JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGYVolume 17, Number 3, 2007© Mary Ann Liebert, Inc.Pp. 275–277DOI: 10.1089/cap.2007.17301

Editorial

The Pharmaceutical Industry, Academic Medicine and the FDA

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WE ARE DELIGHTED to devote a special sec-tion of this issue to a timely, controver-

sial topic. For the past several years, the mediahave frequently reminded us of concerns re-lated to the psychopharmacological treatmentof children and adolescents. The concerns andissues include: The safety of serotonin-selectivereuptake inhibitors (SSRIs), the increasing useof psychotropics in youth, off-label practice,class action suits, conflicts of interest in acade-mia and in the Food and Drug Administration(FDA), the influence of television advertisingof new drug treatments, and incomplete safetyinformation communicated to the public bypharmaceutical companies. To address the re-lationships of the pharmaceutical industry, aca-demic researchers, practicing child and adoles-cent psychiatrists, and the FDA, we invited anumber of experts to address the question fromtheir perspective. Below, we cite a few of thehighlights to whet your appetite for the fullcourse.

In a historical review, Dr. Leon Eisenbergtells us of the profound growth of the diagno-sis of attention-deficit/hyperactivity disorder(ADHD) and treatments for this condition. Heindicates that the growth of the community-based diagnosis of ADHD and treatment withstimulants far exceeds validation from epi-demiologic research (Angold et al. 2000). Hecalls for more epidemiologic research to ascer-tain whether the recent survey estimate of 8%of U.S. children aged 4–17 years clearly war-rants the diagnosis of ADHD and to what ex-tent medications for this disorder maintaintheir benefit. It is time, Dr. Eisenberg suggestsfor the National Institute of Mental Health(NIMH) and the FDA to convene senior inves-

tigators, clinicians, and epidemiologists to planlarge-scale systematic research on matters ofserious consequence for child health in Amer-ica. Perhaps, the time is right for a “Framing-ham” cohort study for child and adolescentmental health. Much has been learned fromother mental health cohort studies, e.g., GreatSmoky Mountains study (Costello et al. 1996)and the now-classic Isle of Wight study (Rut-ter et al. 1970). Given the growing access toelectronic medical records and school records,there is much to be learned about who istreated, for how long, and with what social aswell as medical benefit. Such information maynot be as difficult or costly to collect as wasonce the case.

Dr. Donald Klein, another emeritus distin-guished investigator, gives a first-hand accountof his early relationship with industry-fundedpsychopharmacologic trials. He recounts thediminished role of federal money in such trialsas the years have progressed and wonders ifsuch decisions were in the best interest of pa-tient care. Industry–academic relations havechanged a great deal and leave the professionopen to criticism by those who are not engagedin these relationships. He is particularly con-cerned about the inadequacy of the currentpostmarketing surveillance system (Klein 2006)to address safety questions for marketed med-ications given the weak incentives for industryto conduct such studies. Despite 6-month ex-clusivity incentives and mandates for furtherstudy of pediatric off-label indications from theBest Pharmaceuticals for Children ResearchAct, the industry response and meager publicfunding are unlikely to overcome present re-search limitations.

Dr. A.J. Allen brings his experience in childpsychiatry and the pharmaceutical industry tothis discussion of the relationship betweenacademe, the industry, and the FDA. Dr. Allenmakes a case for improving the existing post-marketing surveillance system. Among theshortcomings he raises are: The inadequate sta-tistical power of clinical trials to assess rare ad-verse events, variations in reporting methodsacross companies, low reporting rates, and re-porting bias due to the length of time since mar-keting (Weber Effect). Large administrativedatabases are suggested as an addition to pre-marketing information sources but are limitedregarding the type of safety question that canbe addressed. For example, how likely is it thatreliable information on the association of at-tempted or completed suicides with actual ex-posure to an SSRI will be obtained from ad-ministrative claims data? Perhaps, augmentingprevalence of use from claims data with aprospective survey to verify drug exposure andoutcome could take us further along the post-marketing surveillance path.

Dr. Chris Varley, a University of Washingtonprofessor in charge of residency training, dis-cusses the most prominent psychopharmacologycontroversy facing us today: The efficacy andsafety of SSRIs for the treatment of pediatric de-pression. After reviewing the highlights of pol-icy decisions leading to European contraindica-tions for all but fluoxetine and FDA decisions toadd Black Box Warnings, he applauds the re-quirement to register trials with http://www.clinicaltrials.gov, but admonishes us that as yet,posting results is not required. Dr. Varley iden-tifies inadequate National Institutes of Health(NIH) funding for studies modeled after theTreatment of Adolescents with Depression(TADS) study (March et al. 2004) as a major bar-rier in sorting out the complex dimensions ofdrug safety and efficacy for the SSRIs, which heviews as still unresolved.

Dr. Mary Burke presents a clinician’s view-point and offers her experience with two diffi-cult cases she treated in a community mentalhealth setting. The need for family support (ed-ucation and intervention) as well as eachchild’s severe problems were apparent. Dis-trust and confusion resulting from publicationbias, imbalanced funding, and limited assess-ment of research on the various biopsychoso-

cial approaches to mental health theory frominvestigators, e.g., Rutter, McClellan, andHammen, as opposed to the vast industry sup-port for psychopharmacologic studies leavesthis child psychiatry practitioner dissatisfiedwith the information sources she was trainedto use.

The special section concludes with a secondacademic commentary, this one from the eastcoast. Dr. Mark Riddle leads the Child Psychi-atry Division at Johns Hopkins, one of the in-stitutions most identified with the develop-ment of child psychiatry. Hopkins was hometo Dr. Leo Kanner, the physician who authoredthe first textbook of child psychiatry in 1935.Dr. Riddle’s commentary identifies a numberof current barriers to ideal relationships amongthe industry, academe, practice, and the FDA.Barriers he cites include: (1) The media; (2) pub-lic distrust due to biased media reporting, di-rect-to-consumer advertising, and problematicsafety reporting by the industry, e.g., the de-lays related to publication of Vioxx risk; (3) so-cial stigma due to negative, emotion-laden re-actions to the use of medication in the pediatricpopulation; and (4) an inadequately trainedworkforce to assess, diagnose, and treat young-sters and their families. Dr. Riddle’s proposalsto reduce these barriers include revised extra-mural conflict of interest criteria for academicresearchers and thought leaders similar tothose NIH developed for intramural scientists.Complete transparency in academic-industryrelations is a goal, he suggests, that will reducethe negative perceptions common in the media.

Readers, your comments and letters are wel-come! The idea for this special section grewout of a discussion at the Journal of Child andAdolescent Psychopharmacology annual boardmeeting in July, 2006. Several members ex-pressed the need for a national dialogue onchild and adolescent mental health treatmentissues. Where shall we go from here? A na-tional conference to advocate for changes inthe current inadequate payment system; formore complete medical insurance coverage ofyouth; the current very limited post-market-ing surveillance system; new approaches to in-crease the level of evidence on off-label med-ication treatment in children? Is it time for amore visible role for the American Academyof Child and Adolescent Psychiatry (as sug-

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gested by Dr. Tom Anders, President of AA-CAP) to address the imbalances identified bymany of the commentators in this issue?Would independently funded postmarketingdrug safety and effectiveness studies be a goodstart? Other ideas?

REFERENCES

Costello J, Angold A, Burns BJ, Stangl DK, Tweed DL,Erkanli A, Worthman CM: The Great Smoky Moun-tains Study of youth. Functional impairment and seri-

ous emotional disturbance. Arch Gen Psychiatry53:1129–1136, 1996.

Klein DF: The flawed basis for FDA post-marketing safetydecisions: The example of antidepressants and chil-dren. Neuropsychopharmacology 31:689–699, 2006.

March J, Silva S, Petrycki S, Curry J, Wells K, Fair-banks J, Burns B, Domino M, McNulty S, Vitiello B,Severe J, for the Treatment for Adolescents with De-pression Study (TADS) Team. JAMA 292:807–820,2004.

Rutter M, Tizard J, Whitmore K: Education, Health andBehaviour. New York, Wiley and Sons, 1970.

Julie Magno Zito, Ph.D.Harold S. Koplewicz, M.D.

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