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 Methylphenidate Treatment of Attention Deficits in Epilepsy (NCT02178995), a non-randomized phase 4 study. The primary outcome is Conners' Continuous Performance Test (CPT) (Double-blind Portion, Primary Variables).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02178995 |
| Phase | Phase 4 |
| Condition | Epilepsy, Cognitive Deficits, Attention Deficits |
| Allocation | Non-Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 55 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Kimford Jay Meador |
| Results posted | Yes |
2. Clinical Question
Population
Adults with epilepsy and attention or other cognitive complaints were the population of interest. The registry lists epilepsy, cognitive deficits, and attention deficits as conditions. It does not report further eligibility details or a fuller description of the primary analysis population.
Intervention
The intervention was methylphenidate. In the double-blind portion, participants received single doses of 10mg, 20mg, and placebo in different sequences, followed by cognitive testing and questionnaires. An open-label portion offered interested participants a four-week treatment trial after the final randomized visit.
Comparator
For the double-blind assessment, methylphenidate doses were compared with placebo within the medication sequences. Healthy controls completed the neurocognitive batteries and questionnaires but did not receive study medication; they were included primarily for an open-label comparison. The record labels the overall allocation as non-randomized, while describing randomized order for the single-dose medication sequence.
Primary question
The primary question was whether scores on selected Conners' Continuous Performance Test variables differed between methylphenidate 20mg, methylphenidate 10mg, and placebo. The measures were intended to assess attentiveness, vigilance, and response time. The registry record does not report numerical primary outcome results, estimated differences, confidence intervals, or p-values, so the size and precision of any observed differences cannot be described.
3. Trial Design
This was a completed Phase 4 study with a crossover model and triple masking listed in the registry. The overall allocation is recorded as non-randomized. At the same time, the double-blind arm descriptions say that participants received single doses of placebo, 10mg methylphenidate, and 20mg methylphenidate in randomized order. These descriptions refer to different aspects of the design and should not be collapsed into a claim that the entire study was a randomized trial. The registry record does not explain the non-randomized allocation designation.
The double-blind portion used different sequences of the three single-dose conditions, with cognitive testing and neuropsychiatric questionnaires. The primary outcome timeframe describes administration at weeks 2, 3, or 4. After the final randomized visit, interested participants could enter an open-label four-week treatment trial. The arm description states that the open-label dose began at 10mg twice daily and could be increased to 20mg twice daily as tolerated.
Healthy controls completed the same neurocognitive batteries and questionnaires but were not exposed to study medication. The record says they were included primarily for an open-label comparison. It also describes one participant who received a 40mg dose, developed tachycardia, and was withdrawn from the double-blind portion. The description says the 40mg doses were removed from the study, but the remaining text is incomplete, so the further handling of that sequence is not reported in the registry record.
Registry enrollment was 55. The study start is listed as 2014-08, primary completion as 2015-09, and status as completed. The record does not report the number included in each primary analysis or explain losses between enrollment and analysis.
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: 4 participants signed their consent form, but did not complete any study visits and therefore produced no study data. Therefore, 55 participants are 'enrolled,' but only 51 actually participated in the study flow.
Only the first 6 of 9 groups are shown.
Double Blind
| Stage | Participants With Epilepsy (Open-label) | Healthy Controls | 10mg, 20mg, Then Placebo (Double-blind) | 10mg, Placebo, Then 20mg (Double-blind) | Placebo, 20mg, Then 10mg (Double-blind | Placebo, 10mg, Then 20mg (Double-blind) |
|---|---|---|---|---|---|---|
| STARTED | 0 | 16 | 5 | 6 | 6 | 6 |
| COMPLETED | 0 | 15 | 5 | 6 | 6 | 5 |
| NOT COMPLETED | 0 | 1 | 0 | 0 | 0 | 1 |
Reasons for not completing this period:
| Reason | Participants With Epilepsy (Open-label) | Healthy Controls | 10mg, 20mg, Then Placebo (Double-blind) | 10mg, Placebo, Then 20mg (Double-blind) | Placebo, 20mg, Then 10mg (Double-blind | Placebo, 10mg, Then 20mg (Double-blind) |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
Open Label
| Stage | Participants With Epilepsy (Open-label) | Healthy Controls | 10mg, 20mg, Then Placebo (Double-blind) | 10mg, Placebo, Then 20mg (Double-blind) | Placebo, 20mg, Then 10mg (Double-blind | Placebo, 10mg, Then 20mg (Double-blind) |
|---|---|---|---|---|---|---|
| STARTED | 30 | 14 | 0 | 0 | 0 | 0 |
| COMPLETED | 28 | 14 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 2 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Participants With Epilepsy (Open-label) | Healthy Controls | 10mg, 20mg, Then Placebo (Double-blind) | 10mg, Placebo, Then 20mg (Double-blind) | Placebo, 20mg, Then 10mg (Double-blind | Placebo, 10mg, Then 20mg (Double-blind) |
|---|---|---|---|---|---|---|
| Adverse Event | 2 | 0 | 0 | 0 | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Total number of individuals who signed consents = 55. 4 of these individuals with epilepsy signed their consent but did not follow through and participate in the study. The remaining 51 (35 epilepsy, 16 controls) are represented here.
| Characteristic | Unit | Participants With Epilepsy | Healthy Controls | Total |
|---|---|---|---|---|
| Participants analysed | 35 | 16 | 51 | |
| Age, Continuous | years | 37 (20 to 64) | 45 (22 to 62) | 39.5 (20 to 64) |
| Sex: Female, Male: Female | Participants | 19 | 10 | 29 |
| Sex: Female, Male: Male | Participants | 16 | 6 | 22 |
| Mean years of education | years | 15 (12 to 20) | 15 (12 to 18) | 15 (12 to 20) |
| Mean duration of epilepsy | years | 12.5 (1 to 41) | 0 (0 to 0) | NA (NA to NA) |
| Seizure type: Focal | participants | 26 | 0 | 26 |
| Seizure type: Generalized | participants | 6 | 0 | 6 |
| Seizure type: Unclassified (GTCS) | participants | 3 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Conners' Continuous Performance Test (CPT) (Double-blind Portion, Primary Variables), measured over difference in scores on specific variables between MPH 20mg, 10mg, and placebo (randomized to administration at weeks 2, 3, or 4).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Units |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the Conners' Continuous Performance Test (CPT) during the double-blind portion. The registry identifies two primary variables, D' and HRTSD, and describes them as continuous scores reported as means with standard deviations. The stated timeframe concerns differences between the 20mg dose, the 10mg dose, and placebo, administered at weeks 2, 3, or 4.
D' is described as a detectability measure: it reflects a participant's ability to distinguish target stimuli from non-target stimuli and incorporates response-time and accuracy factors. Its derivation is proprietary to the test. The registry states that a higher, or less negative, D' score is considered worse. HRTSD is the standard deviation of hit reaction times across different stimulus types. It is described as a measure of the ability to maintain attention across the test, with a higher score indicating more response-time variability and considered worse.
These variables were chosen to quantify attentiveness, vigilance, and response-time performance using a structured cognitive test. Their interpretation depends on the direction stated in the registry: a numerically higher score is not automatically an improvement. The record does not report the observed means, standard deviations, treatment contrasts, confidence intervals, or p-values for either primary variable. Therefore, the endpoint definitions are available, but the numerical results and their precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary outcome and explains how its scores should be read, but it does not report numerical results for D' or HRTSD. There are no posted primary means, standard deviations, estimated treatment differences, confidence intervals, or p-values in the record. Consequently, it is not possible to characterize the direction, size, or precision of the primary comparisons from this information. No conclusion about the observed cognitive test results can be drawn from the endpoint description alone.
The direction of scoring matters. For D', a higher or less negative score is defined as worse; for HRTSD, a higher score represents greater variability in hit reaction time and is also defined as worse. A comparison must therefore be interpreted using each measure's stated direction, rather than treating every higher score as favorable. The registry record does not give the estimated differences needed to apply these definitions to the study findings.
The design included repeated single-dose conditions in different sequences, and the record describes randomized order within the double-blind portion. General statistical context: in a crossover design, observations from the same participant under different conditions may be related. An analysis can account for that within-participant relationship; treating all observations as independent can misrepresent uncertainty. The statistical model and the handling of period, sequence, or carryover effects are not reported in the registry record, so it is not possible to say how those features were incorporated.
The record identifies 20 outcome measures and 81 analyses. Examining many outcomes or analyses can increase the chance of at least one apparently notable result when many tests are conducted. General statistical context: multiplicity procedures can control that risk, but their use and any prespecified hierarchy are not reported in the registry record. Without the analysis plan and full results, isolated findings would need cautious interpretation, and the primary outcome cannot be compared with secondary findings on a common evidential basis.
The study also had an open-label phase, which differs from the masked single-dose assessment. General statistical context: results from an open-label period may be affected by expectations and other changes over time, because participants and investigators know treatment is being given. The registry describes the treatment schedule and repeat assessments, but does not report numerical open-label outcome results or methods addressing these possible influences.
In short, the registry record permits a description of the study question, outcome definitions, and design, but not an appraisal of the size or statistical uncertainty of the primary effect. Numerical estimates and their uncertainty are not reported in the registry record.
9. Statistical Methods Explained
The registry describes a continuous primary endpoint summarized as a mean and standard deviation. A mean gives the central value of a set of scores, while a standard deviation describes how dispersed individual scores are around that mean. General statistical context: a mean difference between conditions describes the direction and size of a contrast on the original measurement scale; its uncertainty depends on the amount and variability of the data and on the analysis design. The record does not give the endpoint summaries or contrasts, so no such estimate can be interpreted for this study.
How should crossover data be understood?
The double-blind portion used sequences in which participants received the same single-dose conditions in different orders. The registry calls the study model crossover and describes randomized order for the doses. In a crossover study, participants can serve as their own comparison because measurements under different conditions are collected from the same person. General statistical context: this can reduce the influence of stable differences between people, but it also means that measurements within a person are related. A suitable analysis generally accounts for that dependence.
The registry's overall allocation label is non-randomized, while the arm descriptions refer to randomized order for single doses. These statements should be reported together rather than assuming that the overall study allocation was randomized. The specific statistical approach, the treatment of sequence and period, and any assessment or adjustment for carryover are not reported in the registry record. It is also not reported whether the primary comparisons used paired contrasts, a repeated-measures model, or another method.
What do the outcome scores represent?
D' and HRTSD are both continuous CPT variables, but they reflect different aspects of performance. D' is a detectability statistic combining response time and accuracy factors, with a proprietary derivation. HRTSD reflects variability in hit reaction times and is described as an attention-maintenance measure. Both are defined so that higher values indicate a worse score. General statistical context: the meaning of an estimated difference depends on the measurement scale, the direction of scoring, and the comparison being made. The registry record gives these definitions but not numerical outcome estimates.
What can a confidence interval tell a reader?
General statistical context: a confidence interval gives a range of values compatible with the data and the assumptions of the analysis, and indicates the precision of an estimate. It is not a guarantee that the true effect lies within the particular interval. The registry record does not report confidence intervals for the primary outcomes, so the precision of any treatment contrast cannot be assessed. P-values and numerical standard deviations are also not reported in the registry record.
How should multiple analyses be considered?
The record lists 20 outcome measures and 81 analyses. General statistical context: when many hypotheses are tested, some results may appear unusual by chance even if no corresponding underlying effect exists. Prespecified primary outcomes, a testing hierarchy, or multiplicity adjustments can help interpret a collection of analyses. The registry record does not report whether such a plan or adjustment was used, nor does it describe interim analyses. It is therefore not possible to determine how the reported analyses, if any, were selected or how their error rates were handled.
What do the sample-size illustrations mean?
General statistical context: a sample-size calculation estimates the number of participants needed under specified assumptions; it does not describe the number who actually experienced an outcome. The stated planning illustration uses the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a fraction of the observed effect. Such illustrations are planning exercises, not observed power. The record does not report the trial's own sample-size justification, and the numerical planning estimates are not reported in the registry record.
The record does not report whether outcome distributions were assessed, how missing measurements were handled, which analysis population was used, or whether the analyses adjusted for baseline scores or other variables. These details affect what a statistical estimate represents and how reliably it can be interpreted. They should not be inferred from the crossover label or from the availability of outcome definitions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures and 81 analyses. Those counts indicate a broad set of assessments, but do not by themselves establish which analyses were prespecified, which were exploratory, or how results were selected for reporting. The statistical plan, any hierarchy among primary and secondary outcomes, and any multiplicity adjustment are not reported in the registry record. General statistical context: testing many outcomes can increase the chance of false-positive findings, so findings across a large analysis set are most interpretable when the testing strategy is stated in advance and reported clearly.
The primary endpoint is identified as CPT D' and HRTSD in the double-blind portion. The record also lists secondary assessments of CPT scores, seizure frequency or severity, selected QOLIE-89 cognitive subscales, and open-label CPT outcomes. Numerical results for these outcomes are not reported in the registry record. Thus, neither the relationship between primary and secondary results nor the consistency of findings across measures can be assessed.
Missing-data procedures are not reported in the registry record. It does not state how incomplete test sessions, missed visits, withdrawal, or unavailable outcome values were handled. The analysis populations are also not reported: the record does not specify which participants contributed to each outcome analysis or whether all available observations were used. The one participant withdrawn from the double-blind portion after tachycardia on a 40mg dose is described, but the record does not report the treatment of that participant's data in analyses.
Interim analyses and stopping rules are not reported in the registry record. The absence of these details in the record should not be read as evidence that a particular procedure was or was not used.
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 |
|---|---|---|---|
| Participants With Epilepsy (Open-label) | 0 | 30 | 0.0% |
| Placebo, 20mg, Then 10mg (Double-blind) | 0 | 6 | 0.0% |
| Placebo, 10mg, Then 20mg (Double-blind) | 0 | 6 | 0.0% |
| 10mg, 20mg, Then Placebo (Double-blind) | 0 | 5 | 0.0% |
| 10mg, Placebo, Then 20mg (Double-blind) | 0 | 6 | 0.0% |
| 20mg, 10mg, Then Placebo (Double-blind) | 0 | 6 | 0.0% |
| 20mg, Placebo, Then 10mg (Double-blind) | 0 | 5 | 0.0% |
| 40mg, 20mg, Then Placebo (One Participant) | 0 | 1 | 0.0% |
| Healthy Controls | 0 | 15 | 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 |
|---|---|
| Participants With Epilepsy (Open-label) | 2 of 30 |
| Placebo, 20mg, Then 10mg (Double-blind) | 0 of 6 |
| Placebo, 10mg, Then 20mg (Double-blind) | 1 of 6 |
| 10mg, 20mg, Then Placebo (Double-blind) | 0 of 5 |
| 10mg, Placebo, Then 20mg (Double-blind) | 1 of 6 |
| 20mg, 10mg, Then Placebo (Double-blind) | 2 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Participants With Epilepsy (Open-label) | Placebo, 20mg, Then 10mg (Double-blind) | Placebo, 10mg, Then 20mg (Double-blind) | 10mg, 20mg, Then Placebo (Double-blind) | 10mg, Placebo, Then 20mg (Double-blind) | 20mg, 10mg, Then Placebo (Double-blind) |
|---|---|---|---|---|---|---|---|
| Anxiety/panic attack | Psychiatric disorders | 0 of 30 | 0 of 6 | 1 of 6 | 0 of 5 | 1 of 6 | 2 of 6 |
| Increased anxiety | Psychiatric disorders | 1 of 30 | 0 of 6 | 0 of 6 | 0 of 5 | 0 of 6 | 0 of 6 |
| Fatigue | General disorders | 1 of 30 | 0 of 6 | 0 of 6 | 0 of 5 | 0 of 6 | 0 of 6 |
| Tachycardia | Cardiac disorders | 0 of 30 | 0 of 6 | 0 of 6 | 0 of 5 | 0 of 6 | 0 of 6 |
The registry lists serious adverse events as 0 in each displayed group. This applies to the open-label epilepsy group, each listed double-blind sequence, the one-participant 40mg sequence, and healthy controls. The group-specific numbers at risk are recorded separately; for example, the open-label epilepsy group has 30 at risk, and the 40mg sequence has 1 at risk. These are group-level counts and do not establish comparative safety between treatments, particularly because the study is not described as a like-for-like control comparison and the single-dose sequences differ.
Other adverse events are reported in some groups: 2 among 30 at risk in the open-label epilepsy group; 1 among 6 at risk in the placebo, 10mg, then 20mg sequence; 2 among 6 at risk in the 20mg, 10mg, then placebo sequence; and 1 among 1 at risk in the 40mg, 20mg, then placebo sequence. The other listed double-blind sequences and healthy controls have 0 other adverse events recorded. The registry does not supply event terms for these counts in the listed data, so their nature and severity cannot be described from these figures alone.
Death counts are not reported in the registry record. The adverse-event entries should be read as reported group counts, not as proof that no unrecorded events occurred or as estimates of comparative risk. The record describes tachycardia in the participant exposed to 40mg and withdrawal from the double-blind portion, but does not report a broader event-level account in the information available.
12. What the Result Does, and Does Not, Mean
This study addressed a measurable cognitive question: whether scores on selected CPT variables differed across single doses of methylphenidate and placebo in adults with epilepsy. The registry record specifies the intended comparisons, describes the test measures, and gives the direction in which higher scores should be interpreted. It also describes an open-label treatment period and a healthy-control group that did not receive study medication.
Those design details do not establish what the study found. Numerical primary results, estimates of differences, uncertainty intervals, and p-values are not reported in the registry record. As a result, the direction and magnitude of any observed difference, and how precisely it was estimated, cannot be stated. The absence of numerical results in the record is not evidence that the treatments had identical outcomes or that an effect was present.
The registry's non-randomized allocation label and its description of randomized order for the single-dose conditions should both be kept in view. The record does not explain the overall allocation designation or provide enough information to establish the analysis approach. The crossover model may support within-participant comparisons when analyzed appropriately, but the model alone does not show how period, sequence, or carryover were handled.
The open-label phase is another distinct part of the study. It involved interested participants after the final randomized visit and a four-week treatment trial. Its design and results should not be treated as equivalent to the masked single-dose comparison. The registry does not report the numerical open-label results or the methods used to account for changes over time.
Therefore, the available record supports a description of the question and measurement strategy, but not a conclusion about the effect of methylphenidate on the primary outcomes. It also does not support a broad comparative safety conclusion from the adverse-event counts alone. Those interpretations require fuller outcome reporting and analysis details.
13. Why This Trial Matters Statistically
The study is statistically notable for combining a masked, single-dose crossover assessment with a subsequent open-label treatment period. These phases answer different kinds of questions and have different interpretive strengths. In the double-blind portion, different medication conditions were administered in varying sequences, allowing the intended cognitive comparisons to be made under masking. The later open-label period involved treatment known to participants and a repeat assessment after four weeks. Keeping the phases distinct is essential when interpreting any results.
The study also illustrates why registry design labels and arm descriptions need to be read together. The overall allocation is recorded as non-randomized, while the double-blind arm descriptions state that dose order was randomized. The record does not explain the relationship between those descriptions. That distinction matters because randomization is a feature of how participants or treatments are assigned, and a statement about dose sequence does not, by itself, resolve the overall allocation method.
The endpoint definitions are especially important for interpretation. Both primary CPT variables are defined so that higher values are worse, and D' has a proprietary derivation that incorporates response-time and accuracy factors. A simple statement that a score increased would not be enough to characterize the direction as favorable. Numerical estimates and their uncertainty are needed to understand the size and precision of a difference.
Finally, the record lists 20 outcome measures and 81 analyses, while not reporting a multiplicity strategy or numerical results for the primary outcomes. This makes transparent reporting of analysis plans and complete outcome estimates particularly relevant. The study offers a defined framework for evaluating cognitive measures in epilepsy, but the registry entries alone do not establish the findings.
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 does not report numerical results for the primary CPT variables. Without means, standard deviations, treatment contrasts, confidence intervals, or p-values, neither the size nor the precision of the primary comparisons can be evaluated. Numerical results for the listed secondary outcomes are also not reported in the record.
There is ambiguity in the design description: overall allocation is labeled non-randomized, while the double-blind sequences are described as randomized in order. The registry does not explain this difference. The statistical model and treatment of within-participant dependence, period, sequence, and possible carryover are not reported. The analysis populations, missing-data procedures, and handling of the withdrawn participant's data are also not reported.
The record lists many outcomes and analyses but does not report a multiplicity strategy, a testing hierarchy, or whether analyses were prespecified. It does not report interim analyses or a stopping rule. These gaps limit assessment of how much emphasis should be placed on any individual finding, even if numerical results were available.
The study includes a masked single-dose portion and an open-label treatment period, which should not be conflated. The record does not provide numerical open-label results or describe methods for accounting for changes over time. Healthy controls did not receive study medication, so their role is described as an open-label comparison rather than a medication comparison. The record does not report enough detail to assess the comparability of those groups.
The adverse-event record gives group counts, but does not provide a detailed account of the other adverse-event terms in the listed data. Death counts are not reported in the registry record. These limitations restrict interpretation of both efficacy-related outcomes and safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Methylphenidate Treatment of Attention Deficits in Epilepsy — NCT02178995.
- Registry record last updated 2017-05-30; status last verified 2017-04.
- Results first posted 2016-08-31.
- 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 record describes a completed Phase 4 study of methylphenidate for attention and cognitive deficits in adults with epilepsy. It lists a crossover model, triple masking, and non-randomized overall allocation; the double-blind arm descriptions state that the single-dose conditions were administered in randomized order. Participants received placebo, 10mg, and 20mg single doses in different sequences, followed by cognitive testing and questionnaires. An open-label four-week treatment period was offered to interested participants after the final randomized visit.
The primary endpoint was CPT D' and HRTSD in the double-blind portion. Both are defined so that higher scores are worse. The registry lists 20 outcome measures and 81 analyses, but numerical primary outcome results, uncertainty estimates, and analysis details are not reported in the registry record. Serious adverse event counts are 0 in each listed group; deaths are not reported. The available record supports description of the design and measures, but does not establish the magnitude or precision of the primary findings.