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 Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON) (NCT02796274), a registered phase not stated study. The primary outcome is In Eyes With VA Assessment Made ≤1 Year After Onset of Symptoms: Proportion of Eyes With Clinically Relevant Recovery (CRR) of VA (Measured by Change in ETDRS Letters) From Baseline (BL) or in Which BL VA Better Than 1.0 logMAR Was Maintained at 12 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02796274 |
| Phase | Phase not stated |
| Condition | Leber's Hereditary Optic Neuropathy (LHON) |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 219 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Santhera Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with LHON and a genetically confirmed diagnosis were the intended population. The record states that data were obtained for 219 patients and 438 eyes; 96 eyes had a visual acuity assessment made ≤1 year after symptom onset.
Intervention
There was no assigned treatment intervention. The study was a historical case record survey collecting visual acuity data to describe the clinical course and visual acuity outcomes in LHON.
Comparator
No concurrent comparator group or randomized treatment comparison is described. The survey was intended to generate data that could serve as a comparator for the open-label study SNT-IV-006.
Primary question
Among eyes assessed within the specified period after symptom onset, what proportion had clinically relevant visual acuity recovery, or maintained baseline visual acuity better than 1.0 logMAR, at 12 months?
This is a descriptive natural-history question, not a test of whether one treatment is better than another. The endpoint description defines clinically relevant recovery as improvement from off-chart ETDRS to 5 letters on-chart, or an on-chart improvement of 10 letters. It also includes maintenance of baseline visual acuity better than 1.0 logMAR. The record does not report the number of eyes meeting either condition, an estimate of the proportion, or uncertainty around that estimate.
The study's stated purpose was to establish clinical course and visual acuity outcomes in genetically confirmed LHON. Its intended role as a comparator for a separate open-label study does not make this survey a controlled comparison: no treatment assignment, concurrent control arm, or direct treatment-effect estimate is reported in the registry record.
3. Trial Design
The registry classifies NCT02796274 as an “other” study and marks it completed. The study is titled “Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON)” and is sponsored by Santhera Pharmaceuticals. The recorded start is 2016-05 and the primary completion is 2018-03.
The design described is a historical survey of case records. Its purpose was to collect visual acuity data and describe natural history and visual acuity outcomes in patients with a genetically confirmed LHON diagnosis. The record states that information was obtained for 219 patients and 438 eyes. Of these, 96 eyes had a visual acuity assessment made ≤1 year after symptom onset, the population identified for the primary outcome.
This is not a randomized trial. The registry does not describe assigned treatment arms, allocation, blinding, or a concurrent control group. It therefore does not support a like-for-like comparison between treatments. The stated comparator purpose relates to a separate open-label study, SNT-IV-006; the survey itself is not described as an intervention study.
The primary outcome timeframe is 12 months. The record does not explain how historical records were located, which visits or measurements were eligible, how records were selected, or how visual acuity assessments were standardized across sources. Those procedures are not reported in the registry record. The precise observational design features beyond the historical case record survey label are likewise not reported in the registry record.
The registry lists one outcome measure and zero analyses. It provides an outcome definition and descriptive measurement fields, but no numerical findings for that outcome. The completed status indicates the study's registry status, not that results have been posted or that the stated outcome can be evaluated from this record.
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 | LHON Patients Case Record Cohort |
|---|---|
| STARTED | 219 |
| COMPLETED | 219 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Data from a total of 219 LHON patients and 438 eyes were obtained from this study, out of which 96 eyes had a VA assessment made ≤1 year after the onset of symptoms (primary outcome measure).
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: Visual Acuity (VA) at Baseline (logMAR)
| Characteristic | Unit | LHON Patients Case Record Cohort |
|---|---|---|
| Participants analysed | 219 | |
| Age, Categorical: <=18 years | Participants | 49 |
| Age, Categorical: Between 18 and 65 years | Participants | 169 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 26.0 (18.0 to 41.0) |
| Sex: Female, Male: Female | Participants | 44 |
| Sex: Female, Male: Male | Participants | 175 |
| Region of Enrollment: Netherlands | participants | 24 |
| Region of Enrollment: Belgium | participants | 30 |
| Region of Enrollment: Poland | participants | 40 |
| Region of Enrollment: Italy | participants | 20 |
| Region of Enrollment: United Kingdom | participants | 20 |
| Region of Enrollment: France | participants | 29 |
| Region of Enrollment: Germany | participants | 56 |
6. Primary Endpoint
The registry lists the primary outcome as In Eyes With VA Assessment Made ≤1 Year After Onset of Symptoms: Proportion of Eyes With Clinically Relevant Recovery (CRR) of VA (Measured by Change in ETDRS Letters) From Baseline (BL) or in Which BL VA Better Than 1.0 logMAR Was Maintained at 12 Months, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ETDRS letters |
| Endpoint classification | not reduced to a single comparison |
The primary outcome concerns eyes with visual acuity assessment made ≤1 year after symptom onset and evaluates status at 12 months. Its title describes the proportion of eyes with clinically relevant recovery of visual acuity from baseline, or eyes in which baseline visual acuity better than 1.0 logMAR was maintained. The definition of clinically relevant recovery is an improvement from off-chart ETDRS to 5 letters on-chart, or an on-chart improvement of 10 letters.
Visual acuity measured in ETDRS letters provides a way to describe change in ability to read letters on a standardized chart. The recovery definition distinguishes a change from off-chart to an on-chart measurement from an improvement among eyes already measured on-chart. The maintenance condition addresses a different trajectory: retaining a specified baseline visual acuity status at the follow-up assessment rather than meeting the recovery definition.
These are clinically interpretable categories for describing visual course, but the registry does not report how many eyes met each category or whether they were combined in the final endpoint calculation. There is also a mismatch in the record's fields: the outcome title refers to a proportion, while the measurement parameter is MEDIAN, the unit is ETDRS letters, and dispersion is listed as Inter-Quartile Range. The record does not clarify whether the intended reported result was a proportion, a distribution of letter changes, or both. The endpoint's value and precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the context and definition for the primary outcome, but does not give an analyzed result. It reports that 219 patients and 438 eyes contributed data, and that 96 eyes met the stated timing condition for the primary outcome. Those counts describe the records included in the study and the identified outcome population; they do not establish how many eyes experienced recovery or maintained baseline visual acuity.
The outcome is framed as a proportion of eyes, with a 12-month assessment and specified visual acuity criteria. However, the registry also labels the parameter as MEDIAN, gives ETDRS letters as the unit, and lists Inter-Quartile Range as dispersion. Because the record does not resolve this difference in presentation, a reader cannot determine the exact statistical estimand or which numerical summary was intended to carry the primary conclusion. No estimate, interval, test statistic, or p-value is reported in the registry record.
The absence of a reported analysis is particularly important for interpreting the completed status. Completion is a status field; it is not itself evidence about the frequency or course of recovery. The record lists zero analyses. Consequently, the registry entry does not allow an assessment of the magnitude, variability, or precision of visual acuity outcomes. It also does not state whether the intended endpoint was evaluated in all 96 eyes, whether any assessments were unavailable at 12 months, or how incomplete records were treated.
The survey is observational and based on historical case records. Its purpose is to describe the natural history of visual acuity in LHON and generate comparator data for a separate open-label study. It is not a randomized comparison, and no treatment contrast is reported. Any use as an external comparator would require careful consideration of whether the patients, measurements, timing, eligibility criteria, and outcome definitions are comparable across the survey and the separate study. The registry record does not report methods for making or validating such a comparison.
The record's summary population is expressed at both the patient and eye levels. Both eyes from a patient may contribute data; in general, measurements from two eyes belonging to the same person may be statistically related. How that dependence was handled in an analysis is not reported in the registry record. This matters because treating correlated eyes as independent observations can make statistical uncertainty appear smaller than it is. There is no reported uncertainty estimate to assess in this case.
Accordingly, the posted registry information supports a description of study purpose, sample counts, and endpoint definition, but not a conclusion about observed visual acuity recovery. The direction, frequency, and precision of the outcome are not reported in the registry record. No claim about treatment benefit or lack of benefit follows from these missing results.
9. Statistical Methods Explained
The available record describes the study and outcome but contains no analysis results. The methods below explain the statistical concepts relevant to the fields recorded, while distinguishing those general concepts from procedures actually documented for this survey.
What does a proportion measure?
In general, a proportion expresses how many members of a defined group meet a specified condition relative to the group eligible for that assessment. For this endpoint, the title identifies eyes assessed within the stated period after onset and classifies them according to recovery or maintenance criteria at 12 months. To interpret a proportion, a reader needs a clear numerator, denominator, and rule for handling eyes without a 12-month measurement. The registry record identifies 96 eyes in the primary outcome population, but does not report the number meeting the criteria, the final denominator used, or how missing assessments were handled.
The outcome title says “proportion of eyes,” while the measurement fields identify a median in ETDRS letters with an interquartile range. These summaries answer different questions. A proportion would describe the share meeting a categorical definition. A median and interquartile range would describe the distribution of a numerical measurement, such as letter changes. The record does not clarify whether the fields represent separate aspects of the endpoint or an inconsistency in how the outcome was entered. No interpretation should silently substitute one summary for the other.
What do the median and interquartile range describe?
In general, a median is the middle value in an ordered set of observations. It can describe a typical value without being as sensitive to extreme observations as a mean. The interquartile range describes the spread of the middle half of a distribution. These summaries are often useful when data are skewed or include values that make a mean and standard deviation less representative. Their usefulness depends on knowing what was measured, the analysis population, and how observations were obtained. Here, the registry lists ETDRS letters as the unit but does not explain precisely which letter quantity would be summarized or give the median or interquartile range.
Dispersion and uncertainty are not interchangeable. An interquartile range describes variability among observations; it is not, by itself, a confidence interval for the estimated median. In general, a confidence interval gives a range of values compatible with an estimate under the analysis assumptions, and reflects uncertainty in the estimate. No confidence interval or other uncertainty measure for the primary outcome is reported in the registry record.
Why does the patient and eye level matter?
The record reports 219 patients and 438 eyes, so the data are represented at more than one level. In general, when both eyes from one person contribute measurements, those measurements may be correlated because they share patient-level characteristics and history. Analyses that account for this structure can differ in their uncertainty from analyses that treat every eye as fully independent. The registry record does not report whether one or both eyes were included in each analysis, whether a patient-level method was used, or whether correlation between eyes was addressed. Because no analysis is posted, there is no method to evaluate on this point.
Historical case records can also differ in completeness and timing. In general, variation in measurement schedules, assessment practices, and documentation can affect comparability of observations. The record identifies a timing condition for the primary population, but selection rules, measurement standardization, and handling of visits outside the target timing are not reported in the registry record.
What do the planning illustrations mean?
The registry's statistical planning assumptions describe illustrations computed from an observed effect, not the design justification for this survey. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events; other planning quantities are participants per arm. These are planning illustrations, not observed power and not observed study findings.
Those assumptions describe a hypothetical two-arm comparison, whereas the registry describes a historical survey with no randomized arms or like-for-like control comparison. The observed effect used for the illustrations and the numerical planning results are not reported in the registry record. Thus the illustrations cannot be interpreted as a sample-size justification for the survey, nor as evidence that its primary outcome was sufficiently precise. In general, a planning calculation depends on its assumptions and target effect; it cannot substitute for reporting the outcome estimate and its uncertainty.
Finally, the registry lists zero analyses. This means the statistical methods used to analyze the primary outcome, if any, are not described in the record. The information needed to assess model choice, adjustment, uncertainty calculation, sensitivity analyses, or a prespecified analysis plan is not reported in the registry record. General methodological explanations do not fill those gaps or establish what the investigators actually did.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and zero analyses. It identifies a primary outcome but does not report an analysis plan, a hierarchy of outcomes, or a procedure for addressing multiplicity. Whether additional outcomes were collected outside the registry entry, or whether multiple subgroup or timepoint analyses were considered, is not reported in the registry record. Without an analysis report, the effect of any multiplicity strategy on interpretation cannot be assessed.
The primary outcome population is described as 96 eyes with a visual acuity assessment made ≤1 year after symptom onset, out of data collected for 219 patients and 438 eyes. The record does not say how many of those eyes had an evaluable 12-month assessment, whether any data were missing, or whether the 96 eyes were all included in the final analysis. It does not report a missing-data definition, imputation method, sensitivity analysis, or reason for absent measurements. Missingness should not be inferred from the difference between the overall collection and primary population counts, because the latter is defined by assessment timing.
The registry also does not define analysis populations beyond the stated primary outcome population. Eligibility and selection rules for historical records, the handling of repeated assessments, and the unit of analysis are not reported in the registry record. Nor is it stated whether both eyes from one participant could contribute to the primary analysis or how their potential dependence was handled. These gaps limit assessment of both the representativeness of the analyzed eyes and the precision of any result.
11. What the Result Does, and Does Not, Mean
The registry record establishes that a historical survey was conducted to collect visual acuity information in LHON and that its primary outcome concerned recovery or maintenance at 12 months. It gives counts for the data collection and the eyes identified for the primary outcome. These details describe the intended scope, but do not reveal the observed frequency or distribution of visual acuity outcomes.
No numerical primary outcome result is reported in the registry record. Therefore, the record does not show how many eyes met the clinically relevant recovery definition, how many maintained the specified baseline visual acuity status, or how precise either estimate was. The apparent completion of the study does not fill this reporting gap. The outcome title and measurement fields also describe different kinds of summaries, and their relationship is not clarified.
The data were intended to characterize natural history and potentially serve as a comparator for a separate open-label study. A historical survey can provide context about outcomes recorded outside a randomized comparison, but comparisons across studies can be affected by differences in patient selection, record completeness, timing, and measurement practices. The registry record does not report a method for controlling these differences or a direct comparison with SNT-IV-006.
These registry entries do not establish that a treatment is effective or ineffective, and they do not support medical decisions. They support only a description of the registered purpose, population counts, endpoint definition, and the absence of posted analysis results. Any stronger interpretation would require outcome data and methods not reported in the registry record.
12. Why This Trial Matters Statistically
This record illustrates an important distinction between registering an outcome and reporting an outcome. The registry describes a clinically meaningful visual acuity question, defines recovery using ETDRS-letter criteria, and identifies the timepoint and eye population. Those details help readers understand what investigators intended to measure. Without an estimate and its uncertainty, however, the central statistical question remains unanswered in the registry.
The survey also has a potentially useful role as a source of natural-history information and as a proposed comparator for a separate open-label study. Such a role depends on transparent descriptions of how historical records were selected, how measurements were aligned, and how differences between populations are considered. Those details are not reported in the registry record. The distinction between a descriptive cohort and a randomized comparison is essential: the survey is not a treatment-effect comparison merely because it may serve as external context.
There is also a reporting lesson in the difference between the endpoint title and the statistical measurement fields. A proportion, a median, and an interquartile range communicate different features of data. Clear specification of the estimand and its summary is needed for readers to know what result would answer the clinical question. The record does not resolve this distinction or provide an analysis.
Finally, the patient and eye counts make the analysis unit relevant. Statistical methods need to reflect the structure of observations when both eyes from a participant may be included. Since the registry gives no methods or findings, this cannot be evaluated. The study therefore matters statistically as an example of why outcome definitions, analysis populations, missing-data handling, and results with precision all contribute to an interpretable natural-history record.
13. 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 of the registry record for statistical interpretation is the absence of reported outcome results. Although the study is marked completed and includes a primary outcome definition, it lists zero analyses. There is no estimate, distribution, uncertainty measure, or analysis report from which to assess the observed visual acuity course.
The endpoint fields are not fully aligned: the title describes a proportion, while the parameter is MEDIAN, the unit is ETDRS letters, and dispersion is listed as Inter-Quartile Range. The record does not explain how these descriptions relate or specify which summary was intended to answer the primary question. The recovery and maintenance criteria are stated, but the number meeting either criterion and the exact calculation of the outcome are not reported in the registry record.
The study uses historical case records, but the record does not describe case identification, selection, measurement standardization, record completeness, or handling of repeated assessments. These omissions prevent assessment of how representative the assembled records are or how comparable their measurements may be. The primary population is identified as 96 eyes assessed within the stated period after symptom onset, but the final 12-month analysis denominator and missing-data approach are not reported.
Counts are given for both patients and eyes, but the analysis unit and handling of possible within-patient correlation are not reported in the registry record. No randomized allocation or concurrent control is described, and the proposed comparator role for a separate study does not resolve potential differences between studies. Adverse event fields show zero participants at risk or affected and no serious terms listed; the record does not explain adverse-event ascertainment, so these entries cannot establish that no events occurred.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON) — NCT02796274.
- Registry record last updated 2020-01-30; status last verified 2020-01.
- Results first posted 2020-01-30.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
17. Record Summary
NCT02796274 is a completed historical case record survey sponsored by Santhera Pharmaceuticals. The recorded study dates are 2016-05 to primary completion in 2018-03. Its purpose was to describe natural history and visual acuity outcomes in genetically confirmed LHON and to generate data for use as a comparator for the open-label study SNT-IV-006.
The record reports data for 219 patients and 438 eyes, including 96 eyes with a visual acuity assessment made ≤1 year after symptom onset for the primary outcome. The outcome concerns recovery or maintenance of visual acuity at 12 months, but the record lists zero analyses and does not report numerical results. The endpoint's proportion wording and median/IQR measurement fields are not reconciled. No treatment comparison, missing-data approach, or analysis methods are reported in the registry record.