Cardiovascular Effects of Adderall in Healthy Adults.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cardiovascular Effects of Adderall in Healthy Adults. (NCT02979327), a randomized phase 4 study. The primary outcome is Systolic Blood Pressure.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, double-masked, phase 4 crossover trial sponsored by Mayo Clinic. Its status is completed. The record gives a start date of 2018-06-01 and a primary completion date of 2021-07-23. Enrollment is listed as 30.

In a crossover design, participants receive more than one study treatment in a sequence. The listed sequences were Adderall first and placebo second, or placebo first and Adderall second. Randomization assigns participants to a sequence, rather than simply assigning each participant to a single treatment for the whole study. This structure can allow comparisons within participants, but such a comparison requires an analysis that accounts for the repeated measurements and treatment sequence.

The record labels the trial double-masked. It does not identify which people were masked, describe how masking was maintained, or state whether masking was assessed. The study is described as having two study visits, but the time between visits, any washout interval, and the procedures used to limit or assess carryover are not reported in the registry record. These details matter in crossover trials because effects from an earlier treatment could potentially influence observations during a later period.

The listed primary endpoint is systolic blood pressure, with a timeframe of baseline and 3 hours. The registry also lists plasma norepinephrine as a secondary outcome. It identifies five outcome measures overall, but lists zero analyses. Therefore the design information describes the intended comparison and measurements, not an analyzed estimate of the effect of Adderall relative to placebo.

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.

First Intervention

Reasons for not completing this period:

Second Intervention

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Systolic Blood Pressure, measured over Baseline and 3 hours.

Systolic blood pressure is the upper value in a blood pressure reading. It measures pressure in the arteries during a heartbeat. The registry identifies this as the primary outcome and gives its unit as mmHg. The stated timeframe is baseline and 3 hours, and the outcome parameter is a mean.

Blood pressure is relevant to the trial's stated cardiovascular focus. The registry describes the broader aim as investigating cardiovascular response, including blood pressure, heart rate, electrocardiographic response and blood vessel reactivity response. Systolic blood pressure is one measurable component of that broader set of responses; it does not, by itself, represent every cardiovascular outcome named in the study summary.

The record specifies standard error as the dispersion measure for the primary outcome. In general, a standard error describes the precision of an estimated mean, rather than the spread of individual measurements. It is therefore not interchangeable with a standard deviation, which describes variability among observations. No mean values, standard errors, confidence intervals, or treatment-effect estimate for systolic blood pressure are reported in the registry record.

The timing description includes baseline and 3 hours, but the registry does not give a single reported numerical contrast that can be interpreted as the change attributable to Adderall relative to placebo. The record also flags the primary outcome as involving several categories or time points and does not reduce it to one comparison. Without a reported analysis, the endpoint definition alone cannot establish the direction, size, or precision of any treatment difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a randomized crossover design compare?

In a parallel-group trial, each participant is generally assigned to one treatment group. In a crossover trial, participants receive treatments in different periods, with assignment to a treatment sequence. Here, the listed sequences are Adderall followed by placebo and placebo followed by Adderall. Random allocation can help distribute participant characteristics across sequences, while the crossover structure allows treatment observations to be made in the same participants.

Within-participant comparisons can be statistically useful because each participant can serve as a reference for their own measurements. But repeated observations from one participant are not independent. An analysis that treats every observation as unrelated can misstate uncertainty. A crossover analysis therefore needs to account for the participant-level pairing and the timing of measurements. The registry identifies the crossover design but does not report the statistical model used to handle these features.

Why can treatment period and sequence matter?

In crossover studies, the treatment received in an earlier period may influence measurements in a later period. This is commonly called carryover. Period effects can also arise if measurements change over time for reasons not caused by the assigned treatment. Randomizing the order of treatments helps balance sequence assignment, but it does not by itself demonstrate that carryover is absent or that period effects were addressed.

The record describes two study visits, but does not state the interval between them, a washout procedure, or an analysis of carryover or period effects. It also does not identify whether the treatment comparison was estimated with a paired method, a repeated-measures model, or another method. Those elements are not reported in the registry record, so no particular analysis should be assumed.

What do mean and standard error convey?

The primary outcome is specified as a mean systolic blood pressure, with standard error as its dispersion measure. In general, the mean describes the central value of a set of measurements. The standard error describes how precisely an estimated mean is determined from the data. A smaller standard error indicates greater precision for that estimate, while a larger one indicates less precision. It does not describe the range of individual blood pressure measurements; that is a different kind of variability.

A treatment comparison would ordinarily need an estimated contrast and a measure of uncertainty. A confidence interval is a general statistical tool that gives a range of values compatible with the data and the analysis assumptions. It helps readers distinguish a comparatively precise estimate from one that remains uncertain. No confidence interval or treatment contrast for the primary outcome is reported in the registry record, so the precision of an Adderall-versus-placebo effect cannot be assessed.

Why is the analysis model important?

The endpoint is recorded at baseline and 3 hours. A trial can use baseline information in different ways, and the choice affects what estimate is being described. For example, a model might account for baseline measurements when estimating a follow-up contrast, or it might focus on change over time. In a crossover design, the method also needs to account for the fact that observations within a participant are related and that treatment is administered across periods. The registry does not identify the estimand, model, covariates, or handling of repeated measurements.

For a continuous outcome, model assumptions matter. General examples include how the outcome is distributed, whether variability is adequately represented, and whether the relationship between model terms and the mean is appropriate. If observations have more variability than a model assumes, uncertainty estimates can be too small unless the analysis accounts for that over-dispersion. The registry does not report diagnostics or assumptions, and no claim about the fit of any model can be made.

How should the planning illustration be read?

The record describes sample-size planning as an illustration based on an observed effect, rather than as the trial's own design calculation. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated planning quantities are participants per arm. These are planning assumptions, not observed trial findings.

Such an illustration does not establish the trial's original sample-size justification, and it is not observed power. Planning calculations depend on assumptions about the effect and analysis; they do not replace an estimate with uncertainty from the trial. The trial's sample-size justification is not reported in the registry record. Because the registry lists zero analyses and no primary effect estimate, a planning illustration cannot be treated as evidence about the observed cardiovascular response.

What can be inferred when no analysis is listed?

With zero analyses reported, there is no posted inferential result for the primary endpoint to interpret. The design and outcome descriptions explain what was planned or measured as recorded, but they cannot establish an effect's direction, magnitude, statistical significance, or precision. A result that is absent from the registry record should not be replaced with an assumption based on the trial title, study aims, or adverse-event counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies five outcome measures and zero analyses. Plasma norepinephrine is named as a secondary outcome. The broader study summary also mentions heart rate, electrocardiographic response and blood vessel reactivity response, alongside blood pressure. The record does not give a complete analysis plan showing how these outcomes relate to the primary question or how they were to be tested.

Multiplicity arises when several outcomes, time points, groups, or statistical comparisons are examined. In general, the more comparisons made, the greater the chance that at least one result may appear notable by chance if each is interpreted separately. Researchers can address this through prespecified outcome hierarchies, adjusted procedures, or careful emphasis on estimation and uncertainty. The registry does not report a multiplicity strategy, and the absence of listed analyses means it is not possible to determine whether adjustment was applied.

The primary outcome is described at baseline and 3 hours, and the record notes that it has several categories or time points rather than one reduced comparison. The exact planned contrast and the treatment of the time points are not reported in the registry record. That makes the primary inferential question less specific than a single reported estimate would be.

Information about missing data is also not reported in the registry record. The outcome-specific number of observations, reasons for missing measurements, and any imputation or sensitivity analyses are not given. The record's population field for the primary outcome is blank, so the analysis population and its inclusion criteria are not reported either. These gaps limit assessment of whether the analyzed participants and measurements corresponded to the randomized design.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry lists serious adverse events for Adderall and placebo separately. For each treatment listing, 29 participants are recorded as at risk, with zero serious adverse events affected and zero deaths. These are the registry's reported counts; they do not provide a detailed event-by-event description in the information available for this analysis.

The record also lists other adverse events: one affected participant under Adderall and two under placebo, with 29 at risk in each listing. These counts are descriptive. The record does not report a statistical comparison, event-level details, or an analysis accounting for the crossover sequence. They therefore should not be interpreted as evidence that one treatment caused more or fewer events.

In a crossover study, treatment-specific safety counts can depend on how events are attributed and recorded across periods. The registry information does not explain the attribution rules or provide further timing details. The zero serious-event counts do not establish that serious harms are impossible, and the listed other-event counts do not by themselves establish a difference in safety. They describe what was recorded in these groups, not a comprehensive estimate of risk.

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

The record establishes that a randomized, double-masked crossover trial was conducted to investigate cardiovascular responses in healthy adults. It identifies Adderall and placebo capsules, two treatment sequences, and systolic blood pressure as the primary outcome. It also identifies baseline and 3 hours as the measurement timeframe and lists plasma norepinephrine as a secondary outcome.

These design details define the question the trial was intended to address, but they are not results. The registry lists zero analyses and does not report a treatment-effect estimate, means, standard errors, or confidence interval for the primary endpoint. As a result, the posted information cannot show whether systolic blood pressure differed between treatments, in which direction any difference went, or how precise an estimate would be.

The study's healthy-adult population, as described in its title and summary, also sets a boundary on interpretation. A finding from a study population cannot automatically be extended to people who were not represented. Further characteristics of participants and eligibility criteria are not reported in the registry record, so the population's detailed scope cannot be assessed from this information alone.

The listed adverse-event figures should likewise be interpreted narrowly. They record zero serious adverse events and zero deaths in each treatment listing, alongside other-event counts. Those observations do not establish that an intervention is safe in all contexts or that a treatment difference exists. Nor can they substitute for a complete safety analysis, which is not reported in the registry record.

In general, a useful clinical trial interpretation combines the estimated effect, its uncertainty, the analysis population, and the design's limitations. Here, the record supplies design and outcome definitions but not the primary results or analytical detail needed for that assessment. It is therefore appropriate to describe the trial's question and what the registry records, while leaving the cardiovascular treatment effect unresolved.

13. Why This Trial Matters Statistically

This trial is statistically interesting because the crossover design changes what a treatment comparison means. Participants were assigned to receive both Adderall and placebo in different sequences, rather than only one treatment. That structure can make within-participant comparisons informative, but it also requires analysis that accounts for repeated observations and the period in which each treatment was received.

The endpoint is continuous and is specified as a mean systolic blood pressure, with standard error as its dispersion measure. This makes the distinction between the central estimate and its precision important. A mean alone would not show how uncertain the estimated treatment contrast is, while a standard error for a mean is not a description of how much individual measurements vary.

The record also highlights why a clearly defined estimand matters. The primary outcome timeframe includes baseline and 3 hours, but the registry does not reduce it to one comparison or report the contrast used in an analysis. Without knowing whether the question concerns follow-up values, change from baseline, or another prespecified quantity, readers cannot attach a precise interpretation to an unreported treatment effect.

Finally, the record identifies multiple outcome measures but no analyses. This makes multiplicity, missing data, and the analysis population especially relevant to interpretation, yet the corresponding details are not reported. The trial's design and outcome descriptions can guide a statistical discussion, but they cannot substitute for estimates and uncertainty. The key statistical lesson is to distinguish a study's question and design from evidence about its result.

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 most important limitation of the available record is that it lists zero analyses. There is no reported estimate for the primary endpoint, no confidence interval, and no treatment-specific mean or standard error. As a result, neither the magnitude nor the precision of a cardiovascular effect can be evaluated from the registry information.

The primary outcome description gives baseline and 3 hours, while the record notes that the outcome involves several categories or time points and is not reduced to one comparison. The exact primary contrast is therefore not reported. The record also does not state which analysis model was used or how within-participant correlation, treatment period, sequence, or possible carryover were handled.

Several design details that could affect interpretation are not reported in the registry record, including the interval between visits, a washout procedure, and the handling of missing observations. The primary outcome population field is blank, and the analysis population is not described. The trial's sample-size justification, protocol-level statistical plan, and multiplicity strategy are also not reported.

The record describes the population as healthy adults but does not provide fuller eligibility or participant-characteristic information in the registry record for this analysis. Further, the adverse-event counts are limited summaries and do not include detailed event descriptions or an inferential comparison. These limitations mean the registry record can describe the trial's structure and recorded counts, but does not permit a comprehensive evaluation of either efficacy or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cardiovascular Effects of Adderall in Healthy Adults. — NCT02979327.
• Registry record last updated 2025-01-14; status last verified 2025-01.
• Results first posted 2025-01-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT02979327, titled “Cardiovascular Effects of Adderall in Healthy Adults.” It is a completed phase 4 randomized, double-masked crossover trial sponsored by Mayo Clinic. The record lists enrollment of 30, a start date of 2018-06-01, and a primary completion date of 2021-07-23.

The intervention sequences were Adderall followed by placebo and placebo followed by Adderall. Systolic blood pressure, measured at baseline and 3 hours, is the primary outcome; plasma norepinephrine is named as a secondary outcome. Five outcome measures are listed, but the record lists zero analyses. It therefore contains no reported primary treatment-effect estimate. The listed serious adverse-event counts are zero for both treatment listings, with zero deaths in each; other adverse-event counts are one for Adderall and two for placebo.