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 Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta (NCT00181714), a na phase 4 study. The primary outcome is Cigarette Smoking.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00181714 |
| Phase | Phase 4 |
| Condition | ADHD |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 203 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Youths aged 12–17 who met DSM-IV criteria for ADHD were the intended study population. The primary-outcome description identifies the analyzed adolescents as those who took at least one dose of OROS MPH after baseline assessment; that analysis population is reported as N=154.
Intervention
The intervention was extended-duration methylphenidate, also identified as OROS MPH and methylphenidate HCl (Concerta). The study summary describes a six-week open-label treatment period.
Comparator
There was no concurrent comparator group. The design is identified as single group, allocation is listed as NA, and masking is listed as none. The registry record therefore does not describe a randomized, like-for-like treatment comparison.
Primary question
The primary outcome concerned cigarette smoking over 24 months, assessed by youth self-report using a modified version of the Fagerstrom Tolerance Questionnaire. The researchers hypothesized that OROS MPH treatment would be associated with low rates of smoking. A numerical primary-outcome result is not reported in the registry record.
The question is about smoking observed during follow-up among adolescents with ADHD who received open-label OROS MPH, rather than about a difference between treatment groups. Because there is no comparator, the record cannot show whether smoking outcomes differed from those that would have occurred under another treatment or no study treatment. The registry record gives an enrollment of 203, while the primary-outcome description specifies an analysis population of N=154. These figures describe different parts of the record and should not be treated as interchangeable.
3. Trial Design
The registry identifies this as a completed Phase 4 study sponsored by Massachusetts General Hospital. It lists ADHD as the condition, a single-group model, allocation as NA, and masking as none. The study title and intervention identify methylphenidate HCl (Concerta), with the arm described as open treatment with extended-duration methylphenidate, or OROS MPH. The record gives enrollment as 203.
The summary describes a six-week open-label treatment period followed by monthly visits for 24 months. The intended participants were youths aged 12–17 who met DSM-IV criteria for ADHD. The registry lists the study start as 2003-11 and primary completion as 2011-01, and its status is completed.
These design features matter for interpretation. An open-label, single-group study can describe outcomes observed during treatment and follow-up, but it does not provide a concurrent control group for estimating a comparative treatment effect. Since allocation is NA and no comparator arm is listed, treatment-versus-control contrasts, randomized group balance, and masking-based protection against expectations are not part of the design described in the registry record.
The primary outcome is cigarette smoking at the 24-month timeframe. Its description says smoking was assessed by youth self-report using a modified version of the Fagerstrom Tolerance Questionnaire. The analyzed population is described as adolescents who took at least one dose after baseline assessment, with last observation carried forward for participants who did not complete the full 24-month schedule. The registry reports no analysis entry, so additional detail about the actual analytic procedure is not reported in the registry record.
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.
Signed Consent/Enrolled
| Stage | OROS-Methylphenidate |
|---|---|
| STARTED | 203 |
| COMPLETED | 154 |
| NOT COMPLETED | 49 |
Began Treatment With OROS-MPH
| Stage | OROS-Methylphenidate |
|---|---|
| STARTED | 154 |
| COMPLETED | 30 |
| NOT COMPLETED | 124 |
Analysis population for the primary outcome, as defined in the registry: Clinical trial subjects included in this analysis included those adolescents who took at least one dose of OROS MPH following baseline assessment (N=154), with the last observation carried forward (LOCF) for subjects who did not complete the full study schedule of 24 months
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 | OROS-Methylphenidate |
|---|---|---|
| Participants analysed | 154 | |
| Age, Categorical: <=18 years | Participants | 154 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age Continuous | years | 15.3 (SD 1.8) |
| Sex: Female, Male: Female | Participants | 40 |
| Sex: Female, Male: Male | Participants | 114 |
| Region of Enrollment: United States | participants | 154 |
6. Primary Endpoint
The registry lists the primary outcome as Cigarette Smoking, measured over 24 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percent |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled Cigarette Smoking, uses a percent unit, and is described with a number parameter. Its timeframe is 24 months. The registry record says youth self-report was collected using a modified version of the Fagerstrom Tolerance Questionnaire. This identifies the outcome as a reported smoking measure rather than an outcome established through a comparator-group contrast.
Smoking is relevant to the study’s stated question because the researchers hypothesized that OROS MPH treatment would be associated with low rates of cigarette smoking in ADHD youth. The endpoint description, however, does not give a numerical count or percentage for smoking. Although it specifies the unit as percent, the result itself is not reported in the registry record. Consequently, the magnitude of the observed outcome and its precision cannot be assessed from the posted registry information.
The outcome description defines the analysis population as participants who took at least one dose of OROS MPH after baseline assessment, reported as N=154. For participants who did not complete the full study schedule, the description says last observation carried forward was used. The record does not explain how the questionnaire was modified, how a smoking response was categorized for the reported endpoint, or how observations were handled beyond the stated carry-forward approach; those details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study context: an open-label, single-group study of OROS MPH in youths with ADHD, with cigarette smoking assessed over 24 months. It also gives an analysis population of N=154 and says last observation carried forward was used for participants who did not complete the full schedule. These details clarify whom the stated analysis concerns and how one form of incomplete follow-up was addressed.
However, the posted results do not include a numerical primary-endpoint value. The record identifies the outcome as cigarette smoking, with a percent unit, but does not report the percentage, event count, or an estimate of uncertainty. Thus, the registry record does not allow readers to determine the observed smoking level, how precisely it was estimated, or whether it was close to the researchers’ stated hypothesis of low rates. No primary-outcome confidence interval or test result is reported in the registry record.
The single-group design also limits what an outcome value could establish, even if it were available. Without a concurrent comparator, the study description would not support a direct estimate of how outcomes differed under OROS MPH versus another treatment or no study treatment. A smoking outcome observed during follow-up could reflect many influences; the registry record does not isolate the contribution of treatment. The researchers’ stated hypothesis is an expectation, not a reported result.
The registry gives enrollment as 203 and describes the primary analysis population as N=154. The record does not explain the difference between these figures, so reasons for non-inclusion in the analysis population should not be inferred. Nor does the endpoint description give a complete account of follow-up or missingness beyond its stated use of last observation carried forward for participants who did not complete the full schedule.
The record lists adverse-event counts and selected serious-event terms, but those are separate from the primary smoking endpoint. They do not fill the gap in the primary result, and they do not establish that any event was caused by treatment. Overall, the registry permits a description of the design, outcome definition, analysis population, and some safety reporting, but not a quantitative interpretation of the primary endpoint.
9. Statistical Methods Explained
The registry record describes a single-group study, not a randomized comparison. That distinction determines what the analysis can estimate. A single-group outcome describes what was recorded among participants in that group. It does not, on its own, estimate a treatment contrast, because there is no concurrent group representing what might have happened under a different treatment or without the study treatment. This is a general statistical distinction, not a claim about an unreported analysis.
What does a percent endpoint represent?
In general, a percentage expresses a count relative to a defined denominator. To interpret one, readers need both the outcome definition and the population used to calculate it. Here, the registry labels the primary endpoint as Cigarette Smoking, gives percent as the unit, and identifies the analysis population as adolescents who took at least one dose after baseline assessment, reported as N=154. But the numerical percentage and its associated count are not reported in the registry record. It is therefore not possible to reconstruct the endpoint value or verify its denominator from the posted information.
What would uncertainty measures add?
In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. It conveys precision as well as the point estimate; a point estimate alone cannot show how much sampling uncertainty surrounds it. The registry record does not report a primary-endpoint estimate or confidence interval. A p-value, if reported, would address a different question about compatibility with a specified null model and would not replace the estimate or its interval. No primary-outcome p-value is reported in the registry record.
What does the single-group design imply?
For a treatment comparison, random allocation and a concurrent comparator can help distinguish treatment-group differences from other differences between participants and from changes over time. This study is recorded as single group, with allocation listed as NA and masking as none. Therefore, a within-group smoking result would be descriptive of the observed group, not a randomized estimate of treatment effect. The study’s stated hypothesis that treatment would be associated with low rates is not itself evidence that a particular rate was observed or that treatment caused it.
How should the planning assumptions be read?
The registry includes general assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also says that non-time-to-event planning entries are expressed as participants per arm, while time-to-event entries use a total number of events. These are planning conventions, not evidence that this trial used a two-arm design or had that allocation. The actual study is listed as single group.
The assumptions refer to an observed effect, but a numerical primary-endpoint result and the numeric planning illustrations are not reported in the registry record. As a result, no planning value can be interpreted or checked from the posted information. In general, sample-size calculations based on a hypothetical effect describe the size of a future study under chosen assumptions; they are not a measure of the probability that the completed study found an effect. They should not be described as observed power.
Why does missing follow-up matter?
The primary-outcome description states that last observation carried forward was used for participants who did not complete the full 24-month schedule. In general, this method substitutes a participant’s last recorded value for later values that are missing. It can make the analysis depend on an assumption that the last available value is a reasonable stand-in for the unobserved outcome. If outcomes could change after the last measurement, that assumption may not reflect the true follow-up experience. The registry does not report a sensitivity analysis or enough detail to evaluate this assumption.
The registry reports no analysis entries. It does not describe an estimator, model, confidence-interval method, hypothesis test, covariate adjustment, or detailed endpoint derivation. These methods are not reported in the registry record. Statistical interpretation should therefore remain limited to the information explicitly recorded: a single-group design, a self-reported smoking outcome at 24 months, the stated analysis population, and the stated carry-forward handling of incomplete schedules.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure and reports zero analyses. It does not provide a multiplicity strategy, such as a prespecified hierarchy among several primary tests or an adjustment across multiple outcomes. With no analysis entries or numerical primary result, it is not possible to determine which tests, if any, were carried out or how any multiplicity was handled. A multiplicity plan is not reported in the registry record.
The primary-outcome population is defined as adolescents who took at least one dose after baseline assessment, reported as N=154. The description says last observation carried forward was used for participants who did not complete the full 24-month schedule. It does not state how many participants had incomplete follow-up, how much information was missing, or whether the carry-forward method was used for every missing assessment. Those details are not reported in the registry record.
In general, missing-data methods matter because results may depend on how unobserved outcomes are treated. Last observation carried forward fills a missing later value with the last recorded value, which assumes that the carried-forward value is an adequate representation of the missing outcome. The record does not report a sensitivity analysis using alternative assumptions, so the robustness of the primary result to missing-data choices cannot be assessed.
The record does not describe whether an intention-to-treat population, a per-protocol population, or another analysis population was planned. It identifies the primary analysis population by post-baseline treatment exposure, but does not provide a fuller population strategy. Interim analyses, stopping rules, and a detailed statistical analysis plan are not reported in the registry record. These omissions limit assessment of the prespecification and completeness of the analysis.
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 |
|---|---|---|---|
| OROS-Methylphenidate | 5 | 154 | 3.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.001% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| OROS-Methylphenidate | 45 of 154 |
Most frequent serious adverse event terms
| Event term | Organ system | OROS-Methylphenidate |
|---|---|---|
| leg fracture | Injury, poisoning and procedural complications | 2 of 154 |
| viral illness | General disorders | 1 of 154 |
| spontaneous pneumothorax | Respiratory, thoracic and mediastinal disorders | 1 of 154 |
| unintentional carbon monoxide poisoning | Injury, poisoning and procedural complications | 1 of 154 |
Most frequent non-serious adverse event terms
| Event term | Organ system | OROS-Methylphenidate |
|---|---|---|
| decreased appetite | General disorders | 19 of 154 |
| headache | General disorders | 14 of 154 |
| insomnia | General disorders | 7 of 154 |
| heart racing | General disorders | 6 of 154 |
| upper respiratory infection | Infections and infestations | 5 of 154 |
| acne | Skin and subcutaneous tissue disorders | 4 of 154 |
| congestion | General disorders | 4 of 154 |
| dizziness | General disorders | 4 of 154 |
| initial insomnia | General disorders | 4 of 154 |
| nausea | Gastrointestinal disorders | 4 of 154 |
Serious events with the highest arm-level rate: leg fracture (1.3%), viral illness (0.6%), spontaneous pneumothorax (0.6%), unintentional carbon monoxide poisoning (0.6%).
The registry lists one OROS-methylphenidate group with 154 participants at risk for serious adverse events and 5 affected, and 154 at risk for other adverse events and 45 affected. These are separate safety summaries; they should not be added together or treated as the primary smoking outcome. The record does not state in this summary whether the figures represent unique participants across categories, and no such interpretation should be assumed.
The registry also lists serious-event terms with percentages: leg fracture, 1.3%; viral illness, 0.6%; spontaneous pneumothorax, 0.6%; and unintentional carbon monoxide poisoning, 0.6%. These entries describe reported event terms. A listed event does not by itself establish that treatment caused it, and the percentages should not be interpreted as comparative risks because no control group is described.
The death count is not reported in the registry record. Further details about event timing, severity criteria, relatedness assessment, or the way event terms were counted are not reported in the registry record. The safety entries should therefore be read as registry-reported counts and terms, not as a causal assessment or a comparison with another treatment.
12. What the Result Does, and Does Not, Mean
The registry record supports a limited description of the study: youths aged 12–17 with ADHD received open-label OROS MPH in a single-group study, and cigarette smoking was assessed by self-report over 24 months. The primary outcome description specifies an analysis population of N=154 and states that last observation carried forward was used for participants who did not complete the full schedule. The record also includes selected adverse-event information.
It does not report a numerical result for cigarette smoking. Without that value, readers cannot judge the observed level of smoking or the precision of the estimate. The stated hypothesis about low rates is not a result. The record also does not report a primary-outcome confidence interval, test statistic, or p-value, and it lists no analysis entries.
Even a reported single-group rate would not establish a treatment effect. Since the study has no comparator arm and is not described as randomized, there is no concurrent estimate of the outcome under an alternative condition. The observed course could not be attributed to OROS MPH on the basis of this design alone. The registry record does not establish what would have happened to these participants without treatment.
The endpoint is based on youth self-report using a modified questionnaire. The record does not describe the modification or provide details about how reports were converted into the reported percent. It also does not explain the difference between overall enrollment of 203 and the primary analysis population of N=154. These are material limits on interpreting the outcome and its generalizability.
The safety counts and serious-event terms add descriptive information, but do not establish treatment causality or comparative safety. Overall, the registry record outlines a clinical question and study structure, but does not contain enough primary-outcome results to determine whether the observed smoking outcome was low or how precisely it was measured.
13. Why This Trial Matters Statistically
This study illustrates why design and outcome reporting must be read together. The clinical question concerns cigarette smoking during follow-up after open-label OROS MPH treatment, but the study is recorded as single group, with no allocation to a comparator and no masking. The design therefore supports a descriptive account of outcomes in the treated group, not a direct randomized comparison.
The primary outcome is specified with a timeframe, a self-report instrument, an analysis population, and a missing-data approach. Those details help define what the intended result would represent. At the same time, the registry record does not include the actual numerical smoking result. An endpoint definition without its estimate cannot answer how much smoking was observed or how precisely it was estimated. This distinction is central to clinical interpretation: design and measurement details are not substitutes for outcome results.
The record also separates overall enrollment from the stated primary analysis population. Because it does not explain why the analysis population is smaller, readers cannot determine from this record how participant inclusion and follow-up may have shaped the result. The stated use of last observation carried forward identifies one approach to incomplete schedules, but no sensitivity analysis is reported to show how conclusions might depend on that choice.
Finally, the registry includes planning assumptions that use a hypothetical two-arm framework, while the actual design is listed as single group. This is a useful reminder that planning illustrations do not describe the completed trial unless their relationship to that design is explicitly established. The observed primary effect and numerical planning illustrations are not reported in the registry record. Keeping design, analysis, planning, and results distinct prevents unsupported conclusions about treatment effects or statistical power.
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.
Several limitations specific to this trial record constrain interpretation. The most direct is that the registry identifies cigarette smoking as the primary outcome but provides no numerical result. The endpoint is labeled as a percent, yet no percentage, count, or measure of uncertainty is recorded. Consequently, the central outcome cannot be quantitatively evaluated from the registry record.
The study is described as open-label and single group, with no comparator. This prevents a controlled estimate of the treatment effect and leaves changes over follow-up open to explanations other than treatment. The record does not describe a method to account for those alternative explanations.
The smoking measure relied on youth self-report using a modified version of the Fagerstrom Tolerance Questionnaire. Details of the modification, outcome categorization, and assessment schedule are not reported in the registry record. The primary analysis population is reported as N=154, while enrollment is 203; the record does not explain the difference. It also does not give the amount or pattern of incomplete follow-up, beyond stating that last observation carried forward was used for participants who did not complete the full schedule.
No analysis entries are listed. The statistical model, uncertainty estimates, hypothesis tests, multiplicity handling, interim analyses, and sensitivity analyses are not reported in the registry record. The safety summary gives counts and selected terms, but does not provide a comparative group or enough detail to establish whether events were related to treatment. These limitations are specific to what the registry record documents and do not establish what may have been reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta — NCT00181714.
- Registry record last updated 2013-05-07; status last verified 2013-05.
- Results first posted 2012-02-07.
- 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 describes a completed Phase 4, open-label, single-group study sponsored by Massachusetts General Hospital, with enrollment of 203 and OROS MPH as the intervention. The intended population was youths aged 12–17 meeting DSM-IV criteria for ADHD. The summary describes six weeks of treatment followed by monthly visits for 24 months.
The primary outcome was cigarette smoking at 24 months, assessed by youth self-report using a modified Fagerstrom Tolerance Questionnaire. The primary analysis population is reported as N=154, with last observation carried forward for participants who did not complete the full schedule. The numerical primary outcome and its uncertainty are not reported in the registry record. The record lists no analyses and does not describe a concurrent comparator. Selected adverse-event counts and serious-event terms are recorded, while the death count is not reported in the registry record.