Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Disruptive Behaviors in Children With Subaverage Intelligence by Michael G. Aman, Ph.D., Goedele De Smedt, M.D., Albert Derivan, M.D., Ben Lyons, Ph.D., Robert L. Findling, M.D., and the Risperidone Disruptive Behavior Study Group American Journal of Psychiatry
Received Aug. 1, 2001; revision received March 20, 2002; accepted April 3, 2002. From the Nisonger Center UAP, Ohio State University; the Janssen Research Foundation, Beerse, Belgium, and Titusville, N.J.; and the Departments of Psychiatry and Pediatrics, Case Western Reserve University, Cleveland. Address reprint requests to Dr. Aman, Nisonger Center UAP, Ohio State University … Supported by the Janssen Research Foundation.
Let me be clear about my question here. Why would Dr. Biederman be reporting on retrospectively analyzed partial data from a five year old Janssen funded study previously published by a group from Ohio? with four of his usual cohorts and a Janssen employee?
The reason it was nagging my mind was recalling this email from some court documents
released into the public domain [Pharmalot
] copied in its entirety:
This was previously mentioned as an example of ghost-writing. Janssen did the analysis and wrote the abstract, sending it to Dr. Biederman to sign on as the author. That’s ghost-writing, period, signing on to a abstract/study you didn’t do. So now, I realize that it was bigger than that – it’s the study they published. Dr. Biederman and his group were the authors of record on a published version of the study in the journal Clinical Therapeutics
. Was it ghost-written too
? There’s something else odd about this article by Biederman et al in 2006. It begins:
Background: Despite the increasing recognition of bipolar disorder in childhood, there have been no controlled, randomized clinical trials of atypical antipsychotics in this population. Preliminary data from openlabel trials in children suggest that these agents might be effective in treating pediatric bipolar disorder, however.
But the original study by Aman et al in 2002 never
mentions the word "bipolar" – ever. Is there any other evidence that the Biederman study might be ghost-written?
How about this? At the bottom of the first page of the Biederman et al article, it says, "Printed in the USA. Reproduction in whole or part is not permitted. Copyright © 2006 Excerpta Medica, Inc.
" Remember Excerptia Medica
? It’s the medical information company around the corner from Janssen headquarters in NJ, the one implicated in ghost-writing any number of Janssen articles by the Rothman Report
] [see my post gpp?…
This study started off being about medicating disruptive, low IQ kids for behavior control with Antipsychotics. It was later revived as treating "bipolar" kids. And it looks like the shots were being called from Janssen corporate offices with Biederman and the Harvard group added on for prestige.
I repeat – detestable!…
Further Thoughts [07/04/2011 AM]: I found the original study on clinicaltrials.gov and trialscentral.org:
Here’s the writeup at the time the study was done:
Primary Outcome Measures: Change in the Conduct Problem subscale of the Nisonger Child Behavior Rating Form [N-CBRF] at end of treatment compared with baseline
Secondary Outcome Measures: Changes in Aberrant Behavior Checklist [ABC], Behavioral Problems Inventory [BPI], and Clinical Global Impression [CGI] at end of treatment compared with baseline; incidence of adverse events throughout study
Study Completion Date: October 1998
Detailed Description: Conduct and psychiatric disorders are found among a higher proportion of people with mental retardation than among people who are not mentally retarded. Among the many different treatment approaches to conduct disorder are drug therapy, behavioral treatment, psychotherapy, and training for cognitive and social skills. Studies have suggested that neuroleptic drugs, such as risperidone, may be beneficial in treating conduct disorder in mental retardation. This is a randomized, double-blind, placebo-controlled study to evaluate the effectiveness of risperidone (0.02 to 0.06 mg/kg/day) compared with placebo in the treatment of children 5 to 12 years of age with mild, moderate, or borderline mental retardation, and who display destructive behaviors. The study has two phases: a run-in phase of 1 week and a treatment phase of 6 weeks. Patients receive placebo to be taken orally once a day during the first week (run-in). On the basis of scores on the Nisonger Child Behavior Rating Form (N-CBRF) and the Vineland Adaptive Behavior Scale after the first week, patients either continue in the double-blind treatment phase or discontinue the study. During the treatment phase patients receive an oral solution of risperidone (increasing gradually to a maximum dose of 0.06 mg/kg) or placebo to be taken once daily for 6 weeks. A parent or caregiver evaluates the child’s behavior and symptoms at scheduled office visits during the course of treatment. The primary measure of effectiveness is the change in the Conduct Problem subscale of the Nisonger Child Behavior Rating Form (N-CBRF) at end of treatment compared with baseline. Additional assessments of effectiveness include: the Aberrant Behavior Checklist (ABC), the Behavioral Problems Inventory (BPI), and the Clinical Global Impression (CGI). Safety assessments include the incidence of adverse events throughout the study; weekly measurement of vital signs (pulse, temperature, blood pressure) and evaluation of the presence and severity of extrapyramidal symptoms by the Extrapyramidal Symptom Rating Scale (ESRS); and clinical laboratory tests performed both before study initiation and at the end of treatment. The study hypothesis is that risperidone is well tolerated and effective for the treatment of conduct disorder in children aged 5 to 12 years with mild, moderate, or borderline mental retardation. Risperidone oral solution 1 mg/mL or placebo oral solution, once daily on Days 1 and 2 at dose of 0.01 mg/kg body weight. Dose is 0.02 mg/kg on Day 3, increasing gradually to 0.06 mg/kg (maximum) once daily through 6 weeks. Dosage may be increased or decreased at investigator’s discretion.
There’s something wrong with the write-up on clinicaltrials.gov. The study says it was completed in 1998. Under Publications, the Aman et al 2002 paper was listed. Yet the History starts in December 2005, close to the time the Biederman paper was submitted. It’s just strange, that’s all. The write-up doesn’t give the locations of the study sites [nor does either paper], but reading the history, I’m guessing the study was run from Belgium through the Risperidone Disruptive Behavior Study Group
[whose members varied across the globe from paper to paper].
Here’s the best I can do with that. In the early days, they planned to market Risperdal as a safe way to medicate retarded, autistic, etc. kids for behavior control. There were even guidelines etc. developed [Google Dr. Aman for details]. That indication apparently didn’t fly, so they shifted gears and tried to call the disruptive behavior comorbid bipolar disorder, and revived their old data with a new set of authors, the bipolar child gurus at Harvard. That’s perhaps the reason there are so many bipolar comorbidities – ADHD, DBD, CD, Autism, etc. This is just a hunch based on all the odd comorbidity papers in the bipolar literature and the retooling of old data [in 1998 when the study was done, there was no "bipolar child"].
Like I said – detestable!…