# Presentation: 799443

## Risk Management Options

- Russell Ellison, MDChief Medical OfficerVice President, Medical Affairs
- Roche Laboratories, Inc.

## Accutane and Pregnancy

- Accutane use is increasing
- The pregnancy rate is declining
- The pregnancy rate in women on Accutane is about 80-90% less than for those with normal contraceptive use (0.3% vs. 1-5%)
- For every 1000 women treated with Accutane, pregnancy has not occurred in 997

## The absolute goal  is

-  the prevention of pregnancy

## HOWEVER:

- While an individual’s risk of pregnancy is decreasing, the total public health burden has not.
-  	i.e: the absolute number of exposed pregnancies has not decreased

## To Prevent Pregnancy

- Every patient has to avoid pregnancy every day of therapy
- 1st trimester teratogens require patient not to be pregnant at start of treatment or to become pregnant during treatment as well
- later trimester teratogens require the physician to avoid prescription during pregnancy

## FDA OPTIONS: TPPP PLUS

- Option 1..
- Mandatory registration of all female patients
- External data sources monitoring program impact
- Option 2 #1 plus
- No dispensing unless pharmacist confirms a documented negative pregnancy prevention test
- Option 3 #2 plus
- Pharmacist confirms that appropriate patient compliance with contraceptive practices, drug sharing and blood donation guidelines has been documented
- Option 4 #3 plus
- Pharmacists would have to be trained, registered, and authorized before allowed to dispense Accutane

## every woman must avoid pregnancy every day Mandatory Programs

- Try to obtain compliance through conditional access to the drug,  does not achieve active participation through motivation and knowledge
- Require a single channel of distribution and access to the drug

## every woman must avoid pregnancy every day Mandatory Programs

- Stress completeness of documentation of compliance *(in public at the pharmacy counter),* not effectiveness of practice
- Enforce a population standard for all patients; not an optimal program for the individual

## every woman must avoid pregnancy every day Mandatory Programs

- Through the manufacturer, to be implemented by the pharmacist:
- require additional qualifications or conditions from the prescriber to be fulfilled  for the dispensing of a drug beyond the State’s licensure of the prescriber and/or the State Medical Board’s regulations

## every woman must avoid pregnancy every day Mandatory Programs

- The pharmacist is now being asked to control the behavior of the doctor and the patient...
- 		*Is this appropriate?*
*	**	**Is this feasible?*

## FDA OPTIONS: TPPP PLUS

- Option 1..
- Mandatory registration of all female patients
- External data sources monitoring program impact
- Option 2 #1 plus
- No dispensing unless pharmacist confirms a documented negative pregnancy prevention test
- Option 3 #2 plus
- Pharmacist confirms that appropriate patient compliance with contraceptive practices, drug sharing and blood donation guidelines has been documented
- Option 4 #3 plus
- Pharmacists would have to be trained, registered, and authorized before allowed to dispense Accutane

## every woman must avoid pregnancy every day Mandatory Registration

- Does not reduce the risk of pregnancy
- Only benefit is a denominator of 100%
- Coercive:  condition of drug is public registry vs.  private consent
- Considerable risk of poor follow-up (response) and reliability and chance of erroneously low pregnancy and compliance rates

## every woman must avoid pregnancy every day Mandatory Programs

- Common feature of all four options:
*Excessive burden on physicians and patients **with no perceived individual benefit*
*Will produce an indiscriminate barrier to access*

## Risk Management Programs: PregnancyWhat experience do we have?

- Accutane PPP: voluntary, initiated 1989
- evaluated, published, publicly reviewed
- pregnancy rate known with tight CI
- successful at reducing individual risk from normal contraceptive practice
- 200,000 women treated per year
- young healthy patients
- well known unique drug
- alternate channels available

## Risk Management Program - TPPP

## Risk Management Program-TPPP

## Risk Management Programs: Pregnancy What experience do we have?

- STEPS (Thalidomide) mandatory, introduced 1997
- basic design is publicly known
- no evaluation or review of results publicly available
- small population (majority are ill, older women)
- >50% have malignancies
- alternate channels for patient access??

##  Based on what we know, and balancing:
likelihood of  success
risk of compromising current success
risk of denying treatment to patients who would not become pregnant

- likelihood of  success
- risk of compromising current success
- risk of denying treatment to patients who would not become pregnant

## To prevent pregnancy in women prescribed Accutane, mandatory programs :
are untested
have unknown benefits over the T-PPP and unquantifiable risks which will be difficult to ascertain and reverse

- are untested
- have unknown benefits over the T-PPP and unquantifiable risks which will be difficult to ascertain and reverse

## every woman must avoid pregnancy every day 

- Pregnancy Prevention for women taking Accutane is a shared responsibility of:
- Roche
- Prescriber
- Pharmacist, nurse, reproductive health professional
- PATIENT
- The TPPP is the best method to assure active participation of all parties to prevent pregnancy, and has the optimal chance of success with least risk

## Roche is committed to the absolute goal of pregnancy prevention and the continual improvement of the TPPP