Year 2 and Beyond

In Year 2, we will capitalize on the groundwork laid in Year 1 to continue our work around the program's themes.

Developing Knowledge

We will improve knowledge by completing the demonstration projects at individual research centers and developing synergy among centers.

Children and Adolescents

We will continue our effort to understand the relation between rickets and breast-feeding, by monitoring how many breast-feeding women are getting vitamin D, tracking new cases of rickets, and repeating our survey of doctors' recommendations about vitamin use to their patients.

Another project will assess the usefulness of a large health-maintenance organization (HMO) database for studying the safety of and reasons for antibiotic use in children. This will allow us to identify targets to improve prescribing, to ensure that children receive antibiotics when needed but avoid the unnecessary prescribing that gives rise to antibiotic resistance.

Adults

Although the 87 percent rate of aspirin use in people with heart disease is encouraging, we intend to survey the remaining men and women to find out why they were not taking aspirin. Depending upon the results, we will design an intervention to increase the use of aspirin or similar drugs whenever possible.

A similar survey in the beta-blocker project is identifying the specific drugs and doses being used, if any, or the reasons for not taking these drugs. We will determine physician awareness, understanding, agreement, and adoption of the beta-blocker recommendations. We also will try to identify barriers to the use of beta-blockers in medical practice, and develop an intervention to improve the rate of use.

We will continue our work to identify drugs that prolong the QT interval and cause torsades de pointes, and to identify related risk factors for this complication.

For the dofetilide project, we will examine nationwide prescribing patterns for all antiarrhythmic drugs, including dofetilide. We hope to identify trends in use by practitioner characteristics. We also will evaluate compliance with the FDA-required risk-management program for dofetilide use.

We will survey caregivers and administrators to assess their perceptions, understanding, and acceptance of the risk-management program. We will obtain a time-cost estimate to implement this program. We also will evaluate inpatient-prescribing patterns of all antiarrhythmic drugs at one hospital.

The last component of the dofetilide project will be a nationwide survey of physicians and nurses, to assess their understanding about the risks of using drugs, including dofetilide, that prolong the QT interval on the electrocardiogram. With all of this information, we hope to develop a nationwide continuing medical education program to improve understanding and minimize the risk with the use of these agents. A manuscript also is planned on the differences in the approval and marketing of two antiarrhythmic drugs for atrial fibrillation.

Almost 16 million people in the United States have diabetes, and the costs of treatment range up to $98 billion each year. Most people with diabetes do not require insulin injections but rather take drugs by mouth to control their disease. We will assess the usefulness of a large HMO database for studying the safety and effectiveness of oral drugs for diabetes.

An estimated 4.6 million Americans have heart failure, and this number is increasing each year. The death rate from heart failure at 5 years is 50 percent, and Medicare paid $3.6 billion in heart failure costs in 1996. We will assess the usefulness of a large HMO database for studying the safety and effectiveness of drugs to treat heart failure.

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"First weigh the considerations, then take the risks."

—Helmuth von Moltke

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Managing Risk

We will work to assess the effects, maximize the benefits, and minimize the harm of therapies by working jointly among the research centers, AHRQ, and the FDA. We will evaluate the use of a range of approved medical products, including therapeutic devices, nonsteroidal anti-inflammatory drugs, and systems to report adverse events in children.

Children and Adolescents

We will be analyzing data available from our Year 1 project on a new reporting system for adverse drug events and releasing the results as soon as possible.

We will continue our efforts to improve the care of children and teens with asthma. A new project in a Medicaid population will test different interventions designed to increase the appropriate use of corticosteroids in asthma.

Children with cystic fibrosis are susceptible to decreases in bone mass and outright loss of bone tissue. Late in 2001, we will begin to assess the effects on the bones of replacing vitamin D and calcium in children and adolescents with cystic fibrosis.

Adults

For the TMR project, we hope to develop a surveillance mechanism that manufacturers of cardiovascular devices easily could use to fulfill their regulatory requirements.

We will host a conference with representatives from academia, the FDA, the device industry, and professional societies. The goal is to develop more efficient models for studying approved cardiovascular devices. In conjunction, we will submit a "white paper" that describes current ways to monitor approved devices and proposes a model to address the limitations of these methods.

The increasingly high cost of therapy is a problem for many areas of disease. This is especially true for rheumatoid arthritis, where new biological agents have been shown to be very effective but also carry heavy costs. We will compare these newer treatments with traditional drug regimens.

Ever since antibiotics emerged in the 1940s, we have encountered the problem of resistant germs. Some bacteria and viruses are sensitive to almost all antimicrobial drugs; others are resistant to several drugs. The latter problem threatens our ability to treat many common community- and hospital-acquired infections.

These observations highlight a unique aspect of antimicrobial drugs—their misuse threatens not only individuals but also society as a whole. How to reduce antibiotic resistance is the subject of five projects that will begin in Year 2.

The first project will examine ways to reduce the use of antibiotics for acute bronchitis in outpatients. Another will assess how the drugs approved for use at different hospitals may affect the rate of antibiotic resistance for two types of bacteria. A third project will assess the effects of tetracycline on patterns of antibiotic resistance in people with acne. Fourth, we will study the use of a large, general-practice database in measuring the patterns of antibiotic use that place people at risk for pneumonia caused by drug-resistant bacteria.

The fifth project will explore the greater use of meta-analysis, a way to combine the results from different studies, in measuring rare side effects of antibiotics.

Results from different studies often are combined to overcome two possible problems of single studies: smaller populations, which can have a rate of rare events too low to measure accurately; and systematic bias, which can mask the true effect of therapy. The problem is that the most convenient mathematical methods for such analyses can produce results not easily applied to clinical situations.

We will develop statistical approaches to estimate risk that people can readily use to evaluate therapies, for overall populations and for subgroups by sex, age, and race.

Improving Practice

We will collaborate to produce reports on effective methods of changing practice. We will share knowledge gained from demonstration projects aimed at both increasing the use of beneficial therapies and reducing the use of harmful ones.

Children and Adolescents

The ADHD project, once the data are complete, will be providing a standard "toolkit" to caregivers. The hope is that use of the materials will improve the diagnosis and treatment of the disorder.

We should have substantial data compiled on the incidence of Type 2 diabetes in adolescents during Year 2. If, as we suspect, this disease is more common in this group than has been realized, we can begin to develop better ways to screen for it.

Another project, on ear infections, will involve collaboration with a Medicaid organization. We will assess outcomes by choice of drugs prescribed, send personalized information to the physicians, and assess whether this intervention can improve prescribing and reduce costs for this condition.

The NC Immunization Registry, set to begin in May 2001, aims to improve the ability of primary-care doctors to monitor children's immunization schedules. We will be working with the state Department of Public Health to achieve this goal.

Because drugs typically have not been tested in children, pediatricians may not be familiar with how to participate in clinical trials. We will conduct seminars in pediatric clinical trials, provide pediatric pharmacology fellowships, and perform public outreach.

The results of a collaboration with Research Triangle Institute, on evidence-based tools to assess the health status of children, also will be disseminated.

Adults

We will release a patient education brochure and video on the use of beta-blockers in CHF. Other interventions could include education through an Internet-based technology (Medical CyberSessions™), a training session for nurses to start community-based support groups, and brochures for caregivers on the use of beta-blockers. We will give physicians feedback on their rates of beta-blocker use before and after intervention, and a toll-free Helpline will be available for questions.

The methods used in the aspirin and beta-blocker projects (using a database to obtain use rates of drugs) may be applied to study of other therapies, such as drugs to lower cholesterol in people with CAD. After we develop and apply the beta-blocker intervention, we could tailor similar interventions to improve the use of other life-saving drugs. We also may study which components of interventions work best for specific types of therapies, physicians, or medical practices. This would be critical for tailored, cost-effective future interventions.

Based on the data gathered from the glucocorticoid project, we will begin to design programs to improve the identification and treatment of osteoporosis caused by these drugs. A collaboration of two CERTs centers will look at preventing fractures due to postmenopausal osteoporosis in people at risk.

For our studies of drug interactions, the goal for Year 2 is to develop targeted educational programs to reduce interactions in specific groups. We will select groups according to the potential for a drug interaction and by screening a large insurance database. We will expand upon our prototype approach, a Web-based international registry for cases of drug-induced torsades de pointes.

We will address the training needs of future caregivers by developing a curriculum for preventing drug errors, which will be made available to training programs. We also will evaluate curricula for therapies in women, a group often neglected in clinical research and medical education.

We should have substantial data by Year 2 on the use of aspirin, beta-blockers, and drugs to reduce cholesterol in a large Medicaid population. With this information, we aim to identify targets for education, including caregivers, patients, insurers, and policymakers.

We also should have data available from the COX-2 inhibitors project. Once analyzed, we will begin to release the information to the public.

Informing Policies

We will work with governmental agencies to inform policymakers about issues involving the use of therapeutic products as they arise.

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Conclusion

In November 1999, just after the CERTs demonstration program began, the Institute of Medicine reported that drug errors alone kill up to 7000 Americans each year—more than are killed by workplace injuries. Thousands more are inconvenienced, harmed, or disabled by errors in therapies, whether drugs or other products. Clearly the time has come for CERTs.

For the first time, the public and private sectors have come together to address critical questions about the way medical products are and should be used in the United States. By continuing to have a broad pool of collaborators and support, we can persevere in our effort to answer questions so important to society.

Partners in CERTs, whether government agencies, academic groups, practitioners, drug and device companies, commercial research groups, or consumer representatives, are committed to seeking answers together, putting society's interests first. This makes CERTs unique.

Already, the knowledge gained from CERTs has been translated into action that will improve health—the bottom line for us. Hundreds of breast-fed infants in one State now receive free vitamin D supplements, because of a CERTs pilot study. Parents of these infants, and soon perhaps of infants in all States, will have one less thing to lose sleep over: rickets.

We have started to answer important questions, but much work remains. We are excited to be a part of this program and look forward to making a difference in all the years to come.

The CERTs Group

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CERTs

• Developing knowledge.
• Managing risk.
• Improving practice.
• Informing policies.

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The CERTs Organization

Administration

Agency for Healthcare Research and Quality, Rockville, MD
Contact: Lynn Bosco, M.D., M.P.H.
Fax: (301) 427-1520
E-mail: LBosco@ahrq.gov

Coordinating Center

Duke University Medical Center, Durham, NC
Principal Investigator: Robert M. Califf, M.D.
Contact: Leanne Madre, M.H.A., J.D.
Fax: (919) 668-7068
E-mail: madre005@mc.duke.edu

Research Centers

Duke University Medical Center, Durham, NC
Principal Investigator: Elizabeth R. DeLong, Ph.D.
Contact: Nancy Allen LaPointe, Pharm.D.
Fax: (919) 668-7068
E-mail: allen003@mc.duke.edu

Georgetown University Medical Center, Washington, DC
Principal Investigator: Raymond L. Woosley, M.D., Ph.D.
Contact: Sally Yasuda, MS, Pharm.D.
Fax: (202) 687-4872
E-mail: yasudas@gunet.georgetown.edu
http://georgetowncert.org
http://www.torsades.org
http://www.qtdrugs.org
http://www.drug-interactions.com

HMO Research Network, Boston, MA
Principal Investigator: Richard Platt, M.D., M.Sc.
Contact: Rachel Dokholyan, M.P.H.
E-mail: rachel_dokholyan@havardpilgrim.org

University of Alabama at Birmingham
Principal Investigator: Kenneth G. Saag, M.D., M.Sc.
Contact: Jeroan Allison, M.D.
Fax: (205) 975-6859
E-mail: jallison@uab.edu

University of North Carolina at Chapel Hill
Principal Investigator: William H. Campbell, Ph.D.
Contact: Sue Tolleson-Rinehart, Ph.D.
Fax: (919) 843-9477
E-mail: suetr@unc.edu
http://www.sph.unc.edu/

University of Pennsylvania, Philadelphia
Principal Investigator: Brian L. Strom, M.D., M.P.H.
Contact: Brian L. Strom, M.D., M.P.H.
Fax: (215) 573-5315
E-mail: strom@cceb.med.upenn.edu

Vanderbilt University Medical Center, Nashville, TN Principal Investigator: Wayne A. Ray, Ph.D.
Contact: Marie Griffin, M.D.
Fax: (615) 343-8722
E-mail: marie.griffin@mcmail.vanderbilt.edu

Steering Committee

Hugh Tilson, M.D., Dr.P.H.
(Chair)

Lynn Bosco, M.D., M.P.H.
CERTs Program Officer,
AHRQ

Robert M. Califf, M.D.
Principal Investigator,
Coordinating Center

William H. Campbell, Ph.D.
Principal Investigator,
University of North Carolina at Chapel Hill Research Center

Lisa Egbuonu-Davis, M.D.
Vice President,
Global Outcomes Research and Medical Services, Pfizer Pharmaceuticals Group

Linda Golodner
President,
National Consumers League

Peter Honig, M.D., M.P.H.
Director, Office of Postmarketing Drug Risk Assessment,
U.S. FDA

Judith M. Kramer, M.D., M.S.
Co-principal Investigator,
Duke University Research Center

Richard Platt, M.D., M.Sc.
Principal Investigator,
HMO Research Network Research Center

Wayne A. Ray, Ph.D.
Principal Investigator,
Vanderbilt University Research Center

Kenneth G. Saag, M.D., M.Sc.
Principal Investigator,
University of Alabama at Birmingham Research Center

Marcel Salive, M.D., M.P.H. Medical Officer,
Prevention Scientific Research Group, National Heart, Lung, and Blood Institute, National Institutes of Health

Brian L. Strom, M.D., M.P.H.
Principal Investigator,
University of Pennsylvania Research Center

Karen Williams
President,
National Pharmaceutical Council

Raymond L. Woosley, M.D., Ph.D.
Principal Investigator,
Georgetown University Research Center

Public-Private Partnerships

Principles

Issues of Public Interest. CERTs is a major initiative to improve the rational use of therapies through research and education activities that are in the public interest but may not be done otherwise.

Public-Private Partnership. CERTs is a public-private partnership. Centers should seek useful, appropriate relations with private organizations to support and enhance education, research, and demonstration projects. AHRQ will work with the centers to establish appropriate agreements to optimize use and sharing of resources.

Conflicts of Interest. Potential conflicts of interest likely exist in any public-private partnership and cannot be completely avoided or eliminated. The obligation is to disclose fully and manage potential conflicts in a way that both minimizes the risk of those conflicts and maximizes progress to achieve CERTs' goals.

Academic Integrity. Persons conducting projects under the CERTs umbrella will make decisions about study design, analysis, conclusions, and publication and will ensure that the work complies with their local institutions' conflict-of-interest rules.

CERTs Activities. CERTs activities are defined as projects supported in whole or in part by AHRQ funds under the CERTs program. These are subject to processes established for the CERTs program, such as review of possible conflicts of interest. Persons affiliated with the centers conduct education and research activities outside of CERTs that are not subject to CERTs processes.

Partners

(through August 2000)

We gratefully acknowledge the following partners for providing resources for initial CERTs efforts and helping create a model for future collaborators:

• AdvancePCS
• Aetna U.S. Healthcare
• American Association of Colleges of Pharmacy
• American Pharmaceutical Association
• American College of Cardiology
• AstraZeneca L.P.
• Aventis Pharma
• Berlex Laboratories, Inc.
• Bristol-Myers Squibb Company
• Columbus Children's Hospital
• Dade Behring, Inc.
• F. Hoffman-LaRoche, Ltd.
• Glaxo Wellcome, Inc.
• Janssen Pharmaceutica, Inc.
• Lederle Laboratories, Inc.
• Medtronic, Inc.
• Merck & Co., Inc.
• National Cancer Institute
• National Institute of General Medical Sciences
• NC Department of Health and Human Services
• Pharmacia Corporation
• Pfizer Pharmaceuticals, Inc.
• ProtoGene Laboratories, Inc.
• Quintiles Transnational Corporation
• Research Triangle Institute
• Sanofi Pharmaceuticals, Inc.
• SmithKline Beecham
• Society of Thoracic Surgeons
• U.S. Quality Algorithms
• United States Pharmacopeial Convention, Inc.
• UnitedHealth Group
• University of Illinois Chicago College of Pharmacy
• Wyeth-Ayerst Laboratories

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CERTs Projects

For browsers that don't support tables, select the text listing.

Project Description	Year Begun	Status	Center
NC asthma improvement project	1	Complete	UNC
Drug metabolism in children with and without cystic fibrosis	1	Complete	UNC
Tailored implementation strategy for pediatric therapeutic guidelines	1	Complete	UNC
Evidence-based tools to assess pediatric population	1	Ongoing	UNC
Efficacy, safety, and pharmacokinetics of drugs in pediatric HIV	1	Ongoing	UNC
Prevalence of Type 2 diabetes in childhood	1	Ongoing	UNC
Prescribing patterns of psychotropic drugs for adolescents	1	Ongoing	UNC
Fellowships and education programs: pediatric pharmacology, pediatric clinical trials, and public outreach	1	Ongoing	UNC
CERTs Summer Institute: Using the Evidence on Therapeutics to Enhance Quality of Care	1	Ongoing	UNC
MedMARx monitoring and surveillance project	1	Ongoing	UNC
Aspirin use and nonuse in cardiovascular disease	1	Ongoing	Duke
Beta-blocker use in heart failure	1	Ongoing	Duke
Dofetilide in atrial fibrillation	1	Ongoing	Duke
Transmyocardial laser revascularization devices	1	Ongoing	Duke
Identification of, testing of, and education about drug interactions, especially in women	1	Ongoing	Georgetown
International registry for drug-induced arrhythmias	1	Ongoing	Georgetown
National medication-errors survey of third-year medical students, internal medicine clerkship, and residency programs	1	Ongoing	Georgetown
Postmarketing/pharmacoeconomic study of cyclooxygenase (COX)-2 anti-inflammatory drugs in Medicaid population	1	Ongoing	Vanderbilt
Study of policy changes as they relate to quality of pharmacotherapy in Medicaid population: loss of coverage in pediatric asthma, change in third-party mental-health carrier, differences in drug formularies	1	Ongoing	Vanderbilt
Effects of separate mental-health coverage on compliance in schizophrenia	1	Ongoing	Vanderbilt
Use of beta-blocker, aspirin, and lipid-lowering therapy after heart attack	1	Ongoing	Vanderbilt
Long-term safety and toxicity monitoring of nonsteroidal anti-inflammatory drugs	1	Ongoing	UAB
Attention deficit/hyperactivity disorder (ADHD) project	2	Ongoing	UNC
Pediatric adverse drug event and reaction reporting program	2	Ongoing	UNC
Skeletal effects of oral replacement of vitamin D and calcium in adolescents with cystic fibrosis	2	Ongoing	UNC
Prevalence of vitamin D-deficient rickets in minority infants	2	Ongoing	UNC
Optimizing prescribing and treatment for otitis media	2	Planned	UNC
Usefulness of large HMO databases in studying oral drugs for diabetes	2	Planned	HMO Research
Effect of provider profiling on management of glucocorticoid-induced osteoporosis (GIOP)	2	Planned	UAB
Selecting cost-effective treatments for rheumatoid arthritis	2	Planned	UAB
Increasing adherence to drugs to prevent osteoporosis	2	Planned	UAB
Secondary prevention of fractures due to osteoporosis	2	Planned	Duke/UAB
Reducing the use of antibiotics for acute bronchitis in outpatients	2	Planned	Penn
Effect of formulary changes on the resistance patterns of E. coli and Klebsiella	2	Planned	Penn
Use of tetracycline for acne in an outpatient clinic: effects on antibiotic resistance patterns	2	Planned	Penn
Using a large database to study the epidemiology of resistant Pneumococcus pneumonia	2	Planned	Penn
Expanding the use of meta-analysis to study rare side effects of antibiotics	2	Planned	Penn
Usefulness of large HMO database for studying the safety and efficacy of antibiotics in children	2	Planned	HMO Research
Usefulness of a large HMO database for studying the safety and efficacy of drugs to prevent heart failure	2	Planned	HMO Research
NC immunization registry	3	Planned	UNC

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Peer-reviewed CERTs Publications

Campbell W, Sleath B. Encyclopedia of Clinical Pharmacy. Washington, DC: Agency for Healthcare Research and Quality.

Meredith S, Feldman P, Frey D, Hall K, Arnold K, Brown NJ, Ray WA. Possible medication errors in home health care patients. J Am Geriatr Soc 2001 Jun;49(6):719-24.

Merlino L, Bagchi I, Taylor T, Utrie P, Chrischilles E, Mudano A, Saag K. Preferences for fractures and other glucocorticoid-associated adverse effects among rheumatoid arthritis patients. Med Decis Making 2001 Mar-Apr;21(2):122-32.

Mudano A, Casebeer L, Burst N, Carillo A, Gilbert D, Seay K, Saag K. Racial variation in use of hormone replacement therapy (HRT) and osteoporosis prevention in a large managed care population. Arthritis Rheum 2000;43:S282.

Sleath B, Rubin R, Campbell W, Gwyther L, Clark T. Physician-patient communication about OTC medications. Soc Sci Med 2001 Aug;53(3):357-69.

Smalley WS, Shatin D, Wysowski DK, Gurwitz J, Andrade SE, Goodman M, Chan KA, Platt R, Schech SD, Ray WA. Contraindicated use of cisapride: the impact of an FDA regulatory action. JAMA 2000 Dec 20;284(23):3036-9.

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This report was developed under the auspices of the Agency for Healthcare Research and Quality through grant number U18 HS10548, although its contents are solely the responsibility of the Centers for Education and Research on Therpeutics.

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Internet Citation:

Centers for Education and Research on Therapeutics: Annual Report: Year 1. October 2000. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/y1certs1.htm

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