# Presentation: 884718

## FDA Hearing on Drug Safety and the Rosiglitazone Controversy

**Richard Hellman, MD, FACP, FACE**
- President,
- American Association of Clinical Endocrinologists
- Clinical Professor of Medicine
- University of Missouri/Kansas City School of Medicine
- Member, Executive Committee
- Physician Consortium for Performance Improvement
**July 30, 2007**

## The Unanswered Questions Regarding Rosiglitazone

- Why were epidemiologic studies regarding special high risk populations not yet complete?
- Why were there relatively few comparative studies of efficacy?
- Why were the clinical trials available not adequately powered to test for cardiovascular risk?
- Were these shortcomings in safety data unique to rosiglitazone?

## The problem highlighted by rosiglitazone is a system problem – the shortcomings of our national post-approval drug safety surveillance .

## Post-approval Drug Safety Issues

- As the patient pool becomes much larger, uncommon but serious side effects will be more evident, _but only if data is captured_
- High risk populations or special ethnic groups may need special monitoring
- The longer duration of drug exposure may lead to new risks for the patient and new challenges for surveillance
- The widespread use of the approved drug is very variable and often substandard

## Post-approval Drug Safety

- Funding at present is problematic:
- The FDA is seriously under-funded
- The Prescription Drug User Fee Act (PDUFA) is not yet adequate for all needed safety and efficacy studies
- There is an inherent conflict of interest when the pharmaceutical company that created the drug provides nearly all of the funds for the post-approval drug safety research and monitoring
- Post-approval drug safety funding from major foundations and from NIH, AHRQ, and FDA is very limited

## Loscalzo J. N Engl J Med 2006:354:1665-1667

**Loscalzo J. N Engl J Med 2006:354:1665-1667**

## Drug Safety Systems Issues

- Drug safety is not a given – it is not an inherent feature of most medical systems
- There is a lack of easy-to-use educational resources on drug safety and efficacy which are available on demand, at the point of care
- Limited funds to teach all those involved in drug safety as to how to best protect against patient injury
- The cost of maintaining drug safety is rarely planned for in clinical settings
- Inadequate electronic information systems for physicians, pharmacists, FDA, and CMS

## Current Drug Safety System

***PATIENT INJURY***

***POTENTIAL RISK FOR PATIENT***

**FDA**

## “CULTURE OF SAFETY”

**Initial physician orders**

**Unintended **
**Injury**

**No injury**

**Nurse **
**on**
**team**

**   ****Back-up**
**check **
**by peer**

**TIME**

**CORRECTION**
**BY**
**PHYSICIAN**

**Intended **
**therapeutic**
**result**

**Scope of awareness**

**Defective culture**
**No Barriers**

**“****Culture of safety”**

- Richard Hellman ©2005

## “CULTURE OF SAFETY” with system under stress

**Initial physician orders**

**Unintended **
**Injury**

**No injury**

**Nurse **
**on**
**team**

**Back-up**
**check **
**by peer**

**TIME**

**CORRECTION**
**BY**
**PHYSICIAN**

**Intended **
**therapeutic**
**result**

**Scope of awareness**

**Defective culture**
**No Barriers**

**Unintended **
**Injury**

- Richard Hellman ©2005

## Drug Safety

- Data collection is inadequate
- The power of informatics to provide high quality epidemiologic data is hampered by the small number of medical centers and physicians using EMR’s
- The forms provided for reporting data are impractical and are seriously underutilized

## Cognitive Issues Interfere With Drug Safety

- Patients frequently neither know what they are taking nor how _best_ to use it safely
- Physicians and allied health professionals often are _not knowledgeable_ about the medications they use in practice and their hazards
- Medication reconciliation is seldom done well – often, at the most crucial moment, no one is fully aware of what has or has not been taken by the patient

## Proposed Solutions

- Make drug safety a collective responsibility
- Funding should be from industry, government and foundations
- Increase FDA funding for post-approval drug safety
- Increased responsibility and budget for NIH and AHRQ for post-approval drug safety research RTC’s, case-control and epidemiologic studies
- Increased involvement of physician groups, patient groups and allied health groups in attaining and maintaining drug safety
- Robust information technology systems to support such an effort

## Improved Drug Safety System

***PATIENT INJURY***

**FDA**

**AHRQ & NIH**

**Physician Organizations**

**Allied Health Organizations**

**Patient Organizations**

***POTENTIAL RISK FOR PATIENT***

**Adapted from Dr. James Reason**