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Lina María Ruiz

Paula Andrea Duque

Residentes Psiquiatría infantil

Tipo de estudio:Randomizado, doble ciego, comparado con placebo

Clinical trial registration information—A Randomized Double-Blind Study of

Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD

Se realizó la asignación de los pacientes a los tratamientos de manera aleatoria?

- SIPatients were randomized in a 1:1 ratio to receiveeither placebo or atomoxetine. Both atomoxetine andplacebo were titrated in 3 weeks to a fixed once-dailydose of 1.2 mg/kg/day (first week: 0.5 mg/kg/day;second week: 0.8 mg/kg/day; third week: 1.2 mg/kg/day). Atomoxetine and placebo were available as capsulesand were identical in appearance. Atomoxetinecapsules contained 5, 10, 20, 25, or 40 mg. To preservethe blinding, all doses were given in two capsules,which had to be taken together in the morning.

¿Se tuvieron en cuenta adecuadamente todos los pacientes incluidos en el ensayo y se los consideró a la conclusión del mismo? SI

¿Se consideraron todos los pacientes en la conclusión del ensayo? SI

Following the intent-to-treat principle, the analyses were based on all patients who were randomly assigned, including the three patients who did not meet full inclusion criteria.

¿Se realizó un seguimiento completo? - Si We obtained ADHD-RS ratings, CGI, Conners, CTRS-

R:S at baseline, after 5 weeks and after 8 weeks of treatment.

Safety was assessed by the same clinician who did the clinical ratings through open-ended questioning for adverse events by telephone after 1 and 2 weeks of treatment, and in person after 5 and 8 weeks of treatment.

¿Se analizaron los pacientes en los grupos a los cuales fueron asignadosde manera aleatoria (intención de tratar) Si

• Se mantuvo enmascarada la aplicación del tratamiento hacia los pacientes del ensayo, los clínicos y el personal del estudio? SI

Independent pharmacists dispensed either placeboor atomoxetine capsules according to a computergenerated randomization list. All study personnel and

participants were blinded to treatment assignment forthe duration of the study. The code was not revealed tothe researchers until data collection for the study hadbeen fully completed. The study statisticians were alsoblinded until completion of the analyses. Thus, maximumallocation concealment has been achieved.

¿Eran similares los grupos, en sus características de base, al iniciar el ensayo? Si

¿Aparte de la intervención experimental bajo estudio, se trataron los grupos de la misma forma en otras co-intervenciones? Si

- Candidates for inclusion in the study were childrenand adolescents between 6 and 17 years with a clinicaldiagnosis of ASD and concomitant ADHD symptoms,who had been referred to one of nine participating - For inclusion in the study, children had to have aconfirmed diagnosis of ASD and to have concomitantADHD symptoms according to our study criteria, plusan intelligence quotient (IQ) of at least 60 on a WechslerIntelligence Scale

- ASD diagnoses were confirmed through clinical assessment by certified child and adolescent psychiatrists

- Atomoxetine and placebo were available as capsulesand were identical in appearance. To preserve the blinding, all doses

were given in two capsules, which had to be taken together in the morning

¿Cómo se evalúan estadísticamente los resultados del tratamiento? Changes from baseline of the primary efficacy measure were

compared between groups using mixed models for repeated measure (MMRM) and treatment comparisons for secondary efficacy were analyzed using analysis of covariance (ANCOVA) imputing missing values based on last observation carried forward (LOCF)

The CGI-ADHD-I was analyzed using Fisher’s exact test

Según la magnitud de la RRR, es eficaz el tratamiento? No se midió la reduccion del riesgo relativo

La estimación del efecto es precisa (Intervalo de Confianza)? Si

El intervalo de confianza utilizado fue? >90% El grado de significancia estadística fue P<0.05

El tamaño de muestra utilizado, fue calculado ? y su número fue: n=89

The initial assumption was that the improvement onthe ADHD-RS would be approximately 7.0 pointsin the atomoxetine group and approximately 1.2 pointsin the placebo group, based on prior atomoxetinestudies for children with ASD.16,17 With a presumedSD of nine points, 43 patients were needed in eachgroup (n 86) to achieve a power of 80%, using atwo-sided significance level of 5%. Taking into accounta drop-out rate of 15%, a total sample size of 100patients was determined.

Aplicación de los Resultados • ¿Pueden aplicarse los resultados del estudio a la

asistencia de mis pacientes? no, pues la muestra presenta varias limitaciones, como tener pocos adolescentes, solo raza blanca, mayoría de género masculino y la necesidad de tener un IQ mayor de 70

• ¿ Se consideraron los resultados clínicamente importantes? SI

• ¿Cuáles resultados faltaron? sería interesante comparar la atomoxetina con el Gold standard que es el metilfenidato

¿Los beneficios que se obtienen de la intervención, compensan los

riesgos, costos o efectos secundarios de la intervención? Si

Comentarios adicionales, generales o particulares, del estudio. Califíquelo en cuanto a validez y resultados de 1 a 5.

(3) RegularPero aplicable a la poblacion de raza blanca, género

masculino y con IQ mayor de 60

This study was funded by Eli Lilly and Co.This work was presented in part at the International Conferencesponsored by the European Society for Child and Adolescent

Psychiatry(ESCAP) in Budapest, Hungary, August 25, 2009.We thank all participating sites in the Netherlands and Eli Lilly

and Co.personnel, especially Simone Knijff and Nicole Dieteren

Conclusiones No especifican NNT, NI RR Limitan la muestra a raza blanca y no agregan hispanos,

por lo cual no es aplicable a nuestra población La muestra es predominantemente en género masculino,

lo que limita su reproducibilidad Habiendo un gold standard como el metilfenidato, se

debio comparar con este

No especifican que otros tratamientos habian recibido previamente

No especifican otras intervenciones No son aplicables a nuestra poblacion