The Effect of Methylphenidate Treatment on Oxidative Stress Levels in Children Diagnosed With Attention Deficit Hyperactivity Disorder (ADHD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Methylphenidate Treatment on Oxidative Stress Levels in Children Diagnosed With Attention Deficit Hyperactivity Disorder (ADHD) (NCT06844812), a registered phase not stated study. The primary outcome is Change in Total Oxidant Status.

2. Clinical Question

3. Trial Design

The registry describes a completed, non-interventional study sponsored by Saglik Bilimleri Universitesi. The recorded study start date is 2024-06-26, and the primary completion date is 2025-01-06. Enrollment is listed as 39. The intervention entry states that patients already planned to start methylphenidate were invited to participate; the study did not administer or change treatment.

The planned measurement schedule was within-patient: serum measurements immediately before treatment initiation and after treatment had begun, up to the 3rd month. The primary outcome is change in TOS. The study summary also names TAS, OSI, MDA, Ox-LDL, and SOD as measures of oxidative stress. The registry describes the primary outcome as a mean with standard deviation and gives U/ml as its unit.

This design records change over time among patients who began treatment as part of their planned care. It does not include a reported untreated or alternative-treatment control group. Consequently, the before-and-after comparison can describe observed change in the measured group, but cannot by itself distinguish a treatment-related change from other changes over time. Random allocation is not reported, and the registry explicitly notes that this is not a randomized comparison.

Details such as the recruitment setting, eligibility criteria, follow-up completion, and the statistical analysis plan are not reported in the registry record. Although the record is marked completed, that status does not supply the missing outcome estimates or analysis details.

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: Initially, 39 patients were enrolled in the study, and each patient who dropped out of the study during follow-up was replaced by a new patient in accordance with the protocol. Thus, a total of 53 patients were included in the study and 14 patients left the study for various reasons.

Overall Study

Reasons for not completing this period:

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 Change in Total Oxidant Status, measured over Immediately before starting the treatment and up to the 3rd month of treatment..

The primary endpoint is change in Total Oxidant Status (TOS), a serum measure identified by the registry as an indicator of oxidative status. The registry states that TOS was measured using a human ELISA kit protocol. The stated measurement times are immediately before treatment and up to the 3rd month of treatment. The endpoint is described as a mean, with standard deviation, and its unit is U/ml.

In general, measuring the same outcome before and after an exposure can describe how that measure changes over time within the observed group. TOS is the primary outcome in this record; the other named measures are TAS, OSI, MDA, Ox-LDL, and SOD. The summary frames these measures as a set for investigating oxidative stress, while the primary outcome specifically focuses on TOS.

The registry gives laboratory-procedure details, including the use of serum, an ELISA kit protocol, and optical-density reading. Those procedural details describe how the measurement was made; they do not establish the reliability of the assay in this study or the clinical meaning of a particular value. Such validation and interpretation are not reported in the registry record. Nor are the observed TOS means, variability, or change reported, so the size and precision of the endpoint result cannot be assessed from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

The primary outcome is specified as a mean of a continuous measure. In general, a mean summarizes the center of a set of measured values, while the standard deviation describes how spread out individual values are around that center. Neither summary alone describes the full distribution. For example, unusual values or a skewed distribution may affect the mean, and the same standard deviation can arise from data with different shapes.

For a before-and-after design, a key distinction is whether the analysis summarizes each time point separately or calculates a change for each participant. A paired analysis uses the within-person differences and reflects the fact that measurements from the same person are related. An analysis treating the two sets of measurements as independent would not make that allowance. The registry describes a before-and-after comparison, but the specific statistical method used to estimate the change is not reported in the registry record.

How should uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data under the assumptions of the analysis. Its width conveys precision: a narrower interval indicates greater precision for the estimated quantity, while a wider interval indicates more uncertainty. A confidence interval for a mean change would help readers judge which magnitudes of change remain compatible with the observed data. No confidence interval is reported in the registry record, so precision cannot be evaluated.

A p-value, when reported, measures how unusual the observed data or more extreme data would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry record does not report a p-value for the primary outcome or identify the test used. A result should not be inferred from the completed status or from the fact that an outcome was registered.

Why does the before-and-after structure matter?

Repeated measurements can account for stable differences between people when the analysis is based on paired changes. But a within-person comparison does not create a control group. In general, changes that occur over time alongside treatment can contribute to an observed difference. Without a reported concurrent comparison group and an analysis that addresses potential sources of bias, a before-and-after estimate is descriptive of the observed group rather than an isolated estimate of a treatment effect.

The record says that methylphenidate was already planned independently of study participation and that no additional treatment was administered or altered by the study. This explains the observational character of the design. The allocation method is not stated, and randomization is not reported. The registry does not provide enough information to evaluate how participants were selected, whether all eligible patients enrolled, or whether the measurement schedule was followed consistently.

What does the sample-size illustration represent?

The planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration considers an effect expressed as a stated fraction of the observed effect. These are planning assumptions, not a report of the study’s design rationale or observed power. The registry record does not report the study’s sample-size justification, and numerical planning outputs are not available in the record.

Those assumptions also refer to two arms, whereas the clinical design described for this study is a before-and-after measurement in patients planned to start treatment, with no reported control arm. The planning illustration should not be read as evidence that the study actually used a two-arm design. In general, sample-size calculations depend on the target effect, variability, analysis method, and design assumptions. A planning estimate does not establish that a study was adequately powered for its actual analysis, and observed power should not be substituted for an estimate and its uncertainty.

Why can variability and distribution matter?

Many common analyses of a mean rely on assumptions about the distribution of the data or of the within-person differences. In general, strong skew, influential outliers, or substantial heterogeneity can affect estimates and standard errors. For count data, over-dispersion means that variability exceeds what a simple model assumes; accounting for it can prevent uncertainty from being understated. The primary endpoint is continuous, and the registry does not report distribution checks, outlier handling, or model diagnostics. These are general considerations, not claims that any particular problem occurred in this study.

For a paired comparison, the spread of the individual changes is particularly relevant. Separate standard deviations at baseline and follow-up do not, by themselves, reveal that spread because the relationship between each person’s two measurements also matters. The record identifies standard deviation as the dispersion measure but does not report the values or correlation between repeated measurements. Accordingly, the precision of a change estimate cannot be reconstructed from the registry information.

In general, interpretation should combine the estimated change, its uncertainty, the measurement scale, and the study design. A statistical test alone does not indicate whether a change is large or meaningful. Here, the missing outcome estimates prevent even a description of the observed magnitude, while the nonrandomized before-and-after design would remain important when considering causal interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry summary names six oxidative-stress measures: TOS, TAS, OSI, MDA, Ox-LDL, and SOD. TOS is identified as the primary outcome. The record also lists five analyses, but does not describe their relationship to the six measures or specify which analyses were confirmatory. The analysis plan and any adjustment for multiple comparisons are not reported in the registry record.

In general, evaluating several outcomes can make an isolated small p-value less persuasive if no multiplicity strategy was planned. Possible approaches include identifying a primary outcome in advance, adjusting the threshold for a family of tests, or interpreting secondary results as exploratory. Which approach was used is not reported. The primary-outcome designation helps identify the main question, but does not by itself show how the other outcomes were handled.

Missing-data methods and the analysis population are also not reported in the registry record. The outcome description says serum samples from 39 patients were compared, but this does not state whether all scheduled measurements were available or how incomplete pairs were treated. In general, excluding participants with missing follow-up can affect interpretation if the reasons for missingness are related to measurements or participant characteristics. No such reasons or handling procedures are described.

Further details that would support assessment of the analysis—including protocol deviations, prespecified exclusions, imputation, and sensitivity analyses—are not reported in the registry record. Without these details and the numerical results, readers cannot assess the robustness of the outcome analyses.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event entry lists the group as patients diagnosed with attention deficit and hyperactivity. It records 53 in the at-risk fields for both serious and other adverse events, zero serious events, 26 other adverse events, and zero deaths. These are registry figures; the record does not provide event descriptions or explain how the counts were derived.

The at-risk figure of 53 differs from the listed enrollment of 39. The registry record does not explain this discrepancy, so the relationship between those figures cannot be determined from the record. The count of other adverse events should not be interpreted as a count of affected participants unless the registry specifies that meaning; that detail is not reported. The record also does not state whether events were judged related to methylphenidate, how they were collected, or what observation period applied to the safety entry.

In general, a zero count for serious events in a registry entry does not establish that risk is absent, particularly when the denominator and ascertainment details are unclear. These figures are a limited safety record, not a comparison of event rates between treatment groups: no control group is described.

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

The study addresses a focused laboratory question: whether serum TOS changes from before methylphenidate initiation to the measurement after treatment has begun, up to the 3rd month. The registry also identifies five additional oxidative-stress measures. The recorded methods and timing indicate an intention to examine within-patient biomarker change among children whose treatment was already planned.

The registry record does not report the measured values or estimated changes for TOS or the other biomarkers. It also does not report uncertainty intervals or test results. Therefore, the posted record does not establish whether any measure increased, decreased, or remained similar, nor how precisely a change was estimated. Completion status alone cannot answer those questions.

Even with reported before-and-after results, the observational design would limit causal conclusions. A change during the period after treatment initiation could reflect treatment, time, or other factors that changed alongside treatment. Since no untreated or alternative-treatment comparison is reported, this design cannot isolate the effect of methylphenidate from those possibilities.

The results would also concern measured serum biomarkers, not necessarily symptoms, functioning, or other clinical outcomes. The registry record does not report those clinical outcomes. In general, a laboratory measurement can be informative about a biological question without directly establishing a clinical benefit or harm. Interpretation would depend on the size and uncertainty of the biomarker changes, the measurement’s validity, and the broader evidence, none of which can be assessed fully from this record.

The appropriate reading is thus limited: the record documents a completed observational study with a specified primary biomarker endpoint and planned pre-treatment and follow-up measurements. It does not report findings that would support a conclusion about the direction, magnitude, or clinical implications of any change.

13. Why This Trial Matters Statistically

This study illustrates a common distinction in clinical research: a registered outcome and a completed study are not the same as a reported result. The registry specifies TOS as the primary endpoint, gives a measurement schedule, and describes laboratory procedures. Yet the outcome values and their uncertainty are not reported in the registry record. Without them, readers cannot evaluate the magnitude or precision of the primary comparison.

Its design also highlights the difference between measuring change and estimating a causal effect. Repeated measurements can describe how a biomarker varies within the participating group. But a before-and-after comparison without a concurrent control group cannot show whether an observed change is attributable to treatment rather than other changes over time. This distinction matters even when the treatment began before study participation and was not altered by the study.

The record names multiple oxidative-stress measures, making clear why prespecifying a primary outcome and documenting how secondary analyses are handled are important. Without a reported multiplicity strategy, analysis plan, and outcome estimates, readers cannot judge whether secondary findings were exploratory or how they should be interpreted.

Finally, the discrepancy between listed enrollment and the adverse-event at-risk figures illustrates the value of transparent denominators and clear definitions. The registry does not explain that difference. Careful reporting of analysis populations, missing measurements, and safety ascertainment would help readers understand both what was measured and how much confidence to place in the estimates.

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 central limitation for interpreting findings is that numerical results for the primary outcome and the other oxidative-stress measures are not reported in the registry record. No estimate of change, confidence interval, or test result is available. The direction, size, and precision of the biomarker findings therefore cannot be assessed.

The design is observational and uses measurements before and after treatment initiation without a reported untreated or alternative-treatment control group. This limits causal interpretation of any change over time. The registry does not report random allocation, and the allocation method is not stated. Details needed to evaluate selection, confounding, or the representativeness of the participants are not reported in the registry record.

The registry identifies enrollment as 39 and describes samples from 39 patients for the primary comparison, but does not report completeness of follow-up or the analysis population. Missing-data handling, exclusions, protocol deviations, and sensitivity analyses are not reported. The relationship between the six named measures and five listed analyses, as well as any multiplicity adjustment, is also not described.

Safety interpretation is limited because the at-risk figures are 53 while enrollment is 39, and the record does not explain the discrepancy. Event definitions, ascertainment procedures, observation period, and attribution to treatment are not reported. These limitations do not show that a particular bias or safety issue occurred; they identify uncertainties that the registry entry leaves unresolved.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of Methylphenidate Treatment on Oxidative Stress Levels in Children Diagnosed With Attention Deficit Hyperactivity Disorder (ADHD) — NCT06844812.
• Registry record last updated 2025-06-08; status last verified 2025-05.
• Results first posted 2025-06-08.
• 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 lists NCT06844812 as a completed, non-interventional study sponsored by Saglik Bilimleri Universitesi. The recorded start date is 2024-06-26, the primary completion date is 2025-01-06, and enrollment is 39.

Children diagnosed with ADHD who were already planned to start methylphenidate were invited to participate. The primary outcome is change in serum TOS, measured before treatment and up to the 3rd month. TAS, OSI, MDA, Ox-LDL, and SOD are also named in the study summary.

The primary outcome is described as a mean with standard deviation and unit U/ml. The registry record does not report the outcome estimates, their uncertainty, or the statistical analysis details needed to interpret the findings. It describes no untreated or alternative-treatment control group.