Friday, May 20, 2005

CAPTN: Practical Clinical Trials in Psychiatry
By Brandon Hines

In the field of psychiatry, there has been insufficient clinical evidence to find the best treatments for mentally ill patients. High costs, lack of funding, and methodological burdens have, in part, contributed to this unreliability of clinical research. In an effort to successfully apply clinical research to medical practice, practical clinical trials have been put to use.

John March, MD

The authors state that the primary goal of practical clinical trials is "asking a question that, when answered, will inform decision makers who are making decisions about the care of patients."

A practical clinical trial is a study design that compares clinical outcomes resulting from different treatment options. It differs from other clinical trials in that it includes a random and diverse population of study participants to avoid bias, a range of practice settings that simulate real clinical practice, clinically relevant health outcomes. These trials also tend to minimize the burden on patients and researchers by having simple and straightforward tests that do not incorporate a lot of data.

Practical clinical trials are well-suited for broad applications to medical practice by providing a wide range of outcomes relevant to public health. Even so, they can also identify small, specific effects due to the patient diversity and large sample size. For example, practical clinical trials are ideal for answering the question, "Which treatment for which patient with what subgrouping characteristics?" Subgrouping variables, such as race, gender, and age, can be investigated individually or in combination with each other.

An additional advantage to practical clinical trials is that they address the balance between benefit and harm in treatment options. The large sample size enables a more precise prediction of what the poor outcomes for a particular treatment might be for real patients. Therefore, the risk associated with treatments can be closely evaluated in clinical practice; thus, the safety of treatment is enhanced.

Various scientific fields use practical clinical trials. Due to network development and funding, practical clinical trials are now popular in cardiology and in pediatrics. Until just recently, practical clinical trials have been used in psychiatry thanks to funding by the National Institute of Mental Health (NIMH).

"A partnership between researchers at Duke University and the American Academy of Child and Adolescent Psychiatry, the NIMH-funded Child and Adolescent Psychiatry Trials Network (CAPTN) is an investigator-initiated proof-of-concept effort to establish a practical clinical trial network in pediatric psychiatry." CAPTN aims to improve research and evidence validity of child and adolescent psychiatry by using "randomized trials of the effectiveness of widely used but understudied combined drug treatments."

The authors, however, point out that not enough consistently funded networking exists today for practical clinical trials in psychiatry. Therefore, a coordinating network is needed that has access to researchers and others capable of conducting practical clinical trials. An important aspect to network coordination is the development of systems for data management and analysis. This includes a quality assurance procedure which documents both the methodology and the compliance of patients to conduct the study.

In addition, in the field of psychiatry, practical clinical trials still do not provide an evidence base of clinical practice. For example, when treating children, there is no single-drug standard; rather, there is a complex multi-drug treatment, and the correct combination of these drugs is different for each child. No scientific evidence suggests which combination is appropriate for what child. Nonetheless, what is lacking from this fault in research provides a direction to further revise a practical clinical trial's design.

Practical clinical trials in psychiatry have been criticized for having "soft" behavioral outcomes, such as depression; whereas, cancer and cardiovascular clinical trials have "hard" unmistakable outcomes, like death. The "hard" outcomes are easier to analyze. However, the authors defend this notion by saying that it is possible to overestimate the "hardness" of the results, such as the cause for heart attack or suicide, and to underestimate the "softer" results, such as the quality of life. Therefore, the "soft" endpoints may, in fact, reveal a lot to the researcher.

New methodology, research design, data entry, and statistical analysis techniques have to be made, since practical clinical trials are new to psychiatry. According to the authors, these types of trials will lead to a collaboration of scientists "from diverse academic backgrounds, including epidemiology, statistics, behavioral and social science, engineering, computer science, and public policy."

Practical clinical trials in psychiatry depend on public and private funding. To maintain or gain additional funding, the clinical and health policy decision makers have to make these trials a priority. "Until recently no well-established funding mechanism for network studies has existed in the NIMH portfolio." The authors emphasize the urgent need to support, via NIH/NIMH resources, networks of independent, skilled clinicians and researchers who are interested in sponsoring and performing practical clinical trials "especially when the potential profits are low but the scientific interest is high."

Members of the DCRI research team for this study were Susan G. Silva, Ph.D., Mark Shapiro, M.A., and Robert Califf, M.D., as well as Scott Compton, Ph.D. and Ranga Krishnan, M.D. with the Duke Department of Psychiatry and Behavioral Sciences.

This report was supported by NIMH grants 1 K24 MH-01557 and 1 P30 MH-66386 and by NIMH contract 98-DS-0008 to Dr. March.