FDA’s "Decelerated" Approval
FDA’s "Decelerated" Approval Initiative for New Cancer Drugs
November 8, 2005: Presentation to the Oncologic Drugs Advisory Committee By Steven Walker
Abigail Alliance for Better Access to Developmental Drugs
abigail-alliance.org
Includes:
..."Despite the stark truth of what the FDA’s new policies would do in slowing translation of new therapies to the clinic and the patients that needed them to live, the FDA forged ahead – rolling out its plans to turn accelerated approval and Phase IV clinical trials into a high risk minefield for sponsors. In fact, on that day in March 2003, the FDA effectively eliminated the accelerated approval pathway as a viable mechanism - the exact opposite of what the FDA should have been doing in this time of accelerating scientific progress against cancer.
I would now like to take you through the start and evolution of the FDA’s decelerated approval initiative. I am going to read to you some of the statements made by FDA in ODAC meetings to launch the decelerated approval initiative, then talk about a couple of examples that illustrate the effect those policies have had on the effectiveness and ethics of our clinical trials and translation system."...
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June 1, 2007: The Problem with the FDA Drug Approval Process
By: Bartley J. Madden, Health Care News, The Heartland Institute
(Excerpted from More Choices, Better Health: Free to Choose Experimental Drugs, by Bartley J. Madden--the first in series)
heartland.org
includes:
..."We have grown accustomed to the FDA's monopoly on market access to drugs. But prior to 1962, new drugs had to pass only safety trials to be legally marketed. Effectiveness was left to consumers and doctors to evaluate.
Today, for drugs to be marketed as FDA-approved, they must pass a Phase I safety trial, followed by Phase II safety as well as effectiveness testing in a small sample of patients, followed by a Phase III clinical trial with a much larger number of patients.
On average, the three clinical trials take seven years. Next comes a new drug application (NDA) containing relevant data to be examined by the FDA. On average, that review process takes an additional 18 months. Thus, those who might benefit from a promising new drug cannot get it for, on average, eight-and-a-half years after it enters FDA clinical testing.
Not only do the clinical trials and NDA submission take time, they also take money. Drug developers experience a substantial outflow of hard cash, a long delay in possible revenues, ... and no guarantees the drug will be approved at all.
That combination boosts drug prices for consumers."...
In the section, "Making Tradeoffs":
..."When FDA errs on the side of excessive caution, thousands of patients may die who could have been saved. But those deaths are rarely documented and never make the nightly news. Thus, it should not be surprising that in practice FDA is much more concerned with avoiding highly visible errors and clearly identified victims than with the hidden, rarely identified victims of denied access to drugs in the FDA approval pipeline.
For FDA officials, approving an unsafe drug brings public humiliation from the media, affected patients, and politicians. That far outweighs any benefit they might receive for more quickly approving an effective new drug.
What has been the overall effect of FDA's extreme focus on minimizing bad publicity? "....
Daniel Klein and Alexander Tabarrok have assembled a large body of research on FDA.
fdareview.org
In their essay "Is the FDA Safe and Effective?" they conclude:
..."We argue that FDA control over drugs and devices has large and often overlooked costs that almost certainly exceed the benefits. We believe that FDA regulation of the medical industry has suppressed and delayed new drugs and devices, and has increased costs, with a net result of more morbidity and mortality. A large body of academic research has investigated the FDA and with unusual consensus has reached the same conclusion."...
Madden article's section titled, "Focusing the Debate"
..."A serious debate about FDA's regulatory role should begin with a focus on the common-sense principle that the power to make medical decisions rightly belongs first and foremost to patients and their doctors.
Last year, the U.S. Court of Appeals of the D.C. Circuit gave support to this principle by affirming the right of dying patients to access not-yet-FDA-approved drugs, in Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach.
Because of FDA's lengthy drug-approval process, a second focus should be on the harm done by the long delays before drug innovations reach the public. FDA's one-size-fits-all approval procedure is simply not attuned to the fast pace of twenty-first medical innovations.
A third focus should be on solving an emerging dilemma facing pharmaceutical companies that are gaining insights into how diseases (often rare diseases) relate to patients' genetic profiles. The dilemma is that the greater the gain in personalizing medicine, the smaller the target population for such drugs, the smaller the prospective revenues, and the less likely there will be a worthwhile return on investment. This is due, for the most part, to the high cost of having to conduct the full set of FDA clinical trials."...
Bartley J. Madden's article ends with:
Given these top priorities, what could be the structure and optimum level of FDA regulatory power? Neither Congress nor FDA knows, because the optimum level depends on the tradeoff decisions (risk versus benefits) that only individuals and their doctors should make. The current FDA regulatory approach ignores or suppresses these decisions.
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Subject related research material:
NOTE: FDA last year lost case in front of a three-judge panel. The three-judge panel found that the agency ...."is violating the due-process rights of terminally ill patients through its experimental drug access policy"... The FDA agency requested a rehearing by the full Washington, D.C., Court of Appeals.
Abigail Alliance v. Eschenbach
pacer.cadc.uscourts.gov
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Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, etc: Nov 2005, For a FDA 3-tiered approval system (S. 1956)
....To amend the Federal Food, Drug, and Cosmetic Act to create a new three-tiered approval system for drugs, biological products, and devices that is responsive to the needs of seriously ill patients, and for other purposes....
abigail-alliance.org
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May 2007: FDA's 'Draconian Policies' Should Be Checked by Court, Op-Ed Says
(Walker, Wall Street Journal, 5/4).
kaisernetwork.org
...."FDA's handing of Genasense lays bare the all too common, aggressive incompetence of the FDA's cancer-drug division and should lead to an immediate examination of its policies and leadership, followed by swift corrective action," Steven Walker, co-founder and chief adviser for the Abigail Alliance for Better Access to Developmental Drugs, writes in a Wall Street Journal opinion piece.
Walker details FDA's handling of the melanoma and chronic lymphocytic leukemia drug Genasense, manufactured by Genta. Walker writes, "Despite compelling evidence that Genasense is making progress in fighting both" melanoma and CLL, FDA "appears determined to kill the drug."
The Abigail Alliance filed a lawsuit against the agency to challenge its "refusal to grant access to investigational drugs, even as a last resort for terminally ill patients," Walker writes.
FDA last year lost the case in front of a three-judge panel, which found that the agency "is violating the due-process rights of terminally ill patients" through its experimental drug access policy, according to Walker. The agency has requested a rehearing by the full Washington, D.C., Court of Appeals.
Walker writes that "we can only hope the appeals court disagrees" that FDA has "unlimited" power "to control us and even deny us the pursuit of life itself." He concludes, "An agency that blocks progress against deadly diseases -- while arguing that its power to do so is above challenge -- is in dire need of a court supervised review"...
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Daniel Klein and Alexander Tabarrok:
fdaReview's Daniel Klein and Alexander Tabarrok have a menu on the left side of their webpage and also a drop-down menu to select a subject. For example, "Sensible Alternative: The Voluntary Provision of Assurance"
fdareview.org
Starts off:
..."We believe that it would be desirable to move toward a voluntary system in which private firms, organizations, and perhaps also other governments and a voluntary FDA assured consumers of drug safety and efficacy. The desirability of a voluntary system, however, depends not just on how poorly the FDA performs but also on how well such a system would perform in its stead. In this section, therefore, we provide further information on how voluntary practices assure drug safety and efficacy."...
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Saying No to Penelope (four years old)--- Father Seeks Experimental Cancer Drug, But a Biotech Firm Says Risk Is Too High
online.wsj.com
ends with:
Mr. London said, talking in another room out of Penelope's earshot
..."We go into this with our eyes open," .... "The chance of anything bringing her back from the abyss now is very low. But the only thing I know for sure is if we don't treat her, she will die."...
Long and moving article includes:
..."deadlock reflects an increasing tension between individual patients and companies using the revolution in understanding biology to develop new medicines.
Ideas for treating deadly diseases are proliferating, and the Internet carries hints of promising results into the homes of dying patients. They are pushing for the chance to bypass the laborious approval process and receive quick access to experimental drugs when all else has failed.
In the U.S. Court of Appeals in Washington last month, a lawyer for a patient-advocacy group argued that patients' constitutional rights are violated when they are deprived of medicines in testing that could save their lives."...
and
Patty Delaney, director of the FDA's cancer liaison program said:
..."This is a huge dilemma we face as a society -- it's moral and it's ethical,"..."We have the incredible pain of an individual -- sometimes it's a 4-year-old child, which pulls at everyone's morality -- versus the societal issue of what happens if a small biotech company diverts its resources"...
Neotropix:
..."nine months ago, the FDA put Neotropix's trial on hold because the first patient died. Only after four months of testing and analysis was Neotropix able to resume its trial, having demonstrated that the patient died from cancer and not the therapy. That delay was on Mr. Lanciano's mind when Mr. London and his supporters began calling. The CEO says he wanted to help, but he thinks the drug is too early in testing to be used safely by a child."...
Mr. Lanciano of Neotropix said:
..."The question is: Can we really help or would we do more harm?"...
...Mr. Lanciano and Neotropix board members have expressed concern that the FDA will force Neotropix to put its trial on hold again if Penelope dies....
Lanciano, 50, says:
..."he sympathized, having lost his wife several weeks earlier to cancer at age 51. He tried to get her in clinical trials for pancreatic-cancer treatments, but she didn't qualify,"...
Neff, partner at the venture-capital firm that has invested in Neotropix said:
..."If I were that father and mother with a dying 4-year-old, I'd be doing exactly the same thing,"..."There is no right answer,"..."But in a small company with limited financial resources and a high risk profile, you really have to reduce the risks to drug development."...
FDA :
..."FDA officials called Neotropix and reassured the company that this isn't the case,"... Despite the verbal FDA assurances, the company's CEO, Lanciano, says he is still worried. ...."You never have the ability to wash your hands of any adverse events the patient has,"...
FDA officials, agreeing only to speak generally about the issue, said:
..."the agency would not hold a company accountable for the death of a very sick patient receiving therapy as a desperate effort."...
FDA's Richard Klein, director of the agency's HIV program:
...."The FDA has good appreciation for the fact that we're dealing with people mortally ill and this is a last-ditch effort," ... " The notion that the FDA would halt trials over a death in such circumstances is more of a myth, or urban legend,"...
Ms. Delaney, the FDA's cancer liaison, however says:
..."Nonetheless, there aren't any absolutes,"..."We can never say: We won't pay any attention to safety' when a patient gets a drug."... |
