1 Boring Old Man

Methodological Issues and Controversies in Clinical Trials with Child and Adolescent Patients with Bipolar Disorder:
Report of a Consensus Conference
^{[authors listed below]}
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY 2003 13(1):13-17.

Abstract
^{Objective: To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents.
Method: The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities [including adult psychiatrists with expertise in bipolar disorder] and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing:
[1] inclusion/exclusion criteria,
[2] investigator training needs and site selection,
[3] assessment and outcome measures,
[4] protocol design and ethical issues unique to trials involving children/adolescents, and
[5] regulatory agency perspectives on these deliberations.
Results: Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10–17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic “gatekeepers” screen youths’ eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/ rage and cognitive function, while using the best available instruments [e.g., Young Mania Rating Scale] in the interim.
Conclusions: Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.}

^{Several trends recently have converged to add urgency to the need to address unresolved issues surrounding the conduct of psychopharmacologic treatment studies in child/adolescent bipolar disorder. These trends include the increasing frequency with which bipolar disorder is being diagnosed in children and adolescents, an increase in off-label prescribing of antipsychotic and anticonvulsant medications to treat children/adolescents presumed to have the disorder, and mounting pressure on the pharmaceutical industry to include in clinical trials the specific populations for whom medications will be prescribed. However, considerable controversy persists surrounding core issues that are central to successful clinical trials of bipolar disorder in younger populations, including, for example, the definition of the illness in this age group and measures to assess it [Biederman et al., 1998; Carlson, 1998, 1999]. In the absence of consensus among researchers, industry sponsors, federal regulators, and families on both the feasibility of and ground rules for conducting high-quality clinical trials for this population, children and adolescents will likely be deprived of the opportunity to receive efficacious and effective treatments for bipolar disorder, and the field will remain at a standstill…}

But the second part of the paragraph bears reflection: "In the absence of consensus … children and adolescents will likely be deprived of the opportunity to receive efficacious and effective treatments for bipolar disorder." So is the "urgency" a question of the accuracy of diagnosis? Or is the "urgency" to get these treatments prescribed to the afflicted and to get the blocks to doing clinical trials out of the  way?

Here are the attendees to the conference:

Going down the list of academics, see if you can find someone who hasn’t reported a conflict of interest on a bipolar study. I couldn’t. Try to find a non-Pharma funded support group on the list. I couldn’t. In fact, if there’s anyone at the conference [not counting the Government] who is not in some way invested in this "new child bipolar" diagnoses and the pharmaceutical industry’s agendas for treatment, I don’t know who it might be. The presence of the FDA and NIMH just served to legitimize the consensus. In this 2003 conference, it was "urgent." With the 2005 Guidelines [not much solid ground…], it was "desparate." The two sides of this story? An action group to initiate needed treatment in an under-served population of bipolar children and adolescents OR a PHARMA-financed mob racing into a fresh market before the drug patents ran out.

We’re all human and know that from the inside that it’s never so simple as the dichotomy presented in the last paragraph. I’m sure the people at the conference worked to come up with a consensus on how to proceed and they wrote lofty things about how to help the hypothesized sea of bipolar children while protecting them from harm. I expect they meant what they said in their workgroups – even the PHARMA types. They just didn’t think about the fact that they were being paid by the pharmaceutical companies that make the drugs, or that their [lucrative] pharm-scripted speeches were telling primary care physicians that giving antipsychotics to disruptive kids was okay, in fact, desirable, because they are really bipolar. They didn’t notice that they were making up a completely new disease, giving it a time-honored name, and treating it with medication that had no scientific rationale, a medication that is anything but benign. It didn’t occur to them that everyone at the conference was being paid by PHARMA for something or another. And they didn’t think about the fact that there were no dissenting voices among the attendees. After all, it was an honor to be at a conference assembled by the American Academy of Child and Adolescent Psychiatry. They were experts sharing expertise and it was a brave new world of neuroscience, moving ahead with recent advances in the neurobiology of this-that-and-the-other.