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 A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall (NCT00468143), a randomized phase 4 study. The primary outcome is Medication Event Monitoring System (MEMS®) Dosage Adherence.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00468143 |
| Phase | Phase 4 |
| Condition | Attention Deficit Hyperactivity Disorder |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 62 |
| Arms in the primary outcome | 2 |
| Lead sponsor | NYU Langone Health |
| Results posted | Yes |
2. Clinical Question
Population
Adults with Attention Deficit Hyperactivity Disorder who completed the study. The registry lists an enrollment of 62, while the primary outcome description identifies the population as participants who completed the study. The outcome entries list 49 participants for each treatment.
Intervention
Adderall XR, the extended-release formulation. Participants received the formulations in a counterbalanced crossover design, with a washout period between treatment periods.
Comparator
Adderall immediate release. The study compared the formulations within a crossover design rather than describing separate parallel groups that each remained on one formulation.
Primary question
What percentage of participants met the registry's medication-adherence threshold while receiving each formulation? Adherence was defined using Medication Event Monitoring System bottle openings relative to prescribed doses, with adherence set at at least 75% of doses.
The registry describes this as a pilot study comparing the formulations in terms of effectiveness and side effects for adult ADHD. The posted primary outcome, however, is specifically about dosage adherence, not a direct measure of symptom improvement or treatment effectiveness. It reports 42.7% for immediate release and 66.2% for extended release, with 49 listed for each treatment outcome. Those percentages describe the registry's adherence endpoint; they do not by themselves establish whether the formulations differ reliably or clinically.
The crossover design is relevant to the question because participants could receive each formulation during different treatment periods. That structure can make within-person comparisons possible, but the record does not post a statistical comparison accounting for the paired or repeated observations. The primary question that can be answered from the posted result is therefore descriptive: what adherence percentages were recorded for the formulations? Whether the observed pattern reflects a treatment difference beyond chance, and how precisely it estimates that difference, is not reported in the registry record.
3. Trial Design
This was a phase 4, randomized, single-masked, counterbalanced crossover study sponsored by NYU Langone Health. The condition listed is Attention Deficit Hyperactivity Disorder. The registry lists enrollment of 62 and a completed status. The study began in 2007-08, and primary completion was recorded in 2009-01.
Participants received immediate-release and extended-release Adderall in different treatment sequences. The arm descriptions indicate that one sequence began with extended release and another began with immediate release. Participants then received the alternate formulation after a washout period. The descriptions also refer to trial phases 2 and 3, but the available wording is incomplete. The duration and operational details of the washout period are not reported in the registry record. The record identifies masking as single but does not specify which participants, clinicians, or study personnel were masked.
In a crossover trial, each participant can contribute information under more than one treatment condition. The comparison can therefore involve within-participant observations, rather than a simple comparison of independent groups. Counterbalancing treatment order can help distribute order effects across sequences, while a washout is intended to limit carryover between periods. These are general features of crossover designs; the registry record does not describe how order, period, or carryover effects were handled analytically.
The recorded enrollment and the outcome population are not interchangeable descriptions. The primary outcome states that its population consists of participants who completed the study, and the outcome entries list 49 for each formulation. The registry does not explain the movement from enrollment to the outcome population, whether all completers contributed data to both treatments, or how incomplete treatment periods were handled.
The study lists pill count and self report as secondary outcomes, along with five outcome measures overall. No statistical analysis entries are posted. The registry record does not report a sample-size justification, interim analysis plan, detailed statistical analysis plan, or the identity of the party masked.
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: Individuals who were currently receiving amphetamine or methylphenidate treatment underwent a 7-day washout period before the baseline visit; those receiving atomoxetine or other medications for ADHD were required to undergo a 28-day washout period before the baseline visit. While 62 subjects started the study, only 49 finished the full study.
First Intervention (3 Weeks)
| Stage | Extended Release First | Immediate Release First |
|---|---|---|
| STARTED | 31 | 31 |
| COMPLETED | 28 | 27 |
| NOT COMPLETED | 3 | 4 |
Reasons for not completing this period:
| Reason | Extended Release First | Immediate Release First |
|---|---|---|
| Withdrawal by Subject | 3 | 4 |
Second Intervention (3 Weeks)
| Stage | Extended Release First | Immediate Release First |
|---|---|---|
| STARTED | 28 | 27 |
| COMPLETED | 25 | 24 |
| NOT COMPLETED | 3 | 3 |
Reasons for not completing this period:
| Reason | Extended Release First | Immediate Release First |
|---|---|---|
| Withdrawal by Subject | 3 | 3 |
Analysis population for the primary outcome, as defined in the registry: These is the total of participants who completed the study.
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 | All Participants |
|---|---|---|
| Participants analysed | 62 | |
| Age, Continuous | years | 35.7 (SD 10.3) |
| Sex: Female, Male: Female | Participants | 28 |
| Sex: Female, Male: Male | Participants | 34 |
| Race/Ethnicity, Customized: Caucasian | Participants | 46 |
| Race/Ethnicity, Customized: African American | Participants | 7 |
| Race/Ethnicity, Customized: Hispanic | Participants | 5 |
| Race/Ethnicity, Customized: Asian | Participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Medication Event Monitoring System (MEMS®) Dosage Adherence, measured over The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants adherent |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is Medication Event Monitoring System dosage adherence, expressed as the percentage of participants adherent. The registry defines the underlying adherence measure as the number of bottle openings divided by the number of doses prescribed. A participant was counted as adherent when the measure reached at least 75% of prescribed doses. The endpoint is therefore a threshold-based summary of medication-taking behavior, rather than a continuous summary of the proportion of doses taken.
The registry says MEMS information was noted at clinic visits 3, 4, 5, 7, 8, and 9 over 8 weeks. Electronic bottle-opening records can provide a measure of medication access behavior over time. As a general limitation, an opening is a recorded event and does not prove that a dose was swallowed. A threshold endpoint also compresses variation: participants just below and well below the cutoff are grouped as not adherent, while participants at or above it are grouped as adherent.
The endpoint can help characterize whether participants followed the prescribed dosing schedule, which is relevant when comparing formulations. It is not, by itself, a symptom, functioning, or safety outcome. The registry reports percentages of participants classified as adherent, but does not report the underlying distribution of adherence values or a confidence interval for either percentage.
The posted result gives 42.7% for immediate release and 66.2% for extended release. The record lists 49 for each treatment outcome and describes the population as participants who completed the study. It does not provide further detail about how missing monitor records or incomplete periods affected endpoint classification.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is descriptive. The registry reports that 42.7% of participants met the adherence criterion with immediate release, compared with 66.2% with extended release. The criterion was at least 75% of prescribed doses, based on the ratio of bottle openings to prescribed doses. The outcome entries list 49 participants for each formulation.
These percentages give the observed adherence classifications in the registry, but they do not establish the precision of the comparison. No confidence interval, p-value, adjusted estimate, or sponsor-reported statistical test is posted. A confidence interval, as a general statistical concept, describes a range of values compatible with the data under a specified method; without one, readers cannot gauge the uncertainty around the reported percentages from the registry results alone. The record also does not post a treatment-effect estimate from an analysis that accounts for the crossover structure.
The same people may contribute observations under both formulations in a crossover study. Thus, the outcome entries should not be read as if they necessarily represent unrelated participant groups. The registry does not report the overlap in participants contributing to each treatment outcome or the participant-level paired outcomes. A comparison that ignores the relationship between observations could misrepresent uncertainty. Conversely, a suitable within-person analysis would need information on the paired measurements and the handling of treatment sequence and period.
The difference in the posted percentages is not enough to infer a statistically reliable treatment effect, a clinically important difference, or an effect on ADHD symptoms. The primary endpoint concerns adherence, and the record does not post the inferential analysis needed to quantify uncertainty. It also does not supply a prespecified threshold for what would count as a clinically meaningful adherence difference.
The study is described as a pilot, but no sample-size justification or precision target is reported in the registry record. The enrollment and outcome counts alone do not determine whether the comparison was adequately powered. Sample-size calculations are planning exercises based on stated assumptions; they are not evidence that an observed effect is real, and they should not be described as observed power.
The posted adverse-event figures separately list 0 serious adverse events in each treatment group and an other-adverse-event figure of 53 in each group. These are registry summaries, not a basis for comparing safety without details on event definitions, event types, timing, and analysis. The record does not report deaths. Overall, the outcome values describe adherence classifications and adverse-event counts, while the degree of statistical uncertainty and the results of any formal treatment comparison remain unreported.
9. Statistical Methods Explained
What does a crossover design change?
In a parallel-group trial, participants are assigned to one treatment group and generally remain in that group for the comparison. In a crossover trial, participants receive treatments in sequence, so observations under different treatments can come from the same participant. This can allow a within-person comparison, which controls for characteristics that stay relatively stable within a participant. That is a general design advantage, not a guarantee of an unbiased estimate.
Period effects can occur when outcomes change over time regardless of treatment. Carryover can occur if the effects of an earlier treatment persist into a later period. Treatment order can also matter. Counterbalancing and a washout period are design features that may address some of these concerns, but their presence does not show that such effects were absent. The registry record does not report tests or adjustments for period, sequence, or carryover effects.
Why does pairing matter for uncertainty?
When the same participant contributes an outcome under each formulation, the observations are statistically related. A within-person comparison uses that relationship. The uncertainty of a paired treatment comparison depends on how the two measurements vary together, not just on the separate percentages. The record gives the treatment-specific adherence percentages and lists 49 for each outcome, but it does not provide participant-level paired data or a paired estimate. Consequently, the uncertainty of the within-person contrast cannot be reconstructed from the posted summaries.
General methods for a binary outcome could include comparing paired classifications, or modeling the repeated observations with an approach that accounts for participant-level dependence. The appropriate choice depends on the analysis plan and data structure. The statistical method used for the posted result is not reported in the registry record. The listed outcome is a percentage meeting a threshold, but the record does not identify a model or test used to compare those percentages.
What does the adherence threshold do?
The endpoint classifies participants using a cutoff of at least 75% of prescribed doses. Dichotomizing a measure can make a result easier to summarize, but it loses information about how far each participant's adherence is from the cutoff. It can also make classification sensitive to small differences around the threshold. These are general properties of threshold-based outcomes. The registry does not post the continuous adherence values, so the distribution and proximity of observations to the cutoff cannot be assessed.
MEMS counts bottle openings, and the registry defines adherence using bottle openings divided by prescribed doses. As a general measurement consideration, a recorded opening may not correspond exactly to taking a dose, and a dose may be taken without a recorded opening. The record does not describe validation procedures or how these possibilities were addressed. Nor does it say how missing monitor data were treated.
How should the percentages and counts be read?
The primary outcome reports 42.7% for immediate release and 66.2% for extended release. Those are the posted percentages classified as adherent, not modeled probabilities or adjusted treatment effects. The entries list 49 for each formulation. Because this is a crossover study, the treatment-specific entries should not be added to describe a total participant count: the same participant may contribute to more than one treatment condition. The registry says the endpoint population includes participants who completed the study, but does not explain exactly how many contributed valid adherence data in each period or how incomplete records were handled.
A confidence interval would communicate uncertainty around an estimate under a specified statistical procedure. A p-value would summarize the compatibility of data with a statistical null model under stated assumptions. Neither is posted for this primary endpoint. Their absence does not establish that a difference is or is not statistically significant; it means the registry result does not provide those inferential quantities.
What can planning calculations tell readers?
Sample-size calculations are prospective planning illustrations. In general, they depend on assumptions about the effect to detect, significance level, allocation, and statistical model. They do not show that a trial achieved a particular power after observing its results, and they are not evidence that an observed effect is reliable. The record's stated planning assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect described as a fraction of the observed effect. No sample-size illustration values are reported in the registry record, and those assumptions should not be confused with the trial's own design justification.
The registry lists 0 analysis entries. It does not report the statistical analysis plan, a treatment-effect estimate with uncertainty, adjustment for the crossover structure, multiplicity procedures, or interim analyses. The posted information therefore supports a descriptive reading of the adherence percentages, but not a reconstruction of the trial's inferential analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures overall and identifies pill count and self report as secondary outcomes. It does not report results or statistical analyses for those secondary outcomes in the available record. The record lists 0 analysis entries. It does not describe which outcomes were prespecified for formal testing, whether the primary outcome was tested once or through multiple analyses, or how any multiplicity was handled.
Multiplicity arises when several outcomes, time points, subgroups, or analysis choices are tested. In general, the more tests conducted, the greater the chance of at least one apparently unusual result under a null model. Methods such as adjustment or hierarchical testing can address this, but the registry record does not say whether any such approach was used. It is therefore not possible to determine how multiplicity might affect interpretation of any unposted analyses.
The primary outcome population is described as participants who completed the study. The record does not report an intention-to-treat analysis, a per-protocol definition, or another named analysis population. It also does not explain how participants with missing adherence information, incomplete treatment periods, or deviations from the prescribed schedule were handled. Missing-data assumptions and imputation methods are not reported in the registry record.
These omissions matter particularly for a crossover study because completion and availability of measurements under each treatment can affect which within-person comparisons are possible. The registry does not give a flow of participants through the treatment sequences or explain whether the listed 49 per treatment represents complete paired outcome data. No conclusions about the impact of missingness or analytic exclusions can be drawn from the posted record.
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 |
|---|---|---|---|
| Extended Release | 0 | 62 | 0.0% |
| Immediate Release | 0 | 62 | 0.0% |
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 |
|---|---|
| Extended Release | 53 of 62 |
| Immediate Release | 53 of 62 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Extended Release | Immediate Release |
|---|---|---|---|
| Insomnia | General disorders | 14 of 62 | 19 of 62 |
| Loss of Appetite/Anorexia | General disorders | 23 of 62 | 5 of 62 |
| Dry Mouth | General disorders | 14 of 62 | 10 of 62 |
| Headache | Vascular disorders | 4 of 62 | 11 of 62 |
| Anxiety | Psychiatric disorders | 7 of 62 | 4 of 62 |
| Feeling Speedy or Wired or Jittery | Psychiatric disorders | 6 of 62 | 4 of 62 |
| Trismus | Musculoskeletal and connective tissue disorders | 1 of 62 | 2 of 62 |
| Nausea | Gastrointestinal disorders | 0 of 62 | 2 of 62 |
The registry lists 62 participants at risk in each treatment group for serious adverse events, with 0 serious adverse events affecting participants in each group. It also lists an other-adverse-event figure of 53 in each group, with 62 at risk in each. The registry does not provide event terms for serious adverse events, and the death figures are not reported.
These figures should be read as separate treatment-group registry entries, not added to create a combined participant total. The crossover design means participants may contribute to both treatment conditions. The record does not clarify whether the other-adverse-event figure refers to participants with one or more events or provides a fuller breakdown by event type, severity, timing, or treatment period. It also does not explain how events occurring across periods were assigned.
A count of 0 serious adverse events in a registry entry does not establish that no safety risk exists. Safety interpretation generally depends on event definitions, exposure, follow-up, severity, and the precision of estimates. No comparative safety analysis or uncertainty interval is posted. The adverse-event summaries therefore describe what the registry records for these categories, but do not support a detailed comparative assessment.
12. What the Result Does, and Does Not, Mean
The result that can be read directly is that the registry reports 42.7% adherence for immediate release and 66.2% for extended release, using a cutoff of at least 75% of prescribed doses. The outcome entries list 49 for each treatment, and the endpoint population is described as participants who completed the study. These figures characterize the posted adherence outcome for this study.
They do not establish that extended release improves ADHD symptoms, functioning, or quality of life. Adherence is a measure of medication-taking behavior, not a clinical outcome. Although the registry's brief summary frames the pilot as a comparison of effectiveness and side effects, the posted primary endpoint is adherence. The record does not give a symptom-based primary result or a formal inferential comparison for adherence.
The observed percentages also do not, on their own, establish a causal difference of a particular size or precision. In a crossover design, observations can be paired within participants, and the record does not post the paired analysis or information needed to calculate its uncertainty. No p-value or confidence interval is reported for the primary endpoint. The record therefore does not establish statistical significance or exclude a chance explanation.
The trial is recorded as completed and lists enrollment of 62. Its outcome population is described as completers, and its treatment outcomes list 49 for each formulation. The registry does not explain the relationship among these counts or the handling of missing observations. Readers should not interpret the treatment-specific entries as independent groups or add them together as a participant total.
More broadly, the result is specific to the participants and measurement procedures recorded in this pilot study. The registry does not provide enough information to assess generalizability, adjustment for sequence or period, or the robustness of the adherence classification. It provides a descriptive comparison, not a complete account of efficacy or safety.
13. Why This Trial Matters Statistically
This study raises a useful statistical issue: a crossover comparison and a simple two-group comparison are not the same analysis. Participants can contribute outcomes under both formulations, so the relationship between their measurements matters. A treatment comparison that recognizes this pairing may have different uncertainty from one that treats each treatment entry as independent. The registry record reports treatment-specific percentages but does not post the analysis needed to assess that within-person relationship.
The endpoint also illustrates how measurement choices shape interpretation. MEMS bottle openings are used to form a ratio and then classify participants using a threshold of at least 75%. The resulting percentage is straightforward to communicate, but it does not show the range of adherence values or how close participants were to the cutoff. The thresholded outcome and the underlying behavior are related, but not interchangeable descriptions.
Another important distinction is between descriptive results and inferential results. The registry supplies adherence percentages, while a formal comparison would also report an estimate of uncertainty and explain how the crossover design was handled. Without those elements, readers cannot judge the precision of the apparent difference or determine what conclusions a prespecified analysis supported.
Finally, this record highlights the value of transparent reporting about populations and missing data. The outcome describes completers, and the entries list 49 for each treatment, while enrollment is 62. Without an account of participant flow, available paired records, and missing-data handling, the analysis population is difficult to characterize. These considerations are central to evaluating a crossover result, not merely technical details.
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 registry record leaves several trial-specific details unclear. The primary outcome identifies completers as its population, but does not explain how participants moved from enrollment of 62 to the outcome entries listing 49 for each treatment. It does not report how many participants contributed usable MEMS records in each period, whether the listed treatment outcomes comprise complete within-person pairs, or how incomplete treatment periods were treated.
The treatment sequence descriptions are incomplete, including a truncated description of the washout period. The record does not report the washout duration, treatment duration, dose details, or the identity of the party masked. It also does not explain whether or how the statistical analysis addressed treatment sequence, period effects, or carryover. These details affect interpretation of crossover data.
The endpoint is based on bottle openings relative to prescribed doses and a threshold of at least 75%. The record does not provide continuous adherence values, details about missing monitor readings, or validation information. Therefore, the sensitivity of the reported classification to measurement error or the chosen threshold cannot be assessed from the registry result.
No confidence interval, p-value, treatment-effect estimate, or formal analysis is posted for the primary endpoint. The registry lists 0 analysis entries and does not report multiplicity procedures, an interim analysis plan, a sample-size justification, or a detailed statistical plan. Secondary outcomes are named, but their results are not reported in the registry record. Finally, the adverse-event summary lacks event-level detail and a comparative analysis, and death figures are not reported. These limitations constrain interpretation of both the adherence result and safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall — NCT00468143.
- Registry record last updated 2016-06-02; status last verified 2016-04.
- Results first posted 2016-06-02.
- 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 completed phase 4 study was a randomized, single-masked, counterbalanced crossover comparison of immediate-release and extended-release Adderall in adults with ADHD. NYU Langone Health is listed as sponsor. The study began in 2007-08, had primary completion in 2009-01, and recorded enrollment of 62.
The primary endpoint was the percentage of participants meeting an adherence threshold of at least 75% of prescribed doses, based on MEMS bottle openings over 8 weeks. The registry reports 42.7% for immediate release and 66.2% for extended release, with 49 listed for each treatment outcome. Pill count and self report are listed as secondary outcomes.
No formal statistical analysis of the primary comparison is posted. Confidence intervals, p-values, missing-data methods, and details of analysis accounting for the crossover design are not reported in the registry record. The serious adverse-event entries report 0 in each treatment group; other-adverse-event figures are 53 in each group. Detailed event terms and death figures are not reported.