Genetic Screening for Filaggrin Mutation in Atopic Dermatitis and Ichthyosis Vulgaris in the African American Population: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genetic Screening for Filaggrin Mutation in Atopic Dermatitis and Ichthyosis Vulgaris in the African American Population (NCT01016106), a non-randomized na study. The primary outcome is Heterozygous for Filaggrin (FLG) Null Mutations.

2. Clinical Question

The investigators’ stated objective was to identify common and rare filaggrin mutations among African American patients diagnosed with atopic dermatitis and ichthyosis vulgaris. The record describes a control group as well as participants with both conditions, with DNA obtained from buccal swabs during a single visit. The genetic work focused on three regions of FLG exon 3.

This is a genetic-screening question, not a test of a treatment. The study did not randomly assign participants to receive an intervention, and the recorded intervention is buccal swab collection and genetic analysis. The control group offers context for interpreting genetic findings, but the registry explicitly cautions that the arms are not a like-for-like control comparison.

The primary outcome is titled “Heterozygous for Filaggrin (FLG) Null Mutations” and is measured as a count of participants. The record describes nucleotide changes noted in the population tested, but does not report the primary outcome counts by group. It therefore does not establish from the posted results how frequently the specified heterozygous status occurred or whether its frequency differed between the groups.

3. Trial Design

The registry identifies this as a completed, non-randomized, single-group study with double masking recorded. The study enrolled 35 participants. Its listed conditions are atopic dermatitis and ichthyosis vulgaris, and Northwestern University is named as sponsor. The record lists the study start as 2010-06 and primary completion as 2010-10.

Although the design model is recorded as single-group, the arm descriptions distinguish African American participants with atopic dermatitis and ichthyosis vulgaris from African American control subjects without a personal or family history of ichthyosis vulgaris or atopy. The registry cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Group membership therefore reflects participant characteristics rather than random assignment.

The procedure described for both groups was completion of a subject data collection form and collection of a buccal swab during a single visit, followed by DNA extraction and analysis. The study’s genetic work used polymerase chain reaction to amplify three regions of FLG exon 3, followed by sequencing and review of sequence results. The record gives a primary outcome timeframe of 1 month.

The study is not a therapeutic trial: no treatment comparison or clinical treatment effect is specified. The registry does not report the rationale for its enrollment target, how participants were recruited, eligibility criteria beyond the group descriptions, or further details about masking. It also does not report a statistical analysis plan or an inferential comparison between the groups. The completed status indicates the registry’s recorded study status, but does not itself supply missing outcome counts or establish that every planned analysis was performed.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Heterozygous for Filaggrin (FLG) Null Mutations, measured over 1 month.

The primary outcome is the number of participants heterozygous for filaggrin (FLG) null mutations. It is a count-based measure: each participant either meets the stated genetic classification or does not. The registry lists the unit as participants and gives a timeframe of 1 month.

This type of endpoint is used to describe how often a specified genetic finding occurs in the study population. In a screening study, a count can provide a basic descriptive summary, while group-specific counts and denominators are needed to understand how the finding was distributed across the groups. A statistical comparison would require an analysis method suited to the outcome and study design; the registry record does not report such an analysis.

The methods description says DNA was purified from buccal swabs, quantified, and amplified from three regions of FLG exon 3. Sequencing results were examined, and nucleotide changes were noted. It lists 30 single nucleotide polymorphism (SNP) changes in the population tested, with T454A, H2507Q, and G2545R described as the most common coding changes, and t2508c as a silent change. These descriptions do not provide participant-level or group-level frequencies for the primary endpoint.

The primary outcome counts and their distribution by group are not reported in the registry record. Consequently, the endpoint’s measured value cannot be interpreted from the posted results, and the listed nucleotide changes should not be treated as a reported count of participants with heterozygous FLG null mutations.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a non-randomized study with a genetic endpoint measured as a count of participants. That design determines what statistical interpretation is possible. The study groups were defined by clinical and family-history characteristics; participants were not randomly assigned. General statistical interpretation of a non-randomized group comparison must account for the possibility that groups differ in ways other than the condition used to define them. The record does not report an adjusted comparison or the details needed to evaluate confounding.

What does a participant count show?

A count records how many people meet an outcome definition. For a binary classification such as heterozygous for a specified mutation, the count is meaningful alongside the number evaluated in that group and a clear rule for classifying a result. A count alone does not show the precision of a frequency estimate or whether group differences are larger than could be expected from sampling variation. The registry gives the primary outcome’s unit but does not report its observed counts by group, so neither group-specific frequencies nor their uncertainty can be assessed.

How should a confidence interval be understood?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of a chosen statistical method. A narrow interval indicates greater precision than a wide interval, but precision is not the same as freedom from bias. In a non-randomized study, an interval can describe sampling uncertainty without resolving differences in group composition or selection. No primary outcome estimate or confidence interval is reported in the registry record.

What does non-randomized mean for comparison?

Random allocation is one way trials aim to balance participant characteristics between groups, on average. Here, group membership is based on the study’s clinical descriptions rather than random allocation. The registry itself warns that the arms are not a like-for-like control comparison. General caution is therefore appropriate: a simple difference between groups, if one were available, would not by itself identify a causal effect. No statistical adjustment strategy is reported, and no causal treatment effect is the stated purpose of this genetic-screening study.

What can the sequencing description establish?

The record describes DNA purification from buccal swabs, quantification, amplification of three regions of FLG exon 3, electrophoresis, purification, duplicate cycle sequencing reactions, capillary electrophoresis, and review of sequence results using software. It says nucleotide changes were noted, including 30 SNP changes in the population tested. This describes laboratory procedures and reported variant observations. It does not give the number of participants with each change, group-specific variant counts, or details of quality-control thresholds and classification criteria. Those items are not reported in the registry record.

What does the planning illustration represent?

The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are hypothetical planning calculations: they describe the group size that would be associated with a chosen effect under stated assumptions. They are not observed power and do not demonstrate that the study was adequately powered. In this record, the primary outcome results and the corresponding illustration values are not reported in the registry record, so there is no numerical planning estimate to interpret.

More generally, planning calculations depend on the assumed effect, outcome variability or event rate, allocation, significance level, and analysis method. If an assumed effect is uncertain, the resulting planning estimate is uncertain too. A planning illustration based on an observed effect should not be read as independent confirmation of that effect: an estimate from a small or selected study can be unstable. These are general statistical considerations, not details of an unreported protocol.

Why can over-dispersion matter?

For count outcomes, a statistical model may need to account for variation that exceeds the model’s simplest assumptions. General methods for count data can differ in how they handle such extra variability. The registry does not report an analysis model for the primary endpoint, and the outcome is presented as a participant count rather than a repeated count per person. There is therefore no basis for saying that an over-dispersion adjustment was used or required in this study.

Because the primary result is missing, statistical methods cannot recover the main finding from the laboratory description alone. The posted record supports describing the design and assay approach, but not estimating mutation frequency, comparing groups, or judging the precision of a difference.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("African American (AA) Control Subjects", "AA Subjects With Atopic Dermatitis and Ichthyosis ")
n      <- c(17, 18)
events <- c(1, 4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  African American (AA) Control Subjects  17  1  5.9  0.1  28.7  1.0  27.0  1.4  27.3
ARM  AA Subjects With Atopic Dermatitis and Ichthyosis   18  4  22.2  6.4  47.6  9.0  45.2  9.1  45.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure: the number of participants heterozygous for FLG null mutations. It also describes noting nucleotide changes during sequencing, but does not identify a formal hierarchy of secondary outcomes or specify whether each listed variant was treated as a separate hypothesis. A multiplicity plan, including any adjustment for multiple comparisons, is not reported in the registry record.

Multiplicity matters in general when many outcomes or subgroup comparisons are tested: the chance of observing at least one apparently notable result can increase as the number of tests grows. That general concern cannot be quantified for this study from the posted record. The record does not report p-values or an inferential analysis of the named nucleotide changes.

Missing-data procedures are not reported in the registry record. It does not state whether any participants lacked an interpretable swab or sequencing result, how incomplete genetic data were handled, or whether participants were excluded from the primary endpoint analysis. The listed group counts in the safety section do not establish the analysis population for the genetic endpoint.

The registry also does not define an analysis population, such as whether the primary outcome was assessed in all enrolled participants or only those with usable sequencing data. No participant flow or exclusions for the primary outcome are reported. These gaps limit assessment of possible missing-data bias and of how completely the endpoint reflects those enrolled.

Finally, no statistical analysis plan or model for the endpoint is reported. It is therefore not possible to determine whether the analysis was prespecified, how any comparisons were handled, or whether subgroup analyses were planned. These are reporting limitations, not evidence that a particular procedure was or was not followed outside the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry reports zero serious adverse events among the African American control subjects and zero among the participants with atopic dermatitis and ichthyosis vulgaris. It also reports zero other adverse events in each listed group. These are the posted safety counts; they are separate from the genetic primary outcome and do not indicate how often FLG mutations occurred.

The record lists 17 control subjects and 18 participants with the two conditions as at risk for serious and other adverse events. The death fields are null, which means death counts are not reported in the registry record; a null entry should not be interpreted as a reported zero.

Zero reported events in these groups describes what the registry reports for the safety categories and risk sets. In general, an absence of reported events does not prove that an event is impossible or that a procedure has no risk. Interpretation also depends on how events were defined, collected, and followed. Details of event definitions, ascertainment, and safety follow-up are not reported in the registry record.

The listed primary outcome timeframe is 1 month, but the safety fields do not establish the exact safety observation period. These counts should be read as registry-reported event summaries, not as a comprehensive assessment of safety or as evidence about treatment benefit.

13. What the Result Does, and Does Not, Mean

This study record concerns genetic screening in African American participants with atopic dermatitis and ichthyosis vulgaris, with a control group described by the absence of a personal or family history of ichthyosis vulgaris or atopy. The objective was to identify common and rare mutations in the filaggrin gene. Buccal swabs were used to obtain DNA, and the methods describe sequencing three regions of FLG exon 3.

The record reports that 30 SNP changes were noted in the tested population and names T454A, H2507Q, and G2545R as the most common coding changes, along with the silent change t2508c. These are statements in the laboratory narrative. The registry does not report participant-level counts or group-specific frequencies for those changes, and it does not give the number meeting the primary endpoint of heterozygous for FLG null mutations.

As a result, the posted information does not establish how common the primary endpoint was, whether its frequency differed between groups, or how precise any estimated difference might be. There is no reported effect estimate, confidence interval, or p-value for the primary outcome. The study’s non-randomized group structure also means that a group comparison would not, on its own, establish causality.

The findings should not be interpreted as showing that a genetic variant causes either condition, predicts an individual’s clinical course, or changes the effect of a treatment. The record does not report those analyses or questions. Nor does the small, specifically described study population support a population-wide frequency estimate from the information available.

What the record can support is a description of the study objective, participant groups, genetic laboratory procedures, and the sequence changes noted in the narrative. What it cannot support from the posted results is a quantitative answer to the primary endpoint question or a conclusion about a clinical effect.

14. Why This Trial Matters Statistically

This record illustrates an important distinction between describing a study’s objective and reporting its results. The registry identifies a specific genetic question and a primary endpoint, and it gives a detailed laboratory workflow. Yet the primary outcome counts by group are not reported. Without those counts, the central question cannot be answered quantitatively from the posted record.

It also illustrates why genetic variant observations and participant-level endpoint results are not interchangeable. A list of nucleotide changes may document what the sequencing work noted, but it does not show how many participants carried a change, how findings were distributed across groups, or how many met a defined null-mutation endpoint. Those distinctions matter when moving from laboratory description to statistical inference.

The design is another key statistical feature. The groups were not randomized and were defined by clinical and history characteristics. The registry cautions that the arms are not a like-for-like control comparison. This makes clear reporting of group-specific results, participant eligibility, analysis populations, and any adjustment methods especially useful for readers evaluating comparability.

Finally, the record demonstrates that completion status and safety summaries do not substitute for primary outcome reporting. A completed registry entry can still leave the main endpoint and its uncertainty unavailable. For clinical researchers and biostatisticians, this is a reminder to separate what a protocol set out to examine, what the laboratory methods did, and what the posted results actually quantify.

15. 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 important limitation for interpretation is that the primary endpoint counts are not reported in the registry record. No group-specific result, estimate of a difference, confidence interval, or p-value is available. The reported nucleotide changes do not fill this gap because their participant-level frequencies and relationship to the endpoint are not given.

The non-randomized design limits comparisons between the groups. The registry explicitly cautions that they are not a like-for-like control comparison. The record does not describe an adjusted analysis or provide participant characteristics that would allow assessment of group comparability. It also does not report recruitment details or broader eligibility criteria beyond the group descriptions.

Details needed to assess the genetic endpoint are not reported in the registry record, including the number of usable sequencing results, handling of incomplete or ambiguous results, criteria for classifying a mutation as null, and any participant-level quality-control or validation results. The laboratory procedures are described, but these details are not.

The statistical analysis plan, analysis population, and procedures for missing data or multiple comparisons are also not reported. The record does not state whether any planned comparisons were conducted or whether the endpoint was assessed for all enrolled participants. The listed safety risk sets should not be assumed to be the primary endpoint analysis population.

Finally, the record describes a study in a specifically defined population and does not provide enough outcome detail to estimate mutation frequency or generalize such an estimate. Its findings should be read as a registry description of study aims and methods, with limited reported genetic results, rather than as a complete statistical report of the primary outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Genetic Screening for Filaggrin Mutation in Atopic Dermatitis and Ichthyosis Vulgaris in the African American Population — NCT01016106.
• Registry record last updated 2015-05-01; status last verified 2015-04.
• Results first posted 2013-06-20.
• 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.

19. Record Summary

NCT01016106 is a completed, non-randomized genetic-screening study sponsored by Northwestern University. It enrolled 35 participants and describes African American participants with atopic dermatitis and ichthyosis vulgaris alongside African American control subjects. Buccal swabs were collected for DNA extraction and analysis, with sequencing focused on three regions of FLG exon 3.

The primary outcome was the number of participants heterozygous for FLG null mutations, with a timeframe of 1 month. The methods narrative reports 30 SNP changes in the tested population and names several examples, but primary outcome counts by group and statistical analyses are not reported in the registry record. The record also reports zero serious and zero other adverse events in both listed groups; death counts are not reported.

The available information describes the study question and laboratory approach, but does not quantify the primary endpoint or permit assessment of its precision or a group difference.