Subject: Editorial: The Alzheimer's Morass
Date: Published: 3/26/91 (103 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    REVIEW & OUTLOOK (Editorial):
    The Alzheimer's Morass

    The more you watch the federal government handle matters
 relevant to sick patients and new drugs, the more you come to
 see why AIDS advocates act up so much.  We've said this
 before, we'll say it again with the federal management of the
 Alzheimer's drug tacrine, or THA. The families of the
 disease's four million sufferers are now discovering still
 more about the Rube Goldberg system that "approves"
 medications for sick people.
    A week ago Friday, an FDA advisory committee apparently
 refused to recommend that THA be approved by the agency,
 which retains the final authority.  We say "apparently"
 because there seems to be no consensus on what precisely this
 committee decided around 10:30 p.m, after 14 hours of
 intricate -- and to some observers, frequently pointless --
 discussion.  It heard a presentation of two clinical studies
 presented on THA's behalf by its sponsor, Warner-Lambert Co.,
 and learned that if the FDA was going to require yet more
 studies, the results wouldn't be available for 12 to 18
 months.  The committee approved the main study and voted both
 ways on the supporting one, then assumed that under the FDA
 Rules of Order this meant the drug failed, and went home.
    This outcome produced an outcry on all sides, including a
 strong response from the Alzheimer's Association, not
 previously known for criticizing the status quo:  "THA is the
 first drug presented to the FDA for review that was developed
 specifically to treat symptoms of AD. We had hoped to see a
 crystal-clear assessment of the drug trial data, but there
 seemed to be a great deal of confusion, even disagreement
 among the scientists on the panel."  At a meeting days later
 with Journal editors, the head of the American Association of
 Retired Persons, Horace Deets, said of the committee's
 turndown that "people ought to have the right, if the risks
 are fully disclosed, to decide themselves how much risk
 they want to assume" from drugs such as THA. 
    By week's end, FDA officials had come up with a way to
 recover from an advisory-committee meeting widely viewed as a
 fiasco.  This past Friday they sent a letter to
 Warner-Lambert, suggesting that the company now undertake a
 "good-sized, relatively low-tech, parallel design study of
 several doses of tacrine."  FDA officials are scheduled to
 meet today with Warner-Lambert to discuss such details as
 whether this means distributing the drug to the nation's four
 million Alzheimer's patients, or if not, who makes the
 ethical calls on who gets it and who doesn't.
    Usually manufacturers provide experimental drugs for free,
 so maybe Warner-Lambert gets to pay for treating the whole
 Alzheimer's population.  Though the agency's letter doesn't
 mention it, an agency spokesman said that during this
 distribution period the drug maker presumably would be able
 to recover its "costs," whatever that means.  The cost of the
 past clinical trial, the cost of the present one, the cost of
 ongoing research, the cost of research on the next drug, the
 cost of capital?  In our world, even shareholder dividends are
 a cost, so we await the FDA decision on how what it calls
 "costs" differs from any other price.
    It is difficult to view this latest turn as much more than
 another face-saving dodge inside the FDA labyrinth, where
 even "reforms," such as expanded-access or parallel-track
 trials, come to be seen mainly as an excuse to avoid having
 to make a decision.  The FDA's history with THA persistently
 invites doubts about the agency's values and motives.  Early
 on, the agency's enforcement division threatened the drug's
 discoverer, Dr. William Summers, with loss of his
 investigator's license because of his record-keeping
 procedures.  Simultaneously government investigators recruited
 Warner-Lambert to carry out a study of Dr. Summers's
 discovery in a clinical trial overseen and approved by the
 agency.  The trial finally ends, and when the study is
 presented for approval it encounters a tendentious
 statistical analysis of its results by the FDA.  Finally,
 after an often surreal hearing before the agency-appointed
 committee of advisers, the drug fails approval and falls into
 its current nether world in which scientists, executives,
 bureaucrats, statisticians, lawyers and accountants will
 wrangle over its fate.
    The Warner-Lambert study confirmed the two things already
 known or suspected about this drug:  (1) It helps some
 Alzheimer's patients, maybe 40%, re-establish varying degrees
 of contact with the world around them.  And (2) it causes
 liver toxicity in some patients, which is reversible by
 stopping the drug.
    Surely we would learn further details if the drug were
 given to a large population of patients, whether you call the
 distribution a clinical trial or a post-marketing
 surveillance program.  The agency proposes a
 betwixt-and-between compromise simply to avoid admitting its
 own repeated errors, to avoid facing up to the pattern of
 foot-dragging that in this one case leaves four million
 patients without any therapy.  With its Friday proposal the
 agency is saying that Alzheimer's patients ought to have
 access to tacrine, so why not simply approve it?  

[This article is made available here by Dow Jones Co. for the 
personal and non-commercial use of callers to this bbs, in the 
hope that it will be of some help to those who are suffering 
from the disease and others who are seeking to help them.]