Analog Classroom Assessment of a Once-Daily Mixed Amphetamine Formulation, SLI381 (ADDERALL XR), in Children With ADHD

May combine two claims.

SLI381 10 mg demonstrated significant reductions in Attention problem ratings at 4.5, 6.0, 7.5, and 10.5 hours postdose, and Deportment problem ratings from 4.5 to 9.0 hours postdose.

“SLI381 10 mg demonstrated significant reductions in Attention problem ratings at 4.5, 6.0, 7.5, and 10.5 hours postdose, Deportment problem ratings from 4.5 to 9.0 hours postdose.”

May combine two claims.

Analyses of the effects of SLI381 20 mg and 30 mg showed both beneficial effects at the first postdose assessment (1.5 hours postdose) and maintenance of these improvements throughout 12 hours for the majority of assessments.

“Analyses of the effects of SLI381 20 mg (equivalent to 10 mg of Adderall b.i.d.) and 30 mg (equivalent to 15 mg of Adderall b.i.d.) showed both beneficial effects at the first postdose assessment (1.5 hours postdose) and maintenance of these improvements throughout 12 hours for the majority of assessments.”

May combine two claims.

Adderall 10 mg was associated with significant decreases in SKAMP ratings for Attention problems from 1.5 to 7.5 hours and for Deportment problems from 1.5 to 10.5 hours postdose.

“Adderall 10 mg was associated with significant decreases in SKAMP ratings for Attention problems from 1.5 to 7.5 hours and for Deportment problems from 1.5 to 10.5 hours postdose.”

May combine two claims.

SLI381 20 mg just missed attaining statistical significance for Attention problem ratings at 1.5 hours (p = .0513) and Deportment problem ratings at 12 hours (p = .0531), but ratings were significant (p < .01) at all other postdose time points.

“SLI381 20 mg just missed attaining statistical significance for Attention problem ratings at 1.5 hours (p = .0513)and Deportment problem ratings at 12 hours (p = .0531),but ratings were significant (p < .01)at all other postdose time points.”

May combine two claims.

For Adderall XR 10 mg, improvement in SKAMP Attention and Deportment ratings were observed by 4.5 hours postdose, and math problems attempted and correct were increased.

“For Adderall XR 10 mg, equivalent to 5 mg of Adderall administered b.i.d., improvement in SKAMP Attention and Deportment ratings (as decreases in attention and behavior problems) were observed by 4.5 hours postdose, and math problems attempted and correct were increased.”

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Adderall 10 mg demonstrated increases versus placebo at 1.5, 6.0, 7.5, and 9.0 hours postdose for number attempted; for number solved significance was found at the 1.5, 4.5, 6.0, and 9.0 time points.

“Adderall 10 mg was found to demonstrate increases versus placebo at 1.5, 6.0, 7.5, and 9.0 hours postdose for number attempted; for number solved significance was found at the 1.5, 4.5, 6.0, and 9.0 time points.”

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At the 12-hour session, placebo children attempted 17% fewer math problems and were correct on 25% fewer than at the initial assessment.

“At the 12-hour session, placebo children attempted 17% fewer math problems and were correct on 25% fewer than at the initial assessment.”

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By 10.5 hours postdose, placebo subjects were attempting 35% fewer math problems and correctly answering 43% less than at the first assessment session.

“By 10.5 hours postdose, subjects on placebo were attempting 35% fewer math problems and were correctly answering 43% less than at the first assessment session.”

May combine two claims.

The study design was randomized, double-blind, crossover, placebo- and active-controlled.

“The study design which followed the first study day was randomized, double-blind, crossover, placebo-and active-controlled.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Swanson et al. (1998) demonstrated a pattern of deterioration on placebo in performance across morning into afternoon assessments.

“It is interesting that the Swanson et al. (1998) report also demonstrated the pattern of deterioration on placebo in performance across morning into afternoon assessments, highlighting the importance of providing appropriate control groups for time-response studies.”

• cites Swanson et al., 1998 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The schedule and procedures for the analog classroom days were based on a modification of well-validated procedures used in previous time-response stimulant studies.

“The schedule and procedures for the analog classroom days were based on a modification of well-validated procedures used in previous timeresponse stimulant studies (Pelham et al., 1995;Swanson et al., 1978Swanson et al., , 1998Swanson et al., , 2000)).”

• cites Pelham et al., 1995 sourceNot checked yet

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• cites Swanson et al., 1978 sourceNot checked yet

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• cites Swanson et al., 1998 sourceNot checked yet

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May combine two claims.

James et al. (2001) described locomotor activity effects of amphetamine preparations up to 12 hours postdose but did not repeatedly probe disruptive behavior or academic performance.

“James et al. (2001) recently described locomotor activity effects of amphetamine preparations up to 12 hours postdose, but they did not repeatedly probe disruptive behavior or academic performance.”

• cites James et al., 2001 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A Latin square design was used to determine the randomization sequence, with approximately one fifth of the sample randomized to each of five treatment sequences.

“A Latin square design was used to determine the randomization sequence for individual subjects for the first 5 weeks with approximately one fifth of the sample randomized to each of five treatment sequences.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Each classroom contained two observers who simultaneously rated behaviors using a behavioral observation system described previously.

“In addition, each classroom contained two observers who simultaneously rated the behaviors of one half of the study group, using a behavioral observation system described previously (Swanson et al., 1998(Swanson et al., , 2000)).”

• cites Swanson et al., 1998 sourceNot checked yet

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• cites Swanson et al., 2000Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Pelham et al. (1999) found apparent benefits of Adderall up to 7 hours after administration in a summer treatment program.

“Pelham et al. (1999) studied Adderall effects in a summer treatment program and found apparent benefits up to 7 hours after administration.”

• cites Pelham et al., 1999 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Concentrations of d- and l-amphetamine were assayed using validated liquid chromatography-mass spectroscopy methodology at a central laboratory.

“Concentrations of d-and l-amphetamine were assayed using validated liquid chromatography-mass spectroscopy methodology at a central laboratory.”

Classified as probably not a substantial claim.

To avoid confounding observation of medication effects, no behavioral or other treatment approaches were used during the analog classroom days.

“To avoid confounding observation of medication effects, no behavioral or other treatment approaches were used during the analog classroom days.”

May combine two claims.

Test-retest reliability and concurrent validity of the SKAMP are high.

“Test-retest reliability and concurrent validity of the SKAMP are high (Wigal et al., 1998).”

• cites Wigal et al., 1998Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Because the study protocol did not include a 3-hour postdose assessment, it is not known exactly at what point between 1.5 and 4.5 hours the SLI381 10-mg dose may have attained statistical significance versus placebo.

“Because the study protocol did not include a 3-hour postdose assessment, it is not known exactly at what point between 1.5 and 4.5 hours the SLI381 10-mg dose may have attained statistical significance versus placebo.”

Probably not a substantial claim: may not pass S3 (load-bearing).

All classroom raters had completed reliability training for behavioral assessments.

“All classroom raters had completed reliability training for behavioral assessments.”

May combine two claims.

Adderall XR showed excellent efficacy and tolerability and displayed a time course of action that extended beyond that of immediate-release Adderall at the 10-mg q.d. dose used as a positive control, and by comparison to prior reports of the pharmacodynamic time course for Adderall as assessed by similar measures, even for doses as high as 20 mg q.a.m.

“Overall, Adderall XR showed excellent efficacy and tolerability and displayed a time course of action that extended beyond that of immediate-release Adderall at the 10-mg q.d.dose used as a positive control in this study, and by comparison to prior reports of the pharmacodynamic time course for Adderall as assessed by similar measures (Swanson et al., 1998), even for doses as high as 20 mg q.a.m.”

• cites Swanson et al., 1998 sourceNot checked yet

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• AssumptionRests on an assumption: SLI381 is designed to release two pulses of active medication, modeling the PK profile of Adderall administered twice daily with doses approximately 4 hours apart.
• AssumptionRests on an assumption: The classroom and play settings in the analog classroom are generally comparable to those regularly experienced by the children in school.

Probably not a substantial claim: may not pass S3 (load-bearing).

The classroom performance variable is restricted in its ability to reflect any child's overall academic performance across multiple subjects, demands, and tasks.

“In addition, the classroom performance variable is restricted in its ability to reflect any child's overall academic performance across multiple subjects, demands, and tasks.”

Probably not a substantial claim: may not pass S3 (load-bearing).

As a fixed-dose study, it was not intended to achieve minimal side effects.

“As a fixed-dose study, it also was not intended to achieve minimal side effects.”

Classified as probably not a substantial claim.

The study was not designed to ascertain optimal dose levels for individual subjects.

“The study was not designed to ascertain optimal dose levels for individual subjects, which are well known to vary considerably among individuals.”

May combine two claims.

Our data suggest that new drug delivery systems such as SLI381 (Adderall XR) represent a successful strategy to extend the benefits of psychostimulant treatment of ADHD without incurring added side effects, thereby avoiding some compliance issues raised by shorter-acting stimulant preparations.

“Our data suggest new drug delivery systems such as SLI381 (Adderall XR) represent a successful strategy to extend the benefits of psychostimulant treatment of ADHD without incurring added side effects, thereby avoiding some of the compliance issues raised by shorter-acting stimulant preparations (Brown et al., 1987;Firestone, 1982;Kauffman et al., 1981).”

• cites Brown et al., 1987 sourceNot checked yet

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• cites Firestone, 1982 sourceNot checked yet

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• cites Kauffman et al., 1981Not checked yet

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May combine two claims.

The study used techniques for behavior and performance assay which have been described in prior ADHD treatment research with extensive training used across the four research sites in the reliable implementation of use of analog classroom procedures.

“use of techniques for behavior and performance assay which have been described in prior ADHD treatment research (Swanson et al., 2000) with extensive training used across the four research sites in the reliable implementation of use of analog classroom procedures.”

• cites Swanson et al., 2000Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The analog classroom, although attempting to mimic a regular school classroom, represents a unique setting that may influence behavior.

“Although the analog classroom attempts to mimic many aspects of a regular school classroom, it admittedly represents a unique setting that may influence behavior (Barkley, 1991).”

• cites Barkley, 1991 sourceNot checked yet

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May combine two claims.

The 12-hour differences correspond to dimensionless effect sizes of approximately 0.3 to 0.5 and represent at least suggestive evidence of clinically significant remaining treatment benefit from SLI381 for ADHD as long as 12 hours after administration.

“As these differences calculate to dimensionless effect sizes of between approximately 0.3 and 0.5, we would argue that they represent at least suggestive evidence of “clinically significant” (Kraemer, 1992) remaining treatment benefit from this extended-release preparation for ADHD as long as 12 hours after administration.”

• cites Kraemer, 1992 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Arnold (2000), Swanson et al. (1998), and others (Elia et al., 1991) have stated that head-to-head comparisons of amphetamine agents versus methylphenidate suggest nearly equivalent group effects, although Arnold (2000) has raised the question of differential benefits in some symptom domains.

“Arnold (2000), Swanson et al. (1998), and others (Elia et al., 1991) have stated that head-to-head comparisons of amphetamine agents versus methylphenidate suggest nearly equivalent group effects, although Arnold (2000) has raised the question of differential benefits in some symptom domains.”

• cites Arnold (2000)Not checked yet

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• cites Swanson et al. (1998) sourceNot checked yet

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• cites Elia et al., 1991 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The level of staffing may have influenced behavior.

“Furthermore, the level of staffing may have influenced behavior, although mean behavior problem ratings on the SKAMP were clearly elevated during the placebo condition, and treatment effects were robust.”

May combine two claims.

The analog assessments included only ADHD subjects; no control or normal subjects were available for comparison.

“The analog assessments included only ADHD subjects; no control or normal subjects were available for comparison.”

May combine two claims.

SLI381 has the potential to work throughout the day and into the early evening after a single morning administration, thus avoiding in-school administration for children who need extended therapy.

“It has the potential to work throughout the day and into the early evening after a single morning administration, thus avoiding in-school administration for those children who need extended therapy.”

May combine two claims.

These data demonstrate clear and compelling therapeutic effects of stimulants by documenting improvements in both classroom behavioral and performance measures.

“Furthermore, these data demonstrate the clear and compelling therapeutic effects of stimulants, by documenting improvements in both classroom behavioral and performance measures.”