Effects of ethnicity on treatment attendance, stimulant response/dose, and 14-month outcome in ADHD

Effects of Ethnicity on Treatment Attendance, Stimulant Response/Dose,and 14-Month Outcome in ADHD

L. Eugene Arnold, Michael Elliott, and Larry SachsOhio State University

Hector BirdColumbia University

Helena C. KraemerStanford University

Karen C. WellsDuke University Medical Center

Howard B. AbikoffNew York University, School of Medicine

Anne ComardaOhio State University

C. Keith ConnersDuke University Medical Center

Glen R. ElliottUniversity of California, San Francisco

Laurence L. GreenhillColumbia University

Lily HechtmanMcGill University

Stephen P. HinshawUniversity of California, Berkeley

Betsy HozaPurdue University

Peter S. JensenColumbia University

John S. MarchDuke University Medical Center

Jeffrey H. NewcornMt. Sinai Medical Center

William E. PelhamState University of New York, Buffalo

Joanne B. SevereNational Institute of Mental Health

James M. SwansonUniversity of California, Irvine

Benedetto VitielloNational Institute of Mental Health

Timothy WigalUniversity of California, Irvine

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder—arandomized clinical trial of 579 children ages 7–9 years receiving 14 months of medication management,behavioral treatment, combination, or community care—the authors matched each African American andLatino participant with randomly selected Caucasian participants of same sex, treatment group, and site.Although Caucasian children were significantly less symptomatic than African American and Latinochildren on some ratings, response to treatment did not differ significantly by ethnicity after controllingfor public assistance. Ethnic minority families cooperated with and benefited significantly from combi-nation (multimodal) treatment (d � 0.36, compared with medication). This incremental gain withstoodstatistical control for mother’s education, single-parent status, and public assistance. Treatment for lowersocioeconomic status minority children, especially if comorbid, should combine medication and behav-ioral treatment.

In a review of psychotherapy outcome research, Weisz, Huey,and Weersing (1998) noted the paucity of empirical research onthe outcomes of treatment of ethnic minorities and recognized that

many recommendations about treatment of minorities are based onanecdotal and experiential reports. As a substudy of the metanaly-ses previously carried out by Weisz and colleagues (Weisz, Weiss,

Journal of Consulting and Clinical Psychology Copyright 2003 by the American Psychological Association, Inc.2003, Vol. 71, No. 4, 713–727 0022-006X/03/$12.00 DOI: 10.1037/0022-006X.71.4.713

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Han, Granger, & Morton, 1995), the authors identified 19 treat-ment studies in which the majority of participants were ethnicminority children or families. Comparing among studies, theyconcluded that, in general, treated minority children improvedmore than did similar minority children in control conditions.Nevertheless, many questions remain unanswered by availableresearch, including whether outcome is influenced by interactionof treatment type with ethnic group, the impact on outcome ofmatching therapist and client on ethnicity, and possible usefulethnic adaptations of therapy. Weisz et al. (1998) noted that theempirical literature lacks studies with direct, within-study compar-isons using adequate numbers of minorities and nonminorities to

allow proper matching of ethnic groups and treatment conditions.To our knowledge, no research addresses the specific moderatingeffects of culture or ethnic biology (e.g., race) on outcome in thetreatment of attention-deficit/hyperactivity disorder (ADHD).Some indirectly relevant findings are reviewed here asbackground.

Earlier work has led to a delineation of cultural attitudes that arecharacteristic of particular ethnic groups. These attitudes couldinfluence service seeking and service delivery and could act asbarriers to services, indirectly affecting outcome. For example,investigations of Latinos/Hispanics (Abad, 1987; Acosta, Evans,Hurwic, & Yamamoto, 1987; Yamamoto & Silva, 1987) havenoted the higher stigma prevalent in this population regardingmental disorder, a consequent tendency to use nonpsychiatricphysicians (or even alternative nonmedical resources, such asspiritual healers) for psychiatric problems (Bird & Canino, 1981),difficulty in obtaining services that are culturally sensitive and intheir own language, general belief in the lack of efficacy ofavailable treatments, and financial barriers to obtaining services orto remaining in services once they are obtained. This earlier work,however, did not examine ethnicity effects on treatment outcomesper se.

In general, the issue of ethnicity effects on outcome has gainedattention only during the latter part of the past decade, and most ofthe published literature or the papers presented at national meet-ings have dealt with the adult population and with medical condi-tions or psychiatric disorders other than ADHD. However, insofaras they are chronic conditions, like ADHD, needing sustainedtreatment, they may be illuminating. For example, in a study ofpanic disorder symptoms (Smith, Friedman, & Nevid, 1999), Af-rican Americans more often used such coping strategies as “count-ing one’s blessings” or religiosity rather than seeking services. Ifthis finding is extrapolatable to ADHD and to children, it isconceivable that African Americans who finally do seek servicesare those who have a more severe disorder, are more impaired, andhave greater comorbidity. Levy and Hawks (1996) noted thetendency among Hispanic persons with diabetes to view absenceof symptoms as evidence of cure, therefore leading to a prematurediscontinuation of treatment and subsequent relapse. Levy andHawks also noted the importance of extended family networks assustenance and support and, more important, as participants in thehealth care decision process. Therefore the educational aspects oftreatment should include the extended family, who could easilyundermine the treatment, for example, by criticizing the use ofrewards in behavior shaping.

Other investigators have noted the need to disaggregate theeffects of ethnicity from those of socioeconomic status (SES). Forexample, in a study of asthma (another chronic disorder) treatmentcompliance, Vargas and Rand (1999) suggested that treatmentnoncompliance is more a function of lower SES and lower edu-cational level than of ethnicity. A study of HIV/AIDS treatment(Williams, 1997) challenged the assumption that African Ameri-can patients were more likely to be nonadherent to a treatmentregimen than their more educated Caucasian counterparts: Thosewho attended an AIDS class did much better than those who didnot, regardless of ethnicity.

On the pharmacological level, Winsberg and Comings (1999)reported in an African American ADHD sample that patients

L. Eugene Arnold, Department of Psychiatry, Ohio State University;Michael Elliott, School of Public Health, Ohio State University; LarrySachs, School of Allied Medical Professions, Ohio State University; Hec-tor Bird, Laurence L. Greenhill, and Peter S. Jensen, Department ofPsychiatry, Columbia University; Helena C. Kraemer, Department of Psy-chiatry, Stanford University; Karen C. Wells, C. Keith Conners, and JohnS. March, Department of Psychiatry and Behavioral Sciences, Duke Uni-versity Medical Center; Howard B. Abikoff, Child Study Center, NewYork University School of Medicine; Anne Comarda, Nisonger Center,Ohio State University; Glen R. Elliott, Children’s Center at Langley Porter,University of California, San Francisco; Lily Hechtman, Department ofPsychiatry, McGill University; Stephen P. Hinshaw, Department of Psy-chology, University of California, Berkeley; Betsy Hoza, Department ofPsychological Sciences, Purdue University; Jeffrey H. Newcorn, Depart-ment of Psychiatry, Mt. Sinai Medical Center, New York; William E.Pelham, Department of Psychology, State University of New York, Buf-falo; Joanne B. Severe, Biostatistics and Data Management Unit, Divisionof Services and Intervention Research, National Institute of Mental Health(NIMH); James M. Swanson and Timothy Wigal, Department of Pediat-rics, University of California, Irvine; Benedetto Vitiello, Child and Ado-lescent Treatment and Prevention Intervention Research Branch, NIMH.

The Multimodal Treatment Study of Children with ADHD (MTA) is acooperative treatment study performed by six independent research teamsin collaboration with the staff of the Division of Clinical and TreatmentResearch of the National Institute of Mental Health (NIMH), Rockville,Maryland, and the Office of Special Education Programs of the U.S.Department of Education. The NIMH Principal Collaborators are Peter S.Jensen, L. Eugene Arnold, John E. Richters, Joanne B. Severe, DonaldVereen, and Benedetto Vitiello. Principal Investigators and Coinvestigatorsfrom the six sites are as follows: University of California at Berkeley/SanFrancisco (UO1 MH50461): Stephen P. Hinshaw and Glen R. Elliott; DukeUniversity Medical Center (UO1 MH50447): C. Keith Conners, Karen C.Wells, and John S. March; University of California at Irvine/Los Angeles(UO1 MH50440): James M. Swanson, Dennis P. Cantwell, and TimothyWigal; Long Island Jewish Medical Center/Montreal Children’s Hospital(UO1 MH50453): Howard B. Abikoff and Lily Hechtman; New York StatePsychiatric Institute/Columbia University/Mount Sinai Medical Center(UO1 MH50454): Laurence L. Greenhill and Jeffrey H. Newcorn; Univer-sity of Pittsburgh (UO1 MH50467): William E. Pelham and Betsy Hoza.Helena C. Kraemer (Stanford University) is statistical and design consul-tant. The OSEP/DOE Principal Collaborator is Thomas Hanley. The opin-ions and assertions contained in this article are the private views of theauthors and are not to be construed as official or as reflecting the views ofthe Department of Health and Human Services or the National Institutes ofHealth.

Correspondence concerning this article should be addressed to L. Eu-gene Arnold, 479 South Galena Road, Sunbury, Ohio 43074. E-mail:[email protected]

714 ARNOLD ET AL.

homozygous for the 10-repeat allele of the dopamine transportergene were nonresponsive to methylphenidate. Unfortunately, therewas no Caucasian comparison group in this study to tell if this wasan ethnic effect, but the proportion of nonresponders (14 out of 30)was considerably higher than reported in samples with more di-versity (a two thirds to three fourths response rate is customarilyquoted), raising a question of possible lower stimulant responserate in African Americans (Winsberg & Comings, 1999). (Wald-man et al., 1998, did not find an ethnic difference in the dopaminetransporter gene.) The lower response rate may or may not berelated to the finding by Epstein, March, Conners, and Jackson(1998) that teachers tend to rate African American children higheron ADHD and conduct symptoms, which may reflect either actualbehavioral differences or rating bias. When teacher ratings areused as an outcome measure (the usual practice in ADHD re-search), an assessment problem could arise if teachers fail to seereal improvement in the African American students.

The 579-subject sample of the National Institute of MentalHealth Multimodal Treatment Study of Children with ADHD (theMTA) provides an unprecedented opportunity to explore ethnicityeffects in ADHD treatment because of its broadly representativerecruitment from six sites (MTA Cooperative Group, 1999a). Infact, it was conceived to answer such secondary questions, whichwere included in the overarching question of the concept paper(Richters et al., 1995). One of the secondary purposes of the MTAwas to identify patient characteristics (demographic, comorbidity)that might affect treatment outcome. However, because the studywas not specifically powered to detect such moderator effects,these investigations are exploratory. Many such characteristicshave already been reported (Abikoff et al., 2002; Hoza et al., 2000;Jensen, 2001; Jensen et al., 2001; March et al., 2000; MTACooperative Group, 1999b; Newcorn et al., 2001; Rieppi et al.,2002), in addition to the primary intention-to-treat analysis of thefour treatment conditions (MTA Cooperative Group, 1999a). Theset of exploratory analyses reported here focuses on ethnic/racialeffects on treatment compliance, medication sensitivity, and 14-month clinical outcome.

MTA Treatments and Possible Ethnicity Interactions

The intensity of the MTA treatments suggests possibilities forethnicity interactions. The medication management (MedMgt) wasa carefully crafted and monitored strategy with an initialrandomized-order multiple-repeats comparison of placebo andthree doses of methylphenidate, which required daily parent rat-ings and weekly visits the 1st month, followed by 13 monthlymaintenance visits, and sometimes additional visits as needed(Greenhill et al., 1996). Thus, compliance/attendance over timewas a major consideration. The behavioral treatment (Beh) was anintensive multicomponent intervention including 35 sessions ofparent training, an 8-week full-time summer treatment program, 12weeks of half-time behaviorally trained aide in the classroom afterthe summer program, 10–16 teacher consultations, daily reportcard with home-based reinforcement, home token economy, andup to 8 possible supplementary sessions for emergencies. Thisdemanding regimen presents obvious possibilities for cultural in-teractions. Parenting strategies, a focus of the parent training, areinfluenced by culture (Harkness & Super, 1995; Ogbu, 1981,

1985). For example, Peters (1981) reported that African Americanparents, compared with Caucasian parents, show an increasedemphasis on shared parenting duties among community membersand an increased use of physical punishment. Kazdin (1990) foundthat African American families dropped out of psychosocial treat-ment both at a greater rate and earlier in treatment than didCaucasian families. Despite such differences, parent training pro-grams have been created and assessed almost exclusively withchildren from European American heritage (Forehand & Kotchick,1996), and very little research has studied the relationship betweenethnicity and psychosocial treatment. The few studies that do existhave largely failed to show significant associations between eth-nicity and the results of psychosocial treatment (e.g., Capage,Bennett, & McNeil, 2001). Clearly, more work is needed to clarifythe relationship of ethnicity to behavioral treatment for children.

The MTA sample allows a within-study exploration as recom-mended by Weisz et al. (1995, 1998). Our only hypotheses, basedon the reports of Kazdin (1990) and Winsberg and Comings(1999), respectively, were that African American parents wouldhave lower attendance than Caucasian parents at parent trainingand African American children would have a lower response rateto methylphenidate in the placebo-controlled initial titration. Theliterature does not provide a basis for other hypotheses; thus, theremaining analyses are exploratory.

Method

Aims of Analyses

The descriptive and exploratory analyses presented here focus on thefollowing issues:

1. Ethnic/racial effects on treatment outcome in ADHD.

2. Ethnic/racial effects on acceptance of and compliance withtreatment.

3. Ethnic/racial effects on sensitivity and response to commonlyused medication for ADHD.

4. Socioeconomic and other potential explanations of any signifi-cant ethnic effect found.

5. Informant differences (parent vs. teacher) by ethnicity of child.

These aims are parenthetically referenced in the description of analyticstrategy below.

MTA Sample

Details of the MTA design and sample have been reported elsewhere(Arnold et al., 1997a, 1997b; Hinshaw et al., 2000; MTA CooperativeGroup, 1999a). Briefly, 579 children ages 7–9.9 with rigorously diagnosedDiagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM–IV) ADHD, combined type (American Psychiatric Association, 1994),were recruited from multiple sources at six sites and randomly assignedwith equal probability to either intensive state-of-art MedMgt (the MTAmedication management algorithm) alone (Greenhill et al., 1996), intensivestate-of-the-art Beh alone (Wells et al., 2000), the combination of MedMgt

715ETHNICITY EFFECTS ON ADHD TREATMENT

and Beh (Comb), or routine community care (CC).1 The first three groupswere treated by study staff for 14 months, and the fourth was referred backto the community to seek routine community treatment of their ownchoosing. Some details of treatment were reported earlier in the introduc-tion. All of the groups were assessed at baseline and at 3, 9, and 14 months.In the entry demographics form, parents were asked to designate the child’sethnicity in standardized categories. The sample included 352 (61%) Cau-casian, 115 (20%) African American, 49 (8%) Latino (Hispanic), and 63(11%) other (Asian, Native American, Pacific Islander, mixed, etc.) chil-dren. Of the 566 who had data at 14 months, there were 345 Caucasian, 111African American, 47 Latino, and 63 other children. The analyses reportedhere use an intent-to-treat analysis with the last observation carried for-ward, making the entry count applicable.

An intent-to-treat analysis of the whole sample (MTA CooperativeGroup, 1999a) indicated that for ADHD symptoms, MedMgt and Combdid not differ significantly and were both superior to Beh and CC, whichdid not differ significantly. For other symptomatic (oppositional/aggres-sive, anxiety/depression) and functional (social skills, achievement,parent–child relations) domains, Comb was consistently superior to CC,whereas MedMgt and Beh generally did not differ significantly from eachother. Although site differences were significant as expected in this diversesample, site-by-treatment interactions were not; thus, the relative effect oftreatments was the same across sites. Secondary analyses with a globalcomposite outcome measure (Conners et al., 2001) and with a narrowcomposite score focused on ADHD and oppositional-defiant (ODD) symp-toms (Swanson et al., 2001) showed overall significant superiority ofComb over MedMgt alone with a small effect size (Cohen’s d � 0.26), amuch larger effect of the MTA medication algorithm, and negligibleadvantage of Beh over CC. Moderator analyses showed no effect for sex orprior history of medication, but a tendency for Beh and Comb to berelatively more effective in the presence of comorbid anxiety or publicassistance than for other patients (MTA Cooperative Group, 1999b). Otherstudies with finer grained analyses confirmed that comorbid anxiety, and tosome extent comorbid ODD or conduct disorder, tended to make Beh andComb more effective relative to CC and MedMgt (Jensen et al., 2001;March et al., 2000). With this background, we undertook analyses toexplore ethnic/racial effects on treatment acceptance/attendance, dosing,and treatment outcome.

Measures

The outcome measures include two symptom domains—ADHD andODD, each with two informants (parent and teacher)—the response to thedouble-blind methylphenidate titration (responder vs. nonresponder), thetitration-determined optimal dose for responders, initial satisfaction withrandom treatment assignment, overall treatment attendance, parent trainingattendance, and final medication dose. The rationale for selecting these wasas follows: ADHD and ODD symptoms were prime targets of the treatment(Aim 1), and perception of these may differ culturally between parent andteacher (Aim 5); satisfaction with initial assignment and overall attendanceallows comparisons of the three MTA-treated groups on attitudes towardand cooperation with treatment, whereas parent training (two MTA-treatedgroups) is the attendance measure believed most culturally sensitive(Aim 2, and one of the two a priori hypotheses); titration outcomes tap theembedded titration study for conceptually distinct issues and involve one apriori hypothesis (Aim 3); and final dose is heuristic about what happensto dose under clinical circumstances (Aim 3).

ADHD symptoms were measured by parent and teacher ratings on the 18DSM–IV symptoms on a 0–3 metric (SNAP–IV; Swanson, 1992). TheODD symptoms were measured by the 8 ODD symptoms on the SNAP–IV. Attendance at treatment sessions and medication monitoring visits wasused as a proxy for compliance, as in the original moderator–mediatorarticle (MTA Cooperative Group, 1999b). A dichotomous general atten-

dance variable had been constructed, with excellent, as-intended atten-dance defined as 75% or more of assigned parent training and 80% or moreof other assigned treatment sessions and medication monitoring visits.Satisfaction with randomized treatment assignment was measured by a 1–6clinician-rated estimate of the family’s satisfaction with the assignmentderived from a debriefing immediately after randomization.

Medication dose and response were measured as follows: Those as-signed to receive medication by the MTA algorithm, whether in MedMgtor Comb, had a 1-month initial placebo-controlled double-blind multiple-repeats daily-switch methylphenidate (MPH) titration to find the best doseand determine responder status as judged from graphed data by blindedexpert clinicians. This was followed by 13 months of closely monitoredmaintenance during which dose could be adjusted. Thus, both a titration-recommended dose and an end-of-treatment dose can be used as measuresof a patient’s optimal dose (Greenhill et al., 2001; Vitiello et al., 2001). Forpurposes of the end-of-treatment dose analysis presented here, doses ofother drugs (taken by MPH nonresponders), such as d-amphetamine, wereconverted to MPH equivalents using standard relative potencies. Also, eachparticipant was blindly classified as methylphenidate responder, placeboresponder, or nonresponder by an expert panel at the end of the placebo-controlled methylphenidate titration, allowing calculation of percentageMPH responders and nonresponders in each ethnic/racial group.

Measures for SES and other potential confounders (Aim 4). Mother’seducational level, public assistance, and single-parent status, were selectedas measures of potential socioeconomic (SES) confounders based onconceptual considerations and previous findings of effect on treatmentoutcome in this sample (MTA Cooperative Group, 1999b; Rieppi et al.,2002). Mother’s education was coded on six levels from less than 7thgrade to graduate professional; receipt of public assistance was a dichot-omous variable based on anyone in the family receiving public assistance;and single-parent status was dichotomous, defined as other than living withtwo parent figures (natural, step, or common-law). Comorbidity was de-termined by a baseline Diagnostic Interview Schedule for Children–parentversion (Shaffer et al., 1996) and was found in previous analyses to affecttreatment outcome (Jensen et al., 2001; March et al., 2000; MTA Coop-erative Group, 1999b). Baseline symptom severity was found in a previousanalysis (Owens et al., in press) to affect treatment outcome.

Overall Analytic Strategy

Analysis for ethnicity presents an extreme case of a problem that to someextent also threatens SES and gender analyses in this or any study notspecifically designed to study such effects: The imbalance in subgrouprepresentation from site to site may confound site with subgroup. Majorsite differences in outcome have been reported (e.g., MTA CooperativeGroup, 1999a), presumably due to site demographics and possibly subtledifferences in selection, management, treatment, and evaluation. Thereforeeach participant can be compared validly only against other participants atthe same site in the same treatment group. However, the sites differremarkably in representation of minority groups (Table 1), and suchimbalance may confound site with ethnicity effects.

To resolve such problems at least partially, we adopted a matched-pairstrategy, controlling for site, treatment group, and sex. Using a table ofrandom numbers, an African American participant was randomly selected

1 In the cited methodology papers for this study, the treatment assign-ments were called medication (med), psychosocial treatment (PS), com-bined treatment (CT), and community-treatment assessment and referral(A&R). To more accurately reflect the actual treatments, the terminologyis changed for all outcome papers to these clearer and more specific terms:medication management (MedMgt), behavioral treatment (Beh), combinedtreatment (Comb), and community comparison (CC).

716 ARNOLD ET AL.

and then a Caucasian match was randomly selected from all of the Cau-casian participants of the same sex in the same treatment group at that sitenot already selected as matches. Of the 115 African American participants,it was thus possible to match 92. A total of 8 girls and 15 boys could notbe matched because of an insufficient number of Caucasian children of thesame sex and treatment group at their site. Latino children were similarlyrandomly matched with Caucasian children, resulting in 37 matches outof 49 Latino participants, with 1 girl and 11 boys unable to find Caucasianparticipants matches. A preponderance of the failed matches for both ethnicminorities were at Site 3, where Caucasian children were the actualminority.

Yet another special problem is within-ethnicity differences: New YorkLatino children of Caribbean derivation are not culturally or even raciallyidentical to California Latino children of Mexican derivation. This sub-subgrouping problem, of course, extends also to Caucasian children: Cal-ifornia Caucasian children are not culturally identical to Carolina or Penn-sylvania Caucasian children (let alone Montreal Caucasian children).However, inspection of the distribution (Table 1) shows that splitting anyof the ethnic groups would create groups too small for meaningful com-parison. This issue limits the generalizability of the results.

The special situation of Site 3 offered an opportunity for a three-waycomparison of African American, Latino, and Caucasian children. Inparticular, this is the only chance to compare the two minority ethnicgroups meaningfully. The matching strategy was not used for this second-ary single-site comparison because site is already controlled and there areenough of each ethnic group for adequate representation in each treatmentgroup.

Statistical Analyses

The outcome contrasted is the 14-month endpoint scores for the repeatedmeasures symptom scores (with last observation carried forward), or dos-age, attendance, responder status, or satisfaction with random assignment.The unit of analysis was the pair. For each continuous outcome measure,we computed the pair difference (African American–Caucasian; Latino–Caucasian) by computing the difference for each matched pair and thencomputing means for treatment groups on these difference scores. We thenused multiple regression with the pair difference as the dependent measureand three orthogonal contrast indicators as the independent contrasts:

1. The MTA medication algorithm effect: CC � �0.5, MedMgt ��0.5, Comb � �0.5, Beh � �0.5.

2. The multimodal superiority effect: CC � 0, MedMgt � �1,Comb � �1, Beh � 0.

3. The behavioral substitution effect: CC � �1, MedMgt � 0,Comb � 0, Beh � �1.

The main effect of ethnicity is tested by the intercept in this model, theinteraction effects of ethnicity and treatment by the regression coefficients.Thus, a significant regression coefficient for the MTA med algorithmeffect, for example, indicates an interaction between ethnicity and theMTA med algorithm treatment effects, that is that the response differentialof those receiving versus not receiving that medication algorithm is sig-nificantly different for African American and Caucasian participants. Insuch a case, the treatment effect associated with medication is different forthe two ethnic groups, the direction and magnitude of that difference shownby comparisons of means and effect sizes. The effect sizes used areCohen’s d for matched pairs: the mean of the appropriate matched pairsdifferences divided by the standard deviation of the differences. For atten-dance data (available only for the MTA-treated groups) and for dosage(which included only Comb and MedMgt), only one contrast was possible.

For noncontinuous data (overall dichotomously defined attendance andtitration response), we used SAS CATMOD, yielding a main effect ofethnicity and interaction of ethnicity with the treatment group contrast,which is essentially the same as the orthogonal contrast of the continuousvariables. Again, because not all of the groups were involved and becauseof the limitations of CATMOD for matched-pair analyses, only one con-trast, Comb versus MedMgt, was possible.

Because this is an exploratory or hypothesis-generating study, weelected to put major stress on descriptive statistics and effect sizes, usingstatistical significance levels only to focus attention on the most promisingresults. Consequently, we did not adjust for multiple testing, but used a 5%significance level throughout. This strategy reduces the probability of aType II error, which is already high because of small cell sizes. Also, wenote nonsignificant large effect sizes that deserve further exploration.

Strategy for Evaluation of SES and Other PotentialConfounders

It has long been noted that what appear to be ethnic differences mayarise, not specifically because of ethnicity but because of factors closelyassociated with ethnicity, such as SES, language facility, or poverty-associated comorbidity (Vargas & Rand, 1999). Such potential confound-ers include mother’s education, poverty (e.g., need for public assistance),single parenthood, baseline severity scores, and comorbidity. Therefore weadopted the following three-part strategy to control for these and to exploretheir contribution to any differences found: (a) We first did each set ofethnic comparisons “clean,” without considering potential confounders. Ifno significant difference was found, there is no need to look further; the

Table 1MTA Subject Count at Each Site by Ethnicity and Sex

Site no.

Caucasian African American LatinoOthertotal Total allBoys Girls Total Boys Girls Total Boys Girls Total

Site 1 57 20 77 11 2 13 0 0 0 5 95Site 2 54 13 67 4 0 4 9 0 9 16 96Site 3 18 3 21 30 7 37 28 4 32 6 96Site 4 40 13 53 24 2 26 1 1 2 17 98Site 5 52 19 71 14 9 23 0 0 0 2 96Site 6 57 6 63 9 3 12 6 0 6 17 98

Totals 278 74 352 92 23 115 44 5 49 63 579

Note. Approximately one fourth of each marginal total was randomly assigned to each of the four treatment groups. MTA � Multimodal Treatment Studyof Children with Attention–Deficit/Hyperactivity Disorder.


issue of SES or other confounders is moot for nonsignificant ethnicdifferences. For any significant ethnic difference we found on the cleananalyses, we invoked the following, Parts (b) and (c). (b) Using thematched pairs, we compared ethnic groups on each likely potential con-founder, to determine whether the ethnic groups differed significantly.Potential confounders were thus identified that differed significantly byethnic group. (c) For each outcome variable that showed a statisticallysignificant ethnic effect, the original analysis was repeated with eachsignificant potential confounder as a covariate to see if the putative eth-nicity effect could be explained by the potential confounder.

Three-Way Ethnic Comparison

For the secondary three-way comparison of the 37 African American, 32Latino, and 21 Caucasian participants at Site 3, we used repeated measuresanalyses of variance with time (two levels, baseline and 14 months),ethnicity (three levels), and treatment group (4 levels) as independentvariables, and the four symptom ratings (two by parents, two by teachers)as the dependent variables.

Results

Main Matched-Pairs Analyses

Tables 2 and 3 display the sample sizes and 14-month (end-point) means and standard deviations by ethnic group for thematched pairs of African American–Caucasian and Latino–Caucasian participants, respectively, with ethnic effect sizes foreach treatment group and for the total group. The ethnic differ-ences for CC give a rough notion of how the ethnic groups woulddiffer without the MTA interventions.

Symptom Outcomes

There are significant main effects of ethnicity for African Amer-ican children on teacher-rated ADHD and ODD symptoms, withbetter outcomes reported for Caucasian participants (effect size:d � 0.31 and 0.59).

One significant ethnicity by treatment outcome was detected forthe African American participants: The advantage of Beh aloneover CC in reducing parent-rated ODD symptoms was signifi-cantly ( p � .04) greater than for Caucasian children (effect size:d � 0.59).

There was a main effect of ethnicity for Latino children onparent-rated ODD symptoms, with better outcomes reported forCaucasian participants (d � 0.58).

One significant ethnicity-by-treatment interaction was detectedfor the Latino participants: On parent-rated ODD, the advantage ofadding Beh to MedMgt in Comb (compared with MedMgt alone)was significantly ( p � .04) greater than for Caucasian children(effect size: d � 0.93).

Acceptance of and Attendance at Treatment

Upon randomization, African American parents showed remark-ably little difference from Caucasian parents in their satisfactionwith each randomly assigned treatment condition. In contrast, theLatino–Caucasian difference on satisfaction with assignment toBeh versus CC showed a very large effect (d � �1.82), in thedirection of Caucasian participants preferring Beh over CC more

than did the Latino participants, but this was not significant. Theethnic groups did not differ significantly on parent training atten-dance, with all of the groups attaining a respectable mean atten-dance rate of two thirds or better. Although African Americanchildren had 12% lower attendance at parent training than didCaucasian children (d � 0.29), the hypothesis of lower parenttraining attendance missed statistical ( p � .08) significance. Theoverall global excellent attendance rate was 13% less for AfricanAmerican than for Caucasian participants ( p � .09) and 15% lessfor Latino than for Caucasian participants ( p � .10). AlthoughLatino children had three times as good attendance at MedMgt asat Comb in sharp contrast to Caucasian children, the ethnic dif-ference in global attendance difference between Comb and Med-Mgt missed significance ( p � .07).

Medication Response and Sensitivity

Of the 289 participants assigned to the MTA medication man-agement (in MedMgt and Comb), 19 did not complete the initialdouble-blind methylphenidate titration; these were distributedacross ethnic groups in rough proportion to the sample ethnicproportion (13 Caucasian, 5 African American, 1 Latino). Withinthe relevant matched pairs (44 African American and 22 Latinopairs in the two relevant treatment groups), there were 7 Cauca-sian, 5 African American, and 1 Latino participants who did notcomplete titration. For some affected pairs, it was possible to findan alternate randomly selected match of the same sex at the samesite in the same treatment assignment who did complete titration,thus retaining 37 African American and 21 Latino matched pairs inthe two relevant treatment groups for the titration outcome anal-yses. Although the MPH nonresponse rate for African Americanchildren was almost twice as high as for Caucasian children (7 vs.4), the difference was not significant at these numbers ( p � .40)and was due mainly to lower placebo response (2 vs. 4), with theactual response rate to methylphenidate almost identical (76% vs.78%). Thus, the hypothesis of lower response rate among AfricanAmerican children is not supported. The titration response profilefor Latino children was similar. Of MPH responders, the besttitration dose tended to be consistently (but not significantly) lowerfor both minorities than for Caucasian participants. In contrast, bythe end of 14 months of clinically adjusted treatment, dosesreached a 50% higher level ( p � .09) for African American thanfor Caucasian participants in MedMgt, although the Comb dosesfor African American and Caucasian children were almost identi-cal. The comparison of Comb and MedMgt ethnic effects on thislast dose, although of medium effect (d � 0.59), missed signifi-cance ( p � .09). Similarly, the moderate-to-large effect size(d � 0.78) by which Latino 14-month MedMgt doses exceededComb doses more than did Caucasian doses was not significant.

SES and Other Possible Confounders

Tables 4 and 5 show possible confounders, that is, possibleexplanations of ethnic differences. For the African American ver-sus Caucasian comparison, there were some baseline differences,but stronger differences in measures related to SES: mother’seducation, public assistance, single parent, as well as a significantdifference in comorbid anxiety disorders. For the Latino versus

718 ARNOLD ET AL.

Table 2Matched Pairs Comparison of 92 African American and 92 Caucasian ADHD Children at 14 Months (End of Treatment)

Outcome measure andtreatment group African American Caucasian Ethnic difference

Ethnic effect size

Cohen’s d OR p

ADHD symptoms: Mean parent rating (SD)a

CC (n � 20) 1.29 (0.74) 1.28 (0.68) 0.01 (1.12) 0.01MedMgt (n � 24) 1.07 (0.60) 1.11 (0.72) �0.04 (0.81) �0.05Comb (n � 20) 1.07 (0.59) 1.01 (0.61) 0.07 (0.81) 0.09Beh (n � 28) 1.19 (0.65) 1.35 (0.55) �0.16 (0.80) �0.20Total 1.15 (0.64) 1.20 (0.64) �0.04 (0.87) �0.05 � .7

ADHD symptoms: Mean teacher rating (SD)a

CC (n � 20) 1.61 (0.62) 1.28 (0.65) 0.33 (1.02) 0.32MedMgt (n � 24) 1.49 (0.82) 1.27 (0.78) 0.22 (1.01) 0.22Comb (n � 20) 1.25 (0.69) 0.82 (0.67) 0.43 (0.95) 0.45Beh (n � 28) 1.57 (0.84) 1.32 (0.74) 0.25 (0.98) 0.26Total 1.49 (0.76) 1.19 (0.73) 0.30 (0.98) 0.31 .004

ODD symptoms: Mean parent rating (SD)a

CC (n � 20) 1.18 (0.86) 0.82 (0.43) 0.36 (1.00) 0.36**MedMgt (n � 24) 1.01 (0.85) 0.87 (0.65) 0.14 (0.97) 0.14Comb (n � 20) 0.81 (0.51) 0.76 (0.72) 0.05 (0.92) 0.05Beh (n � 28) 0.90 (0.91) 1.12 (0.58) �0.22 (0.99) �0.22**Total 0.97 (0.81) 0.91 (0.61) 0.07 (0.98) 0.07 � .4

ODD symptoms: Mean teacher rating (SD)a


Mean satisfaction with treatment assignment (SD)b

CC (n � 16) 3.00 (1.26) 2.81 (1.56) 0.19 (1.60) 0.12MedMgt (n � 17) 3.71 (1.61) 3.41 (1.46) 0.30 (2.20) 0.14Comb (n � 14) 5.71 (0.47) 5.43 (0.85) 0.28 (1.07) 0.26Beh (n � 23) 5.17 (1.11) 5.22 (1.28) �0.05 (1.72) �0.03Total 4.43 (1.58) 4.27 (1.71) 0.15 (1.69) 0.09 � .3

Parent training, Mean % sessions attended (SD)Comb (n � 20) 68.5 (28.2) 72.9 (36.6) �4.4 (50.0) �0.09Beh (n � 28) 66.3 (27.7) 84.3 (21.3) �18.1 (37.1) �0.49Total 67.2 (27.6) 79.5 (28.9) �12.4 (43.0) 0.29 .08

Good overall attendance, %MedMgt (n � 24) 75.0 75.0 0 1.00c

Comb (n � 28) 42.8 67.9 �25.1 0.63c

Beh (n � 20) 50.0 65.0 �15.0 0.77c

Total 55.6 69.4 �13.8 0.80c .09MPH response: Responders/nonresponder/placebo

MedMgt (n � 18) 11/6/1 13/2/3 �2/4/�2 0.85c

Comb (n � 19) 17/1/1 16/2/1 1/�1/0 1.06c

Total 28/7/2 29/4/4 �1/3/�2 0.97c � .3Titration best dose: Mean mg/d MPH (SD)d

MedMgt (n � 8) 31.9 (15.6) 34.4 (15.0) �2.5 (19.3) �0.13Comb (n � 15) 26.7 (13.5) 29.3 (15.9) �2.7 (17.3) �0.15Total 28.5 (14.1) 31.1 (15.4) �2.6 (17.6) �0.15 � .5

Final dose (mg/d MPH) M (SD)e

MedMgt (n � 15) 48.7 (25.4) 32.4 (21.8) 16.3 (28.0) 0.58*Comb (n � 15) 25.7 (19.4) 25.6 (16.4) 0.1 (22.1) 0.01*Total 37.2 (25.0) 29.0 (19.3) 8.2 (26.1) 0.31 .086

Note. n � number of pairs. Total rows � main effects for ethnicity. The MPH response is based on a double-blind placebo-controlled titration. ADHD �attention-deficit/hyperactivity disorder; OR � odds ratio; CC � community comparison group; MedMgt � medication management; Comb � combinationtreatment; Beh � behavioral treatment alone; ODD � oppositional-defiant disorder; MPH � methylphenidate; mg/d � milligrams per day.a Lower scores were better on a 0–3 scale and negative d indicates better outcome for African American participants. b Higher scores indicated “moresatisfied” on a 1–6 scale. c OR indicates the chance of African American participants having good attendance or MPH response compared with Caucasianparticipants. d For titration, MPH was actual MPH. e For final dose, MPH was either actual MPH or dose of other stimulant converted to MPHequivalents on potency basis.* Ethnic differences in last-dose difference between Comb and MedMgt missed significance at p � .09 (with a 16.2 mg/d greater Comb-MedMgt differencefor African American participants than Caucasian participants). ** Ethnic difference in advantage of Beh over CC was significant at p � .04 (d � 0.59)for parent-rated ODD. No other ethnic differences in orthogonal contrasts between treatment groups were either significant or marginally significant.


Table 3Matched Pairs Comparison of 37 Latino and 37 Caucasian ADHD Children in 14 Month Clinical Outcomes

Outcome measure andtreatment group Latino Caucasian Ethnic difference

Ethnic effect size

Cohen’s d OR p

ADHD symptoms: Mean parent rating (SD)a


ADHD symptoms: Mean teacher rating (SD)a


ODD symptoms: Mean parent rating (SD)a

CC (n � 6) 1.25 (0.58) 1.00 (0.36) 0.25 (0.59) 0.42MedMgt (n � 12) 1.53 (0.79) 0.64 (0.54) 0.89 (1.06) 0.84*Comb (n � 10) 0.70 (0.71) 0.55 (0.38) 0.15 (0.52) 0.29*Beh (n � 9) 1.54 (0.82) 1.07 (0.42) 0.47 (0.80) 0.59Total 1.26 (0.80) 0.78 (0.48) 0.48 (0.83) 0.58 .003

ODD symptoms: Mean teacher rating (SD)a


Mean satisfaction with treatment assignment (SD)b

CC (n � 4) 2.75 (1.71) 1.75 (0.50) 1.00 (1.41) 0.71MedMgt (n � 6) 3.67 (1.37) 3.67 (1.75) 0.00 (2.97) 0.00Comb (n � 4) 4.50 (1.73) 6.00 (0.00) �1.50 (1.73) �0.87Beh (n � 6) 4.83 (1.17) 5.67 (0.52) �0.83 (0.75) �1.11Total 4.00 (1.56) 4.35 (1.90) �0.35 (2.01) �0.17 � .4

Mean parent training attended, % sessions (SD)Comb (n � 10) 66.7 (34.5) 84.3 (23.8) �17.6 (30.8) �0.57Beh (n � 9) 74.2 (38.1) 86.0 (17.9) �11.8 (48.6) �0.24Total 70.3 (35.4) 85.1 (20.6) �14.8 (39.2) �0.38 .13

Overall good attendance, %MedMgt (n � 12) 91.7 83.3 8.30 1.10c,d

Comb (n � 10) 30.0 70.0 �40.0 0.43c,d

Beh (n � 9) 55.6 77.8 �22.2 0.71c

Total 61.3 77.4 �16.1 0.79c � .1MPH response: responders/nonresponders/placebo

MedMgt (n � 11) 7/2/2 9/2/0 �2/0/2 0.78c

Comb (n � 10) 8/1/1 9/1/0 �1/0/1 0.89c

Total 15/3/3 18/3/0 �3/0/3 0.83c .68Titration best dose: Mean mg/d MPH (SD)e

MedMgt (n � 6) 22.5 (10.8) 25.8 (12.8) �3.33 (20.7) �0.16Comb (n � 7) 29.3 (14.8) 33.6 (11.8) �4.28 (12.4) �0.35Total 26.2 (13.1) 30.0 (12.4) �3.85 (16.0) �0.24 � .4

Final dose (mg/d MPH) M (SD)f

MedMgt (n � 10) 43.4 (30.6) 35.0 (17.5) 8.4 (33.7) 0.25Comb (n � 8) 19.4 (9.0) 32.6 (22.7) �13.3 (24.9) �0.53Total 32.7 (26.1) 33.9 (19.4) �1.2 (31.3) �0.04 � .7

Note. n � number of pairs. Total rows � main effects for ethnicity. The MPH response is based on a double-blind placebo-controlled titration. ADHD �attention-deficit/hyperactivity disorder; OR � odds ratio; CC � community comparison group; MedMgt � medication management; Comb � combinationtreatment; Beh � behavioral treatment alone; ODD � oppositional-defiant disorder; MPH � methylphenidate; mg/d � milligrams per day.a Lower scores were better on a 0–3 scale and negative d indicates better outcome for Latino participants. b Higher scores indicated “more satisfied” ona 1–6 scale. Negative effect size indicates lower Latino satisfaction. c OR indicates the chance of Latino participants having good attendance or MPHresponse compared with Caucasian participants. d Ethnic difference in the Comb-MedMgt difference for overall good attendance missed significance atp � .07. e For titration, MPH was actual MPH. f For final dose, MPH was either actual MPH or dose of other stimulant converted to MPH equivalentson potency basis. Negative d indicates lower dose for Latino participants.* Ethnic difference in advantage of Comb over MedMgt was significant at p � .04 (d � 0.93) for parent-rated ODD. No other ethnic differences inorthogonal contrasts between treatment groups were either significant or marginally significant.

720 ARNOLD ET AL.

Caucasian contrast, there was no significant difference detected atbaseline and no difference in comorbidity. Again, however, therewere major differences in variables associated with SES.

To check whether the significant ethnicity effects found inTables 2 and 3 are accounted for by such confounders, we presentin Tables 6 and 7, for each significant effect in Tables 2 and 3, thesignificance level (and where possible the adjusted effect size)adjusted for each of the significant possible confounders. All of themain effects of ethnicity detected remain significant after adjust-ment for any of the possible confounders. However, both of theEthnicity � Treatment interaction effects become nonsignificantwhen the SES factor of public assistance is controlled. Thus, itmay very well be that the Ethnicity � Treatment interactionsdetected in Tables 2 and 3 are not due to ethnicity per se, but to thesocioeconomic factors associated with ethnicity.

Single-Site Three-Way Ethnic Comparison: AfricanAmericans Versus Latinos

To make a direct comparison of African American and Latino,with Caucasian children as a descriptive anchor, Table 8 usesSite 3, which had substantial representation of all three ethnicgroups. Teacher-rated ODD symptoms showed a main effect of

ethnicity generally favoring Caucasian and disfavoring AfricanAmerican children, with Latino children between. The effect sizes(d) for paired comparisons ranged from 0.23 to 0.85. This maineffect remained significant even after covarying mother’s educa-tion, public assistance, and single-parent status. The ethnic effecton change over time was significant at p � .04 for parent-ratedADHD, with the greatest improvement occurring in Caucasian andleast in Latino children, with African American close to Caucasianparticipants. A similar tendency with parent-rated ODD does notreach significance ( p � .08). The significant finding on parent-rated ADHD was rendered nonsignificant ( p � .33) by covaryingmother’s education, suggesting that SES factors explain the ethniceffect on change over time. No time-by-ethnicity-by-treatmentinteraction was significant.

Parent and Teacher Perceptions by Ethnicity

In Table 8, African American parents generally perceived theirchildren as improving to a degree similar to that of the perceptionof Caucasian parents, but Latino parents perceived their childrenimproving considerably less (effect size difference d � 0.60 fromCaucasians, 0.46 from African Americans). In contrast, teachersperceived Latino children improving at least as much as African

Table 5Possible Confounders of Statistically Significant Ethnic Differences in Outcomes on Table 3

Potential confounders Latino Caucasian Ethnic difference

Effect size

pd OR

Baseline ODD sx, M (SD)Parent ratings 1.53 (0.74) 1.34 (0.62) 0.19 (0.92) 0.21 .21

Mother’s education, M (SD) 2.56 (0.97) 3.58 (1.16) �1.03 (1.73) 0.60 .001Public assistance, % 51.4 13.5 37.9 3.8 .003Single parent, % 40.5 13.5 27.0 3.0 .01Baseline comorbid anxiety disorder, % 27.0 51.4 �24.4 0.53 .09Baseline comorbid ODD/CD, % 45.9 62.2 �16.3 0.74 .26

Note. n � 37 matched pairs. OR � odds ratio; ODD � oppositional-defiant disorder; sx � symptoms; CD � conduct disorder. For ODD and CDsymptoms, lower score (0–3 metric) is better; for mother’s education, higher score is better on a 6-level scale.

Table 4Possible Confounders of Statistically Significant Ethnic Differences in Outcomes on Table 2

Potential confounder African American Caucasian Ethnic difference

Effect size

pd OR

Baseline ADHD sx, M (SD)Teacher rating 2.28 (0.48) 2.11 (0.52) 0.17 (0.69) 0.25 .02

Baseline ODD sx, M (SD)Parent rating 1.43 (0.85) 1.40 (0.68) 0.03 (0.12) 0.25 .80Teacher rating 1.86 (0.82) 1.22 (0.89) 0.64 (1.31) 0.49 � .001

Mother’s education, M (SD) 3.10 (1.00) 3.53 (1.14) �0.43 (1.63) �0.26 .01Public assistance, % 35.9 7.6 28.3 4.7 � .001Single parent, % 55.4 18.5 36.9 3.0 � .001Baseline comorbid anxiety disorder, % 38.0 17.4 20.6 2.2 .003Baseline comorbid ODD/CD, % 53.3 54.3 �1.0 0.98 1.0

Note. n � 92 matched pairs. OR � odds ratio; ADHD � attention-deficit/hyperactivity disorder; sx � symptoms; ODD � oppositional-defiant disorder;CD � conduct disorder. For ADHD and ODD symptoms, lower score (0–3 metric) is better; for mother’s education, higher score is better on a 6-levelscale.


American children. The ethnic swing in the difference betweenperceptions of teachers and perceptions of parents for the twominorities is d � 0.65 for ADHD symptoms.

Multimodal Superiority in Caucasians and PooledMinorities

Heuristic inspection of the data in Tables 2 and 3 raised thepossibility that the multimodal superiority effect (Comb advantageover MedMgt) reported by Swanson et al. (2001) and Conners etal. (2001) may have been confined to ethnic minorities. As a checkon this speculation, we did a further tertiary exploration subgroup-ing all Caucasian children (352) and all non-Caucasian children(227, pooled minorities), to see whether this would descriptivelydemonstrate a more impressive benefit for minorities than forCaucasians of adding behavioral treatment to medication. Thehypothesis was that minorities but not Caucasians would show aclinically meaningful and statistically significant multimodal su-periority effect. We used a single outcome measure, the SNAPdisruptive behavior disorder composite developed by Swanson etal.; it consists of the item average of the 18 ADHD symptomsand 8 ODD symptoms rated by parents and teachers (a total of 52items) on a 0–3 metric. Using this measure, Swanson et al.reported a significant multimodal superiority effect for the wholesample (d � 0.26). For missing 14-month data, we carried the last

observation forward for an intent-to-treat analysis of all 352 Cau-casian and all 227 minority participants.

For this tertiary exploration, Table 9 shows the means andstandard deviations of the baseline-to-14-month change scores foreach ethnic group (Caucasian vs. minority) in each treatmentgroup. In separate multiple regressions for each ethnic group of14-month scores with baseline score, site, and the three orthogonalcomparisons entered, the multimodal superiority effect was signif-icant ( p � .02, d � 0.36) for pooled minorities but not forCaucasian participants ( p � .59, d � �0.04). In fact, the negli-gible effect size for Caucasians runs trivially the wrong direction(actually multimodal inferiority). The pooled-minority multimodalsuperiority effect remains significant after controlling for mother’seducation ( p � .04), public assistance (p � .02), single-parentstatus ( p � .02), and all three simultaneously ( p � .03). However,this apparent ethnic difference in the differential benefit of Comband MedMgt does not withstand a statistical test that includes bothethnic groupings in the same analysis ( p � .10 for the differencebetween Caucasians and non-Caucasians).

Discussion

All comment on these findings must be tempered by realizationof the limitations characterizing all exploratory analyses.

Main Effects of Ethnicity on Clinical Symptom Outcomes

The results have shown an overall outcome difference (regard-less of treatment received) in teacher-rated ADHD and ODDsymptoms between African American and matched Caucasianparticipants and an overall difference in parent-rated ODD symp-toms between Latino American and matched Caucasian partici-pants, in all cases with minority groups rated as more symptom-atic. The single-site three-way comparison also showed asignificant main effect (regardless of time or treatment) ethnicdifference on teacher-rated ODD favoring Caucasian and disfavor-

Table 7Significant Outcomes for Latino Versus Caucasian Participants(Table 3) Reanalyzed With Significant Potential Confounders(Table 5) Covaried

Outcome measure and covariateMain effect of

ethnicity p

Ethnicdifference

Comb-MedMgta

d p

ODD symptomsParent rating

Mother’s education .003 1.21 .008Public assistance .03 0.62 .15Single parent .03 0.55 .22

Note. Only significant findings from Table 3 are analyzed. Significantpotential confounders in Table 5 are covaried. Comb � combinationtreatment; MedMgt � medication management; ODD � oppositional-defiant disorder.a Ethnic difference in multimodal superiority is the difference betweenLatino and Caucasian participants in the respective differences of Comb-MedMgt.

Table 6Significant Outcomes for African American Versus CaucasianParticipants (Table 2) Reanalyzed With Significant PossibleConfounders (Table 4) Covaried

Outcome measure and covariateMain effect of

ethnicity p

Ethnicdifference

Beh vs. CCa

d p

ADHD symptomsTeacher rating

Baseline score .008Mother’s education .003Public assistance .03Single parent .02Comorbid anxiety disorder .02

ODD symptomsParent rating

Mother’s education 0.60 .04Public assistance 0.16 .60Single parent 0.78 .02Comorbid anxiety disorder 0.38 .23

Teacher ratingBaseline score �.001Mother’s education �.001Public assistance �.001Single parent �.001Comorbid anxiety disorder �.001

Note. Only significant findings from Table 2 are retested. Significantpotential confounders from Table 4 are covaried. Beh � behavioral treat-ment alone; CC � community comparison group; ADHD � attention-deficit/hyperactivity disorder; ODD � oppositional-defiant disorder.a Ethnic difference in behavioral effect is the difference between AfricanAmerican and Caucasian participants in the respective differences ofBeh-CC.

722 ARNOLD ET AL.

ing African American children. These differences did not disap-pear when adjusted for baseline levels, socioeconomic factors, orcomorbidity. It is not possible to ascertain from these data whetherthese overall effects are due to rater bias or to the minorities thatare affected by ADHD being more symptomatic, at least in certainsettings.

Parent Versus Teacher Perceptions

For African Americans, the ethnic outcome difference is seenonly for teachers, not for parents, which would support the hy-pothesis of informant bias (assuming that the teachers were mostlynot African American, which is not known from this data set).However, for Latinos, the ethnic difference is seen only for par-ents, not for teachers, which would argue against teacher-raterbias. It is interesting that teacher-rated ODD showed the advantage

for Caucasians over African Americans even in the secondaryanalyses of Site 3, where African Americans were the dominantgroup and Caucasians were in the minority. Epstein et al. (1998)also reported higher teacher ADHD and ODD symptom ratings forAfrican American than for Caucasian children.

The Site 3 analysis offers some suggestive evidence for culturaldifference in rater perceptions in the moderate-size swing of rel-ative symptom ratings between parent and teacher raters; teachersrated improvement of the three ethnic groups more similarly thandid the parents and rated in the order of Caucasian most favorable,then Latino. In contrast, parents rated in the order of Caucasianmost favorable, then African American, with Latino considerablylower. This contrast may help explain why the significant overallethnic differences in the matched pairs analysis were by teachersfor African American matched pairs and by parents for Latino pairs.

Table 8Change Scores From Baseline to 14 Months for African American, Latino, and Caucasian Children at Site 3

Outcome measure and treatment group

AfricanAmerican(n � 37)

Latino(n � 32)

Caucasian(n � 21)

African American vs. Latino:d of differenceaM (SD) M (SD) M (SD)

ADHD symptoms: Parent ratingCC �0.78 (0.61) �0.38 (0.43) �0.63 (0.84) �.75MedMgt �0.53 (0.76) �0.36 (0.56) �0.94 (0.58) �.25Comb �0.89 (0.48) �0.59 (0.89) �1.56 (0.65) �.70Beh �0.43 (0.37) �0.37 (0.61) �0.40 (0.37) �.12Totalb �0.66 (0.58) �0.44 (0.65) �0.90 (0.71) �.36

ADHD symptoms: Teacher ratingCC �0.43 (1.09) �0.59 (0.90) �1.25 (0.88) .16MedMgt �0.57 (0.82) �1.00 (0.81) �0.86 (0.81) .52Comb �1.18 (0.60) �1.13 (0.77) �2.14 (0.33) �.07Beh �0.82 (0.95) �0.99 (1.10) �0.77 (0.87) .17Total �0.74 (0.90) �0.95 (0.88) �1.22 (0.89) .29

ODD symptoms: Parent ratingCC �0.43 (0.44) 0.02 (0.40) �0.09 (0.57) �1.05MedMgt �0.52 (0.83) 0.15 (0.92) �0.60 (0.53) �.77Comb �0.66 (0.70) �0.58 (0.63) �1.23 (0.39) �.12Beh �0.25 (0.71) �0.17 (0.56) 0.03 (0.46) �.13Totalc �0.46 (0.67) �0.19 (0.67) �0.50 (0.67) �.40

ODD symptoms: Teacher ratingCC 0.27 (0.84) �0.34 (0.74) �0.84 (0.73) .76MedMgt �0.21 (0.64) �0.87 (0.93) �0.68 (1.07) .87Comb �1.28 (0.93) �0.64 (0.76) �1.18 (1.18) �.76Beh �0.73 (1.04) �0.44 (1.49) �0.13 (1.07) �.24Totald �0.47 (1.03) �0.56 (0.98) �0.70 (1.04) .09

Note. For outcome measures, decreased scores are better. The African American participants totaled 37, distributed by group as follows: communitycomparison group (CC) n � 10, medication management (MedMgt) n � 9, combination treatment (Comb) n � 9, behavioral treatment alone (Beh) n � 9.The number of Latino participants totaled 32 distributed by group as follows: CC n � 8, MedMgt n � 6, Comb n � 10, Beh n � 8. The Caucasianparticipants totaled 21, distributed by group as follows: CC n � 4, MedMgt n � 7, Comb n � 5, Beh n � 5. Time � Treatment � Ethnicity effects wereall nonsignificant, failing to document any ethnicity effect on differential treatment outcome. ADHD � attention-deficit/hyperactivity disorder; ODD �oppositional-defiant disorder.a African American versus Latino effect size d was calculated from means and weighted average standard deviation of the change scores of the two ethnicgroups. Negative effect size indicates more improvement for African American children. b In repeated measures analysis of variance, ethnic effect onchange over time is significant at p � .041 for parent-rated ADHD symptoms. Probability value was increased to nonsignificant level by covarying mother’seducation ( p � .33), public assistance ( p � .051), or single parent ( p � .052) or all three socioeconomic status (SES) variables simultaneously ( p �.29). c Ethnic effect on change over time: p � .076 for parent-rated ODD. d Main effect of ethnicity is significant at p � .001 for teacher-rated ODD(F � 7.48). (For African American versus Latino participants, d � 0.62 at baseline and 0.33 at 14 months, favoring Latino participants. For AfricanAmericans versus Caucasian participants, d � 0.85 at baseline and 0.67 at 14 months, favoring Caucasian participants. For Latino versus Caucasianparticipants, d � 0.23 at baseline and 0.34 at 14 months, favoring Caucasian participants.) This main effect remained significant even after covaryingmother’s education ( p � .01), public assistance ( p � .002), single parent ( p � .009), or all three SES variables simultaneously ( p � .049).


Teacher ratings of improvement in the three MTA treatments, ifused as a common anchor for comparison, agreed closely withCaucasian parents, lagged those of African American parents, andexceeded those of Latino parents. Furthermore, heuristic exami-nation of the Site 3 CC data alone, as the best window intonaturalistic ethnic differences at this site without the MTA inter-ventions, shows dramatically diverging tendencies for parents ofCaucasian children to rate them as less improved than do teachers(d � 0.72 and 1.15) and for parents of African American childrento rate them as more improved than do teachers (d � 0.44 and1.06). These sum to a Caucasian versus African American ethnicswing in informant effect of d � 1.13 for ADHD symptomsand 2.21 for ODD symptoms. CC ratings for Latino childrenshowed a more mixed pattern. Such differences in parental (andpossibly teacher) perceptions may result from cultural differencesin expectations of children or from rater bias, or they could reflectactual differences between home and school behavior for thedifferent ethnic groups, or some combination of factors. Thegeneralizability of the Table 5 comparisons is severely limited bythe fact that they were derived from only one site, the only sitehaving enough of each ethnic group for such comparisons.

Ethnic Effects on Differential Treatment Response

Returning to Tables 2 and 3, we detected two significant Treat-ment � Ethnicity interactions, both of them on parent-rated ODD

symptoms: for African American versus Caucasian for the behav-ioral substitution effect (Beh vs. CC), and for Latino versus Cau-casian for the multimodal superiority effect (Comb vs. MedMgt).Both of these showed a more favorable response of the minoritygroup to behavioral treatment, either as substituted for CC or asadded to MedMgt. African Americans responded more favorablythan did Caucasians to Beh compared with CC, and Latinosresponded more favorably than Caucasians to Comb comparedwith MedMgt. In both cases, the interaction effect attenuated to anonsignificant level when controlled for public assistance, suggest-ing that both are related more to socioeconomic factors rather thanto ethnicity per se.

Ethnic Treatment Acceptance and Attendance/Cooperation

The data on satisfaction with treatment assignment and atten-dance at treatment do not support ethnic differences in acceptanceof, and cooperation with, either medication or behavioral treat-ments. Initial satisfaction with treatment assignment, for which nosignificant difference was found, was remarkably similar for Af-rican Americans and Caucasians, and to some extent for Latinos.Admittedly, this sample is biased by self-selection for those will-ing to be assigned to any of the four treatment conditions, but allof the ethnic groups showed a definite preference for the twotreatments that included behavioral treatment (Beh and Comb),and this preference is not appreciably different by ethnic group.

In regard to treatment attendance, the tendency for poorer at-tendance at behavioral treatments by minority families missedsignificance, and their attendance rate at parent training (67%–70%) was acceptable compared with published attendance ratesfrom other studies. For example, Forehand, Middlebrook, Rogers,and Steffe (1983) reported good results from parent training witha 28% dropout rate in a shorter course. (The MTA nonattendanceat parent training occurred more toward the end, beyond theduration of other published studies). The good attendance byethnic minorities seems remarkable in view of the adversities thatdisadvantaged ethnic parents had to overcome to attend (sitters,transportation, risk of attending evening sessions and returning tounsafe neighborhoods, etc.).

Medication Response and Sensitivity

Although the response rate to MPH showed a slight tendency inthe direction of more nonresponders among African Americans assuspected by Winsberg and Comings (1999), this was not signif-icant and seemed clinically trivial. The actual placebo-controlledAfrican American response rate was over 75% in this carefullymonitored titration, making a trial clinically desirable in well-diagnosed cases. The fact that the optimal dose was no higher thanfor the matched Caucasian participants also suggests a similarMPH response. However, the higher average dose after 14 monthsof open clinical adjustment in the MedMgt condition is puzzling.Although not significant ( p � .09), the clinically nontrivial mag-nitude of difference (50% higher than Caucasian doses) raises thepossibility of a Type II error. Possibly this could reflect greaterdevelopment of tolerance in African Americans over the 13-monthperiod, but it is noteworthy that this increase over time occurredonly for MedMgt alone; the addition of Beh in the Comb strategy

Table 9Disruptive Behavior Disorder (ADHD � ODD) Composite ofParent and Teacher Ratings: Change Scores Baseline to 14Months

Treatmentgroup

Non-Caucasianminorities Caucasian

Cohen’s dan M (SD) n M (SD)

CC 55 �0.53 (0.49) 91 �0.59 (0.48) 0.13MedMgt 53 �0.75 (0.57)b 91 �0.90 (0.58) 0.26Comb 58 �0.95 (0.55)b 87 �0.88 (0.49) �0.14Beh 61 �0.63 (0.53) 83 �0.62 (0.56) �0.02

Total 227 �0.72 (0.56) 352 �0.75 (0.55) 0.05

Note. Larger score decreases indicate more improvement. Superiority ofMTA Med Algorithm (MedMgt & Comb) over the other two treatmentgroups was significant at .001 (d � 0.5) for both ethnic groups; neitherethnic group showed significant superiority of Beh over CC ( p � .3).ADHD � attention-deficit/hyperactivity disorder; ODD � oppositional-defiant disorder; CC � community comparison group; MedMgt � medi-cation management; Comb � combination treatment; Beh � behavioraltreatment alone.a Effect size d is for ethnic difference in treatment effect (Non-Caucasian �Caucasian), calculated as difference in mean improvement divided byweighted average standard deviation. Negative sign indicates more im-provement for non-Caucasian minority children. b For non-Caucasians,superiority of Comb over MedMgt was significant at p � .02 (d � �0.36).(For Caucasians, p � .59, d � 0.04, opposite direction.) Effect size for thiscontrast was calculated from change score means and pooled standarddeviation for Comb and MedMgt. The superiority of Comb over MedMgtfor minority children remains significant after controlling for mother’seducation ( p � .039), public assistance ( p � .018), single-parent status( p � .015), and all three ( p � .031). However, the ethnic difference in thiscontrast missed significance ( p � .10, 2-tailed).

724 ARNOLD ET AL.

apparently held the African American doses to the same level asthe Caucasian doses. Possibly the added behavioral treatment inComb was able to neutralize adverse socioeconomic conditionsthat in MedMgt alone exacerbated symptoms to the point ofeliciting dose increases. This speculation is compatible with thetwo significant clinical outcomes (Tables 2 and 3) in which theethnic-minority children showed differentially better response tobehavioral treatment either alone or in combination with medica-tion, and with the fact that these two findings attenuated to non-significance when controlled for public assistance.

Role of SES in Ethnic Differences

Socioeconomic factors clearly covary with ethnicity. Tables 4and 5 document that mother’s education, public assistance, andsingle-parent status differ significantly between Caucasians andthe two ethnic minorities analyzed here. Insofar as they can influ-ence treatment outcome, they can confound the interpretation ofoutcome ethnic differences. Within the MTA sample, Rieppi et al.(2002) have reported that SES factors significantly moderate bothADHD and ODD symptom outcomes. For example, mother’seducation moderates ADHD symptoms so that children of highereducation mothers show more benefit from Comb than from Med-Mgt, whereas those of lower education mothers show no signifi-cant difference between Comb and MedMgt. This result seemsintuitive in that one would expect better educated mothers to bebetter able to understand and cooperate with the behavioral treat-ment added to the medication in the Comb treatment, hence morefully utilizing the multimodal advantage. In this light, one mightexpect that the lower maternal education in the ethnic minoritieswould tend to mask or attenuate any ethnic difference favoringbetter Beh or Comb response by the ethnic minorities even thoughother SES variables may exaggerate or explain apparent ethnicdifferences. It is therefore not surprising that the two significantethnic differences in differential treatment response, favoringComb over MedMgt for Latinos and Beh over CC for AfricanAmericans, both withstood covariate control for mother’s educa-tion, although covarying public assistance wiped out the signifi-cance (Tables 6 and 7). For Latinos, single-parent status alsowiped out the significance.

It is surprising that the four significant main effects of ethnicity(at outcome in Tables 2 and 3, and regardless of timepoint in Table8) seemed resistant to SES covariate control, remaining significantfor all covariate analyses. However, most of those main effectswere on teacher ratings, for which cultural bias may be onepossible explanation, as was discussed earlier. Of note, Rieppi etal. (2002) reported a tendency for high-education mothers to rateADHD symptoms slightly more severely than did low-educationmothers at both baseline and outcome.

Rieppi et al. (2002) also reported that, as-intended treatmentattendance significantly correlated with higher income, higherparental education, higher occupation, and general higher SES.Those findings suggest that the nonsignificant tendencies forpoorer treatment attendance by the minorities would be easilyexplained by SES factors even if they were significant.

Caucasians and Lack of Multimodal Superiority

One of the more remarkable findings was the serendipitousnoting of complete lack of multimodal superiority effect amongthe 352 Caucasian participants in the sample (Table 9), whichcontrasts with the significant small-to-medium effect for thepooled minorities and for the whole sample on the same measure,the SNAP composite (Swanson et al., 2001). The difference be-tween Caucasians and pooled minorities is not significant ( p �.10, 2-tailed), but if it were, the significance would undoubtedly belargely explained by socioeconomic differences, as seen with thetwo matched pairs significant orthogonal contrasts. In fact, Rieppiet al. (2002) reported that lower SES participants but not higherSES participants benefited significantly more from Comb thanfrom MedMgt on ODD symptoms, which constitute one third ofthe composite measure used for this analysis.

This speculative tertiary analysis, of course, may be somewhatconfounded for non-Caucasians by site effects (see Table 1),despite controlling for site in the regression analysis, but theabsolute lack of multimodal superiority effect in the 352 Caucasianparticipants cannot be explained by site effects; 352 is a respect-able size sample spread over six sites with representation in all ofthe treatment groups at all sites. Therefore, the burden of proofappears to be on anyone who says the results for Caucasianparticipants are not representative of middle-class Caucasians withcombined-type ADHD. However, those results reflect only ADHDand ODD symptoms, not necessarily other important domains offunction, such as achievement, social skills, family relations, andinternalizing symptoms. They also reflect only an average, notnecessarily applicable to every single patient.

Limitations and Precautions

Because the MTA was not powered for such subgroup analyses,there is a great danger of false negative error, which we guardedagainst by eschewing Bonferroni correction for experiment-wiseerror and by focusing on effect sizes. This, of course, increases thechance of false positives. However, we believe that the heightenedchance of false positives is the more acceptable risk for this mainlyheuristic analysis. Little has been explored in the area of ethnicdifferential treatment response, and it is important not to misssomething that could generate hypotheses for later testing.

Although the measures used were carefully selected, the selec-tion was driven partly by the need for parsimony, and the resultsare far from complete, let alone exhaustive of the comprehensiveMTA assessment battery (Hinshaw et al., 1997). One might argue,for example, whether a more direct measure of impairment shouldhave been included, as well as domains such as achievement andsocial skills.

The matched-pairs strategy, although necessary to solve prob-lems of unbalanced site and treatment–assignment distribution,brought its own problems, mainly technical. For example, SASCATMOD could not handle the matched-pairs differences as flex-ibly and completely as ordinary data. The matched pairs also didnot allow using all of the minority participants, with about one fifthof the minority participants lost for lack of a Caucasian match inthe same site, treatment, and sex. This particularly hurt the Latinomatches, leaving only 37 pairs, with as few as a half dozen in one


treatment group. Consequently, we urge extra caution in interpret-ing the Latino findings.

As with all clinical trials results, the generalizability of theresults is limited by sample selection and self-selection, includingthe unlisted inclusion criterion of being willing to be randomizedto treatment. All of the results of such secondary analyses shouldbe applied in light of all other secondary analyses, not out ofcontext, and with awareness that the MTA sample, as large as itwas, was not designed to answer such subgrouping questionsdefinitively.

Clinical Implications

The results described here are exploratory and subject to bothType I and Type II error, and may not be generalizable beyondpatients with characteristics of those participating in the MTA:prepubertal with moderate or severe combined type ADHD. How-ever, taken together with other reported secondary analyses (Hin-shaw et al., 2000; Jensen et al., 2001; March et al., 2000; MTACooperative Group, 1999b; Rieppi et al., 2002; Wells et al., 2000),the patterns of responses and covariates suggest the following forconsideration in treatment planning for ADHD: The placebo-controlled response rate to MPH among African Americans (andLatinos) is substantial and clinically similar to that for Caucasians,justifying individual carefully monitored empirical trials in well-diagnosed cases regardless of ethnicity. Most middle-class Cauca-sians without combined comorbid anxiety and disruptive behaviordisorder (ODD or CD) and especially without significant parent–child problems, may require only carefully managed stimulantmedication and may not gain appreciably from addition of behav-ioral treatment, at least for treatment of ADHD and ODD symp-toms. Conversely, children of low SES, or with comorbid anxietyand disruptive behavior disorder (ODD or CD), especially if ofethnic minority, can benefit from addition of behavioral treatment.Ethnic minority families of low SES can cooperate adequatelywith behavioral treatment to show significant benefit from addingit and in this study did not differ substantially from Caucasianfamilies in their preference for various treatments. Extra care isadvisable in evaluating parent and teacher ratings of improvementfor minority children, for whom informants may not agree as wellas they do for Caucasian children. Individual children, of course,may differ from the MTA averages.

Future Research Directions

The data presented here suggest future research focused onvalidity of parent and teacher perceptions of ADHD and ODDsymptoms as affected by culture and other ethnic and SES con-siderations. This would ideally involve some kind of more objec-tive observation of child behavior to which the parent and teacherperceptions could be compared. Ethnicity of the rating teachersshould be factored into such investigations. Another thrust mightbe investigations of strategies for preventing the escalation ofdosage of medication; how much and what kind of supplementarybehavioral treatment is needed? Perhaps the easiest and quickestresearch could be additional analyses of the MTA data set, usingsuch outcome variables as social skills and achievement.

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Received November 28, 2001Revision received July 2, 2002

Accepted July 14, 2002 �


Effects of ethnicity on treatment attendance, stimulant response/dose, and 14-month outcome in ADHD

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