Dermatologists Frustrated With Problematic iPledge Program

Bonnie Darves

March 09, 2006

March 9, 2006 (San Francisco) — The largest and arguably most complex risk-management program ever undertaken by the US Food and Drug Administration is sparking a commensurate measure of controversy — outright anger, in fact — among many American dermatologists. Despite vigorous protests from the American Academy of Dermatology (AAD), the iPledge program, an online restricted-distribution program for prescribing the acne drug isotretinoin (Accutane), launched on schedule March 1.

At the AAD's annual meeting, dermatologists complained that the program — which has the primary goal of preventing pregnancy among women of child-bearing potential who are prescribed the known teratogen — is inordinately onerous, structurally flawed, and not ready for "prime time."

"This mandatory program is very large in scope and the devil is in the details — more so, I think, than anyone could have anticipated," Diane Thiboutot, MD, chair of the AAD's Ad Hoc Task Force on Isotretinoin, told Medscape. "iPledge was developed in a very rapid fashion with little opportunity for input from those who would use it."

The details of the iPledge program are indeed complex. Developed by the New Jersey drug-development services firm Covance according to a design jointly devised by the FDA and the Isotretinoin Product Manufacturers Group, iPLEDGE uses a technically elaborate Internet-based system that requires the registration of all wholesalers distributing isotretinoin, all healthcare professionals prescribing isotretinoin, all pharmacies dispensing isotretinoin, and all patients — both men and women — prescribed isotretinoin.

Female patients cannot obtain or fill their first prescription unless they meet stringent requirements, including initial screening and 2 negative blood or urine pregnancy tests with documented results verified by the prescriber and entered into the password-protected system. Female patients also must promise to use 2 forms of contraception for 1 month before, during, and for 1 month after isotretinoin therapy, and these methods must be cited in the initial program registration. Each month thereafter, the patient must have a negative pregnancy test result, and this result as well as verification of the 2 methods of contraception being used must entered by the prescriber into the iPledge system.

Dermatologists who voluntarily registered in iPLEDGE prior to its official launch identified several glitches in the program — with passwords, call center responsiveness, and untimely processing of identification cards and materials orders — and pushed for a less burdensome structure. For example, the program requires registered patients to pick up their isotretinoin prescription within 7 days of the office visit or the prescription will "expire," and office visits must be scheduled no sooner than 30 days after the previous visit. The system also imposes registration requirements on male patients and on women who cannot — or by choice will not — become pregnant.

At the other end of the prescribing spectrum, pharmacists must obtain authorization by phone or via the iPledge Web site before dispensing the medication. As such, the risk management program is far broader in scope than its sticker-based predecessor and more elaborate and stringent than the one used to control thalidomide prescribing. Hundreds of thousands of prescriptions are written annually for isotretinoin, Dr. Thiboutot noted.

The net effect, say dermatologists, is a bottleneck in office operations, delays in patient care, and, ultimately, barriersto delivery of a drug that has proved the only effective therapy for many patients with severe, recalcitrant acne.

"Members [of the AAD] believe that the flaws and inefficiencies of the program have not been sufficiently addressed and remain concerned that the program will not work as intended, likely impeding patient access to this important medication," the AAD's immediate past president Clay Cockerell, MD, wrote in a recent statement.

"Among the many very large philosophical concerns we have about iPledge, the main one right now is that we can't use the thing," Dr. Thiboutot told Medscape. "It's the failure or at least the lack of a communication plan that's the key issue right now. We're in a crisis situation — and a lot of things were underestimated. The Web site is not adequately powered for the volume." She added that the AAD had heard that some members who called the iPledge call center "were getting put on hold for hours" when they tried to seek clarification on vexing registration problems or glitches.

That sentiment of utter frustration, along with some dermatologists' disagreement with the program's philosophical underpinnings, was palpable during a somewhat hastily convened iPledge focus session held March 6, during the AAD's annual meeting.

After a presentation by Jill Lindstrom, MD, the FDA's acting deputy director of the division of dermatological and dental products, on the rationale for the program and an overview by Covance Director James Shamp, attendees flocked to the microphones to express their concerns.

"Many dermatologists feel that this program will not lead to a pregnancy rate decrease — and that if it fails, it will lead to removal of Accutane as a treatment for our often very depressed patients," said Harvey Weinberg, MD, a Parsippany, New Jersey, dermatologist.

"Most of us think iPledge is doomed and that it will scare away patients. We're concerned that the program will lead to a marked reduction in use of this very good, very important drug," Dr. Weinberg later told Medscape.

Dr. Lindstrom had earlier acknowledged the widespread opposition to the FDA's implementation of the program. "I have received an abundance of e-mails, through the AAD and through the DrugWatch program. I've even received some hate mail," she told attendees. She defended the FDA's mandating of iPledge on the basis that the less restrictive sticker-based "SMART" program (System to Manage Accutane Related Teratogenicity) initiated in 2002 had been ineffective in reducing the incidence of fetal exposure to isotretinoin. In the year before SMART was initiated, 127 isotretinoin-exposed pregnancies were reported compared with 120 the year after it launched. She also noted that some large pharmacy chains had opted out of complying with its programmatic requirements.

Dr. Lindstrom told attendees that the FDA was acknowledging their concerns and seeking public comment, and that the agency would consider requested modifications. She did not, however, promise that iPledge would be modified in any material manner.

Attendees who took philosophical issue with the program's complex requirements claimed that the actual number of birth defects associated with isotretinoin is small given the number of prescriptions, and that its design — specifically the monthly reporting requirement and documentation of birth control methods — assumes patients are either unable or unwilling to take steps to prevent pregnancy. That, some say, places dermatologists and other prescribers in the awkward, untenable position of trying to determine whether their patients are telling them the truth.

Finally, because program materials are currently available in only English and Spanish, many non-English-speaking patients cannot understand the program materials or manage even the phone-based iPledge system. Providers have also expressed concerns about the limited availability of the materials, and the fact that patient materials state a potential link between isotretinoin use and development of diabetes but do not substantiate that link.

On another regulatory front, confusion persists about whether and how HIPAA security and privacy regulations enter into the picture, because the computer program requires extensive patient identifier details. That situation is confounded by the fact that certain physician providers, by virtue of their size or other factors, are exempt from HIPAA. "We're seeking clarification on that because it's urgently needed," said Dr. Thiboutot.

Attendees and AAD officials also noted that the FDA has not gone to such lengths to restrict access to other potentially teratogenic drugs — or to regulate alcohol purchases by women of childbearing age, to possibly reduce the incidence of fetal alcohol syndrome.

"There are a lot of dangerous drugs out there — some that are more dangerous than Accutane. Our concern is that if this program doesn't work, the FDA will say it has continuing concerns — and a valuable drug will be removed," said William Ramsdell, MD, an Austin, Texas, dermatologist.

AAD 64th Annual Meeting. Focus session, March 6, 2006.

Reviewed by Kristin Richardson

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