Response to AHCPR on CERTs:

Julie Magno Zito, National Center for Psychotherapeutic Drug Effectiveness in Children and Adolescents
December 17, 1998

This proposal responds to the call for a center to provide the following required activities:

1. The conduct of state-of-the-art clinical research for the following purposes:
   1. To increase awareness of:
      1. The use of off-label medications for the treatment of youths with psychiatric or behavioral disorders based on information from prevalence studies that the CERT undertakes.
      2. The use of concomitant psychotherapeutic agents that lack scientific evaluation regarding effectiveness and safety.
2. To provide objective clinical information on the above to the following individuals and entities:
   1. Health care practitioners with prescribing privileges.
   2. Non-profit and for-profit health care systems, e.g., staff model HMOs and other managed care organizations.
   3. Public sector health care systems, e.g., state Medicaid systems and public clinics.
   4. Parents of consumers of psychotherapeutic agents and adolescent consumers.
3. To improve the quality of health care and measure the cost of health care through:
   1. Regular systematic monitoring of treatment outcomes.
   2. Defining "appropriateness" based on benefit to risk assessments that incorporate the following types of information: efficacy, safety, effectiveness, cost-effectiveness and therapeutic efficiency.
4. The conduct of research on the comparative effectiveness and safety of psychotherapeutic medications for children and adolescents with specific emphasis on off-label and concomitant drug regimens; undertake a range of studies using creative methods to evaluate effectiveness, for example, N of 1 studies; ABAB designs; comparative trials (study drug or combination versus standard drug) in community-based settings, e.g., Medicaid clinics, county clinics and staff model HMOs.

Supplementary Information

Organization of the Centers

The CERTs should be organized according to topic areas so that the most appropriate specialists in research and clinical practice for a particular topic are engaged in the development of the CERT. This CERT proposes to include a range of specialists in the areas of pharmacoepidemiology, child psychiatric research, practice research networks in psychiatry and pediatrics, biostatistics and research design, health services research and clinical administrators of health service systems. Many of these individuals are working together and share common interests and experience in the evaluation of psychotherapeutic medications for children and adolescents. Infrastructure currently exists among the investigators listed above, e.g., federally funded research sites at academic centers for drug studies, pharmacoepidemiology research and a center for child mental health services research including economic studies. Despite these resources, little attention has been systematically paid to the issue of effectiveness of marketed medications for youth. Additional new players in the proposed center would include several representatives of key government agencies, e.g., National Institute of Mental Health (NIMH) and Food and Drug Administration (FDA), in order to help establish priorities for the Center and avoid duplication of studies fundable by other means.

Additional funding partners

One of the collaborators listed below directs a Research Unit Pediatric Psychopharmacology (RUPP) which can be utilized as part of the infrastructure of the proposed Center. This enables randomized studies to be conducted in the public sector. Given the lack of incentive for pharmaceutical companies to answer research questions related to new uses of marketed medications, the presence of the RUPP makes studies both feasible and independent. Foundation support for these medication evaluations might be more easily achieved for the CERT than has been true in the past.

Initial areas of emphasis and high-priority research topics within the areas of emphasis

As illustrated above (1A-C, 2) the CERT would conduct (1) prevalence studies (2) effectiveness studies and (3) promulgate findings to both professional and consumer groups. High-priority research topics in each area include:

1. Off-label and multiple concomitant medications in children; these are being prescribed at unprecedented rates and with great variation by age, gender, ethnicity, medical specialty, service system and geography. Little is known about the outcomes of therapy according to these variables. The relationship of increased co-morbid psychiatric diagnoses and multiple medications should be further explored.
2. Postmarketing surveillance in a continuously enrolled cohort for 2-5 year periods would produce outcomes for long-term use of medications in developing youngsters. The advent of computerized data from staff model HMOs and Medicaid clinic populations make cohort studies more feasible than previously thought.
3. Utilizing data from several sources of prescribing information, e.g., practice research networks in psychiatry and pediatrics, computerized administrative claims data from Medicaid and managed care settings, large clinic populations, and school data, to adequately map psychotherapeutic practice patterns. Daily dosage, length of treatment and patient satisfaction are priority variables.

In summary, this topic meets most criteria as outlined in the notice on CERTs. The Center emphasizes an understudied population, namely youth, and would provide information on racial and economic disparities, geographic and medical specialty variations that influence the prescription practice patterns in the usual practice setting. Postmarketing surveillance would readily be conducted using a variety of data sources. Effectiveness research would be launched based on the frequency of occurrence of medications for off-label or multiple medications as identified from data-based research. In addition, medication uses of concern or controversy would be the target of studies. The capacity of the CERT to influence prescribing clinicians and consumers will depend on the ability of the CERT investigators to develop academic detailing models for dissemination of their findings relating to appropriateness, cost-effectiveness and benefit to risk assessment. Finally, the CERT would produce information designed to serve the FDA's need for additional product labeling regarding effectiveness of medications in children.

Julie Magno Zito, Ph.D.
Associate Professor of Pharmacy and Medicine
Telephone: 410-706-0524
Fax: 410-706-1736
zito@pharmacy.ab.umd.edu

In collaboration with:

Daniel J. Safer, M.D., Research Child Psychiatrist, Johns Hopkins Medical Institutions
Mark Riddle, M.D., Research Child Psychiatrist, Johns Hopkins Medical Institutions
Philip Leaf, Ph.D., Mental Health Services Research, Johns Hopkins School of Public Health & Hygiene
Leslie Elwood, M.D., Chief of Pediatrics, Kaiser Permanente, Fairfax, Virginia
Sheila Weiss, Ph.D., Epidemiologist, University of Maryland, Baltimore
Michael Fox, D.Sc., Health Services Research, University of Kansas
Deborah Zarin, M.D., Deputy Medical Director, American Psychiatric Association
Kelly Kelleher, M.D., Mental Health Policy and Research, University of Pittsburgh
Andrew S. Rowland, Ph.D., Epidemiologist, National Institute of Environmental Health Sciences
Staff model HMOs, and State Medicaid Research Staffs

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