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 EvAluating Genotypes While Using Lucentis 2 (NCT01464723), a na phase 4 study. The primary outcome is To Determine the Genotype at VEGF and HTRA1 SNPs of Patients Gaining ≥ 0 Letters of Visual Acuity in Response to Ranibizumab Treatment Over a 4 Month Period..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01464723 |
| Phase | Phase 4 |
| Condition | Age-Related Macular Degeneration |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 66 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Diego |
| Results posted | Yes |
2. Clinical Question
The study was intended to examine whether response to ranibizumab (Lucentis) for exudative age-related macular degeneration was associated with variation in VEGF and HTRA1. The primary question focused on the genotypes at single-nucleotide polymorphisms (SNPs) in those genes among patients whose visual acuity gained at least 0 letters over a 4 month period. That question concerns the characteristics of people meeting a specified visual-acuity response criterion; it is not, by itself, a comparison of ranibizumab with an untreated or alternative-treatment group.
The registry also lists related aims: describing genotypes among people with visual-acuity change below 0 letters at 4, 6 and 12 months, examining whether change in retinal thickness is correlated with genotype, and determining the mean number of injections per year. These aims indicate interest in both visual acuity and retinal thickness as clinical measures, alongside treatment burden. The record does not report the genotype findings, visual-acuity results, retinal-thickness results, or injection counts.
Population
People with age-related macular degeneration; the study summary describes exudative disease. The record lists enrollment of 66.
Intervention
Ranibizumab (Lucentis), described as open-label intravitreal treatment. The regimen specified monthly 0.5 mg treatment for the first 4 months, then treatment as needed for a total duration of 12 months.
Comparator
No randomized comparator is described. The study is listed as single-group, with allocation recorded as NA.
Primary question
Which VEGF and HTRA1 SNP genotypes were present among patients gaining at least 0 letters of visual acuity over 4 months of ranibizumab treatment?
Because the registry says that the study data could not be found, the intended question remains unanswered in the posted record. The association between genotype and response cannot be estimated from the information available in the registry record.
3. Trial Design
This is a Phase 4, completed, single-group study sponsored by the University of California, San Diego. The record gives a start date of 2008-05 and a primary completion date of 2011-12. Enrollment is listed as 66. These details describe the registered study, but do not establish how many participants contributed data to any particular outcome.
The study is listed as open-label, with masking recorded as none. Its design is single-group and allocation is listed as NA. Therefore, the registry does not describe a randomized comparison between ranibizumab and a control treatment. The record's own design note cautions that the arms are not a like-for-like control comparison. The listed regimen was intravitreal ranibizumab (Lucentis), at 0.5 mg monthly for the first 4 months and then as needed, for a total duration of 12 months.
The study sought to relate genetic variation in VEGF and HTRA1 to treatment response in age-related macular degeneration. Its primary outcome title specifies genotypes among patients gaining at least 0 letters of visual acuity over a 4 month period. The registry lists a timeframe of 5 years for that outcome. The record does not explain the relationship between that timeframe and the 4 month response period, so the two descriptions should be kept distinct rather than reconciled by assumption.
The registry lists 4 outcome measures and no analysis entries. It also states that the principal investigator had left the institution, efforts to contact the investigator or study team were unsuccessful because all team members had left the University, and attempts to locate the study data were unsuccessful. Thus, the record contains design and aim information but not the results needed to evaluate the intended genotype-response question. Details such as the planned sample-size justification, the statistical plan, and interim analyses are not reported in the registry 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.
Before assignment: The Principal Investigator has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful due to all study team members having left the University. No study data are available, attempts were made to find the data but were unsuccessful.
Overall Study
| Stage | Lucentis |
|---|---|
| STARTED | 0 |
| COMPLETED | 0 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The Principal Investigator has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful due to all study team members having left the University. No study data are available, attempts were made to find the data but were unsuccessful.
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: The Principal Investigator has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful due to all study team members having left the University. No study data are available, attempts were made to find the data but were unsuccessful.
| Characteristic | Unit | Lucentis |
|---|---|---|
| Participants analysed | 0 | |
| Sex: Female, Male: Female | — | |
| Sex: Female, Male: Male | — |
6. Primary Endpoint
The registry lists the primary outcome as To Determine the Genotype at VEGF and HTRA1 SNPs of Patients Gaining ≥ 0 Letters of Visual Acuity in Response to Ranibizumab Treatment Over a 4 Month Period., measured over 5 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is described as determining the genotypes at VEGF and HTRA1 SNPs among patients whose visual acuity gained at least 0 letters in response to ranibizumab over a 4 month period. In plain terms, the endpoint concerns which genetic variants occur in the group meeting that visual-acuity criterion. It does not specify a numerical treatment effect, and the registry does not report genotype counts or results.
Visual acuity is used in the study description as a measure of response. Defining a responder group by a threshold can make a genetic description easier to frame, but it also means the interpretation depends on the threshold and the way visual-acuity change is measured. The posted record does not provide the measurement procedures, the genotype assay details, or the operational definition of the time point beyond the wording in the outcome title. Those details are not reported in the registry record.
The outcome's registry timeframe is listed as 5 years, while its title refers to a 4 month treatment-response period. The record does not explain this difference. Most importantly, the registry reports that study data were unavailable after attempts to locate them. Without participant-level or summary outcome data, it is not possible to describe which genotypes were observed, quantify their frequency, or assess any relationship between genotype and visual-acuity response.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study's intent and design, but not a conclusion about its primary scientific question. It identifies a single-group, open-label ranibizumab study investigating whether VEGF and HTRA1 genetic variation was associated with visual-acuity response in age-related macular degeneration. It does not provide genotype results, response counts, effect estimates, confidence intervals, or statistical tests. The primary outcome data could not be located, according to the record's explanation.
Accordingly, no direction or magnitude of an association can be established from the posted results. It would not be appropriate to say that a genotype predicted response, that genotypes had no relationship to response, or that the treatment changed visual acuity. The lack of available findings is not evidence of no association or no treatment effect. It means that the record does not permit an estimate.
The design also limits what this study could establish about treatment. A single-group study without a randomized comparator cannot, from a before-and-after pattern alone, separate treatment-related change from other explanations such as the natural course of disease, measurement variability, or other influences. This is a general limitation of uncontrolled comparisons. Here, even descriptive change estimates are unavailable, so the registry record cannot show the course of visual acuity or retinal thickness during follow-up.
The registry lists secondary aims concerning visual-acuity change below 0 letters at 4, 6 and 12 months, correlation between retinal-thickness change and genotype, and mean injections per year. No results for these aims are reported in the registry record. The number of outcome measures listed does not supply evidence about their results, and the absence of analysis entries means there is no posted analysis to interpret for these outcomes.
The adverse-event information also does not establish that adverse events were absent. The listed Lucentis group has 0 participants at risk for serious events and 0 at risk for other events, with 0 affected in each category and 0 deaths. With no participants recorded as at risk in those fields, the zeros cannot be read as observed safety rates or as proof of no events. The registry record does not provide an interpretable safety denominator or further adverse-event detail.
Any precision statements would ordinarily depend on estimates and their uncertainty. Since neither the primary results nor their statistical analysis are available, no confidence interval or p-value can be interpreted for the genetic-response question. The record therefore documents an intended investigation, not a result that supports or rules out a genotype-response association.
9. Statistical Methods Explained
The record gives the study's design labels and outcome aims, but it does not provide analysis results or a detailed statistical plan. The explanations below describe general statistical concepts relevant to interpreting this type of question; they are not claims about procedures that this study used.
What does the single-group design permit?
In general, a single-group study can describe outcomes observed among participants receiving an intervention and can explore whether participant characteristics vary with those outcomes. Without a concurrent randomized comparator, it cannot by itself establish what would have happened to the same participants under a different treatment or no treatment. This matters for interpretation of change over time: an observed change may reflect several influences, not solely the intervention. In this record, there are no posted outcome data even for a descriptive account, so the possible strengths and limitations of the observed results cannot be evaluated.
The study is identified as open-label, meaning the record does not describe masking. In general, awareness of treatment or study participation can affect outcome assessment or participant behavior, depending on the outcome and measurement process. The registry does not report whether visual-acuity assessors were masked, how visual acuity was measured, or how the genotypes were assessed. Those methodological details are not reported in the registry record and should not be inferred from the design label alone.
How should the responder threshold be understood?
The primary outcome defines a group by gaining at least 0 letters of visual acuity over a 4 month period, then asks which VEGF and HTRA1 SNP genotypes occur in that group. In general, threshold-based responder definitions turn a measured outcome into categories. This can make a question easier to communicate, but discards information about the degree of change within each category. People just on either side of the cutoff may have very similar measurements, while people within one category may have different amounts of change.
The registry does not report how many participants met the threshold, how many had each genotype, or whether the outcome was analyzed as a continuous measure as well. It also does not state how missing visual-acuity measurements or unobserved genotypes were handled. Without those details and the results, the balance of the groups and the precision of any association are unknown.
Why does uncertainty matter?
In general, a confidence interval describes a range of estimates compatible with the observed data under a statistical model and its assumptions. Its width conveys precision: wider intervals indicate less precise estimates, while narrower intervals indicate greater precision. A p-value, when reported, addresses compatibility of the observed data with a specified null model; it does not quantify the size or clinical importance of an association. Neither confidence intervals nor p-values are available for this primary outcome in the registry record. There is therefore no statistical uncertainty estimate to interpret.
For genotype-response analyses, the number of people in each genotype and response category is important. Sparse categories can yield unstable estimates and wide uncertainty. This is a general consideration, not a statement about the distribution in this study: the registry does not report genotype counts or category sizes. Likewise, the record does not identify a genetic model, such as how genotype categories might have been grouped, and the analysis approach is not reported in the registry record.
What do the sample-size conventions mean?
In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. It is not a study result and is not evidence that an achieved analysis had a particular probability of finding an effect. The registry's planning-illustration description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. It also distinguishes total event counts for time-to-event calculations from participants per arm for other calculations.
Those conventions do not describe this registered single-group design, which has no randomized two-arm comparison in the study description. The registry record does not report the trial's own sample-size justification, and it provides no outcome estimates with which to assess the planning illustration's assumptions. Any sample-size illustration should therefore be treated as planning information, not as observed power or as evidence about the study findings.
In general, over-dispersion is variability greater than expected under a chosen statistical model. Accounting for it can prevent uncertainty from being understated when observations vary more than the model assumes. The registry does not report whether over-dispersion is relevant to any analysis in this study, nor does it provide an analysis model to assess. It would be speculative to attribute a particular model or correction to the investigators.
What can be concluded from the analysis record?
The registry lists 4 outcome measures and 0 analysis entries. This means the posted record does not offer a statistical result for the outcomes described. It does not establish that no analyses were ever conducted; the record specifically explains that data could not be located after the principal investigator and study team members had left the institution. The distinction is important: absence of a posted analysis is not itself a null finding. In general, a reproducible interpretation would require outcome definitions, analysis populations, statistical models, missing-data handling, and estimates with measures of uncertainty. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record describes a primary genotype outcome and several additional aims involving visual-acuity change, retinal thickness, and injection frequency. When a study examines multiple outcomes, time points, genetic variants, or subgroup definitions, the number of statistical comparisons can affect how easily chance findings arise. In general, investigators may plan approaches to account for multiple testing, define a primary comparison in advance, or interpret exploratory results cautiously. The registry record does not report a multiplicity strategy, nor does it give a complete list of individual SNPs or analysis comparisons.
The registry's primary outcome title specifies visual-acuity response over a 4 month period, while the listed secondary visual-acuity aim refers to people with change below 0 letters at 4, 6 and 12 months. It also lists correlation of retinal-thickness change with genotype and mean injections per year. The record does not state how these outcomes were prioritized or whether their analyses were prespecified in a statistical analysis plan. That information is not reported in the registry record.
Analysis populations and missing-data procedures are also not described. The record does not say which participants had usable visual-acuity measurements, genotype data, retinal-thickness measurements, or follow-up information, nor how incomplete observations were handled. It reports that study data could not be located, so the available registry record cannot support an assessment of exclusions or missingness in the actual analyses. Enrollment of 66 should not be treated as the denominator for any specific endpoint without outcome-level data.
These gaps prevent assessment of whether reported findings, if any, might be sensitive to outcome selection, missing data, or analysis population. The record lists 0 analysis entries, and no outcome-specific estimates are available to evaluate.
11. What the Result Does, and Does Not, Mean
The record establishes that investigators planned a Phase 4 study of ranibizumab and genetic variation in age-related macular degeneration. Its primary question concerned VEGF and HTRA1 genotypes among patients meeting a visual-acuity response threshold. It also documents a single-group, open-label design and a treatment regimen. These registry entries describe the investigation's purpose and structure; they do not establish its findings.
The record does not show whether any genotype was more common among people meeting the visual-acuity threshold, whether genotype was associated with retinal-thickness change, how many injections participants required, or what visual-acuity changes were observed. No effect estimate or measure of precision is available. The appropriate interpretation is that the posted record cannot answer these questions, not that the study found no association or no change.
Even if outcome data had been available, a single-group design would not provide the same basis for causal comparison as a randomized controlled comparison. In general, an association between genotype and outcome within a treated group does not establish that the genotype specifically modifies the effect of treatment. Establishing treatment-effect modification ordinarily requires comparing treatment effects across genotype groups with an appropriate treatment comparison. The registry does not describe such a comparator.
The adverse-event entries should also be read cautiously. They record 0 at risk and 0 affected for serious and other events, and 0 deaths. Since the risk denominators are recorded as 0, these entries cannot establish that no adverse events occurred among treated participants. The registry does not provide additional safety data that would resolve this.
Thus, the record is useful for identifying the study question, planned treatment, design, and the reason results are unavailable. It cannot support a clinical conclusion about ranibizumab or a genetic marker. Those conclusions would require results and methods that are not reported in the registry record.
12. Why This Trial Matters Statistically
This study matters statistically because it illustrates the difference between a registered research question and evidence capable of answering that question. The record defines an intended relationship between genetic variation and visual-acuity response, but reports that the underlying data could not be located. Without the observations and analysis, there is no estimate to assess for magnitude, direction, or precision. A clearly stated question is not a substitute for an analyzable result.
It also highlights the distinction between association and treatment-effect modification. A study can examine whether outcomes differ by genotype among people receiving one treatment, but that pattern alone cannot determine whether the treatment effect itself differs by genotype. A comparator and an appropriate analysis would be needed to separate a treatment-specific interaction from other genotype-outcome associations. This is a general statistical distinction, especially relevant to claims that genetic markers identify differential treatment response.
The design information further clarifies the scope of possible inference. A single-group open-label study can be useful for describing treatment experience and generating hypotheses, but it does not have a randomized control comparison in the registry description. Here, no outcome findings are available even for those descriptive purposes. The distinction between a design's potential and the evidence actually posted is central to responsible interpretation.
Finally, the record shows why documentation of analysis plans, outcome definitions, data availability, and denominators matters. Such information helps readers distinguish an inconclusive record from a negative result, understand which participants contributed to each analysis, and evaluate uncertainty. The registry's unavailable data statement is explicit, but the missing outcome estimates mean the genetic-response question remains unresolved in this 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 most consequential limitation is the registry's statement that no study data are available. The principal investigator had left the institution, attempts to contact the investigator or study team were unsuccessful because all study team members had left the University, and attempts to find the data were unsuccessful. This prevents verification or interpretation of the primary and secondary outcomes and leaves no basis for assessing statistical precision.
The single-group, open-label design has no randomized comparator described in the registry. As a result, the design does not provide a like-for-like control comparison for estimating a causal treatment effect. The record also does not report whether outcome assessors were masked, how measurements were made, or how genetic data were collected and categorized. These details are not reported in the registry record.
The primary outcome description has a timeframe listed as 5 years, while its title specifies a 4 month visual-acuity period. The relationship between these descriptions is not explained. The record also does not report the statistical analysis plan, sample-size justification, analysis populations, missing-data methods, or handling of multiple comparisons. Each of these omissions limits assessment of how the intended question would be translated into a reliable estimate.
The adverse-event listing gives 0 at risk in the recorded categories, so its zeros cannot be interpreted as event rates among an assessed treatment population. Finally, enrollment of 66 does not establish the number contributing to any outcome or analysis. No outcome-level denominators or results are reported in the registry record.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Study EvAluating Genotypes While Using Lucentis 2 — NCT01464723.
- Registry record last updated 2019-08-14; status last verified 2019-07.
- Results first posted 2019-08-14.
- 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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17. Record Summary
The registry identifies NCT01464723 as a completed Phase 4, single-group, open-label study sponsored by the University of California, San Diego. The listed condition is age-related macular degeneration, and the intervention is ranibizumab (Lucentis). Enrollment is recorded as 66, with a start date of 2008-05 and primary completion date of 2011-12.
The primary question concerned VEGF and HTRA1 SNP genotypes among patients gaining at least 0 letters of visual acuity over a 4 month period. The registry also lists aims concerning visual-acuity change at additional time points, retinal thickness, and injection frequency. It lists 4 outcome measures and 0 analysis entries.
The record states that study data could not be located after the investigator and team members had left the institution. Consequently, no primary or secondary results can be interpreted from the posted record. Its design and aims are documented, but the genotype-response question remains unanswered.