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 Attention Deficit Disorder Medication Response Study (NCT01727414), a randomized phase 4 study. The primary outcome is Attention Deficit Hyperactivity Disorder Total Symptom Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01727414 |
| Phase | Phase 4 |
| Condition | ADHD - Inattentive Type, ADHD - Combined Type |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 171 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Children's Hospital Medical Center, Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
Children with ADHD-inattentive type or ADHD-combined type. The study summary describes recruiting children ages 7-11 whose primary difficulty was attention problems and who had never taken behavioral or psychiatric medications. The registry record lists both ADHD types as conditions and describes separate groups for inattentive and combined type.
Intervention
OROS-methylphenidate given at low, medium, and high doses, each for one week. In the arm descriptions, every participant receives all three active dose levels and placebo during the titration trial.
Comparator
Placebo, also given for one week during the trial. The sequence of placebo and active-dose weeks was randomized, so treatment condition was not tied to a common calendar week across all participants.
Primary question
How do ADHD total symptom scores, rated by parents and teachers, vary across placebo and the three methylphenidate dose conditions, and how does the response relate to ADHD type? The registry record names the score and measurement conditions but does not report numerical outcome results or a specific statistical comparison answering this question.
The clinical question has two connected parts: describing symptom ratings under each dose condition and examining response in children with inattentive-type versus combined-type ADHD. The record’s brief summary frames the study as investigating whether response differs between these groups. It also describes weekly parent and teacher ratings of behavior and side effects during the titration trial. The registered primary outcome is the ADHD Total Symptom Score, assessed at the end of each treatment condition. However, the registry record does not report the group means, standard deviations, estimated differences, confidence intervals, or test results for those conditions. The question can therefore be identified from the study design and registered outcome, but the posted information does not establish the size, precision, or statistical strength of any dose or ADHD-type contrast.
3. Trial Design
The registry identifies this as a phase 4, randomized, quadruple-masked crossover trial, with an enrollment of 171 and a completed status. The listed conditions are ADHD-inattentive type and ADHD-combined type. The sponsor is Children's Hospital Medical Center, Cincinnati. The recorded study start is 2006-06, and primary completion is recorded as 2013-07.
The crossover structure means that participants were assigned to treatment sequences and received multiple conditions over the course of the trial, rather than being assigned to only one condition for the entire study. The arm descriptions state that every participant in each ADHD-type group received low-dose, medium-dose, and high-dose methylphenidate, along with placebo, for one week each. The primary-outcome description explains that the order was randomized and that treatment conditions therefore cannot be mapped to the same calendar week for all participants. This design supports within-participant comparisons in principle, because measurements can be observed under more than one condition for the same child. The record does not describe the statistical model used to account for repeated measurements or treatment sequence.
The masking information is not fully consistent across the record. The trial-design field says quadruple masking, while the arm descriptions say triple-blinded. The summary says the study doctor, family, and teacher would not know the assigned condition for a given week. The registry record does not explain the difference between these descriptions, so the exact set of masked roles cannot be resolved from the posted information.
The summary describes parent and teacher ratings during each treatment week and says families met with the study doctor for a physical examination and discussion. Some children were also to undergo neuropsychological testing, but the registry record does not provide a corresponding result for that testing as a registered primary outcome. The recorded primary endpoint is the symptom score.
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
| Stage | Inattentive Type | Combined Type |
|---|---|---|
| STARTED | 126 | 45 |
| COMPLETED | 123 | 45 |
| NOT COMPLETED | 3 | 0 |
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: Children meeting DSM-IV criteria for ADHD-inattentive type are in the Inattentive Type Arm, while children meeting DSM-IV criteria for ADHD-combined type are in the Combined Type Arm.
| Characteristic | Unit | Inattentive Type | Combined Type | Total |
|---|---|---|---|---|
| Participants analysed | 126 | 45 | 171 | |
| Age, Continuous | years | 8.6 (SD 1.3) | 7.9 (SD 1.0) | 8.4 (SD 1.3) |
| Sex: Female, Male: Female | Participants | 40 | 9 | 49 |
| Sex: Female, Male: Male | Participants | 86 | 36 | 122 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 15 | 21 |
| Race (NIH/OMB): White | Participants | 109 | 30 | 139 |
| Race (NIH/OMB): More than one race | Participants | 8 | 0 | 8 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Attention Deficit Hyperactivity Disorder Total Symptom Score, measured over End of placebo dose week, End of low dose week, End of medium dose week , End of high dose week.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the Attention Deficit Hyperactivity Disorder Total Symptom Score, reported as a mean with a standard deviation. It is assessed using parent and teacher Vanderbilt Attention Deficit Hyperactivity Disorder Rating Scales completed during each of the four treatment weeks: placebo, low dose, medium dose, and high dose.
The score ranges from 0 to 54 and sums 18 symptom items. Each item is rated from 0, meaning none, through 3, meaning very often. Higher total scores indicate worse outcomes. In general, a summed rating scale can turn responses to several related questions into a single measure, making it possible to describe symptom burden under different treatment conditions. The parent and teacher forms offer ratings from two observers, although the registry record does not specify how those ratings were combined or whether they were analyzed separately.
The endpoint is relevant to the stated clinical question because it records symptom ratings under placebo and each active dose. Its repeated measurement across conditions also fits the crossover design. Interpretation still depends on knowing the reported values and how comparisons were conducted. The registry record does not provide numerical means or standard deviations for any condition, nor does it report an estimated contrast, confidence interval, or test result. It therefore specifies what was measured and how to interpret the direction of the scale, but not the observed primary-outcome findings.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized crossover study and a continuous primary outcome measured under four treatment conditions. It does not report numerical primary-outcome results. In particular, no condition-specific means or standard deviations, estimated treatment contrasts, confidence intervals, or significance tests are included in the posted results described by the record. The size and precision of the observed symptom-score differences therefore cannot be evaluated from this information.
The outcome’s direction is specified: higher ADHD Total Symptom Scores indicate worse outcomes. This allows a reader to understand the direction of any reported means or contrasts if they are available elsewhere in the registry record. But the direction alone does not show whether scores differed across placebo and active doses, whether dose conditions differed from one another, or whether the patterns differed between the ADHD-type groups. Those results are not reported in the registry record.
The study’s crossover structure is important to interpretation. In general, measurements from the same child under different conditions are related, rather than independent observations. Statistical comparisons should account for that within-participant relationship; treating each condition as if it came from unrelated groups can misstate uncertainty. The registry record does not report the model or method used for the primary analysis, so it is not possible to determine how repeated measurements, dose sequence, or ADHD type were handled.
The score was assessed by both parents and teachers. These are different sources of ratings, and their observations need not be identical. The record does not state whether the two ratings were analyzed separately, combined into a single score, or handled in another way. This missing detail matters because it affects what the endpoint estimate represents and how precisely it can be interpreted.
The record lists one primary outcome measure with multiple treatment conditions. It also indicates that the outcome was not reduced to one comparison because it has several categories or time points. The registry record does not report which contrasts were designated as primary, whether adjustment for multiple comparisons was used, or what inferential procedure was planned. Without these details and the numerical estimates, no conclusion about evidence for a dose pattern or a difference by ADHD type can be drawn from the posted primary-outcome information.
The enrollment figure and the adverse-event counts provide context about the study record, but they do not substitute for primary-outcome results. The fact that the trial is marked completed does not itself supply estimates of symptom change. The defensible interpretation is therefore limited: the registry describes a randomized, masked, multi-condition crossover design and defines the symptom scale, while the numerical findings needed to quantify treatment-condition differences are not reported in the registry record.
9. Statistical Methods Explained
The methods can be understood by separating the design, the outcome scale, and the missing information about the analysis. The trial is described as randomized and crossover. Randomization concerns assignment to an order of conditions; crossover means participants experience multiple conditions. The registry says participants received placebo and three active methylphenidate dose levels for one week each, in randomized order. This arrangement differs from a parallel-group design in which a participant remains in one assigned condition throughout.
Why does crossover structure matter?
In general, repeated observations from one participant tend to share features because they come from the same person. A comparison that uses each participant’s ratings across conditions can account for that relationship. In contrast, a method that treats every condition’s observations as independent may not represent the data structure appropriately. Crossover trials can also require attention to treatment sequence and possible carryover: a prior condition could affect observations during a later condition. These are general statistical considerations, not claims that such effects occurred in this study. The registry record does not report whether carryover was assessed, how sequence was modeled, or which analysis method was used.
What does the mean and standard deviation describe?
The primary endpoint is continuous, and the record specifies the mean and standard deviation as its summary statistics. In general, a mean describes the center of a set of scores, while a standard deviation describes how spread out scores are around that center. Those summaries can help describe the distribution within a treatment condition, but they do not by themselves provide an adjusted comparison between conditions. For a crossover design, the variation in within-participant changes can be especially relevant to the precision of a treatment contrast. The posted record does not give the condition-specific means or standard deviations, nor a measure of within-participant variation.
How should a confidence interval be read?
In general, a confidence interval presents a range of values compatible with an estimate under the assumptions of the statistical method. Its width gives information about precision: a narrower interval indicates greater precision than a wider interval, all else equal. An interval for a treatment contrast would also show which directions and magnitudes remain compatible with the data. No confidence interval for the primary endpoint is reported in the registry record, so the precision of any condition comparison cannot be assessed from the posted information.
What does the scale’s range mean?
The total score ranges from 0 to 54 and sums 18 symptom items scored from 0 to 3. The record states that higher scores indicate worse outcomes. In general, bounded rating scales have limits on possible values, so the observed distribution may not always behave like an unbounded, normally distributed measure. Whether that concern is important depends on the actual data and the analysis. The registry record does not provide distributions, diagnostic checks, or details about any transformations or alternative models.
What is over-dispersion, and is it relevant?
Over-dispersion is a general issue when observed variability is larger than a model’s assumptions allow; it can make uncertainty estimates too small if ignored. It is often discussed for count outcomes, while this trial’s registered primary measure is a continuous summed rating score analyzed as a mean with standard deviation. The record does not report a model or evidence of over-dispersion, so it would be inappropriate to claim that over-dispersion affected this analysis. The broader lesson is that variability and model assumptions should be checked against the type and distribution of the actual outcome.
How should dose patterns and group differences be tested?
The stated question involves several active doses, placebo, and two ADHD types. In general, researchers may examine individual contrasts, an overall condition effect, or whether the condition pattern differs by group. These are distinct statistical questions. Multiple comparisons can increase the chance of a false-positive finding if a suitable strategy is not planned or used. The registry record does not report a statistical plan, a hierarchy of contrasts, or a multiplicity adjustment. It therefore does not establish which of these questions was tested or how results should be interpreted jointly.
What does the planning illustration represent?
The record describes a sample-size planning illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are planning illustrations, not observed power and not trial results. The record says that non-time-to-event illustrations use participants per arm, while time-to-event illustrations use a total event count. It does not report numerical planning outputs in the information available for interpretation here, and these assumptions should not be mistaken for the trial’s original design justification. The registry record does not report the original sample-size justification.
Overall, the design and endpoint are described, but the statistical analysis plan and numerical estimates are not. General principles explain why repeated measurements, outcome variability, and multiple comparisons matter; they do not fill in the missing analysis details or establish an effect for this trial.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is measured under placebo and three active dose conditions, and the study includes two ADHD-type groups. This creates several possible comparisons, including condition differences within a group and differences in condition patterns between groups. The registry record does not identify which contrasts were prespecified as primary or report a method for controlling the risk of false-positive findings across multiple tests. The outcome entry also indicates that the measure has multiple categories or time points and was not reduced to one comparison. Without a stated testing strategy and posted results, the statistical status of any individual contrast cannot be assessed.
The registry record does not report how missing outcome ratings were handled. It does not state whether all randomized participants contributed ratings under all conditions, how incomplete records were treated, or whether any sensitivity analyses were performed. In general, missingness can affect both the estimate and its uncertainty, especially when the availability of a rating is related to the participant’s condition or response. That is a general concern, not evidence that a particular missing-data problem occurred in this study.
Analysis populations are also not described in the posted information. The record does not state whether analyses followed an intention-to-treat principle, used participants with complete crossover measurements, or applied another population definition. The registry lists enrollment, but enrollment alone does not tell a reader how many participants contributed to each outcome analysis or how exclusions were handled.
Finally, the record does not report the statistical model, covariates, handling of repeated measures, or whether parent and teacher ratings were combined. These omissions limit assessment of both the analysis choices and the reliability of any treatment-condition inference.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Inattentive Type | 0 | 123 | 0.0% |
| Combined Type | 0 | 45 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Inattentive Type | 0 of 123 |
| Combined Type | 0 of 45 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Inattentive Type | 17 of 123 |
| Combined Type | 8 of 45 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Inattentive Type | Combined Type |
|---|---|---|---|
| Irritability | Nervous system disorders | 17 of 123 | 8 of 45 |
The registry’s adverse-event entries distinguish serious adverse events from other adverse events. For the Inattentive Type group, the record lists 0 serious adverse events among 123 at risk and 17 with other adverse events among 123 at risk. It lists 0 deaths. For the Combined Type group, it lists 0 serious adverse events among 45 at risk and 8 with other adverse events among 45 at risk, with 0 deaths.
These are the counts recorded in the registry, not a complete description of the events. The record does not list serious-event terms, and it does not give details about the nature, timing, duration, or severity of the other adverse events in the information. The zero counts for serious events and deaths describe what was recorded; they do not demonstrate that no unrecorded events occurred or establish comparative safety between treatment conditions.
The groups are defined by ADHD type, not by placebo versus a particular dose. The posted safety figures therefore should not be read as a dose-specific comparison. The registry record also does not describe a statistical comparison of adverse-event counts or explain how participants were assigned to these safety reporting groups. In general, adverse-event counts are most informative when their definitions, observation periods, and treatment exposure are clear. Those details are not reported sufficiently to support a more detailed safety interpretation.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this study was designed to compare symptom ratings across placebo and three methylphenidate dose conditions in a randomized crossover setting, with children in inattentive-type and combined-type ADHD groups. It also specifies the rating scale, its score range, and the direction of interpretation. These details make the intended clinical question understandable.
However, the posted information does not include the numerical primary-outcome results. There are no condition-specific means or standard deviations, no estimated contrasts, and no confidence intervals or test results. As a result, it is not possible to quantify the observed symptom-score pattern, its precision, or the evidence for differences among conditions or between ADHD types. The registry’s completed status does not replace those estimates.
The design alone cannot establish the direction or size of an outcome effect. Randomization and crossover can support useful comparisons when the analysis appropriately reflects repeated observations and treatment sequence, but the registry record does not report the analysis method or the handling of missing data. The lack of those details does not show that the analysis was inadequate; it means readers cannot evaluate the method from the posted record.
The adverse-event entries are limited as well. They report the listed serious and other adverse-event counts by ADHD-type group, but do not identify events by dose condition or provide descriptions of the other events. They therefore cannot be used to make a dose-specific comparison from the information recorded.
The careful conclusion is narrow: the trial record documents a completed randomized crossover study and a defined symptom-rating endpoint, but the primary numerical findings needed to assess treatment-condition differences are not reported in the registry record. No claim about whether a treatment works or does not work follows from the design description alone.
13. Why This Trial Matters Statistically
This trial raises several statistical issues that are central to interpreting crossover studies. A participant contributes measurements under multiple conditions, so the observations are connected. In general, analysis should reflect that pairing rather than treat condition groups as wholly independent. The registry record identifies the crossover design but does not state the model used to represent repeated ratings.
The randomized order is another relevant feature. The outcome description explains that placebo and active doses were given in varying order, so calendar week does not correspond to a common treatment condition for everyone. This is important for understanding the time frame of the endpoint and for avoiding comparisons that confuse treatment condition with week. The record does not explain how the analysis accounted for sequence or possible period effects.
The endpoint also illustrates how a clinical question can involve multiple related tests. There are several dose conditions and two ADHD-type groups, and the record does not state which comparisons were primary or how multiplicity was handled. Prespecifying a testing strategy helps readers distinguish a focused hypothesis from exploratory contrasts. Without that information and the numerical results, the evidence for any particular comparison remains unavailable.
Finally, the outcome is rated by parents and teachers. Considering how different observers’ ratings are combined or separately interpreted is important because they represent distinct sources of measurement. The registry record defines the scale and its direction, but not the treatment of the two rating sources in the analysis.
These issues matter beyond this trial: a clear design description is only one part of statistical interpretation. Readers also need the estimates, uncertainty, analysis population, missing-data approach, and multiplicity plan to judge what the data support. The record gives a useful framework for the question but does not provide those elements for the primary outcome.
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 principal limitation for interpreting the registered primary outcome is that numerical results are not reported in the registry record. Without condition-specific summaries and comparative estimates, the magnitude, direction, and precision of differences cannot be assessed. The score definition alone does not reveal how participants’ ratings changed across conditions.
The registry does not report the primary analysis method. This is particularly relevant for a crossover design with repeated observations, multiple treatment conditions, randomized sequence, and two ADHD-type groups. The record also does not explain how parent and teacher ratings were combined or whether they were analyzed separately. Those details are needed to understand the target of the estimate and how uncertainty was calculated.
Further information is absent about missing outcome data, analysis populations, exclusions, and sensitivity analyses. The record does not report a multiplicity strategy for the several possible condition and group comparisons. These omissions prevent a full appraisal of the analysis, but they should not be treated as proof that the trial had missing data, inappropriate methods, or biased results.
The masking description is inconsistent: the design field identifies quadruple masking, while the arm descriptions state triple-blinded treatment. The brief summary names the study doctor, family, and teacher as unaware of the weekly condition, but the record does not reconcile these accounts. The exact masking roles are therefore unclear from the registry record.
Safety information is also limited to counts by ADHD-type group. The record does not describe the other adverse events or report dose-specific safety comparisons. Finally, the study summary describes a particular pediatric population, including ages 7-11 and no previous behavioral or psychiatric medication, while the outcome entry does not provide further population-specific analysis details. The posted record does not establish how broadly findings would apply beyond the groups described.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Attention Deficit Disorder Medication Response Study — NCT01727414.
- Registry record last updated 2021-05-18; status last verified 2021-04.
- Results first posted 2017-07-18.
- 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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18. Record Summary
The registry identifies NCT01727414 as the Attention Deficit Disorder Medication Response Study, with the official title Medication Response in Children With Predominately Inattentive Type ADHD. It is listed as phase 4, randomized, crossover, and completed, with quadruple masking indicated in the design field. Enrollment is 171. The listed conditions are ADHD-inattentive type and ADHD-combined type.
The study record describes four one-week conditions: placebo and low, medium, and high doses of OROS-methylphenidate. The primary outcome is the ADHD Total Symptom Score, assessed from parent and teacher Vanderbilt ratings and reported as a mean with standard deviation. The score ranges from 0 to 54, with higher scores indicating worse outcomes.
The record gives serious and other adverse-event counts by ADHD-type group and reports 0 deaths in each group. Numerical primary-outcome results, the statistical analysis method, missing-data handling, and a multiplicity strategy are not reported in the registry record. The masking description also differs between the design field and arm descriptions.