# Presentation: 878030

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***Public Hearing on CDER's ***
***Current Risk Communication Strategies for Human Drugs***
**December 7 & 8, 2005**

- Stephen A. Goldman, M.D., FAPM, FAPA
- Managing Member
- Stephen A. Goldman Consulting Services, LLC
- Morris Plains, New Jersey, USA
*Former Medical Director, MedWatch*
*U.S. Food and Drug Administration*
- sagcs@aol.com
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**©****Stephen A. Goldman Consulting Services, LLC ****2005****All rights reserved. No part of this presentation may be reproduced in any material form without the written permission of the copyright holder.**

*How easily accessible and understandable are FDA's Internet-based sources of drug information?*
*What are the strengths and weaknesses of  communication tools listed:*
- Patient and Healthcare Professional Information Sheets
- Talk Papers
- Public Health Advisories (PHAs)
- Press Releases
- MedWatch Safety Updates
- Patient Safety News program* *
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*What information is available about awareness, use, and perceptions of effectiveness by health care professionals and by public in general?*
*Do these tools provide right kind and amount of risk and other information that*
- Health professionals need to make informed decisions about whether to prescribe drug products,
- 					*AND *
- Public needs to make informed decisions about whether to use those products?
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*“**Fellow citizens, we cannot escape history.”*
- Abraham Lincoln, President of the United States, *Second Annual Message to Congress *(December 1, 1862)* *

## Accessibility

- Documents readily available on FDA website, so apparently follows they are easily accessible
- However, health professionals and consumers need to_ know_ material posted and how to navigate website
- Methods
- MedWatch Partners:
- Expands notification and information dissemination
- FDA's free e-mail listservs, e.g.,
- MedWatch
- CDER Consumer Information
- FDA Drug Information
- FDA Consumer
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- 	**Goldman SA. Communication of medical product risk: how effective is effective enough? **
**	*****Drug Safety***** 2004;27:519-534**1
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## Critical Questions1

- Labeling changes/large-scale health professional notification: *are they effective, and what is standard for effectiveness?*
- Interventions to improve medication use: *do they actually result in modified behavior?*
- Educational efforts regarding medical product risk: *do they make any difference?*
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## Labeling Changes/Large-Scale Health Professional Notification1

***Disparate Categories of Risk**** *
***Drug-drug interactions*** (terfenadine; cisapride)
***Off-label use*** (bromfenac)
***Recommended blood test monitoring*** (troglitazone)
***Teratogenicity*** (acitretin)
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## Drug-Drug Interactions: Cisapride   

***Coprescription with Contraindicated Meds ***
*After notification*:
- 3.4% overlap of cisapride with at least 1 contraindicated drug2
- 3.1% of patients used  1 potentially interacting drug(s)3
*After implementation of computerized alerting system*4
- Decrease from 9% to 3.1% in proportion of patients receiving contraindicated drug with cisapride
- Discharge on potentially hazardous drug combination: 36.2% to 7.7%**	**** **
**2****Jones JK, et al. *****JAMA***** 2001;286:1607-1609**
**3****De Bruin ML, et al. *****Ann Pharmacother***** 2002;36:338-343**
**4****McMullin ST, et al. *****Arch Intern Med***** 1999;159:2077-2082**** ****	**** ****	**** **
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## Drug-Drug Interactions: Cisapride   

- Impact on desired standard of care seen as demonstrating notification to have been almost total failure5
- Effect of notification content6
*1998*: 58%  in concomitant dispensing w/drugs specifically denoted as contraindicated, but not those exemplifying/implied as members of drug class
- 1999 letter stressing proscribed medical conditions had no discernible effect on coprescription
- 	***Findings seen as indicative of tantamount importance of wording to actual content in altering physician behavior***
**5****Smalley W, et al. *****JAMA***** 2000;284:3036-3039****	**
**6****Weatherby LB, et al. *****Clin Pharmacol Ther***** 2002 Dec;72:735-742**
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## Notification Wording/Content   

- Apparent key features of successful drug notification:
- Specificity	Prominence
- Brevity		Does not depend on secondary information
- Publicity	Personal discussions6
- Do content, organization and formatting of Dear Doctor letters affect physician response?
- Deficient areas identified
- Clarity
- Readability
- Proportion of perceived relevant information to supporting information
- Easy discernability of critical information
- Preference for letters with formatting that highlights key information7
**7****Mazor KM, et al. *****Pharmacoepidemiol Drug Saf***** 2005;14:869-875**
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## Information Provided to Health Professionals and Consumers  

***Low Molecular Weight Heparins (LMWHs)/Heparinoids***
***12/97***: FDA releases PHA of reported epidural/spinal hematomas in association with LMWHs and spinal/epidural or LP, w/subsequent neurologic injury (including long-term/permanent paralysis)8*** ***
***2/98***: 2/5/98 Advisory Committee transcript posted on website
***5/98***: Q & A’s re LMWHs/heparinoids and spinal/epidural anesthesia released, with updated safety information provided9:
- Common clinical aspects
- Signs/symptoms of spinal/epidural hematoma in reports
- Factors to consider in performing procedures
- Where to find further information
**8****Lumpkin MM. FDA Public Health Advisory. December 15, 1997**
**9****FDA. Q & A’s: Low Molecular Weight Heparins/Heparinoids and Spinal/Epidural Anesthesia. May 6, 1998**
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## Information Provided to Health Professionals and Consumers  

***COX-2 Selective and Non-Selective NSAIDs***
***April 7, 2005***: FDA announces planned regulatory actions  for valdecoxib, celecoxib & prescription/OTC NSAIDs10
**Public Health Advisory**
**Drug Information Page**
**Q’s and A’s**
- Product-specific information, including
- Perceived benefit/risk profiles
- Requested labeling changes (including boxed warnings)
- Related issues (e.g., Advisory Committees; informational basis for FDA decisions)
**10****www.fda.gov/medwatch/SAFETY/2005/safety05.htm**
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## Information Provided to Health Professionals and Consumers  

***NSAIDs***
***June 15, 2005***: FDA issues supplemental request letters to sponsors of all NSAIDs asking for labeling changes for their products, and posts on website11
***Prescription***:
**Supplemental request letter**
**Labeling template**** **
**Medication Guide (which uses Q’s and A’s format)**
***OTC***:
**Supplemental request letter and labeling template**** **
**11****www.fda.gov/cder/drug/infopage/COX2/default.htm**
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## Teratogenicity: Acitretin12

- Adequate dissemination from health authorities/company/ professional association to health professionals, but despite use of multi-media approach to inform those at risk:
- Personal contact with health professional (35% never contacted), *and/or*
- Media (press, radio, TV)
- 45% read in newspaper (57% of regular readers couldn’t recall message)
- 60% followed message on radio and TV (35% couldn’t recall message)
- 9% of women at risk did not use any contraception method
- Effect seen as moderate, with recall of message 6-12 months after warning low
*	**Overall effectiveness deemed poor because of *
*	**insufficient personal communication with those at risk*12
**12****Sturkenboom MCJM,***** *****et al. *****Eur J Clin Pharmacol***** 1994;47:125-132**
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## Multifacted Approach13

- Notable decrease in flucloxacillin use (desired due to association with adverse hepatic reactions) in relation to various interventions seen as resulting from combination of actions, rather than any individual event
- Caution that evaluation by any one organization of its intervention without consideration of other factors might lead to false conclusion, in either very positive or negative direction
- Sustaining of desired change entails coordination of activities and ensuring concordance of all (educational, regulatory, promotional) disseminated messages13
**13****Roughead EE, Gilbert AL, Primrose JG. *****Soc Sci Med***** 1999;48:845-853**
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## Risk Communication Effectiveness: Physician to Patient 

- Social influences on responses to health risk information about which physicians should be aware:
- Extent to which informational source is trusted
- Relevance of information to everyday life/decision-making
- Relation to other understood risks
- Concordance with prior knowledge/experience
- Difficulty/significance of choices/decisions14
- Improvement in risk communication entails building of trust and awareness of patients’ access to varied and conflicting sources of risk information
**14****Alaszewski A, Horlick-Jones T. *****Br Med J *****2003;327:728-731****	****	**
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## Risk Communication Effectiveness: Physician to Patient 

- Physicians need to be aware of possible confusion in relaying medical statistics with health risk information15:
- Single event probabilities, e.g., statement of “`30% chance of rain tomorrow’” can be interpreted by some people as:
- Tomorrow it will rain in 30% of area, or
- Tomorrow will see rain 30% of the time, or
- There will be rain on 30% of days like tomorrow
- Conditional probabilities (specificity; sensitivity)
- Relative risk
- Confusion can be reduced or eliminated with good, simplified representation of risk
**15****Gigerenzer G, Edwards A. *****Br Med J *****2003;327:741-744****	****	****	**
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## Lessons Learned: Labeling Changes and Large-Scale Notification1 

- In choosing communication methods/assessing effectiveness, major categor(ies) of perceived risk must also be part of evaluative process
- As behaviors associated with each category of risk may well differ, so may communication methods optimally utilized
***	******Given that all risks are NOT the same,*** ***one size of risk notification tool may NOT fit all***
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## Lessons Learned: Labeling Changes and Large-Scale Notification1 

- Multiple modes of risk communication and maximal publicity may well heighten overall  effectiveness
- In assessing effectiveness of risk communication, desired results MUST be clearly stated
- A fair degree of achieved success may not be seen as effective enough to prevent market withdrawal
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## Lessons Learned: Labeling Changes and Large-Scale Notification1 

- Medical products differ in perceived benefit/risk,
- 	based on such factors as
- Disease entity or population treated
- Availability of other products
- Reversibility of AE(s) in question
- Thus, each case merits individualized assessment, rather than formulaic, “cookie-cutter” approach
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## Lessons Learned: Labeling Changes and Large-Scale Notification1

- Understanding how HPs use risk information critical to improvement in communication methods
- Examine varied information sources and related factors impacting practitioner behavior
- Optimum use of promising new communication technologies (e.g., Internet; computerized pharmacy systems) is global learning process
- Information overload/increasing time demands on HPs must be acknowledged and considered when planning/ assessing risk communication
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## Lessons Learned: Information Provided1

- Risk information intended for health professionals should be as clinically oriented and relevant to patient care as possible
- FDA generation/dissemination of Q’s & A’s based on latest safety information for particular drug of concern should be encouraged/modeled
- Specifically targeted to treating healthcare community and consumers
- Address perceived leading concerns/issues for both sectors
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## Lessons Learned: Risk Communication1

- For optimal risk communication effectiveness:
- Awareness of social and psychological factors that impact risk information receipt and perception
- Clarity of presentation and minimization of ambiguity/possible sources of confusion
- Establish deserved trust in informational sources
- Critically evaluate sources of risk information
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*“**The speed of communication is wondrous to behold. It is also true that speed can multiply the distribution of information that we know to be untrue.”*
- Edward R. Murrow (1908-1965)

## Lessons Learned: Health Professional Education1

- Drug safety/risk management education for HPs should not be exclusively product-specific
- Goals should include
- Greater awareness of medical product-induced disease
- Recognition
- Management
- Reporting
- Enhanced knowledge/application of pharmacotherapy, and of impact individual patient factors can have on pharmacotherapy
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## Lessons Learned: Health Professional Education1

- Education efforts need to involve
- ALL levels and health professional disciplines
- Professional schools
- Training programs
- Post-graduate continuing education
- Based in care delivery setting (e.g., hospitals; clinics)
- MUST be ongoing
- One-shot programs not nearly enough
- No quick fix -- must be commitment of resources
- Partnerships/cooperation among stakeholders
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## Conclusion1

- Do these risk communication modalities result in desired outcomes?
- Based on current knowledge/experience gained, answer of “yes, but not in all circumstances, not every time, and not always to the ideal extent” appears reasonable
- New methods/novel combinations need to be sought/ tested to minimize preventable AEs/use errors and protect patients to greatest degree possible
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## Summary

- _Shared_ responsibility for risk management16
- FDA			Industry
- Health professionals	Patients
- Other federal groups	Healthcare delivery systems
- Professional societies
***	******FDA communication tools need to be seen as part of overall risk minimization efforts incorporating other methods (e.g., clinically-based teaching; consumer education) that may well employ FDA-provided information ***
**16****Task Force on Risk Management. Report to the FDA Commissioner: managing the risks from medical product use: creating a risk management framework. Rockville, MD: U.S. DHHS, FDA, May 1999:  available @ www.fda.gov/medwatch/articles.htm**
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*“**History repeats itself; that’s one of the things that’s wrong with history.”*
- Clarence Darrow (1857-1938)* *