PSYCHIATRIC SERVICES o ps.psychiatryonline.org o February 2010 Vol. 61 No. 2
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WWe ei ig gh hi in ng g S Sc ci ie en nt ti if fi ic c E Ev vi id de en nc ce e: : L Le et t’ ’s s K Ke ee ep p t th he e B Bl li in nd df fo ol ld d O Of ff f
Lady Justice—or Justitia, the Roman goddess of justice—holds a double-edged
sword in her right hand and a scale in her left, and sometimes she is blindfold-
ed. The blindfold symbolizes the ideal of weighing evidence with impartiality.
However, in the case of scientific evidence, scrutiny and deliberation are re-
quired to find the balance point in measuring the strength of evidence and its
applicability to a clinical decision.
The findings of a study reported in this issue, “Evidence-Based Use of Second-
Generation Antipsychotics in a State Medicaid Pediatric Population, 2001–2005,”
require careful scrutiny because they could be misinterpreted as indicating over-
use or inappropriate use of these agents to treat children. Conclusions about the
appropriateness of medication treatment that are based on claims data are limit-
ed because the validity of the diagnosis cannot be established from such data and
the clinical rationale for prescribing a particular drug is missing. The authors of the
report acknowledge that they were unable to link the diagnoses recorded in the
Medicaid claims to the index prescription of the antipsychotic.
Nevertheless, on the basis of the design and sample size of published studies and
diagnoses from claims data, these investigators rated the strength of evidence for
each initial prescription of a second-generation antipsychotic for 11,700 children
between 2001 and 2005. During this period none of these agents were approved
for pediatric use by the Food and Drug Administration (FDA), and the majority of
published reports that included children were open-label studies involving risperi-
done. One medication, aripiprazole, was approved for adult use in November 2002.
Was the study premature to apply ratings of evidence strength? Or by applying the
ratings at a time when the evidence base was not strong, did the study simply re-
flect the fact that prescribers were exercising their clinical judgment in making
medication decisions for high-risk children?
Either way, the study illuminates the larger debate about what constitutes sub-
stantial evidence of the safety and effectiveness of psychotropic medications pre-
scribed to children. In 1962 the proposed FDA criterion for “substantial evidence”
of effectiveness was “at least two adequate and well-controlled studies, each con-
vincing on its own, to establish effectiveness.” With the FDA Modernization Act of
1997, the criterion was relaxed to “one adequate and well-controlled clinical inves-
tigation and confirmatory evidence,” and rules were revised to allow for extrapola-
tion from adult efficacy data to pediatric patients. National efforts have also been
made to standardize approaches to rating scientific evidence. These approaches ac-
knowledge a subjective component in the assessment of research methods to
“weigh” scientific evidence. Given the need for more long-term studies to establish
the safety and efficacy of antipsychotics for children in real-world settings, let’s keep
Lady Justice’s blindfold off during our deliberations.—BONNIE T. ZIMA, M.D.,
M.P.H., UCLA–Semel Institute for Neuroscience and Human Behavior
Psychiatric Services, established in 1950, is published monthly by the American Psychiatric Associ-
ation for mental health professionals and others concerned with treatment and services for persons
with mental illnesses and mental disabilities, in keeping with APA’s objectives to improve care and
treatment, to promote research and professional education in psychiatric and related fields, and to
advance the standards of all psychiatric services and facilities.
E Ed di it to or r
E Ed di it to or ri ia al l B Bo oa ar rd d
E Ed di it to or r E Em me er ri it tu us s
B Bo oo ok k R Re ev vi ie ew w E Ed di it to or r
Jeffrey L. Geller,M.D.,M.P.H.
S St ta at ti is st ti ic ca al l C Co on ns su ul lt ta an nt t
C Co on nt tr ri ib bu ut ti in ng g E Ed di it to or rs s
Paul S. Appelbaum,M.D., Law &
Francine Cournos,M.D.,and Stephen
Lisa B.Dixon,M.D.,M.P.H.,and Brian
Jeffrey L.Geller,M.D., M.P.H., Personal
William M.Glazer, M.D., Best Practices
Amy M.Kilbourne,Ph.D.,M.P.H., and
Tami L.Mark,Ph.D., Datapoints
Matt Muijen,M.D.,Ph.D., Mental
Health Care Reforms in Europe
Fred C.Osher,M.D., State Mental
Jules M.Ranz,M.D.,and Susan M.
Deakins,M.D.,Case Studies in
Steven S.Sharfstein,M.D.,Haiden A.
Huskamp,Ph.D., and Alison Evans
Cuellar,Ph.D., Economic Grand
E Ed di it to or ri ia al l C Co on ns su ul lt ta an nt ts s
José Miguel Caldas de Almeida,M.D.
Marcia Kraft Goin,M.D.,Ph.D.
M.Susan Ridgely, J.D.
Laura Van Tosh
E Ed di it to or ri ia al l S St ta af ff f
Constance Grant Gartner, Managing
Christine Hamel, Associate Editor
Demarie S.Jackson, Associate Editor
Wendy Lieberman Taylor, Production
Kourtney R.Skinner, Editorial Support
A Am me er ri ic ca an n P Ps sy yc ch hi ia at tr ri ic c A As ss so oc ci ia at ti io on n
David Fassler,M.D., Secretary-
Gary S.Weinstein,M.D.,Speaker, APA
James H.Scully,M.D., Medical Director