Genetic and Biochemical Markers of Interferon-Induced Depression.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genetic and Biochemical Markers of Interferon-Induced Depression. (NCT00252538), a registered phase not stated study. The primary outcome is Phenotype and Genotype Based on Presence of Interferon Induced MDD..

2. Clinical Question

3. Trial Design

This was an observational, multi-site study concerning people with chronic hepatitis C who were candidates for interferon therapy. Rather than assigning participants to treatments, the study grouped participants according to whether they developed major depressive disorder while receiving interferon alpha therapy. The stated aim was to identify predictors and biochemical markers associated with interferon-induced depression.

The registry lists the study as completed and reports enrollment of 133. The recorded start is 2006-04, and primary completion is 2009-09. The study description says enrollment was planned to last for 40 months and until the end of the study. The record does not explain how that planned period relates to the recorded dates.

The primary outcome description refers to structured psychiatric interviews and depression symptom rating scales, used to assess the association between the depression phenotype and genotype. The study examined genes considered relevant to depression and antiviral treatment response. It specifically describes three polymorphisms of the IL-28b gene, identified as c/c, c/t and t/t. A subsequent analysis of VA participants examined proinflammatory cytokines and serotonin levels in relation to depression symptoms.

The registry lists one primary outcome measure and one analysis. The allocation method is not stated, and the record does not describe a randomized comparison. It also does not provide the group-specific results, the number of participants included in each analysis, or a detailed statistical analysis plan. The stated enrollment is not, by itself, evidence that every enrolled participant contributed data to each analysis.

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: Exclusion Criteria: 1. Diagnosis of active: depression, psychotic symptoms, or bipolar disorder (or history of bipolar disorder) during the previous 3 months 2. On antidepressant medications for any reason 3. Currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months.

Overall Study

Analysis population for the primary outcome, as defined in the registry: This is an observational study that segregates patients with HCV and on interferon alpha treatment into 2 groups based on whether they develop major depressive disorder (MDD) while on interferon alpha therapy for HCV and then examines genes that may confer risk for MDD development. group 1 MDD and group 2 no MDD. total sample from multiple sites.

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 Phenotype and Genotype Based on Presence of Interferon Induced MDD., measured over The proposed enrollment began after funding notification and enrollment will last for a period of 40 months and until end of study..

The primary outcome is titled Phenotype and Genotype Based on Presence of Interferon Induced MDD, with the unit recorded as participants and the parameter described as a number. The outcome description says structured psychiatric interviews and symptom rating scales for depression were used to determine the association between the depression phenotype and genotype. In this context, the phenotype is whether major depressive disorder developed during interferon alpha therapy; the genetic measures include variants considered potential markers of vulnerability.

These assessments serve a different purpose from a comparison of assigned treatments. They characterize participants and make it possible to examine whether genetic or biochemical features are associated with the depression classification. The record also describes examination of three IL-28b polymorphisms and, in a subsequent analysis limited to VA participants, proinflammatory cytokines and serotonin relative to depression symptoms.

The endpoint is therefore intended to connect a clinically assessed depression outcome with biological characteristics. However, the registry does not report the operational diagnostic criteria, the timing or frequency of assessments, the endpoint counts by genotype, or the association estimates. The presence of an outcome definition does not establish that any marker was associated with depression, and the results needed to evaluate that question are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of comparison does the design support?

General statistical explanation: an observational study records characteristics and outcomes without assigning participants to exposure groups. Here, the description groups participants according to whether major depressive disorder developed during interferon alpha therapy and examines biological characteristics in relation to that classification. Such a comparison can describe associations. It does not, on its own, establish that a marker caused the outcome or that altering the marker would change the outcome.

The registry does not state an allocation method, and the study is not described as randomized. The record also cautions that its arms are not a like-for-like control comparison. That distinction matters: treatment-trial methods designed to compare randomized treatment groups cannot be assumed to apply to the participant groupings in this study. Potential differences between people classified with and without depression may complicate interpretation. Whether the analysis measured or adjusted for such differences is not reported in the registry record.

What does a binary outcome represent?

General statistical explanation: a binary outcome classifies each participant into one of two outcome states, such as presence or absence of a defined condition. Counts and proportions can describe how often the outcome occurred in a group. An association analysis can then assess whether outcome frequency varies across categories such as genotype. The registry identifies the primary outcome as a participant count and describes the depression phenotype, but does not report the group-specific counts, proportions, or association estimates.

Counts alone would not show how precisely an association was estimated. A confidence interval, when reported, describes a range of values compatible with the data under the analysis assumptions. A narrow interval generally indicates greater precision than a wide interval, while an interval spanning values that imply little or no association would indicate substantial uncertainty about the association's direction or magnitude. No confidence intervals are reported in the registry record, so precision cannot be evaluated from the posted results.

How should p-values be read?

The study description states that p-values above 0.05 were considered statistically insignificant. General statistical explanation: a p-value evaluates how compatible the observed data are with a specified statistical model under a null hypothesis. It does not measure the probability that the null hypothesis is true, the probability that a finding is due to chance, or the clinical importance of an association. A threshold is a decision convention, not a measure of effect size.

The registry does not report the p-values for the primary outcome or the genetic and biochemical comparisons. It is therefore not possible to determine from this record whether any reported comparison met the stated convention. Even if a p-value were available, interpretation would also require the corresponding estimate and uncertainty, along with clarity about the tested hypotheses and analysis choices.

Why do multiple markers matter?

General statistical explanation: assessing multiple markers or hypotheses creates more opportunities for apparently unusual results to occur by chance. Multiplicity methods can adjust how evidence is interpreted or control a specified error rate across a family of tests. The description mentions genes of interest and three IL-28b polymorphisms, as well as a subsequent analysis of cytokines and serotonin among VA participants. The registry does not report whether multiplicity was addressed, how hypotheses were grouped, or whether analyses were prespecified.

The record lists one analysis, but that listing does not explain the full set of tests conducted or how the listed analysis relates to the various markers described. The full statistical analysis plan and any correction for multiple comparisons are not reported in the registry record. Consequently, the number and selection of tests underlying any potential finding cannot be assessed from this entry.

What do the planning assumptions mean?

General statistical explanation: sample-size planning estimates the amount of information a future study may need to detect a specified effect under stated assumptions. A planning illustration based on an observed effect is not an observed-power calculation and does not establish that the completed study was adequately powered. The stated planning 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. Time-to-event planning uses a total event count, while other planning results are expressed as participants per arm.

These assumptions describe planning illustrations, not the study's own design. The registry does not report the study's sample-size justification or show that the participants were allocated equally. The illustrations cannot be taken as evidence about the precision of the actual genetic or biochemical analyses, especially because the analysis-specific participant counts and outcome estimates are not reported.

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("Group 1- MDD", "Group 2- no MDD")
n      <- c(19, 114)
events <- c(19, 114)
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  Group 1- MDD  19  19  100.0  82.4  100.0  83.2  100.0  83.2  99.9
ARM  Group 2- no MDD  114  114  100.0  96.8  100.0  96.7  100.0  96.8  100.0

11. Multiplicity, Missing Data and Analysis Populations

The study description refers to genes related to depression and antiviral treatment response, three IL-28b polymorphisms, and a subsequent VA-only analysis of proinflammatory cytokines and serotonin. The registry lists one analysis, but does not describe the full set of statistical tests, whether hypotheses were prespecified, or whether any adjustment for multiple comparisons was used. This matters because general statistical practice recognizes that testing multiple markers can increase the chance of finding an apparently noteworthy result even when no true association is present. The registry's stated p-value convention does not, by itself, address multiplicity.

Missing-data methods are not reported in the registry record. The record does not say how missing psychiatric assessments, genetic measurements, or biochemical measurements were handled, or whether participants with incomplete data were excluded from particular analyses. The listed enrollment of 133 does not establish the number included in each analysis.

The analysis population is also not fully described. Although the study concerns people with chronic hepatitis C who were candidates for interferon therapy, the complete eligibility criteria are not available in the record. It does not report participant flow, characteristics of those analyzed, or whether the primary outcome analysis included all enrolled participants. The subsequent analysis is specifically described as involving VA participants, but its size and selection procedures are not reported. These omissions limit evaluation of potential selection effects and the extent to which findings could apply beyond the analyzed participants.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: elevation of alpha fetoprotein (0.8%).

The registry's serious adverse event figures list Group 1 with 133 participants at risk and 1 affected. The other adverse event figures list 133 participants at risk and 0 affected. The record also lists Elevation of Alpha Fetoprotein among the top serious terms, with 0.8% shown. These are the posted safety figures; the registry does not provide further detail about the event's timing, clinical context, severity criteria, or relationship to interferon therapy.

The figures should not be treated as a complete account of safety without knowing how events were defined, collected, and attributed. The record does not report whether all participants had the same duration of follow-up or whether the listed event term corresponds to the single serious event entry. Deaths are not reported in the registry record. The safety information also does not answer the primary genetic-association question, which concerns depression classification and biological markers rather than a randomized comparison of treatments.

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

The record describes a completed observational study that sought genetic and biochemical markers associated with depression during interferon alpha treatment for hepatitis C. It identifies the intended depression assessment methods, genetic focus, and a subsequent VA-participant analysis of cytokines and serotonin. These details clarify the research question and the types of measurements considered.

The record does not report the primary association results. There are no outcome counts by depression status or genotype, no effect estimates, no confidence intervals, and no p-values. As a result, the posted information cannot show whether any marker was associated with depression, how large an association might have been, or how precisely it was estimated. It also cannot show whether findings were robust to alternative analyses or adjustment for other participant characteristics.

Even if an association were reported, this observational design would not establish that a genetic or biochemical marker caused depression. The study grouped participants according to whether depression developed during therapy; it did not describe random assignment to a marker or treatment. General statistical interpretation: an observed association can be useful for generating or evaluating hypotheses, but causal conclusions require careful consideration of design, measurement, confounding, and supporting evidence.

The enrollment figure of 133 gives the scale of the registered study, but it does not identify the analysis-specific sample sizes or the amount of missing data. The record does not report the sample-size justification, detailed analysis plan, or multiplicity procedures. Nor does it provide enough information to assess the representativeness of participants or the generalizability of any potential findings.

Accordingly, the registry supports a description of the study's aims and broad methods, not a conclusion about whether the proposed markers predicted or were associated with interferon-induced depression. The result itself is not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it frames a clinically assessed outcome as an association question involving genetic and biochemical characteristics. The registry links structured psychiatric interviews and depression symptom scales with an intended examination of genotype, including three IL-28b polymorphisms. It also describes a subsequent analysis of proinflammatory cytokines and serotonin among VA participants. This combination illustrates how an observational study can investigate candidate markers without assigning participants to marker-defined groups or treatment conditions.

The design also highlights the distinction between prediction and causal explanation. A marker may be associated with an outcome in observed data without causing that outcome. Establishing the strength and practical value of a predictive association would require reported estimates, uncertainty, and sufficient methodological detail to judge how the analysis was conducted. Those results are not reported in the registry record.

The study description raises statistical issues that are common in biomarker research. Multiple candidate genes and biochemical measures can involve multiple comparisons, while the record does not state whether multiplicity was handled. Missing information about analysis populations, missing data, and potential confounder adjustment also limits assessment of reliability. These are not minor details: they affect how readers distinguish a stable association from an uncertain or selectively reported result.

The registry entry is therefore useful for identifying the scientific question and the intended measurements, while also showing why outcome reporting and analysis transparency are essential. Without group-specific results and precision estimates, neither the magnitude nor the reliability of any marker association can be evaluated.

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 primary limitation for interpretation is that the registry record does not report the primary outcome results. It gives no depression counts by genotype, association estimates, confidence intervals, or p-values. The entry therefore does not permit assessment of effect direction, magnitude, or precision.

The design is observational, and the record does not describe random allocation. Participants were grouped by whether major depressive disorder developed during interferon alpha therapy. Potential confounding is therefore relevant as a general design concern, but whether measured factors were adjusted for is not reported in the registry record. The detailed statistical analysis plan is also not reported.

The clinical and biological measurement procedures are described only at a broad level. Structured psychiatric interviews and symptom rating scales are named, but diagnostic thresholds, assessment schedules, and procedures for classifying outcomes are not reported. The record identifies genetic and biochemical measures without giving their measurement protocols or analysis-specific results.

The enrollment was 133, but the registry does not report how many participants contributed to each analysis, how missing measurements were handled, or whether all enrolled participants were included in the primary analysis. Full eligibility criteria are not available in the registry record. The subsequent VA-only analysis is mentioned without its participant count or selection details.

Finally, the record does not describe whether multiple comparisons were addressed, despite naming several candidate markers and polymorphisms. It does not report a sample-size justification or explain the relationship between the planned enrollment period and the recorded study dates. These gaps limit interpretation of the study's precision, reproducibility, and applicability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Genetic and Biochemical Markers of Interferon-Induced Depression. — NCT00252538.
• Registry record last updated 2014-12-11; status last verified 2014-12.
• Results first posted 2014-12-11.
• 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

The registry describes a completed, multi-site observational study of genetic and biochemical markers associated with depression during interferon alpha therapy for chronic hepatitis C. It lists enrollment of 133, a start date of 2006-04, and primary completion in 2009-09. Participants were classified according to whether major depressive disorder developed during therapy.

The primary outcome description refers to psychiatric interviews, depression symptom rating scales, and genotype assessment. The study examined three IL-28b polymorphisms and describes a subsequent VA-participant analysis of cytokines and serotonin. The registry does not report the primary association results, analysis-specific participant counts, or detailed statistical methods for missing data and multiplicity. The available record establishes the study's aims and broad design, but not whether the proposed markers were associated with depression or how precisely any association was estimated.