CERTs

ANNUAL REPORT

YEAR7
This report was supported by grant HS13474 from the

Agency for Healthcare Research and Quality (AHRQ) for

the Centers for Education & Research on Therapeutics

(CERTs).
Vision

To serve as a trusted national resource for people seeking to improve health through

the best use of medical therapies.

Mission

To conduct research and provide education that will advance the optimal use of drugs,

medical devices, and biological products.

1

CERTs

October 2005 – September 2006

YEAR7
Values

Public Interest. Research must be conducted to answer important questions that

otherwise may not be addressed, with higher priority given to projects that offer better

opportunities to achieve our mission and vision.

Public-Private Partnership. Collaboration of groups with different perspectives and

resources—patients, health care providers, government, academia, delivery systems,

payers, purchasers, and manufacturers of medical products—is a cost effective way

to achieve results of mutual benefit and with greater responsiveness to the needs and

interests of more sectors in society.

Multidisciplinary Alliances. The best research harnesses the collective expertise of

medical practitioners, biostatisticians, clinical pharmacologists, health services

researchers, clinical epidemiologists, pharmacists, clinical researchers, and others

involved in health care.

Communication. The information from the CERTs must be made readily available to

all relevant audiences.

Education. Education of current and future health care providers, policymakers, and

patients is critical to improving health.

Public Policy. Policymakers must be provided with the best available evidence upon

which to base policies.

Accountability. Americans should expect the CERTs to be a trusted resource of

scientific evidence regarding therapeutics when they need answers to questions about

therapies.

2
Contents

Letter from the Agency for Healthcare Research and Quality.......................................................................4

Letter from the Steering Committee ..........................................................................................................5

Introduction..............................................................................................................................................7

CERTs Progress .......................................................................................................................................9

CERTs Research Centers Added in 2006.................................................................................................25

CERTs Program Resources .....................................................................................................................28

CERTs Partnerships and Collaborations....................................................................................................30

Partnerships to Advance THerapeutics (PATHs) .......................................................................30

Partnership and CERTs Medical Devices Workshop..................................................................31

Conclusion ............................................................................................................................................33

The CERTs Organization..........................................................................................................................34

Principles of CERTs Public-Private Partnerships ........................................................................................39

CERTs Project Partners...........................................................................................................................40

Peer-Reviewed Publications: October 1, 2005-September 30, 2006 .........................................................43

Referenced Publications.........................................................................................................43

Additional Publications ...........................................................................................................45

3
Dear Colleague:

This report from the

Agency for Healthcare

Research and Quality

(AHRQ) outlines the work

of the Centers for

Education & Research on

Therapeutics (CERTs) in

their seventh year. We are

pleased to present this

summary of CERTs

contributions to the

optimal use of medical therapeutics.

Optimal use of medicines and devices involves many

components dealing with safe and effective

prescribing or use by clinicians and patients. The

CERTs research summarized in this report illustrates

multiple CERTs efforts, in consultation with the Food

and Drug Administration (FDA), to identify risks

and/or the most effective use of medications and

devices. Relative to devices, a preliminary CERTs

study suggested children with diabetes who use

continuous glucose monitoring systems could

improve their hemoglobin A1c without increased risk

of hypoglycemia. The CERTs also convened a

multidisciplinary expert workshop on the evaluation

of diagnostic imaging technologies and therapeutics

devices and published the key issues that were

identified.

From a medication safety standpoint, the CERTs

studied the consequences of using ACE inhibitors

early in pregnancy. Adverse events of

antidepressants and steroids were examined for

children and adolescents as well. Other CERTs

research aimed to determine how often dosing

errors occur when medicines are prescribed (for

pediatric medicines or for treating gout). Research

on safe prescribing dealt with computerized alert

systems, including those on PDAs (personal digital

assistants) and in drug alert systems in pharmacies.

In addition, CERTs research addressed optimal

prescribing in situations where pretesting of patients

is needed to avoid adverse consequences, such as

TB testing in association with prescribing infliximab,

a medication for rheumatoid arthritis and Crohn’s

disease. Pretesting can determine whether patients

are harboring latent TB infection that could be

activated by use of the medicine.

As always, AHRQ is focused on the needs of

consumers. One CERTs study evaluated the quality

of online consumer drug information and provided a

list of recommended sites providing free information.

And, while it is important that medicines be

prescribed appropriately, it is also important that

patients take their prescribed medicines as directed,

a subject examined this year in relation to medicines

for myocardial infarction, heart failure, and

osteoporosis. Likewise, the CERTs examined

methods of patient education to increase adherence

to statins (which help prevent heart attacks and

strokes.)

With the addition of four new CERTs research

centers in 2006, we look forward to even greater

productivity and impact of the CERTs Program.

Carolyn M. Clancy, M.D.

Director

4

Letter from the Agency for Healthcare Research and Quality
Dear Fellow Citizens:

On behalf of the Steering

Committee for the

Centers for Education &

Research on Therapeutics

(CERTs) I am pleased to

present the CERTs Year 7

Annual Report.

We made unprecedented

progress this year in our

mission to provide the

public with a trusted national resource. We

conducted research and provided education in

therapeutics, and brought researchers with related

agendas together to work on a broad range of

projects to further our vision of improved public

health through the safe and effective use of drugs,

medical devices, and biological products.

This year we are particularly excited to welcome

four new centers to the CERTs program: the

University of Texas MD Anderson Cancer Center and

Baylor College of Medicine; Rutgers, The State

University of New Jersey; the University of Iowa; and

the Weill Medical College of Cornell University. With

the addition of these new centers, our areas of

research cover an even broader array of critical

areas in therapeutics research, including consumer

and patient education, mental health, aging and the

elderly, and medical devices.

This report highlights the ongoing work of the

CERTs, summarizes but a few of the projects

completed this year, and introduces the efforts from

the new centers. These projects range from the

study of herbal supplement use to an examination of

health care spending and comparative costs of

particular therapeutics. An important focus is

development of methodology to better ensure drug

safety and to fulfill the academic components of the

national strategy to implement the recommendations

of the landmark 2006 Institute of Medicine report on

the future of drug safety.

As we complete our seventh year, we remain

committed to generating and providing independent,

unbiased, and useful information about the benefits

and risks of important therapeutic products. We

thank our extensive list of public and private

partners in this enterprise. Working together, we can

move toward our shared vision: to better inform

health care providers, patients, policymakers, and

others about the drugs, devices, and biological

products that play such an important role in our daily

lives.

Sincerely,

Hugh H. Tilson, MD, DrPH

Chair, on behalf of the CERTs Steering Committee

Georges C. Benjamin, MD, FACP; Marc L. Berger, MD; Enriqueta C.

Bond, PhD; Lynn A. Bosco, MD, MPH; Janice K. Bush, MD; Robert M.

Califf, MD; Elizabeth A. Chrischilles, PhD; Stephen Crystal, PhD; Susan

N. Gardner, PhD; Harry A. Guess, MD, PhD; Judith M. Kramer, MD, MS;

Alvin I. Mushlin, MD, ScM; Richard Platt, MD, MS; Wayne A. Ray, PhD;

Kenneth G. Saag, MD, MSc; Marcel E. Salive, MD, MPH; David G.

Schulke; Paul J. Seligman, MD, MPH; Scott R. Smith, RPh, PhD; Steven

L. Solomon, MD; Alan D. Stiles, MD; Brian L. Strom, MD, MPH; Maria

E. Suarez-Almazor, MD, PhD; Myrl Weinburg, CAE; Raymond L.

Woosley, MD, PhD

5

Letter from the Steering Committee

The Centers for Education & Research on

Therapeutics (CERTs) program serves the American

people by providing valuable information to health

care providers, patients, and policymakers about the

safety and effectiveness of therapeutics—drugs,

medical devices, and biological products such as

vaccines. The CERTs conduct state-of-the-art

research about the safe use, risks and benefits, and

cost-effectiveness of therapeutics.

The CERTs program currently consists of a network

of 11 research centers, public and private partners,

a coordinating center, and a national steering

committee — all dedicated to making improvements

to the quality and safety of therapeutics. This year

four new research centers joined the CERTs

program to build on and enhance the work of the

existing centers.

Since the inception of the CERTs program in 1999,

the centers have developed a portfolio of nearly 400

projects. Subjects range from therapies for mental

health to therapies for older adults and the effects

of aging. As we complete our seventh year of work,

we remain involved in research related to some of

the most challenging medical issues of the day. In

addition to research, the centers take a leading role

in providing objective information to educate

patients, doctors, pharmacists, health plan

providers, and others about the drugs, devices, and

biological products that play such an important role

in our daily lives.

This report highlights the various CERTs research

and educational projects completed over the past

year, as well as several projects in progress.

7

Introduction

The CERTs program is funded and managed as a cooperative agreement by the Agency for Healthcare

Research and Quality (AHRQ) in consultation with the U.S. Food and Drug Administration (FDA). The CERTs

receive funds from both public and private sources, with AHRQ providing core financial support.
Arizona CERT at The Critical Path Institute (C-Path): Detection and prevention of adverse drug

interactions

Duke University Medical Center: Therapies for disorders of the heart and blood vessels

HMO Research Network: Use, safety, and effectiveness studies of therapeutics, using health plans for

defined populations

*Rutgers, The State University of New Jersey: Therapies for mental health

University of Alabama at Birmingham: Therapies for musculoskeletal disorders

*University of Iowa: Therapies for older adults and the effects of aging

University of North Carolina at Chapel Hill: Therapies for children

University of Pennsylvania School of Medicine: Therapies for infection; reduction in antibiotic resistance

*University of Texas MD Anderson Cancer Center and Baylor College of Medicine: Risk and health

communication; patient, consumer, and professional education; health decisionmaking and decision

support; therapeutic adherence

Vanderbilt University Medical Center: Prescription drug use in Medicaid and veteran populations

*Weill Medical College of Cornell University: Therapeutic medical devices

Therapy Examples

Drugs: Prescription medications; over-the-counter medicines

Medical devices: Coronary stents; blood glucose monitors

Biological products: Vaccines; blood products

8

Examples of Medical Therapies

*New center as of April 2006.

Centers and Their Emphases
Herbal Supplement Use and Interactions

in Diabetes

Treating and controlling diabetes usually includes

diet, exercise, blood glucose testing, and in many

cases, using oral or injected medications such as

insulin to control hyperglycemia. However, herbal

remedies are used by many Mexican Americans in

the Southwestern United States, where there is a

long history of using plants to treat a variety of

ailments. Because of this practice, it is important for

physicians to understand the possible adverse

effects and potential drug interactions that may

occur in persons with diabetes who use herbal

remedies.

CERTs investigators examined the use of herbal

remedies by Hispanic women with type II diabetes in

two community health centers in the southwestern

United States.1 A total of 91 percent of the

participants interviewed reported using one or more

herbal remedies, and 6.7 percent used herbal

remedies intended specifically for diabetes.

Researchers found that most of the 77 herbal

remedies identified were included as part of

commercial preparations and were used by patients

to supplement standard medical therapies for

diabetes. Although herbal supplements may have

adverse effects or interactions with other

medications, those found in use in this study were

unlikely to have a significant effect on outcomes in

diabetes.

Categorizing Antibiotic Use To

Understand Antibiotic Resistance

Antibiotic resistance is an important concern. Many

studies have sought to identify risk factors for

resistant infections. While many of these studies

explore the association between antibiotic use and

resistance, little attention has been paid to the

methods by which prior antibiotic use is defined

(e.g., by agent, class, and/or the spectrum of

activity against different organisms). To best identify

targets for intervention, it is critical to establish

whether a resistant pathogen is associated with use

of a specific class of antibiotics or whether the

specific agents used are associated with certain

spectra of activity.

The objective of this project2 was to explore the

variability and possible impact of methods of

categorizing antibiotic use on the association

between prior antibiotic use and resistant infection.

Using infections due to extended-spectrum betalactamase-producing Escherichia coli and Klebsiella

species (ESBL-EK) as a model, researchers

conducted a systematic review of the existing

literature and reanalysis of the database from a

previous study of risk factors for ESBL-EK infection.

The literature revealed tremendous variability across

studies in the categorization of prior antibiotic use,

with no study justifying its method for

categorization. The reanalysis of a past data set

also showed great variability across bivariate and

9

CERTs Progress
multivariate analyses, depending on which

antimicrobial use categorization (i.e., class of agent

vs. spectrum of activity) was employed.

Identifying modifiable risk factors is paramount in

efforts to curb the further emergence of antibiotic

resistance. This study is the first to investigate the

impact of different methods of antibiotic use

categorization on the epidemiological study of

resistance.

Future studies assessing risk factors for antibiotic

resistance should describe which antibiotics were

assessed and how they were categorized. Such

information is essential to inform antibiotic use

interventions and to facilitate comparison of results

across studies.

Patient Adherence to Preventive

Cardiovascular Medications

Beta-blockers—Although beta-blockers have been

shown to improve survival after myocardial infarction

(MI) and reduce the frequency of recurrent MI, little

attention has been paid to the need to sustain betablocker therapy long term.

In collaboration with the Council for Affordable

Quality Healthcare (CAQH), a not-for-profit

organization of health plans that promotes

collaborative initiatives for administrative

simplification and quality, CERTs investigators

examined the long-term use of beta-blockers over

the first year after MI in patients with commercial

health insurance and prescription drug benefits.3 The

investigators also looked at adherence in relation to

time from discharge, type of health plan, age, sex,

and region. In this study, patients were considered

adherent if they had prescription claims for betablockers for 75 percent or more of the days during

the first year after MI.

Over the first year after discharge, only 45 percent

of the 17,000 patients adhered to beta-blocker

therapy. Lower adherence occurred in patients with

Medicare-Plus-Choice plans, patients in the

Southeast, and young females in commercial health

plans. The study suggests that factors in addition to

cost affect long-term adherence.

Beyond targeting physicians who prescribe betablockers, educational efforts need to target patients

and their families to encourage continued use of

beta-blocker therapy during long-term outpatient

care. Since this study showed that compliance fell

off the most between 30 and 90 days after

discharge, interventions to improve adherence need

to be initiated early after discharge.

Quality measures that focus on long-term

persistence of beta-blocker therapy can help move

practice in the right direction. The first example of

such a tool is the new 2005 HEDIS® (Healthcare

Effectiveness Data and Information Set) measure

from the National Committee for Quality Assurance

(NCQA), derived by the same methods used in the

CAQH study. This HEDIS measure looks at

persistence of beta-blocker therapy over the first 6

months after MI. Certainly, the interests of all parties

(physicians, patients, health plans, pharmaceutical

companies, pharmacists, and nurses) should be well

10
aligned to promote patients’ long-term adherence to

this life-saving medication.

Secondary prevention therapies—A great deal of

research is directed toward understanding and

improving in-hospital and discharge prescription

practices of doctors, but less goes toward

determining long-term adherence to these

medications by patients. To address this issue,

CERTs researchers analyzed data from the Duke

Databank for Cardiovascular Disease from 1995 to

2002 in order to determine adherence to several

secondary preventive medications, including betablockers, aspirin, angiotensin-converting enzyme

(ACE) inhibitors, and lipid-lowering therapies.4

Starting in 1995, a routine followup questionnaire

was sent to patients who had undergone a

cardiovascular procedure at 6 and 12 months after

their procedure and yearly thereafter. Patients were

prompted to report all medications they were using.

Based on these surveys, patterns of long-term

medication use were described. Consistent use was

defined as use reported on two or more consecutive

surveys up to an endpoint of death, withdrawal, or

the end of the study.

From one perspective, the results of this analysis

were encouraging, showing that patient-reported use

of medications after discharge has increased

steadily since the beginning of the study. In 2002,

use of aspirin was 83 percent; beta-blockers, 61

percent; and lipid-lowering agents, 63 percent.

However, these overall rates of medication use are

still suboptimal. In addition, many patients do not

use these medications consistently. Aspirin is the

oldest and least expensive drug used in secondary

prevention and the one with the fewest absolute

contraindications and least controversy over its

indication for secondary prevention, but only 71

percent of these patients used it consistently. Only

46 percent of patients consistently used prescribed

beta-blockers, 44 percent used prescribed lipidlowering agents, and only 21 percent consistently

used a prescribed combination of aspirin, betablockers, and lipid-lowering agents. Further,

consistent use was lowest among patients who had

the greatest potential for benefit from these agents,

including the elderly, patients with diabetes, and

patients with heart failure. Although quality

improvement initiatives have shown modest success

in encouraging adherence to medications, much

more research is needed to determine the most

effective means of bolstering long-term medication

adherence.

Physician Oversight of NSAIDs Use

Nonsteroidal anti-inflammatory drugs (NSAIDs) are

among the most common medications prescribed to

older Americans, and they often are prescribed

inappropriately. Adverse events associated with longterm NSAID use are common and often result in

substantial illness and death. Physician adherence to

guidelines recommending NSAID safety monitoring

practices is low.

Researchers conducted a randomized trial to

determine whether providing audit/feedback and

educational materials to prescribing physicians

would improve adherence to three

11
recommendations: laboratory monitoring for blood

counts, laboratory monitoring for kidney function,

and use of cytoprotective agents (medications to

prevent stomach problems).5

There were no significant differences in performance

between intervention and control physicians before

or after the intervention for any of the three

recommendations. However, results suggested a

trend toward higher performance among physicians

who reported receipt of the intervention materials

and participated in the continuing medical education

activities. Provider and patient factors and health

services use were more strongly associated with

adherence to NSAID safety-monitoring guidelines

than were the educational materials tested.

The results highlight the challenges of interventions

designed to improve adherence to NSAID safetymonitoring guidelines. No single intervention or set

of interventions has proven effective in altering

physician practice patterns in all settings. Although

multimodal interventions have been effective for

changing practice in other chronic diseases, no

significant difference in NSAID safety-monitoring

practices was found in this study.

The clinical and methodological insights gained from

this work may lead future studies to greater success

in improving physician adherence to evidence-based

practice guidelines.

ACE Inhibitor Use and Risks in Early

Pregnancy

Use of angiotensin-converting enzyme (ACE)

inhibitors during the second and third trimesters of

pregnancy has been associated with an increased

risk of fetal abnormalities. In contrast, until now,

based on several small, uncontrolled studies and

unpublished reports, first-trimester use of ACE

inhibitors had not been linked to adverse fetal

outcomes. However, because angiotensin II

receptors are widely expressed in fetal tissue and

could play an important role in fetal development, it

was postulated that first-trimester exposure to ACE

inhibitors could increase the risk of congenital

malformations.

Using a large Medicaid database, investigators

assessed the association between exposure to ACE

inhibitors during the first trimester of pregnancy and

the risk of congenital malformations.6

Infants with exposure to ACE inhibitors solely in the

first trimester had an increased risk of major

congenital malformations compared with infants who

had no exposure to antihypertensive medications.

Use of other antihypertensive medications did not

confer an increased risk. Infants exposed to ACE

inhibitors were at increased risk of malformations of

the cardiovascular system and the central nervous

system.

As the approved uses for ACE inhibitors have

expanded, their use among women of childbearing

age has increased. This increase in use is likely to

result in an increase in first-trimester fetal

exposures. These data suggest that such exposures

cannot be considered safe and should be avoided.

Continuous Glucose Monitoring Devices

and Their Effectiveness in Children

Controlling blood glucose levels delays the long-term

complications from type 1 diabetes mellitus but

12
increases the risk for hypoglycemia. The continuous

glucose-monitoring system (CGMS) gives blood

glucose readings every 5 minutes and is very

accurate and reliable in adults. However, there is not

much information available about how effective this

system is in children.

CERTs researchers conducted a study to determine

whether the CGMS would improve blood glucose

control in 27 children with type 1 diabetes mellitus.7

Children were assigned to one of two groups. Both

groups wore the CGMS for 72-hour periods. Therapy

was adjusted for the intervention group based on

the CGMS and self-monitoring data. Therapy for the

control group was based only on self-monitoring

data. Hemoglobin A1c levels were determined and

the change from 0 to 6 months for the two groups

was compared. At the beginning of the study,

hemoglobin A1c levels were similar for the two

groups, but by the end of the study, they were

significantly lower for the intervention group. The

decrease in the intervention group was statistically

significant, but the decrease in the control group

was not.

The CGMS may improve blood glucose control in

children with type 1 diabetes mellitus without

increasing the risk for hypoglycemia. However, the

long-term benefits of the CGMS on metabolic control

remain to be determined.

Vaccine Coverage – Unexpected

Benefits and Challenges

Reduced pneumococcal bacteremia in adults

when children in the home are vaccinated—A

new pneumococcal conjugate vaccine containing

seven serotypes was released in February 2000 for

use in infants and children. In the following years,

several observations were published linking the

vaccine to a reduced rate of invasive pneumococcal

disease among adults. CERTs investigators sought

to determine if pediatric vaccination lowers the risk

of pneumococcal bacteremia in adults living in the

same home.8

The study had two parts: a 2-year prospective

population-based surveillance for pneumococcal

bacteremia in adults and a case-control study of risk

factors for the disease. The study was carried out in

a five-county region of Pennsylvania. The surveillance

tracked all cases of pneumococcal bacteremia,

while the case-control study involved contacting and

interviewing both adults with the disease and a

healthy control population.

Although the overall rate of pneumococcal

bacteremia for the adults in the study decreased by

a statistically insignificant 9 percent from 2002 to

2004, there was a significant 22-percent decrease

in the cases that involved serotypes included in the

new vaccine. The results of this study showed that

vaccination of the youngest child in the home

corresponded to an 80-percent reduction in the

odds of the disease among adults in the same

home.

Examining surgeons’ attitudes about hepatitis

B vaccination—In the 1990s, prior to the

Occupational Safety and Health Administration

(OSHA) mandate to offer hepatitis B vaccination to

all health care workers, studies showed that many

13

surgeons were not adequately vaccinated. It is

unknown if vaccination rates have improved since

the OSHA mandate. Inadequately vaccinated

surgeons may be a risk to their patients.

CERTs investigators sought to identify the proportion

of U.S. transplant surgeons adequately vaccinated

against the hepatitis B virus, identify characteristics

associated with inadequate vaccination, and assess

the proportion that had been evaluated for

immunization after potential exposures to the

hepatitis B virus.9

Of the 619 eligible surgeons, 347 (56.1 percent)

returned completed questionnaires. A total of 23

percent had received fewer than the recommended

three injections. Some factors associated with

inadequate vaccination were increasing length of

time a surgeon was in clinical practice, an increased

fear of infection from patients, and a lack of recent

testing for the hepatitis C virus. Of the 94 surgeons

(27.3 percent) reporting at least one needle-stick

exposure while operating on a patient with the

hepatitis B virus, 14 (14.9 percent) were

inadequately vaccinated; of these 14, only 5 (35.7

percent) sought appropriate testing and counseling

for active immunization. Surgeons underestimated

both the risk of exposure while operating and the

risk of becoming infected if exposed.

Despite the mandate from OSHA that all health care

workers be offered hepatitis B virus vaccination,

some transplant surgeons are inadequately

vaccinated and do not seek appropriate postexposure evaluation. This increases risks to both the

surgeons and their patients.

Determining the reasons for inadequate vaccination

may help target interventions that promote

vaccination and a change in behavior. Because

inadequately vaccinated surgeons underestimate

their risk of exposure, although they also express

fear of acquiring hepatitis B, education regarding

true transmission risks may increase the number

willing to be vaccinated.

Interventions to Change Physician

Behavior

Changing prescribing for heart failure—Despite

the incorporation of beta-blocker use into clinical

practice guidelines for the treatment of heart failure,

use of this proven therapy remains low. This may

result from previously held beliefs that beta-blockers

are harmful in heart failure and from the typically

slow translation of evidence into practice.

A study was conducted to develop and test a

multifaceted intervention using Internet-based

academic detailing, physician feedback, and patient

education to improve outpatient use of beta-blockers

in patients with heart failure.10

Practices receiving intervention did not have a

significantly higher use of beta-blockers than a

control group of medical practices given written

educational materials. However, a trend toward

greater use of beta-blockers in the intervention

group, coupled with results of prespecified

secondary analyses demonstrating significantly more

patients starting a beta-blocker than stopping a betablocker in intervention practices, put the findings in

a more encouraging light.

15
The survival benefit associated with beta-blockers in

patients with heart failure is large. Therefore,

interventions with even modest increases in betablocker use could result in substantial benefits.

Investigators should continue to explore new types

of interventions, physician incentives, and

technological advances to stimulate adherence to

guidelines for recommended therapies for heart

failure.

Testing for tuberculosis before starting

infliximab—After infliximab was approved by the

Food and Drug Administration (FDA) to treat Crohn’s

disease (1998) and rheumatoid arthritis (1999),

tuberculosis was reported in the FDA’s spontaneous

reports as one potential infliximab-related adverse

event.

Researchers conducted a study to examine the

impact of Federal, industry, and academic efforts to

communicate this risk to users of infliximab.11 The

effectiveness was evaluated by the proportion of

patients getting tuberculin skin tests, which assess

whether patients are harboring latent tuberculin

infection before or soon after taking infliximab. The

investigators also wanted to determine if there was

a difference in tuberculin skin testing rates among

the various medical specialists who treated patients

requiring infliximab.

Tuberculin skin testing rates doubled over a 30-

month period as the risk communication efforts

continued. Rheumatologists were the only specialists

who showed a significantly higher than average rate

of tuberculin skin testing among their patients.

The study showed that risk-communication efforts

can increase physician compliance in tuberculosis

testing of their patients, and, in this case, might

decrease the risk of activating latent tuberculosis

infection potentially associated with infliximab.

The findings of this study suggest opportunities for

further research to determine what types of

communications elicit the greatest compliance,

whether multiple communications are more

effective, and whether repetition of messages

further increases compliance, thus optimizing public

health.

Patient Self-Reporting of Medication Use

NSAIDs use—Each year an estimated 16,000

people die from NSAID-induced gastrointestinal

complications. Patients frequently fail to report to

their doctors that they are taking over-the-counter

NSAIDs, and serious problems may occur when

nonprescription NSAIDs are used alone or in

combination with other medications.

CERTs investigators sought to determine if selfreported use of nonprescription and prescription

NSAIDs matched the information in the patient’s

medical records, and to determine which of two

survey formats aided patients’ recognition and recall

of medication use.12

Patients in a rheumatology clinic completed 361

surveys: 182 in list format and 179 in open-ended

format. Medical records review confirmed 26.1

percent of patient-reported nonprescription NSAID

use and 59.1 percent of patient-reported

16
prescription NSAID use. For patients using both

prescription and nonprescription NSAIDs, both

medications were confirmed in only 2.3 percent of

the medical records. Fewer patients reported

nonprescription NSAID use with the open-ended

format survey (24.0 percent) than with a checklist

format (41.8 percent).

Agreement between self-reported NSAID use and

medical record documentation is especially poor for

nonprescription NSAIDs. This lack of communication

and understanding about concomitant prescription

and nonprescription medication use may lead to

serious adverse reactions, including death.

Although this study did not test an intervention, it

suggests that using a checklist for obtaining history

of medication use might increase patient-physician

communication regarding NSAID use. Addressing

NSAID use at the point of purchase (pharmacies)

using a list-type survey may offer a unique

opportunity to decrease risky concomitant

prescription and nonprescription NSAID use.

Osteoporosis medications—Pharmacy and linked

claims databases are used to determine whether

patients receive medications as a quality-of-care

measure. However, these databases have not been

compared with self-reported data for patients

receiving medications used to treat glucocorticoidinduced osteoporosis.

CERTs researchers examined agreement between

filled prescriptions in a pharmacy database and selfreported current use of several osteoporosis

medications among chronic glucocorticoid users

enrolled in a large U.S. managed care plan.13

Chronic glucocorticoid use was defined as 60 or

more days of filled outpatient oral glucocorticoid

prescriptions from July 2001 to December 2002.

Agreement between the pharmacy data and the selfreported data was high, and underreporting of

current osteoporosis medication was uncommon

among chronic glucocorticoid users enrolled in

managed care. Both sources of information seem to

be appropriate in assessing exposure to

osteoporosis medications.

CERTs investigators found that use of pharmacy

data alone is unlikely to lead to an underestimate of

osteoporosis treatment, but there is a need for a

longer assessment period in studies that rely only on

pharmacy data.

Assessing Risks of Medication Errors

and Adverse Events

Pediatric dosing errors—Prescription dosing

errors are common in children. Their smaller size

makes them more vulnerable to dosing errors and

less able to communicate signs and symptoms that

indicate a problem. CERTs investigators analyzed the

prevalence of potential outpatient prescription errors

in the dosages of 22 medications commonly

prescribed to children.14

A total of 15 percent of the 22 most commonly

prescribed medications for children appeared to

have dosing errors, 8 percent of which involved

overdosing and 7 percent of which involved

underdosing. The most frequently potentially

17
overdosed drugs were the four analgesics

examined—acetaminophen with codeine, ibuprofen,

naproxen, and oxycodone. The most frequently

underdosed drugs were antiepileptics. Medications

prescribed “as needed” were the most likely to be

overdosed when the projected total daily dose was

calculated as the amount a child would possibly

receive if given the upper range of the dose at the

most frequent dosing interval. The formulation of the

drug did not affect the number of dosing errors. The

number of errors also was not affected by one site’s

use of computerized prescription order entry (CPOE)

that contained decision support for some

medications, but no child-specific decision support,

calculation of doses, or error checking.

Particularly disturbing was the high rate of

overdosing of analgesics, since these drugs can

have serious or fatal adverse events. Also, the

youngest children and children with complex health

conditions appeared to be the most vulnerable to

potential dosing errors.

Only one medication, trimethoprim-sulfamethoxazole,

was dosed within the recommended weight-based

dosing range for all doses dispensed. This

medication had only a few outpatient formulations

and a simple standard weight-based dosing range

for most uses. If such simplicity in formulation and

dosing helps correct dosing, then standardization of

medication dosing regimens for children may be an

important strategy for preventing dosing errors.

All parties, health care providers and parents, need

to be vigilant with drug prescriptions for children. In

addition, computerized prescription systems need to

take into account the complexities of medication

dosing for children’s weight. Standardization and

simplification of medication dosing regimens merit

further consideration as a means to lower the risk of

medication dosing errors.

Measuring EKG changes related to

arrhythmias—Over 25 drugs on the market can

have an effect on the electrocardiogram to prolong

the QT intervals. This effect is associated with the

development of life-threatening ventricular

arrhythmias called torsades de pointes. FDA

guidelines recommend that the QT interval of people

taking these medicines be monitored for the

excessive prolongation that increases the risk of

torsades de pointes. Because the QT interval

changes when the heart rate changes, guidelines

recommend that the interval be corrected for any

differences in heart rate. Over 15 different rate

correction formulas have been recommended, of

which the Bazett and Fridericia formulas are most

commonly used. The formulas have not been

thoroughly evaluated to determine if they can be

applied when monitoring the effects of drugs that

can prolong the QT interval.

CERTs investigators developed a standardized

clinical exercise protocol that accurately defined the

QT interval over a wide range of heart rates.15 They

then administered an intravenous infusion of ibutilide,

an antiarrhythmic drug chosen for use because it

prolongs the QT interval. A total of 18 male and

female volunteers were enrolled and performed the

exercise protocol before and during the ibutilide

infusion. Four heart rate correction formulas were

18
applied to the data and compared with the results

obtained during exercise (uncorrected). The most

commonly used formulas, the Bazett and Fridericia

formulas, overestimated the change in QT interval.

However, the Framingham and Hodges formulas did

not change the accuracy of the assessment of QT

interval change. This study found that the standard

Bazett and Fridericia formulas can introduce

significant errors in the assessment of drug effects

on the QT interval. If the results of this study are

verified using additional drugs, then practicing

cardiologists and the manufacturers of

electrocardiogram machines may require changes to

the rate correction formulas that they use.

Errors with the use of allopurinol and

colchicines—Gout-specific medication dosing

errors are common, often having harmful or even

fatal consequences. CERTs researchers examined

gout-specific medication errors using an Internetaccessible error-reporting system, MEDMARX®.

16

Of the medication errors reported in MEDMARX over

a 5-year period, 0.15 percent occurred with goutspecific medicines: primarily allopurinol, followed by

colchicine, probenecid, and sulfinpyrazone. Errors

involving allopurinol and colchicine were more likely

than other medication errors to result from

prescribing errors rather than drug-administration

errors. Physicians were the health care providers

most responsible for these errors. This study

explores the reasons for gout-related medication

errors by looking at personnel involved, contributing

factors, harm rates, and error type and origin.

Quality improvement measures need to be initiated

in gout management, focusing on physician practice

and prescribing behaviors.

Adverse events associated with

glucocorticoids—The prevalence and severity of

adverse events associated with glucocorticoid use

are unknown, and concern for the possible

occurrence of such events often limits use of these

drugs. Potential adverse events may range from

mild (acne, weight gain, sleep disturbances) to

severe (osteoporosis, fractures, cataracts).

CERTs investigators sought to determine the

prevalence of glucocorticoid-associated adverse

19
events in a large U.S. managed care population.17 In

the survey of 2,446 managed care enrollees,

glucocorticoid users reported weight gain (80

percent) as the most common adverse event,

followed by skin bruising/thinning and sleep

disturbances. Cataracts and fractures were reported

less frequently. Strong dose-response relationships

were observed between glucocorticoids and most

adverse events, and such events were reported

relatively frequently, even at lower doses. A high

prevalence of self-reported adverse events is

associated with glucocorticoid use among

individuals treated long term for a variety of

conditions.

Physicians should closely monitor patients for

glucocorticoid-related adverse events and should

provide counseling about possible risks before

beginning glucocorticoid therapy.

Using Health Information Technology To

Reduce Medication Interactions and

Errors

Warfarin medication interactions—The use of

computerized systems to help clinicians avoid

making medication errors through a system of

automatic alerts and reminders has been shown to

be effective in hospitals and clinics. It is not known

how effective such systems are at preventing

outpatient medication errors, or how effective they

are at preventing problems that occur due to the

interaction of two or more medications.

The objective of this study was to assess the

effectiveness of computerized alerts in electronic

medical records in preventing prescriptions of

medications that interact with warfarin, a commonly

prescribed drug known to have many potential drug

interactions with possibly serious consequences.18

Almost one-third of the patients included were found

to have a prescription that interacted with warfarin.

The use of computerized alert systems in the

electronic medical record resulted in a relative

reduction of 15 percent in the observed rate of

interacting prescriptions at 12 months. The

reduction was immediate, with a progressive

monthly reduction for interacting prescriptions over

the followup period. Special training for groups of

clinicians, sometimes called “academic detailing,”

did not appear to have an additional effect in

reducing prescriptions of interacting medications.

This study supports using computer assistance to

prevent potential medication errors in the outpatient

care setting, but effects on patient outcomes (e.g.,

bleeding) were not part of the study design.

Further studies should focus on finding the best

strategies for incorporating academic detailing

efforts in the context of electronic alerts, as well as

estimating effects on patient outcomes.

Computerized drug-drug interaction alerts in

community pharmacy—Community pharmacies

play a vital role in the safe use of medications and in

helping to prevent potentially harmful drug-drug

interactions (DDIs). CERTs researchers sought to

examine community pharmacists’ attitudes about the

20
usefulness of computerized DDI alerts and to

determine what factors are associated with

favorable perceptions of these alerts.19

The researchers found that pharmacy managers did

not think that DDI alerts are a waste of their time,

but there was some concern that their computer

systems might not be providing them with potential

DDI (PDDI) alerts. The majority of pharmacists were

confident in their ability to identify and discuss PDDIs

with physicians. More favorable perceptions of PDDI

alerts were found in pharmacies with software that

provided detailed DDI information and allowed

pharmacists to customize PDDI alerts.

Pharmacy technicians and computerized

alerts—Community pharmacies are important in

identifying and preventing serious DDIs. Technicians

in community pharmacies are often the first to

become aware of alerts about potential DDIs.

CERTs researchers examined the role of pharmacy

technicians in managing PDDI alerts in community

pharmacies and the possible relationship to the

pharmacy manager’s attitude about PDDI alerts.20

Pharmacy managers in 3,000 community

pharmacies across the United States were surveyed,

and data were collected about demographics,

workload issues, handling of DDIs, and pharmacists’

attitudes toward computerized DDI alerts.

It was found that technicians were often allowed to

override the less significant PDDI alerts without

having to consult the pharmacist. In some

pharmacies (2.1 percent), technicians were allowed

to override interactions with the highest potential

clinical significance. In pharmacies with the highest

use of technology, technicians were less likely to be

allowed to override insignificant interactions. The

pharmacies that allowed technicians to override

clinically significant interactions were more likely to

feel that the alerts are a waste of time and that the

volume of alerts makes it difficult to determine

which are important and which are not.

The education and role of pharmacy technicians

continue to evolve and the quality of decision

support provided with alerts is improving. Since

pharmacy technicians are likely to play an

increasingly important role in managing PDDI alerts,

further study of this evolution and how it impacts

patient care and pharmacy efficiency is needed.

Drug-drug interaction software for personal

digital assistants—Medication errors, including

DDIs, have been estimated to cause 106,000

deaths annually in hospitalized patients. Personal

digital assistants (PDAs) allow health care

professionals to check for potential DDIs at the point

of care, thereby reducing the time needed to consult

traditional references, which are often out of date.

PDAs, however, can only be as effective as the

software programs they use.

CERTs investigators in this study21 examined the

capacity of drug-drug interaction software programs

manufactured for Palm OS-compatible PDAs in

detecting important DDIs. A prospective evaluation

of the ability of eight software programs for PDAs to

detect important DDIs was conducted. Sensitivity

(the ability to correctly indicate that an interaction

exists) and specificity (the ability to indicate correctly

21
that no interaction exists) were measured for each

of the software programs. Five of the programs had

a perfect score on sensitivity; only one program had

a perfect score on specificity.

To provide high-quality health care, all health care

providers who prescribe and/or dispense

medications need to catch prescribing errors before

patients receive the medication. As more drugs

appear on the market, the potential for DDIs

increases, making the value of timely information

even more important. It is critical that software

correctly identify important interactions. Because

evaluation of any program is a point-in-time

determination and manufacturers are constantly

striving to update and improve their products,

programs should be periodically evaluated and

compared.

Web-Based Provider and Patient

Education

Online education on drug interactions—Six of

the last 19 drugs removed from the market were

found to cause a potentially lethal heart rhythm

abnormality, torsades de pointes, especially when

there was an interaction with other drugs that

caused the drug levels to increase. Over 25 drugs

with this potential remain on the market, making it

important for health care providers to understand

this particular form of cardiac toxicity, its relation to

prolongation of the QT interval on the

electrocardiogram, and the important role of drug

interactions. In an analysis of drugs prescribed to

over five million people, CERTs investigators found a

high frequency of coprescribing of drugs that each

prolong the QT interval, thereby putting these

patients at risk of torsades de pointes.

To address the need to make better information

available for prescribers, CERTs investigators

maintain an educational Web site, www.QTdrugs.org.

Based on an ongoing evidence-based process to

monitor and assess drugs for their potential to

prolong the QT interval and cause torsades de

pointes, drugs are classified into lists according to

risk. In 2006, there were 344,689 visitors to the

site and the QT Drug Lists received 41 percent of all

page views. In addition, CERTs investigators provide

a free online version of an educational module titled

Preventable Adverse Drug Reactions: A Focus on

Drug Interactions. Created in collaboration with the

22
FDA, the module contains teaching slides, sample

questions, references, and a pocket reference tool

showing how to predict and prevent the major

metabolic drug interactions. The educational module

has been downloaded from www.QTdrugs.org

28,000 times in the last 3 years and more than

12,000 times in the last year.

Online consumer drug information—The Internet

has become an increasingly important source for

consumers searching for drug information. Over 25

percent of Americans have used the Internet to

search for prescription drug information. However,

seeking health information online can be a

formidable task. The abundance and technical

complexity of such information are overwhelming,

and consumers often lack the knowledge to

efficiently search the Internet for dependable drug

information or how to distinguish high-quality from

poor-quality drug information.

With this dilemma in mind, CERTs investigators

conducted a systematic search of prescription drug

information Web sites and evaluated them for

information quality and utility for consumers.22

CERTs pharmacists and health communication

specialists created a Webliography, or annotated list

of recommended Web sites providing free

prescription drug information, and made it available

online along with a printable brochure and patient

information sheet (available at www.azcert.org).

Health Care Spending and Costs

Spending on post-approval drug safety—Recent

withdrawals of high-profile drugs have focused

attention on post-approval safety surveillance by

pharmaceutical manufacturers and the FDA. The

public relies on such surveillance to detect rare and

unexpected reactions to new medications that go

undetected before they are approved. Currently, the

primary post-approval method for tracking adverse

drug reactions relies on spontaneous reporting—

i.e., patients or clinicians report adverse events

(AEs) directly to the FDA or to the manufacturer (who

must report them to the FDA within a specific

timeframe). Depending on the number and severity

of AEs reported, a manufacturer may be required to

take action, which may include new research,

revised labeling, or removal of the drug from the

marketplace.

To gauge the amount of funding devoted to postapproval surveillance efforts, CERTs researchers

surveyed 25 large pharmaceutical companies, 11 of

which responded.23 Those 11 companies’ sales

accounted for 71 percent of sales by the top 20

pharmaceutical manufacturers in 2003. Using the

safety spending data provided by these

respondents, the researchers estimated that the top

20 companies spent $800 million (or 0.3 percent of

their total sales) on post-approval safety in 2003. In

the same year, drug companies spent 15.6 percent

of sales on research and development. The study

also reported that the U.S. government budgeted

$22.1 million for the FDA’s Office of Drug Safety in

2003, less than the average spending on postapproval safety by any one drug company surveyed.

The United States is where most new and innovative

drugs are launched, so the need for effective and

23
well-financed post-approval safety surveillance is

great. The CERTs survey, the first of its kind, will

help to inform ongoing discussions about proposed

changes to the system.

Impact of cost-sharing on use of oral

hypoglycemics—Increased cost-sharing

(copayments) for chronic-disease medications may

lead to their reduced use, which over time could

lead to increased medical complications.

Segmented time-series regression models were

used to estimate the effects of small ($1-$6),

moderate ($7-$10), and large (more than $10)

increases in cost-sharing for a 30-day supply of an

average daily dose of oral hypoglycemics among

adults with type 2 diabetes in five managed care

organizations.24 Large copayment increases were

associated with an immediate and continued

decrease in the average daily dose of oral

hypoglycemics. Other studies have shown that

adults with diabetes mellitus who report cost-related

medication underuse also report poorer glycemic

control and worse health status than patients who

do not report cost-related medication underuse.

Collectively, studies of the impact of cost-sharing on

medication use suggest that drug-benefit plans

should be designed in a way that lessens the

potential adverse effects of large cost-sharing

increases among patients requiring essential

chronic-disease medications.

Health care costs of undertreated heart

failure—In a study of managed care heart failure

patients, it was found that fewer than 14 percent

adhere to pharmacotherapeutic or drug regimens to

treat their disease, resulting in significantly higher

rates of hospitalization and health care costs.

A team of CERTs investigators sought to evaluate

the effect of regular use of four heart failure agents

(angiotensin-converting enzyme inhibitors, betablockers, loop diuretics, and digoxin) on rates of

hospitalization and total health care costs in patients

enrolled in managed care organizations.25

Patients who received none of the four heart failure

agents were at 2.5 times greater risk of

hospitalization and had 43.6 percent higher health

care costs compared with all other heart failure

patients. Patients who consistently used the agents

had 80 percent fewer hospitalizations and incurred

70 percent less health care costs than the patients

receiving no therapy.

Physicians treating patients with heart failure may

need to monitor their patients’ drug therapies,

identify patients not being treated according to

guideline recommendations, and prescribe the

appropriate regimens for these patients.

24
In April 2006, four new research centers were

added to the CERTs program: the University of

Texas MD Anderson Cancer Center and Baylor

College of Medicine; Rutgers, The State University of

New Jersey; Weill Medical College of Cornell

University; and the University of Iowa. Investigators

at these new centers are working on a wide range

of topics, including consumer and patient education

and adherence, mental health therapeutics, medical

devices, aging, and the elderly.

Consumer and Patient Education and

Adherence

Improving outcomes for multiple morbidities—

Despite the demonstrated efficacy and costeffectiveness of treatment and prevention strategies

for many chronic conditions, many older persons,

especially those with comorbid conditions, continue

to suffer from uncontrolled hypertension,

hyperglycemia, and other predictors of poor health

outcomes. To address this gap in the

implementation of effective and efficient medical

care, CERTs researchers will develop and test a

model of collaborative group clinics that seeks to

empower older patients to adopt goal-setting

behaviors and communicate with their health care

provider to improve diabetes-related outcomes.

Informed decisionmaking about statins—

Studies have consistently shown that statins reduce

the risk of heart attack and stroke by 30-40

percent. Despite this, many patients reject or stop

taking statins because of concerns about potential

side effects and other problems. A patient education

intervention that improves statin compliance would

likely prevent many heart attacks and strokes.

Researchers are working to develop and evaluate

the potential efficacy of a new statin decision aid in

Spanish and English for low-literacy primary care

patients.

Mental Health Therapeutics

Pharmaceutical care for mental illness under

Medicare Part D—Pharmaceutical care provided

through the Medicare Part D program is critical for

elderly and disabled persons with mental illnesses. A

particular concern involves persons dually eligible

for Medicare and Medicaid, a population that

includes many with severe chronic mental illness.

To address this problem, CERTs researchers are

examining the provision, quality, and outcomes of

pharmaceutical care for beneficiaries with mental

illness under the Medicare Part D program.

Psychotropic therapy among children and

adolescents—Rates and use of psychotropic

medications among children and adolescents have

increased sharply in recent years, raising a number

of concerns related to safety, quality,

appropriateness, and management of these

regimens. Since there is considerable variation in

treatment patterns, studies are needed to examine

patterns across multiple States, especially for

economically disadvantaged children and

adolescents. CERTs researchers are examining

treatment patterns, predictors, and trends in the use

of psychotropic medications among child and

adolescent Medicaid patients.

25

CERTs Research Centers Added in 2006
SSRI use and suicidality in depressed children

and adolescents—Scientific uncertainty and

controversy continue over the possible impact and

magnitude of selective serotonin reuptake inhibitors

(SSRIs) on suicidality, particularly among depressed

youths. Recent analyses raise significant safety

concerns about such effects. Analyses of large

administrative databases such as Medicaid can

support informed treatment decisionmaking by

physicians, patients, families, and others.

Investigators are examining the rates of suicide and

suicide attempts in high-risk youths who received

treatment for depression with SSRIs.

Medical Devices

Impact of regionalization—Regionalization of

complex surgical procedures involves moving

patients from low-volume sites and moving surgeons

to high-volume sites. This may lead to better shortand long-term outcomes, but the impact on patient

populations, including rural and minority populations,

has not been assessed. CERTs researchers are

evaluating whether the regionalization of total joint

replacement procedures would lead to a reduction

of in-hospital adverse events.

Volume-outcome relationships—Automatic

implantable cardioverter defibrillators (AICDs) are

being used more frequently across a wide

population of patients with cardiovascular disease. It

is not clear whether physician and hospital

experience is associated with improved short-term

outcomes. CERTs investigators are conducting

research to determine whether there is a relation

between physician volume of AICD implantation and

short-term complication rates.

Prospective registry—Predictors of short- and

long-term outcomes from total joint replacement,

variations in outcomes across different models of

joint prostheses, and cost-effectiveness of joint

prosthetic devices are important areas of concern in

light of the growing use of these procedures in the

aging population. CERTs researchers are working to

determine the clinical, demographic, patient, and

device characteristics associated with improved

outcomes for patients undergoing total joint

replacement procedures.

Aging and the Elderly

Guideline implementation—Numerous studies

have documented that practitioners are not

providing care in a manner that conforms to clinical

practice guidelines. Blood pressure is controlled in

only 34 percent of patients with hypertension,

despite six sets of guidelines over the last 30 years.

Most cases of uncontrolled hypertension occur in

patients who are over 65 years of age with access

to health care and relatively frequent contact with

physicians. It is possible that physicians’ decisions

and behavior, rather than limited access to care,

may be factors contributing to poor blood pressure

control. Improving adherence to hypertension

guidelines is critical, but little information is available

about underlying factors that contribute to poor

adherence rates. Investigators are evaluating blood

pressure control and guideline adherence among

elderly patients. In addition, they are identifying

26
barriers to achieving and sustaining blood pressure

control and developing strategies for improvements

in blood pressure management.

Medical decisionmaking for persons with

lymphoma—Older adulthood is a time of complex

decisionmaking regarding medical issues. A

significant proportion of healthy older adults have

impaired cognitive decisionmaking abilities.

Cognitive studies have suggested age-related

declines in the amount of information used and in

the thoroughness of the information search process

undertaken by older adults engaged in various

decisionmaking tasks. Treatment decisionmaking is

particularly complex for the low-grade non-Hodgkin’s

lymphomas. A popular treatment choice

(anthracycline-based combinations of chemotherapy)

has the potential for significant morbidity, with

uncertain impact on long-term disease control.

Therefore, such patients must make difficult

treatment decisions (e.g., short-term cost vs. longterm benefit). Older patients may be at increased

risk for disadvantageous decisionmaking.

Investigators are evaluating which patient-related

variables predict both strong and poor

decisionmaking capacity. They are creating

abbreviated and extended “menus” of medical

treatment options that are appropriate for poor and

strong medical decisionmakers.

Botanical dietary supplements—There is growing

use of dietary supplements in the United States, with

sales for 2004 estimated at $19 billion. At least 15

million American adults are at potential risk for

interactions between botanical dietary supplements

and medications. Most physicians are not aware of

their patients’ use of botanical dietary supplements

and are not able to advise their patients because

they do not have sufficient knowledge about the

safety and effectiveness of these supplements. As

data become available, it is critical that they be

widely disseminated to consumers and health care

professionals. Investigators are developing new

venues for disseminating information about the

safety and efficacy of botanical dietary supplements

for the elderly.

27
ADHD Online Toolkit for Providers, Patients, and

Families: Web Tool

nichq.org/resources/toolkit

Arthritis Outcomes Initiative Resource for Patients

and Families: Web Resource

www.engalitcheff.uab.edu

Arthritis Self-Help for Patients: Web Site

www.arthritispatient.cme.uab.edu/

Beta-Blocker Fact Sheet for Providers

dukecerts.dcri.duke.edu

Challenging Cases in Musculoskeletal Medicine:

Online Education Course for Providers

www.giop.certs.cme.uab.edu/

Doubly Robust SAS Macro: Data Analysis Tool

HarryGuess.unc.edu

Drug Interaction Card: Reference Guide for Providers

and Patients

www.drug-interactions.com

Drugs That Prolong the QT Interval and/or Induce

Torsades de Pointes: List for Providers and Patients

www.qtdrugs.org

Harry Guess Virtual Research Community: WebBased Repository of Pediatric Therapeutics Tools

HarryGuess.unc.edu

Head and Chest Colds: Brochure for Patients

http:www.cceb.upenn.edu/cert/consumers.html

Medications That Interact with Methadone: Wallet

Card for Patients and Providers

www.arizonacert.org/methadone-card.pdf

Osteoporosis Management: Online Case-Based

Disease Education Program for Providers

www2.edserv.musc.edu/osteo/index.lasso

Over-the-Counter Medicine “Interaction” Cabinet: Web

Tool for Patients

www.arizonacert.org/consumers/MCsurvey/

router.asp

Preventable Adverse Drug Reactions—A Focus on

Drug Interactions: Education Course for Providers

www.arizonacert.org/medical-pros/education/

module01.cfm

REACH: REducing Antibiotics for CHildren: Education

for Providers, Patients, and Families

www.reachmass.org/

Safer Use of Nonsteroidal Anti-Inflammatory Drugs:

Online Education Course for Providers

www-cme.erep.uab.edu/nsaids/nsaids.html

Saving Lives with Beta-Blockers: CyberSession for

Providers

dukecerts.dcri.duke.edu

Tools and Techniques of Improved Medication Use:

Web Site for Providers

http://www.ahip.org/content/default.aspx?bc=

38|77|529

Treating Congestive Heart Failure with Beta-Blockers:

Brochure and Videotape for Patients

dukecerts.dcri.duke.edu

Understanding the QT Interval—Web-Based

Education Module for Providers

qtmodule.mc.duke.edu

NOTE: For additional information about CERTs

program resources, please contact the CERTs

Coordinating Center at certs@kpchr.org.

28

CERTs Program Resources

Public-private partnership is a cornerstone of the

CERTs program. Program activities are greatly

enhanced by working with partner organizations.

Collaboration among organizations with similar

missions is essential to accomplishing program

objectives. In addition to the many partnerships that

enable the CERTs centers to study issues

concerning therapeutics, the CERTs also collaborate

with other public and private organizations on

initiatives to support and enhance other program

projects.

Partnerships to Advance THerapeutics

(PATHs)

Established by the CERTs in 2001, the PATHs

program is a means to cultivate partnerships among

national organizations interested in promoting the

safe and effective use of therapeutics.

Every year, the CERTs host a meeting for PATHs

partners. Participating organizations represent

patients, health care providers, government,

academia, delivery systems, payers, purchasers,

and manufacturers of medical products.

The annual PATHs meeting provides a forum for

organizations to plan and implement goals related to

the improvement of therapeutics. With the expansion

of the program this year (four new centers were

added midyear), no annual meeting was held. In lieu

of the meeting, program activities focused on the

development of internal partnerships through a

comprehensive orientation process. As a core value

of the program, centers will continue to build upon

this strong base of partnership within the program

to help attract new external partners.

30

CERTs Partnerships and Collaborations

The PATHs program is an integral part of the CERTs program and exemplifies the value of public-private

partnership. See the list of project partners in this report. A registry of PATHs partner projects can be

accessed through the CERTs Web site at: www.certs.hhs.gov/partners/paths/regis/.
Partnership and CERTs Medical Devices

Workshop*

As published in the July 2006 issue of the American

Heart Journal, the CERTs convened a group of

experts to discuss the key issues affecting the

development and use of medical devices in this

country. Medical devices include products such as

coronary stents, glucose monitoring devices, and

joint prosthetic devices.

Although many new medical devices are available in

the United States, there are many knowledge gaps

concerning benefits and risks. This lack of

information impacts patients and physicians, as well

as decisionmakers at insurance companies and

government agencies. Everyone involved needs

sensible, evidence-based information to determine

which products offer the best long-term benefits

without unnecessary risks. These decisionmakers

need cost-benefit information when weighing policy

decisions so that they can be good stewards of

society’s health care dollars.

The United States would benefit from efficient ways

to evaluate medical devices. Given our aging

population, the number of patients in whom medical

devices could be used poses a significant impact to

the health care budget. The goal of the workshop

was to develop a list of ideas for future research

projects to improve our current system.

Representatives from the Centers for Medicare &

Medicaid Services, health services researchers,

practitioners, device manufacturers, and regulators

discussed various perspectives, issues, and hurdles

surrounding the limitations in knowledge about

medical devices. Funding shortages were identified

as a central issue; therefore, the group shared ideas

for developing better public-private partnerships to

help increase research funding. In addition, the

workshop participants discussed ideas for priority

setting, ways to improve current research methods,

and new approaches to integrate the Federal

agencies to address needs.

31

*Califf RM, for the Workshop Participants. Evaluation of diagnostic imaging technologies and therapeutics

devices: better information for better decisions: proceedings of a multidisciplinary workshop. Am Heart J

2006;152:50-8.

Although drugs and other therapeutic products have

improved the lives of many Americans, our current

health care system does not always guarantee that

they will be used safely and effectively, nor that all

adverse effects will be identified before they are put

on the market. Today, with more choices available

than ever before, people need independent,

unbiased information about the benefits and risks of

various therapeutic products. While government, the

medical products industry, and others have made

progress, vital questions remain unanswered. The

CERTs program was created to address this need

and continues to conduct research and disseminate

information about the benefits and risk of the various

therapeutic options available.

Whether the challenge is using technology to reduce

medical errors or developing ways to improve

communications to help people make more informed

decisions, CERTs researchers are undertaking

projects on a wide range of topics to improve

everyday health care for the American people.

This year the CERTs program expanded, with the

addition of four new centers and several new

partners. We look forward to increasing the scope

of our projects as we continue to advance

knowledge of medical therapeutics in ways that will

inform health care providers, patients, policymakers,

and others, leading to improvements in the safe and

effective use of therapeutics.

33

Conclusion
Agency for Healthcare Research and Quality

Center for Outcomes and Evidence (COE)

Rockville, Maryland

Director, COE: Jean R. Slutsky, PA, MSPH

Contact: Anne Trontell, MD, MPH

CERTs Program Director

Fax: 301-427-1520

E-mail: anne.trontell@ahrq.hhs.gov

Alternate contact: Carmen Kelly, PharmD, RPh

E-mail: carmen.kelly@ahrq.hhs.gov

Web: www.ahrq.gov

Coordinating Center

Duke University Medical Center

Durham, North Carolina

Principal Investigator: Robert M. Califf, MD

Web: www.certs.hhs.gov

Centers

Arizona CERT at The Critical Path Institute

(C-Path)

Tucson, Arizona

Principal Investigator: Raymond L. Woosley, MD, PhD

Contact: Linda Johnson

Fax: 520-547-3456

E-mail: ljohnson@c-path.org

Web: www.arizonacert.org

Duke University Medical Center

Durham, North Carolina

Principal Investigator: Judith M. Kramer, MD, MS

Contact: Nancy Allen LaPointe, PharmD

Fax: 919-668-7166

E-mail: allen003@mc.duke.edu

Web: https://dukecerts.dcri.duke.edu/

HMO Research Network

Boston, Massachusetts

Principal Investigator: Richard Platt, MD, MS

Contact: Kimberly Lane, MPH

Fax: 617-859-8112

E-mail: kimberly.lane@channing.harvard.edu

Web: www.certs.hhs.gov/centers/hmo.html

Rutgers, The State University of New Jersey

Newark, New Jersey

Principal Investigator: Stephen Crystal, PhD

Contact: Emily Peterson, MBA

Fax: 732-932-8579

E-mail: epeterson@ifh.rutgers.edu

Web: www.certs.hhs.gov/centers/rutgers.html

University of Alabama at Birmingham

Birmingham, Alabama

Principal Investigator: Kenneth G. Saag, MD, MSc

Contact: Mary Melton

Fax: 205-975-6859

E-mail: melkins@uab.edu

Web: www.uab.edu/certs

University of Iowa

Iowa City, Iowa

Principal Investigator: Elizabeth A. Chrischilles, PhD

Contact: Angela Kuehl, PharmD, MS

Fax: 319-335-8253

E-mail: angela-kuehl@uiowa.edu

Web: www.public-health.uiowa.edu/cert/

34

The CERTs Organization
University of North Carolina at Chapel Hill

Chapel Hill, North Carolina

Principal Investigator: Harry A. Guess, MD, PhD

(October-January)

Alan D. Stiles, MD (January-September)

Contact: Sue Tolleson-Rinehart, PhD

Fax: 919-966-2089

E-mail: stolleso@email.unc.edu

Web: www.certs.unc.edu; HarryGuess.unc.edu

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania

Principal Investigator: Brian L. Strom, MD, MPH

Contact: Judith L. Kinman, MA

Fax: 215-573-5315

E-mail: jkinman@cceb.med.upenn.edu

Web: www.cceb.upenn.edu/pages/cert/

University of Texas MD Anderson Cancer

Center and Baylor College of Medicine

Houston, Texas

Principal Investigator: Maria E. Suarez-Almazor, MD,

PhD

Contact: Carol Looney

Fax: 713-563-4491

E-mail: cmlooney@mdanderson.org

Web: www.certs.hhs.gov/centers/houston.html

Vanderbilt University Medical Center

Nashville, Tennessee

Principal Investigator: Wayne A. Ray, PhD

Contact: William O. Cooper, MD, MPH

Fax: 615-343-6249

E-mail: william.cooper@vanderbilt.edu

Web: www.certs.hhs.gov/centers/vanderbilt.html

Weill Cornell Medical Center

New York, New York

Principal Investigator: Alvin I. Mushlin, MD, ScM

Contact: Alvin I. Mushlin, MD, ScM

Fax: 212-746-8544

E-mail: aim2001@med.cornell.edu

Web: http://www.med.cornell.edu/cert

Steering Committee

Hugh H. Tilson, MD, DrPH

Chair, CERTs Steering Committee

Georges C. Benjamin, MD, FACP

Executive Director

American Public Health Association

Marc L. Berger, MD

Vice President, Outcomes Research and

Management

Merck & Company Inc.

Enriqueta C. Bond, PhD*

President

Burroughs Wellcome Fund

Lynn A. Bosco, MD, MPH

CERTs Program Officer

Agency for Healthcare Research and Quality

Janice K. Bush, MD*

Vice President, Quality, Education, and Business

Support

Johnson & Johnson Pharmaceutical Research and

Development

35

*Alternate member
Robert M. Califf, MD

Principal Investigator

CERTs Coordinating Center

Elizabeth A. Chrischilles, PhD

Principal Investigator

University of Iowa

(April-September)

Stephen Crystal, PhD

Principal Investigator

Rutgers, The State University of New Jersey

(April-September)

Susan N. Gardner, PhD

Director, Office of Surveillance and Biometrics

Center for Devices and Radiological Health

U.S. Food and Drug Administration

Harry A. Guess, MD, PhD

Principal Investigator

University of North Carolina at Chapel Hill

(October-January)

Judith M. Kramer, MD, MS

Principal Investigator

Duke University Medical Center

Alvin I. Mushlin, MD, ScM

Principal Investigator

Weill Cornell Medical Center

(April-September)

Richard Platt, MD, MS

Principal Investigator

HMO Research Network

Wayne A. Ray, PhD

Principal Investigator

Vanderbilt University Medical Center

Kenneth G. Saag, MD, MSc

Principal Investigator

University of Alabama at Birmingham

Marcel E. Salive, MD, MPH

Director

Division of Medical & Surgical Services

Centers for Medicare & Medicaid Services

(October-April)

David G. Schulke

Executive Vice President

American Health Quality Association

Paul J. Seligman, MD, MPH

Associate Director for Safety Policy and

Communication

Center for Drug Evaluation and Research

U.S. Food and Drug Administration

Scott R. Smith, RPh, PhD

Senior Service Fellow for Pharmaceutical Outcomes

Research

Agency for Healthcare Research and Quality

Steven L. Solomon, MD

Associate Director for Healthcare Systems

Centers for Disease Control and Prevention

(Alternate Member: October-April)

36
Alan D. Stiles, MD

Principal Investigator

University of North Carolina at Chapel Hill

(January-September)

Brian L. Strom, MD, MPH

Principal Investigator

University of Pennsylvania School of Medicine

Maria E. Suarez-Almazor, MD, PhD

Principal Investigator

University of Texas MD Anderson Cancer Center and

Baylor College of Medicine

(April-September)

Myrl Weinburg, CAE

President

National Health Council

Raymond L. Woosley, MD, PhD

Principal Investigator

Arizona CERT at The Critical Path Institute (C-Path)

37

Issues of Public Interest. CERTs is a national

initiative to foster the optimal use of therapeutics

through research and education activities that are in

the public interest but would not otherwise be done.

Public-Private Partnership. CERTs is a publicprivate partnership on two levels: (1) between the

U.S. Department of Health and Human Services and

the CERTs centers and (2) between CERTs centers

as representatives of the government-sponsored

CERTs program and other research-sponsoring

organizations. In the latter relationship, the CERTs

centers seek useful, appropriate interactions with

private organizations to support and enhance

education, research, and demonstration projects.

AHRQ works with the centers to establish

appropriate agreements to optimize use and sharing

of resources.

Conflicts of Interest. Public-private partnerships

typically present the potential for conflicts of

interest. While these potential conflicts of interest

cannot be completely avoided or eliminated, a

CERTs center has an obligation to disclose fully and

to manage conflicts in a manner that minimizes the

risk of those conflicts, while at the same time

permitting as much progress as possible to achieve

CERTs goals within the constraints of maintaining

respected research activity.

Academic Integrity. As academic researchers,

individuals conducting projects under the CERTs

umbrella make the final decision about study design,

analysis, conclusions, and publication in any

partnership with other organizations and ensure that

their work complies with their respective institutions’

conflict-of-interest rules.

Activities. CERTs activities are defined as projects

supported in whole or in part by AHRQ funds under

the CERTs demonstration program. Activities such

as the review of potential conflicts of interest are

subject to processes established for the CERTs

program. Individuals affiliated with the centers also

conduct education and research activities outside of

CERTs that are not subject to CERTs processes.

39

Principles of CERTs Public-Private Partnerships
We gratefully acknowledge the

following organizations for their

expertise and support of

CERTs research and education

projects:

Academic Medicine and

Managed Care Forum

AccessCare, Inc.

Advanced Medical Technology

Association

Aetna Inc.

Agency for Healthcare

Research and Quality

Agouron Pharmaceuticals, Inc.

Alabama Chapter of the

American College of Physicians

Alabama Department of Public

Health

Alabama Practice-based

Continuing Medical Education

and Research Network

Alacare Home Health Care

American Academy of Family

Physicians

American Academy of

Pediatrics

American Association of

Colleges of Pharmacy

American College of Cardiology

American College of Clinical

Pharmacy

American College of

Rheumatology

American Heart Association

American Pharmaceutical

Association Foundation

American Pharmacists

Association

America’s Health Insurance

Plans

Amgen

Arizona Area Health Education

Centers

Arthritis Foundation

Arthritis Foundation, Alabama

Chapter

Arthritis Foundation, Maryland

Chapter

AstraZeneca

Aventis, Inc.

Berlex, Inc.

Blue Cross/Blue Shield of

Alabama

Bowman Gray School of

Medicine

Brigham and Women’s Hospital

Bristol-Myers Squibb Company

Bureau of TennCare

Cancer Research Network

Caremark

Carolina Medical Review

Center for Health Care Policy

and Evaluation/UnitedHealth

Group

Centers for Disease Control

and Prevention

Centers for Disease Control

and Prevention Foundation

Centers for Medicare &

Medicaid Services

Children’s National Medical

Center

Cincinnati Children’s Hospital

Medical Center

Columbus Children’s Hospital

Community Cares of North

Carolina

Community Health Centers

Computer Sciences

Corporation (CSC)/Clinical Data

Abstraction Center (CDAC)

Conceptis Technologies

Council for Affordable Quality

Healthcare

Critical Path Institute (The)

Crohn’s & Colitis Foundation of

America

Department of Veterans Affairs

Duke Clinical Research Institute

Duke Educational Media

Services

Duke Heart Center

Duke Infection Control

Outreach Network

Duke University Department of

Psychology

40

CERTs Project Partners
Duke University Health System

Eli Lilly and Company

Express Scripts, Inc.

Fallon Community Health Plan

Genentech, Inc.

General Practice Research

Database/EPIC

Georgetown University

GlaxoSmithKline

Group Health Cooperative of

Puget Sound

Harvard Pilgrim Health Care

Harvard School of Medicine

Harvard School of Public Health

Harvard Vanguard Medical

Associates

Health Resources and Services

Administration

HealthPartners

Henry Ford Health System

IMS Health

Infectious Diseases Society of

America

Institute for Healthcare

Improvement

Institute of Medicine

Integrative Pain Center of

Arizona

International Society for

Pharmacoepidemiology

Iowa Women’s Health Study

Janssen Pharmaceutica

John A. Hartford Foundation

Kaiser Permanente Colorado

Kaiser Permanente Georgia

Kaiser Permanente Northern

California

Kaiser Permanente Northwest

Kaiser Permanente Southern

California

La Frontera Hope Center

Lincoln Technologies

Massachusetts Department of

Public Health

Massachusetts Division of

Medical Assistance

Medco Health Solutions

Medical Review of North

Carolina, Inc.

Medtronic MiniMed, Inc.

Merck

Nanogen, Inc.

National Committee for Quality

Assurance

National Foundation for

Infectious Diseases

National Health and Medical

Research Council Clinical Trials

Centre, Sydney, Australia

National Initiative for Children’s

Healthcare Quality

National Institutes of

Health/National Cancer Institute

National Institutes of

Health/National Institute of

Allergy and Infectious Diseases

National Institutes of

Health/National Institute of

Arthritis and Musculoskeletal

and Skin Diseases

National Institutes of

Health/National Institute of

Diabetes & Digestive & Kidney

Diseases

National Institutes of

Health/National Institute of

General Medical Sciences

National Institutes of

Health/National Institute of

Mental Health

National Institutes of

Health/National Institute of

Nursing Research

National Institutes of

Health/National Institute on

Aging

National Institutes of

Health/Office of Research on

Women’s Health

National Patient Safety

Foundation

North Carolina Access Care

North Carolina Area Health

Education Centers

41
North Carolina Association of

Pharmacists

North Carolina Center for

Children’s Healthcare

Improvement

North Carolina Department of

Health and Human Services

North Carolina Medicaid

North Carolina State Children’s

Health Insurance Program

North Carolina Women, Infants,

and Children Program

Ortho-McNeil Pharmaceutical,

Inc.

Parke-Davis Pharmaceutical

Pediatric Research in Office

Settings

Penn Center for AIDS Research

Pennsylvania Department of

Public Health

Pennsylvania Pharmaceutical

Assistance Contract for the

Elderly

Pfizer Inc.

Pharmaceutical Research and

Manufacturers of America

Pharmacia & Upjohn

Pharmacogenetics Network

Premier

Proctor and Gamble

ProVantage Health Services,

Inc.

QED Solutions, Incorporated

Reliant Pharmaceuticals, Inc.

Robert Wood Johnson

Foundation

Roche Laboratories, Inc.

RTI Health Solutions

RTI International

SAS

Society for Healthcare

Epidemiology of America

Society for Women’s Health

Research

Society of Thoracic Surgeons

South Carolina Office of

Research and Statistics

Southeastern Regional

Osteoporosis Board

TAP Pharmaceutical Products,

Inc.

Tennessee Department of

Health

UCLA/RAND Center for

Adolescent Health Promotion

U.S. Department of Health and

Human Services/Office on

Women’s Health

U.S. Food and Drug

Administration

U.S. Food and Drug

Administration/Office of

Women’s Health

U.S. Public Health Service

U.S. Quality Algorithms, Inc.

United Mine Workers of

America Health and Retirement

Funds

United States Pharmacopeial

Convention, Inc.

UnitedHealthcare of Alabama

University of Arizona

Department of Communication

University of Arizona National

Center of Excellence in

Women’s Health

University of Arizona Poison

and Drug Information Center

University of Illinois at Chicago

University of Massachusetts

Medical School

University of Pennsylvania

Health System

University of Pennsylvania

School of Medicine

University of Texas Health

Science Center at San Antonio

University of Washington

Wake Forest Baptist Medical

Center

Walgreens Co.

WellPoint, Inc.

Whitehall-Robbins Inc.

Wyeth

Wyeth-Ayerst Laboratories

42
Referenced Publications

1. Johnson L, Strich H, Taylor

A, Timmermann B, Malone

D, Teufel-Shone N,

Drummond R, Woosley R,

Pereira E, Martinez A. Use of

herbal remedies by diabetic

Hispanic women in the

southwestern United States.

Phytother Res 2006;20:250-

5.

2. MacAdam H, Zaoutis TE,

Gasink LB, Bilker WB,

Lautenbach E. Investigating

the association between

antibiotic use and antibiotic

resistance: impact of

different methods of

categorising prior antibiotic

use. Int J Antimicrob Agents

2006;28:325-32.

3. Kramer JM, Hammill B,

Anstrom KJ, Fetterolf D,

Snyder R, Charde JP,

Hoffman BS, Allen LaPointe

N, Peterson E. National

evaluation of adherence to

beta-blocker therapy for 1

year after acute myocardial

infarction in patients with

commercial health

insurance. Am Heart J

2006;152:454.e1-8.

4. Newby LK, LaPointe NM,

Chen AY, Kramer JM,

Hammill BG, DeLong ER,

Muhlbaier LH, Califf RM.

Long-term adherence to

evidence-based secondary

prevention therapies in

coronary artery disease.

Circulation 2006;113:203-

12.

5. Curtis JR, Olivieri J, Allison

JJ, Gaffo A, Juarez L, Kovac

SH, Person S, Saag KG. A

group randomized trial to

improve safe use of

nonsteroidal antiinflammatory drugs. Am J

Manag Care 2005;11:537-

43.

6. Cooper WO, Hernandez-Diaz

S, Arbogast PG, Dudley JA,

Dyer S, Gideon PS, Hall K,

Ray WA. Major congenital

malformations after firsttrimester exposure to ACE

inhibitors. N Engl J Med

2006;354:2443-51.

7. Lagarde WH, Barrows FP,

Davenport ML, Kang M,

Guess HA, Calikoglu AS.

Continuous subcutaneous

glucose monitoring in

children with type 1 diabetes

mellitus: a single-blind,

randomized, controlled trial.

Pediatr Diabetes

2006;7:159-64.

8. Metlay JP, Fishman NO, Joffe

M, Edelstein PH. Impact of

pediatric vaccination with

pneumococcal conjugate

vaccine on the risk of

bacteremic pneumococcal

pneumonia in adults. Vaccine

2006;24:468-75.

9. Halpern SD, Asch DA,

Shaked A, Stock P,

Blumberg EA. Inadequate

hepatitis B vaccination and

post-exposure evaluation

among transplant surgeons:

prevalence, correlates, and

implications. Ann Surg

2006;244:305-9.

10. LaPointe NM, DeLong ER,

Chen A, Hammill BG,

Muhlbaier LH, Califf RM,

Kramer JM. Multifaceted

intervention to promote betablocker use in heart failure.

Am Heart J 2006;151:992-

8.

11. Shatin D, Rawson NS, Curtis

JR, Braun MM, Martin CK,

Moreland LW, Becker AF,

43

Peer-Reviewed Publications:

October 1, 2005-September 30, 2006
Patkar NM, Allison JJ, Saag

KG. Documented tuberculin

skin testing among infliximab

users following a multi-modal

risk communication

interventions.

Pharmacoepidemiol Drug

Saf 2006;15:11-8.

12. Abdolrasulnia M, Weichold N,

Shewchuk R, Saag K,

Cobaugh DJ, LaCivita C,

Weissman N, Allison J.

Agreement between medical

record documentation and

patient-reported use of

nonsteroidal antiinflammatory drugs. Am J

Health Syst Pharm

2006;63:744-7.

13. Curtis JR, Westfall AO,

Allison J, Freeman A, Kovac

SH, Saag KG. Agreement

and validity of pharmacy

data versus self-report for

use of osteoporosis

medications among chronic

glucocorticoid users.

Pharmacoepidemiol Drug

Saf 2006;15:710-8.

14. McPhillips HA, Stille CJ,

Smith D, Hecht J, Pearson J,

Stull J, Debellis K, Andrade

S, Miller M, Kaushal R,

Gurwitz J, Davis RL.

Potential medication dosing

errors in outpatient

pediatrics. J Pediatr

2005;147:761-7.

15. Indik JH, Pearson EC, Fried

K, Woosley RL. Bazett and

Fridericia QT correction

formulas interfere with

measurement of druginduced changes in QT

interval. Heart Rhythm

2006;3:1003-7.

16. Mikuls TR, Curtis JR, Allison

JJ, Hicks RW, Saag KG.

Medication errors with the

use of allopurinol and

colchicine: a retrospective

study of a national,

anonymous Internetaccessible error reporting

system. J Rheumatol

2006;33:562-6.

17. Curtis JR, Westfall AO,

Allison J, Bijlsma JW,

Freeman A, George V, Kovac

SH, Spettell CM, Saag KG.

Population-based

assessment of adverse

events associated with longterm glucocorticoid use.

Arthritis Rheum

2006;55:420-6.

18. Feldstein AC, Smith DH,

Perrin N, Yang X, Simon SR,

Krall M, Sittig DF, Ditmer D,

Platt R, Soumerai SB.

Reducing warfarin

medication interactions: an

interrupted time series

evaluation. Arch Intern Med

2006;166:1009-15.

19. Abarca J, Malone DC,

Skrepnek GH, Rehfeld RA,

Murphy JE, Grizzle AJ,

Armstrong EP, Woosley RL.

Community pharmacy

managers’ perception of

computerized drug-drug

interaction alerts. J Am

Pharm Assoc (Wash DC)

2006;46:148-53.

20. Murphy JE, Malone DC,

Skrepnek GH, Armstrong EP,

Abarca J, Grizzle AJ, Rehfeld

RA, Woosley RL. The role of

technicians in managing

computerized drug-drug

interaction alerts in

community pharmacies and

the relationship to

pharmacist managers’

attitudes. J Pharm Technol

2005;22:155-60.

44
21. Perkins NA, Murphy JE,

Malone DC, Armstrong EP.

Performance of drug-drug

interaction software for

personal digital assistants.

Ann Pharmacother

2006;40:850-5.

22. Ko Y, Brown ML, Frost R,

Woosley RL. Brief report:

development of a

prescription medication

information webliography for

consumers. J Gen Intern

Med 2006;31:1313-6.

23. Ridley DB, Kramer JM, Tilson

HH, Grabowski HG,

Schulman KA. Spending on

postapproval drug safety.

Health Aff (Millwood)

2006;25:429-36.

24. Roblin DW, Platt R, Goodman

MJ, Hsu J, Nelson WW,

Smith DH, Andrade SE,

Soumerai SB. Effect of

increased cost-sharing on

oral hypoglycemic use in five

managed care organizations:

how much is too much? Med

Care 2005;43:951-9.

25. Skrepnek GH, Abarca J,

Malone DC, Armstrong EP,

Shirazi FM, Woosley RL.

Incremental effects of

concurrent

pharmacotherapeutic

regimens for heart failure on

hospitalizations and costs.

Ann Pharmacother

2005;39:1785-91.

Additional Publications

Abdolrasulnia M, Weichold N,

Shewchuk R, Saag K,

Cobaugh DJ, LaCivita C,

Weissman N, Allison J.

Agreement between medical

record documentation and

patient reported use of

nonsteroidal

antiinflammatory drugs. Am

J Health Syst Pharm

2006;63:744-7.

Albrecht SJ, Fishman NO,

Kitchen J, Nachamkin I,

Bilker WB, Hoegg C, Samuel

C, Barbagallo S, Arentzen J,

Lautenbach E. Reemergence

of gram-negative health careassociated bloodstream

infections. Arch Intern Med

2006;166:1289-94.

Allen LaPointe NM, Curtis

LH, Chan KA, Kramer JM,

Lafata JE, Gurwitz JH,

Raebel MA, Platt R.

Frequency of high-risk use of

QT-prolonging medications.

Pharmacoepidemiol Drug

Saf 2006;15:361-8.

Apter AJ, Kinman JL, Bilker

WB, Herlim M, Margolis DJ,

Lautenbach E, Hennessy S,

Strom BL. Is there crossreactivity between penicillins

and cephalosporins? Am J

Med 2006;119:354.e11-19.

Bradburn MJ, Deeks JJ,

Berlin JA, Localio AR. Much

ado about nothing: a

comparison of the

performance of metaanalytical methods with rare

events. Stat Med

2007;26:53-77 (Published

online April 2006).

Criswell LA, Saag KG, Mikuls

TR, Cerhan JR, Merlino LA,

Lum RF, Pfeiffer KA, Woehl

B, Seldin MF. Smoking

interacts with genetic risk

factors in the development

of rheumatoid arthritis

among older Caucasian

women. Ann Rheum Dis

2006;65:1163-7.

45

Curtis JR, Westfall AO,

Allison JJ, Freeman A, Saag

KG. Channeling and

adherence with alendronate

and risedronate among

chronic glucocorticoid users.

Osteoporos Int

2006;17:1268-74.

Gasink LB, Fishman NO,

Weiner MG, Nachamkin I,

Bilker WB, Lautenbach E.

Fluoroquinolone-resistant

Pseudomonas aeruginosa:

assessment of risk factors

and clinical impact. Am J

Med 2006;119:526.e19-25.

Gross R, Zhang Y, Grossberg

R. Medication refill logistics

and refill adherence in HIV.

Pharmacoepidemiol Drug

Saf 2005;14:789-93.

Guess HA. Exposure-timevarying hazard function

ratios in case-control studies

of drug effects.

Pharmacoepidemiol Drug

Saf 2006;15:81-92.

Harrold LR, Yood RA, Mikuls

TR, Andrade SE, Davis J,

Fuller J, Chan KA, Roblin D,

Raebel MA, VonWorley A,

Platt R, Saag KG. Sex

differences in gout

epidemiology: evaluation and

treatment. Ann Rheum Dis

2006;65:1368-72

(Published online April

2006).

Hass DJ, Lewis JD. Quality

of manufacturer provided

information on safety and

efficacy claims for dietary

supplements for colonic

health. Pharmacoepidemiol

Drug Saf 2006;15:578-86.

Hicks RW, Becker SC,

Cousins DD. Harmful

medication errors in children:

a 5-year analysis of data

from the USP’s MEDMARX

program. J Pediatr Nurs

2006;21:290-8.

Katchman AN, Koerner J,

Tosaka T, Woosley RL, Ebert

SN. Comparative evaluation

of HERG currents and QT

intervals following challenge

with suspected torsadogenic

and nontorsadogenic drugs.

J Pharmacol Exp Ther

2006;316:1098-106.

Kovac SH, Mikuls TR,

Mudano A, Saag KG. Healthrelated quality of life among

self-reported arthritis

sufferers: effects of

race/ethnicity and residence.

Qual Life Res 2006;15:451-

60.

Lautenbach E, Fishman NO,

Metlay JP, Mao X, Bilker WB,

Tolomeo P, Nachamkin I.

Phenotypic and genotypic

characterization of fecal

Escherichia coli isolates with

decreased susceptibility to

fluoroquinolones: results

from a large hospital-based

surveillance initiative. J Infect

Dis 2006;194:79-85.

Lautenbach E, Metlay JP,

Bilker WB, Edelstein PH,

Fishman NO. Association

between fluoroquinolone

resistance and mortality in

Escherichia coli and

Klebsiella pneumoniae

infections: the role of

inadequate empirical

antimicrobial therapy. Clin

Infect Dis 2005;41:923-9.

Linkin DR, Paris S, Fishman

NO, Metlay JP, Lautenbach

E. Inaccurate

communications in telephone

calls to an antimicrobial

stewardship program. Infect

Control Hosp Epidemiol

2006;27:688-94.

47
Lipworth AD, Hyle EP,

Fishman NO, Nachamkin I,

Bilker WB, Marr AM, Larosa

LA, Kasbekar N, Lautenbach

E. Limiting the emergence of

extended-spectrum Betalactamase-producing

enterobacteriaceae:

influence of patient

population characteristics on

the response to antimicrobial

formulary interventions.

Infect Control Hosp

Epidemiol 2006;27:279-86.

Malone DC, Hutchins DS,

Haupert H, Hansten P,

Duncan B, Van Bergen RC,

Solomon SL, Lipton RB.

Assessment of potential

drug-drug interactions with a

prescription claims

database. Am J Health Syst

Pharm 2005;62:1983-91.

Mizuta M, Linkin DR,

Nachamkin I, Fishman NO,

Weiner MG, Sheridan A,

Lautenbach E. Identification

of optimal combinations for

empirical dual antimicrobial

therapy of Pseudomonas

aeruginosa infection:

potential role of a

Combination Antibiogram.

Infect Control Hosp

Epidemiol 2006;27:413-5.

Pearson EC, Woosley RL. QT

prolongation and torsades

de pointes among

methadone users: reports to

the FDA spontaneous

reporting system.

Pharmacoepidemiol Drug

Saf 2005;14:747-53.

Skrepnek GH, Armstrong EP,

Malone DC, Abarca J,

Murphy JE, Grizzle AJ,

Rehfeld RA, Woosley RL.

Workload and availability of

technology in metropolitan

community pharmacies. J

Am Pharm Assoc (Wash DC)

2006;46:154-60.

Wagner AK, Chan KA,

Dashevsky I, Raebel MA,

Andrade SE, Lafata JE,

Davis RL, Gurwitz JH,

Soumerai SB, Platt R. FDA

drug prescribing warnings: is

the black box half empty or

half full? Pharmacoepidemiol

Drug Saf 2006;15:369-86.

48

U.S. Department of

Health and Human Services

Agency for Healthcare Research and Quality

540 Gaither Road

Rockville, Maryland 20850

www.ahrq.gov

AHRQ Pub. No. 09-0063

May 2009