |
| 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 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: China | participants | 9 |
6. Primary Endpoint
The registry lists the primary outcome as The Best Corrected Visual Acuity(BCVA), measured over Up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | logMAR |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was best corrected visual acuity (BCVA), expressed in logMAR, with a timeframe of up to 3 years. Visual acuity measures how clearly a person can see under a defined testing condition; “best corrected” indicates assessment with the best available optical correction used for the test. The record states that lower logMAR represents a better outcome, so interpretation of change depends on the direction of the scale as well as the size and precision of any estimate.
BCVA is used as an outcome because it gives a quantitative measure of visual function that can be compared across assessments. In this study, the stated analysis compared measurements before and after treatment. The registry record says the data are expressed as mean±standard error and that a paired t-test was used. A paired approach is intended for measurements linked within the same participant, rather than treating the before-treatment and after-treatment values as unrelated groups.
The registry record does not include the numerical BCVA means, standard errors, change estimate, confidence interval, or p-value. It therefore does not allow the magnitude, direction, or precision of the observed change to be described. The endpoint title and analytic description identify what was intended to be measured and compared, but they are not results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a before-and-after comparison of BCVA in a single group, using logMAR measurements and a paired t-test. It states that lower logMAR represents a better outcome and that a probability value below 0.05 was considered statistically significant. However, numerical BCVA results are not reported in the registry record. There is no posted mean, standard error, paired change estimate, confidence interval, or p-value with which to assess the outcome.
That absence limits interpretation in several ways. The direction of any observed change cannot be established from the recorded information. Its magnitude cannot be evaluated, and its precision cannot be described. A statement of the planned significance threshold does not show whether the observed comparison met that threshold. Nor does the endpoint definition establish that a change occurred.
Even if a before-and-after difference were reported, its interpretation would require attention to the design. A single group has no concurrent control group to show what might have happened over the same period without the intervention. Changes could reflect the course of the condition, measurement variability, other care, or other factors; the registry record does not report information that would establish their role. A paired analysis can account for the fact that observations come from the same participants, but it does not by itself resolve these broader design limitations.
The record reports enrollment of 9, but does not provide the number with evaluable BCVA measurements at each assessment or explain whether all enrolled participants contributed to the primary analysis. It also does not report missing-data handling or analysis populations. Consequently, it is not possible to assess whether the analysis included all enrolled participants, whether follow-up was complete, or how exclusions or incomplete observations may have affected the estimate.
The record lists 7 outcome measures and no analysis entries. That does not establish which outcomes were analyzed, which results were prespecified, or how multiple comparisons were handled. The registry description alone is therefore not enough to assess selective reporting or multiplicity. Overall, the posted information describes a planned endpoint and method, but not a numerical efficacy result. No conclusion about the size or statistical significance of a BCVA change can be drawn from the reported record.
9. Statistical Methods Explained
The registry record describes BCVA as a continuous measure, expressed in logMAR, and reports that values were summarized as mean±standard error. It states that before-and-after comparisons were analyzed with a paired t-test and that a probability value below 0.05 was considered statistically significant. Those details describe the stated method, but the numerical results needed to interpret its application are not reported in the registry record.
What does a paired t-test address?
In general, a paired t-test analyzes differences between linked measurements, such as a participant’s measurement before treatment and that same participant’s measurement after treatment. It uses the within-person differences rather than treating each assessment as if it came from unrelated people. This can be appropriate when the study question concerns change within participants and paired observations are available.
In general, the test relies on assumptions about the distribution of those paired differences. The registry record does not report diagnostic checks, alternative analyses, or details about the distribution of observed differences. The name of the test alone does not establish whether its assumptions were evaluated. The record also does not report the number of paired observations used in the analysis, so the analysis set cannot be confirmed from the information recorded.
How should mean and standard error be read?
A mean describes the average value in the analyzed observations. Standard error describes the precision of an estimated mean, rather than the spread of individual participants’ measurements. In general, a standard error is used to quantify uncertainty in an estimate; it is not interchangeable with a standard deviation, which describes variability among observations. The record specifies mean±standard error, but does not report the actual BCVA means or standard errors. It is therefore not possible to describe either the average values or their precision.
For a before-and-after analysis, the estimate of interest is usually the average paired change. In general, that change should be interpreted with its uncertainty, such as through a confidence interval, which gives a range of values compatible with the data under the analysis assumptions. The registry record does not report a paired change estimate or confidence interval. Neither can be reconstructed from the available description.
What does the stated significance threshold mean?
The record states that a probability value below 0.05 was considered statistically significant. In general, a p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It does not measure the probability that a treatment works, the size of an effect, or the clinical importance of a change. A threshold is a decision convention; it does not substitute for an estimate and its uncertainty.
No p-value is reported for the BCVA comparison. It is therefore not possible to determine whether the stated threshold was met. Even when a p-value is available, a confidence interval and the underlying effect estimate are useful for understanding precision and the range of changes consistent with the data. Those quantities are not reported in the registry record.
Why does over-dispersion matter in general?
Over-dispersion is a general concern for some statistical models when observed variability is greater than the model assumes. It can make uncertainty estimates too small if the model does not account for the extra variability. The primary endpoint is described as continuous and analyzed with a paired t-test; the registry record does not report an over-dispersion assessment or a model for count data. This concept should not be mistaken for a reported feature of this study.
How does the planning illustration relate to the study?
The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also state that the effect to detect is a specified fraction of the observed effect. The illustration is distinct from the study’s single-group design and is not evidence that the study itself had two randomized arms. Sample-size illustrations are planning tools, not observed power, and cannot establish the precision of the actual result. Since the numerical BCVA effect is not reported in the registry record, the reported description does not enable an independent appraisal of that effect or its use in planning.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 7 outcome measures, including BCVA as the primary outcome and several secondary outcomes: intraocular pressure, neutralizing antibody assay, retinal nerve fiber layer thickness by optical coherence tomography, and computerized visual field measures. It reports no analysis entries. The record does not describe a multiplicity procedure, a hierarchy of hypotheses, or how the interpretation of results across outcomes was to be managed. It is therefore not possible to determine whether or how the possibility of chance findings across multiple outcomes was addressed.
Missing-data methods and analysis populations are also not reported in the registry record. The record gives enrollment of 9, but does not state how many participants had measurements at each follow-up, how incomplete assessments were handled, or whether the primary analysis included all enrolled participants. It does not describe imputation, exclusion rules, sensitivity analyses, or a definition of an evaluable participant.
These omissions matter because a before-and-after analysis depends on paired observations. If a participant lacks a measurement at either assessment, the record does not explain whether that participant was excluded from the paired comparison or handled another way. Without participant-level counts and an analysis description, the completeness of the endpoint data and the effect of missing observations cannot be assessed.
The absence of these details does not establish that multiplicity or missingness was mishandled. It means the registry record does not provide enough information to evaluate those issues. Numerical outcome estimates, analysis populations, and missing-data procedures 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 |
|---|---|---|---|
| Short-term Affects | 0 | 9 | 0.0% |
| Long-term Affects | 0 | 9 | 0.0% |
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 |
|---|---|
| Short-term Affects | 0 of 9 |
| Long-term Affects | 0 of 9 |
The registry record lists separate short-term and long-term adverse-event groups. For each group, 9 participants were at risk for serious adverse events and 0 were recorded as affected. For other adverse events, 9 participants were at risk and 0 were recorded as affected. These figures describe the participant counts entered in the registry record for the listed categories.
The death entries are null, so deaths are not reported in the registry record; a null entry should not be read as a count of zero. The record does not list serious adverse-event terms. It also does not give further detail about how adverse events were defined, how long the short-term and long-term periods lasted, how events were collected, or whether every participant completed safety follow-up.
Zero affected participants in the recorded categories is not proof that no adverse events occurred under any definition or beyond the reported follow-up. It is a registry count, not a complete description of event types, timing, severity, or attribution. With enrollment of 9, the safety entries should be read in the context of the small study and the limitations of the recorded information. They do not establish the frequency of events in a broader population or settle the safety profile of the intervention.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed single-group study evaluated rAAV2-ND4 in people with LHON associated with the 11778 mutation, with BCVA in logMAR named as the primary outcome. The record describes an intended before-and-after comparison and identifies a paired t-test as the analysis. It also states that lower logMAR represents a better outcome. These details clarify the study question and the direction of the measurement scale.
What the registry record does not establish is the numerical BCVA outcome. No mean, standard error, paired change, confidence interval, or p-value is reported. The direction and size of any measured change therefore cannot be stated, and the reported information does not show whether the stated significance threshold was met. The endpoint description is not a result, and the absence of numerical results should not be interpreted as evidence of either benefit or no benefit.
The design also limits what a change could mean. Because the study is single group and has no control arm described, a before-and-after difference would not by itself separate a treatment-associated change from other changes over time. The registry record does not report enough information to assess the influence of the condition’s course, measurement variability, other care, or other factors.
The safety entries record zero affected participants for serious and other adverse events in both the short-term and long-term categories, with 9 at risk in each category. These entries should be interpreted as recorded counts, not as proof of the absence of all possible harms. Deaths are not reported in the registry record.
Overall, the registry record supports a description of the study’s design, endpoint, planned analysis, and selected safety counts. It does not support a quantitative conclusion about BCVA change, statistical significance, or the intervention’s effect. Missing results and analysis details leave uncertainty about the magnitude, precision, completeness, and robustness of the findings.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a clearly named outcome and a fully interpretable result. BCVA is identified as the primary endpoint, with a stated scale, direction, assessment timeframe, summary measure, comparison, and significance threshold. Those elements help a reader understand what the investigators intended to measure and how they described the planned comparison.
At the same time, the registry record does not report the numerical outcome or an analysis entry. Without the mean values, paired change, uncertainty estimate, and p-value, the stated method cannot be connected to a result. This illustrates why an endpoint definition and a statistical test are not substitutes for effect estimates and precision. A reader needs the estimated change and its uncertainty to judge what range of outcomes is compatible with the data.
The single-group design also highlights a basic distinction in clinical-trial interpretation. A paired analysis can use the relationship between a participant’s repeated measurements, but it does not create a concurrent control comparison. Statistical adjustment for paired observations and causal attribution are separate questions. The design described in the record does not provide a randomized control contrast.
The record’s safety counts show another reporting issue: event counts must be understood alongside their observation periods, definitions, and follow-up completeness. The entries give participant counts at risk and affected, but do not report the details needed to characterize events fully. Taken together, the study record is useful for understanding the intended measurement and broad design while also showing how unreported estimates and analysis details constrain statistical interpretation.
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 primary limitation for interpreting this study record is that numerical BCVA results are not reported in the registry record. Although BCVA is named as the primary outcome and a paired t-test is described, the record does not give the means, standard errors, paired change, confidence interval, or p-value. The direction, magnitude, and precision of the primary outcome therefore cannot be assessed.
The study is described as single group, with allocation listed as NA and masking as none. No concurrent comparator is described. This means that even a reported before-and-after change would have limited ability to distinguish an intervention-associated change from time trends or other influences. The registry record does not report further design information that could clarify how these possibilities were addressed.
Enrollment was 9, but the number contributing paired BCVA measurements is not reported in the registry record. Follow-up completeness, missing-data handling, analysis populations, and reasons for any unavailable measurements are also not reported. These gaps prevent assessment of the endpoint analysis set and the possible effect of incomplete data.
The record lists 7 outcome measures but reports no analysis entries. It does not describe multiplicity handling, sensitivity analyses, or additional model checks. The safety information reports zero affected participants in the listed serious and other adverse-event categories, but definitions, observation-period details, and complete follow-up information are not reported. Death entries are not reported in the registry record. These limitations concern the available record and do not establish what may have been documented elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON) — NCT01267422.
- Registry record last updated 2018-01-31; status last verified 2018-01.
- Results first posted 2016-05-02.
- 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, single-group study of rAAV2-ND4 for LHON associated with the 11778 mutation. Enrollment was 9, and the official title describes a single intravitreal injection. The primary outcome was BCVA in logMAR, assessed up to 3 years. Lower logMAR represents a better outcome. The stated analysis used a paired t-test and considered a probability value below 0.05 statistically significant.
The record lists 7 outcome measures and no analysis entries. Numerical BCVA results and details about missing data and analysis populations are not reported in the registry record. Safety entries list 0 affected participants for serious and other adverse events in both the short-term and long-term categories, with 9 at risk in each; deaths are not reported in the registry record. The single-group design does not include a control comparison in the recorded information.