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 Adult Study / OROS Methylphenidate Hydrochloride (HCL) (OROS MPH) in Adults With Attention Deficit Hyperactivity Disorder (ADHD) (NCT00937040), a randomized phase 4 study. The primary outcome is Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Score (AISRS) Over Time Using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Fourth Edition for Diagnosis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00937040 |
| Phase | Phase 4 |
| Condition | Attention Deficit Disorder With Hyperactivity |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 357 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ortho-McNeil Janssen Scientific Affairs, LLC |
| Results posted | Yes |
2. Clinical Question
Population
Adults with attention deficit hyperactivity disorder (ADHD). The primary-outcome population is defined as the Intent-to-Treat (ITT) analysis set: randomized subjects who received at least one dose of study medication and had post-baseline efficacy data, excluding ASRS data from that definition. The record does not report the number of participants in this analysis set.
Intervention
OROS methylphenidate hydrochloride (OROS MPH), with an individualized optimal patient dose from 18 mg to 72 mg, taken once daily by mouth for 6 weeks.
Comparator
Placebo matched to the 18 mg to 72 mg dose range, taken once daily by mouth for 6 weeks. The study is described as placebo controlled, randomized, double blind, and parallel group.
Primary question
The study was intended to compare ADHD symptom response between adults treated with OROS MPH and adults treated with placebo. The primary measure was the Adult ADHD Investigator Symptom Rating Score (AISRS), assessed at baseline and endpoint, defined as 42 days or early discontinuation. Numerical group results and an estimate of the treatment contrast are not reported in the registry record, so the magnitude and precision of the comparison cannot be assessed from that record.
3. Trial Design
This completed Phase 4 study was randomized, double blind, and parallel group. Its official title describes a placebo-controlled, individualized-dosing study intended to optimize treatment to an effective response with OROS methylphenidate in adults with ADHD. The registry lists enrollment as 357. The study start is recorded as 2009-07, and primary completion as 2010-02.
The active-treatment arm received OROS MPH at an individualized optimal patient dose from 18 mg to 72 mg, once daily by mouth for 6 weeks. The comparison arm received matching placebo once daily by mouth for 6 weeks. Although the record identifies random allocation, it does not report the allocation ratio, the method used to generate the allocation sequence, or the method used to conceal allocation. The description of double masking does not specify which study roles were masked.
The primary-outcome population was not simply all enrolled participants. It was defined as randomized subjects who received at least one dose of study medication and had post-baseline efficacy data, with ASRS excluded from the stated definition. The size of this analysis population and the number included in each arm are not reported in the registry record. Safety counts use different arm-specific denominators: 175 for placebo and 174 for OROS MPH.
The registry lists 19 outcome measures and 19 analyses. It includes cognitive and executive-function measures, work productivity, daily functioning, and dyadic satisfaction among secondary outcomes. The registry record does not report the detailed protocol, dose-adjustment schedule, or statistical analysis plan. In particular, it does not explain how doses were selected or how the individualization process was implemented.
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 | PLACEBO | OROS MPH |
|---|---|---|
| STARTED | 179 | 178 |
| COMPLETED | 138 | 141 |
| NOT COMPLETED | 41 | 37 |
Reasons for not completing this period:
| Reason | PLACEBO | OROS MPH |
|---|---|---|
| Adverse Event | 5 | 8 |
| Lost to Follow-up | 12 | 12 |
| Protocol Violation | 3 | 0 |
| Withdrawal by Subject | 13 | 7 |
| NONCOMPLIANCE WITH STUDY DRUG | 3 | 2 |
| POST ENROLL EXCLUSIONARY LAB(S)/ECG FIND | 5 | 8 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) analysis set was defined as all randomized subjects who have received at least one dose of the study medication and have any post-baseline efficacy data (not including ASRS).
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.
| Characteristic | Unit | PLACEBO | OROS MPH | Total |
|---|---|---|---|---|
| Participants analysed | 179 | 178 | 357 | |
| Age, Categorical: <=18 years | Participants | 3 | 3 | 6 |
| Age, Categorical: Between 18 and 65 years | Participants | 175 | 173 | 348 |
| Age, Categorical: >=65 years | Participants | 1 | 2 | 3 |
| Age Continuous | years | 34.6 (SD 11.53) | 36.8 (SD 11.87) | 35.7 (SD 11.73) |
| Sex: Female, Male: Female | Participants | 79 | 86 | 165 |
| Sex: Female, Male: Male | Participants | 100 | 92 | 192 |
| Region of Enrollment: USA | participants | 179 | 178 | 357 |
6. Primary Endpoint
The registry lists the primary outcome as Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Score (AISRS) Over Time Using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Fourth Edition for Diagnosis, measured over Baseline, endpoint (42 days or early discontinuation).
| 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 Adult ADHD Investigator Symptom Rating Score (AISRS), reported as a mean with standard deviation. It assesses 18 core ADHD symptoms corresponding to DSM-IV diagnostic symptoms for adult subjects. An investigator rates each symptom on a four-point scale: 0 for none, 1 for mild, 2 for moderate, and 3 for severe. The total score is the sum of the symptom ratings; its stated range is 0 to 54, with higher scores indicating greater symptom severity.
The record specifies assessment at baseline and endpoint, where endpoint is 42 days or early discontinuation. A symptom scale can give a structured way to summarize multiple symptom ratings and compare the pattern of scores between study groups. Repeated assessment also makes it possible to describe scores at more than one point in the study. Those general purposes do not establish which statistical contrast was used in this trial.
The record states that a single missing item is imputed, while a total score is treated as missing if more than one item is missing. It does not describe the item-imputation method. Numerical mean scores, standard deviations, changes from baseline, between-group estimates, confidence intervals, and p-values are not reported in the registry record. Without those results, the scale’s definition can be described, but the trial’s primary outcome cannot be quantitatively interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the intended comparison: individualized-dose OROS MPH versus matching placebo for adults with ADHD. It also defines the primary measure and the assessment times. However, it does not report numerical AISRS results for either arm. In particular, there are no posted means or standard deviations at baseline or endpoint, no reported change from baseline, and no reported between-group estimate. The direction, size, and precision of the primary-outcome contrast therefore cannot be determined from the registry record.
The endpoint is a continuous score, so a mean describes the average score in a group, while a standard deviation describes how spread out participant scores are around that mean. Those summaries would help characterize the observed scores, but a group mean alone would not establish the size or uncertainty of a comparative effect. A direct between-group estimate and its confidence interval would be needed to describe the estimated contrast and its precision. Such results are not reported in the registry record.
The registry’s indication that the primary outcome has several categories or time points means it was not reduced to a single comparison in the available analysis. Baseline and endpoint are specified, but the record does not make a single numerical endpoint contrast available. It also does not state whether the primary analysis compared endpoint scores, changes from baseline, or another summary across time. No particular analysis approach should be inferred from the endpoint description alone.
The study’s enrollment is listed as 357, while the safety denominators are 175 for placebo and 174 for OROS MPH. These figures describe different aspects of the record; the safety denominators should not be treated as the primary-outcome analysis counts. The registry’s definition of the ITT analysis set requires receipt of at least one dose and post-baseline efficacy data, but its actual size is not reported.
The available safety counts can be read descriptively, but they do not resolve the missing primary-outcome information. Serious adverse events affected 1 of 175 participants in the placebo group and 0 of 174 in the OROS MPH group. Other adverse events affected 49 of 175 and 100 of 174, respectively. These counts do not provide a statistical comparison or establish a causal explanation. The registry record does not report the primary-outcome estimate, its uncertainty, or a statistical test, so no conclusion about the comparative symptom response can be drawn from the posted primary-outcome information.
9. Statistical Methods Explained
What does a mean and standard deviation describe?
The primary outcome is a continuous measure summarized as a mean and standard deviation. In general, a mean is the arithmetic average of the observed scores in a group. It gives a location summary, not a description of every participant’s score. The standard deviation describes variation around that group mean. A larger standard deviation indicates more spread in the scores; a smaller one indicates that scores are more concentrated around the mean. These are general interpretations of the statistics named in the registry record.
For an outcome measured at baseline and endpoint, it is possible to report scores at each time, changes from baseline, or a modeled pattern over time. These approaches answer related but not identical questions. A comparison of endpoint scores asks how the groups differ at endpoint. A comparison of changes asks how much the groups’ scores moved from baseline relative to one another. A repeated-measures model can use observations across multiple times. The registry record does not say which approach was used for the primary analysis, and the posted results do not include the numerical outcome values needed to reconstruct a comparison.
What would a confidence interval add?
In general, a confidence interval gives a range of values compatible with an estimated effect under the assumptions of the analysis. It communicates uncertainty as well as the estimate itself. Its interpretation depends on the statistical method and assumptions used. A narrow interval indicates greater precision than a wide interval, while an interval spanning values in both directions may leave the direction of the underlying contrast uncertain. These are general statistical concepts, not descriptions of an interval reported for this trial. A confidence interval for the primary comparison is not reported in the registry record.
A p-value, in general, describes how compatible the observed data are with a specified null hypothesis under a statistical model. It is not a measure of the probability that a treatment effect is true, nor does it describe the size or clinical importance of an effect. A p-value for the primary outcome is not reported in the registry record. The record also does not state the test or model used to analyze the outcome.
What is the role of randomization and masking?
In general, random assignment is intended to make treatment groups comparable, on average, with respect to measured and unmeasured baseline characteristics. Masking is intended to limit influences on care, assessment, or reporting that could arise when treatment assignment is known. This study is recorded as randomized and double blind, but the registry record does not provide the randomization procedure, allocation concealment method, or details about who was masked. These design labels alone do not reveal whether those procedures were implemented successfully.
The parallel-group design means that participants were assigned to one study group rather than crossing between the two treatment conditions as part of the described comparison. The record identifies two arms and their six-week regimens. It does not report adherence, treatment discontinuation counts, or the distribution of dose adjustments, so those aspects cannot be evaluated from the record.
What does the planning illustration mean?
In general, a sample-size planning calculation asks how many participants would be needed under specified assumptions to detect an effect with a chosen error rate and power. It is a planning exercise, not an observed trial result. The assumptions listed for the planning illustration use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the calculation is described in terms of participants per arm. These settings are not evidence that the trial was designed using those assumptions, and they do not constitute observed power.
The registry record does not report the trial’s own sample-size justification. Nor does the available primary-outcome information include the observed effect needed to interpret a planning illustration based on a fraction of that effect. No planning count or trial-specific power can be inferred from the registry entries included in the record.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variation than the data contain, its uncertainty estimates may be too small, which can make statistical evidence appear more precise than it is. Different outcome types and models handle variation differently. The primary AISRS measure is described as continuous, and the registry record does not identify a model or report an over-dispersion assessment for it. This general concept should not be taken to imply that over-dispersion was present or that a particular adjustment was used in this trial.
Overall, the registry record supplies design and endpoint definitions but not enough primary-outcome results or analysis detail to assess the treatment contrast statistically. A full interpretation would require the reported group summaries or model estimate, its uncertainty, and a clear account of the analysis population and method.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 19 outcome measures and 19 analyses. The listed secondary outcomes cover several cognitive and executive-function domains, as well as functioning and self-reported measures. Examining multiple outcomes can raise a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. Statistical plans may address this through a prespecified hierarchy, adjustment, or another strategy. The registry record does not report whether any multiplicity strategy was planned or used, how outcomes were prioritized, or whether the listed analyses correspond to distinct hypothesis tests.
The primary outcome itself is described across baseline and endpoint, with endpoint defined as 42 days or early discontinuation. It was not reduced to a single comparison in the available analysis. The record does not report how the multiple categories or time points were handled statistically, nor does it provide numerical results for those comparisons. No adjustment method or primary contrast should be inferred.
For the AISRS, the stated item-level rule is that a single missing item is imputed, while a total score is treated as missing if more than one item is missing. The specific imputation method is not reported in the registry record. The record also does not report the extent or pattern of missing AISRS data, how missing baseline or endpoint observations were handled, or any sensitivity analyses assessing the influence of missing data.
The ITT analysis set is defined as all randomized subjects who received at least one dose of study medication and had any post-baseline efficacy data, excluding ASRS from that definition. This definition is narrower than a definition based solely on randomization. The record does not report the analysis-set size, participant flow by arm, or whether other populations were analyzed. The extent to which the analysis retained the protection afforded by randomization cannot be assessed from the available details.
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 |
|---|---|---|---|
| PLACEBO | 1 | 175 | 0.6% |
| OROS MPH | 0 | 174 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PLACEBO | 49 of 175 |
| OROS MPH | 100 of 174 |
Most frequent serious adverse event terms
| Event term | Organ system | PLACEBO | OROS MPH |
|---|---|---|---|
| Suicidal Ideation | Psychiatric disorders | 1 of 175 | 0 of 174 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PLACEBO | OROS MPH |
|---|---|---|---|
| Headache | Nervous system disorders | 20 of 175 | 33 of 174 |
| Decreased Appetite | Metabolism and nutrition disorders | 7 of 175 | 25 of 174 |
| Dry Mouth | Gastrointestinal disorders | 3 of 175 | 27 of 174 |
| Initial Insomnia | Psychiatric disorders | 3 of 175 | 17 of 174 |
| Upper Respiratory Tract Infection | Infections and infestations | 9 of 175 | 9 of 174 |
| Nausea | Gastrointestinal disorders | 8 of 175 | 9 of 174 |
| Irritability | General disorders | 6 of 175 | 11 of 174 |
| Insomnia | Psychiatric disorders | 4 of 175 | 12 of 174 |
| Anxiety | Psychiatric disorders | 2 of 175 | 12 of 174 |
| Feeling Jittery | General disorders | 2 of 175 | 11 of 174 |
Serious events with the highest arm-level rate: suicidal ideation (0.6%).
The registry lists serious adverse events separately from other adverse events. In the placebo group, 1 of 175 participants was affected by a serious adverse event; in the OROS MPH group, 0 of 174 were affected. These are participant counts, not a comparison adjusted for follow-up or other factors. The record does not provide a statistical test or confidence interval for this contrast.
For other adverse events, the registry reports 49 affected participants in the placebo group, with 175 at risk, and 100 affected participants in the OROS MPH group, with 174 at risk. These counts should be read as the registry’s reported affected-participant totals; they do not specify the number of distinct event episodes or describe each event’s severity, duration, or relationship to treatment. The record does not provide a statistical comparison of these figures.
Suicidal Ideation is listed among the top serious adverse event terms with a value of 0.6%. The registry entries do not identify a treatment group for that term in the information. The serious-event counts are descriptive and do not establish why an event occurred or whether a treatment caused it. Safety counts also do not replace the missing numerical primary-outcome results.
12. What the Result Does, and Does Not, Mean
The registry record gives a clear description of the question the trial set out to address: whether symptom response differed between adults with ADHD assigned to individualized-dose OROS MPH and those assigned to matching placebo. It identifies a relevant symptom scale, the assessment timing, the treatment regimens, and the randomized, double-blind, parallel design. Those details explain the intended comparison but do not reveal its result.
The record does not report numerical AISRS scores by group, a between-group effect estimate, a confidence interval, or a p-value. Consequently, it does not show the direction or magnitude of the primary-outcome contrast or how precisely that contrast was estimated. No statement that one group had a greater or smaller symptom response is supported by the primary-outcome details available in the registry record.
Even if numerical group means were available, a mean difference would need to be interpreted alongside uncertainty, missing-data handling, analysis population, and the method used to account for measurements over time. A statistical difference, if reported, would not by itself establish clinical importance. Conversely, the absence of a reported statistical result in this record is not evidence that the groups were the same. It means the comparative result cannot be evaluated from the posted primary-outcome information.
The adverse-event counts provide a limited descriptive view of affected participants in each group. They do not establish a causal relationship, compare event timing or severity, or quantify uncertainty around a group contrast. The registry also lists secondary outcomes, but does not provide their numerical results in the information. Therefore, the record supports an account of the study design and intended outcomes, not a conclusion about comparative symptom response or a comprehensive account of safety.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why a detailed design description and a reported result are different things. Randomization, double masking, a parallel-group comparison, and a defined symptom measure describe how the study was intended to generate evidence. They do not substitute for the group data and comparative estimate needed to evaluate that evidence.
The endpoint definition is specific: an investigator-rated total across 18 core symptoms, using a four-point rating for each symptom, with higher totals indicating greater severity. A clear definition supports interpretation of what the score represents. However, statistical interpretation also depends on the analysis contrast, handling of repeated measurements, missing-data methods, and uncertainty around the estimate. Those details are not reported in the registry record.
The registry also illustrates the need to distinguish enrollment from an outcome analysis population. Enrollment is listed as 357, while the primary-outcome population is defined by treatment receipt and availability of post-baseline efficacy data. The actual number analyzed is not reported. Such distinctions matter because analysis denominators affect how readers understand the amount of available information and the population represented by an estimate.
Finally, 19 outcome measures and 19 analyses are listed, while the primary outcome has multiple categories or time points and is not reduced to one comparison. Without a reported analysis plan or multiplicity approach, readers cannot determine how the outcomes were prioritized or how the statistical evidence was interpreted across them. The record makes the study’s intent visible, but its incomplete numerical results limit the statistical conclusions that can be drawn.
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 statistical interpretation is the absence of numerical primary-outcome results. The registry describes the AISRS and its assessment times but does not report group means, standard deviations, a treatment contrast, confidence intervals, or p-values. The outcome is also not reduced to a single comparison because it has several categories or time points. As a result, the primary comparison’s direction, magnitude, and precision cannot be assessed.
Important analysis details are not reported in the registry record. These include the trial-specific statistical analysis plan, the primary contrast, the method for handling measurements across time, the primary-outcome analysis-set size, and any approach to multiplicity. The record lists 19 outcome measures and 19 analyses but does not explain their hierarchy or whether statistical adjustments were used.
Missing-data information is also limited. The AISRS scoring rule specifies how a total score is treated when items are missing and says a single missing item is imputed, but the imputation method is not stated. The number and pattern of missing assessments, the handling of missing endpoint scores, and sensitivity analyses are not reported. The actual sizes of the primary analysis groups are not available.
The design description does not report the randomization sequence method, allocation concealment, or which roles were masked. The individualized-dose description does not explain the dose-adjustment process, and adherence and discontinuation information are not reported. Safety counts are descriptive, without uncertainty estimates or a treatment-group attribution for the listed 0.6% serious-event term. These limitations restrict evaluation of both the efficacy analysis and the context of the safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Adult Study / OROS Methylphenidate Hydrochloride (HCL) (OROS MPH) in Adults With Attention Deficit Hyperactivity Disorder (ADHD) — NCT00937040.
- Registry record last updated 2013-07-30; status last verified 2013-07.
- Results first posted 2011-08-05.
- 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
NCT00937040 is a completed Phase 4 randomized, double-blind, parallel-group study of OROS MPH versus matching placebo in adults with ADHD. The active arm used an individualized dose from 18 mg to 72 mg once daily by mouth for 6 weeks; the placebo arm used matching placebo for the same period. Enrollment is listed as 357, and the primary outcome was the investigator-rated AISRS at baseline and endpoint, defined as 42 days or early discontinuation.
The registry lists 19 outcome measures and 19 analyses. It defines the AISRS scoring range and an item-level missing-data rule, and it reports descriptive adverse-event counts by group. Numerical primary-outcome results and key analysis details are not reported in the registry record. The available record therefore describes the intended comparison and measurement but does not permit a quantitative assessment of the primary treatment contrast.