Evaluation of IFNγ and Inflammatory Mediators in Patients With Hemophagocytic Lymphohistiocytosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of IFNγ and Inflammatory Mediators in Patients With Hemophagocytic Lymphohistiocytosis (NCT06047210), a registered phase not stated study. The primary outcome is Mean Serum Concentration of Inflammatory Biomarker - C-X-C Chemokine Ligand 10 (CXCL10).

2. Clinical Question

The study’s stated aim was to better understand the potential use of interferon gamma (IFNγ) and IFNγ-inducible chemokines as markers of HLH disease activity in adults, as well as the potential of IFNγ as a therapeutic target. The primary outcome focuses on CXCL10 concentration, rather than on a treatment effect or a clinical event.

The registry does not report a specific hypothesis comparing the two groups, a planned contrast between them, or a causal question. The outcome description says that serum samples were collected at various times after diagnosis. It does not specify a single collection visit or state that every participant had measurements at the same time. Thus, the central question that can be identified from the record is descriptive: what CXCL10 concentrations were observed among patients with available outcome data? Any group comparison or interpretation as a marker of disease activity would require details and analyses that are not reported in the registry record.

3. Trial Design

This is an observational, multicenter study of adults with HLH. The study status is COMPLETED. The registry lists a start date of 2016-12-14 and a primary completion date of 2019-10-30. Enrollment was 14. These dates describe the registry’s study timeline; they do not establish how long each participant was followed or when each blood sample was taken.

The study has two described groups: A-HLH Patients and Malignancy-Associated Hemophagocytic Lymphohistiocytosis (M-HLH) Patients. The first group is described as patients diagnosed with A-HLH; the second consists of patients diagnosed with HLH in the context of a malignancy. The record does not report the number of participants in each group. It also does not state how participants entered either group, whether group definitions were applied at enrollment, or whether participants could change classification over time.

The listed intervention is “Blood Draws Data Collection,” categorized as OTHER. This denotes data collection rather than a randomized therapeutic intervention. Allocation is not stated, and the groups should not be treated as interchangeable treatment and control arms. Differences between them, if reported, would be observational and could reflect differences in the patients or their clinical circumstances as well as any biomarker pattern.

The registry lists 39 outcome measures and zero analyses. For the primary measure, the record describes serum sampling at various times after HLH diagnosis and gives an 11-month timeframe. It does not report the sampling schedule, the number of samples per participant, or a statistical model for repeated measurements. The record also does not report a sample-size justification, randomization procedure, masking, or an analysis plan. These details are not reported in the registry record and should not be inferred from the completed status or enrollment count.

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: A total of 14 patients were enrolled in the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The enrolled set included all patients who signed an informed consent. Only patients with data collected for this outcome measure are reported.

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 enrolled set included all patients who signed an informed consent.

6. Primary Endpoint

The registry lists the primary outcome as Mean Serum Concentration of Inflammatory Biomarker - C-X-C Chemokine Ligand 10 (CXCL10), measured over 11 months.

The primary outcome is the mean serum concentration of C-X-C Chemokine Ligand 10 (CXCL10), measured in picogram/milliliter (pg/mL). The registry describes CXCL10 as an inflammatory biomarker and states that serum samples were collected at various times after HLH diagnosis to determine its concentration. The stated timeframe is 11 months.

A mean gives a measure of the central level of a continuous biomarker across the observations included in the outcome. The specified accompanying measure of spread is the standard deviation. In general, the standard deviation describes how dispersed individual measurements are around their mean; it is not a measure of uncertainty in the mean itself. The registry record does not state the number of measurements used to calculate the mean or standard deviation, or whether the calculation is based on one value per patient or multiple samples.

Measuring CXCL10 is relevant to the study’s stated aim of assessing IFNγ and IFNγ-inducible chemokines as potential markers of HLH disease activity. However, a biomarker concentration alone does not establish that the marker tracks disease activity, predicts outcomes, or has a causal role. Those interpretations would require suitable timing, clinical context, and analyses. The registry record does not report a numerical CXCL10 result, a reference range, a target value, or a formal analysis relating concentrations to disease activity. The endpoint definition therefore identifies what was intended to be measured, but not what level was observed or what it means clinically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record defines the primary outcome as a continuous measurement: serum CXCL10 concentration in picogram/milliliter (pg/mL). It specifies a mean and standard deviation as the summary statistics. The record does not report numerical values for either statistic or describe how repeated samples, if any, were handled.

What does a mean describe?

In general, a mean is the arithmetic average of the values included in a summary. It describes the center of those values, but it can be influenced by unusually high or low observations. For a biomarker, the mean is most interpretable when the included measurements represent a clearly defined population and measurement occasion. Here, the record says samples were collected at various times after diagnosis, but does not specify whether the reported mean would be based on a single selected value per patient, all available samples, or another summary. That distinction matters because a mean over samples and a mean over patients need not give the same weight to each participant.

What does the standard deviation describe?

In general, the standard deviation describes the spread of individual observations around the mean. A larger standard deviation indicates more variability in the measured values in the analyzed set. It is not, by itself, a confidence interval, a standard error, or a measure of how certain the mean is. Assessing uncertainty in a mean also depends on the number of independent observations and on how the data were collected. The outcome-specific number of participants and the number of samples are not reported in the registry record, so the standard deviation’s numerical interpretation cannot be assessed.

Why does sample timing matter?

For longitudinal or disease-activity measurements, values taken at different times can reflect different states of the condition. In general, if measurements are repeated over time, observations from the same participant are related rather than independent. Analyses that treat each sample as independent may understate uncertainty when within-person correlation is present. Other approaches can account for repeated measurements, but the appropriate method depends on the sampling schedule and the scientific question. The registry does not report the schedule, number of measurements per participant, or an analysis method for repeated samples. It is therefore not possible to say how time or within-person dependence was handled.

What can a group comparison establish?

In general, comparing means between two groups can describe a difference in observed levels. In a randomized study with appropriate conduct, random allocation can support causal interpretation of a treatment contrast. This study is described as observational, allocation is not stated, and the groups represent different clinical classifications rather than a stated treatment and control comparison. A difference, if one were reported, would therefore be descriptive or associational unless further design and analysis information supported a stronger interpretation. No numerical contrast or group-comparison analysis is reported in the registry record.

How should uncertainty be read?

In general, a confidence interval is a range of estimates that reflects sampling uncertainty under the assumptions of a statistical method. It is distinct from the standard deviation, which describes variation among observed measurements. A confidence interval can help readers judge both the precision of an estimate and the range of values compatible with the data and model. No confidence interval or inferential analysis for the primary outcome is reported in the registry record, so precision cannot be quantified from the posted results.

Why can biomarker data be difficult to summarize?

In general, biomarker measurements may have a skewed distribution or a small number of extreme values. When the distribution is strongly asymmetric, a mean and standard deviation may not fully convey its shape; medians, quantiles, or a model suited to the distribution may also be informative. These are general statistical considerations, not findings about CXCL10 in this study. The registry does not report the observed distribution or diagnostic checks, so it is not possible to assess whether the specified summaries adequately characterize the measured values.

The record lists zero analyses. It does not state a statistical analysis plan, adjustment variables, model assumptions, handling of missing values, or multiplicity strategy. The absence of those details should not be filled in by assuming a standard method. The primary outcome can be described from its definition, but statistical claims about differences, trends, associations, or precision require results and methods that are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("A-HLH Patients", "M-HLH Patients")
n   <- c(9, 2)
m   <- c(2079.286, 15197.143)
sp  <- c(2659.228, 21288.948)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  A-HLH Patients  9  2079.286  2659.228  35.222  4123.350
CARM  M-HLH Patients  2  15197.143  21288.948  -176076.466  206470.752

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 39 outcome measures, while the record lists zero analyses. It does not identify a multiplicity strategy, such as prioritizing a limited set of hypotheses or adjusting interpretation for multiple statistical tests. In general, when many outcomes or comparisons are tested, the chance of finding at least one apparently unusual result can increase. The appropriate way to address that concern depends on which outcomes were planned, which were exploratory, and what inferential claims are intended. Those details are not reported in the registry record. The count of outcome measures alone does not show that tests were conducted or that any particular multiplicity problem occurred.

The primary outcome population includes patients who signed informed consent, but only patients with data collected for this outcome are reported. The number with outcome data is not stated. The record does not describe reasons for missing measurements, whether missingness differed between the two groups, or how unavailable values were handled. In general, missing data can affect a summary if the participants with observed measurements differ systematically from those without measurements. Its effect depends on why values are missing and on the analysis approach; it cannot be determined from the enrollment count alone.

The study’s sampling description also raises a distinct issue: values were collected at various times after diagnosis. The record does not say whether every participant contributed a value at a common time, whether participants contributed repeated samples, or how the outcome population was defined across the 11-month timeframe. These are not interchangeable questions with ordinary missingness, because unequal timing or repeated measurements can change what the summary represents.

The statistical analysis plan, analysis population details beyond the outcome description, and any imputation or sensitivity analyses are not reported in the registry record. Consequently, neither the impact of missing data nor the handling of multiple outcomes can be evaluated from the posted information.

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

The registry record describes an observational study intended to assess IFNγ and other inflammatory mediators in adults with HLH. Its primary outcome is the mean serum concentration of CXCL10, with standard deviation as the specified measure of spread. The study aims to inform understanding of potential biomarker use and the potential of IFNγ as a therapeutic target. Those aims do not themselves establish that CXCL10 is a useful marker or that IFNγ is a therapeutic target.

No numerical primary outcome value, standard deviation, group contrast, confidence interval, or p-value is reported in the registry record. The record therefore does not establish the observed CXCL10 concentration, how much it varied, or whether the two described groups differed. It also does not report an analysis relating CXCL10 to disease activity. A study’s stated objective is not a result, and an outcome definition is not evidence of an association.

Even if group-specific concentrations were available, this observational design would require cautious interpretation. A-HLH and M-HLH are clinical group descriptions, not a stated randomized intervention and control. Differences between groups could reflect their different clinical contexts or other factors; the record does not report adjustment methods or enough detail to assess such explanations. The various sampling times after diagnosis also mean that timing would need to be considered when comparing measurements.

The record reports an enrollment of 14, but does not state how many had data for the primary outcome or how many belonged to each group. Thus, enrollment alone does not indicate the amount of information available for the biomarker estimate or its precision. The record’s zero analyses should not be interpreted as a null finding: they indicate that no analysis is listed, not that an analysis demonstrated no effect or association.

In practical statistical terms, the posted record supports statements about what the study set out to measure and how the groups were described. It does not support a conclusion about biomarker performance, clinical usefulness, causation, treatment benefit, or the absence of an effect. Such results are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically interesting because it frames HLH biomarker measurement as an observational question rather than a randomized treatment comparison. That distinction determines what the data can establish. Describing concentrations can help characterize measurements in a defined group, while attributing a difference to a treatment or clinical classification requires design and analysis support beyond a group label.

The outcome also highlights the importance of measurement timing. The record describes samples collected at various times after diagnosis over an 11-month timeframe. For a biomarker intended to reflect disease activity, the time at which a value is measured is part of its meaning. A single pooled summary may conceal changes over time or differences in sampling patterns. Appropriate analysis depends on whether observations are repeated, how closely they are timed, and whether the goal is to describe levels at particular visits or their course. Those design details and analyses are not reported in the registry record.

The study’s scope includes 39 outcome measures, but no analyses are listed. This makes transparent reporting of outcome definitions, populations, and inferential plans especially important for readers assessing which findings are confirmatory and which are exploratory. Without reported analyses, the record cannot show how uncertainty or the number of outcomes was handled.

Finally, the primary endpoint is a continuous biomarker summary, not a clinical event or direct measure of patient experience. Its interpretation depends on the observed distribution, the number of contributing participants, data completeness, and the relationship to clinical activity. The registry record defines the measurement but does not provide those results. The statistical value of the record is therefore in clarifying the intended question and the information still needed to evaluate it—not in establishing a biomarker conclusion.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting the primary outcome is that its numerical results are not reported in the registry record. No mean CXCL10 concentration, standard deviation, confidence interval, or group-specific estimate is available in the record. Without these, neither the level of the biomarker nor the precision of an estimate can be judged.

Although total enrollment is 14, the number with primary-outcome data is not reported. The record also does not give the number in each clinical group. This limits assessment of the analyzed population and prevents evaluation of whether data availability or group sizes could have influenced a comparison. Reasons for missing outcome data and approaches to handling it are not reported.

The sampling plan is described only as collecting samples at various times after diagnosis during an 11-month timeframe. The timing, frequency, and number of samples per participant are not reported. It is therefore unclear whether the endpoint summarizes one measurement per person or repeated measurements, and whether measurements reflect comparable points in the disease course. No method for accounting for repeated observations or time trends is stated.

The study is observational, allocation is not stated, and its two groups are defined by clinical context. They are not a like-for-like control comparison. The record does not report a causal analysis, adjustment variables, or a statistical model. This constrains interpretation of any hypothetical difference between groups.

The registry lists 39 outcome measures but zero analyses. It does not report a multiplicity strategy, a sample-size justification, or an inferential analysis plan. The listed zero counts for adverse-event categories also do not explain event ascertainment or reporting. These limitations mean the registry record can describe study intent and endpoint definition, but not provide a complete statistical account of the primary result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of IFNγ and Inflammatory Mediators in Patients With Hemophagocytic Lymphohistiocytosis — NCT06047210.
• Registry record last updated 2024-09-19; status last verified 2024-04.
• Results first posted 2024-09-19.
• 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.

18. Record Summary

The registry identifies NCT06047210 as an observational, multicenter study titled “Evaluation of IFNγ and Inflammatory Mediators in Patients With Hemophagocytic Lymphohistiocytosis.” Its stated focus is adults with HLH, including a group with malignancy-associated HLH. The sponsor is Swedish Orphan Biovitrum. The record lists a start date of 2016-12-14, a primary completion date of 2019-10-30, COMPLETED status, and enrollment of 14.

Blood draws for data collection are the listed intervention. The primary outcome is mean serum CXCL10 concentration in pg/mL, with standard deviation, over a stated 11-month timeframe. The record says samples were collected at various times after diagnosis and that only participants with data for this outcome are reported.

The registry lists 39 outcome measures and zero analyses. It does not report the primary outcome’s numerical results, group-specific counts, or the statistical methods used to analyze the measurements. Accordingly, the study’s intended measurement can be described, but its primary biomarker findings cannot be evaluated from the registry record.