1. Lectura crítica de un artículo
Lina María Ruiz
Paula Andrea Duque
Residentes Psiquiatría infantil
2.
3. 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
4. Se realizó la asignación de los pacientes a los
tratamientos de manera aleatoria?
- SI
Patients were randomized in a 1:1 ratio to receive
either placebo or atomoxetine. Both atomoxetine and
placebo were titrated in 3 weeks to a fixed once-daily
dose 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 capsules
and were identical in appearance. Atomoxetine
capsules contained 5, 10, 20, 25, or 40 mg. To preserve
the blinding, all doses were given in two capsules,
which had to be taken together in the morning.
5. ¿Se tuvieron en cuenta adecuadamente todos los
pacientes incluidos en el ensayo y se los consideró
a la conclusión del mismo? SI
6. ¿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.
7. ¿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.
8. ¿Se analizaron los pacientes en los grupos a los
cuales fueron asignadosde manera aleatoria
(intención de tratar) Si
9. • Se mantuvo enmascarada la aplicación del
tratamiento hacia los pacientes del
ensayo, los clínicos y el personal del
estudio? SI
Independent pharmacists dispensed either placebo
or atomoxetine capsules according to a computer
generated randomization list. All study personnel and
participants were blinded to treatment assignment for
the duration of the study. The code was not revealed to
the researchers until data collection for the study had
been fully completed. The study statisticians were also
blinded until completion of the analyses. Thus, maximum
allocation concealment has been achieved.
10. ¿Eran similares los grupos, en sus características de base,
al iniciar el ensayo? Si
11. ¿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 children
and adolescents between 6 and 17 years with a clinical
diagnosis of ASD and concomitant ADHD symptoms,
who had been referred to one of nine participating
- For inclusion in the study, children had to have a
confirmed diagnosis of ASD and to have concomitant
ADHD symptoms according to our study criteria, plus
an intelligence quotient (IQ) of at least 60 on a Wechsler
Intelligence Scale
12. - ASD diagnoses were confirmed through clinical assessment by
certified child and adolescent psychiatrists
- Atomoxetine and placebo were available as capsules
and were identical in appearance. To preserve the blinding, all doses
were given in two capsules, which had to be taken together in the
morning
13. ¿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
14. Según la magnitud de la RRR, es eficaz el
tratamiento?
No se midió la reduccion del riesgo relativo
15. 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
16.
17. El tamaño de muestra utilizado, fue
calculado ? y su número fue: n=89
The initial assumption was that the improvement on
the ADHD-RS would be approximately 7.0 points
in the atomoxetine group and approximately 1.2 points
in the placebo group, based on prior atomoxetine
studies for children with ASD.16,17 With a presumed
SD of nine points, 43 patients were needed in each
group (n 86) to achieve a power of 80%, using a
two-sided significance level of 5%. Taking into account
a drop-out rate of 15%, a total sample size of 100
patients was determined.
18. 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
19. ¿Los beneficios que se obtienen de la intervención, compensan los
riesgos, costos o efectos secundarios de la intervención? Si
20. Comentarios adicionales, generales o
particulares, del estudio. Califíquelo en cuanto a
validez y resultados de 1 a 5.
(3) Regular
Pero aplicable a la poblacion de raza blanca, género
masculino y con IQ mayor de 60
21. This study was funded by Eli Lilly and Co.
This work was presented in part at the International Conference
sponsored 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
22. 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
23. No especifican que otros tratamientos habian recibido
previamente
No especifican otras intervenciones
No son aplicables a nuestra poblacion
