Annette Friedman, the Flawed Lottery, and Clinical Trials
Annette Friedman, the Flawed Lottery, and Clinical Trials
Annette Friedman, who sought access to an experimental monocolonal antibody drug that might have had action against her breast cancer, died in January 1997, shortly after the following was written.
A large number of women and men who know each other through an Internet mailing list but most of whom have never met one another and never met Annette Friedman, decided in November 1996 to move beyond dealing with their own medical issues and to become activists on breast cancer matters. They decided as their first action to try to help Annette, a member of the Breast-Cancer mailing list, to obtain the anti-HER2 monoclonal antibody.
In the process, they discovered flaws in the lottery set up by Genentech, Inc., for distribution of their experimental medicine. These pages trace the Annette story; some of them include discussion of flaws in the clinical trials lottery, replies to those charges by the companies involved, and an analysis of those replies. The clinical research organization has denied my description of flaws in their lottery, but has thus far refused to provide any documentation supporting their new version of how the lottery supposedly works.
Annette's death will not have been in vain if, as appears possible, the activism engendered by her struggle turns into a major campaign to make information on clinical trials on breast cancer therapies more known to women and men and their doctors (much of it is only sporadically known and some of it is secret), more accessible to them, and fairer.
Legislation has been introduced in Congress toward the goal of a unified database of clinical trials information; activists are themselves seeking ways ot finding and organizing the available information as well. They hope that the Annette Friedman story, while the last chapter of her women and men and their doctors (much of it is only sporadically known and some of it is secret), more accessible to them, and fairer.
Legislation has been introduced in Congress toward the goal of a unified database of clinical trials information; activists are themselves seeking ways ot finding and organizing the available information as well. They hope that the Annette Friedman story, while the last chapter of her life, will be the first chapter of new levels of activism on breast cancer issues in North America.
John E. Bonine
Thus far, however, efforts of her oncologist, Dr. Charles Vogel, and dozens of friends around the world to get Genentech Corp. to allow her to try an experimental treatment have been foiled by a computer running a flawed lottery program.
Annette Friedman, 58, of Boca Raton, her doctor and her friends have begged the South San Francisco company to help. They want Genentech, Inc., to let her try the company's anti-HER2 monoclonal antibody to treat the breast cancer that has spread to her lungs and other parts of her body. Those pleas have fallen on deaf ears.
Conventional chemotherapy treatments, begun after her 1995 diagnosis, failed the lawyer and mother of two. Last summer, Friedman tested positive for a protein "receptor" on the HER2 proto-oncogene and Vogel offered her some hope that Genentech's monoclonal antibody could prolong her life. The drug binds itself to the HER2 cell-receptor, thought to be "overexpressed" in one-quarter to one-third of breast cancer patients, and in some patients has reversed or slowed the growth of tumors.
Six times Friedman has entered Genentech's quarterly lottery to compete against other breast cancer patients like herself, and six times she has lost.
Only recently, friends working on her behalf, found that the lottery, run by NCGS and Associates Inc. of Charleston, S.C., has not allocated all of the 25 slots available each quarter, leaving dosages of the antibody unused and patients like Friedman, who "lost" in up to three tries in each of two quarters of the lottery, literally dying to try it.
Friends, writing pleas to Genentech officers for compassionate dosages of the drug, received only a form letter from the company's communications department, sympathizing with Friedman's case, but offering no hope for access to the drug.
In another letter, responding to further inquiries on Friedman's behalf, Dr. Susan Hellmann, vice president of Medical Affairs at Genentech, said the lottery uses "a portion of what remains an exteremly limited supply of the drug for patients who are ineligible for our Phase III trails and who have very few other treatment options."
The lottery was hammered out in 1994 in response to demonstrations by the Breast Cancer Action Committee of San Francisco and ACT-UP Golden Gate, an AIDS activist group, who campaigned for the company to institute a "compassionate use" policy for patients who do not qualify for existing trials or further chemotherapy treatments.
BCA members embraced the lottery, believing it would help 100 patients a year who otherwise would not receive the drug.
But a clinical trial specialist at NCGS and Associates, the company running the lottery, said it isn't so: The computer program was written in anticipation of a higher demand for the drug than has been demonstrated and in many quarters, the 25 slots have not been filled. This flaw, friends believe, leaves doses of the drug unused and patients dying for lack of it.
Though it is a quarterly lottery, participants' names are submitted to the NCGS computer as they apply and learn immediately whether they will receive the drug or not. Patients also may reapply for the lottery every 30 days after having blood tests and meeting the company's 18 eligibility requirements.
The NCGS clinical trial specialist, in a Dec. 20 conversation with University of Oregon Law Professor John E. Bonine, said the program makes adjustments during the last two weeks of the quarter, to try to fill the unfilled slots, giving applicants at that time a greater chance of receiving it.
"A lottery may or not be a fair way to allocate limited supplies of an experimental drug," said Bonine, "but this lottery is flawed. It doesn't award all the prizes."
"I am confident that Genentech is great at biotechnology, but their debugging of computer lottery programs leaves something to be desired," Bonine said.
Friedman's friends -- from throughout the U.S. and as far away as Israel and Eastern Europe -- and her doctor have pleaded with Genentech for access to one of the unallocated dosages to no avail. As another quarter ends, they are sure more of what could be a life-saving drug will go unused, while Friedman and others like her die waiting for their next chance to gamble their lives.
The American Cancer Society estimates that breast cancer claims more than 44,000 lives each year. Within that time period, another 184,500 will be diagnosed with the disease.
Genentech is a $918 million a year biotechnical company that develops, manufactures and distributes pharmaceuticals worldwide. Among its approved products are Actimmune, which is for treating chronic granulomatous disease; Activase, for victims of heart attack; Nutropin and Protropin, both human growth hormones used to treat growth deficiency in children; and Pulmozyme for the treatment of cystic fibrosis. Apart from the computerized lottery for their anti-HER2 medicine, they are also involved in several trials involving the anti-HER2 drug, the largest of which involves450 women at several centers. These trials are required before final approval by the Food and Drug Administration.
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