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Alvimopan RiskMAPAlvimopan RiskMAP

Joyce Weaver, Pharm.D., BCPS

Office of Surveillance and Epidemiology

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What is a RiskMAP?What is a RiskMAP?**

• A RiskMAP is a strategic safety program – Designed to meet specific goals and objectives in

minimizing product risks – Uses one or more RiskMAP tools to meet goal(s) – Goes beyond FDA-approved labeling

* Guidance for Industry: Development and Use of Risk Minimization Action Plans (RiskMAP); available at http://www.fda.gov/cder/guidance/6358fnl.pdf

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How do RiskMAPs Work?How do RiskMAPs Work?• Limit use to settings or patients with favorable risk-

benefit profile– Prevent use in high-risk settings or patients

• Encourage/mandate safety-related monitoring• Start therapy in closely monitored settings• Empower patients to participate in medication-related

decisions and safety monitoring– Education– Informed consent

• Educate healthcare providers on safety-related medication issues and monitoring

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RiskMAP ComponentsRiskMAP Components• Goals & Objectives - Desired end result (with intermediate steps), most

often stated in terms of one or more health outcomes to avoid

• Tools - processes or systems beyond labeling intended to achieve goals and objectives– Education and outreach – Reminder/prompting systems – Restricted Distribution Systems; aka Performance-linked Access Systems

(PLAS)

• Evaluation -The performance of the overall RiskMAP and tools in achieving its goals and objectives– Health outcomes or surrogates of health outcomes – numbers or rates of an

outcome or event– Compliance with important RiskMAP processes and procedures – Assessment of comprehension, knowledge or desired behavior (e.g., surveys)

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Targeted Education and Targeted Education and OutreachOutreach

• Purpose: to communicate risks and appropriate safety behaviors to healthcare practitioners and patients

• Examples:– DHCP letters – Training programs for HCPs or patients– Continuing Education – Patient labeling such as Medication Guides and Patient Package

Inserts– RiskMAP program guides– Videos/DVDs – Limits in marketing or promotion such as no DTC or detailing

only certain specialties

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Reminder/Prompting SystemsReminder/Prompting Systems• Purpose: to assist healthcare providers in following appropriate

prescribing practices• Examples:

– Limited supply of product per prescription such as dispensing only a 30-day supply

– Limits on the number of refills or not allowing refills– Prescription expiration such as requiring a prescription to be filled in a

certain period of time – Specialized packaging –

• requiring certain warnings • packaging to include MG or PPI• pharmacist checklist• limiting the amount packaged

– Prescriber or other HCP attestation of conditions of safe use – MD/patient agreement (e.g., informed consent)

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Restricted Distribution/ Restricted Distribution/ Performance-Linked Access SystemsPerformance-Linked Access Systems

• Purpose: to target the population and conditions of use most likely to confer benefits and to minimize particular risks. Includes prescribing, distribution, dispensing, and/or administering restrictions

• Examples:– Prescriptions only by specially certified HCPs– Product dispensing limited to pharmacies or HCPs that elect to be specially

certified– Mandatory pharmacy enrollment to dispense– Mandatory enrollment of infusion center or hospital to administer– The drug be dispensed or administered only in certain healthcare settings– Product dispensing only to patients with evidence or other documentation

of safe use (e.g., required pregnancy testing)– Wholesaler agreement to distribute product only to registered entities

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When Should a RiskMAP be When Should a RiskMAP be Considered?Considered?

• Products with important benefits should be considered for a RiskMAP in one or more of the following situations:– Risks are serious and preventable– Safe and effective use may call for specialized

healthcare skills or settings– When a RiskMAP encourages appropriate use to

increase benefits relative to risks – Product is in a class of products with similar risks that

require a RiskMAP

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Proposed Alvimopan RiskMAPProposed Alvimopan RiskMAP

• Addresses cardiovascular risk• Sponsor has not made a complete RiskMAP

submission– No goals, objectives, supporting documents, detailed

implementation plans, evaluation plan, metrics, RiskMAP reporting to FDA

• RiskMAP outline based on assumption that cardiovascular safety risks will be minimized by limiting use to inpatient settings

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Do we understand the risks?Do we understand the risks?

• Follow-up in short-term trials not sufficient to ascertain cardiovascular events and other risks (neoplasms, fractures) discovered with long-term testing

• Proposed daily dosage is 24 X higher than the dose that produced cardiovascular safety signal in long-term testing

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Proposed Alvimopan RiskMAPProposed Alvimopan RiskMAP

• Agreements with pharmaceutical wholesalers to sell only to hospitals

• Targeted education, sales, promotion

• Packaging that specifies hospital use

• Alert system for outpatient pharmacies not to dispense alvimopan on an outpatient basis

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Alvimopan RiskMAP Alvimopan RiskMAP ConcernsConcerns

• Current proposal may not prevent longer term use or outpatient use– Pharmaceutical wholesalers do not have a definition of “acute-care

hospital”– Many hospital pharmacies dispense for outpatients– Physicians may want patients to finish a course of therapy at home– Extended inpatient stays possible– Alert system for outpatient pharmacies

• Available in 50% pharmacies• Pharmacist can override

• No collection of medical outcomes to determine if CV events are minimized

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Alvimopan RiskMAP Tool Alvimopan RiskMAP Tool ConsiderationsConsiderations

• Hospital registration and attestation that a safe-use protocol is in place (dofetilide example)

• Sponsor retention of responsibility for who purchases the product (eculizumab example)

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Alvimopan RiskMAP ConclusionsAlvimopan RiskMAP Conclusions

• Much more detail needed about goals, objectives, implementation plans, evaluation plan, metrics, RiskMAP reporting to FDA

• Operational changes needed– Sponsor should retain control over supply chain– Need systematic program for hospitals to prevent

diversion to outpatient use, longer term IP use• Even with these changes, RiskMAP framework

acceptable only if – Short-term use is safe– Process evaluation of RiskMAP sufficient; medical

outcomes will not be measured