# Presentation: 485425

## Improving the Effectiveness of Risk Communication

***Prepared for***
**FDA Hearing on Risk Communication**
**Elizabeth B. Andrews, PhD, MPH, **
**VP, Pharmacoepidemiology and Risk Management**
**December 7, 2005**

## Overview

- Two examples:
- Risk communication in Alosetron risk-management program
- Effect of risk communication format on patient risk-benefit tradeoffs for hormone replacement therapy
- Lessons:
- Patients and physicians can understand quantitative risk information and make informed choices
- Risk perceptions and risk attitudes can depend on presentation method

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## Example of Effective Communication:  Alosetron

- Patient-oriented messages on benefits, risks, and what action patients should take
- Physician-patient agreement form (PPA)
- Medication guide provided by physician and pharmacist
- Evaluation of communication process and knowledge using patient survey
- Voluntary follow-up survey (mail and phone)
- Recruitment card from physicians and in product packaging
- Data collected at initiation, 5 weeks, 10 weeks, and quarterly for one year
- Enroll 35% of users

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## Results of Alosetron Patient Follow-up Survey through December 31, 2003 (n=3,219)

| Indicators of Compliance with RMP | % |
| --- | --- |
| Signed a Physician-Patient Agreement form  | 93 |
| Discussed possible risks of Lotronex with doctor | 96 |
| Discussed with doctor how Lotronex can help | 97 |
| Discussed with doctor reasons to stop taking Lotronex | 95 |
| Discussed when to call the doctor | 94 |
| Received medication guide from doctor  | 91 |
| Received medication guide from pharmacist | 90 |
| Read the medication guide (of those receiving it) | 98 |
| Received prescription with blue sticker | 87 |

- .

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## Knowledge Questions 1-3 (added based on cognitive testing)

**New or worsening pain in the bowels is a sign that a patient could**
**be experiencing a serious problem related to Lotronex**
- o True
- o False
- o Don’t Know
**If a patient experiences new or worsening pain in the bowels,**
**which is the best action to take?**
- o Continue taking Lotronex as prescribed
- o Lower the dose for a few days
- o Stop taking Lotronex, and call the Doctor
- o Don’t Know
**Blood in the stool is a sign that a patient could be experiencing a**
**serious problem related to Lotronex**
- o True
- o False
- o Don’t Know

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## Knowledge Questions 3-6 (added based on cognitive testing)

**If there is blood in the stool, which is the best action to take?**
- o Continue taking Lotronex as prescribed
- o Lower the dose for a few days
- o Stop taking Lotronex, and call the Doctor
- o Don’t Know
**Constipation is a sign that a patient could be experiencing a serious problem related to Lotronex**
- o True
- o False
- o Don’t Know
**If a patient becomes constipated, which is the best action to take?**
- o Continue taking Lotronex as prescribed
- o Lower the dose for a few days
- o Stop taking Lotronex, and call the Doctor
- o Don’t Know

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## Potential Reasons for Success of Alosetron Medication Guide and PPA

- Motivated population receiving treatment
- Most severely affected by IBS symptoms
- Many had received Alosetron prior to product withdrawal
- Good physician compliance
- Enrolling in prescribing program
- Prescribing only to patients meeting clinical criteria
- Counseling patients
- Signing physician-patient agreement form
- Reporting adverse events
- Effective communication using multiple approaches
- Physician-patient agreement form
- Medication guide
**Lesson - Importance of careful development and testing of**
**Communication instrument**
**Measurement instrument**

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## Effect of Risk Communication on Hormone Replacement Therapy (HRT) Preferences

- Women’s Health Initiative Study: benefits of HRT not greater than health risks
- Decreased risk of hip fracture
- Increased risk of myocardial infarction and breast cancer
- Did not consider benefits of relief from vasomotor symptoms of menopause

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## Effect of Risk Communication on HRT Stated Preferences

- Risk-benefit tradeoff study
- Objectives
- Estimate stated willingness to trade risk for vasomotor symptom control
- Test effect on stated preferences of absolute-risk versus relative-risk measures
- Maximum Acceptable Risk measured by Conjoint-analysis methods
- Rigorous conceptual framework
- Ordinal utility theory
- Choice-based preferences
- Advanced statistical modeling

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## HRT Study Design

- Web-enabled survey
- Choices between realistic treatment alternatives
- Efficacy features: symptom severity, frequency, and duration
- Risk features: infarct, cancer, and fracture
- Risks presented either as absolute risks or relative risks
- Internal validity tests incorporated in design
- 523 women aged 46-60

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## Example Conjoint Task

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## Risk-Benefit Tradeoffs

**Δ****Risk**

**Δ**** ****Symptom Control**

- None

- Full

- Some

- Risk-Benefit Tradeoff Curve

**               ****Δ**** Efficacy Satisfaction**
** **
**    ****Δ**** Satisfaction per 1% risk decrease**

**=**

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**Notes:**
In this case benefit measured simply as level of pain control.
Reed’s section ends here.

## HRT Maximum Acceptable Myocardial Infarction Risk

**WHI Risk**

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## HRT Maximum Acceptable Breast Cancer Risk

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## Conclusions

- Women had a higher tolerance for risk when the risk was presented as absolute risk
- Women were willing to accept risks greater than WHI risk estimates to obtain good symptom control

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## Conclusions

- Patients and physicians can understand risk information and make informed choices
- Careful design and testing is needed for both the communication and evaluation instruments
- The type of risk to be communicated (relative,  absolute, or both) is important
- The patient perspective on trade-offs between risks and benefits can be evaluated in a scientifically robust manner and inform policy decisions

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## References Cited

- US Food and Drug Administration. Update on Risk Management Activities for Lotronex (alosetron hydrochloride), 2004 http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4040B1_16_FDA-Tab-1.doc
- Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349(6):523-534.
- Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in health postmenopausal women. The Women’s Health Initiative Randomized Trial. JAMA. 2003; 289(24):3243-3253.
- Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003; 290(13):1729-1738.

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