Evaluating Drug Names for Similarities: Methods and Approaches Public

Meeting

June 26, 2003

Bill Campbell, PhD

Dean, UNC School of PharmacyDirector, UNC Center for Education and

Research on Therapeutics (CERTs)

Sometimes similar drug names are approved contingent on a pre-marketing agreement for a risk management program….

1. What role should a pre-marketing commitment for a risk management plan play in the approval of a proprietary name that has some potential for sound- alike or look-alike confusion with other marketed products?

2. What components of a risk management plan should be considered in order to minimize the risk associated with proprietary name confusion?

3. What should be the measurable goal(s) of such a risk management plan?

Risk Management Program (RMP): a strategic safety program designed to decrease product risk by using one or more interventions or tools beyond the package insert 1 i.e., a “safety net”

General categories of RMP:

Specialized educational materials for health practitioners or patients

Processes or forms to increase compliance with reduced-risk prescribing and use,

Systems that modify conventional prescribing, dispensing, and use of the product to minimize specific risks

1 FDA Concept Paper: Risk Management Programs

What role should a pre-marketing commitmentfor a risk management plan (RMP) play in the approval of a proprietary name that has some potential for sound-alike or look-alike confusion with other marketed products?

a. CERTs Theme: “Manage the Risk, Benefit the Patient”

b. Analogous to premarketing clinical assessment: Efficacy vs. Effectiveness

c. Can an approved RMP reduce the time to market?

a. CERTs Theme: “Manage the Risk, Benefit the Patient”

There will always be risk, it cannot be totally eliminated.

Welcome the opportunity to manage risk, since this is the only way to deliver benefit.

The challenge is to identify the maximum acceptable risk,

manage it, and maximize the benefits.

What components of a risk management program should be considered in order to minimize the risk associated

with proprietary name confusion?

Components of a RM Program:

“Dear Provider” LettersActive SurveillancePassive SurveillanceSticker (attestation)

Patient RegistrationPrescriber RegistrationRestricted DistributionRestricted PrescribingMandatory Education ProgramCard System800 numberPharmacovigilance AnalysisCME

What components of a risk management plan should be considered in order to minimize the risk associated with proprietary name confusion?

Components of a RM Program: (continued)

Educational Programs (journal ads, direct mailing)Usual Promotional ActivitiesPrescriber CredentialingPatient MonitoringPharmacist RegistrationPharmacist MonitoringNo-refill PolicyRestricted DistributionInformation Technology Solutions

CPOEInternetPersonal Electronic Medical Record

(Permutations and Combinations)

What components of a risk management plan should be considered in order to minimize the risk associated with proprietary name confusion?

Suggested Components of a RM Program (tailored to Proprietary Name Confusion)

Written prescription only (no verbal prescription)Attestation of Potential for ConfusionRMP using two namesPrescriber Validation by Feedback

etc.

“There are no gold standards, only hypotheses to be tested”

“Systems Approach preferred to ‘One-up’ Approach”

b. Efficacy vs. Effectiveness

Similarities to predicting “real world” practice from RCT data…

Cognitive medical psychology Application Software Behavioral laboratoryFocus groupsCase studiesModeling and MappingExpert CommitteesSurveys etc.

…but without the RCT as reference

Role of drug name efficacy studies for RMP:

Describe expected risks

Identify risks not previously suspected

Provide estimate of risk (rate & measure)

Identify benefits not previously suspected

Provide estimate of benefit (rate and measure)

Inform RMP and evaluation

c. Can an approved RMP reduce time to market? Hypothetical Case:

Proposed drug name “Appesate”Existing drug name “Apresolate”

Scenario A:

Approve with required RMP to defineand reduce unknown risk of substitution/confusion(reduced time to market)

Scenario B:

Defer approval until premarketing studies eliminatepotential for error (no effect on time to market)

(Should it reduce time to market?}

Should a RMP ever be used to reduce time to market?

Criteria for approving a drug contingent on RM Plan:

When no alternative therapy is available

When substantial therapeutic advantage exists for new product

When therapy is for serious and/or life threatening

When Risk/Benefit of therapy can be effectively communicated to provider and patient

When no alternative therapy is availableWhen substantial therapeutic advantage existsWhen therapy is for serious or life threateningWhen Risk/Benefit of therapy can be effectively communicated to provider and patient

Do any of these conditions apply for choosing a confusing name?

No alternative name? (17,000 current proprietary names)Substantial therapeutic advantage for a new name? (Ziagra)Treated condition made less serious by name?Risk/Benefit of name can be communicated?

CONCLUSION: Reduction of time to market is not a rational goal for a name-based RMP

What components of a risk management plan have been shown to be effective in minimizing

risk associated with proprietary name confusion?

Face Validity:

Restricted DistributionRestricted Prescribing

Unproven:

All others

Hypotheses:

Effectiveness of individual elements not known

Effectiveness of combinations not known

(a large, and unfunded, research agenda)

What should be the measurable goal(s) of such a risk management program?

1. What is the baseline?

2. What is the maximum acceptable risk?

3. What is the measure of success?

4. What is the target?

What is the baseline?

Baseline: the error rate for a proprietary name with no projected “look-alike, sound-alike” confusion.

(Baseline = α, where α > 0)

requires knowledge of risk

requires data on current practice (prescribing, dispensing, use)

What is maximum acceptable risk?

Maximum Acceptable Risk: acceptable error rate for a proprietaryname with a potential look-alike, sound-alike comparitor;

Maximum Acceptable Risk = β, where β > α > 0

requires knowledge of R/B of proposed name

requires knowledge of R/B of distracter names

What is the measure of success?

Measure of Success (γ):

A range of error rates ETLT maximumacceptable risk (β), but ETGT baselinerisk (α)

(Measure of Success = γ, where 0 < α < γ <β )

What are the targets for a RMP?

A target is a specific, quantitative goal for error rate established a priori by a RMP;i.e., an “expected rate” (ε)

ε = γ1…γn, where γ1 < ε < γn

OPTIONS:

Hurricanes and Tropical Storms 1. Gender specific names 2. Alternating genders 3. Name acquires attributes

of the drug (e.g., Floyd)

Thoroughbred Horses1. Initially an alphanumeric designator (CF321)2. Secondarily a name (Secretariat)

OPTION B: Status Quo

17,000 Proprietary Drug Names

1. “First come” driven names 2. Class naming by competition 3. Drug acquires attributes of

the name (e.g., Viagra)

Conclusions and Recommendations

1. RMP can improve Risk/Benefit Ratio,but the choice of individual elements or an optimum combination requires primary research.

Conclusions and Recommendations

2. In order to have an effective RMP there must be measurable quantitative goals for baseline risk, acceptable risk, success, and targets.

Conclusions and Recommendations

3. Given the state-of-the-art of research in proprietary name-

related RMP, this is not amechanism for reducing time to market.