Life After iPLEDGE

On a Saturday morning in early July, dermatologist Robert Greenberg, M.D., made an unplanned trip to his Vernon, CT, office, at 5:30 a.m. before leaving for vacation. He wanted to ensure that one of his female patients on isotretinoin — who had flown into town for her visit because she was working out of state — didn’t end up outside the iPLEDGE “window” for obtaining her prescription.
“Here was a patient who had done everything right — she was on two forms of birth control and had a negative pregnancy test result — but the system wouldn’t take our entry,” Dr. Greenberg explains, because the requisite 30 days had not elapsed between appointments.

To comply with the new risk-management program’s requirements, Dr. Greenberg had to confirm counseling and enter required data into the system on the weekend because of the July 4th holiday and the patient’s return flight.

“For a program to be so inflexible that it doesn’t take into consideration the holiday or a patient’s extenuating circumstances is such an impediment. It happens often that the 30-day window runs into the weekend when offices are closed,” he says. “This [iPLEDGE] isn’t the way things are done in the real world,” he adds, where a 1-month follow-up appointment is actually 28 days.

Burdensome Requirements

This particular requirement has caused so much consternation among dermatologists that Sen. Dick Durbin (D-IL) and Sen. Judd Gregg (R-NH) in June wrote to FDA Acting Commissioner Andrew Eschenbach, M.D., to request more flexibility in iPLEDGE requirements and modifications to the program to reduce the burden on practices.

The requirement that isotretinoin prescriptions be filled within 7 days is also causing headaches for dermatologists and patients, as well as practice personnel and pharmacists who receive the complaints when the system “locks out” the prescription and patients must wait another 30 days.

“Nurses are having the same frustrations as doctors regarding difficulties of getting the drug to patients and patients’ complaints,” says Cathy Boeck, R.N., D.N.C., who is Immediate Past President of the Dermatology Nurses Association and works at the University of Minnesota. “It has a huge impact on resources if someone is waiting on hold with iPLEDGE and is also taking calls from patients who are upset and frustrated. That’s what we’ve heard from members.”

Under the previous program, dermatologists could call the pharmacy to request that a slightly “overdue” prescription be filled. On the plus side, however, iPLEDGE allows registered prescribers to fax prescriptions or send them via electronic systems, which ultimately reduces phone calls to pharmacies and can expedite pickup for patients.

A Time-Consuming Program

That convenience is offset to some extent by one hassle factor many dermatologists have cited: The iPLEDGE computer system doesn’t allow “edits” when information is entered incorrectly, which means that prescribers or office staff must call iPLEDGE to rectify the error. For example, if the patient enters the two forms of contraception in a different order than the physician does, the user cannot complete the entry without making the phone call. That task, in itself, can take up to 30 minutes, sources interviewed for this article reported.

“If you put in the wrong birthdate for a patient, you have to call the iPLEDGE representative — and that’s a bit much,” says Jonette Keri, M.D., who cares for all patients on isotretinoin (about 60) treated at the University of Miami in Florida. “Compared the to the sticker [predecessor] program, it’s an extra 30 minutes when there’s a problem.” In general, dermatologists have reported that complying with iPLEDGE takes up to twice as much time compared to the previous SMART (System to Manage Accutane Related Teratogenicity) program.

The new program also requires that pregnancy tests be conducted the day of the office visit for female patients, which can translate into extra trips to the lab for patients and additional clinical coordination for dermatologists and their office staff. Finally, dermatologists and patients take issue with the fact that male patients and female patients not of child-bearing potential must comply with a program whose primary intent is to prevent fetal exposure to isotretinoin.

A Decrease in Prescriptions

Nearly 6 months into the program that’s been called confusing at best and inordinately complex and cumbersome at worst, dermatologists are either putting up with the hassles or opting out. Certain early technical and logistical problems, such as long telephone wait times — more than an hour, in some cases — to reach the iPLEDGE call center and conflicting responses from representatives to inquiries, have been largely resolved. But the rigidity of the requirements (even the FDA acknowledges that iPLEDGE’s complexity is unprecedented) and time consumed in complying with those requirements, have prompted some dermatologists to say “no thanks” to iPLEDGE — which went into effect March 1 despite requests from the AAD and others to delay its implementation.

“There are some dermatologists who are no longer prescribing isotretinoin because of the difficulties encountered with the system and the problems with timing office visits,” says Diane Thiboutot, M.D., who chairs the American Academy of Dermatology’s Ad Hoc Task Force on Isotretinoin and practices in a 24-dermatologist group practice at Pennsylvania State University in Hershey, PA.
“The issues we raised prior to iPLEDGE’s implementation — the timing of office visits, in particular — remain.” In her own practice, for example, they have assumed “block schedules” similar to those some obstetricians use, for the purpose of seeing patients on isotretinoin. “It works to ease the scheduling issues, but I find it to be a loss in terms of my enjoyment of interacting with my patients,” she says.

“We have physicians who won’t prescribe the drug, and patients who won’t deal with the restrictions,” Dr. Thiboutot says, referring to task force reports.

“Even one deformed baby is too many, but I think we’re going to have a lot of patients who end up with scarring acne because of this program,” Dr. Keri adds.

Dr. Thiboutot and representatives of the AAD say they don’t know the number of dermatologists who have stopped prescribing isotretinoin since iPLEDGE was implemented. But some sources interviewed reported that they have heard from drug company representatives that sales of the drug are down.

According to IMS Health, a Plymouth Meeting, PA, pharmaceutical information and consulting company, dispensed total prescriptions for January to June 2006 were -52% for Accutane, -16% for Amnesteem and +1% for Sotret compared to the same time period in 2005. Data for Claravis was not available. Lance Longwell, a spokesperson for IMS, says that sales of branded Accutane and “the entire drug class” have been down every year since 2002 but did not venture whether that had to do with risk-management programs. “It [Accutane] is a shrinking drug in a shrinking class,” Mr. Longwell says. According to IMS, in 2005 dispensed total prescriptions were up 20% for Sotret, -3% for Amnesteem and -46% for Amnesteem from 2004.

Dermatologists in private or small group practices are taking other steps to mitigate the burden on themselves and staff (see Tips sidebar). Some are identifying nearly everyone else in the practice as their designees on the computer system, so that activities can be conducted and data entered in a more expedient manner. Others are simply reducing the number of patients for whom they consider the drug, to avoid dealing with iPLEDGE unless it’s the only means to an end.

The Politics of iPLEDGE

“Due in large part to the iPLEDGE program, I'm more judicious in my use of isotretinoin,” says New York City dermatologist Noah Scheinfeld, M.D.

“I advocate its use to patients by noting that it’s one of the few drugs in dermatology that effects an actual and longstanding cure,” he says. Dr. Scheinfeld says that he’ll continue to prescribe isotretinoin to patients with acne who haven’t responded to other treatments.

“The bottom line is that isotretinoin is an effective medication — I think patients need hope, and this medication gives them hope. But this program is the wrong way of going about it — it’s too heavy-handed,” he says. Dr. Scheinfeld and other dermatologists suggest that iPLEDGE’s strict framework is more a product of a complex political move than a schema that enhances the patients’ well-being and health.

“Why is iPLEDGE so complicated? Clearly, it’s for political reasons,” says Dr. Greenberg. “Because the answer to a pregnancy [on isotretinoin] is a termination, and this administration is against terminating pregnancies.” (The patient booklet discusses “emergency contraception” as the appropriate response to suspected pregnancy and also states that “abstinence without appropriate contraception is not recommended” — positions some dermatologists think are more morally directed than medically based.)

Despite Hassles, Many Still Prescribing Isotretinoin

Dermatologists who have persisted as the bugs in the program, which is administered by the Princeton, NJ, drug-development services firm Covance, have been worked out, see light on the horizon — even if they disagree with iPLEDGE’s reach, complexity and burden.
Although the AAD received upwards of 300 complaints in the weeks after the program’s implementation, the frequency of those reports has declined as Covance has increased call-center staffing. A company spokesperson said that as of late June “the call center capture rate had improved to 93% and call waiting times have significantly declined.” To date, about 150,000 patients and 16,000 prescribers have activated their iPLEDGE registration.

“Phone call wait times [for the call center] are down, but it still often takes 10 minutes — and some of my staff ended up making calls at home in the evening,” says Ned Ryan, D.O., a Drexel Hill, PA, dermatologist in private practice who has been prescribing isotretinoin since it was approved.

“I can say that there is clearly a doubling of physician and staff time with iPLEDGE, compared to the sticker-based [SMART] program. And some of my patients look at me strangely after I’ve repeated the counseling two or three times.” iPLEDGE requires that prescribers repeat counseling about the drug’s risks and program requirements regarding contraception and other issues on each visit — a requirement dermatologists say is “overkill.”

But it’s the requirement that males and females who aren’t of child-bearing potential comply that really irks many dermatologists. “They [the FDA and drug manufacturers] want a wide net, understandably. But this is completely over the top,” Dr. Ryan says.
Stephen P. Stone, M.D., current AAD President and Professor of Dermatology at the Southern Illinois University School of Medicine in Springfield, concurs with Dr. Ryan’s position.

“The absurdity of the complexity of this kind of program for a male is a problem that won’t go away, and people won’t tire of complaining about it,” Dr. Stone says. He illustrated his frustration with an example from his own practice: a male patient who failed to take his iPLEDGE ID card to the pharmacy on the last day in the 7-day window was unable to obtain his prescription the next day.

A Need to Decrease Pregnancy

At the same time, some dermatologists say that they can’t quibble with iPLEDGE’s likely effect on pregnancy rates and do hope that the intended decline actually occurs. An estimated 160 infants with isotretinoin-induced effects have been born since the drug’s approval in 1982, and the restrictive nature of iPLEDGE might reduce that figure —provided female patients do “follow the rules” and aren’t so deterred by the restrictions that they seek other ways to secure the drug.

“I do think iPLEDGE will reduce pregnancy rates. And although a few of my patients have dropped out [of treatment] because of iPLEDGE, most of them, by the time they get to me, really want the drug,” Dr. Keri says. “So one positive thing is that patients are taking this medication more seriously now with iPLEDGE — they’re not missing their appointments because they’re so frustrated with the 30-day blockout.” Still, she wonders why female patients who miss the visit window cannot simply repeat the pregnancy test to ensure their treatment isn’t interrupted. “That’s been hashed around a bit, but we’ve been told it wouldn’t work,” she says.

On the big-picture front, Dr. Keri is concerned about potential unintended consequences of iPLEDGE. She has not only heard reports about patients obtaining the drug from other countries or via the Internet, she has seen evidence of that in her own practice.

“I have had patients come in and say, ‘I’m getting my Accutane from South America. Can you order my blood test?’ And that’s the responsible patient, so who knows what’s really going on?” Dr. Keri explains.

Will the Program Be Modified?

Dr. Thiboutot notes that the AAD has asked the FDA and program sponsors to modify the visit-timing and 30-day window aspects of the program, and possibly the 7-day prescription fill requirements when extenuating circumstances occur, to make iPLEDGE less burdensome. No changes have been made to date, but that doesn’t mean none will be forthcoming, FDA officials have said.

One aspect of iPLEDGE that some dermatologists may overlook is that while the program was approved by the FDA, and was developed in response to the agency’s concern about fetal exposure rates, the complex design was the brainchild of the drug’s manufacturers in concert with Covance. As such, those entities could — and may — propose modifications that would allow more flexibility, according to Jill Lindstrom, M.D., Lead Medical Officer in the FDA’s Division of Dermatological and Dental Products.
“The FDA is … interested in any proposal the sponsors would have to minimize the burden on any stakeholder group — prescribers, pharmacists or patients — that would still ensure that conditions of safe use were satisfied,” Dr. Lindstrom said in mid-July. “You have to remember that this is a sponsored program that the [drug] manufacturers contracted with Covance to run.”

She declined to divulge proposed modifications the FDA has received from stakeholder groups, but did say the FDA would “rapidly review and would not delay implementation of proposed improvements or changes.” A Covance spokesperson said the manufacturers and Covance “are working closely with the FDA on enhancements to the program,” but that it is “still too early to provide details.”

Proposed Modifications

Following are some modifications dermatologists and pharmacists have proposed in the interest of reducing iPLEDGE’s burden and complexity:

• Eliminate the 30-day lockout period, especially for males, or at least allow a single exception under extenuating circumstances during active treatment. “There should be a supervisor at Covance who can make exceptions,” Dr. Greenberg explains.

• Add an online help program with “live” e-mail response capability, so that dermatologists and other users can obtain answers to basic questions without waiting on the phone.

• Allow patients to enter a new 7-day “window” immediately, if they miss the prescription fill date but have complied with other requirements. “If patients comply with all other elements of the program, they shouldn’t be ‘punished’ by being unable to get isotretinoin for another 23 days,” says Stefan Merlo, Pharm.D., Manager of Pharmacy Practice and Opera-tions for the National Association of Chain Drug Stores in Alexandria, VA.

• Allow edits within the system, by registered prescribers, when a simple data entry-type error has occurred. Regardless of which modifications, if any, move forward, the primary goal of any improvement should be to reduce unnecessary complexity for patients and dermatology practices, Dr. Ryan says.
“We now have patients who aren’t using Accutane because of the restrictions. The complexity is mind-boggling to them — and that’s why some females are suffering with their acne rather than doing iPLEDGE,” he says. “And at a recent meeting I attended, about 20% of the dermatologists said, ‘I’m just not going to prescribe isotretinoin anymore.’”